PROCEEDINGS

of the
XXXIII National Continuing
Medical Education Programme
in Surgery

SURGERY UPDATE 2015

Compiled by:

Dir. Prof. A.K.Sarda

MS, FAIS, FACS, FICS

Prof. Rajdeep Singh

MBBS, MS

On behalf of the
Department of Surgery
Maulana Azad Medical College
& associated
Lok Nayak Hospital
New Delhi
Year of publication: 2015

Price of extra copy of Proceedings: Rs.750/-

NOTE: The Organizing Committee of SURGERY UPDATE 2015 takes no

responsibility for the contents of the lectures which are the sole
responsibility of the concerned authors. None of the lectures has been
edited in part or in whole. A part or whole of the lecture may be reproduced
with the prior permission of the concerned author.
 FOREWORD
The National Continuing Medical Education Programme in Surgery organized by the
department of Surgery, Maulana Azad Medical College, New Delhi is in its twenty
ninth year of existence. During this period has blossomed into a six day academic
exercise eagerly looked forward to by the surgeons all over the country and has
established itself as the gold standard for Continuing Medical Education
Programmes. One of its endearing features is the CME lectures brought out in a
bound format simply named the PROCEEDINGS, introduced and published in 1998
The PROCEEDINGS have become an integral part of the update since then. It is
satisfying to note that the bound lectures are carried by postgraduates all over the
country preparing for examinations or for interviews. Those who miss out on
attending the CME programme, still manage to procure copies of the
PROCEEDINGS in its photocopied form. This year also it gives us great pleasure to
present a book on the PROCEEDINGS OF THE XXXIII NATIONAL CONTINUING
MEDICAL EDUCATION PROGRAMME IN SURGERY, similar to previous years.

Every surgical disorder in the scientific programme has been chosen carefully in the
context of its importance to the attending delegates. All the authors are well-
recognized authorities with a vast personal clinical experience on the particular
subject they were chosen to elaborate. As will be evident from the written texts, they
have contributed a very comprehensive account of the respective topics and are also
to be commended for submitting the latest references at the end of each chapter for
ready referral. The quality of their text reflects their involvement in our programme. A
sincere effort has been made to format the book in a uniform manner without any
effort to edit the text provided by the contributors.

This years programme is a full day comprehensive CME on selected topics of

particular interest to the postgraduate. Emphasis is on subjects with more bearing on
their clinical application. Every years Proceedings can be considered one part of the
trilogy of books which will cover nearly the whole course for the postgraduate student
over a three year period.

We sincerely thank the contributors for their effort. We also wish to thank all the
colleagues in the department for their encouragement and guidance in making this
project possible. Especial thanks are to Prof. Rajdeep Singh, who has been
instrumental in collecting the articles and majorly formatting the text to its final form.
Our sincere thanks are also due to the resident staff who worked for procuring, proof
reading and formatting the text. Finally, we must emphasize the contribution of the
authors who have always given an overwhelming response to our endeavor of
bringing out the written text of our CME programme over the years. We sincerely
hope that the Proceedings will meet the stiff demands of the delegates and serve as
a nodal point of learning for the postgraduates.

Prof. Sanjeev Kumar Tudu Dir. Prof. Anil Kumar Sarda

HOD, Surgery, MAMC & LNH Hospital Organizing Secretary
& Organizing Chairman SURGERY UPDATE 2015
SURGERY UPDATE 2015
 CONTRIBUTORS
Metastatic Carcinoma Breast Troubleshooting equipment and procedural
Dr. Ajit Sinha difficulties
Consultant, Department of Surgery Dr. Deborshi Sharma
VardhmanMahavir Medical College, Professor of Surgery,
New Delhi Lady Hardinge Medical College, New Delhi

MEN Syndrome Short bowel Syndrome

Dr. Amit Agarwal Dr. Deepak Ghuliani
Professor of Endocrine Surgery, Associate Professor, Surgery,
Sanjay Gandhi Postgraduate Institute of Medical Maulana Azad Medical College &
Education and Research, Lucknow assoc. Lok Nayak Hospital, Delhi

Approach to a patient with thyroid disease Robotic prostatectomy

Dr. Anjali Mishra Dr. Gagan Gautam
Additional Professor Endocrine Surgery, Head of Urologic Oncology & Robotic Surgery,
Sanjay Gandhi Postgraduate Institute of Medical Medanta The Medicity,
Education and Research, Lucknow Gurgaon

Investigations for peripheral vascular disease
Dr. Anjali Prakash
Professor of Surgery,
Maulana Azad Medical College &assoc. Lok
Nayak Hospital, New Delhi
Management of the Axilla in Carcinoma Breast
Dr. Gaurav Agarwal
Professor Endocrine Surgery,
Sanjay Gandhi Postgraduate Institute of Medical
Education and Research, Lucknow

Motility disorders of oesophagus Approach to a patient with breast disease

Dr. Anubhav Vindal Dr. Geeta Kadayaprath
Associate Professor of Surgery, Head, Breast Surgical Oncology
Maulana Azad Medical College & Max Cancer Centre
assoc. Lok Nayak Hospital, Delhi New Delhi

Diagnostic Laparoscopy Early breast Cancer

Dr Anurag Mishra Dr. Harit Chaturvedi
Assistant Professor Surgery, Chief Consultant & Director Surgical Oncology,
Maulana Azad Medical College & Max Healthcare Hospitals,
assoc. Lok Nayak Hospital, Delhi New Delhi

Endourologic procedures for stones Urethral Injuries

Dr. Atul Goswami Dr. Iqbal Singh
Senior Consultant & Coordinator Urology Professor of Surgery,
Max Superspeciality Hospital, University College of Medical Sciences &
New Delhi assoc. Guru Teg Bahadur Hospital, Delhi

Subdiaphragmatic Abscess Hand Infection

Dr. Chandra B. Singh Dr. Jainendra K. Arora
Professor of Surgery, Associate Professor Surgery,
Maulana Azad Medical College & Vardhman Mahavir Medical College and
assoc. Lok Nayak Hospital, Delhi assoc. Safdarjung hospital, Delhi
 Paraneoplastic Syndromes
Dr. Jitendra Kumar
Asstt. Professor of Surgery,
Lady Hardinge Medical College & assoc. Smt.
SuchetaKriplani Hospital, New Delhi
Management of Renal Malignancies
Dr. Kim Mammen
Professor & Head of Urology,
Christian Medical College
Ludhiana, Punjab
Radiotherapy in Carcinoma breast
Dr. Kishore Singh
Director Professor of Radiotherapy,
Maulana Azad Medical College & assoc.
LokNayak Hospital, New Delhi
Gastrointestinal polyps
Dr. Lalit Agarwal
Associate Professor of Surgery,
Lady Hardinge Medical College & assoc. Smt.
SuchetaKriplani Hospital, New Delhi
Cholecystectomy
Dr. Lovenish Kumar
Asstt. Prof. of Surgery,
Dr. BSAmbedkar Medical College,
New Delhi
Carcinoids
Dr. Manoj Andley
Professor of Surgery,
Lady Hardinge Medical College &
assoc. Smt. Sucheta Kriplani Hospital, Delhi
Gastrointestinal stromal tumours
Dr. Nikhil Talwar
Assistant Professor, Surgery
Lady Hardinge Medical College &assoc. Smt.
Sucheta Kriplani Hospital, New Delhi
Operative Procedure for Breast Cancer
Dr Nikhil Talwar
Assistant Professor, Surgery
Lady Hardinge Medical College &assoc. Smt.
Sucheta Kriplani Hospital, New Delhi
Stapled heamorrhoidopexy
Dr. P. N. Agarwal
Director Professor of Surgery,
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
Locally advanced Carcinoma breast
Dr. P. N. Agarwal
Director Professor of Surgery,
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
Urinary Diversion
Dr. Pawan Lal
Professor of Surgery,
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
Approach to a patient with Obstructive Jaundice
Dr. Pramod K. Mishra
Consultant GI Surgeon,
Govind Ballabh Pant Hospital,
Delhi
Cleft lip & Palate
Dr. R.B. Ahuja
Professor of Plastic Surgery
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
Blood Component Therapy
Dr. R.N. Makroo
Consultant Transfusion Medicine, Molecular
Biology & Immunology,
Indraprashtha Apollo Hospital, New Delhi
Energy Source in surgery
Dr. Rajdeep Singh
Professor of Surgery,
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
Fundoplication
Dr. Randeep Wadhawan
Director & Head, Minimal Access Surgery,
Bariatric Surgery & Gastrointestinal Surgery,
Fortis Hospital, VasantKunj, Delhi
Carcinoma tongue
Dr. Ravi Kannan
Director & Consultant Surgical Oncologist,
Cachar Cancer Hospital and Research Centre,
Silchar, Assam
Ergonomics in Lap Surgeries
Dr. Ravindra S. Mohil
Consultant Surgeon & Professor Surgery,
Vardhman Mahavir Medical College and assoc.
Safdarjung hospital, Delhi
Radiology in Breast Disease Abdominal Compartment Syndrome
Dr. Richa Bansal Dr. Shaji Thomas
Consultant, Radiology Director Professor, Surgery,
Max Healthcare Hospitals, Lady Hardinge Medical College &
New Delhi assoc. Smt. Sucheta Kriplani Hospital, Delhi

Management of BPH Ischaemic bowel disease

Dr Rishi Nayyar Dr. Sundeep Saluja
Assistant Professor of Urology, Professor of Gastrointestinal Surgery,
All India Institute of Medical Sciences, GovindBallabh Pant Hospital,
New Delhi New Delhi

Undescended Testis Primary hyperparathyroidism

Dr. S.K. Jain Dr. Sunil Chumber
Professor of Surgery Professor of Surgery,
Maulana Azad Medical College & All India Institute of Medical Sciences,
assoc. Lok Nayak Hospital, Delhi New Delhi

Role/Impact of telemedicine in surgery Parasitic Infestations of Liver

Dr. S.K.Mishra Dr. Sushanto Neogi
Professor & Head of Endocrine Surgery, Professor of Surgery,
Sanjay Gandhi Postgraduate Institute of Medical Maulana Azad Medical College &
Education and Research, Lucknow assoc. Lok Nayak Hospital, Delhi

Tumour Markers in management of breast disease Sentinel Lymph node biopsy

Dr. S.V.S. Deo Dr. V. Seenu
Professor of Surgical Oncology, BRA-IRCH, Professor of Surgery,
All India Institute of Medical Sciences, N. Delhi All India Institute of Medical Sciences,
New Delhi

Thoracic Outlet Syndrome Venous Ulcer

Dr Sabyasachi Bal Dr. Vivek Agrawal
Director & Head Professor of Surgery,
Thoracic Surgery & Thoracic Oncology University College of Medical Sciences & assoc.
Fortis Escorts Hospitals, Delhi Guru TegBahadur Hospital, New Delhi

Anorectal malformations
Dr Satish K Aggarwal
Director Professor of Paediatric Surgery,
Maulana Azad Medical College &
assoc. Lok Nayak Hospital, Delhi
 INDEX

1. Undescended Testis 1
Dr. S.K. Jain, Dr. Amit Gupta

2. Anorectal malformations 5
Dr. S.K. Aggarwal

3. Cleft lip & Palate 11

Dr. R.B. Ahuja, Dr.Vybhav Deraje

4. Urethral Injuries 18
Dr. Iqbal Singh

5. Urinary Diversion 23
Dr.Pawan Lal, DrSanjeev K. Tudu

6. Management of BPH 30
Dr. Rishi Nayyar, Dr.Ashish Kumar

7. Management of Renal Malignancies 39

Dr. Kim Mammen, Dr.Abhinav Jaiswal

8. Approach to a patient with renal disease 55

9. Benign Diseases of Breast 65

10. Sentinel Lymph node biopsy 74

Dr. V. Seenu, Dr. Piyush Ranjan Mishra

11. Tumour Markers in management of breast disease 77

Dr. S.V.S. Deo, Dr.Ashish Jakhetiya

12. Early breast Cancer 80

Dr. Harit Chaturvedi

13. Locally advanced Carcinoma breast 92

Dr. P.N. Agarwal, Dr.Vivek Wadhawa

14. Management of the Axilla in Carcinoma Breast 97

Dr. Gaurav Agarwal, Dr. Sendhil Rajan

15. Operative Procedure for Breast Cancer 103

Dr. Nikhil Talwar

16. Metastatic Carcinoma Breast 117

Dr. Ajit Sinha

17. Radiotherapy in Carcinoma breast 123

Dr. Kishore Singh

18. Approach to a patient with breast disease 125

Dr. Geeta K.

19. Radiology in Breast Disease 128

Dr.Richa Bansal

20. Hand Infection 139

Dr. Jainendra Arora

21. Venous Ulcer 145

Dr. Vivek Agrawal
22. Thoracic Outlet Syndrome 155
Dr. S. Bal

23. Primary hyperparathyroidism 160

Dr. Sunil Chumber, Dr. Pratyusha Priyadarshini

24. Surgery for Hereditary MEN-related tumors 162

Dr. Amit Agarwal, Dr.Navneet Tripathi, Dr.Roma Pradhan

25. Carcinoids 167

Dr. Manoj Andley

26. Paraneoplastic Syndromes 173

Dr. Jitendra Kumar

27. Approach to a patient with thyroid disease 181

Dr. Anjali Mishra, Dr.Chandan K.Jha, Dr.Niraj Kumari, Dr.Zafar Neyaz

28. Cystic Lesions of pancreas 186

29. Gastrointestinal stromal tumours 192

Dr. Nikhil Talwar, DrRigved Gupta

30. Motility disorders of oesophagus 196

Dr. Anubhav Vindal, Dr.Sachin Mittal

31. Short bowel Syndrome 201

Dr. Deepak Ghuliani, Dr.Abhinav Agrihari

32. Parasitic Infestations of Liver 209

Dr. Sushanto Neogi

33. Subdiaphragmatic Abscess 218

Dr. C.B. Singh, Dr Suresh R.

34. Ischaemic bowel disease 222

Dr. Sundeep Saluja, Dr.Harsh Shah

35. Abdominal Compartment Syndrome 229

Dr. Shaji Thomas

36. Approach to a patient with Obstructive Jaundice 234

Dr. P.K. Mishra, Dr.Arvind P.S., Dr.P. Narang

37. Diagnostic Laparoscopy 238

Dr. Anurag Mishra

38. Ergonomics in Lap Surgeries 247

Dr. R.S. Mohil, Dr.Sharmistha Bhattacharyya

39. Troubleshooting equipment and procedural difficulties 253

Dr. Deborshi Sharma, Dr.Swati Sattawan

40. Current status of laparoscopy for abdominal malignancies 259

41. Robotic prostatectomy 265

Dr. Gagan Gautam, Dr.K. Rupala, Dr.V. Mittal

42. Retrograde Intrarenal Surgery 271

Dr. Atul Goswami

43. Gastroesophageal Reflux Disease 271

Dr. Randeep Wadhawan
44. Stapled heamorrhoidopexy 275
Dr. P. N. Agarwal, Dr. Anurag Mishra

45. Cholecystectomy 277

Dr. Lovenish Kumar, Dr.A.K. Sarda

46. Carcinoma tongue 283

Dr. Ravi Kannan

47. Gastrointestinal polyps 299

Dr. Lalit Agarwal

48. Regional Anaesthesia 246

49. Blood Component Therapy 310

Dr. R.N. Makroo

50. Energy Source in surgery 317

Dr. Rajdeep Singh

51. Functional imaging 322

52. Role/Impact of telemedicine in surgery 331

Dr. S.K. Mishra

53. Investigation for peripheral vascular disease 336

Dr. Anjali Prakash
 Undescended Testes

Sudhir Kumar Jain, Amit Gupta

Cryptorchidism (from the Greek KRYPTOS meaning hidden, and ORCHIS meaning testis) refers to absence
of a testis from the scrotum. During embryonic life, the testes form beside the mesonephric kidneys and descend
via the inguinal canal to the scrotum. If this process is faulty, a cryptorchid testis may halt along the normal path
of descent (undescended or retractile testis), may travel off the normal path of decent (ectopic testis), or may die
or never develop (absent testis). Therefore, the terms cryptorchid and undescended are not synonymous.
Isolated cryptorchidism is the most common congenital anomaly of the male genitalia, affecting almost 1% of
fullterm infants at the age of 1 year. Despite intense study both experimentally and clinically for the last century,
the cause of this condition remains poorly understood. Although there have been surgical advances in the
techniques of orchiopexy, areas of clinical controversy remain.

TESTICULAR DESCENT
Testicular descent is necessary for normal spermatogenesis, which requires the 2 F to 3 F cooler scrotal
environment. Embryonic testicular descent can be divided into three phases:
1. Transabdominal migration of the testis to the internal inguinal ring
2. Development of the processus vaginalis and the inguinal canal
3. Transinguinal descent of the testis to the scrotum

FACTORS IN TESTICULAR DESCENT

Hormonal Factors
Key hormonal factors implicated in testicular descent include the androgens, INSL3, estrogens, and AMH.
Androgens and the Androgen Receptor
Insulin-like Factor 3 and Its Receptor
Estrogens
Anti-mllerian-Inhibiting Substance
Calcitonin Gene-Related Peptide
Epidermal Growth Factor

Mechanical Factors
Perhaps the most important mechanical factor, the gubernaculum begins as a mesenchymal band that originates
on the lower pole of the testis/mesonephric duct and inserts in the scrotum. The exact mechanism through which
the gubernaculum mediates testicular descent is debated and may involve traction, muscular contraction, or
differential growth around a fixed point.

Males with prune-belly syndrome or other abdominal wall defects such as gastroschisis, omphalocele, or
umbilical hernia frequently have cryptorchidism.

Epididymal anomalies are seen adjacent to undescended testes in 33% of cases, but they are five times more
common in patients with an inguinal hernia than in patients with cryptorchidism, suggesting that other factors may
be involved.

DEFINITIONS AND CLASSIFICATION

Cryptorchidism is classified as palpable testes in 80% of the cases, and as nonpalpable testes in 20%. Palpable
testes include true undescended testes and ectopic testes and retractile testes as they are often misdiagnosed
as palpable undescended testes. Nonpalpable testes include intra-abdominal, inguinal, and absent testes.

VANISHING TESTIS
The term vanishing testis indicates that the testicular vessels and a vas deferens are found on surgical
exploration, but a testis is absent. In utero infarction of a normal testis by gonadal vessel torsion after gestational
weeks 12 to 14 is hypothesized, because ipsilateral wolffian duct differentiation and mllerian duct regression,
both of which require ipsilateral testicular hormones, occur normally. Supporting evidence for testicular infarction
includes the common finding of hemosiderin and calcium deposits in testicular remnants (nubbins) found on
exploration.

TESTICULAR AGENESIS
Testicular agenesis may result from failure of the testicular blood supply to develop or from abnormal gonadal
ridge differentiation. An example of the latter is 46,XY complete gonadal dysgenesis.

INCIDENCE AND NATURAL HISTORY

Isolated cryptorchidism is one of the most common congenital anomalies found at birth and affects upward of 3%
of full-term male newborns. Unilateral cryptorchidism is more common than bilateral cryptorchidism, which occurs
in 1.6% to 1.9% of boys. Approximately 33% of premature male infants are cryptorchid. The incidence in full-term

1
males at birth is 2% to 4%, and at age 1 year it is 1%. Approximately 70% to 77% of cryptorchid testes will
spontaneously descend, usually by 3 months of age.

RISK FACTORS
Maternal, Paternal, and Gestational Factors
Maternal obesity, cesarean section, low birth weight, and prematurity have been associated with cryptorchidism,
each independently doubling the relative risk over that of the general population.

Genetic Factors
The familial cluster (risk for an undescended testis in a newborn male if a family member is already affected) is
3.6-fold overall, 6.9-fold if a brother is affected, and 4.6-fold if the father is affected.

Environmental Factors
Prenatal environmental exposure to a growing group of compounds termed endocrine disruptors. Such
compounds include DES (synthetic estrogen), DDT (pesticide), nonylphenol (industrial surfactant), bisphenol-A
and certain phthalates (plastics additives), and natural phytoestrogens (common in soy products).

ASSOCIATED ANOMALIES
Multiple factors are involved in normal testicular descent. As a result, many clinical syndromes that affect genetic
integrity or the endocrine, musculoskeletal, and nervous systems can be associated with this condition. For
example, abnormalities in chromosome number, such as autosomal trisomy, triploidy, and Klinefelters syndrome
(XXY), are commonly associated with cryptorchidism. Deficiencies in pituitary function, testosterone production,
5-reductase activity, and androgen receptor sensitivity effectively interrupt androgen activity and can result in
cryptorchidism.

CLASSIFICATION
Cryptorchid testicular position is most simply described as intra-abdominal, intracanalicular, extracanalicular
(suprapubic or infrapubic), or ectopic.

HISTOPATHOLOGY
The histopathologic hallmarks associated with cryptorchidism are evident between 1 and 2 years of age and
include decreased numbers of Leydig cells, degeneration of Sertoli cells, delayed disappearance of gonocytes,
delayed appearance of adult dark (Ad) spermatogonia, failure of primary spermatocytes to develop, and reduced
total germ cell counts.

WORK UP
If a testis is not in the scrotum, the cryptorchid testis is sought by gently advancing the examining fingers along
the inguinal canal toward the pubic tubercle. This examination is best facilitated by applying lubricant to the groin.
The overall accuracy of radiologic testing for an undescended testis is 44%. The workup for bilateral nonpalpable
testes merits special consideration because it may represent a life-threatening situation if it is associated with
either hypospadias or ambiguous genitalia.

CONSEQUENCES OF CRYPTORCHIDISM

Infertility
Impairment of germ cell maturation is a well-recognized consequence of cryptorchidism.

Neoplasia
It is a well-established fact that children born with undescended testes are at increased risk for testicular
malignancy. The most common tumor that develops from a cryptorchid testis is seminoma. The prevalence of
carcinoma in situ is 1.7% in patients with cryptorchidism.

2
Hernia
A patent processus vaginalis is found in more than 90% of patients with an undescended testis.

Testicular Torsion
The increased susceptibility of the testis to undergo torsion is the result of a developmental anatomic abnormality
between the testis and its mesentery. The mechanism is believed to be related to a greater relative broadness of
the testicle than its mesentery. Although torsion of an undescended testis is rare, it should be considered in any
child with abdominal or groin pain and an empty ipsilateral hemiscrotum.

MANAGEMENT OF CRYPTORCHIDISM
Important principles for the treatment of a child with an undescended testis include the following:
Proper identification of the anatomy, position, and viability of the undescended testis
Identification of any potential coexisting syndromic abnormalities
Placement of the testis within the scrotum in timely fashion to prevent further testicular impairment in
either fertility potential or endocrinologic function
Attainment of permanent fixation of the testis with a normal scrotal position that allows for easy palpation
No further testicular damage resulting from the treatment.

Definitive treatment of an undescended testis should take place between 6 and 12 months of age.Orchiectomy is
typically reserved for postpubescent males with a contralateral normally descended testis when the cryptorchid
testis is either anatomically or morphologically abnormal or too far from the scrotum to allow for tension-free
placement without compromising the vascular integrity of the testis.

Hormonal Therapy
Two types of medical treatment of an undescended testis can be provided: exogenous hCG and exogenous
GnRH or LHRH. The mechanism of action in both cases increases serum testosterone production by stimulation
at different levels of the hypothalamic-pituitary-gonadal cascade. The overall efficacy of hormonal treatment is
less than 20% for cryptorchid testes and is significantly dependent on pretreatment testicular location. Therefore,
surgery remains the gold standard for the management of undescended testes.

Surgical Treatment
It is very useful to examine the child after induction of general and regional anesthesia to reaffirm testicular
position or attempt to establish testicular position in the case of a previously nonpalpable testis.

Standard Orchiopexy
The key steps in this procedure are
(1) complete mobilization of the testis and spermatic cord
(2) repair of the patent processus vaginalis by high ligation of the hernia sac
(3) skeletonization of the spermatic cord without sacrificing vascular integrity to achieve tension-free placement of
the testis within the dependent position of the scrotum.
(4) creation of a superficial pouch within the hemiscrotum to receive the testis.

Techniques for High Undescended Testes

Occasionally, greater mobilization of the proximal spermatic cord structures does not provide adequate length to
allow for tension-free placement of the testis within the scrotum. Greater cord length can be obtained by
mobilizing the spermatic vessels medially. The spermatic vessels are usually the limiting factor in these
circumstances. The Prentiss maneuver was described in 1960 and is occasionally helpful in adding length to the
spermatic vessels by positioning the spermatic vessels medially and thereby choosing the hypotenuse of the
triangle, or the most direct course to the scrotum, created by the natural course of the vessels laterally through
the internal ring.

Fowler-Stephens Orchiopexy
Fowler and Stephens studied the vascular anatomy of the testis and devised a means to repair a high
undescended testis and preserve its blood supply via collateral circulation. The anticipated advantage of a two-
stage orchiopexy with spermatic vessel ligation is twofold: (1) to allow for development of collateral blood supply

3
to compensate for division of the main blood supply to the testis and (2) to allow for greater mobility of the testis
to place it within the scrotum.

Laparoscopic Management of an Undescended Testis

The advantages of laparoscopy over a conventional open surgical approach to a nonpalpable testis include
accurate anatomic assessment of testicular position and viability and, when necessary, optimal accessibility to
the crux of the surgical problem.

Diagnostic Laparoscopy for a Nonpalpable Testis

A nonpalpable testis accounts for approximately one fifth of children with an undescended testis. Diagnostic
laparoscopy is commonly used for the assessment of a nonpalpable testis, with the accuracy of testicular
localization reported to be greater than 95%.By using an already existing port site, diagnostic laparoscopy can
naturally transition to extend the operative procedure from diagnostic to therapeutic.
Laparoscopic Assessment
There are three distinct possible findingsand courses of actionwhen laparoscopy is used to assess a
nonpalpable testis. Findings include
Blind-ending vessels above the internal ring (vanishing testis)
Cord structures entering the internal ring (viable intracanalicular testis versus an intracanalicular or
scrotal atrophic testis)
Intra-abdominal testis

Inguinal versus Laparoscopic Exploration

The choice of traditional surgical exploration versus primary laparoscopy for assessment of a nonpalpable testis
is a matter of debate. Open surgical exploration via an inguinal incision was the procedure most commonly used
before the era of laparoscopy for the management of a nonpalpable testis. It is difficult to criticize traditional
nonlaparoscopic techniques of exploration; however, laparoscopy, whether primary or adjunctive to an open
exploration, offers a logical extension of surgical principles, especially if conversion to a therapeutic laparoscopic
procedure is anticipated.

Laparoscopic Orchidopexy
Laparoscopic orchidopexy is now standard in the urologists' armamentarium of management for an intra-
abdominal testis. A laparoscopic approach in the management of an intra-abdominal undescended testis has
advantages over standard orchidopexy performed through either an extended inguinal incision or a high inguinal
incision (Jones incision). Laparoscopy accurately assesses the presence, absence, viability, and entire anatomy
of an intra-abdominal testis. The age at which laparoscopic orchidopexy should be performed is the same as for
standard orchidopexy, usually between 6 and 8 months and certainly before 1 year of age.

Microvascular Autotransplantation
The indications for performing autotransplantation of an intra-abdominal testis must be weighed in light of the
circumstances of the clinical findings; the indications are similar to those for a Fowler-Stephens orchiopexy. An
important consideration that weighs in favor of this procedure is the variability of collateral blood supply in
patients with a high undescended testis, which may potentially compromise the Fowler-Stephens procedure.

Reoperative Orchiopexy
Reoperative orchiopexy is performed in cases of secondary cryptorchism after orchiopexy or inguinal hernia
repair.

Complications of Orchiopexy
Complications of orchiopexy include testicular retraction, hematoma formation, ilioinguinal nerve injury,
postoperative torsion (either iatrogenic or spontaneous), damage to the vas deferens, and testicular atrophy.
Atrophy of the testis is the most devastating complication, but it is seldom seen with standard orchiopexy.

References

1. Abratt et al., 1992. Abratt RP, Reddi VB, Saremboch LA: Testicular cancer and cryptorchidism. Br J
Urol 1992; 70:656-659.
2. Backhouse, 1982a. Backhouse KM: Development and descent of the testis. Eur J Pediatr 1982; 139:249-252.
3. Backhouse, 1982b. Backhouse KM: Embryology of testicular descent and maldescent. Urol Clin North
Am 1982; 9:315-325.
4. Berkowitz et al., 1993. Berkowitz GS, Lapinski RH, Dolgin SE, et al: Prevalence and natural history of
cryptorchidism. Pediatrics 1993; 92:44-49.
5. Wein: Campbell-Walsh Urology, 9th ed.
6. Bianchi, 1984. Bianchi A: Microvascular orchiopexy for high undescended testes. Br J Urol 1984; 56:521-524.
7. Jordan and Winslow, 1994. Jordan GH, Winslow BH: Laparoscopic single stage and staged orchiopexy. J
Urol 1994; 152:1249-1252.
8. Parkinson et al., 1994. Parkinson MC, Swerdlow AJ, Pike MC: Carcinoma in situ in boys with cryptorchidism: When
can it be detected?. Br J Urol 1994; 73:431-435.
9. Whitaker, 1970. Whitaker RH: Management of the undescended testis. Br J Hosp Med 1970; 4:25.

4
 Anorectal malformations (Imperforate anus)

Satish Aggarwal

Anorectal malformations comprise a SPECTRUM of congenital malformations in which the anus fails to open
normally on to the perineum. At one end are low malformations where the anal canal is present but covered by
perineal skin or there is a perineal opening discharging meconium (perineal fistula). These are easy to treat by a
single perineal operation without the need for a colostomy. At the other end of the spectrum are severe (or high)
malformations where the rectum ends at or above the pelvic floor muscle and communicates with the genitor-
urinary tract; associated malformations are frequent and treatment is more complex- a colostomy is usually
needed at birth as initial management.

The malformations occur with a multifactorial aetiology. The embryological basis for high malformations is the
failure of the urorectal septum to develop resulting in a recto-urinary fistula in males and recto vaginal fistula in
girls. Mesodermal failure at the perineal mound is responsible for low lesions.

Classification

Anatomical Classification is based on the level of termination of the rectum in relation to the levator ani (pelvic
floor), and the part of urethras into which the bowel terminates as fistula. Following malformation types can occur:

High: Rectum ends above the levator. (Supralevator)

Intermediate: Rectum ends within the funnel of the levator.
Low: Rectum ends below the levator. (Translevator)

The typical malformations in males are:

High: Recto vesical fistula. Recto prostatic fistula

Intermediate: Recto-bulbar fistula
Low: perineal fistula, covered anus, anal stenosis, bucket handle anomaly

Typical female defects are:

High: recto vaginal fistula

Intermediate: Recto-low vaginal fistula, Recto-vestibular fistula
Low: Ano vestibular fistula, anterior ectopic anus.

Normal female anatomy Ano-vestibular fistula Recto-vaginal fistula Cloaca

5
Functional classification:
Alberto Pena proposed a functional classification that is much simpler and is aimed at decision making in
management. According to this the anomalies are divided into two groups:
1. Rectum ending within 1 cm of the skin: Suitable for primary perineal operation to create neo anus.
No colostomy needed.
2. Rectum ending more than 1 cm from the skin: Initial colostomy followed by definitive pull through at
6-8 weeks

According to Pena, in 80% patients the decision for colostomy or primary perineal operation can be taken on the
basis of clinical features and the appearance of the perineum. In the rest a prone cross table lateral film is
required to determine the distance of the rectal pouch from the skin. In these cases the above classification
comes handy to take a decision.

Krickenbeck classification
In 2005 a group of surgeons met at Krickenberg, Germany to simplify the classification. The new classification is
as follows:

Major clinical groups:

Perineal (cutaneous) fistula
Rectourethral fistula
o Bulbar
o Prostatic
Rectovesical fistula
Vestibular fistula
Cloaca
No fistula
Anal stenosis

Rare/ regional variants

Pouch colon
Rectal atresia/stenosis
Rectovaginal fistula
H type fistula
Others

Anatomy of sphincters in anorectal malformations:

The muscular component of continence is formed by levator ani, specially the lower most fibres (also called as
pubo-rectalis sling). Further there are the so called subcutaneous and superficial external sphincters that
surround the rectum and the anal canal. During an operation however, it is not possible to identify the different
components of the external sphincter. Surgically, there is a continuum of vertically oriented striated muscle fibres
from the skin at the anal dimple to the lowermost fibres of levator ani. A mid sagittal incision would bisect these
fibres into right and left halves. This is referred to as striated muscle complex. Aim of surgery is to bring the
rectum through the centre of muscle complex in order to restore the sphincter mechanism. Surrounding the
vertical fibres on either side are para-saggital fibres that lie horizontally and run from the perineal body in front to
the skin behind the anal dimple. The sphincters are well developed in low malformations but are poor in high
malformations.

Incidence: 1 in 5000 (similar incidence for TOF and HD)

Male: female :: 3: 2

Associated malformations:
Incidence: 50-60%
60% are genitor-urinary, 25% vertebral, 20% cardiac, 10% GI
15% have VACTERL / CHARGE association.
Severer the anorectal malformation the higher the incidence of associated malformations

Two most important aspects in the initial management are:

1. Is the case suitable for a primary perineal anoplasty without a colostomy or an initial colostomy followed
by delayed repair is more appropriate? (Best decided at 24 hours of age)

2. Is there any other life threatening association that needs more urgent attention e.g. tracheo-
esophageal fistula, severe cardiac malformation? Therefore, always pass a naso- gastric to rule out
oesophageal atresia and leave it for gastric decompression.

6
Clinical features and pathological anatomy

The topic is discussed separately in boys and girls.

Males:
Absent anal opening at birth.

Examine perineum: look for gluteal fold, natal cleft, and palpate spine/sacrum. Is it a flat bottom? Is there a
dimple at the anal site with pigmentation? Is ano-cutaneous reflex present? Is there a fold of skin under which
you can pass a probe (Bucket handle deformity), is there any mass?, can you see a thin white epithelial
thickening in the median raphe suggests anocutaneous fistula, is there any speck of meconium in the perineum
perineal fistula.

Is there any abnormality of the external genitalia bifid scrotum, hypospadias, and undescended testes? Look for
evidence of meconuria gas or meconium discharge per urethra.

Important: The exact level of anomaly may not be evident at birth because it takes time for the ingested air to
reach the rectum. Sufficient intra abdominal pressure builds up in about 24 hours to overcome the resistance of
the pelvic floor, so that meconium or air could force through a fistula.

If within 24 hours you can see meconium on the perineum low anomaly. Go for perineal anoplasty. No need for
colostomy.

If meconium or gas passed per urethra at any stage indicates high anomaly. Go for colostomy.

Prone Cross table lateral shoot abdominal film (If clinical information at 24 hrs insufficient to decide if a
colostomy is needed).

Technique:
Place a radio-opaque marker at the anal site.
Prone position with pelvis elevated leave in this position for 5 minutes before taking the x-ray (to allow
gas to layer on the meconium)
Dead lateral view centring over the greater trochanter.

Interpretation:
See distance of rectal gas from the marker (take care of magnification).
< 1cm: Suitable for primary repair
> 1cm: Colostomy needed.
.
Indicators of high anomaly (colostomy indicated):
No meconium in the perineum
Flat bottom, absent anal dimple/pigmentation, absent anocutaneous reflex,
Sacral abnormality (or on X-ray)
Meconium in urine (or gas in bladder on x ray)
Suggestion of a pouch colon on X ray (>50% of transverse span)
Associated bifid scrotum, proximal hypospadias, bilateral undescended testes

Indications of low anomaly (suitable for primary anoplasty):

Good perineum, pigmented dimple, anocutaneous reflex
Visible fistula in the perineum
Bucket handle deformity a bridge of skin over the anal site under which an instrument can be passed
and meconium can be seen under the skin.

Final decision will depend on many other factors: birth weight, maturity, and other malformations. It is safer to
open a colostomy in doubtful cases.
Although a prone cross table lateral shoot film is not required in majority, a plain abdominal film should be
obtained in all cases to exclude pouch colon, which is common in northern India. A bowel pouch spanning more
than 50% of transverse span of the abdomen suggests pouch colon. If so diagnosed, the child needs a
laparotomy rather than a simple colostomy.

Females:

Most anomalies are low. Look for the number of openings in the vulva/ perineum

3 openings: Ano-vestibular fistula (Commonest), recto-vestibular fistula, perineal fistula, anterior ectopic
anus
2 openings: Recto-vaginal fistula. (Rarely vestibular fistula with vaginal atresia).

7
1 opening: Common Cloaca

Examine in good light keeping the legs apart. The vestibular opening is usually very small and may be hidden
within the posterior fourchette. When probed the catheter may go posteriorly (ano-vestibular fistula) or superiorly
(rectovestibular fistula). This differentiation may be very subtle but is important in that rectovestibular fistula will
almost certainly require a colostomy while ano-vestibular fistula could be repaired primarily.

Colostomy or primary Mini PSARP?

Common cloaca and rectovaginal fistula always require a colostomy. Claoca will also need emergency evaluation
(US) for obstructive uropathy and distended vagina and often needs vesicostomy / vaginostomy in the same
sitting.

When there are three openings in the vulva the decision is more of individual surgeons choice. The safest option
would be to do a colostomy. However, it is not a dire emergency as the gut is getting decompressed, which may
be aided by calibration of the opening or gentle dilatation with Hegar dilators. The options should be discussed
with parents. While primary repair is definitive, saves the child from a stoma, there is a higher risk of wound
breakdown / infection leading to impaired continence, anal stenosis and need for redo surgery. The authors
current approach for ano-vestibular fistula is a primary PSARP at few weeks of age.

Surgery (colostomy or primary repair) may be carried out as a planned acute within the first few days. If the child
develops abdominal distension or decompression is not adequate, early colostomy is indicated.

Remember: if in doubt do a colostomy.

Colostomy:

High divided sigmoid / descending colostomy is performed through an oblique incision in the left iliac fossa.
Leave good skin bridge between the active stoma and the mucus fistula to facilitate application of stoma bag. .

For cloaca Transverse divided colostomy (distal colon may be needed for vaginal reconstruction)

Sigmoid/descending colostomy is easy to manage as the effluent is well formed, fluid loss and skin excoriation is
less, and it is easy to do a distal washout. The incidence of prolapse is low. Patients with large recto urinary
fistula may leak urine into the distal colon. With sigmoid colostomy there is less chance of hyperchloremic
acidosis as the urine comes out through the mucus fistula without getting absorbed significantly. Moreover,
performing a distal cologram is easier and more informative.

Pitfalls in colostomy

Transverse sigmoidostomy: While intending to perform a right transverse colostomy, a distended sigmoid loop
reaching the right hypochondrium is mistaken fro transverse colon and a stoma is created. This puts the distal
limb on traction and does not leave scope for mobilisation during definitive pull through operation. Distal cologram
will diagnose this accurately. Colostomy transplant at left iliac site is needed before considering a pull through.

Too low colostomy: This is the commonest mistake. The apex of the sigmoid loop is brought out as a stoma
leaving small length distally. The best way to prevent this is to identify the fixed portion of colon i.e. distal
descending colon and then come down along the sigmoid colon and form a stoma at a level that comes on the
surface without tension. This will leave most of sigmoid distal to the stoma, which can be used fro mobilisation
during pull through operation.

Loop colostomy: A loop colostomy is less likely to divert completely. Faecal contamination of the distal limb may
cause repeated urinary infections through a fistula, can cause feculomas, and jeopardise the pull though by
infective complications.

Twisted colostomy: The distally situated stoma brings out faeces while the proximally situated stoma acts as a
mucus fistula. This is a technical mistake during surgery and is of no major consequences provided the mother
gives pre-operative washouts through the mucus fistula only. The author has seen distal washouts being given
through the active stoma because the active stoma was the distally located stoma.

Further investigations during initial admission:

Renal and Spinal Ultrasound: to look for renal malformations, tethered cord
Echocardiography

8
 Chest and spine Xray
Sacral Pena ratio
Chromosomal analysis
US spine MRI if US abnormal

Post op after colostomy

Distal loop washout with saline from day 5. Daily until clear, then weekly
Measure stoma output (if >20ml/kg/day start loperamide)
Monitor urinary sodium (if <10mmol/l add supplement to maintain at >10-40 mmol/l)
Prophylactic trimethoprim 2 mg/kg nocte
MCUG / distal loopogram at 4-6 weeks (cover with antibiotics; no cardiac anomaly: iv gentamycin 2
mg/kg; cardiac anomaly: iv gent + iv amoxicillin (250 mg) followed by oral amoxyl 125 mg 6 hrs later. (If
allergic to Penicillin- iv clindamycin (75mg) followed by oral clindamycin (37.5 mg) six hours later.

Post Discharge pre PSARP

Weekly distal washout, monitor weight, urinary sodium, increase trimethoprim as per weight, parental
support for stoma care.

Definitive Repair (PSARP Posterior Sagittal Ano Recto Plasty) is performed at 8-12 weeks.

Pre-op Distal washouts a day before or until clear

Check distal loopogram available.
Antibiotic on induction.
Consent

Operation in boys:
Under general endotracheal anaesthesia, bladder is catheterised. The patient is placed in prone jack knife
position. Buttocks are spread apart with elastic adhesive tape on each side. A mid sagittal incision is placed from
mid sacrum to just anterior to the anal dimple. Keeping in midline the incision is deepened. The muscle complex
and the parasagittal fibres are identified and confirmed with muscle stimulator. The coccyx may need bisection or
division to access the rectal pouch... The levator ani is divided in midline. Endopelvic fascia is divided to identify
the rectal pouch. The pouch is opened in midline between stay sutures and the fistula identified at the lower end
of the pouch. The fistula is closed from within with a purse string fine vicryl or PDS suture. The anterior dissection
immediately above the fistula is performed in the submucosal plane to prevent damage to the urethra. At about 2
cm from the fistula, the rectum can be mobilised full thickness all around. It is mobilised as much as is needed to
bring it down to the site of neo anus, which should be marked in the beginning of the operation at the anterior and
the posterior limit of the striated muscle complex. The levator is closed behind the rectum. The rectum is then
brought in the centre of the muscle complex and anoplasty is performed by muco cutaneous anastomosis at the
marked site of anus.

If the anomaly is very high and the rectal pouch can not be reached from below, a 28 size chest tube is placed in
the centre of muscle complex and the muscle closure is done around the tube as if the tube is the rectum. The
patient is then turned and a laparotomy performed to identify the rectal pouch and rectovesical fistula. After the
fistula is taken down, the rectum is tacked to the tube passed from below. The tube is then gently pulled in the
perineum bringing the rectal pouch at the skin where a muco cutaneous anastomosis is performed.

Operation for ano vestibular fistula in girls:

The position and anaesthesia are the same. Bladder is catheterised after positioning the patient. Incision is from
mid sacrum to the posterior fourchette. Muscle complex is divided in the midline. The vestibular fistula is held in
multiple stay sutures and a circumferential incision is made around it separating it from vagina in front. The key
step is separating the rectum from vagina. They are intimately adherent and share a common wall for varying
lengths, less in ano vestibular and more in recto vestibular fistula. Once sufficiently mobilised, the perineal body
is reconstructed, location of neo anus is decide as in boys. Anoplasty is performed and wound closed.

Post-op If no laparotomy feed 6-12 hrs later

Urinary catheter for 5 days.
Triple antibiotics for 48 hrs, then treatment dose Cephalexin/ trimethoprim until catheter comes out, then
prophylactic until VUR ruled out.
Nil PR for 14 days.
Dilatation to start at 14 days.

Closure of colostomy:
Performed once anal dilatation to adequate size achieved.
Continue dilatations until closure.
Skin preparation dermagard wipes 3/day. May use barrier applications {Adapt (Hollister), stomahesive
(Squibb)}

9
 Continue dilatation post op for 4-6 weeks.

Regimen for anal dilatation post anoplasty

Use Hegar dilators.
First dilatation at 14 days (10 for low malformations)
First begin with size 8, and increase by one size every week to reach 16-18.

Normal size for age:

1-4 months Hegar 12
5-8 months Hegar 13
9-12 months Hegar 14
13 months + Hegar 16
(be wary of poor standardisation in India. Size 16 of one company may be equal to size 10 of another.)

Post colostomy closure:

Restart dilatations BD at the size stated in op notes
Decrease to daily after one month
Decrease to twice weekly after one month
Decrease to weekly after one month
Stop after a month

CONTROVERSIAL ISSUES

Primary PSARP for high malformations in males:

Some surgeons favour primary PSARP without a covering colostomy in selected cases of recto bulbar fistula. It is
a shade better than the standard approach of colostomy followed by PSARP in that the sensory stimulation for
maturation of anorectal continence mechanism is established immediately after birth, which should lead to better
continence mechanism. The tissue planes are easy to define. The child is saved from a colostomy. However, the
downside is that the anatomy is uncertain because the level of fistula has not been ascertained pre-operatively.
Consequently the blind perineal exploration increases the risk of damage to urethra, seminal vesicles, and
ureters. Also the operation is technically demanding. Careful patient selection is important for anaesthetic safety.

Laparoscopic repair of ARM

Laparoscopic approach has been successfully used to perform / aid repair. Colostomy is opened at birth.
Laparoscopic assisted pull through can be performed at about three months age. The colorectum in the pelvis is
mobilised laparoscopically and the fistula taken down. The urethral end of the fistula is closed with an endo-loop.
Many surgeons even leave the fistula open. The site of anus is decided by identifying the stratified muscle
complex by using a muscle stimulator. A small midline incision is made in the centre of this site and a 10 mm
trocar introduced in the pelvis. The mobilised rectum is pulled down through the port and anastomosed to the
skin.

The advantages of laparoscopic approach are clear visualisation of fistula in the deep pelvis, magnification and
accuracy. There is, however, limited experience and long term data is lacking.
The authors personal opinion favours laparoscopic pull through in a case where a laparotomy is necessary in
addition to posterior sagittal approach cases of rectovesical fistula, recto-bladder neck fistula. For rectobulbar
fistula (the commonest anomaly), the author favours a PSARP.

Anterior Sagittal Anorectoplasty (ASARP) in females

Some surgeons perform the pull through operation in females in lithotomy position using the anterior approach.
The operation is essentially the same as the more frequently used posterior approach. Similar outcomes are
reported. Advantage is that cumbersome posterior position is not required, the dissection is limited to anterior
aspect of the muscle complex, and the abdomen can be opened (if necessary) without a change in the position.
The author has no experience with this approach.

References

1. deVries PA, Pena A. Posterior sagittal anorectoplasty. J Pediatr Surg. Oct 1982;17(5):638-43.
2. Hong AR, Acuna MF, Pena A, et al. Urologic injuries associated with repair of anorectal malformations in male
patients. J Pediatr Surg. Mar 2002;37(3):339-44.
3. Parrott TS. Urologic implications of anorectal malformations. Urol Clin North Am. Feb 1985;12(1):13-21.
4. Pena A. Anorectal malformations. Semin Pediatr Surg. Feb 1995;4(1):35-47.
5. Pena A. Current management of anorectal anomalies. Surg Clin North Am. Dec 1992;72(6):1393-416.
6. Pena A. Management of anorectal malformations during the newborn period. World J Surg. May-
Jun 1993;17(3):385-92.
7. Pena A. Posterior sagittal approach for the correction of anorectal malformations. Adv Surg. 1986;19:69-100.

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8. Pena A, Devries PA. Posterior sagittal anorectoplasty: important technical considerations and new applications. J
Pediatr Surg. Dec 1982;17(6):796-811.
9. Pena A, Hong A. Advances in the management of anorectal malformations. Am J Surg. Nov 2000;180(5):370-6.
10. Pena A, Migotto-Krieger M, Levitt MA. Colostomy in anorectal malformations: a procedure with serious but
preventable complications. J Pediatr Surg. Apr 2006;41(4):748-56; discussion 748-56.
11. Shaul DB, Harrison EA. Classification of anorectal malformations--initial approach, diagnostic tests, and
colostomy. Semin Pediatr Surg. Nov 1997;6(4):187-95.

Cleft Lip and Cleft Palate

Rajeev B. Ahuja, Vybhav Deraje

EPIDEMIOLOGY

Oro-facial-clefting is the most common congenital anomaly of the head & neck and is known to occur in 1 in 500
live births. The incidence is highest in Asians and lowest in Africans and African Americans. Clefts of the lip (CL)
may be unilateral or bilateral, complete or incomplete, left or right sided and may occur with or without cleft palate
(CP). They frequently occur as isolated anomalies but maybe associated with syndromes such as Treacher
Collins syndrome, Apert syndrome, Pierre Robin sequence etcd. The reported distribution according to the type
of cleft is 25% CL alone, 50% CL/P and 25% isolated CP.There is a left sided preponderance in CL. For reasons
unknown there is male preponderance in CL/P whereas isolated CP is more common in females.

ETIOLOGY

The etiology remains unknown, but a multifactorial combination of heredity and environmental factors seems
most plausible. When one sibling has a CL/P, the probability of the next child being affected is 4%. When both a
parent and child are affected, the likelihood of the next child having a CL/P increases to 17%. Other factors
implicated to cause clefting are increased parental age, drug use(phenytoin, steroids) and infections during
pregnancy, smoking during pregnancy or folate deficiency.

Three theories exist which describe how embryological failure or errors result in cleft formation. The Fusion
failure theory suggests that clefts are formed when fusion of facial processes fail. The Mesodermal
penetration theory implicates the lack of neuroectoderm and mesoderm penetration into the bilaminar
ectodermal sheets as a result of which they give way. Newer understanding of the neuroembryology underlines
the Neuromeric theory,according to which, the face can be mapped into genetically determined developmental
zones with defined cellular contents and distinct spatial origins in their precursor tissue units. The occurrence of
clefts is nothing more than an orderly progression of deficiency states in the precursor fields resulting in varying
degrees of absence of soft tissue matrix or bone.

EMBRYOLOGY
th th
Facial development takes place between 4 -10 week of intrauterine life. The boundaries of the primitive mouth
(stomodeum) are the paired mandibular prominences inferiorly, paired maxillary prominences (MxPs) laterally
and the frontonasal prominence (FNP) cranially. These five facial prominences in a human embryo form the adult
facial features. Elevation of the margins of the FNP leads to development of median nasal prominence (MNP)
and the lateral nasal prominence (LNP) on each side. The depressed central region of the nasal placode is called
the nasal pit which forms the external nares.

Development of Upper lip: The MxPs migrate medially and fuse first with the LNP and then with the MNP. The
LNP and the MNP also fuse with each other. The lateral portions of the upper lip are formed from the maxillary
prominences from each side.

Cleft Lip: A unilateral CL results from failure of fusion of the MNP and the MxP on one side. A bilateral CL occurs
due to failure of fusion of the MxP on either side with the globular process (merged MNPs). The initial MxP-MNP
fusion remains intact during the early stages of cleft formation, but the MxP becomes somewhat disconnected
with MNP during its later forward growth resulting in an incomplete cleft.

Development of the Palate: From each MxP, a plate like lateral palatine process grows medially.
Simultaneously, a median palatine process forms from the posterior aspect of the merged MNPs. The fusion of
these three elements begins at the junction of the lateral palatine processes with the median palatine process in
the midline (from the point of the incisive foramen) and proceeds both posteriorly towards uvula and anteriorly
towards alveolus. The portion derived from the median palatine process forms the premaxilla which carries the
four incisors, and is called the primary palate; the lateral palatine processes form the secondary palate.

11
Ossification occurs in the primary palate and the anterior portion of the secondary palate to form the hard palate.
The posterior portion of the secondary palate does not undergo ossification and forms the soft palate.

Cleft palate: Clefts of the primary palate occur anterior to the incisive foramen and result from the failure of
fusion of the lateral palatine process(es) with the median palatine process. Clefts of the secondary palate occur
posterior to the incisive foramen and result from the failure of the lateral palatine processes to fuse with each
other and with the nasal septum. Anomalies of the mesenchymal merging of the palatal shelves can result in
submucous cleft palate (SMCP). There occurs imperfect muscle union (muscular diastasis) across the soft palate
with an intact mucosal surface (zonapellucida), bifid uvula and a notched posterior hard palate.

ANATOMY

Upper lip: The upper lip has a centrally placed Cupids bow with philtral tubercle in midline and two peaks-one on
each side at equal distance from philtral tubercle. There are two symmetrical philtral ridges extending from the
each peak of the Cupids bow to the corresponding base of columella. The philtral groove lies in between the two
philtral ridges. Two equal lateral lip elements extend from philtral ridges to the angle of mouth on each side. The
lip has a pinkish wet vermilion, a relatively darker dry vermilion and a white roll of Gillies at the skin-mucosal
junction. The lip has an outer skin, an inner mucosa and the orbicularis oris muscle in between.

The abnormalities seen in cleft lip are the direct consequences of disruption of the orbicularis oris muscle.

Unilateral Cleft Lip: On the affected side, there is a complete diastasis of the orbicularis muscle. The cleft
orbicularis is abnormally inserted to the columellar base medially and alar base and maxilla laterally, pulling them
apart.

Bilateral Cleft Lip: There is bilateral interruption in continuity of the lip white line, vermilion and orbicularis oris
muscle. The muscle gets aberrant insertion to the alar bases bilaterally, pulling them apart laterally. The
premaxilla is attached only to the nasal septum and the vomer.

Cleft lip nasal deformity: The cleft side alar cartilage is splayed out & flared. The angle between the medial and
lateral crus thus becomes obtuse. Caudal edge of nasal septum is deviated towards the normal side. Columella
on the cleft side appears shorter as it extends laterally to a dipped area in the rim of the nostril. The alar base is
usually pulled downward, backward and laterally. The nostril sill on the cleft side is thus larger and the alar-facial
angle is obtuse.

Palate: The palate is divided into hard palate (anterior 2/3rd) and soft palate (posterior 1/3rd). The premaxilla is
situated anterior to the incisive foramen. The anterior portion of the hard palate is formed by the palatine process
of maxilla while the posterior portion is formed by the horizontal plate of the palatine bone. The greater & lesser
palatine neurovascular bundles pass through the greater & lesser palatine foramina respectively which are
located in the posterolateral portion of the palatine bone. Both the palatine process of maxilla and the palatine
bones join the vomer.

12
The muscles in the velopharyngeal region play a role in swallowing, speech production and auditory tube
function. Muscles that insert into the palate are tensor velipalatini, the levatorvelipalatini, the
platoglossus,palatopharyngeus and musculus uvulae. These muscles form the opposing slings that meet in the
midline in the soft palate raphe. The muscle fibres in the soft palate are oriented transversely with no significant
attachment to the hard palate. The levator muscle is the critical muscle involved in the velopharyngeal closure. Its
sling suspends the soft palate from the cranial base and the contraction causes elevation &retrodisplacement of
the velum during speech and swallowing. The tendon of tensor hooks around the hamulus forming a 90 degree
turn as it enters the soft palate. Its fibres are attached to the eustachian tube. Besides tensing the velum, its
contraction dilates the eustachian tube and helping in the middle ear drainage.

Cleft Palate: Clefts of the hard and the soft palate vary in degree from bifid uvula at the posterior end of the soft
palate to a complete cleft in the roof of the oral cavity. Instead of the muscle fibres being transverse in orientation,
they become oriented in an anteroposterior direction converging along the medial border of the cleft. They get
abnormally inserted into the posterior and medial edge of the hard palate.

CLASSIFICATION
Several classification systems have been proposed over the years arranged along morphologic, anatomic, and
embryonic guidelines. In the Indian subcontinent, the Nagpur modification of Davis and Ritchies classification is
commonly used:
Group I: Cleft lip only (Pre alveolar clefts)
Group Ia: Cleft of lip and alveolus
Group II: Cleft palate only (Post alveolar clefts)
Group III: Cleft of lip, alveolus and palate (continuous pre alveolar + post alveolar)
Group I and III clefts are subdivided into unilateral / bilateral, and Group II is subdivided into clefts of hard and
soft palate.

FUNCTIONAL DEFICITS

Although CL/P may not be life threatening, many functions such as feeding, speech, middle ear ventilation,
hearing, maxillofacial growth, dentition, and occlusion can be grossly disturbed due to structures involved. With a
cleft in the alveolus and palate, the infant is unable to press the nipple and suckle the breast properly because of
inability to generate negative pressure in the mouth due to escape of the air through the cleft. Nasal escape of
the air contributes to gross distortions in speech.There may be nasal regurgitation of food due to common nasal-
oral chamber. Many cleft palate patients develop otitis media because of abnormal functioning of the Eustachian
tubes. This may grossly affect the normal hearing which can have grave impact on learning speech as well. A
cleft of the lip alone is operated for cosmetic reasons only.

TEAM APPROACH

The complexities of cleft lip and palate therapy make it necessary for a variety of clinicians to collaborate on the
planning and the delivery of the treatment. A multidisciplinary team approach is ideal where the plastic surgeon is
the main cog responsible for surgical repair and the overall management of the deformity. The orthodontist takes
care of maxillary arch collapse, misalignment of dental arches, malocclusion and dental problems. The speech
therapist is a vital member of the cleft team who assesses and trains these children for development of good
comprehensible speech. ENT surgeon takes steps to prevent any hearing problems. Pathologist, pediatrician,
radiologist, prosthodontist, psychologist, cleft nurse, social worker as well as a photographer complete the cleft
team. All contribute to the care of the cleft individual from infancy to adulthood.

13
TIMING OF SURGERY

There is no agreement on the ideal timing and the ideal technique of repair. More than one treatment plan is
acceptable. The plan usually followed is shown in Table 1.

BIRTH

PRESURGICAL NASOALVEOLAR MOULDING (1-6 weeks)

DEFINITIVE LIP REPAIR,GINGIVOPERIOSTEOPLASTY & PRIMARY RHINOPLASTY (3-6

months)

PALATE REPAIR( 12-18 months)

ALVEOLAR BONE GRAFT (7-11 years)

DEFINITIVE RHINOPLASTY & ORTHOGNATHIC SURGERY (after 17 years)

Table 1.
st
Presurgical orthodontic treatment is begun in the 1 week after birth with the maximum response occurring during
the first six weeks. Whenever presurgical orthopedics is not available and if the child is older than 3 months, a
definitive lip repair with nasal correction(limited open rhinoplasty) is done because presurgical orthopedics is
usually not effective after 3 months.Alveolar closure is also accomplished along with the lip repair by using the
local mucoperiosteal flaps from the alveolar segments (gingivoperiosteoplasty). Palatoplasty is done at the age of
12-18 months (before the baby begins to speak). Timing of alveolar bone grafting relates to the eruption of the
central incisor and canine. It is determined by the orthodontist. This is usually at the age of 711 years. Teeth
are brought into final alignment by orthodontist in tandem with a prosthodontist who replaces the missing teeth.
Definitive rhinoplasty and /or orthognathic surgery, if required, are carried out upon skeletal maturity (after 17
years of age).

PRE-OPERATIVE PARENTAL COUNSELING

Feeding Advice: Babies with only CL can usually suckle well by latching on with the alveolus and palate to suck
rather than using the orbicularis muscle as in the normal infant. They can be breast fed. Expressed breast milk
can also be fed to the baby with a spoon, which is mandatory in patients with cleft lip and palate. The hole in the
nipple can be increased in size by making a cross cut so that the milk flows out easily on its own rather than the
child requiring to press and suckle it. The simple and best method is spoon feeding. The mother should to be
taught that feeding needs to be done with babys head kept up (minimum 45 degrees) and the milk should be
poured from the spoon to the back of the tongue so that it flows easily down the pharynx without escaping
through the nasal passage. This prevents aspiration /coughing/choking. Such children also swallow a lot of air
while being fed. Frequent burping is required after every feed.

ENT checkup has to be done routinely as children with cleft palate are likely to develop recurrent middle ear
problems. If required, a small tube (Grommet) would be placed in the tympanic membraneto prevent damage to
the eardrum.

Speech development: Parents should be well informed that the children with cleft palate may speak differently
from other children. Speech problems occur because of incorrect speech patterns learned before palate repair
and /or the repaired soft palate is short and not mobile enough to achieve velopharyngeal closure. Nasal escape
of the air and the sound occurs producing an incomprehensible speech. Such children would require prolonged
speech therapy after the palate repair is accomplished. Few children may need further surgical interventions for
improvement in their speech (pharyngoplasty operation), aesthetics and alignment of dental arches.

Immunization and weight record: The child must be immunized as per the age schedule. The monthly weight
record needs to be maintained.
The prognosis regarding the number of stages / sequence of proposed surgical interventions as per the deformity
/ time duration involved / need for frequent hospital visits / possibility of surgical interventions till adulthood / final
cosmetic and functional outcome etc. should be clearly explained to parents. Monthly follow up is advised to
confirm that the baby is thriving well.

14
PRESURGICAL ORTHODONTICS
Presurgical maxillary orthopedics attempts to bring the maxillary cleft arches and the protruding premaxilla in
alignment before a definitive lip and anterior repair is accomplished. The simplest technique to achieve this is by
gentle pressure on the protruding premaxilla by the mother. External taping (nonsurgical lip adhesion) by a strip
of micropore tape placed across the cleft is another simple procedure. Nasoalveolar molding also accomplishes
the retraction of premaxilla. It takes advantage of the high degree of plasticity of the nasal cartilages during the
first six weeks after birth. A combined technique for simultaneous nasal and alveolar molding is employed. Acrylic
intraoral molding plate is constructed and modified at weekly intervals to gradually align the alveolar segments
and achieve narrowing of the alveolar gap. The nasal stent arising from the intraoral molding plate is also
modified as it lifts the nasal tip.

GOALS OF SURGERY
Four major goals of surgery on an infant with CL/P are: a) to reconstruct the features of the lip and nose for
maximum aesthetics, b) to separate the oral and the nasal cavities, c) to reconstruct the functional speech
mechanism and d) to encourage adequate normal growth of the facial skeleton. Aim should be to obtain an
anatomical as well as functional repair.

TECHNIQUES OF REPAIR
Unilateral cleft lip: Many normal anatomical landmarks and clues are present on the medial and lateral cleft lip
segments which aid in surgery (Fig.4). The principle is to lengthen the cleft side so that it equals the vertical
dimensions of the non-cleft side. A tissue rearrangement is designed to borrow tissue from the lateral element of
the cleft and introduce it into the medial element.
The most commonly used flap designs can be categorized as a) triangular flap technique and b) rotation
advancement flap technique.

(Fig.4)
Point 1: Lowest point in the arch of Cupids bow, midline of lip /
philtral tubercle
Point 2: Peak of Cupids bow on the non-cleft side. Point 3:
Proposed peak of Cupids bow on the cleft side (distance from 1 to
2)
Point 4: Midpoint of the columella
Point 5: Base of the columella on the non-cleft side.Point 6: Base
of the columella on the cleft side.
Point 7: Alar base on the cleft side
Point 8: Alar base on the non-cleft side
Point 9: Point of disappearance of white roll on the vermilion
cutaneous junction on the cleft side.

Rotation advancement technique

Originally described, and later modified by Millard himself, this technique is popularly known as a cut as you
go technique (Fig.5). The incisions are so designed that the flap on the medial lip segment rotates inferiorly
and a triangular flap designed on the lateral lip segment is advanced under the columella into the defect
created by the movement of the rotation flap. The technique introduces tissues in the upper third of the lip.
The scars are placed in the more anatomically correct position along the philtral column on the cleft side.
Nasal deformity can be corrected simultaneously. It is not an easy method for a beginner to master. Wide
clefts present the greatest challenge to the rotation advancement repair. Insufficient lengthening on the cleft
side is sometimes a problem especially when there is marked discrepancy in height between the cleft and
the non-cleft sides.

(Fig.5)

15
 Triangular flap technique
It introduces tissue in the lower third of the medial segment and has the advantage of producing a pouting
tubercle (Fig.6). It is suitable for all kinds of incomplete and complete clefts (both narrow and wide). It is
comparatively easy to learn and teach as it is based on definite geometrical markings, and permits relatively
inexperienced cleft lip surgeon to obtain acceptable result. Simultaneous nasal correction is possible. The
disadvantages are that the philtral ridge on the cleft side is crossed by the final scar and no changes /
alterations are possible once the incisions have been made in the lip segments. Repaired lips may become
slightly longer than the cleft side which would require secondary surgical correction.

(Fig.6)

Bilateral cleft lip: More than a dozen techniques and their modifications have been described for complete
bilateral lip repair. The technique most commonly used previously wasVeau III straight line repair or its minor
variations. The major drawback of this procedure was lack of muscle to muscle approximation. With increasing
attention to muscular closure in the unilateral deformity, reports began to underscore the importance of
orbicularis oris repair in bilateral clefts.

After elevation of the prolabial flapthe lateral white-roll-vermilion-mucosal flaps are incised and orbicularis muscle
bundles are dissected bilaterally to be approximated in the midline behind the flap (Fig.7). The white roll could be
created using the native prolabial white roll or from the lateral segments.This is followed by alveolar
gingivoperiosteoplasty. Nasal deformity is also corrected primarily by semi open rhinoplasty through bilateral rim
incisions.

(Fig.7)

Cleft lip type nasal deformity

The major corrections required are alar cartilage repositioning and septal deviation. Primary rhinoplasty by a
Limited Open approach addresses both these issues where bilateral rim incisions are given, both the alar
cartilages are dissected free from the overlying skin and along pyriform aperture andstitches are applied to bring
the dome of alar cartilages closer to each other (Fig.8). Anatomic repositioning of the orbicularis muscle and the
alar cartilages helps to reorient the septum.

(Fig.8)

16
Cleft palate:
Veau-Wardill-Kilner operation (V-Y Pushback repair)(Fig.9)
The essence of the pushback repair is V to Y closure on the hard palate to achieve an increase in the
anteroposterior length of the palate at the time of primary palatoplasty. Tendon of tensor palatini is unhooked /
freed from around the hamulus. The greater palatine neurovascular bundle which emerges through the
posterolateral hard palate forms the pedicle of the mucoperiosteal flaps on either side. The levator muscles are
detached, reoriented and sutured either end-on or in an overlapped position. The nasal tissue is released and left
open. Although V-Y lengthening gains length, large open areas are left anteriorly and on the nasal surface. As
these raw areas close by contraction, a good deal of the length gained at surgery is lost by secondary
contraction. These shortcomings have been dealt with by the two flap palatoplaty technique described by
Bardach.

(Fig.9)

BardachsTwo flap palatoplasty(Fig.10)

The relaxing incisions are given along the alveolar margins to the edge of the cleft. It is often possible to close
much of the lateral incision and minimize raw areas. Muscle is completely freed from both the nasal and oral
mucosa followed by midline repair of the nasal layer followed by intra-velar-veloplasty and closure of oral
mucosal layer.

(Fig.10)

Intra-velar-veloplasty
Abnormal insertion of levatorvelipalatini muscles on the posterior border of the hard palate is detached, the
muscle bundles are dissected free from the oral and the nasal mucosa, reoriented in the transverse direction and
overlapped to reconstruct the levator sling. Release of tensor tendon just medial to the hamulus facilitates this
midline overlap to provide appropriate tension on the repair. Excellent speech outcomes have been reported with
this technique.

POST-OPERATIVE CARE
Cleft lip surgery: Spoon feeding can be resumed 4-5 hours after the surgery. Infants can resume breast feeding
after wound healing. Elbow restraints/splints (started preoperatively) are continued post-op for 3-4 weeks. The
arms are splinted with elbows extended to prevent the child from rubbing, scratching or manipulating the wound
causing accidental disruption of the repair. Parents should be informed that the lip scars would feel firm for 5-6
weeks after the repair. Gentle massaging of the scar facilitates its softening.

Cleft Palate Surgery: Palatoplasty patients must be monitored in the recovery for few hours to watch for any
respiratory difficulty, adequate oxygenation and bleeding. Palate repair acutely reorganizes the childs airway.
Sudden narrowing coupled with soft palate oedema and bleeding may partially obstruct the airway causing
respiratory insufficiency in acute postoperative period especially with push-back techniques. A silk stitch through
the tongue which is loosely taped to the cheek postoperatively can be lifesaving in emergency. Traction on this
stitch allows the tongue to be pulled forward without use of nasal or oral airway. Spoon feeds of clear liquids are
usually allowed 6-8 hours after surgery.Feedings are followed by water to clear the food particles. Liquid diet is

17
continued for two weeks after which semisolids are allowed. Arm restraints are removed after 3-4 weeks and a
normal diet is resumed. The patients are sent to speech therapist after four weeks of repair. Several sucking and
blowing exercises, speech stimulation and training is imparted which would require active cooperation from
parents. If the childs speech does not progress satisfactorily, active steps would need to be taken.

COMPLICATIONS
Complications after lip repair could be bleeding, wound infection and dehiscence. The wound may disrupt due to
excessive tension on the suture line or trauma. Infection could initiate or complicate the problem. This may heal
secondarily giving a bad stretched scar or may necessitate a redo which should not be attempted till entire
induration has subsided.
Complications after palate repair include respiratory problems / airway maintenance, bleeding, infection,
dehiscence and oronasal fistula. Airway problem (see above) with bleeding can be life threatening. Bleeding at
the conclusion of surgery must be controlled as it would become worse as the child awakens and the effect of
adrenaline weans off. Bipolar cautery, suture ligatures, adrenaline soaked gauze packs and sustained pressure
on the hard palate all can be employed to achieve haemostatsis. Dehiscence due to injury in first 2-3 weeks can
be repaired immediately. Immediate repair for gradual breakdowns due to inflammation and infection is not
advisable. Tissues should be allowed to settle for 6 months before repair is contemplated. Oronasal fistulas
become a source of persistent nasal air loss, nasal regurgitation, distorted articulation and malodorous breath.
Healing process is often accompanied with diminution in the size of the fistula. Soft palate fistula can be excised
and the defect closed primarily in 2 layers. Persistent hard palate fistulas require double layer closure with large
oral mucoperiosteal flaps 6 months after palatoplasty.

Bibliography

1. McCarthy. Joseph G. Plastic Surgery.1st edn. Philadelphia: W. B. Saunders Co; 1990: Vol 4;2451-2921.
2. Mathes Stephen J.Plastic Surgery.2ndedn. Philadelphia: Elsevier Inc;2006: Vol 4;1-364.
3. Neligan Peter C.Plastic Surgery.3rd edn. London: Elsevier Inc;2013: Vol 3;503-670.
4. Hopper Richard A. Cleft lip and palate: embryology, principles, and treatment. Charles HThorne,K. C. Chung, A
Gosain, G. C. Gurtner, B. J.Mehrara et al. (Eds.), Grabb and Smiths Plastic Surgery, 7th Ed. Philadelphia:
Lippincott-Williams,2014:173-199.
5. Sawhney C.P.Geometry of Single Cleft Lip Repair.Plastic & Reconstructive Surgery,1972;49(5):518-521.
6. Ahuja R.B. Primary Rhinoplasty in Unilateral Cleft Patients: The Limited Open Approach and Other Technical
Considerations.The Cleft Palate-Craniofacial Journal,2006; 43(4):492-8.

Urethral Injuries

Iqbal Singh

SURGICAL ANATOMY: The male urethra is a tubular structure extending from the bladder neck to the external
urinary meatus at the tip of the glans penis. It has four components which are named (from proximal to distal), the
prostatic, membranous, bulbar and penile urethra. The male urethra is divided into the anterior and posterior
urethra. Posterior urethra consists of prostatic urethra and the membranous urethra while
anterior urethra includes bulbar and penile urethra.The prostatic urethra extends from the bladder neck to the
verumontanum and is compressed on either side by the lateral lobes of the prostate, giving it a slit-like
configuration. The verumontanum is a small hillock of tissue indented at its crown by a pit called the utriculus
masculinus which marks the proximal extent of the external urethral sphincter and is an important landmark for
urologists performing transurethral resection of the prostate. The membranous urethra lies just distal to the
verumontanum and is located where the urethra penetrates the pelvic floor and it is the usual site of urethral
rupture at the time of a pelvic fracture, its course runs from the apex of the prostate to the perineal membrane,
spanning an average length of 2-2.5 cm. It is the primary location of continence as a consequence of the
surrounding pelvic floor musculature and external urethral sphincter. The bulbar urethra extends from the
membranous urethra to the penoscrotal junction and is located anteriorly within the corpus spongiosum. The
penile urethra is stretches alomg the length of the penis, lies flattened anteroposteriorly, but distends when filled
with fluid distally it becomes dilated within the glans penis where it is called navicular fossa.

The female urethra is around 23 cm long, extending from the bladder neck to the external urethral meatus.
Continence is maintained by the external striated urethral sphincter, which in women extends for almost the
whole length of the urethra. There is extra support from the surrounding pelvic floor musculature. In contrast to
men, the female bladder neck has little role in the maintenance of continence. The mid urethral region in the
females is urodynamically the zone of maximal urethral closing pressure (MUCP).

INTRODUCTION
Pelvic fractures causing disruption at the bulbomembranous junction is by far the main etiology of strictures in the
1
posterior urethra. Stein et al looked retrospectively at 2,589 patients who underwent urethroplasty procedures
from 2000 to 2011 in the USA, Italy, and India. They reported vehicular accidents as a cause for nearly 36% of

18
 2
urethral strictures in India, vs. 15% in a cohort from the USA and Italy. Singh et al reported that traumatic
etiology was present in 11.9% of total stricture cases, pelvic fracture was the most common cause, and posterior
urethra was the most common site of involvement (60% of traumatic cases).

AETIOLOGY OF URETHRAL INJURIES

Blunt trauma (Vehicular accidents, Fall astride (straddle) e.g. on bicycle, fences, inspection covers and kicks in
the perineum. Sexual intercourse (Penile fractures and Urethral intraluminal stimulation); Penetrating trauma (
Gunshot wounds, Stab wounds, Dog bites, External impalement, Penile amputations); Constriction bands
(Paraplegia) and Iatrogenic injuries (Endoscopic instruments, Urethral catheters/dilators).

THE AMERICAN ASSOCIATION FOR SURGERY AND TRAUMA (AAST) GRADING: The AAST grading
emphasizes the degree of disruption and the degree of urethral separation. It divides urethral injuries into the
following five types:

AAST-URETHRA INJURY SCALE

Table adapted from http://www.aast.org/library/traumatools/injuryscoringscales.aspx#urethra
Grade* Injury type Description of injury
I Contusion Blood at urethral meatus; RGU normal
II Stretch injury Elongation of urethra without contrast extravasation on RGU
III Partial disruption Contrast extravasation on RGU at injury site with visualization in the bladder
IV Complete disruption Extravasation of contrast on RGU at injury site without visualization in the
bladder; <2cm of urethra separation
V Complete disruption Complete transaction with >2 cm urethral separation, or extension into the
prostate or vagina
*Advance one grade for bilateral injuries up to grade III.

3
Goldman classification of urethral injuries is a more widely accepted classification than the one proposed by
the American Association for the Surgery of Trauma (AAST). The Goldman classification is based on anatomical
location of the urethral injury and was initially proposed by Colapinto and McCallum but later modified to include
4,5
type IV, IVa and V injuries.
3
Classification
Type I: Stretching of posterior urethra due to disruption of puboprostatic ligaments, with intact urethra.
Type II: Posterior urethral injury above urogenital diaphragm
Type III: Injury to membranous urethra, extending into proximal bulbous urethra (i.e. with laceration of
urogenital diaphragm)
Type IV: Bladder base injury involving bladder neck extending into the proximal urethra internal sphincter is
injured, hence potential for incontinence
Type IVa: Bladder base injury, not involving bladder neck (cannot be differentiated from type IV radiologically)
Type V: anterior urethral injury (isolated).

POSTERIOR URETHRAL INJURIES

Etiopathogenesis: Urethral disruption injuries typically occur in conjunction with multisystem trauma from
vehicular accidents, falls, or industrial accidents. Urethral injuries may be partial or complete disruption of the
urethra. Posterior urethral injuries are almost exclusively associated with pelvic fractures and occur between 1.5
6,7
and 10% of pelvic fractures; concomitant bladder injuries are present in 15% of such urethral injuries. Fractures
of the anterior pelvic ring or pubic diastasis are almost always present when urethral disruption is encountered.
The highest risk of urethral injury is in straddle fractures with a concomitant diastasis of the sacroiliac joint,
8
followed by straddle fracture alone, and a Malgaigne fracture. Because the posterior urethra is densely adherent
to the pubis via both the urogenital diaphragm and the puboprostatic ligaments, the bulbo-membranous junction
is more vulnerable to injury during pelvic fracture than is the prostate-membranous junction. In children, injuries
are more likelyto extend proximally to the bladder neck because of the rudimentarynature of the prostate.

Diagnosis: Blood at the urethral meatus is the most common finding, although highly variable, present in 37-
9
93%. Other findings include inability to urinate, perineal/genital ecchymosis, palpably full bladderand/or a high-
riding prostate. Meatal blood loss is present in 98% of posterior injuries and in 75% of anterior injuries. Due to the
findings of high-riding prostate or a butterfly perineal hematoma may be absent, urethral disruption is detected
when a urethral catheter cannot be placed or when it is misplaced into a pelvic hematoma.

Females may also develop proximal urethral avulsion injuries, although much more rarely than males; A female
urethral injury should be suspected from the combination of a pelvic fracture with blood at the vaginal introitus,

19
vaginal laceration, haematuria, urethrorrhagia, labial swelling and/or urinary retention. Vaginal examination is
indicated in all female patients with pelvic fracture to assess vaginal lacerations. Direct urethroscopy over
urethrography may be more useful in the initial evaluation of females with suspected urethral injury.

Initial Management:
When blood at the urethral meatus following pelvic trauma merits an urgent retrograde urethrogram to rule out
urethral injury. Blind catheter passage prior to retrograde urethrogram should be discouraged however in the
acute setting of a partial urethral disruption, a single gentle attempt with a well-lubricated catheter may be
attempted by an experienced surgeon/urologist if successful and if blood is present a pericatheter retrograde
urethrogram can be performed to identify any potential missed urethral injury.
Suprapubic Cystostomy.Immediate suprapubic tube placement remains the standard of care in men with
posterior urethral injuries.

Definitive Management:

Immediate Open Reconstruction: Immediate anastomotic reconstruction of posterior urethral disruption injuries
in men is discouraged due to poor outcomes in terms of higher rates of impotence and incontinence, stricture
formation, and blood loss (Webster et al, 1983; Koraitim, 1996). However in female urethral disruption with pelvic
fracture, immediate primary repair, or urethral realignment over a catheter can be attempted so as to minimise
urethrovaginal fistulas or urethral obliteration. Concomitant vaginal lacerations should be repaired to prevent
vaginal stenosis. Delayed reconstruction is challenging in women due to a shorter female urethra (about 4 cm)
less amenable for mobilization during an anastomotic repair when embedded in scar.(Podesta, 2001) however,
these authors found that a suprapubic approach with partial pubectomy provides excellent exposure enabling
female bladder neck reconstruction.

Primary Realignment (PR) & Cystoscopy:. Flexible cystoscopy is an option to diagnose (and manage) an
acute urethral injury. Cystoscopy can also distinguish between incomplete and complete rupture as it is easy and
quick to perform and can be done in a supine position and it may allow a guidewire to be passed into the bladder
for facilitating early catheterization. An attempt at primary realignment of the distraction with a urethral catheter
may be attempted in hemodynamically stable patients, either acutely or within several days of injury. Simple
passage of a coud catheter antegrade from an anterior cystotomy to the urethral meatus, then tying it to another
catheter that is drawn back into the bladder is feasible. I should avoid prolonged attempts at endoscopic
realignment in patients with pelvic fracture associated urethral injury (PFUI). Patients undergoing PR of PFUI
may be benefitted in a subsequent urethroplasty if necessary, which may be more amenable as compared to
patients undergoing SPC diversion alone.

Some Techniques used for primary realignment:

Simple passage of a catheter across the defect. This is feasible only in few cases and in partial ruptures
only.
Endoscopically assisted catheter realignment using flexible, rigid endoscopes, and biplanar fluoroscopy.
Use of interlocking sounds (''railroading'' or magnetic catheters to place the catheter. This is an open surgical
technique used for posterior urethral injury, where the sound is passed per urethra from below as well as
through the bladder urethra is aligned and repaired over a catheter.
Pelvic hematoma evacuation and dissection of the prostatic apex (with or without suture anastomosis) over a
catheter.
Catheter traction or perineal traction sutures to pull the prostate back to its normal location.
Traumatic posterior urethral injury and early realignment using magnetic urethral catheters.
Retrograde and anterograde flexible cystoscopy may be used, although prolonged endoscopic realignment
attempts risk infection of the pelvic hematoma and thus is not routinely recommended. The urethral catheter
is generally removed after 4 to 6 weeks while retaining a suprapubic catheter.Many patients despite
adequate urethral realignment, develop posterior urethral stenosis. In case patients void satisfactorily
through the urethra, the suprapubic catheter may be removed 7-14 days later. Primary realignment may
allow healing without stricture. If realignment is unsuccessful and SPC has been placed, both EAU (2014)
and AUA (2014) guidelines state that delayed primary urethroplasty can be performed up to 14 days after
the injury (as the fibrotic process has not yet begun so as to avoid extended duration of SPC), provided
10
thepatient has a short defect and can lie in the lithotomy position.

The EAU recommends treating posterior urethral distraction defects via a deferred urethral repair at a minimum
of 3 months after trauma. This delay allows time for the healing of orthopaedic injuries, absorption of pelvic
haematoma, descent of the bladder and prostate to more anatomical positions, stabilisation of the scar tissue,
and for the patient to be able to be placed into the lithotomy position

Incomplete urethral tears are best treated by stenting with a urethral catheter.Agentle attempt to place a urethral
catheter should be done, radiographic confirmation of adequate positioning is imperative. Open exploration with
realignment incases of high-riding or pie-in-the-sky bladder or associated bladder neck tear in males can be
done. Associated rectal injuries require open exploration, repair, irrigation, and placement of drains. Thus the

20
timing of the intervention may be : Immediate: < 48 hours after injury; Delayed primary: 2 days to 2 weeks after
injury and Deferred: > 3 months after injury

DELAYED RECONSTRUCTION (CONVENTIONAL URETHROPLASTY):

In posterior urethral disruption the rupture defect between the two severed ends fills with scar tissue, resulting in
a complete lack of urethral continuity. This separation is really not a stricture as it is a true urethral rupture defect
filled with fibrosis. At 3 months, scar tissue at the urethral disruption site is stable enough to allow posterior
urethroplasty to be undertaken safely, provided that associated injuries are stabilized. SPC drainage should be
maintained until the associated injuries have healed and patient can be appropriately positioned for the
reconstructive procedure.

Preoperative Evaluation: Before the reconstructive procedure is planned, imaging studies are necessary to
delineate the characteristics of the urethral rupture defect. A cystogram and retrograde urethrogram should be
obtained simultaneously (up-and-down-o- gram). MRI may be useful to estimate the exact length of the urethral
gap, the degree and direction of prostatic displacement, the degree and extent of fibrotic tissue and to reveal
false paraurethral tracks.

Endoscopic Treatments: Endoscopic treatments like optical/direct-vision internal urethrotomy ( cutting through
the pelvic scar to provide a channel between the two ends of the avulsed urethra cut-to-the-light procedure)
should bereserved for selected short urethral stenoses and partial distraction injuries for which early
catheterization can achieve urethral continuity. If preoperative evaluation indicates defects >1 cm endoscopic
procedures may be ineffective and have no advantage.

Surgical Reconstruction: Open posterior urethroplasty through a perineal anastomotic approach is the
treatment of choice for vast majority of urethral distraction injuries because it definitively cures the patient without
the needfor multiple procedures.

SOME TROUBLE SHOOTING POINTS:

1. Care must be taken to carefully and meticulously excise all fibrotic tissue from the proximal urethral margin
until at least a 28-Fr bougie passes without resistance.
2. The bulbar urethra should be anastomosed in a tension-free manner to the prostatic/membranous urethra.
3. In most patients, posterior urethral anastomosis can be successfully achieved through a perineal approach
alone. Adjunctive manoeuvres such as corporeal separation, inferior pubectomy, corporeal rerouting, may
beimplemented if direct anastomosis proves difficult.
4. In cases with (extensive gaps/severe fibrosis/fistula/prior failed anastomotic urethroplasty/ associated
bladder neck injury)an alternative combined progressive abdomino-perineal approach or PAPA (with or
without total/partial removal of the symphysis pubis) or a staged procedure may be helpful.
5. Staged procedure- marsupialisation/lay opening of urethra with perineal urethrostomy, and delayed repair
with a graft or flap 3 months after the injury if adequate mobilization is not feasible during the initial
surgery. Second stage closure of the laid open marsupialised urethra can be done using the modified
Johansons repair by using the buried skin principle around the urethral plate.

COMPLICATIONS OF URETHROPLASTY
1. Erectile Dysfunction. Some degree of impotence is often noted in up to 82% of patients with pelvic fracture
and urethral distraction injury.(Flynn et al, 2003)The etiology is multifactorial and variably attributed to
cavernous nerve injury, arterial insufficiency, venous leak, and direct corporeal injury. (Narumi et al, 1993;
Munarriz et al, 1995; Shenfeld et al, 2003). At-risk patients undergo preoperative penile arterial duplex
Doppler studies to identify candidates suitable for initial penile revascularization.
2. Recurrent Stenosis. After posterior urethroplasty, 5-15% of patients may have recurrent stenosis at the
anastomosis. (Mundy, 1996; Flynn et al, 2003; Koraitim 2005; Cooperberg et al, 2007). Endoscopic treatment
(e.g., with direct vision internal urethrotomy) is often successful in this setting because the majority of fibrotic
tissue has been eliminated.
3. Incontinence. Incontinence rates after reconstruction are low <4%, (Koraitim, 2005).Urinary continence after
urethral distraction is the rule rather than the exception, despite destruction of the external sphincter from
either the injury itself or repair.

Thus clinicians should monitor patients for complications (e.g., recurrent stricture, erectile dysfunction and
incontinence) for at least one year following urethral injury.

ANTERIOR URETHRAL INJURIES

Etiopathogenesis: Anterior urethral injures may be blunt (e.g., straddle injuries, where the urethra is crushed
between the pubic bones and a fixed object) or penetrating where the urethra may be lacerated, crushed, or
disrupted. In contrast to posterior urethral distraction, anterior injuries are most often isolated. The majority occur
after straddle injury and involve the bulbar urethra, which is susceptible to compressive injury because of its fixed
location beneath the pubis. As with posterior urethral injury, a high index of suspicion must be maintained in all
patients with blunt or penetrating trauma in the urogenital region, and urethrography should be performed in any
case of suspected urethral injury. Clinical signs of anterior urethral injuries include blood at the meatus, perineal

21
hematoma, gross hematuria, and urinary retention. In severe trauma the Buck fascia may be disrupted, resulting
in blood and urinary extravasation into the scrotum. The primary morbidity of straddle injury is urethral stricture,
which may become symptomatic even years later.

Initial Management: Armenakas and McAninch (1996) proposed a simple, practical classification scheme
dividing anterior urethral injuries on the basis of radiographic findings into (i) Contusion, (ii) Incomplete
disruption, and (iii) Complete disruption. Contusions and incomplete injuries can be treated with urethral catheter
diversion alone.

For penetrating injuries to the anterior urethra, both the EAU and AUA recommend open surgical repair,
except when there are other life-threatening injuries. The urethral ends are spatulated and an end-to-end
anastomosis is made. If an anastomotic urethroplasty cannot be performed, typically if the disruption is >23 cm
long in the bulbar urethra and >1.5 cm in the penile urethra, then the urethra should be marsupialised/lay open,
and delayed repair with a graft or flap can occur at 3 months after the injury.

For blunt trauma to anterior urethra, both the EAU (2014) and AUA (2014) recommend suprapubic or urethral
catheter placement and delayed treatment, as the extent of injury is not easy to document. Initial SPC continues
to be the accepted standard of care for major straddle injuries involving the urethra (Park and McAninch, 2004);
however, primary anterior urethral realignment has shown promising results with respect to stricture rate and
erectile dysfunction in patients with straddle injuries of lesser magnitude (Ying-Hao et al, 2000; Yu et al, 2007).
Primary repair should not be undertaken if the patient is unstable, the surgeon lacks expertise in urethral surgery
or in the setting of extensive tissue destruction or loss. Debridement of the corpus spongiosum after trauma
should be limited because corporeal blood supply is usually robust, enabling spontaneous healing of most
contused areas. Urinary diversion is maintained for 2 and 3 weeks for partial and complete ruptures, respectively.
Delayed Reconstruction: Before any planned procedure, a retrograde urethrogram and voiding cystourethrogram
should be obtained to define the site and length of the obliterated urethra clearly. Urethral ultrasound examination
may help delineate the length and severity of stricture.

Anastomotic urethroplasty is the procedure of choice for totally obliterated bulbar urethra after a
straddle injury. The typical scar is 1.5-2 cm long and can be completely excised. The proximal and distal urethra
can be mobilized for a tension-free, end-to-end anastomosis. This is a highly successful procedure in more than
95% of cases (Santucci et al, 2002). Endoscopic incision through the scar tissue of a totally obliterated urethra is
contraindicated. Partial urethral narrowing can be initially treated by endoscopic incision or dilation with a higher
success rate. Open repair should be delayed for several weeks after instrumentation to allow the urethra to
stabilize, and a 2-month period of suprapubic urinary diversion may be prudent preoperatively to optimize
conditions for repair of complex or recurrent strictures that have been catheter dependent.

IATROGENIC URETHRAL TRAUMA

Catheter placement is the most common cause of iatrogenic urethral trauma. Iatrogenic urethral injuries also
occur after radical prostatectomy, pelvic radiotherapy, and other abdominopelvic surgery. The main consequence
of iatrogenic trauma is urethral stricture. False passages should be treated with urethral catheter placement if
possible, while strictures should be managed endoscopically with incision or resection initially, followed by
urethral reconstruction if endoscopic management fails. The most common iatrogenic urethral trauma after
radical prostatectomy is anastomotic stricture. The EAU recommends dilation or endoscopic incision as the first
step in its treatment.

PAEDIATRIC URETHRAL TRAUMA

The recommended radiographic method for diagnostic evaluation of paediatric urethral trauma is RUG. As many
children with urethral trauma are unstable due other associated injuries, the first step in management according
to the Paediatric EAU guidelines is to provide urinary drainage. Transurethral catheterisation can be performed
only if the patient can still void and diagnostic evaluation is not suspicious for urethral rupture. A suprapubic
catheter should be placed, otherwise. According to the Paediatric EAU guidelines, there is no singular accepted
method to manage posterior urethral injuries; either immediate suprapubic drainage with late urethral
reconstruction or immediate primary re-alignment can be performed.

References

1. D.M. Stein, D.J. Thum, G. Barbagli, S. Kulkarni, S. Sansalone, A. Pardeshi, et al.A geographic analysis of male
urethral stricture aetiology and location.BJU Int, 112 (2013), pp. 830834
2. Singh J, Priyadarshi V, Pandey P, Vijay M, Bera M, Chakraborty S et al. Urethral Stricture Aetiology Revisited: An
Indian Scenario.UroToday Int J. 2013; 6(1):art 5. http://dx.doi.org/10.3834/uij.1944-5784.2013.02.05
3. Goldman SM, Sandler CM, Corriere JN et-al. Blunt urethral trauma: a unified, anatomical mechanical
classification. J. Urol. 1997;157 (1): 85-9.
4. Ingram MD, Watson SG, Skippage PL et-al. Urethral injuries after pelvic trauma: evaluation with urethrography.
Radiographics. 2008;28 (6): 1631-43.
5. Kawashima A, Sandler CM, Wasserman NF et-al. Imaging of urethral disease: a pictorial review. Radiographics.
2004;24 Suppl 1 (suppl 1): S195-216.
6. Brandes S and Borrelli J, Jr.: Pelvic fracture and associated urologic injuries. World J Surg 2001; 25: 1578.

22
7. Bjurlin MA, Fantus RJ, Mellett MM et al: Genitourinary injuries in pelvic fracture morbidity and mortality using
the National Trauma Data Bank. J Trauma 2009; 67: 1033.
8. Talan DA, Citron DM, Abrahamian FM, et al. Bacteriologic analysis of infected dog and cat bites.Emergency
Medicine Animal Bite Infection Study Group. N Engl J Med 1999;340(2):85-92.
9. Martinez-Pineiro L, Djakovic N, Plas E et al: EAU Guidelines on Urethral Trauma. Eur Urol 2010; 57: 791.
10. Ysebaert B, Oosterlinck W. Perineal anastomotic urethroplasty for posttraumatic urethral stricture with or
without previous urethral manipulations: a review of 61 cases with long term followup. J Urol 2009; 181: 1196
200

Urinary Diversion

Pawan Lal, Sanjeev K. Tudu

Advancements in bladder replacement construction and continent urinary diversion have reduced
treatment morbidity for patients facing cystectomy.

Historical Review
The quest for an ideal technique for urinary tract reconstruction following cystectomy dates back to 1852 when
15
Simon first reported diversion of urine to a segment of bowel by creating fistulas between the ureters and the
rectum in a patient with bladder exstrophy. Initially, efforts were aimed at either bringing the ureters to the skin or
diverting the urine to the sigmoid colon to benefit from continence provided by the anal sphincter. Prior to the
1950s, the use of the anal sphincter for continence established ureterosigmoidostomy as the urinary diversion of
choice. During this era, techniques of nonrefluxing ureteral anastomoses were improved. However, the risk of
long-term complications with ureterosigmoidostomy was significant (hydronephrosis: 32%; pyelonephritis: 57%;
2
metabolic derangements: 47%). In 1950, Bricker popularized the use of the ileum as a urinary conduit, which
constituted the gold standard for patients who underwent urinary diversion until the 1980s. The need for
improvements in the quality of life of patients led to the era of continent urinary diversion and bladder
replacement. By applying the concepts of a cutaneous catheterizable ileocecal reservoir developed in 1950,
6
several investigators reported encouraging initial results with colonic reservoirs in the mid 1980s, and Kock et al
24
concurrently developed a catheterizable ileal pouch. Camey and LeDuc reintroduced the concept of the
neobladder in 1979, and other investigators improved the technique by applying the experiences of the early
11
continent urinary diversion .

Selection of Type of Urinary Diversion

The goal of surgery in the management of infiltrating bladder cancer is either curative or palliative. If the intent is
palliative, then the simplest and most expeditious type of urinary diversion is best. If the goal is curative, then the
patient is apprised of reconstruction options for the urinary tract and undergoes preoperative evaluation. Although
the psychological impact of surgery and diversion is significant, any type of urinary reconstruction should be
acceptable with good preoperative assessment and education. Factors that affect the choice of urinary diversion
include patient age, manual dexterity, body habitus, physical and mental status, renal function, prognosis of the
primary disease, existing bowel pathology, prior radiation or chemotherapy, the presence of urethral disease, the
expectations, preferences, and fears of the patient, the experience and preference of the surgeon, and cost.
Since there is no unanimous choice for the best method of urinary diversion, all options should be considered.

Indications for an external collecting device diversion (bowel conduit) are either absolute or relative. Absolute
indications include impaired renal function, impaired physical ability to perform self-catheterization, and inability to
understand the significance and possible complications of a continent diversion. Relative indications include
advanced age, need for postoperative chemotherapy, previous pelvic irradiation, bowel disease (Crohn's
disease, colitis, cancer), body habitus, diseased urethra, and impaired functional status.Patient choice also is a
key factor in selection.

Options in Continent Urinary Diversion - the main categories are listed and explained below:

Non-continent cutaneous conduit A conduit from a part of the intestines (normally ileum or colon) is
constructed. It is non-continent, i.e. acts simply as a passage allowing urine to leak into an external collection
device outside of the body.

Continent cutaneous diversion A new bladder is constructed from a segment of the bowel (ileum or colon),
with a passage from the new bladder to an outlet at the body surface. The outlet includes a construction, i.e.
a tissue flap or equivalent, that makes it continent and it requires catheterization to be emptied.

Continent orthotopic diversion (Neobladder) A new bladder is constructed from a segment of the bowel
and connected to the intact urethra, using the urethral sphincter to gain continence after the surgery.

23
Non-continent cutaneous conduits

Ureterosigmoidostomy

One of the first urinary diversions using bowel included the use of ureterosigmoidostomy, where the ureters were
anastomosed to the sigmoid. Its major advantage is the potential for spontaneous emptying of urine with stool,
i.e. continence is maintained by the anal sphincter. However, ureterosigmoidostomy is prone to detrimental upper
tract changes in patients over time, e.g._10 years . Very high intrarectal pressures (up to 200 cm water ) led to
persistent pyelonephritis and incontinence. In addition, the mixture of faecal and urinary streams predisposed
patients to a higher risk of bowel adenocarcinoma. Several modifications of the ureterosigmoidostomy were
developed to decrease the significant complication rate associated with the procedure. The sigma rectum, or
Mainz II pouch, consists of a detubularised colon 6 cm both proximal and distal to the, rectosigmoid junction,
where the ureters are then implanted in a non-refluxing fashion. The objective of this pouch was to create a low-
pressure reservoir to protect the upper tracts, although the risk of adenocarcinoma still remained. Due to
increased complications both metabolic and risk of malignancy, the ureterosigmoidostomy should be avoided as
a urinary diversion approach unless absolutely necessary.

Continent Cutaneous Urinary Reservoir

6
In 1982, Kock et al described a technique for construction of an internal ileal
reservoir that consists of a 80-cm segment of terminal ileum isolated on its
mesentery at approximately 50 cm proximal to the ileocecal valve. Proximal and
distal 17-cm sections are used to construct the afferent and efferent limbs to the
pouch, and two medial 23-cm segments are detubularized, approximated, and
remodeled to form the reservoir. Afferent and efferent continent nipple valves are
then created by intussuscepting sections of bowel 5- to 6-cm in length with strips
of Marlex or polyglycolic acid mesh around the bases of the intussusceptions.
The ureters are anastomosed to the afferent limb using a mucosa-to-mucosa
anastomosis, the pouch is closed, and the efferent limb is brought through the
abdominal wall and fixed to the rectus fascia using a Dexon collar to form a
stoma through which urine can pass.

31
In 1992, Fisch et al described a form of continent urinary diversion termed the Mainz pouch (mixed
augmentation ileum and cecum pouch), which utilized cecum and ileum. To create the reservoir, 10 to 15 cm of
cecum and ascending colon, as well as terminal ileal segments of equal length, are isolated and detubularized.
The posterior wall of the pouch is completed by anastomosis of the ascending colon with the ileal loop, starting at

24
the inferior aspect. The latter is then anastomosed with the next proximal ileal segment. The ureters are
implanted in an antirefluxing manner in an open-end technique through a submucosal tunnel of 4 cm to 5 cm in
length. To create the continence mechanism, an additional 8 to 12 cm of ileum is isolated to form an ileal
intussuscepted valve by invaginating and fixing 6 cm of this latter segment with metal staples. Alternatively,
continence can be achieved by submucosal embedding of the appendix.

Mainz pouch
32
In 1985, Rowland et al described the cecoileal continent urinary reservoir, in which approximately 8 to 10 cm of
terminal ileum and 25 to 30 cm of cecum and ascending colon are isolated. The colonic segment is detubularized
either by incising along its antimesenteric surface with scissors or cautery or by placing a 60- to 75-mm
gastrointestinal anastomosis (GIA) stapler between the two more lateral tenia. The continence mechanism is then
created by tapering the efferent limb (terminal ileum) over a 12F red rubber catheter resting against the
antimesenteric surface of the ileum. A 60-mm GIA metal staple is applied to excise the redundant antimesenteric
portion of the ileum and to create a smooth tube for catheterization using 16F to 18F catheters. The ureters are
tunneled into the tenia of the colonic segment through an inverted "T" incision. A mucosal incision is then made
for the orifice, the ureter is cut either obliquely or spatulated, and a ureter-to-mucosa anastomosis is performed
over a 5F to 8F stent using interrupted 5-0 absorbable, synthetic, monofilament sutures. The cephalad end of the
pouch is folded to the caudal end, and the reservoir is closed with a single layer of running 3-0 braided synthetic
absorbable suture.
34
In 1986, Light et al described Le Bag, in which 20 cm of cecum and ascending colon are isolated with a
corresponding length of terminal ileum. Following detubularization, the free ileal and colonic borders are sutured
together, and the pouch is folded as described in the Kock procedure. The ureters are reimplanted on the colonic
portion of the pouch according to the preference of the surgeon. After tapering and reinforcing the ileocecal valve,
the ileal tail is brought through the
abdominal wall as the continent segment.

Orthotopic Bladder

Orthotopic neobladders represent internal reservoirs connected to the native urethra that rely upon the external
striated sphincter for continence. Reservoirs are typically constructed from detubularised small bowel and then
anastomosed to the native urinary outflow tract. Orthotopic neobladders were initially limited to men, as
women were thought to have an increased risk of local recurrence and voiding dysfunction with orthotopic
diversion. However, with experience and improved understanding of the female rhabdoid sphincteric mechanism,
orthotopic diversion has become more common in women, becoming the procedure of choice for most patients
after cystectomy. However, appropriate patient selection is critical to the success of orthotopic diversions. It
should not compromise the cancer control of a potentially curative surgery, and it is contraindicated if the urethra
is non-functional or involved with tumour. Like continent cutaneous diversions, orthotopic neobladders require
active patient participation to ensure proper maintenance of the reservoir. If medical or psychosocial issues
preclude this level of cooperation, the patient may be better served by an incontinent ileal loop diversion.

Camey and LeDuc,[24] Hautmann et al,[11] and Studer and Turner[37] described the creation of a bladder from
different bowel segments as an alternative for handling continuity of the urinary tract after cystectomy.

25
 Studer Ileal Neobladder
Ileal Neobladder with W-shaped pouch (Hautmann)

Stomach as conduit / pouch

Advantages of gastric pouch
Less metabolic abnormality
Less stone formation
Less infection
No risk of tissue exposed to radiation
Easy to perform anti-reflux mechanism

Disadvantages of gastric pouch

Gastric atony , small stomach syndrome
Dumping syndrome
Hematuria-dysuria syndrome
Severe metabolic alkalosis ( in poor renal function)

Complications Relating to Techniques

Complications from earlier techniques affect 2% of patients with continent urinary diversion and 4.5% of patients
with neoplasms. Complications include infection, wound dehiscence, urinary fistulas, prolonged ileus (longer than
seven days), small bowel obstruction, respiratory distress (atelectasis, pneumonia, pulmonary embolus),
myocardial infarction, deep venous thrombosis, and bleeding.

Metabolic and Nutritional Effects

Possible metabolic and nutritional consequences associated with small and large intestinal segments for
continent diversion of the urinary tract include disturbances of electrolyte metabolism, abnormal drug metabolism,
calculus formation, altered hepatic metabolism, nutritional disturbances, osteomalacia, impaired sensorium,
growth
retardation, infection, and cancer development.

Electrolyte Abnormalities
Hyperchloremic metabolic acidosis develops as a result of sodium secretion (in exchange for hydrogen) and
bicarbonate (in exchange of chloride), as well as re-absorption of ammonia, ammonium, hydrogen ions, and
chloride when these segments are exposed to urine. The mechanism that appears to be most responsible for
hyperchloremic metabolic acidosis is excess absorption of chloride and ammonia, which maintains a chronic
endogenous acid load. Since chloride seems to be more readily absorbed from colonic than from ileal reservoirs
and since electrolytic derangements predominate when longer colonic segments are used for reservoir
construction, the use of an ileal segment may be preferable in patients with impaired renal function.
Hypokalemia and total body depletion of potassium may occur in patients with urinary intestinal diversion.
Potassium depletion is probably the result of renal potassium wasting as a consequence of renal damage,
osmotic diuresis, and gut loss through intestinal secretion.

Hypocalcemia is a consequence of depleted body calcium stores and excessive renal wasting. The chronic
acidosis is buffered by carbonate from the bone with subsequent release of calcium into the circulation, which is

26
then cleared by the kidney and results in a gradual decrease in body calcium stores. An impairment of renal
tubule calcium re-absorption also occurs. Normal bone mineral metabolism requires the interaction of calcium,
magnesium, and phosphate, which are influenced by parathormone, calcitonin, and vitamin D. Osteomalacia in
adults and rickets in children -- essentially the same condition -- are characterized by chronic loss of bone buffers
and calcium and lead to hyper-calciuria and bone demineralization. Mineral losses are eventually replaced by
osteoid with a resultant decrease in bone strength.

Alterations in bone mineral content occur in most patients who have had a urinary intestinal diversion for
extended periods of time.

Stomach : hypochloremic, hypokalemic, metabolic alkalosis

Jejunum : hyponatremia, hyperkalemia, metabolic acidosis

Ileum/colon : hyperchloremic, hypokalemic metabolic acidosis

Calculus Formation
The incidence of renal stone formation increases in patients with intestinal urinary reconstruction. The increases
range between 16.7% and 26.5% with the Kock pouch, 5.4% with the Indiana pouch, and 9.8% with the Mainz
pouch. Generally, the stones are comprised of struvite, calcium oxalate, calcium phosphate, or uric acid, and
mixtures of these minerals often are present in the same stone. Most stones reported to be infectious are
comprised of struvite and/or carbonate apatite and are related to foreign materials and infection. A small but
significant portion of stones are metabolic and consist of calcium phosphate and/or calcium oxalate secondary to
hyperchloremic metabolic acidosis.

Common risk factors for urolithiasis are chronic colonization of the reservoir with bacteria secondary to urine
alkalinity, renal infection with urease-producing bacteria, the presence of foreign materials (eg, sutures, metallic
staples, non-absorbable collars) in the reservoir, retained intestinal mucous, and increased urinary excretion of
phosphate, sulfate, and magnesium, and hypocitraturia.

Major risk for stone formation - hyperchloremic metabolic acidosis.

The incidence of stone formations in different types of conduits are :
Colon conduits : 3% to 4%
Ileal conduits : 10% to 12%
Continent cecal reservoirs : 20%

Nutritional Disturbances
The liver synthesizes and conjugates bile salts that are necessary for proper fat digestion and for the uptake of
vitamins A and D. After fat stimulates their release into the duodenum, bile salts are actively reabsorbed by the
distal ileum and returned to the liver by the enterohepatic circulation to be used again. After ileal resection,
length-dependent alterations in bile metabolism can lead to a multitude of intestinal events that may result in
diarrhea. Even though considerable amounts of bile salts are lost in the colon, the liver can synthesize and
maintain the salt pool after resection of up to 100 cm of ileum. If ileal resection is greater than 100 cm, hepatic
bile salt synthesis cannot match the losses. In this case, micelle formation in the jejunum decreases, and fat
malabsorption leads to steatorrhea (fecal fat of more than 20 g per day) and diarrhea. Hydroxylated fatty acids
directly decrease colonic absorptive capacity, cause active secretion of electrolytes and water, and form soaps,
which are cathartic.

Vitamin B12 is excreted exclusively into the bile. It is highly conserved by active uptake at the terminal ileum and
is returned to the liver by the enterohepatic circulation. Body stores of vitamin B12 may last three to six years in
complete malabsorption and six to 30 years in partial malabsorption. Loss of the distal ileum can impair vitamin
B12 absorption. A loss of 50 cm of terminal ileum appears to be the critical margin for sufficient vitamin B12
absorption. Substitution of vitamin B12 should be prescribed to patients who lose more than 50 cm of terminal
ileum after surgery.

Following removal of the ileocecal valve, the absorptive processes in some patients may be affected due to the
development of high concentrations of bacteria in the ileum. Severe diarrhea may occur as a result of fat
malabsorption or irritation of unreabsorbed bile salts on the colonic mucosa. Diarrhea also may occur when major
portions of the large bowel are removed. In this case, a significant amount bicarbonate can be found in the fecal
fluid, since alkaline ileal contents drain into a shortened large bowel segment, which may result in acidosis and
dehydration.

Infection
Approximately 80% of patients with continent intestinal diversion are bacteriuric with diverse bacterial flora. In the
first year of reconstruction, the incidence of septic episodes varies from 5% to 20%. The frequency of bacteriuria,
pyelonephritis, and sepsis is higher in patients with continent intestinal diversion than in those with an intact
bladder that is subjected to daily instrumentation by intermittent catheterization.

27
Carcinogenesis
The incidence of malignancy in intestinal segments used for urinary reconstruction is currently unknown. If cancer
develops, the most common site is the ureterointestinal anastomosis. The most common types of tumor are
adenocarcinoma (85%) and transitional cell carcinoma (10%), with the remaining 5% consisting of signet ring cell
carcinoma, adenomatous polyps, sarcoma, and undifferentiated carcinoma.[49] A possible mechanism is an
increase in exposure to carcinogens such as N-nitroso compounds, which are highly mutagenic and induce
tumors in many animal species. Nitrate is normally excreted by the kidney into the urine, and many species of
Gram-negative bacteria (Escherichia coli, Proteus, Klebsiella, Pseudomonas) can reduce nitrate and catalyze
the conversion of nitrite and secondary amines present in the urine into N-nitroso compounds. Fecal bacteria are
presumably responsible for the formation of these substances, although the admixture of urine and feces is not
considered an absolute requirement for this production. Long-term surveillance is mandatory for patients who
have undergone urinary reconstruction with intestinal segments.

Complications Related to the Reconstructed System

Obstruction
Ureterointestinal anastomosis obstruction is a serious complication, and surgical intervention is usually required
to preserve the upper urinary tract. Common factors predisposing to anastomotic structure formation are
inadequate ureteral length, poor vascular supply, poor surgical technique with ureteral twisting, and possibly an
increased angulation with chronic reservoir distension. The mean incidence for this complication is 7.5% with
continent reservoirs; with neobladders, the incidence is higher. When the ureters are reimplanted, the incidence
of obstruction is even higher (28%). Ureterointestinal anastomosis obstruction may be managed either by balloon
dilatation and stenting or by an open surgical procedure through a transreservoir approach. The incidence of
acute pyelonephritis ranges up to 5.8% with continent diversions and up to 8.0% with neobladders. In most
cases, its onset is related to obstruction of the ureterointestinal anastomosis.

Reflux
The estimated incidence of intestinoureteral reflux is 2.6% with continent reservoirs and 0.4% with neobladders.
Despite the controversy regarding the optimal type of ureterointestinal reimplantation (tunneled vs nontunneled),
the incidence of reflux is low regardless of which reimplantation technique is used.

Reservoir Complications
Hypertonicity of the bowel reservoir with associated episodes of urine leakage has been noted in 5.6% of
pouches and in 4.2% of neobladders. Whether the bowel is detubularized or left in its original tubular form, bowel
motility resumes in some segments across anastomotic lines. Pressure spikes may be noticed in both
detubularized and tubularized segments of bowel. Spontaneous perforation of the urinary reservoir is a rare
complication. The incidence with continent reservoirs is 4.8%, and no cases have been reported with
neobladders.

Efferent Limb Complications

Dysfunction of the continence segment occurs in 6% of patients with continent reservoirs, and dysfunction of the
intestinourethral anastomosis with neobladders occurs in 2.75% of patients.[46] Dysfunction of the continence
segment (ileocecal valve) may be due to intrinsic factors (eg, a dysfunctional plicated bowel limb) or extrinsic
factors (eg, a parastomal hernia). Multiple abdominal wall scars, weight gain, and a chronic increase in intra-
abdominal pressure due to constipation or chronic obstructive pulmonary disease may favor hernia development.
Difficulty with emptying the reservoir is encountered in 7% of patients with continent cutaneous reservoirs and in
12% of those with neobladders. In the former, the difficulty may be related to a long and tortuous efferent limb,
the creation of a false passage, or the development of a stricture along the efferent limb. For patients with
neobladders, the main causes of difficulty are intestinourethral strictures (6.26%) and urethral cancer recurrence
(3% to 18%). Protrusion of a ventral hernia through the incision line developed in one (1.7%) of our 60 patients.
Other series report an incidence rate of ventral hernia that ranges from 4.4% to 14%. Meticulous closure of the
abdominal wall with appropriate suture materials is the cornerstone in preventing this complication.

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Urol. 1987;137:1154-1155.
30. Benson MC, Slawin KM, Wechsler MH, et al. Analysis of continent vs standard urinary diversion. Br J Urol.
1992;69:156-162.
31. Fisch M, Wammack R, Hohenfellner R. Seven years experience with the Mainz pouch procedure. Arch Exp Urol.
1992;45:175-185.
32. Rowland RG, Mitchell ME, Bihrle R. The cecoileal continent urinary reservoir. World J Urol. 1985;3:185.
33. Rowland RG. Continent cutaneous urinary diversion: the Indiana pouch. In: Vogelzang NJ, Scardino PT, Shipley
WU, et al, eds. Comprehensive Textbook of Genitourinary Oncology. Baltimore, Md: Williams & Wilkins; 1996:479-
485.
34. Light JK, Engelmann UH. Le Bag: total replacement of the bladder using an ileocolonic pouch. J Urol. 1986;136:27-
31.
35. Lockhart JL. Remodeled right colon: an alternative urinary reservoir. J Urol. 1987;138:730-734.
36. Pow-Sang JM, Lockhart JL. Continent urinary diversion: the Florida pouch. Prob Urol. 1991;6:581-586.
37. Studer UE, Turner WH. Ileal low pressure bladder substitute with an afferent tubular isoperistaltic segment. In:
Vogelzang JN, Scardino PT, Shipley UW, et al, eds. Comprehensive Textbook of Genitourinary Oncology.
Baltimore, Md: Williams & Wilkins; 1996:495-508.
38. McDougal WS. Metabolic complications of urinary intestinal diversion. J Urol. 1992;147:1199-1208.
39. Davidsson T, Lindergard B, Mansson W. Long-term metabolic and nutritional effects of urinary diversion. Urology.
1995;46:804-809.
40. McDougal WS. Complications of urinary intestinal diversion. AUA Update Series, Lesson 37. 1992;11:290-294.
41. Davidsson T, Akerlund S, Forsell-Aronsson E, et al. Absorption of sodium and chloride in continent reservoirs for
urine: comparison of ileal and colonic reservoirs. J Urol. 1994;151:335-337.
42. Hall MC, Koch MO, McDougal WS. Metabolic consequences of urinary diversion through intestinal segments. Urol
Clin North Am. 1991;18:725-735.
43. Arai Y, Kawakita M, Terachi T, et al. Long-term followup of the Kock and Indiana pouch procedures. J Urol.
1993;150:51-55.
44. Ginsberg D, Huffman JL, Lieskovsky G, et al. Urinary tract stones: a complication of the Kock pouch continent
urinary diversion. J Urol. 1991;145:956-959.
45. Mastandrea FD, Helal MA, Khan P, et al. The Florida pouch continent urinary diversion: long-term follow-up and
complications. In: Hohenfellner R, Fisch M, Wammack R, eds. Continent Urinary Reconstruction: Second
International Meeting. Abstract Book. Mainz Germany: Oswald OHG; 1995:39.
46. Rowland RG. Complications of continent cutaneous reservoirs and neobladders: series using contemporary
techniques. AUA Update Series, Lesson 25. 1995;14:202-207.
47. Terai A, Arai Y, Kawakita M, et al. Effect of urinary intestinal diversion on urinary risk factors for urolithiasis. J Urol.
1995;153:37-41.
48. Steiner MS, Morton RA. Nutritional and gastrointestinal complications of the use of bowel segments in the lower
urinary tract. Urol Clin North Am. 1991;18:743-754.
49. Treiger BF, Marshall FF. Carcinogenesis and the use of intestinal segments in the urinary tract. Urol Clin North Am.
1991;18:737-742.

29
50. Wilson TG, Moreno JG, Weinberg A, et al. Late complications of the modified Indiana pouch. J Urol. 1994;151:331-
334.
51. Martins FE, Bennett CJ, Skinner DG. Options in replacement cystoplasty following radical cystectomy: high hopes
or successful reality. J Urol. 1995;153:1363-1372.

Management of BPH

Rishi Nayyar, Ashish Kumar

Benign prostatic hyperplasia (BPH) also known as benign prostatic hypertrophy (technically a misnomer), benign
enlargement of the prostate (BEP or BPE), or adenofibromyomatous hyperplasia, clinically refers to the increase
in size of the prostate. As the terminology related to BPH can be very confusing, it is important to clear ambiguity
in the use of various common terms in practice as below:

1) LUTS (lower urinary tract Symptoms) Non specific term for symptoms which may be attributable to lower
urinary tract dysfunction. The two main groups of LUTS are storage LUTS (previously called irritative
symptoms) and Voiding LUTS (previously called obstructive symptoms). The term prostatism is no longer
used clinically because it is refers to non-specific symptom complex of LUTS which need not necessarily be
related to enlargement of prostate (Figure 1).
2) BPH (Benign prostatic hyperplasia) Histological basis for a diagnosis of BEP leading to BOO that results in
LUTS
3) BOO (Bladder outflow obstruction) Urodynamically proven obstruction to passage of urine
4) BPE (Benign prostatic enlargement) The clinical finding of an enlarged prostate, assumed to be due to BPH
5) BPO (Benign prostatic obstruction) BOO caused by BPE
6) OAB (Over active bladder) Symptom syndrome of urgency, with or without urge incontinence, usually
1
accompanied by urinary frequency and nocturia .

Lower urinary tract symptoms (LUTS) are a common complaint in adult men with a major impact on quality of life
(QoL), and substantial personal and societal expenditures. The present chapter offers practical evidence based
guidance on the assessment and treatment of men with various non-neurogenic benign forms of LUTS. The
understanding of the LUTS as a functional unit, and the multifactorial aetiology of these symptoms, means that
LUTS now constitute the main focus, rather than the former emphasis on Benign Prostatic Hyperplasia (BPH). In
this chapter we shall be discussing the clinical assessment of LUTS (not BPH) along with modalities for treatment
of BPH.

Figure 1: Multifactorial etiology of LUTS

Brief epidemiology
2
Worldwide, approximately 200 million men have symptoms related to BPH . The prostate gets larger in most men
as they get older, and, overall, 45% of men over the age of 46 can expect to suffer from the symptoms of BPH if
they survive 30 years. Incidence rates increase from 3 cases per 1000 man-years at age 4549 years, to 38
cases per 1000 man-years by the age of 7579 years. Whereas the prevalence rate is 2.7% for men aged 4549,
3
it increases to 24% by the age of 80 years .

30
CLINICAL PRESENTATION AND DIAGNOSTIC EVALUATION

The clinical assessment of patients with LUTS has two main objectives:
To consider the differential diagnoses, since the origin of male LUTS is multifactorial.
To define the clinical profile of men with LUTS in order to provide appropriate care. The assessment
should ascertain treatment options and identify men at risk of disease progression.

Herein, various parameters important in the management of BPH are presented in accordance with the recent
most recommendations.

Medical History

The diagnosis of BPH can often be suggested on the basis of the history alone, with most patients presenting
with LUTS. Storage symptoms include urinary frequency, urgency (compelling need to void that cannot be
deferred), urgency incontinence, and voiding at night (nocturia). Voiding symptoms include poor urinary stream,
hesitancy (needing to wait for the stream to begin), intermittency (when the stream starts and stops
intermittently), straining to void, and dribbling. Pain and dysuria are usually not present.

The storage and voiding symptoms are evaluated using various available symptom and quality of life scoring
systems like the International Prostate Symptom Score (IPSS) questionnaire or Danish Prostate Symptom Score
(DAN-PSS). A validated symptom score questionnaire with QoL question(s) should be used for the routine
assessment of male LUTS in all patients and should be applied for re-evaluation of LUTS during treatment
4
(Grade of recommendation B, Level of evidence 3 as per EAU guideline 2015 ).

Besides progression of LUTS, BPH if left untreated may progress in the form of precipitation of complications.
Incomplete voiding results in stasis of bacteria in the bladder residue and an increased risk of urinary tract
infection. Urinary bladder stones may form from the crystallization of salts in the residual urine. Urinary retention,
termed acute or chronic, is another form of progression. Acute urinary retention (AUR) is the inability to void,
while in chronic urinary retention the residual urinary volume gradually increases, and the bladder distends.
Some patients that suffer from chronic urinary retention may eventually progress to renal failure, a condition
termed obstructive uropathy.

A sexual history is also important, as epidemiologic studies have identified LUTS as an independent risk factor
for erectile dysfunction and ejaculatory dysfunction in men.

Frequency volume charts and bladder diaries

The recording of volume and time of each void by the patient is referred to as a frequency volume chart. Inclusion
of additional information such as fluid intake, use of pads, activities during recording, or symptom scores is
termed a bladder diary. These should be used to assess male LUTS with a prominent storage component or
nocturia where it underpins the categorization of underlying mechanism(s) (Grade of recommendation B, Level of
4
evidence 3 as per EAU guideline 2015 ) and help in behavioural or medical management. Also they may cause a
bladder training effect, and influence the frequency of nocturnal voids.

Physical examination and digital rectal examination (DRE)

Physical examination to seek potential influences on LUTS, particularly focussing on the suprapubic area, the
external genitalia, the perineum, and lower limbs. Urethral discharge, meatal stenosis, phimosis and penile
cancer must be identified if present besides focused spinal and neurological examination. (Grade of
4
recommendation B, Level of evidence 3 as per EAU guideline 2015 )DRE is an integral part of the evaluation in
men with presumed BPH to evaluate for size, contour and palpable nodules if any. Decreased anal sphincter
tone or the lack of a bulbocavernosus muscle reflex may indicate an underlying neurological disorder.

Urinalysis

Urinalysis (dipstick or sediment) must be included in the primary evaluation of any patient presenting with LUTS
to determine conditions, such as UTI, microhaematuria and diabetes mellitus. (Grade of recommendation A,
4
Level of evidence 3 as per EAU guideline 2015 )

Prostate-specific antigen (PSA)

Probability of prostate cancer: The 2010 update of the American Cancer Society (ACS) guideline for early
5
detection of prostate cancer stresses the importance of involving men in the decision whether to test for prostate
cancer. The ACS recommends that men receive information about the uncertainties, risks, and potential benefits
associated with prostate cancer screening (ie, prostate-specific antigen [PSA] testing and digital rectal
examination [DRE] for prostate cancer).

31
Prediction of progression of BPH: Serum PSA is a stronger predictor of prostate growth than prostate volume and
is highly significant predictor of clinical progression.

Renal function measurement

Renal function assessment must be performed if renal impairment is suspected, based on history and clinical
examination or in the presence of hydronephrosis or when considering surgical treatment for male LUTS. (Grade
4
of recommendation A, Level of evidence 3 as per EAU guideline 2015 ).

Post void residual urine (PVR)

Measurement of PVR in male LUTS should be a routine part of the assessment. (Grade of recommendation A,
4
Level of evidence 3 as per EAU guideline 2015 ) PVR urine can be assessed by transabdominal US, bladder
scan or catheterisation. A large PVR measurement is not a contraindication to watchful waiting or medical
therapy, although large PVR may indicate a poor response to treatment and especially to watchful
waiting.Monitoring of changes in PVR over time may allow for identification of patients at risk of AUR. This is of
particular importance for the treatment of patients using antimuscarinic medication.

Uroflowmetry

Uroflowmetry in the initial assessment of male LUTS may be performed and should be performed prior to any
4
treatment. (Grade of recommendation B, Level of evidence 2b as per EAU guideline 2015 ) Uroflowmetryis
limited as a diagnostic test because it is unable to discriminate between the underlying mechanisms for poor flow.

Imaging

Imaging of the upper urinary tract (with USG) in men with LUTS should be performed in patients with a large
PVR, haematuria or a history of urolithiasis. (Grade of recommendation B, Level of evidence 3 as per EAU
4
guideline 2015 )

When considering medical treatment for male LUTS, imaging of the prostate (either by TRUS or transabdominal
US) should be performed if it assists the choice of the appropriate drug.When considering surgical treatment,
imaging of the prostate (either by TRUS or transabdominal US) should be performed. (Grade of recommendation
4
B, Level of evidence 3 as per EAU guideline 2015 )Assessment of prostate size is important for the selection of
interventional treatment, i.e. open prostatectomy, enucleation techniques, transurethral resection, TUIP, or
minimally invasive therapies. It is also important prior to treatment with 5-ARIs. Prostate volume predicts the
development of progressive symptoms and complications.TRUS is superior to suprapubic (transabdominal)
volume measurement. The presence of a median lobe may guide treatment choice in patients scheduled for a
minimally invasive approach.

Urodynamics

When considering surgery pressure flow study may be used in patients where diagnosis of bladder outlet
obstruction is suspicious like large PVR (>300 ML), age > 80 or <50 yr, long standing diabetes mellitus or
4
neurological diseases. (Grade of recommendation C, Level of evidence 3 as per EAU guideline 2015 )

An algorithm devised by EAU for management of LUTS is given in Figure 2.

TREATMENT

A. Watchful waiting

Wasson et al, 1995 examined the impact of watchful waiting in 556 subjects with moderate symptoms of BPH
randomized to TURP (transurethral resection of prostate) versus watchful waiting. During 3 years of follow-up,
treatment failure was observed in 23 (8.2%) and 47 (17%) of subjects randomized to TURP and watchful waiting,
respectively. Men with mild symptoms are appropriate for watchful waiting. Men with LUTS should always be
offered lifestyle advice prior to or concurrent with treatment. (Grade of recommendation A, Level of evidence 1b
4
as per EAU guideline 2015 )

a. Indication
i. Patient driven as symptom is not bothersome
ii. Treatment complication and/or cost is perceived to be greater as compared with symptom bother

b. Use of simple measures

i. Decreasing total fluid intake especially before bedtime
ii. Moderating the intake of alcohol- and caffeine containing products
iii. Maintaining timed void schedule

32
B. Medical management

The ideal candidate for medical therapy should have symptoms that are bothersome and negatively affect quality
of life so that the patient is willing to make a lifetime commitment to medical therapy, provided the drug is
effective and adverse experiences are either nonexistent or minimal. Individuals presenting with recurrent
urinary retention, recurrent UTIs, renal insufficiency, bladder calculi, and recurrent gross hematuria may
develop life-threatening consequences from their BPH if it is not managed surgically.

a. Indication:
i. Symptoms bothersome and absence of absolute indications of surgery

b. Drugs
i. Alpha adrenergic blockers
ii. 5 alpha reductase inhibitor
iii. Anticholinergic agents
iv. Phosphodiesterase inhibitors
v. Combination therapy
vi. Phytotherapy

Figure 2: Assessment algorithm of LUTS in men aged 40 years or older

Alpha adrenergic blockers:

The 4 subtypes of the -1 receptor include 1a, 1b, 1c and 1d. Of these, the -1a receptor is most specifically
concentrated in the bladder neck and prostate. Provided that the -1a subtype is predominant in the prostate,
bladder neck, and urethra, but not in other tissues, drugs that are selective for this receptor (like tamsulosin) may
have a potential therapeutic advantage.

An approximately 4- to 6-point improvement is expected in IPSS/AUA-SI scores when -blockers are used.
Interestingly, -blocker therapy has not been shown to reduce the overall long-term risk for acute urinary
retention (AUR) or BPH-related surgery.

33
Common side effects of blockers include orthostatic hypotension, ejaculation changes, nasal congestion, and
weakness.

The -blocking agents for BPH can be subgrouped according to receptor subtype selectivity and the duration of
serum elimination half-lives, as follows:
Nonselective -blockers : Phenoxybenzamine
Selective short-acting -1 blockers : Prazosin, Alfuzosin, Indoramin
Selective long-acting -1 blockers : Terazosin, doxazosin, slow-release (SR) Alfuzosin.
Super selective -1a blockers : Tamsulosin, Silodosin
Super selective -1d blockers: Naftopidil

Terazosin: (1mg titrating to maximum of 10 mg) This is long acting titratable 1 selective blocking, single daily
dosing agent that was initially used in the treatment of hypertention. Maximum urine flow increase by 10% to
50%. Maximum tolerable doses have not been defined for any -blocker; however, the higher the dose, the more
likely the adverse events (orthostatic hypotension, dizziness, fatigue, ejaculatory disorder, nasal congestion).
Despite the requirement for dose titration and blood pressure monitoring, these older, often less costly, -
blockers appear to be equally effective to tamsulosin and alfuzosin, and the 2010 AUA guidelines state that they
remain reasonable choices for patients with moderate-to-severe LUTS due to BPH.

Tamsulosin:(0.4 mg) Tamsulosin is considered the most pharmacologically uroselective of the commercially
available agents because of its highest relative affinity for the -1a receptor subtype. This is long acting 1
selective, single daily agent. Thus reducing the incidence of adverse effects like dizziness, postural hypotension
and syncope. Arnold demonstrated a decrease in symptom score by upto 7 points. 25% to 70% improvement in
symptoms. Overall satisfaction was 87%. Ejaculatory dysfunction was also reported with tamsulosin, apart from
other adverse events of blocker.

Alfuzosin SR:(10 mg) Alfuzosin is selective 1 adrenoreceptor antagonist which is effective in the symptomatic
treatment of BPH. Buzelin et al reported peak urinary flow increased by 2.- 3.2 ml/sec and mean flow increase by
30%. Significant improvement was seen in obstructive and irritative symptoms.

Silodosin: In 2008, the US Food and Drug Administration (FDA) approved a new -1a receptor selective blocker,
silodosin for BPH. Since it is very highly selective inhibitor of the 1A adrenergic receptor, it causes practically no
orthostatic hypotension (in contrast to other 1 blockers). On the other side, the high selectivity seems to cause
more problems with ejaculation.

Naftopidil: This is a selctive 1d adrenoreceptor antagonist. Cochrene review suggests that treatment with
naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of
life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to
naftopidil were few and usually mild. Apart from IPSS naftopidil also improves symptoms of detrusor overactivity,
since 1d receptors are also located in the detrusor and are considered to be patho-physiologically involved in
the irritative symptoms associated with BPH.

Androgen manipulation (5 alpha reductase inhibitor):

The rationale for androgen suppression is based on the observation that the embryonic development of the
prostate is dependent on the androgen dihydrotestosterone (DHT). Reducing prostate volume is thought to
decrease the static component of BOO resulting from BPH. It acts better in prostate size > 40 cc and maximum
reduction in volume seen by 6 months (20%).The risk reduction in AUR and BPH related surgery was 57% and
55% respectively using finasteride as per the Proscar Long-Term Efficacy and Safety Study (PLESS). Side
effects include decreased libido and ejaculatory or erectile dysfunction.

Finasteride: a 4-aza-steroid, has demonstrated 5- reductase type 2blocking activity, resulting in the inhibition of
DHT-receptor complex formation. This effect causes a profound decrease in the concentration of DHT
intraprostatically, resulting in a consistent decrease in prostate size. One third of men treated with this agent
exhibit improvement in urine flow and symptoms.

Dutasteride: It has an affinity for both type 1 and type 2 5--reductase receptors. The significance of blockage of
type 1 receptors is currently unknown.

Both finasteride and dutasteride actively reduce DHT levels by more than 80%, improve symptoms, reduce the
incidence of urinary retention, and decrease the likelihood of surgery for BPH. Both finasteride and dutasteride
may reduce serum prostate-specific antigen (PSA) values by as much as 50%. The decrease in PSA is typically
maximally achieved when the maximal decrease in prostatic volume is noted (6 months). Thus, one must take
this into account when using PSA to screen for prostate cancer.

One prospective, randomized, double-blind study by the Enlarged Prostate International Comparator Study
(EPICS) was conducted to compare the efficacy of dutasteride to that of finasteride in men with symptomatic

34
BPH. While this study was conducted over the course of only one year, the data suggest that both of these drugs
were similarly effective in reducing prostate volume, improving Qmax, and LUTS for this population. Also prior to
initiating therapy with 5-ARIs, one should perform appropriate evaluations to rule out prostate cancer.

Combination therapy:
1. alpha blocker with 5 alpha reductase inhibitor
Medical Therapy of Prostatic Symptoms (MTOPS) Trial: This prospective, randomized, double-blind,
multicenter, placebo controlled trial revealed that patients receiving combination therapy were significantly
less likely to experience BPH progression than those receiving either monotherapy or placebo, with risk
reduction rates of 39% for doxazosin, 34% for finasteride, and 67% for combination therapy compared with
placebo.

The Symptom Management After Reducing Therapy (SMART-1) trial demonstrated that after 6 months of
combination therapy, discontinuation of the -1-blocker is possible in men with moderate LUTS. However,
those with severe LUTS may require longer combination therapy16.

2. alpha blocker with anti-cholinergics

For a man with frequency, urgency and urge incontinencesymptoms suggestive of an overactive bladder
one can consider an anticholinergic such as oxybutynin or tolterodine.
There is minimal available evidence on the long-term outcome of medical therapy of mixed OAB and BOO
due to BPH. The short-term data suggest that combination of antimuscarinic and -adrenergic blocker
therapy is safe with minimal risk of retention or AUR in carefully selected men. It would seem advisable to
avoid treating men with a substantial residual urine (200 mL or more in the study), and men on this therapy
who are reporting increased hesitancy or showing signs of increasing PVR or clinical evidence of retention
should be warned to stop the anti-muscarinic element of the combination therapy immediately. Men with
significant obstruction and large, persistent residual urine volumes should be considered for surgical therapy
rather than the addition of antimuscarinic agents.

3. alpha blocker with Phosphodiesterase 5 Inhibitors (PDE5i)

The rationale for the use of PDEIs in the treatment of LUTS/BPH was initially based on demographic data
showing the frequent occurrence of both ED and LUTS in men as they age. This raised the possibility of a
common underlying mechanism at least contributing to both processes. This, in turn, raised the possibility of
new treatment options that might impact on both processes.

There is now good level 1 evidence of a beneficial effect of PDEIs on urinary symptoms. The mechanisms of
effect are still unclear. It is likely that PDEI treatment will be of value, especially for men with LUTS and
significant ED. Because recent U.S. data indicate the proportion of men reporting moderate to severe LUTS
ranges from 8% in those 30 to 39 years old to 26% in those 70 to 79 years old and the prevalence of ED is
also high and increases dramatically with age with 10% of 30- to 39-year-old and 59% of 70- to 79-yearold
men reporting mild to moderate or moderate to severe symptoms, this is clearly a substantial number of men
who may request treatment.

Tadalafil 5 mg od has been FDA approved as a standalone treatment of LUTS in BPH.

Phytotherapy
The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH is
common. Mechanism of action is unknown.The three plausible mechanisms that have received the greatest
attention are anti-inflammatory effects, 5-reductase inhibition, and growth factor alteration. Most of the studies
regarding phytotherapy have been plagued by weak design, definition, preparation of phytotherapy used.

Serenoa Repens (Saw Palmetto Berry): Also known as American saw palmetto, or dwarf palm plant, it is the
most popular phytotherapeutic agent available for the treatment of BPH. Overall, various studies has concluded
that S. repens was not more effective than placebo for treatment of urinary symptoms consistent with BPH.

Pygeum africanum (African Plum): Apart from the prosposed mechanism described, P. africanum (Tadenan) also
has a protective effect on the obstructed bladder. Thus none of those trials meets the guidelines recommended
by the International Consultation Conferences on BPH. Another meta-analysis for the Cochrane collaboration
(Wilt et al, 2002a) concluded that an effect was possible but not proven. Therefore the data concerning the
efficacy of P. africanum are not conclusive.

Hypoxis rooperi (South African Star Grass): Hypoxis rooperi (Harzol) has been studied in both a 6-month double-
blind, placebo controlled trial of 200 patients (Berges et al, 1995) and, subsequently, an open-label follow-up
(Berges et al, 2000). In the initial study, statistically significant improvements were documented for symptom
scores (IPSS), quality of life, PFRs, and PVRs (Berges et al, 1995). This magnitude of improvement has not been
observed with any other medical therapy previously evaluated for BPH.
-sitosterol: It does improve urologic symptoms and urinary flow rates, but its long-term effectiveness, safety, and
ability to prevent the complications of BPH are unknown.

35
Treatment algorithm of male LUTS (Figure 3).

Figure 3. Non-surgical treatment algorithm of male LUTS due to BPH.

C. SURGICAL MANAGEMENT

Open simple prostatectomy

a. Indications:
i. Large gland size (>80 cc)
ii. Sizable bladder diverticula which merits excision
iii. Large associated bladder calculus
iv. Associated conditions precluding lithotomy position e.g ankylosing spondylitis of hip

b. Approach:
i. Suprapubic (transvesical) approach (Freyers)
ii. Retropubic approach (Millins)

ADVANTAGES: When compared with TURP, open prostatectomy offers the advantages of lower re-treatment
rate and more complete removal of the prostatic adenoma under direct vision and avoids the risk of dilutional
hyponatremia (TUR syndrome) that occurs in approximately 2% of patients undergoing standard TURP.

DISAVANTAGES: As compared with TURP, include the need for a lower midline incision and a resultant longer
hospitalization and convalescence period. There also may be an increased potential for perioperative
hemorrhage.

Tolerability and safety: Mortality has decreased significantly during the past two decades (<0.25%). The
estimated transfusion rate is about 7-14%. Long-term complications include urinary incontinence (up to 10%),
bladder neck contracture (2-5%) and urethral stricture (about 6%). Erectile dysfunction occurs in 3% to 5% of
patients undergoing an open prostatectomy and is more common in older men than in younger men. Retrograde

36
ejaculation occurs in 80% to 90% of patients after surgery. The most common nonurologic adverse effects
include deep vein thrombosis, pulmonary embolus, myocardial infarction, and a cerebrovascular event. The
incidence of any one of these complications is less than 1% and the overall mortality rate resulting from this
operation should approach zero.

Practical considerations: Open prostatectomy is the most invasive but also the most effective and durable
procedure for the treatment of LUTS/BPO. In the absence of an endourological armamentarium and a holmium
laser, open prostatectomy is the surgical treatment of choice for men with prostates > 80 mL.

Minimally invasive surgery

Depending upon the level of energy used and temperature reached in the tissue where the energy source
(monopolar or bipolar electrocautery or laser energy) is applied and the type of electrode or laser fiber being
used, the prostate tissue may get ablated (coagulated and gradually shed away over time), incised or resected
into pieces or vaporized. Based upon this there are many types of procedures available, some of which are listed
below.
1. TURP (Transurethral resection of prostate)
2. TUIP (Transurethral incision of prostate)
3. TUVP (Transurethral vaporization of prostate)
4. TUMT (Transurethral microwave therapy)
5. TUNA (Transurethral needle ablation)
6. Laser
a. HoLEP (Holmium laser enucleation of prostate)
b. HoLAP (Holmium laser ablation of prostate)
c. Photoselective vaporization of prostate (KTP / green light laser)

TURP and TUIP

TURP is considered gold standard for the surgical management of BPH.TURP removes tissue from the transition
zone of the gland. TUIP involves incising the bladder outlet without tissue removal. This technique may replace
TURP in selected cases, especially in prostate sizes < 30 mL without a middle lobe.TURP results in a substantial
mean Qmax improvement (+162%), a significant reduction in IPSS (-70%), QoL score (-69%), and PVR (-77%).
TURP delivers durable outcomes as shown by studies with a follow-up of 8-22 years. There are no similar data
on durability for any other surgical treatment for BPO.

Tolerability and safety: Peri-operative mortality and morbidity have decreased over time, but the latter remains
considerable (0.1% and 11.1%, respectively). The risk of TUR-syndrome is low (< 1.1%). No case has been
recorded after TUIP. Bleeding requiring transfusion (2.9%). Acute urinary retention 4.5% (0-13.3%), clot retention
4.9% (0-39%), and urinary tract infection (UTI) 4.1% (0-22%) are other complications. Long-term complications
comprise urinary incontinence (1.8% after TUIP vs. 2.2% after TURP), bladder neck contracture (BNC) (4.7%
after TURP), urethral stricture (3.8% after TURP vs. 4.1% after TUIP), retrograde ejaculation (65.4% after TURP
vs. 18.2% after TUIP), and erectile dysfunction (6.5% after TURP).

Practical considerations: TURP and TUIP are effective treatments for moderate-to-severe LUTS secondary to
BPO. The choice should be based primarily on prostate volume (< 30 mL and 30-80 mL suitable for TUIP and
TURP, respectively). No studies on the optimal cut-off value exist but the complication rates increase with
prostate size. The upper limit for TURP is mostly suggested as 80 mL (based on Panel expert opinion, under the
assumption that this limit depends on the surgeons experience, resection speed, and choice of resectoscope
size). The size limit criteria are further blurred by the availability of Bipolar resection technique allowing resection
in saline (TURIS or bipolar TURP)

TUVP
Whereas TURP removes tissue by resection of prostatic tissue and causes hemostasis by fulguration,
transurethral vaporization of the prostate (TUVP) combines the concepts of vaporization and desiccation.For
TUVP, the cutting current power needs to be much higher than for a standard TURP. It is suggested that TURP
and TUVP provide comparable improvements in AUA score and peak flow rate for up to 1 year of follow-up.

TUNA
The aim is to increase prostatic temperature to in excess of 60 C using low-level radiofrequency (RF) energy
that is delivered by needles into the prostate and that produces localized necrotic lesions in the hyperplastic
tissue. The TUNA system (Medtronic, Inc, Minneapolis, MN) consists of a special catheter attached to a
generator. At the end of the catheter are two adjustable needles that are withdrawn into two adjustable shields
made from Teflon. The needles are advanced into the prostatic tissue and can be placed accurately into the
required position. The advantage of TUNA is that it can be delivered under topical anesthesia.The long-term
efficacy of the treatment has not been clearly evaluated, with no large series of patients having long-term follow-
up.

37
TUMT
The current transurethral method has developed from the early transrectal devices that supplied heat ranging
from 42 C to 44 C. The results with this early form of treatment were rather disappointing, and transurethral
catheters were developed that would allow higher temperatures to be used while cooling the urethral mucosa. In
one of these devices currently used, the Prostatron, the cooling fluid in the catheter maintains the urethral
temperature at about 44 C or lower while producing temperatures within the prostate of up to 70 C.

Lasers for BPH

Different types of lasers have been used for treatment of BPH. There are two ways in which lasers can have an
effect on the prostate, either by coagulation or by vaporization.

HoLEP and HoLRP (Holmium laser enucleation and holmium laser resection of the prostate)
Mechanism of action: The holmium:yttrium-aluminium garnet (Ho:YAG) laser (wavelength 2140 nm) is a pulsed
solid-state laser that is absorbed by water and water-containing tissues. Tissue coagulation and necrosis are
limited to 3-4 mm, which is enough to obtain adequate haemostasis.

Efficacy: Metaanalyses covering trials on HoLEP vs TURP found that symptom improvement was comparable or
superior with HoLEP. RCTs indicate that HoLEP is as effective as open prostatectomy for improving micturition in
large prostates, with similar re-operation rates after 5 years (5% vs. 6.7%, respectively).
Tolerability and safety: Dysuria is the most common post-operative complication. Compared to TURP, HoLRP or

HoLEP have shorter catheterisation and hospitalisation times. Potency, continence, and major morbidity at 48
months were identical. HoLEP has a shorter catheterisation time and hospital stay, reduced blood loss, and fewer
blood transfusions, but a longer operation time compared with TURP. HoLEP can be safely performed in patients
using anticoagulant medications. The impact on ED and retrograde ejaculation is comparable between HoLEP
and TURP/OP.

Practical considerations: Holmium laser operations are surgical procedures that require experience and relevant
endoscopic skills. The experience of the surgeon is the most important factor affecting the overall occurrence of
complications.

Greenlight laser or photoselective vaporisation of prostate (PVP) using Potassium-Titanyl-Phosphate (KTP)

Laser
Mechanism of action: The kalium-titanyl-phosphate (KTP) and the lithium triborate (LBO) lasers work at a
wavelength of 532 nm. Laser energy is absorbed by haemoglobin, but not by water. Vaporisation leads to
immediate removal of prostatic tissue, relief of BPO, and reduction of LUTS. There are three different Greenlight
lasers in use: the 80-W (KTP), 120-W HPS (LBO), and the 180-W XPS (LBO) laser systems. They differ in
maximum power output, fibre design, and maximum energy application.

Efficacy: Meta-analysis comparing PVP with TURP show equivalent short term results. Re-operation rates tend to
be higher with PVP (11% vs. 1.8%; p = 0.04).

Tolerability and safety: Significantly longer operating time but shorter catheterisation time and length of hospital
stay is seen with PVP. Blood transfusions and clot retention are also less. The Greenlight laser appears to be
safe in high-risk patients under anticoagulation treatment.

Practical considerations: The evolution of the Greenlight laser from 80-W to 120-W and then to 180-W resulted in
a wide variation in the degree of maturity of each laser therapy. Long-term results on 120-W and RCTs on 180-W
are still pending.

Diode Laser vaporization and Thulium laser enucleation

These are lasers available for clinical use using similar techniques as PVP or HoLEP, but make use of different
physical properties of the different laser type. Long term studies are still awaited for these lasers.

Intraprostatic stents
Their role is only in the management of patients who were unfit for surgery, in either the short or the long term, in
which the alternative would have been months or, indeed, a lifetime of indwelling urethral catheterization.In
general, stents are subject to misplacement, migration, and poor tolerability because of exacerbation of LUTS
and encrustation. The main immediate adverse events include perineal pain or bladder storage symptoms.
Treatment algorithm of bothersome LUTS refractory to conservative/medical therapy or with absolute surgical
indications is given in Figure 4.

38
 Figure 4. Surgical treatment algorithm of male LUTS due to BPH

Emerging operations
Intraprostatic ethanol injections, Intra-prostatic botulinum toxin injections, minimally invasive (lap or robotic)
simple prostatectomy, prostatic urethral lift device etc are newer options on the horizon for management of BPH.

References

1. LUTS and BPH by Katie Moore and Jay Khastgir. In Medical Therapy in Urology , Ed. Iqbal shergill et al.
Springer-Verlag London Limited., page 73-87 Doi 10.1007/978-1-84882-702-2
2. http://www.nafc.org/index.php?page=facts-statistics
3. Verhamme, K; Dieleman, JP; Bleumink, GS; Van Der Lei, J; Sturkenboom, MC; Artibani, W; Begaud, B; Berges, R
et al. (2002). "Incidence and Prevalence of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic
Hyperplasia in Primary CareThe Triumph Project". European Urology42 (4): 3238. doi:10.1016/S0302-
2838(02)00354-8
4. Gratzke C, Bachmann A, Descazeaud A, et al. EAU Guidelines on the Assessment of Non-neurogenic Male Lower
Urinary Tract Symptoms including Benign Prostatic Obstruction. Eur Urol. 2015 Jun;67(6):1099-109.
5. Wolf AM, Wender RC, Etzioni RB, et al. American Cancer Societyguideline for the early detection of prostate
cancer: update2010.American Cancer SocietyProstate Cancer Advisory Committee. CA Cancer J Clin. 2010 Mar-
Apr;60(2):70-98.

Management of Renal Malignancies

Kim Mammen, Abhinav Jaiswal

Classification
Many classifications for renal masses are present. One of the earlier classifications was given by Glenn in 1980.
Renal masses can be malignant, benign, or inflammatory as classified by Barbaric (1994) or they can be
classified based on radiographic appearance (simple cystic, complex cystic, fatty tumors, and others).

39
40
RADIOGRAPHIC EVALUATION OF RENAL MASSES

1) Intravenous Pyelography (IVP) - Although intravenous pyelography was often the first test that indicated a
renal mass in the past, it is now only occasionally used for the evaluation of hematuria. The lack of sensitivity
and specificity of intravenous pyelography for the detection of parenchyma tumors is well documented.
Features suggestive of malignancy on intravenous pyelography include calcification within the mass,
increased tissue density, irregularity of the margin, and distortion of the collecting system (Zagoria, 2000).

2) Ultrasonography - When a renal mass is identified by intravenous pyelography, unless the mass has
features suggestive of malignancy, ultrasonography should be the next study performed because it is
noninvasive, accurate, and relatively inexpensive (Davidson et al, 1997; Paspulati and Bhatt, 2006).
Ultrasonography is reliable for differentiation of solid tissue from fluid and can establish the diagnosis of a
simple renal cyst. Strict ultrasonographic criteria for simple cysts have been defined and include a smooth
cyst wall, a round or oval shape without internal echoes, and through transmission with strong acoustic
shadows posteriorly. If these criteria are met, observation is sufficient in an asymptomatic patient.

3) Computed tomography (CT) - A renal mass that is not clearly a simple cyst by strict ultrasound criteria
should be evaluated further with computed tomography (CT). A dedicated (thin-slice) renal CT scan remains
the single most important radiographic test for delineating the nature of a renal mass. In general, any renal
mass that enhances with intravenous administration of contrast material on CT by more than 15 Hounsfield
units (HU) should be considered an RCC until proved otherwise (Hartman et al, 2004). Solid masses that
also have substantial areas of negative CT attenuation numbers (below 20 HU) indicative of fat are
diagnostic of AMLs. On occasion, CT demonstrates an enhancing renal segment that is isodense with the
remainder of the kidney, suggestive of a renal pseudotumor.

4) Magnetic Resonance Imaging (MRI) - Magnetic resonance imaging (MRI) is the alternate standard imaging
modality for the characterization of a renal mass (Pretorius et al, 2000; Zhang et al, 2004; Bassignani, 2006).
A basic consideration in the evaluation of a renal mass is that for such a mass to be considered malignant it
must enhance with the intravenous administration of contrast material. Such enhancement can now be
determined equally well by magnetic resonance angiography with intravenous gadolinium-labeled
diethylenetriaminepentaacetic acid, although the assessment is qualitative rather than quantitative. On T1-
weighted scans before and after administration of gadolinium, enhancement (vascularity) of the mass is
detected. This technique is most helpful in patients for whom iodinated contrast medium is contraindicated
because of severe allergy. One concern with MRI with gadolinium is the uncommon but potentially serious
complication of nephrogenic systemic fibrosis (NSF), which is more common in patients with renal
insufficiency.

5) Renal Angiography - Renal arteriography has a limited role in the diagnostic evaluation of renal masses
and is primarily reserved for patients with concomitant renal artery disease. In equivocal cases, the presence
or absence of neovascularity may help establish the diagnosis of RCC.

Simple renal cysts

1. They comprise of 70% of renal masses
2. They are most common benign lesion
3. Common after 50 yrs of age
4. Pathogenesis Renal vascular compromise or tubular obstruction
5. Investigations USG & CT Scan
6. Treat only if symptomatic - Pain, Bleeding or infection
7. Management
a. Percutaneous drainage & sclerosis-
i. With 95% alcohol
ii. Successful in 90% of cases
iii. Relative contraindication - peripelvic location adjacent to the renal vessels
iv. Laparoscopy preferable
v. Multiple treatment sessions may be required to achieve complete ablation
b. Open drainage
c. Laparoscopic drainage

41
Algorithm for renal masses

Renal Adenoma
1. Most common benign tumor
2. Discovered Incidentally or at post-mortem
3. Small, well-differentiated & typically asymptomatic
4. Radiologically - Very difficult to differentiate from RCC
5. Adenoma of any size should be treated Until proved otherwise
6. Treatment - Renal exploration and wedge resection

Metanephric Adenoma
1. Benign tumor
2. Most common incidental finding
3. Males affected more common than females (M:F:: 2:1)
th
4. Usually present in 5 decade of life
5. Features of polycythemia, hypercalcemia
6. Histologically related to epithelial Wilms' tumor
7. Wilms' tumor protein WT-1 + ve
8. Regression documented
9. Excision is done due to fear of malignancy

42
Cystic Nephroma (Multiloculated Cystic Nephroma
1. Well circumscribed and encapsulated tumor
2. Consists of multiple, non communicating, fluid-filled
spaces partitioned by septa - Hobnailed pattern
3. Unilateral and unifocal
th th
4. Bimodal peak 2-3 yrs of life & 4 5 decade
5. M>>F in Children F>>M in adults
6. Benign Course
7. Children Present as asymptomatic abdominal mass
8. Adults Present as abdominal pain, hematuria, urinary
tract infection, or hypertension
9. Children - TOC - Radical Nephrectomy
10. Adults - TOC Radical nephrectomy / NSS

Oncocytoma
1. Benign tumor
2. Origin Convoluted tubules
3. Asymptomatic
4. Pathology -Central stellate scar ( cut section ) Also seen on CT
5. Spoke wheel pattern on Angiogram
6. Sestamibi Scan Efficacy not proven
7. MRI - well-defined capsule, central stellate scar, and distinctive intensities on T1 and T2 images
8. Treatment - Nephrectomy

Angiomyolipoma
1. Benign neoplasm-characterized by 3 histological components - mature adipose tissue, smooth muscle
and blood vessels
2. Sporadic 80%
3. Associated with Tuberous sclerosis-20%
4. Clinical features - anemia, hypertension & massive retro
peritoneal hemorrhage (Wunderlich's syndrome)
5. 50% are Bilateral
6. Investigations
a. USG well defined, hyperechoic shadowing due to fat

b. CT scan - Presence of fat (confirmed by a value of -20

HU or lower)

c. MRI
i. High intensity signal in T 1 and T 2 (Blood
and protein containing fluid)
ii. Fat suppressed images

d. Renal Angio
i. Hypervascular
ii. Tortuous
iii. Pseudo aneurysms
iv. Onion skin
v. No AV shunting

7. Treatment
a. Observe - Asymptomatic & size < 4cm - imaging at 6- to 12-month intervals

43
 b. > 4 cm active intervention
c. Nephron-sparing surgery - selective embolization
or partial nephrectomy
i. Symptomatic small AML with renal
insufficiency
ii. Bilateral tumors
iii. Solitary kidney
d. Total Nephrectomy - Large & Symptomatic tumor

Leiomyoma
1. Slow-growing, benign arises from capsule or peripelvic tissues
and less often, from the renal vein
2. Previously - large masses with pain, hematuria
3. Now - mostly small and asymptomatic
4. Can be purely cystic to complex cystic or purely solid, some
lesions enhance
5. Differentiation from RCC is not possible by clinical or
radiographic means
6. Large Radical Nephrectomy, NSS for peripheral tumours

Mixed Epithelial Stromal Tumor of the Kidney

1. Recently defined
2. Composed of a mixture of epithelial and stromal elements that
form solid and cystic growth patterns
3. Stain strongly for desmin and smooth muscle actin
4. Also seen in peri menopausal women on estrogen therapy
5. Age : 50 years
6. NSS can be offered but so far being managed by Radical
Nephrectomy

Reninoma
1. Specialized form of a hemangiopericytoma from juxtaglomerular cell.
2. Stain for factor VIII and factor VIIIrelated antigens.
3. Hypertension and hypokalemia and associated symptoms such as polydipsia, polyuria, myalgia, and
headaches
rd th
4. 3 or 4 decade, most commonly in females
5. All cured with excision
6. Consider in patients with severe hypertension and increased Renin ( First rule out RAS)

Renal Cell Carcinoma (RCC)

It is adenocarcinoma. Arises from renal tubular cells. It is the commonest renal tumor in adults (75%).

Aetiology - Smoking, Acquired renal cystic disease & Occupational exposure (e.g. Asbestos, cadmium, and
lead)

Associated with Inherited disorders - Von-Hippel Lindau disease & hereditary papillary renal cancer.

Pathology - Classification
1. Renal cell carcinoma
a) Clear cell (70-80%) Arise from proximal tubules. Tumor cells form small
nests, cytoplasm appears optically clear because glycogen and lipids are
removed by chemicals used in processing.
b) Papillary (10-15%) - Multi-focal and bilateral. Low columnar cells arranged in
papillary formations.
c) Chromophobic (3-5%)
d) Collecting duct (1%)
e) Unclassified (1%)

2. Sarcomatoid variants - No longer considered a distinct histologic subtype of RCC

44
Clinical presentation
50% of RCCs are detected incidentally. Also known as Internist tumor. Classic Triad of flank pain, abdominal
mass & hematuria is seen in 10 to 15% of patients.

Clinically may manifest as

1. Gross or microscopic hematuria 40%
2. Flank pain
3. Flank Mass
4. Left Varicocele
5. Anemia
6. Weight loss
7. Fever

Can also be associated with Paraneoplastic Syndromes.

1. Increased ESR 50%
2. Hypertension
3. Anemia
4. Weight loss
5. Fever
6. Abnormal liver function
7. Hypercalcemia
8. Polycythemia
9. Neuropathy/ myopathy

Investigations

Lab investigations Hb, ESR, Urine deposits for RBCs, renal parameters, Serum Calcium, LFT.

Ultrasound Abdomen - Exophytic, isoechoic, inhomogeneous, irregular mass with varying hypoechoic areas of
cystic degeneration.

Helical CT scan Abdomen - Most accurate imaging. Useful in Tumor staging & to find adjacent organ
involvement. Renal mass enhancement with contrast by more than 15 Hounsfield units.

MRI - On T1-weighted scans before and after administration of gadolinium, enhancement (vascularity) of the
mass is detected. On T2 weighted - hyper intense, compared with normal parenchyma. Indications - Contrast
sensitivity, Contraindication to the use of ionizing radiation e.g. pregnancy, IVC thrombus, Raised parameters.

45
PET (Positron Emission Tomography)
1. Uses radioactive glucose (18-fluorodeoxyglucose or FDG)
2. For staging & detecting tumor recurrence
3. Indication
Detection of small malignant nodes
Post Nephrectomy

Bone Scan Indication- High Serum Alkaline phosphatise, Bone pain

Chest CT Indication - Pulmonary symptoms, abnormal chest radiograph

Staging
Robsons staging
Stage I - Tumor within capsule

Stage II - Tumor invasion of perinephric fat (confined to Gerotas fascia)

46
 Stage III -Tumor involvement of regional lymph nodes or renal vein and vena cava

Stage IV - Adjacent organs or distant metastasis

TNM Staging

47
Staging and Prognosis

TREATMENT
1. Radical nephrectomy
1. Principle - Early ligation of renal pedicle
2. Removal of tumor containing kidney & perirenal fat, adrenal gland regional hilar lymph nodes,
with Gerotas fascia

2. Nephron Sparing Surgery

1. Types Partial nephrectomy or Enucleation
2. Indication - Marginal renal function, Bilateral tumors & Solitary kidney

48
 3. Other modalities
1. Radiotherapy
1. Radio resistant tumor
2. Palliative treatment of osseous or brain metastasis, hematuria
2. Chemotherapy - Poor response
3. Immunotherapy - Interferon alpha & Interleukin-2 ( for metastatic RCC )

Localized RCC Treatment

1. Surgery is the only curative therapy for stage I-III
- Radial nephrectomy is gold standard
- Partial nephrectomy in selected patients
2. No role for adjuvant therapy except under investigational protocol
3. 20-30% of patients relapse within 2-3 years
- Metastases to the lung most common 50%
- Local recurrence is rare 2-3%
4. Active Surveillance
5. Other Management Options

Advanced RCC Treatment

1. Primary treatments are systemic therapy with molecularly targeted therapy or immunotherapy
2. Surgery is palliative therapy for -
a. Solitary metastatic site
b. Solitary recurrence following nephrectomy
c. Symptoms related to bulkiness of disease including pain, nausea, or GI obstruction

Targeted Therapy
Angiogenesis in RCC
Agents targeting VEGF (antibody): Bevacizumab
Agents targeting VEGF pathway:
- Sunitinib
- Sorafenib
Other VEGF pathway antagonists:
- Axitinib
- Pazopanib
- Tivozanib
Agents targeting PI3-K/Akt/mTOR pathway :
- mTOR inhibitors (Temsirolimus/ Everolimus)

49
Immunotherapy
1. Immunotherapy with IL-2 activates immune response against RCC resulting in tumor remission rates 10-
20% with median duration of 19-91 months
2. Severe toxicity including hypotension, capillary leak syndrome, MI, renal insufficiency, pulmonary
edema, hepatic dysfunction, CNS dysfunction
3. Treatment requires ICU monitoring
4. Used for patients that can tolerate side effects.

UROTHELIAL TUMORS OF THE UPPER URINARY TRACT

1. Urothelial tumors involving the renal pelvis or ureter are uncommon
2. Multifocal
3. Etiology Smoking, Balkan Nephropathy, Analgesics, Occupation (petroleum and plastics) & Chronic
Inflammation
4. Risk of bladder cancer High

Clinical presentation
1. Hematuria, either gross or microscopic
2. Flank pain
3. Flank or abdominal mass
4. Weight loss
5. Anorexia

Investigations
1. Intravenous pyelography
a. Radiolucent filling defects
b. Obstruction or nonvisualization of the collecting system

2. CT Scan SOL in renal pelvis with or without involvement of parenchyma

Treatment
Nephroureterectomy with cuff of bladder Standard procedure for higher stage tumors

Alternatively Endoscopic resection for low stage tumors

50
WILMS TUMOR (NEPHROBLASTOMA)
1. Most common childhood renal tumor
2. 5% of childhood cancers
3. Peak First 4 yrs of life
4. Aetiology -
1. Mutations of WT1(11p13) or WT2 (11p15) gene
2. Associated syndromes - Beckwith -Wiedemann or WAGR
Pathology
1. 5% - Multicentric, Bilateral & IVC involvement
2. Histology - triphasic
1. Blastemal
2. Epithelial
3. Stromal
3. Prognostic groups Favorable & Unfavorable (anaplasia)

Clinical presentation
1. Abdominal mass -most common presentation
2. Hematuria in 1/4 of patients
3. Abdominal pain or fever
4. Features of renal vein & IVC involvement
5. Hypertension - 25%
6. Metastasis blood stream to lungs ,liver & bones

Investigations
1. Ultrasound
1. Initial study of choice
2. To differentiate from other masses

51
 2. CT Scan tumor extension & status of opposite kidney

3. MRI - study of choice if extension of tumor into the inferior vena cava

Staging
The most important determinants of outcome- Histopathology and Stage
Children's Oncology Group staging- based primarily on imaging, surgical and histopathologic
findings.

Treatment
Radical nephrectomy- Transperitoneal approach
Accurate staging is essential for subsequent determination of the need for radiation therapy and the
appropriate chemotherapy regimen.
Exploration of the contralateral kidney is no longer indicated
Selective sampling of suspicious nodes.
Formal RPLND is not recommended
Gentle handling of the tumor throughout the procedure is mandatory to avoid tumor spillage- sixfold
increase in local abdominal relapse
Complications - hemorrhage and small bowel obstruction

National Wilms Tumor Study Group (NWTSG)

Formed in 1969 to study Wilms' tumor
NWTS-1 (1969 to 1973)

52
 NWTS-2 (1974 to 1978)
NWTS-3 (1979 to 1986)
NWTS-4 (1987 to 1994)
NWTS-5 (1995 to 2003)

Treatment Protocol Used in the NWTSG-5 :-

Stage I & II- Favourable histology

Surgery
RT and CT- Not indicated

Stage III & IV- Favourable histology

Surgery
Chemotherapy- EEA4 regimen- 18 weeks
Dactinomycin- 75ugm/kg/dose
Vincristine - 0.05mg/kg/dose

Stage I Anaplasia
Surgery
Chemotherapy- EEA4 regimen- 18 weeks
Dactinomycin- 75ugm/kg/dose
Vincristine - 0.05mg/kg/dose

Stage II-IV Focal anaplasia

Surgery
Radiotherapy- 1080 cGy (abdominal and metastatic sites + lungs)
Chemotherapy- DD4A- 24 weeks regimen
Dactinomycin- 75ugm/kg/dose
Vincristine- - 0.05mg/kg/dose
2
Doxorubicin- 20 mg/m /dose

Stage II-IV diffuse anaplasia

Surgery
Radiotherapy- 1080 cGy (abdominal, metastastic sites and lungs)
Chemotherapy- Regimen I: 24 weeks
Dactinomycin- 75ugm/kg/dose
Vincristine- - 0.05mg/kg/dose
2
Doxorubicin- 20 mg/m /dose
Cyclophosphamide- 40-50 mg/kg /dose
Etoposide- 60 to 150 mg/m2/dose

Inoperable Tumors
This decision should not be based on preoperative imaging studies. Pretreatment with chemotherapy almost
always reduces the bulk of the tumor and renders it resectable. A patient determined to have an inoperable tumor
should be considered to have stage III and be treated accordingly. Repeat imaging is performed after 6 weeks of
chemotherapy. Majority of the reduction in tumor volume occurs in the first 4 weeks. After adequate shrinkage of
the tumor has occurred, definitive resection can be completed. Patients with progressive disease have a very
poor prognosis, and these patients will require treatment with a different chemotherapeutic regimen.

53
Bilateral Wilms Tumors
Occur in about 5% of children. Preferred approach- Initial biopsy, followed by preoperative chemotherapy. Renal
failure occurs in 9.1% and 18.8%, respectively, of patients with synchronous and metachronous bilateral Wilms'
tumor. Nephrectomy can be avoided entirely in almost 50% of patients who undergo initial biopsy followed by
chemotherapy. After 6 weeks of chemotherapy, repeat imaging is performed to assess response. Tumors not
responding to therapy require open biopsy to determine their histology. Patients with blastemal predominant or
anaplastic tumor should be changed to a different chemotherapeutic regimen. The patient should be reassessed
after an additional 12 weeks of chemotherapy to determine the feasibility of resection.

Options
Partial nephrectomy or wedge excision of the tumors
Radical nephrectomy on one side
Bilateral nephrectomy and dialysis - most common cause of renal failure
Transplantation- Waiting period of 2 years to ensure that metastatic disease does not develop

Partial Nephrectomy for Unilateral Tumors

Patients with the WAGR syndrome have an increased risk for renal failure, 38% at a median of 14 years from
diagnosis after radical nephrectomy. There is also an increased risk for renal failure in children with genitourinary
anomalies and Wilms' tumor. After preoperative chemotherapy, partial nephrectomy can be performed in 10% to
15% of patients. Increased risk for local recurrence after partial nephrectomy 8%.

Surgical protocol
The lesion should be completely excised with a margin of normal renal parenchyma
Frozen sections to confirm a negative margin and also to evaluate the histology
Patients with anaplasia or persistent blastemal predominant tumor after chemotherapy should be treated
by complete nephrectomy.

Outcome

LEIOMYOSARCOMA
1. MC subtype of sarcomas - 50-60 %
2. Cell of origin smooth muscle cell of the capsule or other perinephric structures
3. Female >> Males
th th
4. 4 6 Decade
5. Displaces rather than invading
6. Poor prognosis
7. Clinical features - Very large or rapidly growing renal mass, pain & hematuria
8. Investigation CT Scan or MRI
9. Nodal spread most common after lung involvement
10. Treatment- Radical Nephrectomy with good margins

CARCINOID TUMORS
1. Neuroendocrine cells - Primitive stem cells
2. Most asymptomatic
3. Minority will present with the carcinoid syndromeepisodic flushing, wheezing, and diarrhoea
4. Stain positive for neuron-specific enolase and chromogranin
5. Measurement of urinary or plasma serotonin or its metabolites can be diagnostic
6. CT findings are nonspecific, and most renal carcinoids are small and nonaggressive.
7. Surgical excision is the mainstay of treatment
8. Nephron-sparing surgery is preferred if the diagnosis is suspected preoperatively.
9. Prognosis is good, particularly when it is associated with a horseshoe kidney

LYMPHOMAS / LEUKEMIAS
1. Lymphomas
a. Bilateral
b. Non-Hodgkin's lymphoma - diffuse forms predominate
c. Risk Factors- Immune suppression, AIDS

54
 2. Leukemias
a. Children- diffusely infiltrative
b. Commonly due to lymphocytic leukemia than the myelogenous forms
3. CT scan -Radiographic modality of choice
4. Treatment Chemotherapy (NHL-CHOP protocol), which includes cyclophosphamide, doxorubicin,
vincristine, and prednisolone.
5. Nephrectomy not indicated except in uncontrollable hemorrhage.

METASTATIC TUMORS
1. Most common sources - Lung, Breast & GIT
1. Mostly multifocal
2. Diagnosis - CT (isodense masses that enhance only moderately (5 to 30 HU) hypovascular pattern) or
ultrasound-guided percutaneous renal biopsy
3. Treatment- systemic therapy/palliative care
4. Nephrectomy if uncontrollable renal hemorrhage

References

1. Jonasch E, Matin S, Wood CG, Pagliaro LC. Renal cell carcinoma. In: Kantarjian HM, Wolff RA, Koller CA, eds. MD
Anderson Manual of Medical Oncology. New York, NY: McGraw-Hill; 2006. 757-84.
2. Linehan MW, Berton Z, Bates S. Cancer of kidney and ureter. In: Devita VT Jr, Hellman S, Rosenberg SA,
eds. Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 1362-96.
3. Simon JW, Marshall FF. Kidney and ureter. In: Abeloff MD, Armitage J, Niederhuber J, Kastan M, McKenna W,
eds. Clinical Oncology. 2nd ed. New York, NY: Churchill Livingstone; 2000. 1784-99.
4. Cho E, Curhan G, Hankinson SE, et al. Prospective evaluation of analgesic use and risk of renal cell cancer. Arch
Intern Med. 2011 Sep 12. 171(16):1487-93.
5. Surveillance Epidemiology and End Results. SEER Stat Fact Sheets. National Cancer Institute. Available
at http://seer.cancer.gov/statfacts/html/kidrp.html. Accessed: September 15, 2015.
6. Robson CJ, Churchill BM, Anderson W. The results of radical nephrectomy for renal cell carcinoma. J Urol. 1969
Mar. 101(3):297-301.
7. Robson JS. Advances in the treatment of renal disease. Practitioner. 1969 Oct. 203(216):483-93.
8. Cancer Facts & Figures 2014. American Cancer Society. Available at
http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed:
September 15, 2015.
9. Abdollah F, Sun M, Thuret R, et al. Mortality and morbidity after cytoreductive nephrectomy for metastatic renal cell
carcinoma: a population-based study. Ann Surg Oncol. 2011 Oct. 18(10):2988-96.
10. Heng DY, Xie W, Bjarnason GA, et al. Progression-free survival as a predictor of overall survival in metastatic renal
cell carcinoma treated with contemporary targeted therapy. Cancer. 2010 Nov 18.
11. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670
patients with advanced renal cell carcinoma. J Clin Oncol. 1999 Aug. 17(8):2530-40.
12. Zisman A, Pantuck AJ, Wieder J, et al. Risk group assessment and clinical outcome algorithm to predict the natural
history of patients with surgically resected renal cell carcinoma. J Clin Oncol. 2002 Dec 1. 20(23):4559-66.
13. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology.Kidney
Cancer. 2014. v.3:
14. [Guideline] Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J
Urol. 2009 Oct. 182(4):1271-9.
15. Sauk SC, Hsu MS, Margolis DJ, et al. Clear cell renal cell carcinoma: multiphasic multidetector CT imaging features
help predict genetic karyotypes. Radiology. 2011 Dec. 261(3):854-62

SUGGESTED READINGS
1. Campbell-Walsh Urology, 10th Edition By Alan J. Wein, Louis R. Kavoussi, Andrew C. Novick, Alan W. Partin, and
Craig A. Peters.
2. Smith and Tanagho's General Urology, Eighteenth Edition (Smith's General Urology) by Jack W. Mcaninch, Tom F.
Lue

Investigative workup of a patient with surgical disease of the kidney

An accurate history and careful examination will determine the sequence and spectrum of clinical investigations
required to make a diagnosis or decide on prognosis or treatment.

Description
The urinary tract consists of the kidneys, ureters, bladder, urethra and, in men, the prostate gland.
Imaging of the urinary tract can involve the following tests:
Plain kidney, ureters and bladder (KUB) testing.
Intravenous urogram.
Ultrasonography.
Nuclear medicine - including mercaptoacetyltriglycine (MAG3) and dimercaptosuccinic acid (DMSA)
scans.

55
 Cystography.
Computed tomography (CT) scan.
Magnetic resonance imaging (MRI) scan.
More invasive tests.

Examination of the urine

Midstream urine (MSU) samplethis standard investigation requires consideration of: (1) macroscopic
appearancethis may be suggestive of a diagnosis, e.g. frothy urine suggests heavy proteinuria; (2) stick
testingincluding for pH (<5.3 in an early-morning specimen makes a renal acidification defect unlikely),
glycosuria, specific gravity (should be >1.024 in an early-morning or concentrated sample), nitrite (>90% of
common urinary pathogens produce nitrite) and leucocyte esterase; and (3) microscopyfor cellular elements (in
particular red cells, with the presence of dysmorphic red cells detected by experienced observers indicative of
glomerular bleeding), casts (cellular casts indicate renal inflammation), and crystals.
Quantification of proteinuriathis is important because the risk for progression of underlying kidney disease to
endstage renal failure is related to the amount of protein in the urine. Quantification by 24-h urinary collection is
cumbersome and unreliable in many patients, and has been replaced by estimation of the urinary
albumin:creatinine ratio (ACR; normal is <2.5mg/mmol for men and less than 3.5mg/mmol for women) or
protein:creatinine ratio (PCR; normal is <13mg/mmol) on a spot sample. An ACR of 100mg/mmol approximately
corresponds to proteinuria of 1.5g/day, and 350mg/mmol to nephrotic-range proteinuria.
Low-molecular-weight proteinuriais caused by proximal tubular injury and can be detected with markers
including -glutathione-S-transferase, 1-macroglobulin, and retinol-binding protein.

Estimation of glomerular filtration rate

Knowledge of the glomerular filtration rate (GFR) is of crucial importance in the management of patients, not only
for detecting the presence of renal impairment, but also in the monitoring of all patients with or at risk of renal
impairment, and in determining appropriate dosing of those drugs cleared by the kidney. Measurement of plasma
creatinine remains the standard biochemical test used to assess renal function.
Estimating the glomerular filtration rate (eGFR)from a measurement of plasma creatinine concentration, the
standard method uses the simplified Modification of Diet in Renal Disease (sMDRD) formula, which was based
on a predominantly Caucasoid North American cohort with chronic kidney disease, and requires knowledge of
the patients sex, age, and ethnicity (but not their weight or height). On the basis of the eGFR, stages of chronic
kidney disease (CKD) are classified as follows:
Limitations of the eGFRthis has not been validated in people below 18years of age, hospitalized patients, or
those with acute kidney injury, pregnancy, oedematous states, muscle-wasting disorders, amputations, or
malnourishment. Similarly, it has not been validated for extremes of age or body weight, or for ethnic groups
other than whites of northern European origin and African-Americans. Because of the inaccuracy of the MDRD
equation, particularly for those with eGFRs greater than 60 ml/min, a revised version (CKD-EPI) has been
introduced.
Other methods of measuring GFRisotopic methods can provide the most accurate determination of GFR, but
are not often required in routine clinical practice. Estimation of creatinine clearance with a 24-h urinary collection
remains a useful test, particularly when there is reason to doubt the validity of the eGFR.

Investigation of tubular function

Proximal tubuleanalysis of excretion of the following substances can assist in the diagnosis of proximal tubular
disorders: (1) glucosethe maximum reabsorption rate for glucose (TmG) in the proximal tubule can be
determined following infusion of 20% dextrose and is normally about 15mmol/litre (TmG/GFR); (2) phosphate
the theoretical maximum tubular threshold of phosphate (TMP/GFR) can be estimated by formula from the plasma
and urinary phosphate and creatinine concentrations, or can be measured directly following infusion of
phosphate; and (3) amino acidsfive types of renal aminoaciduria are distinguished: dibasic amino acids, neutral
amino acids (monoaminomonocarboxylic acids), glycine and imino acids, dicarboxylic amino acids, and
generalized amino aciduria (Fanconis syndrome).
Distal tubulea water-deprivation test can help to distinguish patients with primary or secondary nephrogenic or
cranial diabetes insipidus from those with primary polydipsia, who may all present with polyuria.
Renal-induced electrolyte and acidbase imbalances (1) estimation of urinary free-water clearance is useful in
the analysis of patients with hyponatraemia (see Chapter 21.2.1); (2) estimation of transtubular potassium
gradient (TTKG) is advocated by some as useful in analysis of disorders of potassium homeostasis (see Chapter
21.2.2); (3) tests of urinary acidification are discussed in Chapters 21.14 and 21.15.

Renal imaging
Ultrasonographythis noninvasive, safe, versatile and (relatively) inexpensive technique is the first-line method
for imaging the kidney and urinary tract in many clinical circumstances.

Ultrasonography
[3]
Generally ultrasonography is an excellent imaging modality as it is non-invasive, reliable and affordable. It can
be used to investigate the kidney, bladder, and prostate gland. It can also be combined with voiding, providing an
indication of the residual volume. This gives an indirect measure of bladder function.

56
Renal ultrasonography is useful for the following:
Acute kidney injury - mainly looking for post-renal obstruction.
Chronic kidney disease - the presence of small shrunken kidneys suggests irreversible damage. Normal
[3]
kidney size is approx 11 cm (varies with age, gender and race).
Detecting hydronephrosis and hydroureter.
Some children post following a urinary tract infection.[2]
Congenital anomalies - eg, hypoplasia, agenesis, duplex systems.
Renal cysts, abscesses and neoplasms can be detected - eg, simple cysts, polycystic kidneys.
Renal calculi can be detected but they can be mistaken for vessels or calcified tumours. [3]
Renal ultrasound can be combined with Doppler imaging to view the renal artery and vein, which may
help detect thrombosis, stenosis or aneurysms.
The kidneys are well shown by ultrasound which has the valuable property of distinguishing between
renal solid masses and renal cysts. Cysts can also be localised by ultrasound for percutaneous
puncture. Hydronephrosis is also well demonstrated by ultrasound as are polycystic kidneys. In the field
of renal transplantation ultrasound is valuable in showing perirenal fluid and lymph collections
(lymphoceles) and confirming swelling of the kidneys associated with rejection.
The distended bladder is also well shown by abdominal ultrasound and tumours including infiltration of
the wall can be assessed. The prostate can also be demonstrated, but is best examined by endoscopic
transrectal ultrasound. This is now widely used for ultrasound-guided biopsy of suspected prostatic
carcinoma and other prostatic lesions.
Most early carcinomas show as low density areas in the subcapsular zone but require biopsy for
confirmation since the appearance is non-specific. Patients with a raised prostatic serum antigen (PSA)
level or clinical suspicion of prostatic carcinoma may require multiple biopsy of the prostate under
ultrasound guidance.

Fig. Longitudinal ultrasound scan of normal kidney. The renal sinus is echogenic. The pyramids are relatively
hypoechoic compared with the remainder of the parenchyma. The dense echoes (arrows) at the bases of the
pyramids are due to the arcuate arteries.

Fig.Parasagittal section.Simple renal cyst.

57
 RADIOLOGICAL EXAMINATION OF THE URINARY TRACT
The following radiological and imaging methods are available for the investigation of the urinary tract:
1. Simple radiology
2. Intravenous urography
3. Retrograde pyelography
4. Antegrade pyelography
5. Renal angiography
6. Cystography, cystourethrography and dynamic bladder studies
7. Urethrography
8. Cyst puncture
9. Ultrasound
10. Computed tomography
11. Isotope imaging and renography
12. MRI.

Plain X-rays
Plain X-rays of the renal tract are taken as a routine before most kidney investigations. Good quality
films will often show the renal outlines quite clearly, and gross enlargement of the kidney by
hydronephrosis or tumour may be readily recognised. Similarly, gross shrinkage of the kidney from
chronic pyelonephritis or from renal ischaemia may be diagnosed.
Calcification in the renal areas is most commonly due to renal calculi in the calyces or renal pelvis.
Nephrocalcinosis, or calcification within the renal substance, is much less common, and is seen in such
rare conditions as hyperparathyroidism, renal tubular acidosis, and medullary sponge kidney.
Calcification may also be observed in the kidney in renal tuberculosis, and occasionally in renal
tumours.
Plain X-rays will also demonstrate opaque calculi in the ureter and in the bladder. Calcification in the
bladder wall and ureter is seen in schistosomiasis. Very rarely calcification may be detected in bladder
tumours due to encrustations on the surface of a tumour.

Fig. Laminated bladder calculus shown by plain X-ray.

Plain kidney, ureters and bladder imaging

Plain x-rays can reveal opaque renal calculi. They may also be helpful in nephrocalcinosis where there is
increased uptake of calcium by the kidneys. CT scan of kidneys, ureter and bladder is the preferred imaging
modality looking for renal calculi. CT scanning has a higher radiation dose than plain x-ray but it has a much
better sensitivity for detecting a stone both directly and indirectly (eg, by detecting dilated ureter or
hydronephrosis). Spiral CT takes only five minutes and no preparation is required. Furthermore, CT scanning can
[1]
also detect lesions other than renal calculi - for example, perinephric abscesses and tumours.

Micturatingcystourethrogram - this involves instillation of contrast into the bladder following which x-rays are
[2]
taken whilst voiding. It is used in some children following a urinary tract infection.

Intravenous urogram
This is most useful when looking for obstruction in the urinary tract - for example, hydronephrosis due to the
presence of renal calculi. Other uses include diagnosis of medullary sponge kidney. However, it is time-
consuming and the use of contrast can lead to contrast nephropathy (good hydration is essential). Thus it is
important to have renal function tested beforehand and it should be used with caution in the elderly and in those
with renal impairment.

Provided that the kidney is functioning and the blood urea is not too high, intravenous urography will demonstrate
most lesions affecting the normal anatomy of the renal drainage system.

58
 Congenital anomalies, such as double pelves and ureters, or duplex and horse-shoe kidneys, can be
diagnosed with certainty. Polycystic kidneys can also be identified unless renal failure has supervened.
In a typical case both kidneys are enlarged, and there are multiple calyceal deformities.

Local distortion of the renal calyces by a kidney mass is often seen on urography. In many of these
cases it is impossible to differentiate between hypernephromaand a simple cyst from the pyelogram. In
such cases imaging by ultrasound will provide a definitive answer and is the next investigation of choice.
CT will also differentiate renal tumour from cyst. If a cyst is demonstrated the diagnosis can be
confirmed by percutaneous cyst puncture, and the cyst can then be emptied by aspiration. If a tumour is
diagnosed or suggested by ultrasound the diagnosis can be confirmed by CT. This will also help staging
and show whether the renal vein is involved. Arteriography will also confirm the diagnosis of tumour, but
is now little used except where embolisation is being considered.

Fig.Polycystic kidneys. Note the bilateral splaying and deformity of the minor calyces and large size of the
kidneys.

Opaque or suspected non-opaque renal calculi may be further investigated by intravenous urography.
The relationship of an opaque renal calculus or of a suspected renal calculus to the ureter, pelvis or
calyces is clearly demonstrated. Non-opaque calculi are shown as filling defects which may be
obstructing the renal drainage system and causing hydroureter and hydronephrosis proximal to the level
of the obstruction.

Fig.Hydronephrosis with a calculus in the dilated lower calyx.

The bladder is also well shown at intravenous urography. Bladder tumourswhether papillomatous or
carcinomatous can be demonstrated though such tumours may be better visualised by cystography.
With carcinoma, assessment by ultrasound, CT or MRI may be required for staging.

59
Fig. MRI study of bladder carcinoma (arrow), b = bladder; r = rectum; n = nodal metastases on left side of
pelvis.

Prostatic lesions with bladder-neck obstruction are often assessed by intravenous urography. The
enlarged prostate may show as a large rounded filling defect at the neck of the bladder. The bladder
itself may show trabeculation and thickening of its wall and there may also be evidence of back pressure
on the kidneys. Diverticula of the bladder, which are more frequent in the elderly patient with bladder-
neck obstruction, can also be seen. In prostatic problems it is important to obtain a film or ultrasound
scan of the bladder after micturition, as the amount of residual urine gives a good index of the degree of
obstruction.

Hypertension of possible renal origin is investigated by intravenous urography in the first instance. This
will demonstrate unilateral or bilateral hydronephrosis and will direct attention to the unilateral
nonfunctioning kidney or to polycystic kidneys. Intravenous urography may also show a characteristic
pattern in hypertensive patients in whom the cause is unilateral ischaemia of a kidney. In these patients,
in whom the usual causative lesion is an atheromatous plaque stenosing the main renal artery the
ischaemic kidney is small and shows increased density of contrast in the pelvis and calyces as the
examination proceeds. This is because there is a greater percentage of water resorption on the affected
side than on the normal side.

Fig. Atheromatous renal artery stenosis shown by renal arteriography.

Retrograde pyelography
Retrograde pyelography is performed after cystoscopy and the insertion of a radiopaque ureteric
catheter by the surgeon. A small quantity of sterile contrast medium is injected up the catheter to outline
the renal tract and appropriate films are taken. The retrograde pyelogram was once used as a method of
clearly defining the anatomy of the renal drainage system in the patient with a non-functioning kidney or
with a poorly functioning kidney when intravenous pyelography had failed to provide adequate
visualisation. It is less widely practised today than in the past because the modern intravenous contrast
media with the use of high dosage and delayed films often provide diagnostic results where the older
contrast media might have been unsuccessful, and also because cases of suspected tumour or cyst are
now usually investigated by ultrasound or other methods mentioned above.
Retrograde pyelography is still sometimes used to confirm or disprove the relationship of a suspected
small calculus to the ureter. It is also sometimes used to help dislodge a ureteric calculus and 'oil' it
down the ureter.

60
Antegrade pyelography (percutaneous nephrostomy)
Percutaneous antegrade pyelography is a useful method of demonstrating the renal calyces, pelvis and
ureter in cases of suspected urinary tract obstruction where the intravenous method has been
unsuccessful or inconclusive. Unlike retrograde urography it does not require GA and it has a lower
incidence of urinary tract infection. It is also useful in infants and children where cystoscopy is difficult or
impossible.
A dilated renal calyx is punctured percutaneously from the lumbar region using a fine needle, and
contrast medium is injected. The technique can also be used to insert a catheter and provide temporary
drainage. The catheter tract can also be used for a percutaneous approach to renal calculi and for stent
insertions.

Renal angiography
An opaque catheter is passed percutaneously into the aorta and its preshaped tip is screened into the
renal artery origin with the aid of an image intensifier. The whole renal circulation can be beautifully
demonstrated using only a small quantity of low-concentration contrast medium.
The renal angiogram in the past provided a method of making a preoperative differential diagnosis in the
difficult cases in which a mass had been demonstrated in the kidney but it was uncertain whether this
was due to a tumour or cyst. The typical hypernephroma shows excessive vascularity with pathological
vessels throughout the tumour area. The typical cyst appears as a large rounded defect in the
angiogram. The method was highly accurate in differentiating between tumours and cysts though
occasionally a non-vascular tumour was encountered which gave rise to difficulty. As noted above
ultrasound or CT now provide simpler methods of confirming the diagnosis of renal cyst or tumour.
Renal angiography has also been widely used for the embolisation of vascular tumours and for the
investigation of renal hypertension. A small proportion of patients with hypertension are suffering from
renal ischaemia with secondary hypertension. The usual cause is an atheromatous narrowing of the
origin of a renal artery. Other less common causes of renal artery stenosis include a peculiar condition
occurring mainly in female patients and termed fibromuscular hyperplasia of the renal artery (Fig. 10.9).
Renal artery stenosis shown by angiography can now be treated by percutaneous dilatation with a
Gruntzig balloon catheter.

Fig.Atheromatous renal artery stenosis shown by renal arteriography.

Fig. Fibromuscular hyperplasia (1) shown by renal angiography.

Cystography
Cystography is performed after passage of a catheter into the bladder and injection of contrast medium.
The method is useful for outlining tumours of the bladder when intravenous urography has been
unsuccessful or equivocal. Ultrasound can also be used to demonstrate bladder tumours and CT or MRI

61
 enables such tumours to be assessed and staged. The patient can then be asked to void and the extent
of vesicoureteral reflux and urinary stress incontinence can be assessed.
Attention has been drawn to the frequent occurrence of vesicoureteric reflux and to the importance of
this condition in the pathogenesis of chronic pyelonephritis. It is claimed that vesicoureteric reflux is
present in a high proportion of patients with chronic pyelonephritis, and that it may be an important
aetiological factor. Reflux is best demonstrated by performing a micturatingcystogram, though it may
occur spontaneously when the bladder is well filled. As the patient micturates, reflux up the ureters may
be seen as the bladder contracts.

Fig.Spontaneous vesicoureteric reflux after injection of the bladder through an indwelling catheter. There is
already gross hydroureter and hydronephrosis. (Urethral obstruction in a child due to congenital valves.)

Cystourethrography
This examination is used for the investigation of bladder-neck obstruction in males, the various forms of
bladder-neck disturbance seen in postpartum females, and other disorders of the peripheral control of
micturition. The technique is to fill the bladder via a catheter which is then removed. The act of
micturition is observed on the screen and films of the bladder-neck and urethra taken during micturition.
As already noted,vesicoureteric reflux may be observed during this procedure and is an important
finding. The procedure is performed with the aid of an image intensifier. This has the added advantage
that it is possible to take a video film or videorecord of the act of micturition. This can then be played
back and details observed at leisure.
Dynamic bladder studies are indicated in more complicated bladder problems with incontinence,
frequency, disorders of storage function and voiding, neuropathic bladder and postoperative disturbed
function. Various physiological measurements are superimposed upon a video image of the bladder and
urethra during filling and voiding. These measurements are the abdominal and bladder pressures
(recorded by rectal and bladder transducers respectively), the detrusor or intrinsic bladder pressure (the
recorded bladder pressure minus the abdominal pressure) and the urine flow rate. Analysis of these
synchronous recordings permits improved evaluation of the mechanisms of the bladder dysfunction.

Urethrography
Urethrography in the male is usually performed by injection of a viscous contrast medium which
provides excellent contrast throughout the urethra. The contrast medium is injected after insertion of a
tight-fitting nozzle into the meatus and the whole of the urethra is outlined. Obstruction by a stricture can
then be localised, and in the case of prostatic problems the prostatic urethra can be carefully studied.

Computed tomography scanning of the urinary tract

Again this involves a significant radiation dose, thus needs to be considered with care. It is useful in detecting the
following:
Renal calculi - as discussed under 'Plain kidney, ureters and bladder imaging', above.
Renal and bladder neoplasms - for detection and staging.
Renal trauma - detecting perinephric haematoma, for example.

Ultrafast multislice CT scanningthis allows resolution of 2 to 3mm or less and has become the mainstay of
renal imaging. CT urography can be performed with a combination of unenhanced, nephrogenic-phase, and
excretory-phase imaging: the unenhanced images are ideal for detecting urinary calculi; renal masses can be
detected and characterized with the combination of unenhanced, nephrogenic- and excretory-phase imaging; the
excretory phase provides imaging of the urothelium. CT angiography is the first-line investigation in the
evaluation of acute renal trauma, assessment of tumour blood supply in cases of nephron-sparing surgery, and
for the diagnosis of renal artery stenosis and/or aneurysms.

62
MRIthis is an alternative to CT scanning in patients who are allergic to conventional iodine-based radiocontrast
media and has particular value in the staging of renal carcinoma and assessment of complex renal cysts.
Magnetic resonance angiography (MRA) tends to overemphasize the significance of stenoses. Gadolinium
contrast scanning should be carefully considered in patients with eGFR below 30ml/min because of the risk of
nephrogenic systemic fibrosis, which limits the utility of magnetic resonance techniques for many renal patients.

Magnetic resonance imaging scanning of the urinary tract s is used in the following groups of patients:
Those who are at risk of contrast nephropathy.
Those who have an allergy to contrast agents.
Children. Magnetic resonance (MR) urography is being used in children and has the advantage that it
provides both functional and morphological imaging. However, this requires the use of complex
software.
Those with renal cell carcinoma.
Women with chronic urinary tract infections.

Enhanced MRI technology is also proving increasingly important in renal cell carcinoma but is still in an
experimental stage - eg, response to chemotherapy. MRI is also superior to CT scanning in detecting renal cell
carcinoma metastases into the renal vein. It may also be better when trying to determine whether renal lesions
are simply cysts, neoplastic or haematomas. It can also be used in the detection of renal artery stenosis -
magnetic renal angiography (MRA).

More invasive investigations

Ureteropyelography
Anterograde ureteropyelography - this requires puncture via the skin into the renal pelvis. Via the
puncture, contrast is injected and images obtained. This procedure can also be used to relieve
obstruction by insertion of a nephrostomy tube.
Retrograde ureteroscopy - this is performed by insertion of a cystoscope into the urethra and bladder.
This is followed by injection of contrast into the distal ureter, after which images are taken.

Angiography
This can be performed with the aid of CT or MRI. It is invasive and requires cannulation of the renal arteries. It
will provide a definite diagnosis of stenosis and allows angioplasty if necessary. There is also a risk of embolism
resulting from trauma to plaques.

Cyst puncture
Renal cysts can be punctured percutaneously from the lumbar region. This is best done under ultrasound control
when the point of puncture and the depth and size of the cyst can be assessed. The straw-coloured fluid they
contain is aspirated. Once the cyst is entered it can be outlined by injecting a small quantity of contrast medium.
This will show the size of the cyst and the contrast can be used to confirm that most or all of the fluid has been
aspirated.

ISOTOPE SCANNING
m
"Tc DMSA (dimercaptosuccinic acid) is widely used for renal imaging. This compound is fixed in the tubules with
a low extraction rate and good images may be obtained 1-2 hours after injection.
Lesions such as tumours show as filling defects as do benign lesions such as cysts (Fig. 10.14). In chronic
pyelonephritis uptake is often reduced and uneven as it is in other conditions with poor renal function, such as
obstructive uropathy and tuberculosis.

Renography.This method of scanning is widely used in renal' disease. It differs from normal scanning in that a
131 123
graph is obtained of the renal output of the isotope. The radioisotope used is usually I-hippuran or I-
hippuran. This is removed almost entirely from the kidney in one passage and is not reabsorbed. Scanning must
therefore take place immediately after a small intravenous injection of the radioactive isotope. A scintillator
counter is centred evenly over each kidney touching the skin. The normal renogram graph usually shows:
1. A sharp rise of activity within 30 seconds of the injection (A-B)
2. A slower rise during the next 3 to 5 minutes (B-C)
3. Falling off in the next 15 minutes (C-D).

This is the normal pattern but it will be changed in various ways depending on the type of disease from which the
kidney is suffering.

Comparison of the function of the two kidneys is also possible by comparing the results on the two sides.

63
 99 m
Fig.Right renal cyst. Tc DMSA scan.Posterior projection. (A) Normal left image. (B) There is a non-specific
deficit in the upper half of the right kidney due to a cyst.

131
Fig. I-hippuran renogram. Normal. For explanation see text

Nuclear medicine involves low amounts of radiation and provides information regarding renal perfusion,
function and the contribution each kidney is making to total function. Renal nuclear medicine scanning(1)
dimercaptosuccinic acid (DMSA), used in estimation of differential renal function and detection of scarring
(usually associated with reflux); (2) mercaptoacetyltriglycine (MAG3), used in detection of functionally significant
obstruction, estimation of differential renal function, screening for renal artery stenosis, and monitoring of renal
transplants.

FDG-PET scanning combines the functional aspects of a nuclear medicine scan with the anatomical definition of
CT scanning and is used to investigate renal tumours and to diagnose and monitor large vessel vasculitis.

Invasive techniquesthese can allow therapeutic intervention as well as diagnosis, including antegrade or
retrograde ureteropyelography (insertion of stents to relieve urinary obstruction) and angiography (angioplasty or
stenting of the renal artery).
These procedures include 99m Tc-mercaptoacetyltriglycine scanning (MAG3) and 99m Tc-
diethylenetriamine-pentaacetate (DTPA) uptake scans.The latter is mostly being overtaken by the
former. These allow dynamic imaging, as both are filtered by the glomerulus and excreted by the kidney.
MAG3 scanning is useful in hypertension (looking to see whether those who have renovascular disease
will benefit from procedures to improve renal blood flow).MAG3 is also useful in delayed graft function
following renal transplant and discriminating between functional renal obstruction and simple dilatation
[4]
alone.
Scintigraphy can also be performed with DMSA. DMSA is given by intravenous injection and then static
imaging is performed 2-4 hours later. This provides information on the contribution each kidney is
making to total function. Thus it is useful in situations where there is bilateral scarring. It is also used in
some children following a urinary tract infection.

Renal biopsy
A renal biopsy should be considered in any patient with disease affecting the kidney when the clinical information
and other laboratory investigations have failed to establish a definitive diagnosis or prognosis, or when there is
doubt as to the optimal therapy. However, renal biopsy has the potential to cause morbidity and (on rare
occasions) mortality, hence its risk must be outweighed by the potential advantages of the result to the individual
patient. Biopsies which would be of interest but not in the patients interest should not be performed.

64
 Benign Breast Diseases

The vast majority of the lesions that occur in the breast are benign. Much concern is given to malignant lesions of
the breast because breast cancer is the most common malignancy in women in Western countries; however,
benign lesions of the breast are far more frequent than malignant ones. With the use of mammography,
ultrasound, and magnetic resonance imaging of the breast and the extensive use of needle biopsies, the
diagnosis of a benign breast disease can be accomplished without surgery in the majority of patients. Because
the majority of benign lesions are not associated with an increased risk for subsequent breast cancer,
unnecessary surgical procedures should be avoided. It is important for pathologists, radiologists, and oncologists
to recognize benign lesions, both to distinguish them from in situ and invasive breast cancer and to assess a
patients risk of developing breast cancer, so that the most appropriate treatment modality for each case can be
established.

The term benign breast diseases encompasses a heterogeneous group of lesions that may present a wide
range of symptoms or may be detected as incidental microscopic findings. The incidence of benign breast lesions
begins to rise during the second decade of life and peaks in the fourth and fifth decades, as opposed to
malignant diseases, for which the incidence continues to increase after menopause, although at a less rapid
pace.

In this review, the most frequently seen benign lesions of the breast are summarized as developmental
abnormalities, inflammatory lesions, fibrocystic changes, stromal lesions, and neoplasms.

Developmental Abnormalities
Ectopic breast (mammary heterotopia), which has been described as both supernumerary and aberrant breast
tissue, is the most common congenital abnormality of the breast. Supernumerary breast tissue is seen mostly
along the milk line; the most frequent sites are the chest wall, vulva, and axilla. It may vary in its components of
nipple (polythelia), areola, and glandular tissue (polymastia). However, an anatomic location outside the milk line
should not preclude a diagnosis of ectopic breast tissue, because there are many well-documented, unusual sites
of such tissue, including the knee, lateral thigh, buttock, face, ear, and neck. Aberrant breast tissue is usually
located near the breast, most commonly in the axilla. They usually have a nipple and areola and a separate duct
system from that of the normal breast. When the nipple is absent, the presence of the accessory breast tissue is
difficult to identify. The accessory breast tissue responds in the same way as normal breast tissue to
physiological influences. The absence of a duct system may cause symptoms of obstruction during lactation and
may be mistaken clinically for a carcinoma. Accessory breast tissue and polymastia are more common among
Asians, especially Japanese, than whites. Recognition of ectopic breast tissue is important because it can serve
as a milieu for the development of a variety of benign and malignant lesions encountered in the normal breast. It
has been reported that ectopic breast tissue is more prone to malignant change and that ectopic breast cancer
occurs at an earlier age; however, malignancies in ectopic breasts are very rare. Excessive breast growth
(macromastia) can be seen in pregnancy as well as during adolescence.

Underdevelopment of the breast (hypoplasia), when congenital, is usually associated with genetic disorders, such
as ulnar-mammary syndrome, Polands syndrome, Turners syndrome, and congenital adrenal hyperplasia.
Among these disorders, Polands syndrome is the congenital anomaly that has been reported to be associated
with breast cancer most often. There are some recent studies suggesting the association of ulnar-mammary
syndrome and breast cancer; however, breast cancer has not been recorded in patients with Turners syndrome.
Acquired hypoplasia, on the other hand, is usually iatrogenic, most commonly subsequent to trauma or radio-
therapy. The complete absence of both breast and nipple (amastia) or presence of only nipple without breast
tissue (amazia) is rare.

Inflammatory and Related Lesions

Mastitis
A variety of inflammatory and reactive changes can be seen in the breast. While some of these changes are a
result of infectious agents, others do not have a well-understood etiology and may represent local reaction to a
systemic disease, or a localized antigen-antibody reaction, and are classified as idiopathic.
Inflammatory breast cancer, as the name suggests, mimics an infectious or inflammatory etiology. It often
develops without a palpable mass lesion and is often initially misdiagnosed. In fact, most patients with
inflammatory breast cancer are diagnosed after an initial treatment with antibiotics or anti-inflammatory therapies
failed to show clinical improvement. Mammographic and sonographic evaluation are helpful in establishing the
diagnosis. Image-guided biopsy of the abnormal breast parenchyma or skin biopsy confirms the diagnosis. A
negative skin biopsy should not be used to exclude the diagnosis.

Acute Mastitis
Acute mastitis usually occurs during the first 3 months postpartum as a result of breast feeding. Also known as
puerperal or lactation mastitis, this disorder is a cellulitis of the interlobular connective tissue within the mammary
gland, which can result in abscess formation and septicemia. It is diagnosed based on clinical symptoms and

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signs indicating inflammation. Risk factors fall into two general categories: improper nursing technique, leading to
milk stasis and cracks or fissures of the nipple, which may facilitate entrance of microorganisms through the skin;
and stress and sleep deprivation, which both lower the mothers immune status and inhibit milk flow, thus causing
engorgement.

Because the duration of symptoms before starting treatment is found to be the only independent risk factor for
abscess development, early diagnosis and early management of mastitis is of value. However, there is little
consensus on the type or duration of antibiotic therapy and when to begin antibiotics. Because lactation mastitis
is a process of subcutaneous cellulitis, detection of pathogens in breast milk may not always be possible, so
breast emptying with frequent nursing or manual pumping and beginning empiric antibiotherapy seems to be the
most appropriate approach. When puerperal mastitis-associated abscess occurs, incision and drainage are
usually recommended; however, suitable patients assessed by ultrasonography can also be treated without
surgery by needle aspiration and antibiotics with excellent cosmesis.

Granulomatous Mastitis
Granulomatous reactions resulting from an infectious etiology, foreign material, or systemic autoimmune
diseases such as sarcoidosis and Wegeners granulomatosis can involve the breast. Identification of the etiology
requires microbiologic and immunologic testing in addition to histopathologic evaluation. Many different types of
organisms can cause granulomatous mastitis.

Tuberculosis of the breast is a very rare disease. However, both clinical and radiological features of tuberculous
mastitis are not diagnostic and easily can be confused with either breast cancer or pyogenic breast abscess by
clinicians. Remembering the fact that traveling from one place to another in the global world has been increasing
and that the prognosis for complete cure with appropriate antituberculous drug therapy is excellent, this entity
should also be taken into consideration. Definitive diagnosis of the disease is based on identification of typical
histological features under microscopy or detection of the tubercle bacilli with mycobacterial culture.

The term idiopathic granulomatous mastitis is used for granulomatous lesions without an identifiable cause.
This diagnosis can be made only by excluding other possible causes of granulomatous lesions. An autoimmune
localized response to retained and extravasated fat- and protein-rich secretions in the duct has been postulated,
but the etiology of the disease remains largely unknown. Histologically, chronic noncaseating granulomatous
inflammation is typically limited to lobuli. The recommended therapy of idiopathic granulomatous mastitis is
complete surgical excision whenever possible plus steroid therapy. Even when idiopathic granulomatous mastitis
is treated appropriately, in about 50% of the cases, persistence, recurrence, and complications such as abscess
formation, fistulae, and chronic suppuration are encountered, so long-term follow-up is necessary in these
patients.

Foreign Body Reactions

Foreign materials, such as silicone and paraffin, which are used for both breast augmentation and reconstruction
after cancer surgery, may cause a foreign body-type granulomatous reaction in the breast. Silicone granulomas
(siliconomas) usually occur after direct injection of silicone into the breast tissue or after extracapsular rupture of
an implant. Foreign body granulomatous response associated with multinucleated giant cells surround silicone.
Fibrosis and contractions may lead to clinically apparent firm nodules that may be tender.

Recurring Subareolar Abscess

Recurring subareolar abscess (Zuskas disease) is a rare bacterial infection of the breast that is characterized by
a triad of draining cutaneous fistula from the subareolar tissue; a chronic thick, pasty discharge from the nipple;
and a history of multiple, recurrent mammary abscesses. The disease is caused by squamous metaplasia of one
or more lactiferous ducts in their passage through the nipple, probably induced by smoking. Keratin plugs
obstruct and dilate the proximal duct, which then becomes infected and ruptures. The inflammation eventuates in
abscess formation beneath the nipple, which typically drains at the margin of the areola. Abscess drainage to
allow for resolution of the acute inflammation and then complete excision of the affected duct and sinus tract is
successful in most cases, but abscesses may recur when the process develops in another duct.

Mammary Duct Ectasia

Mammary duct ectasia, also called periductal mastitis is a distinctive clinical entity that can mimic invasive
carcinoma clinically. It is a disease of primarily middle-aged to elderly parous women, who usually present with
nipple discharge, a palpable subareolar mass, noncyclical mastalgia, or nipple inversion or retraction. The
pathogenesis and the etiology of the disease are still being debated. Smoking has been implicated as an
etiologic factor in mammary duct ectasia. This association appears to be more important in young women who
smoke. Mammary duct ectasia is usually an asymptomatic lesion and is detected mammographically because of
microcalcifications.

The most important histologic feature of this disorder is the dilatation of major ducts in the subareolar region.
These ducts contain eosinophilic, granular secretions and foamy histiocytes both within the duct epithelium and
the lumen. The inspissated luminal secretions may undergo calcifications that may be the presenting sign in
many patients.

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Mammary duct ectasia generally does not require surgery and should be managed conservatively. There is no
evidence in the literature indicating that mammary duct ectasia is associated with an increased risk for breast
cancer. In some patients, clinical presentation and mammographic findings may suggest malignancy, and biopsy
may be required to exclude malignancy.

Fat Necrosis
Fat necrosis of the breast is a benign nonsuppurative inflammatory process of adipose tissue. It can occur
secondary to accidental or surgical trauma, or it may be associated with carcinoma or any lesion that provokes
suppurative or necrotic degeneration, such as mammary duct ectasia and, to a lesser extent, fibrocystic disease
with large cyst formation.

Clinically, fat necrosis may mimic breast cancer if it appears as an ill-defined or spiculated dense mass,
associated with skin retraction, ecchymosis, erythema, and skin thickness. Mammographic, sonographic, and
magnetic resonance imaging findings may not always distinguish fat necrosis from a malignant lesion. Even the
macroscopic appearance of the benign lesion can suggest a malignant tumor. Histologically, however, the
diagnosis of fat necrosis presents no problem, as it is characterized by anuclear fat cells often surrounded by
histiocytic giant cells and foamy phagocytichistiocytes. Excisional biopsy is required if carcinoma cannot be
excluded preoperatively.

Fibrocystic Changes
Fibrocystic changes (FCCs) constitute the most frequent benign disorder of the breast. Such changes generally
affect premenopausal women between 20 and 50 years of age. Although many other names have been used to
describe this entity over the years, (including fibrocystic disease, cystic mastopathy, chronic cystic disease,
mazoplasia, Recluss disease), the term fibrocystic changes is now preferred, because this process is observed
clinically in up to 50% and histologically in 90% of women.

FCCs may be multifocal and bilateral. The most common presenting symptoms are breast pain and tender
nodularities in breasts. Although the exact pathogenesis of the entity is not clear, hormonal imbalance,
particularly estrogen predominance over progesterone, seems to play an important role in its development. FCCs
comprise both cysts (macro and micro) and solid lesions, including adenosis, epithelial hyperplasia with or
without atypia, apocrine metaplasia, radial scar, and papilloma. Over the years, it has been one of the major
issues to determine whether these lesions are a risk factor for the subsequent development of breast cancer. As
the use of mammography and the identification of benign breast diseases become more common, it is crucial to
identify women who are at an increased risk for breast cancer. Therefore, it is practical to evaluate FCCs under a
classification system first proposed by Dupont and Page as nonproliferative lesions, proliferative lesions without
atypia, and proliferative lesions with atypia (atypical hyperplasia). In various studies, it has been shown that the
great majority of breast biopsies (up to 70%) show nonproliferative lesions.

Nonproliferative lesions include cysts, papillary apocrine change, epithelial-related calcifications, mild epithelial
hyperplasia, as well as ductal ectasia, nonsclerosing adenosis, and periductal fibrosis. Proliferative lesions
without atypia include moderate or florid ductal hyperplasia of the usual type, sclerosing adenosis, radial scar,
and intraductal papilloma or papillomatosis. Proliferative lesions with atypia include atypical ductal and lobular
hyperplasia. In each of these lesions, the subsequent risk for breast cancer is associated with the histologic
appearance of the lesion=: compared with the general population, women with nonproliferative lesions on breast
biopsy have no elevation in breast cancer risk, whereas women with proliferative disease without atypia and
women with atypical ductal or lobular hyperplasia have a greater breast cancer risk, with relative risks ranging
from 1.31.9 and 3.913.0, respectively, according to various studies. Apart from the histologic features, the age
at biopsy and the degree of family history of breast cancer are reported to be the major determinants of breast
cancer risk after the diagnosis of benign breast disease. According to Hartmann et al., the risk for breast cancer
in young women with a diagnosis of atypical epithelial proliferation is twice the risk observed among women over
55 years with a diagnosis of atypical epithelial proliferation. It was also reported, in the same study, that family
history of breast cancer is an independent risk factor and that strong family history may increase breast cancer
risk even in patients with nonproliferative lesions. Absolute risk, however, for both atypical and nonatypical
epithelial proliferations is quite low. More than 80% of patients with a diagnosis of atypical hyperplasia do not
develop invasive cancer during their lifetimes.

Cysts
Cysts are fluid-filled, round or ovoid structures that are found in as many as one third of women between 35 and
50 years old. Although most are subclinical microcysts, in about 20%25% of cases, palpable (gross) cystic
change, which generally presents as a simple cyst, is encountered. Cysts cannot reliably be distinguished from
solid masses by clinical breast examination or mammography; in these cases, ultrasonography and fine needle
aspiration (FNA) cytology, which are highly accurate, are used.

Cysts are derived from the terminal duct lobular unit. In most cysts, the epithelial lining is either flattened or totally
absent. In only a small number of cysts, an apocrine epithelial lining is observed. Because gross cysts are not
associated with an increased risk of carcinoma development, the current consensus on the management of gross
cysts is routine follow-up of the patient, without further therapy.

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Complex (or complicated or atypical) cyst is a sonographic diagnosis that is characterized by internal echoes or
thin septations, thickened and/or irregular wall, and absent posterior enhancement. They are reported in
approximately 5%5.5% of all breast ultrasound examinations. The malignancy rate of complex cysts, which is
0.3% as described by Venta et al., is lower than that for lesions classified as probably benign. These patients
can be managed with follow-up imaging studies. However, if the lesion also includes an intracystic mass
(intracystic nodule), it should be regarded as suspicious for neoplasm and managed as solid lesions. Either a
core needle biopsy or surgical biopsy is indicated for these lesions.

Adenosis
Adenosis of the breast is a proliferative lesion that is characterized by an increased number or size of glandular
components, mostly involving the lobular units. Various types of adenosis have been described, of which
sclerosing adenosis and microglandular adenosis merit detailed description.
Sclerosing adenosis of the breast is defined as a benign lobulocentric lesion of disordered acinar, myoepithelial,
and connective tissue elements, which can mimic infiltrating carcinoma both grossly and microscopically.
Sclerosing adenosis can manifest as a palpable mass or as a suspicious finding at mammography. It is strongly
associated with various proliferative lesions, including epithelial hyperplasias, intraductal or sclerosing papilloma,
complex sclerosing lesion, calcification, and apocrine changes. It can coexist with both invasive and in situ
cancers. Studies found sclerosing adenosis to be a risk factor for invasive breast cancer apart from its
association with other proliferative lesions of the breast.

Sclerosing adenosis. Proliferation of small glands associated with microcalcifications. Low-power examination
demonstrates the lobulocentricity of the lesion.

Microglandular adenosis of the breast is characterized by a proliferation of round, small glands distributed
irregularly within dense fibrous and/or adipose tissue. Most of the glandular structures have open lumina in which
eosinophilic material is usually seen. The most important histological feature of microglandular adenosis is that it
may lack the outer myoepithelial layer seen in other types of adenosis. The lack of myoepithelial layer makes it
harder to differentiate microglandular adenosis from tubular carcinoma. However, the presence of basal lamina
encircling glandular structures, which can also be shown by laminin or type IV collagen immunohistochemical
stains, and the absence of epithelial membrane antigen staining in the luminal epithelial cells distinguish
microglandular adenosis from tubular carcinoma.

Although microglandular adenosis is considered benign, there is some evidence of the potential of this lesion to
become invasive carcinoma. Microglandular adenosis also has a tendency to recur if not completely excised.
Apocrine (adenomyoepithelial) adenosis, which seems to be a variant of microglandular adenosis, was first
described in association with adenomyoepithelioma. It is an apocrine change in deformed lobular units,
sclerosing adenosis, radial scars, and complex sclerosing lesions. The term apocrine adenosis is used to
describe a wide spectrum of apocrine lesions, and to prevent its inappropriate use, this term has been proposed
to describe apocrine changes in the specific underlying lesions.

Tubular adenosis of the breast is another and rare variant of microglandular adenosis that should be
distinguished from tubular carcinoma. The presence of an intact myoepithelial layer around the tubules is the
most helpful feature.

Metaplasia
Apocrine metaplasia is characterized by the presence of columnar cells with abundant granular, eosinophilic
cytoplasm and luminal cytoplasmic projections or apical snouts. These cells line dilated ducts or can be seen in
papillary proliferations. They are more frequently found in younger women. All normal and metaplastic apocrine
cells can be stained with gross cystic disease fluid protein 15.

Atypical apocrine metaplasia should be diagnosed only when the nuclei of the apocrine cells display significant
cytologic atypia.

Clear cell metaplasia of the breast is a rare lesion. Its significance comes from its morphologic similarity to clear
cell carcinoma. However, the similarity of its immunohistochemical staining profile with that of eccrine sweat
glands suggests that clear cell metaplasia may in fact represent eccrine metaplasia.

Epithelial Hyperplasia
Epithelial hyperplasia (ductal or lobular type) is one of the most challenging FCCs to diagnose properly. Epithelial
hyperplasia is the most common form of proliferative breast disease. It can be difficult to distinguish between
ductal and lobular hyperplasias. In addition, it can also be difficult to distinguish between usual ductal or lobular
hyperplasias and their atypical counterpartsatypical ductal hyperplasia and atypical lobular hyperplasia. Table
1 lists the various types of epithelial hyperplasia and associated risk of carcinoma.

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Histologic category of benign breast lesions associated with the relative risk for breast cancer for patients with no
family history

Ductal Lesions
Normally, breast ducts are lined by two layers of low cuboidal cells with specialized luminal borders and basal
contractile myoepithelial cells. Any increase in cell number within the ductal space is regarded as epithelial
hyperplasia. Further classification is based on the degree and architectural and cytologic features of the
proliferating cells. Usual ductal hyperplasia or simple hyperplasia denotes an increased number of cells without
architectural distortion or distention of the ductal contour. Usual ductal hyperplasia does not increase the risk for
breast cancer. In mild hyperplasia of the usual type, proliferating epithelial cells are a three- to four-cell layer,
whereas moderate hyperplasia describes epithelial proliferation more than four cells thick, often with
accompanying bridging of the luminal space. In florid hyperplasia, the lumen is distended and may be obliterated.
The most important cytologic features of mild, moderate, or florid epithelial hyperplasia are an admixture of cell
types (epithelial cells, myoepithelial cells, and metaplastic apocrine cells) and variation in the appearances of
epithelial cells and their nuclei.

Ductal epithelial hyperplasias.(A): Usual ductal hyperplasia. The epithelial proliferation is composed of
polymorphic cell types that partially occlude the lumen. (B): Florid epithelial hyperplasia. Proliferating solid
clusters of hyperplastic cells with the typical appearance of overlapped and uneven distribution of nuclei. The
epithelial proliferation obliterates and distends the ductal lumens. (C): Atypical ductal hyperplasia is characterized
by monotonous proliferation of regularly arranged cells; in this photograph, forming a cribriform pattern. Although
displaying features of low-grade intraductal carcinoma, quantitatively, being a single and small focus, this lesion
is interpreted as atypical ductal hyperplasia.

The term atypical ductal hyperplasia is defined as a type of a ductal hyperplasia that morphologically mimics low-
grade ductal carcinoma in situ (DCIS). Characteristically, it has a uniform population of cells. Most lesions of
atypical ductal hyperplasia are small and focal. They involve only a portion of a duct or only a few small ducts
measuring <2 mm. With the increasing use of mammography, and detection of calcifications, atypical ductal
hyperplasias are being diagnosed more frequently. Atypical ductal hyperplasia is a rare condition among patients
having biopsies for a palpable mass, seen in 4% of symptomatic benign biopsies. In contrast, 31% of biopsies
performed because of microcalcifications show atypical ductal hyperplasia. The significance of this lesion comes
from the fact that the patient has an increased risk for invasive breast cancer, which is about four to five times
that of the general population, and reaching nearly a tenfold risk if the patient has a first-degree relative with
breast cancer. The risk for breast cancer is higher in the ipsilateral breast, but the contralateral breast is also at
risk. Women with atypical ductal hyperplasia develop cancer usually within 1015 years of the diagnosis. The risk
for cancer declines after 15 years. The risk for breast cancer in women with atypical ductal hyperplasia is also
related to the patients menopausal status. Premenopausal women with atypical ductal hyperplasia have a
substantially higher risk than postmenopausal women with that diagnosis. Routine follow-up for both breasts is
recommended. Therapy options, such as chemoprevention, should be determined on the basis of other risk
factors for breast cancer.

Lobular Lesions
Lobular-type epithelial proliferations, both atypical lobular hyperplasia and lobular carcinoma in situ, are
collectively termed lobular neoplasia because, unlike ductal lesions, which exhibit heterogeneous morphologic
features, the histologic features of lobular type epithelial proliferations are very similar, and the only difference
between atypical lobular hyperplasia and lobular carcinoma in situ is the extent and degree of epithelial
proliferation. Because both lesions are regarded and managed as a risk factor rather than well-established
precursor lesions, lobular neoplasia terminology has gained general acceptance. Lobular neoplasia is a relatively

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rare breast lesion. It rarely manifests itself clinically. Lobular neoplasia is identified as an incidental finding in
biopsies excised for other abnormalities. The frequency of detection depends on the volume of tissue removed
during surgery and extent of histological examination. Lobular neoplasia is most prevalent in perimenopausal
women. It is a multifocal lesion, and many patients have lesions involving multiple quadrants of the breast. Both
atypical lobular hyperplasia and lobular carcinoma in situ increase the risk for the subsequent development of
invasive carcinoma, by about fourfold for atypical lobular hyperplasia and tenfold for lobular carcinoma in situ.
Although subsequent carcinomas can occur in either breast without a direct relationship to the previous site of
biopsy, in a recent retrospective study, Page et al. reported that the development of invasive carcinoma after
atypical lobular hyperplasia was three times more likely to arise in the ipsilateral breast than in the opposite
breast. Invasive carcinomas may arise 1520 years after diagnosis. Systemic follow-up and appropriate risk
assessment is recommended for patients with lobular neoplasia.

Lobular carcinoma in situ is considered to be a risk marker rather than an obligatory precursor lesion of invasive
breast cancer; therefore, in general, it does not warrant surgical therapy. Most women with a diagnosis of lobular
carcinoma in situ do not develop invasive breast cancer within their natural lifetimes. The risk for developing
invasive cancer appears to be similar in both the ipsilateral and contralateral breasts. Therefore, if one has to
choose surgery for lobular carcinoma in situ, the only logical approach would be a bilateral total mastectomy.
Because this is an excessively morbid procedure for patients who have a moderate risk associated with the
diagnosis of lobular carcinoma in situ, chemoprevention is the preferred approach for these patients. However, if
the patient has other risk factors, such as a high-risk family history, prophylactic bilateral mastectomy with or
without reconstruction would be a consideration.

Columnar Cell Lesions

Columnar cell lesions of the breast represent a spectrum of lesions that have been encountered with increasing
frequency in needle core breast biopsies because these lesions are commonly associated with
microcalcifications and detected by mammographic screening. A working classification of these lesions has been
proposed by Schnitt and Vincent-Salomon as columnar cell change and columnar cell hyperplasia, each of which
may have atypia or not. Ongoing studies on the clinical significance of atypical columnar cell lesions, which are
also known as flat epithelial atypia, have shown that the likelihood of local recurrence or progression to invasive
breast cancer is exceedingly low. However, based on the foregoing observations, it has been suggested that at
least some lesions are probably neoplastic proliferations that may represent either a precursor of low-grade DCIS
or even invasive carcinoma, particularly tubular carcinoma.

When an atypical columnar lesion is encountered in a needle core biopsy, excision is suggested to exclude more
advanced lesions such as in situ or invasive cancer. On excisional biopsy specimen, a careful histologic search
for areas with diagnostic features of in situ or invasive cancer should be performed. Because this lesion has been
referred to by several different names in the literature, including blunt duct adenosis, columnar alteration of
lobules, hypersecretory hyperplasia with atypia, pretubular hyperplasia, and columnar alteration with prominent
snouts and secretions, it is difficult to assess its significance as a risk marker for development of invasive cancer.
Without having firm data, close follow-up of the patient with columnar cell changes is recommended at this point.

Radial Scar and Complex Sclerosing Lesion

Radial scars are benign pseudoinfiltrative lesions of uncertain significance. They are characterized by a
fibroelastotic core with entrapped ducts, surrounded by radiating ducts and lobules displaying variable epithelial
hyperplasia, adenosis, duct ectasia, and papillomatosis. Previously, radial scars were an incidental finding in
breast specimens excised for other diagnostic reasons, but their incidence has increased dramatically as a result
of population-based screening programs. Some authors have suggested using the term radial scar for lesions
measuring <1 cm, whereas the term complex sclerosing lesion was reserved for lesions measuring 1 cm or
larger.

Radial scars may serve as a milieu for the development of atypical epithelial proliferations, including atypical
intraductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, and DCIS. Over the years, many
authors have studied the biologic significance of radial scars. In a postmortem study by Nielsen et al. these
lesions were commonly associated with benign breast diseases, whereas Jacobs et al found that radial scars
were associated with a doubling of the risk for breast cancer, regardless of the type of primary breast disease,
and that the risk was even greater in women with larger or multiple radial scars.

The radiographic features of radial scars are nonspecific and may mimic carcinoma. The role of FNA cytology in
diagnosis is limited. Recent publications have shown the importance of core needle biopsy of these lesions for
diagnosis, but because malignancy cannot be reliably excluded with limited sampling, a spiculated lesion
suggestive of radial scar or complex sclerosing lesion at mammography may be excised on the basis of its size
and amount of sampling performed by core biopsy.

Radial scar.(A): The mammographic appearance of radial scar. Spiculated lesion with central radiolucency.
Radiating spicules frequently mislead the diagnosis of carcinoma. (B): Low-power view of radial scar shows
fibroelastotic core and radiating ducts exhibiting duct epithelial hyperplasia without atypia, cystic structures, and
microcalcifications.

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Intraductal Papilloma and Papillomatosis
Intraductal papilloma is a discrete benign tumor of the epithelium of mammary ducts. It can arise at any point in
the ductal system and shows a predilection for the extreme ends of the ductal system: the lactiferous sinuses and
the terminal ductules. The central papillomas tend to be solitary, whereas the peripheral ones are usually
multiple. Serous or serosanguinous nipple discharge is the presenting symptom in most women. Papillomas are
characterized by formation of epithelial fronds that have both the luminal epithelial and the outer myoepithelial
cell layers, supported by a fibrovascular stroma. The epithelial component can be subject to a spectrum of
morphologic changes ranging from metaplasia to hyperplasia, atypical intraductal hyperplasia, and in situ
carcinoma. The risk represented by the occurrence of such abnormalities in an otherwise benign papilloma is
currently debated. Central single papillomas have not been considered premalignant or markers of risk when they
are not associated with atypia. Two recent studies found significant correlation between the presence of atypical
ductal hyperplasia in papillary lesions on core biopsies and the presence of invasive or preinvasive carcinoma of
the breast in excisional biopsies. In another clinicopathologic study, MacGrogan and Tavassoli suggested that
the recurrence of papillomas is related to the presence of proliferative breast lesions (including usual ductal
hyperplasia, atypical ductal hyperplasia, and lobular neoplasia) in the surrounding breast tissue. Epithelial atypia,
even to the extent of low-grade DCIS has no known prognostic significance or impact on outcome when it is
confined to the central papilloma. Therefore, if atypia is encountered in a papilloma on an excisional biopsy, the
surrounding breast tissue should be carefully examined for further follow-up of the patient.

Papillomatosis (multiple papillomas) is defined as a minimum of five clearly separate papillomas within a localized
segment of breast tissue, usually in a peripheral or subareolar location. Multiple papillomas are more likely to
occur bilaterally, and their probability of having an in situ or invasive carcinoma is higher than with the central
papilloma. Therefore, in patients with multiple papillomas on excisional biopsy, thorough sampling of the
specimen, as well as diagnostic radiographic imaging of contralateral breast tissue is suggested to rule out
malignancy. All the available data suggest that the finding of a solitary, central, benign duct papilloma does not
carry any increased risk for subsequent breast cancer, while multiple papillomas may indicate a slightly elevated
risk for subsequent breast cancer.

Juvenile papillomatosis of the breast is defined as severe ductal papillomatosis occurring in young women of <30
years old. There are only eight male juvenile papillomatosis cases reported in the literature. This disease is
associated with a heightened risk for breast cancer. Because both a family history of breast cancer and an
increased risk for breast cancer are associated with the diagnosis of juvenile papillomatosis, long-term follow-up
is recommended both for the patient and the family.

Proliferative Stromal Lesions

Diabetic Fibrous Mastopathy

Diabetic fibrous mastopathy is an uncommon form of lymphocytic mastitis and stromal fibrosis. It occurs both in
premenopausal women and (rarely) in men with long-standing type 1 insulin-dependent diabetes mellitus, who
have severe diabetic microvascular complications. Clinically, diabetic fibrous mastopathy is characterized by
solitary or multiple ill-defined, painless, immobile, discrete lesions in one or both breasts that raise the suspicion
of carcinoma. The mammographic and sonographic findings of these lesions are also highly suspicious for breast
cancer, so a biopsy is always essential for definitive diagnosis. The characteristic pathologic findings of this entity
are dense keloid-like fibrosis; periductal, lobular, or perivascular lymphocytic infiltration with predominantly B
cells; lobular atrophy; and epithelioid fibroblasts embedded in dense fibrous stroma. The pathogenesis of diabetic
fibrous mastopathy is unknown. The disease probably represents an immune reaction to the abnormal
accumulation of altered extracellular matrix in the breast, which is a manifestation of the effects of hyperglycemia
on connective tissue.

Routine annual follow-up of patients with diabetic fibrous mastopathy is recommended. Core needle biopsy may
be useful in the diagnosis of recurrent lesions on follow-up.

Pseudoangiomatous Stromal Hyperplasia of the Breast

Pseudoangiomatous stromal hyperplasia (PASH) is a benign myofibroblastic proliferation of nonspecialized
mammary stroma. Its clinicopathologic spectrum ranges from incidental, microscopic foci to clinically and
mammographically evident breast masses. Originally, hormonal stimulation (particularly with progesterone) was
suggested in the etiology of PASH, on the basis of observations that this disease is most frequently seen in
premenopausal women or in elderly women taking hormone-replacement therapy, and because similar histologic
findings are seen in normal mammary stroma during the luteal phase of the menstrual cycle. However, the lesion
has since been found in men and in women not taking hormone therapy, and only a small percentage of PASH
cases are positive for estrogen receptors or for progesterone receptors.

Clinically, rare cases of PASH present as a well-circumscribed, dense, rubbery mass mimicking a fibroadenoma
or a phyllodes tumor. Both the mammographic and sonographic features in PASH are nonspecific, so biopsy of
these lesions is necessary to exclude a malignancy.

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On gross examination, PASH is usually a well-demarcated mass with a smooth external surface. The cut surface
consists of homogeneous white and rubbery tissue. Histologically, a complex network of anastomosing slit-like
spaces within a densely collagenous stroma characterizes PASH. The histologic appearance may cause
confusion with mammary angiosarcoma, so immunohistochemical vascular markers are used for distinction.
Immunohistochemically, the bland spindle cells that line these spaces are strongly positive for vimentin and CD34
and negative for cytokeratin and factor VIII.

The recommended treatment for PASH is wide local excision. Although PASH can recur, patient prognosis is
good.

Neoplasms

Fibroadenoma
Fibroadenoma is the most common lesion of the breast; it occurs in 25% of asymptomatic women. It is usually a
disease of early reproductive life; the peak incidence is between the ages of 15 and 35 years. Conventionally
regarded as a benign tumor of the breast, fibroadenoma is also thought to represent a group of hyperplastic
breast lobules called aberrations of normal development and involution. The lesion is a hormone-dependent
neoplasm that lactates during pregnancy and involutes along with the rest of the breast in perimenopause. A
direct association has been noted between oral contraceptive use before age 20 and the risk of fibroadenoma.
The Epstein-Barr virus might play a causative role in the development of this tumor in immunosuppressed
patients.

Fibroadenoma presents as a highly mobile, firm, non-tender, and often palpable breast mass. Although most
frequently unilateral, in 20% of cases, multiple lesions occur in the same breast or bilaterally. Fibroadenoma
develops from the special stroma of the lobule. It has been postulated that the tumor might arise from bcl-2-
positive mesenchymal cells in the breast, in a manner similar to that proposed for solitary fibrous
tumors.Macroscopically, the lesion is a well-circumscribed, firm mass, <3 cm in diameter, the cut surface of which
appears lobulated and bulging. If the tumor assumes massive proportions (>10 cm), more commonly observed in
female adolescents, it is called giant fibroadenoma. Microscopically, fibroadenoma consists of a proliferation of
epithelial and mesenchymal elements. The stroma proliferates around tubular glands (pericanalicular growth) or
compressed cleft-like ducts (intracanalicular growth). Often both types of growth are seen in the same lesion.
Fibroadenoma.(A): The cut surface of fibroadenoma is lobulated, solid, and gray-white, with a characteristic
bulging appearance. (B): Histologically the lesion consists of densely fibrotic stroma and compressed cleft-like
ducts.

Cytogenetic studies have reported chromosomal aberrations in both epithelial and stromal cells, suggesting that
the two components may involve neoplastic changes. Phyllodes tumor is a fibroepithelial tumor of the breast with
a spectrum of changes. Benign phyllodes tumor is usually difficult to differentiate from fibroadenoma.
Hypercellular stroma with cytologic atypia, increased mitoses, and infiltrative margins of the lesion are the most
reliable discriminators to separate lesions with recurrence and malignant behavior. In terms of surgical treatment
of these tumors, it is important to recognize phyllodes tumor because it should be excised completely with clear
margins to obviate any chance of local recurrence. In cases of recurrent disease, mastectomy is often performed.
Approximately 50% of fibroadenomas contain other proliferative changes of breast, such as sclerosing adenosis,
adenosis, and duct epithelial hyperplasia. Fibroadenomas that contain these elements are called complex
fibroadenomas. Simple fibroadenomas are not associated with any increased risk for subsequent breast cancer.
However, women with complex fibroadenomas may have a slightly higher risk for subsequent cancer. The
presence of atypia (either ductal or lobular) confined to a fibroadenoma does not lead to a greater risk for long-
term breast carcinoma compared with fibroadenomas in general.

Fibroadenomas in older women or in women with a family history of breast cancer have a higher incidence of
associated carcinoma. Two studies, which were considered to provide strong evidence of reliability according to
El-Wakeel et al., show that the relative risk of developing breast cancer in patients who had surgically excised
fibroadenomas increases in the presence of complex features within the fibroadenomas, ductal hyperplasias, or a
family history of breast carcinoma (in a first-degree relative). Progressive somatic genetic alterations that are
associated with the development of breast cancer have been studied in fibroadenomas. No genetic instabilities,
manifested as loss of heterozygosity or microsatellite instability, have been found in any fibroadenoma
components regardless of their association with breast cancer or their histologic complexity.

The current management of patients with clinically or radiologically suspected fibroadenoma varies. Some
physicians prefer excision for tissue diagnosis, but conservative management will likely replace surgical
treatment in the near future, on the basis of the young age of the patient, findings of benign imaging and clinical
characteristics, and benign findings on either FNA biopsy or needle core biopsy. Minimally invasive techniques,
such as ultrasound-guided cryoablation, seem to be an excellent treatment option for fibroadenoma in women
who wish to avoid surgery, or else the lesion may simply be treated with observation and followed up periodically.
Juvenile fibroadenoma is a variant of fibroadenoma that presents between 10 and 18 years of age, usually as a
painless, solitary, unilateral mass >5 cm. It can reach up to 15 or 20 cm in dimension, so although it is an entirely
benign lesion, surgical removal is recommended.

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Lipoma
Lipoma of the breast is a benign, usually solitary tumor composed of mature fat cells. It is occasionally difficult to
distinguish lipoma from other conditions clinically, thus causing diagnostic and therapeutic challenges.
Clinically, a lipoma presents as a well-circumscribed, smooth or lobulated mass that is soft and usually
nontender. FNA biopsy of these lesions reveals fat cells with or without normal epithelial cells. Usually both
mammography and ultrasound scanning give negative results, unless the tumor is large.

If the clinical diagnosis of lipoma is confirmed by either FNA biopsy or core biopsy, and the mammogram and the
ultrasonogram show nothing suspicious for malignancy at the site, the patient is normally followed through
palpation after 6 months. However, if the diagnosis is not certain or the lesion grows rapidly, the tumor should be
surgically removed.

Adenoma
An adenoma is pure epithelial neoplasm of the breast. This lesion is divided into tubular, lactating, apocrine,
ductal, and so-called pleomorphic (i.e., benign mixed tumor) adenoma. Except for lactating and tubular
adenomas, these lesions are uncommon. Both lactating and tubular adenomas occur during the reproductive
ages.

Lactating adenoma is the most prevalent breast mass during pregnancy and puerperium. It presents as a solitary
or multiple, discrete, palpable, freely movable breast mass that tends to be small (<3 cm). On gross examination,
the lesion is well circumscribed and lobulated. It is characterized by hyperplastic lobules in which proliferated
acini are lined by actively secreting cuboidal cells. Lactating adenoma may also develop in ectopic locations,
such as the axilla, chest wall, or vulva. Although the tumor may spontaneously involute, surgical removal may be
necessary because of the mass effect it produces, and in cases when lactation is not of concern, medical therapy
may be given to shrink the tumor. This tumor does not tend to recur locally, and there is no proven malignant
potential.

Tubular adenoma (also termed pure adenoma) of the breast presents as a solitary, well-circumscribed, firm
mass. It may resemble the appearance of noncalcified fibroadenoma radiographically. Histologically, tightly
packed tubular or acinar structures that are very regular in size and shape are seen in a sparsely cellular stroma.
Microcalcifications inside dilated acini have been described; numerous tiny, punctuate, and irregular
microcalcifications are prominent on mammography and ultrasonography.
Both lactating and tubular adenomas, (the true breast adenomas) can be distinguished from fibroadenoma and
nipple adenoma by the presence of scant stroma in the former.

Nipple Adenoma
Nipple adenoma, also known as florid papillomatosis of the nipple ducts or erosive adenomatosis, is a benign
tumor of the ductal epithelium that often clinically mimics Pagets disease and pathologically may be
misinterpreted as an adenocarcinoma. Typically, nipple adenoma presents as a discrete, palpable tumor of the
papilla of the nipple. Erosion of the nipple and nipple discharge are usually seen. Histologically, the tumor is
characterized by proliferating ductal structures that invade the surrounding stroma. A double layer of epithelium
lines these ductal structures. The presence of keratin cysts and tiny apical snouts are other distinguishing
features of the disease. Generally, a biopsy is necessary for diagnosis. Nipple adenoma can be successfully
treated by complete excision of the tumor with normal surgical margins. Recurrences of incompletely excised
lesions have been documented. Nipple adenoma is considered a benign lesion, but rarely malignant change
within or contiguous with nipple adenoma has been defined.

Hamartoma
Hamartoma of the breast is an uncommon benign tumor-like nodule, also known as fibroadenolipoma,
lipofibroadenoma, or adenolipoma, composed of varying amounts of glandular, adipose, and fibrous tissue.
Clinically, hamartoma presents as a discrete, encapsulated, painless mass. Although the pathogenesis of the
lesion is not clear, it is thought to result from a dysgenesis rather than a true tumorous process. Some cases
have been reported to be related to a genetic defect called Cowdens disease. The classic mammographic
appearance is a circumscribed area consisting of both soft tissue and lipomatous elements, surrounded by a thin
radiolucent zone.

On macroscopic examination, hamartomas are typically well-circumscribed lesions with smooth contours.
Histologically, the most characteristic appearance is otherwise normal breast and fat tissue distributed in a
nodular fashion within a fibrotic stroma that surrounds and extends to between individual lobules and obliterates
the usual interlobular specialized loose stroma.

There are some issues that should be taken into consideration when evaluating hamartomas. First, this lesion
can be very easily underestimated if the clinical finding of a distinct lump or breast asymmetry and the imaging
features are not interpreted thoroughly. Second, the pathologist should always be careful about a coincidental
epithelial malignancy occurring in the lesion, and the lesion has a potential problem of recurrence. Third, the
lesion should be placed in the differential diagnosis of biphasic breast tumors.
The current management of hamartomas is surgical removal.

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Granular Cell Tumor
Granular cell tumor is an uncommon, usually benign neoplasm that originates from Schwann cells of the
peripheral nervous system. It is most frequently found in the head and neck region, particularly in the oral cavity.
The tumor occurs in the breast in only 5%6% of cases.

Clinically, granular cell tumor can simulate carcinoma because of its fibrous consistency, fixation to the pectoral
fascia, skin retraction, and ulceration. Mammographic and ultrasonographic findings may further increase the
suspicion of a malignant lesion.

Grossly, granular cell tumor is generally 3 cm or smaller and appears almost well circumscribed when bisected;
in some tumors, however, infiltrative margins suggestive of a malignant lesion may be encountered.
Histologically, nests and sheets of polygonal cells with distinct cell borders and abundant granular eosinophilic
cytoplasm are characteristic. The S-100 protein immunoreactivity of these cells supports the hypothesis that
granular cell tumor derives from Schwann cells.

Granular cell tumor.Sheets or nests of large polygonal cells with abundant, coarsely granular, eosinophilic
cytoplasm and prominent, round to oval nucleus.

Although granular cell tumor is mostly benign, there are a few cases in the literature reported as malignant.
Features suggestive of malignancy are tumor size (>5 cm), cellular and nuclear pleomorphism, prominent
nucleoli, increased mitotic activity, presence of necrosis, and local recurrence .

Wide local excision is the treatment of choice for both benign and malignant granular cell tumors. Complete
removal may require inclusion of muscle and other adjacent structures, and histologically it is recommended that
the margins be completely free of tumor. Incomplete excision may result in local recurrences. Adjuvant therapy is
not given unless the tumor is malignant.

Sentinel lymph node biopsy in breast cancer

V. Seenu, Piyush Ranjan Mishra

Introduction

One of the most significant breakthroughs in breast cancer management in recent times has been in the area of
sentinel lymph node biopsy (SLNB), which is now an established staging technique for assessing regional lymph
node status while minimizing the morbidity associated with conventional axillary lymph node dissection (ALND).
Axillary lymph nodal (ALN) status remains the most important prognostic marker in the management of breast
cancer patients. Evaluation of axillary lymph nodes is critical for accurately staging patients and to decide
adjuvant chemotherapy . In a series of 27,420 pts with carcinoma breast overall incidence of metastasis to ALN
was 46%. The axillary lymph node involvement correlates with the size of the breast tumor ( tumor of size <1 cm,
incidence of axillary metastases is 3-22%; for tumor of 1-2 cm, it is around 36%). In the absence of local
treatment to axilla with either surgery or radiotherapy, the risk of axillary recurrence is high. While ALND provides
staging information and removes any disease in axilla providing regional disease control, there is no evidence
that removal of axillary lymph nodes provides a survival benefit. The 25-year follow up data from the landmark
National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 study clearly showed that there is no survival
advantage associated with ALND . ALND carries with it a significant morbidity in terms of lymphedema,
numbness in the distribution of intercostobrachial nerves, decreased range of motion in the shoulder, and overall
reduced quality of life.

Sentinel node concept

Through the significant efforts of David Krag & Armando Guiliano , SLN concept was introduced into breast
cancer and by late 1990s, it soon became evident that SLNB is a safe, reliable technique that accurately stages
the axilla, allowing the procedure to become accepted for widespread clinical use. The sentinel node concept is
based on the belief that lymphatics from primary tumor go to the first node in regional nodal basin (sentinel node/
hot node). Lymphatic mapping allows us to determine the number and location of these sentinel lymph nodes.
SN can be localized precisely for surgical excision and pathological examination by dye diverted technique (blue
node) or radio tracer guided technology (hot node) method or combination of both. As the sentinel node is most
likely to harbor a metastases, a focused histological analysis can be performed on this concentrated specimen.
The tumor status of this sentinel node will reflect the status of the rest of the regional nodal basin. Thus removal
of only the sentinel node/s can allow avoidance of many complications of ALND in breast cancer patients, while it
has the potential of providing all the staging information.

In validational studies (Table 1), SLNB has been shown to accurately predict the axillary status in early breast
cancer patients

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Validational Studies
Author Tech Success (%) Accuracy (%)
Krag (1993) Tracer 18/22 (82) 18/18
Giuliano (1994) Blue Dye 114/174 (66) 109/114 (96)
Giuliano (1997) Blue dye 100/107 (94) 100/100
Veronesi (1997) Tracer 160/163 (98) 156/160 (97)
Cox (1998) Comb 440/466 (94) 439/440 (99)
Albertini (1997) Comb 57/62 (92) 57/57 (100)
Our study (2010) Blue & Comb 385/423 (91) 378/385 (98)

Subsequently randiomized controlled trials, meta analysis and systematic reviews (Table 2) have shown that
sentinel node biopsy can be an alternative to conventional ALND in patients with clinically negative axilla.

Randomized trials of Sentinel Node Biopsy in Breast cancer

ACSOG Z 10 & 11
NASBP 32
ALMANAC
AMAROS
SNAC
IBCSG23-01
IEO
Veronesi

The primary outcomes measured in RCTs of SLND V/S ALND in breast cancer are axillary recurrence, over all
survival & disease free survival. The secondary outcomes measures are Operating time, morbidity &
complications & quality of life

Veronesi et al randomized patients with Tumors < 2 cm into ALND group (257 pts) v/s SN alone or followed by
ALND group if SN showed metastasis (259 pts). Of the 259 pts SLNB 92 (36%) had positive SN and ALND.
Of 167 who underwent SLNB alone, only 1 axillary recurrence was reported at 79 months. The 5 yr survival was
96.4% in ALND group and 98.4 % in SN group. At a median follow up of 79 mths (15-97) 18 events occurred in
ALND group and 16 in SN group. They concluded that SLNB can be offered as an alternative to ALND as
treatment for axilla in patients with breast cancer <2 cm in size.

Smidt et al reported successful identification of SN in 676 of 696 patients (97%). Sentinel did not reveal any
metastasis in 439 patients (65%) and did not undergo ALND. At a median follow up of 26 months axillary
recurrence occurred only in 2 patients ().46%). They concluded that axillary recurrence rates are low following
SLND alone in early breast cancer.

Bergikvist et al reported that Axillary recurrence following SN bx alone is very low. Out of 3534 pts of early breast
cancer who underwent SLND, 2246 patients did not have metastasis in SN. At median follow up of 37 months,
isolated axillary recurrence in 0.6%; local and axillary recurrence in 0.3%; axillary & distant metastasis in 0.3%.
the estimated 5 yr axillary recurrence following SLNB was 1.1%. The axillary recurrence rate following ALND in
pre Sentinel node era at their centre was was 1%-5 yrs & 1.6%-10 yrs.Van der Ploeg et al reported their results
on SLND in 1019 pts of which 755 paitnes were SLND negative for metastasis. At a median follow up of 46
months, axillary nodal recurrence was observed in 0.25% of patients and the predicted recurrence rate at 5
years was 0.4%. The over all and disease free surivial were 95.9 and 89.7% respectively. Van der Ploeg et al
also reported a systematic review of 14959 patients in 48 published reports. At a median follow up of 34
months, 67 axillary rec urrences were observed (0.3%). Recurrence was reported to be less with use of
radiotracer, superficial injection, performance of procedure at cancer centre and use of frozen section. The
authors also mention the possibiity of low recurrence to use of radiotherapy and use of systemic adjuvant
therapy.

NSABP-32 Trial randomized patients in to SLNB (2001 patients) and SLNB followed by ALND (1975 patients)
with the objective of knowing: whether SLNB alone results in same survival & regional control as SLNBALND.
The results of the study are given in table 4.
SLNB SLNBALND
OS 95% 96%
DFS 81.5% 82.4%
Shoulder dysfunction 13% 19%
Vol diff >5% 17% 28%
Arm numbness 8% 31%
Arm tingling 7% 13%

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The conclusions deduced from the study were
No significant diff. in OS, DFS and regional control between two groups
SLNB with out ALND is safe & effective regional nodal Rx in SN ve breast cancer

In the recently published results of ALMANAC Trial, a randomized study compared conventional axillary
dissection with Sentinel lymph node dissection. The relative risks of any lymphedema and sensory loss for the
SLNB group compared with the standard axillary treatment group at 12 months were 0.37. Drain usage, length of
hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly
lower in the SLNB group (all P <.001). Overall patient-recorded quality of life and arm functioning scores were
statistically significantly better in the SLNB group throughout ( P .003) (33).

In spite of the results of sentinel node biopsy in breast cancer demonstrating its important role in management of
breast cancer, there are still some lacunae in the available literature and limitations to perform sentinel node
biopsy in patients with breast cancer in Indian settings. These can be discussed under the following headings

Sentinel node identification

The currently recommended technique of sentinel node biopsy in breast cancer is the the combination of blue
dye (isosulfan blue or patent blue violet) and radiotracer guided technique. However, neither of the blue dyes are
currently marketed in India, are expensive and not easily available. In India some surgeons use Methylene Blue
for identificationof sentinel node in breast cancer with variable success rates. . However, there are nor
randomized trials comparing the efficacy of Methylene blue vis a vis isosulfan blue or patent blue violet in
identifying sentinel node in literature.

In older patients (>70 yrs) and in obese patients (BMI>30), the sentinel node identification rates reported in
literature are lower and hence these two parameters are considered as relative contraindication by some
investigators. SPECT scan as been shown to improve sentinel node identification rates in these patients.(Ref)
However, there is no randomized study comparing the efficacy of conventional lymphoscinitigraphy and SPECT
scan in identifying sentinel node in obese or polder patients.

False Negative Rate

Ultra sound (US) of axilla is an evolving method of evaluation of axilla in patients of breast cancer with clinically
negative axilla. US of the axilla may provide a significant improvement in the preoperative assessment of lymph
node status. In expert hands, axillary US almost always allows identification of the lymph nodes, assessment of
even the smallest nodes, and in-depth evaluation of node morphology. If US criteria to recognize metastatic
nodes can be consistently identified, axillary US, possibly in association with US-guided FNAC/ biopsy, may
significantly impact the choice of the surgical procedure and thus reduce the false negative rate of sentinel lymph
node biopsy in breast cancer. Obviously, patients with core biopsydocumented positive nodes or US highly
suspicious nodes might undergo straight to total axillary node dissection, saving financial resources and time.

Sentinel node evaluation

Conventioally the sentinel lympoh node biopsy specimen is subjected to conventional &E and lymph nodes that
are negative for metastases on conventional H&E are subjected to immunohistochemistry. However, in Indian
settings where patients present with larger operable breast cancer about 40% of patients with clinically negative
axilla will axillary lymph node metastasis,. In this set of patientst, accurate intraoperative evaluation of SLNs
permits an ALND to be performed during the initial operation if the node is positive, saving the patient both the
time, cost, and burden of a second operation. At present, there is no consensus on the utility of intraoperative
SLN analysis or the optimal method of evaluation. Two available procedures to determine the presence of nodal
metastasis are frozen section and imprint cytology. Table 3 shows the reported results of intraoperative imprint
cytology and frozen section

Imprint cytology Frozen section

sensitivity specificity sensitivity specificity
Miki Mori etal (2006) 47.1 98.3 88.2 100
Leidenius et al. (2003) 68 99 83 99
Beach et al. (2003) 69 100 54 100
Liang et al. (2003) 62.5 100 62.5 100
Nagashima et al. (2003) 70.3 99.6 83.8 100
Sauer et al. (2003) 58 100 77 100
Motomura et al. (2000) 96 90.8 52 100
van Diest et al. (1999) 62 100 87 100
Fisher et al. (1993) 98 100 90.2 100

Although a few studies have shown acceptable sensitivities for frozen section applied to intra-operative
diagnosis, many studies have claimed there are advantages to using imprint cytology in this setting. In 1999, the
College of American Pathologists recommended that SLNs be examined intraoperatively by cytologic methods. A

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key advantage of the imprint cytology over frozen sectioning is the avoidance of the loss of tissue attendant to the
use of a cryostat. Thus, imprint cytology preserves tissue for subsequent focused pathologic analysis of the
SLNs. Thus, it stands to logic that combination of FS & IC should be more accurate than either of the two and it
is relatively easy to perform both techniques on the eexcised sentinel node.Though there are studies in literature
comparing accuracy of FS vis a vis IC, there are no studies comparing combined accuracy of FS & IC vis a vis
conventional H&E. Though immunohistochemistry is the gold standard method of assessing the axilla, MR
spectrosocopy has been shown to identify biochemical markers in metstatic axillary and sentinel lymph nodes in
breast cancer. Howver, larger number of lymph nodes need to be evaluated to confirm the preliminary findings.
Vascular endothelial growth factor C (VEGF C) . It is a protein encoded by a gene which is a member of the
platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family, is active in angiogenesis,
lymphangiogenesis and endothelial cell growth and survival, and can also affect the permeability of blood
vessels. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms
which bind and activate VEGFR-3 receptors. Only the fully processed form can bind and activate VEGFR-2
receptors. This protein is structurally and functionally similar to vascular endothelial growth factor D (VEGF-D).

Tumour markers in Breast Cancer

S.V.S. Deo, Ashish Jakhetiya

Introduction
A tumour marker is a molecular or tissue based process that provides future behaviour of a cancer but requires a
special assay that is beyond routine clinical, radiological or pathological examination. It can be any substance
found in blood, urine or body tissues that can be elevated or altered in cancer. The term tumour marker was
traditionally used to denote such a factor but with current explosive growth in cancer molecular biology and
genetics the term Bio-marker will be more appropriate . Biomarkers are synthesized and released by cancer
cells or produced by host in response to the presence of tumor. Elevated levels of biomarker can indicate
presence of cancer, however there are other causes also. Tumor markers can be measured at multiple levels:
DNA, RNA, protein, cell and tissue. For example, DNA based marker assays might detect gene mutations,
deletions, amplifications. RNA based marker assays which includes micro-RNA (miRNA) might detect over or
under expression of the message, splice differences in the message, or inhibitory miRNAs that prevent
translation of other transcripts. Protein based markers can include overexpression, under expression, or
qualitative abnormalities. One might detect cancer cells in tissues or fluid in which they do not belong, such as
regional lymph nodes, circulation or distant organs (like bone marrow). Biomarkers plays an important role in
management of various malignancies including Serum PSA for prostate cancer, CEA for colon cancer, CA-125
for ovarian cancer, AFP and HCG for germ cell tumours. However role of biomarkers in breast cancer
management is still evolving and few biomarkers are now gained widespread acceptance.

Potential uses of biomarkers

There are several possible clinical uses for a tumor marker. Tumor marker might be used for screening to detect
an established cancer earlier than it would have been using standard clinical signs and symptoms. Biomarkers
can also be used to establish diagnosis and staging of malignancy. The most frequent use of a biomarker is to
determine prognosis in a patient with established cancer. Biomarkers can be used to predict response to
particular therapy. Another important role of biomarkers is for post operative surveillance and monitoring
response to therapy in advanced disease.

Biomarker in breast cancer

Breast cancer is the most common cancer in women worldwide with significant morbidity, impact on health care
cost and mortality. As still there is no uniform adoption to policy of screening, advanced and metastatic
presentations are common, apart from that chemoresistence also contributes to poor outcomes. Breast cancer
treatment has experienced several changes in the past decades due to the discovery of specific prognostic and
predictive biomarkers that enable the application of more individualized therapies to different molecular
subgroups. Now apart for conventional prognostic factors (tumor size, grade, stage, lymph node status)
established molecular markers such as estrogen receptor (ER) and progesterone receptor (PR) plays significant
role in selection of patients benefiting from endocrine therapy. Still reliable biomarker for use in clinical practice
remains unavailable and it is crucial to identify new biomarker with the potential to enhance early diagnosis,
predict prognosis, drug resistance development and treatment choice in breast cancer. The American Society of
Clinical Oncology (ASCO) first published evidence-based clinical practice guidelines for the use of tumor markers
in breast cancer in 1996. ASCO guidelines are updated at intervals by an update committee of the original expert
panel and last updated guidelines were published in 2007.

Estrogen and Progesterone receptor (ER and PR)

ER is most important biomarker in breast cancer and expression of PR is strongly dependent on presence of ER.
Tumors expressing PR but not ER are less than 1%. ER and probably PR content are associated with a
favourable prognosis, and more importantly, highly predictive of benefit from endocrine treatment in both the

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adjuvant and metastatic settings. ASCO guidelines recommend that ER and PR should be measured on every
primary invasive breast cancer and may be measured on metastatic lesions if the results would influence
treatment planning. In both pre- and postmenopausal patients, steroid hormone receptor status should be used to
identify patients most likely to benefit from endocrine forms of therapy in both the early breast cancer and
metastatic disease settings. From presence or absence of these receptors now quantitative assessments of
expression levels are available, still there are deficits in standardization for ER and PR assays (in particular,
immuno-histochemistry [IHC]), and further efforts at defining reproducibility and accuracy for particular reagents
are an important priority.

HER 2
HER2 is a member of the epidermal growth factor receptor (EGFR) family. It is amplified and over expressed in
15%to30% of newly diagnosed breast cancers and is associated with more aggressive behaviour. ASCO
recommends HER2 expression and/or amplification should be evaluated in every primary invasive breast cancer
either at the time of diagnosis or at the time of recurrence, principally to guide selection of trastuzumab in the
adjuvant and/or metastatic setting. Five prospective randomized clinical trials have now been reported in the
adjuvant setting, as well as a single, small, prospective, randomized neoadjuvant clinical trial. Each has shown a
remarkable beneficial effect of trastuzumab on pathologic complete response, disease-free survival, and overall
survival. Level II evidence suggests that overexpression of HER2 (3+by protein or> 2.0 FISH ratio by gene
amplification) identifies patients who have greater benefit from anthracycline-based adjuvant therapy. But at
present use of HER 2 is not recommended for adjuvant chemotherapy decision making. There are insufficient
data to support the use of HER2 as a predictor of response to endocrine therapy, although the evidence does
suggest that in patients with ER-positive tumours, the relative benefit from antiestrogens for those with HER2-
positive cancers is likely to be lower than for those with HER2-negative cancers. While the weight of evidence
suggests that HER2 amplification/over expression are associated with worse outcome, the role of this marker
purely to determine prognosis in clinical practice is unclear and it is not recommended for the sole purpose of
determining prognosis. Circulating HER2 extracellular domain (ECD) levels have been proposed as a surrogate
for tissue measures of HER2, to monitor patients for early relapse or to monitor response to standard therapies or
HER2-targeted therapies. The ECD of HER2 can be detected in serum or plasma, most commonly by a
commercially available enzyme-linked immunosorbent assay (ELISA), and is elevated in approximately 30% of
patients with metastatic breast cancer. It has been proposed to have same utility as of HER2, although
appealing; use of circulating HER2/ECD is hampered by a lack of high-quality studies and a lack of consistent
findings and is not currently recommended for any clinical setting.

CA 15-3 and CA 27.29

CA 15-3 and CA 27.29 are well-characterized assays that allow the detection of circulating MUC-1 antigen in
peripheral blood. Present data are insufficient to recommend CA15-3 orCA27.29 for screening, diagnosis, and
staging. Several well-designed studies have shown that an increase in CA 15-3 or CA 27.29 after primary and/or
adjuvant therapy can predict recurrence an average of 5 to 6 months before other symptoms or tests. Still there
are no prospective randomized clinical trials to demonstrate whether detection and treatment of occult or
asymptomatic metastases using tumor markers impact on the most significant outcomes (disease-free survival,
overall survival, quality of life, toxicity, or cost-effectiveness). For monitoring patients with metastatic disease
during active therapy, CA27.29 or CA 15-3 can be used in conjunction with diagnostic imaging, history, and
physical examination. Present data are insufficient to recommend use of CA 15-3 or CA 27.29 alone for
monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CA 15-
3 or CA 27.29 may be used to indicate treatment failure. Caution should be used when interpreting a rising
CA27.29 or CA 15-3 level during the first 4 to 6 weeks of a new therapy, given that spurious early rises may
occur.

CEA
CEA levels are less commonly elevated than are levels of the MUC-1 assays, CA 27.29, or CA 15-3. Only
50%to60%of patients with metastatic disease will have elevated CEA levels; compared with 75%to90% who have
elevated levels of the MUC-1 antigen. CEA levels are minimally complementary with MUC-1levels and
recommendation for their use is similar as of CA 15-3 and CA 27.29. Available data suggest that it is reasonable
to evaluate one of the MUC-1 assays and CEA initially in a patient with metastatic disease. If the MUC-1 assay is
elevated, there appears to be no role for monitoring CEA, but if not, than CEA levels may provide supplementary
information to the clinician in addition to clinical and radiographic investigations.

Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor 1 (uPA and PAI 1)
uPA and PAI-1 are part of the plasminogen activating system, this system has been shown experimentally to be
associated with invasion, angiogenesis, and metastasis. uPA and PAI 1 levels can be used for the determination
of prognosis in patients with newly diagnosed, node-negative breast cancer patients. Adjuvant chemotherapy
provides substantial benefit in comparison to observation alone, in patients with high risk of recurrence as
determined by high levels of uPA and PAI-1.

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Markers of Proliferation

IHC based markers of proliferation which includes Ki67, Cyclin D, Cyclin E, p27, p21,Thymidine kinase,
Topoisomerase II and DNA flow-cytometry based markers of proliferation like DNA content, S phase ploidy are
presently not recommended for prognostication or any other purposes in breast cancer.

Bone marrow micrometastasis

Bone marrow micrometastasis in breast cancer patients are defined as epithelial cells found within a bone
marrow aspirate that may or may not be breast-derived, malignant, or viable. Only approximately 30% to 50% of
patients whose marrow contains micro metastases from breast cancer will develop clinically apparent breast
cancer metastasis during a 5- to 10-year period of follow-up. Given that 50% to 70% of the women with marrow
micrometastasis do not develop clinically metastatic breast cancer, it is clear that not all detectable breast cancer
cells in the bone marrow will have clinical relevance for a particular patient. ASCO do not recommend use of
bone marrow micro metastases for screening, diagnosis, staging, prognosis, surveillance, or monitoring
treatment of patients with breast cancer.

Circulating tumour cells (CTC)

CTCs are those cells present in the blood that possess antigenic or genetic characteristics of a specific tumour
type. The source of CTCs is unknown and the clinical significance of CTCs is not yet established. The presence
of CTCs in a breast cancer patient may predict for the presence of a micrometastasis or of an aggressive primary
tumor. One cell detection assay, the CellSearch Assay, has recently received US Food and Drug Administration
clearance for application to the metastatic breast cancer patient. At present ASCO do not recommend use of
CTC for diagnosis of breast cancer or to influence any treatment decision.

Multiparameter gene expression analysis

Studies suggest that assessing the expression of multiple genes in a tumor sample may provide useful
information about tumor behaviour. Now molecular subtypes are emerging as powerful predictive markers in
breast cancer depending upon the status of ER, PR and HER 2 receptors.

Oncotype DX: Oncotype DX is RT-PCR assay that measures the expression of 21 genes. This is used to
determine prognosis in newly diagnosed patients with node-negative, ER positive breast cancer who receive
tamoxifen. It has been suggested that tamoxifen-treated patients with an excellent estimated prognosis may be
spared adjuvant chemotherapy. In addition, patients with a high recurrence score (RS) appear to achieve a
higher proportional benefit from adjuvant CMF chemotherapy than those with low or intermediate RS.

Mammaprint (70 gene signature): MammaPrint is a gene expression profiling platform marketed by Agendia.
Appear to identify groups of patients with very good or very poor prognosis. Though FDA approved but ASCO still
do not recommend for clinical use.

Rotterdam (76 gene signature): Specifically studied in all lymph-node-negative breast cancer patients,
regardless of age, tumor size and grade, or ER/PR status. Not recommended for clinical use at present.

Beyond usual biomarkers

Various studies have shown prognostic values of P53, cathepsin D, cyclin E and proteomics in breast cancer,
however none of them is recommended by ASCO at present. Mammaglobin, osteopontin, snail, twist, Zeb-1,
fibroblast growth factor receptors (FGFR), phosphatase and tensin homolog (PTEN) and sirtuins (SIRT) are other
potential biomarkers for the prediction of metastatic disease. Some potential biomarkers for the prediction of
systemic chemotherapy resistance include Cytochrome P450 2D6 (CYP2D6), Phosphatidylinositol-4,5-
biphosphonate-3-kinase (PIK3CA), Retinoic acid receptor alpha (RARA), Signal transducer and activator of
transcription 3 (STAT3), Tissue inhibitor of metalloproteinase 1(TIMP-1) and Lin28. During the last years,
circulating noncoding molecules of RNA (miRNAs) are emerging as an innovative class of cancer biomarkers
since found aberrantly expressed in different human cancers (tissues and serum) and featured by unprecedented
levels of diagnostic specificity and sensitivity. Despite this exciting discovery, common BC specific miRNAs have
yet to emerge across studies, and it is too soon to interpret their functional role.

Conclusion
The current routinely used serum tumor markers have limited usefulness for diagnosis and/or screening of breast
cancer due to their very low sensitivity and specificity as well as to the fact that they can be raised also in case of
some benign conditions. As regards the usefulness of tumor markers for monitoring patients during follow up, the
debate is still open between scientific organizations. Role of tumor markers is emerging as an early warning able
to highlight those patients at risk to have a recurrence due to clusters of tumor cells undetectable by conventional
morphological imaging modalities. Molecular classification is now has good acceptance and prognostic value and
various treatment decisions are now taken by expression of hormonal receptors. The established
clinicopathologic markers, in particular ER and HER2, have clearly defined clinical applicability, but deficiencies
in the methodologies of assessment may still affect their use. Additional tools are required to facilitate clinical
decision-making processes especially for the optimal treatment of early hormone receptor-positive breast cancer.

79
Very few of the many individual prognostic markers evaluated are sufficiently powerful on their own to merit
clinical use.

Despite the significant increase in the amount of research conducted on breast cancer biomarkers in the last five
years, significant gaps remain that must be filled to translate this newly acquired knowledge into clinical practice.
Thus, there is a need to validate the expression of these potential biomarkers in large patient cohorts.

References

1. Harris L, Fritsche H, Mennel R, Norton L, et al. American Society of Clinical Oncology 2007 Update of
Recommendations for the Use of Tumor Markers in Breast Cancer. J Clin Oncol 2007;25:5287-5312.
2. Michael J Duffy. Clinical Chemistry 2006;52(3):345351.
3. Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocrine-
Related Cancer 2010;17: R245R262.
4. Mirabelli P and Incoronato M. Usefulness of Traditional Serum Biomarkers for Management of Breast Cancer
Patients. BioMed Research International Volume 2013, Article ID 685641, 9 pages
http://dx.doi.org/10.1155/2013/685641.
5. Pultz B, Luz F, Faria P, Oliveira A, Arajo R , Silva M. Far Beyond the Usual Biomarkers in Breast Cancer: A
Review. Journal of cancer 2014; 5(7): 559-571.
6. Daniel F Hayes. Biomarkers. Devita, Hellman and Rosenbergs cancer principles and practice of oncology. 9 th
edition. Page 694-701.
7. Hayes DF, Bast RC, Desch CE, et al. Tumor marker utility grading system: a framework to evaluate clinical utility
of tumor markers. J Natl Cancer Inst 1996;88:1456.

Breast Conservation Surgery

Harit Chaturvedi

Although radical and modified radical mastectomy (MRM) werethe historical mainstays of the treatment of Stage I
and IIbreast cancer for decades and MRM continues to be appropriatefor some patients, breast conservation
therapy (BCT) is now well established asoncologically safe treatment for primary breast cancer, andin fact has
1
been deemed the preferable surgical option in a1991 National Cancer Institute (NCI) position statement
onmanagement of early-stage disease. This consensus was reachedafter the completion of several prospective,
randomized clinicaltrials confirming survival equivalence in breast cancer patientsrandomly assigned to receive
BCT versus mastectomy. Follow-upas long as 20 years has been reported as well as ameta-analysis of all
trials2,with stability of the outcomeresults.. Local recurrence after breast preservation may be due to
inappropriatepatient selection, inadequate surgery or radiation therapy,or biologically aggressive disease.
Inadequate surgery may havecontributed to the increased risk of breast recurrence in theNCI and the EORTC
trials. Overall, the incidence of a recurrencein the treated breast ranges from 3 to 20 percent 2,3,4,5,6,7 .The
majority of failures in the treated breast can be salvagedwith mastectomy, and survival following such treatment
is approximately70 percent at five years. Primarymastectomy does not guarantee freedom from local
recurrencein Stage I and II breast cancer. The incidence of chest wallrecurrence ranges from 4 to 14 percent.

Four critical elements in patient selectionfor breast conservation treatment are:

History and physicalexamination.
Mammography and assessment techniques
Histological assessment of theresected breast specimen.
Assessment of the patientsneeds and expectations.

History and Physical Examination

Much of the information needed to determine a patientssuitability for breast conservation therapy can be
obtainedfrom a detailed history and physical examination. It is importantto note that age per se, whether young or
old, is not a contraindicationto breast conservation. In the elderly, physiologic age andthe presence of comorbid
conditions should be the primary determinantsof local therapy.

Mammographic Evaluation
Recent mammographic evaluation (usually within three months)prior to biopsy or definitive surgery plays an
important rolein establishing the appropriateness of breast conservation treatmentby defining the extent of a
patients disease, the presenceor absence of multicentricity, and other factors that mightinfluence the treatment
decision. It is important for evaluatingthe contralateral breast. Bilateral mammography is requiredfor palpable
lesions as well as nonpalpable lesions that canbe identified only radiographically. Nonpalpable masses
andmicrocalcifications comprise an increasing percentage of carcinomastreated with breast conservation.

The breast tumor should be measured in at least two dimensionson the mammographic views or from the
sonogram during ultrasonography,if it is performed. The size of the tumor should be includedin the
mammographic report. If the tumor is a poorly marginatedmass, approximate dimensions can be given from

80
either the mammogramor the sonogram. The skin of the breast in the area of a massshould be evaluated for
thickening that might signify tumorinvolvement. If the mass is associated with microcalcifications,an assessment
of the extent of the calcifications within andoutside of the mass should be made, including the dimensionsof the
area in which calcifications are located. If one or moreclusters of microcalcifications are the only markers of
thetumor, their location and distribution should be described.For evaluation of masses and microcalcifications,
specializedviews with positioning adapted to the location of the abnormalitymay be helpful. Magnification
mammography and spot compressionare important for characterizing microcalcifications and definingthe margins
of masses. Ipsilateral multifocality (in the samequadrant of the breast) or multicentricity (in different quadrantsof
the breast) may be present and influence the treatment selection.In every instance, when one abnormality is
seen, all areas ofeach breast should be fully evaluated for the presence of additionaldisease.

Using magnificationmammography and ultrasound, patients with tumors suitable forbreast conservation can be
8
identified with at least 95% certaintypreoperatively.

INTEGRATING MEDICAL ADVANCES INTO BCT PROGRAMS

Advanced Breast Imaging and BCT

Breast magnetic resonance imaging (MRI) is increasingly beingused, and has been reported to have
9
sensitivity approaching100% in detecting breast cancer. It is therefore potentiallyvaluable in ruling out
multicentric lesions, defining the extentof a primary breast tumor, and it is now standard-of-care managementin
screening patients with axillary metastases from an occultprimary for breast preservation.10-14 .MRI has also
been reported to be particularly useful in definingextent of invasive lobular cancers, and determining eligibilityof
15
these cases for breast-conserving surgery. Rodenko et al found that MRI-assessment of invasive lobular tumor
size correlatedwith pathology findings in 85% of 20 cases, compared to mammographycorrelation in only 32%;
16
Schelfout et al reported similarsuccess with MRI guidance in cases of invasive lobular carcinoma.

Specialized forms of computed tomography (CT) scanning havebeen developed for breast imaging and are
being used for distinguishingpatients with unicentric disease from those with multicentriclesions in hopes of
17
optimizing the selection of BCT candidates.Uematsu et al reported that use of three-dimensional helicalCT
images to plan lumpectomy volumes resulted in an approximatehalving of the positive margin rate. This
technique has alsobeen reported to improve success with lumpectomies performedfor invasive lobular cancer.

Breast ultrasonography has become a routine adjunct in preoperativebreast cancer imaging, and its
18
applications have been expandedto the intraoperative setting. Henry-Tillman et al reportedthat of 25 breast
19
cancers excised with intraoperative ultrasoundguidance, negative margins were obtained in 92%. Rahusen etal
reported similar success with intraoperative ultrasoundfacilitating lumpectomy performance, and demonstrated its
superiorityover standard wire localization for achieving margin controlin a prospective, randomized study of 49
breast cancer patientsrequiring image-guidance for lumpectomy. A major disadvantageof intraoperative
ultrasound is the requirement for either specializedsurgical training or the availability and flexibility of a
committedradiologist.

Whole-breast ultrasound, isnow being utilized for breast cancer screening in high-riskwomen because of its
advantages in imaging dense tissue. A naturalprogression was therefore to evaluate the known cancer-
containingbreast for multicentric disease. Similar to studies of MRI todetect multicentric disease, whole-breast
ultrasound has beenused to evaluate breast cancer patients prior to definitivesurgery, and reported findings have
influenced therapy in approximately15% of cases.20,21

Genetic Testing for Hereditary Breast Cancer Susceptibility

Approximately 5% to 10% of newly diagnosed breast cancers inthe United States are related to an inherited
germline mutation,most frequently in the BRCA1 and BRCA2 genes. BCT can safely be considered in selected
BRCA mutationcarriers, as long as the patient is counseled regarding theincreased risk of new primary tumors
bilaterally.

Studies have demonstratedsimilarly high rates of new contralateral breast cancers inpatients with BRCA
mutations, averaging four- to five-fold higherthan the rates of new contralateral breast cancer seen in
sporadicbreast cancer cases. This increased incidence of contralateraldisease represents further support for the
impression that thehigh rates of developing new ipsilateral breast tumors afterBCT are related to inherent risk in
the breast tissue as opposedto radiation-induced transformations.

Expanded BCT Eligibility

Neoadjuvant CTX and lumpectomy Preoperative chemotherapy (CTX) is standard management for
patientswith locally advanced breast cancer, resulting in primary tumorresponse rates of approximately 80%,
and progression of diseasein only 2% to 3%.22,23,24 This sequence allows for improvedoperability and provides
an in vivo assessment of chemosensitivity.

81
Several randomized, prospective studies have now been completed which prove the oncologic safety of
neoadjuvant CTXin early-stage as well as locally advanced breast cancer, withthe concurrent demonstration that
tumor downstaging does indeedimprove eligibility for BCT without increasing local recurrencerates.25-35 A
surgical component in the multidisciplinarycare of these patients is essential, as the clinical assessmentof
complete response overestimates the pathologic findings byapproximately three-fold, and local recurrence rates
tend tobe higher when radiation therapy is the only local therapy deliveredafter the neoadjuvant CTX.

Induction CTX is a reasonable and safe treatment approach forpatients with breast cancer of any stage if the
clinician iscertain that chemotherapy would be recommended in the postoperativesetting. The risk of
overtreatment can be minimized by obtainingmultiple diagnostic core biopsy specimens to confirm that alesion is
predominantly invasive, as CTX is clearly inappropriatetherapy for large-volume/palpable DCIS tumors or DCIS
with microinvasion.Patients presenting with multiple tumors or extensive calcificationson initial mammogram
should be counseled that preoperative CTXwill not convert them to BCT eligibility, regardless of theextent of
primary tumor shrinkage. Estimation of treatment responsetends to be more challenging with invasive lobular
cancers aswell.36-37 If the tumor is not associated with any microcalcifications,then a radio-opaque clip should
be inserted (preferably underultrasound guidance) either prior to delivery of the neoadjuvantCTX or within the first
couple of cycles. In the event thatthe patient has a complete clinical response to the preoperativeCTX, this clip
will serve as the target for subsequent mammography-assistedwire localization lumpectomy. Lesions associated
with microcalcificationshave an inherent localization target.
Imaging with ultrasound and/or mammogram can be repeated aftera couple of CTX cycles to evaluate tumor
response. Breast MRI may be a more accurate method ofassessing the extent of residual invasive tumor when
expertisewith this technique is available.

Plans for breast-preserving surgery may proceedif there was no evidence of multicentric disease at
presentationand if the tumor is resectable by lumpectomy after the neoadjuvanttreatment.

BCT for subareolar tumors and Paget's disease Tumors involving the subareolar tissue and/or nipple (eg,
Paget'sdisease of the nipple) have previously been considered relativecontraindications to BCT because of the
need for nipple removal.However, if disease appears to be confined to a central unifocalarea, without diffuse
microcalcifications, and if margin negativitycan be achieved, then performing a central segmentectomy isa
reasonable approach. The patient can undergo elective nipple-areolarreconstruction following completion of
breast irradiation, ifshe so desires.

Lumpectomy for multiple breast tumors Early studies of lumpectomy for patients with multiple tumorsrevealed
rates of local failure in excess of 20%, leading tothis feature being widely considered to represent a
contraindicationto BCT.38,39 The generally accepted approach is thatBCT can be attempted in these cases as
long as the tumors canbe encompassed within a single margin-negative lumpectomy specimen,and with a
cosmetically acceptable volume of residual breasttissue.

Pathological Features Influencing Treatment Choice

A number of pathologic factors have been assessed for theirability to predict an increased risk of recurrence in
the treatedbreast in patients undergoing conservative surgery and radiation.These factors include histologic type
and grade, the presenceor absence of tumor necrosis, vascular or lymphatic invasionor an inflammatory infiltrate,
the presence of DCIS in associationwith an invasive ductal carcinoma, margins of resection, andpathologic nodal
status.

Patients with invasive lobular cancers are candidates for conservativesurgery and radiation, provided that the
tumor is not diffusein the breast and that complete excision with negative marginscan be achieved. Under these
circumstances, there has been noincreased risk of breast recurrence in patients with invasivelobular carcinomas
treated with conservative surgery and radiation. Patients with positive axillary nodes do not have an increasedrisk
of breast recurrence when treated with conservative surgeryand radiation. This is in contrast to
patientsundergoing mastectomy where the number of positive axillarynodes correlates with the incidence of chest
wall recurrence.The diminished risk of breast recurrence in node-positive patientsmay be related to the combined
effects of chemotherapy and/ortamoxifen with radiation in these patients.

Pathologic Evaluation

The excised tissue should be submitted for pathology examinationwith appropriate clinical history and anatomic
site specificationsincluding laterality (right or left breast) and quadrant. Forwide excisions the surgeon
shouldorient the specimen (e.g., superior, medial, and lateral) forthe pathologist with sutures or other markers.
Gross examinationshould document the type of surgical specimen (e.g., excisionalbiopsy, ), the size of the
specimen, the measuredsize of the tumor, and the proximity of the tumor or biopsysite to the margins of excision.
The presence or absence oftumor at the margins of excision is determined by marking themwith India ink or
another suitable technique.

82
Frozen section preparation of tissue obtained from image-guidedneedle biopsies of nonpalpable lesions or
tumors less than 1cm is strongly discouraged. Small foci of invasive carcinomaor microinvasive disease may be
lost or rendered uninterpretableby freezing artifact. In general, frozen sections should beprepared only when
there is sufficient tissue that the finaldiagnosis will not be compromised and when the information isnecessary for
immediate therapeutic decisions.

The pathologist includes certain basic data in each surgicalpathology consultation report because they are of
prognosticimportance or are needed for staging or therapy.
Features that should be included in the surgical pathology consultationreport for invasive carcinoma include:
How the specimen wasreceived (e.g., number of pieces, fixative,orientation).
Thelaterality and quadrant of the excised tissue and the typeofprocedure as specified by the surgeon.
The measured size ofthe tumor (in three dimensions if possible),with verificationby microscopic
examination, particularly forpT1 lesions orthose associated with an EIC.
Histologic type and grade.
The presence or absence of coexistent DCIS or an EIC.
Thepresence or absence of peritumoral vascular or lymphaticinvasion.
The presence or absence of gross or microscopic carcinoma(eitherinvasive carcinoma or DCIS) at the
margins of excision.If tumoris not at the margin, the distance of the tumor orbiopsy sitefrom the margin
should be stated, and the locationof the positiveor close margin (superior, medial, etc.) identified.
The presence and location of micro-calcifications.
Lymphnode status. This should be recorded as the number oflymphnodes found in the specimen and
the number of involvednodes,the size of the largest involved node, and the presenceor absenceof
extension beyond the lymph node capsule.

The presence of a focus of tumor measuring two mm or less withina lymph node identified by routine histologic
examination isdefined as a micrometastasis and is classified as pN1a. Theclinical significance of multiple micro-
metastatic foci is unknown;however, it is recommended that they also be classified as pN1auntil further
information becomes available.

It is important to specify the presence of any special histologictypes of invasive breast cancer (e.g., tubular,
mucinous, papillary),most of which are considered low grade. All ordinary invasivecarcinomas (ductal, no special
type [NST]) should be assigneda histologic grade; some authors recommend grading invasivelobular carcinoma
as well.

The assessment of surgical margins is arguably the most importantaspect in the pathologic evaluation of breast
tumor excisionsin patients being considered for breast conservation. Althoughthe definitions of "positive" and
"negative" margins vary amonginstitutions, microscopic margin involvement appears to be associatedwith an
increased risk of local recurrence and, in most cases,indicates a need for further surgery, such as re-excision
ofthe tumor site.

Determination of estrogen and progesterone receptors is standardfor invasive breast carcinomas. . The results
of ancillary studies (such as steroidreceptor analysis, DNA ploidy, proliferative rate, etc.) areusually reported in
an addendum or supplement to the surgicalpathology report.

Patient Preferences

Perhaps the most difficult aspect of patient evaluation is theassessment of the patients needs and expectations
regardingbreast preservation. The patient and her physician must discussthe benefits and risks of mastectomy
compared with breast conservationtreatment in her individual case, with thoughtful considerationof each. Each
woman must evaluate how her choice of treatmentis likely to affect her sense of disease control, self-
esteem,sexuality, physical functioning, and overall quality of life.A number of factors should be considered:
1. Long-term survival.
2. The possibility and consequences of local recurrence.
3. Psychologicaladjustment (including the fear of cancer recurrence),cosmeticoutcome, sexual adaptation,
and functional competence.

Absolute and Relative Contraindications

In the selection of patients for breast conservation treatmentwith radiation, there are some absolute and relative
contra-indications.

Absolute Contraindications
1. Pregnancy is an absolute contraindication to the use of breastirradiation. However, in many cases, it
may be possible to performbreast-conserving surgery in the third trimester and treat thepatient with
irradiation after delivery.

83
 2. Women with two ormore primary tumors in separate quadrantsof the breast or withdiffuse malignant-
appearing microcalci-ficationsare not consideredcandidates for breast conservation treatment.
3. A history ofprior therapeutic irradiation to the breast regionthat wouldrequire retreatment to an
excessively high total-radiationdoseto a significant volume is another absolute contraindication.
4. Persistent positive margins after reasonable surgical attempts.The importance of a single focally positive
microscopic marginneeds further study and may not be an absolute contraindication.

Relative Contraindications
1. A history of collagen vascular disease is a relative contraindicationto breast conser-vation treatment
because published reportsindicate that such patients tolerate irradiation poorly. Most radiation
oncologists will not treat patients with sclerodermaor active lupus erythematosus, considering it an
absolute contraindication.In contrast, rheumatoid arthritis is not a relative or an absolutecontraindication.
2. The presence of multiple gross tumors inthe same quadrant andindeterminate calcifications must be
carefullyassessed forsuitability because studies in this area are notdefinitive.
3. Tumor size is not an absolute contra-indicationto breast conservationtreatment, although there is little
publishedexperience intreating patients with tumor sizes greater thanfour to fivecm. However, a relative
contraindication is thepresence ofa large tumor in a small breast in which an adequateresectionwould
result in significant cosmetic alteration. Inthis circumstance,preoperative chemotherapy should be
considered.
4. Breast size can be a relative contra-indication. Treatmentbyirradiation of women with large or pendulous
breasts is feasibleif reproducibility of patient set-up can be assured and thetechnical capability exists for
greater than or equal to sixMV photon beam irradiation to obtain adequate dose homogeneity.

A family history of breast cancer is not a contraindicationto breast conservation

TECHNICAL ASPECTS OF SURGICAL TREATMENT

When breast conservation treatment is appropriate, the goalsof any surgical procedure on the breast are total
removal ofthe suspicious or known malignant tissue with minimal cosmeticdeformity. These goals apply to either
a diagnostic biopsy ordefinitive local excision prior to radiation therapy. Failureto consider them at all stages may
jeopardize conservation ofthe breast.

In most cases, local anesthesia can be utilized for the biopsy.Frequently, local anesthesia also can be used for
the definitivelocal excision, particularly when it is combined with intravenoussedation in selected patients.

Skin Incision

The placement and performance of the skin incision can be criticalto the quality of cosmesis. Curvilinear skin
incisions followingLangers lines (the natural lines of skin tension) generallyachieve the best cosmetic result .
However, at thethree oclock and nine oclock positions and inthe lower breast, a radial incision may provide a
better result,particularly if skin removal is necessary.

Recommended locations of incisions for performing

breast biopsy. For larger lesions in the lower breast,
particularly when skin must be excised, a radial
incision often results in better cosmesis.

The incision should be over or close to the tumor and of adequatesize to allow the tumor to be removed in one
piece. In the upperinner aspect of the breast, some retraction of the skin maybe necessary to avoid an incision
that may be visible with clothing.Periareolar incisions for lesions in the periphery of the breastare inappropriate.
Excision of a segment of skin rarely is necessary and is undesirablebecause it may alter the position of the nipple
or the inframammarycrease. Preservation of the subcutaneous tissue with separateclosure improves the
cosmetic result. The skin should be closedwith a subcuticular technique.

84
Techniques for Optimizing Success with Lumpectomy and Margin Control

Percutaneous diagnostic needle biopsy Percutaneous needlebiopsies are increasingly being used to
establish a diagnosisof breast cancer, and several studies have demonstratedthat lumpectomies are more likely
to be margin-negative whenthe breast cancer diagnosis has been established via percutaneousneedle biopsy as
opposed to open surgical diagnostic biopsy.Core needle biopsies are more accurate than fine needle
aspirates,and have the advantage of providing adequate tissue for determiningwhether or not the lesion has an
invasive histology. Core needlebiopsies can be done freehand for palpable lesions, or theycan be performed with
stereotactic mammography or ultrasoundguidance for nonpalpable lesions.

Specimen handling and intraoperative margin assessmentDirect communication between the surgeon and
pathologist isthe first step in optimizing margin control. At a minimum, thelumpectomy specimen should be
oriented by the surgeon (whenlogistically feasible, this should be done in the presence ofthe pathologist), and the
tissue margins should be inked (multiple-colorinks may facilitate the orientation of the specimen margins).While
frozen-section analysis of multiple margins is notoriouslytime consuming and inefficient, touch-prep evaluations
are beingincreasingly advocated as a rapid and reliable alternative.

The touch-prep method (also called imprint cytology) is relativelystraight forward, and is based on the premise
that cancer cellsare more adherent to a glass surface than benign cells. Thepathologist touches a microscope
slide against the lumpectomysurface, fixes, and then stains the slide with hematoxylin andeosin. Several surfaces
can be evaluated fairly quickly in thisfashion, and reported results have been very favorable. Coxet al found an
accuracy of 97.3% in use of touch-preps formargin analysis, and Klimberg et al estimated a margin
assessmentsensitivity at 100%.

Breast Tissue Management

The primary lesion should be excised with a rim of grossly normaltissue, avoiding excessive sacrifice of breast
tissue. Verysuperficial tumors in the subareolar area may require excisionof the nipple areolar complex to assure
adequate tumor marginsand to avoid devascularization. (Partial areolar excision withcareful approximation for
small lesions in the immediate subareolararea can provide adequate tissue removal and good cosmesis.)Closure
of the breast tissue may reduce the occurrence of asaucer-like defect, but the overall cosmetic result with
nippleareolar sacrifice will be less than optimal.

Lesions within the substance of the breast should be approachedby incising the overlying breast tissue. A
superior cosmeticeffect is usually achieved when the breast is not reapproximated.Reapproximation that appears
to be adequate with the patientrelaxed and supine often results in distortion of the breastwhen the patient is
upright and mobile.

Meticulous hemostasis is of critical importance. Hematoma formationproduces changes that are difficult to
interpret by physicalexamination. In addition, the evolving scar from a hematomamakes mammography
interpretation difficult. These changes maybe long lasting and lead to unnecessary biopsy because of thedifficulty
in evaluation. Drains in the breast should be avoided.

Specimen orientation by the surgeon with the use of sutures,clips, multicolored indelible ink, or another suitable
techniqueis important. The specimen should not be sectioned before itis submitted to the pathologist, because
this practice may compromiseaccurate evaluation of the surgical margins. The surgeon shouldexamine the
specimen for the determination of a grossly clearmargin. If a clear margin is not evident, re-excision shouldbe
performed at that time. Routine frozen section evaluationof margins is optional and does not guarantee negative
marginsafter a complete examination. Any uncertainty regarding orientationof the specimen should be clarified for
the pathologist by thesurgeon. In addition, clips outlining the breast defect mayaid the planning and execution of
radiation therapy and demarcatethe tumor bed for future imaging studies.

Image-directed Surgery

Nonpalpable carcinoma may be diagnosed by image-directed biopsyor needle localization and excision. If a
patient has a nonpalpablecarcinoma diagnosed by image-guided biopsy, then breast-conservingsurgery should
be conducted with presurgical localization witha guide such as guidewire. This will be facilitated by the
placementof a marker clip when image-guided biopsy is done for smalllesions, which are likely to be completely
removed by the procedure.

Suspicious lesions detected by mammography require presurgicallocalization in order to assure accurate removal
of the abnormalarea and avoid excess sacrifice of breast tissue. The methodsof localization may be by needle-
hookwire, blue dye injection,or a combination of both. The localization should be precise.Labeled craniocaudal
and lateral films that show the hookwireshould be sent to the operating room for the surgeonsorientation. The
surgeon usually should assess the exact locationby triangulation based on the position, depth of penetration,and
angle of the wire and place the incision closest to thetip of the wire in order to achieve the best cosmetic
result.Tunneling should be avoided, and attempts should be made tomake the skin incision as close to the lesion

85
as possible The same principles of skin incision and breast tissue managementused for palpable cancers
should be employed.

Incision placement for needle localization biopsy should be over the

lesion, not at the point of entry of the wire into the breast.

The breast tissue is dissected until the wire is identified within the
parenchyma, and then the wire is stabilized distally and brought into
the field. Traction on the wire should be avoided at all times.

Localization titanium clips may be left in the excision cavityto aid in placement of irradiation boost volume and to
ensureadequate coverage with tangential fields, especially for lateraland medial lesions.

Specimen Radiograph

A radiograph of the specimen should be obtained, preferablyin two dimensions (orthogonal projections).
Magnification andcompression of the specimen will increase the resolution ofthe radiograph. The specimen film
should be correlated witha preoperative mammogram and interpreted without delay. Theradiologists report
should indicate whether the mammographicabnormality (mass or calcifications) is seen in the specimenand if it
has been removed completely, as far as can be determined.

Re-excision of Biopsy Site

Re-excision of the previous biopsy site to assure negative marginsof resection must be carefully performed in
order to accomplishthis goal, to avoid excess breast tissue removal and to achievegood cosmesis. Proper
orientation of the original biopsy specimen(for example, short suture in the superior margin, long suturein the
lateral margin) will allow identification of the individualmargin surfaces involved with tumor. Re-excision can be
limitedto those areas. When the specimen has not been oriented, removalof a rim of tissue around the entire
previous biopsy is necessary.

For larger biopsy cavities, shaving of each individual margin,with marking of the new margin surface with sutures,
clips,or ink allows removal of residual tumor with preservation ofa maximum amount of breast tissue. For very
small cavities,removal of the entire biopsy site as an en bloc specimen isacceptable.

Management of the Axillary Nodes

Axillary dissection is the standard technique for managementof the axillary nodes. A Level I and II axillary
dissectionwill provide accurate staging information and maintain localcontrol in the axilla. In the patient
undergoing mastectomy,axillary dissection should be performed through the mastectomyellipse. In the patient
undergoing breast conservation, thebreast incision and the axillary incision should be separate.A continuous
incision from the breast to the axilla resultsin unnecessary deformity. Occasionally, a tumor in the axillarytail can

86
be removed through the same incision used to removethe axillary nodes. A transverse incision in the low
axillafrom just posterior to the border of the pectoralis major tonearly the anterior border of the latissimus dorsi
obtains anexcellent cosmetic result and excellent exposure. Some surgeonsprefer a vertical incision posterior
and parallel to the borderof the pectoralis major, which also provides good exposure andcosmetically good
results. During dissection, the long thoracicnerve, the thoracodorsal nerve, and the medial pectoral nerveshould
be preserved. Preservation of the intercostal brachiocutaneousnerve is desirable, as numbness of the posterior
upper arm isless likely to occur with nerve preservation. At times, preservationof this nerve should not be
performed because of grossly involvedlymph nodes. Stripping of the axillary vein is unnecessary andshould be
condemned because it increases the incidence of lymphedema.Usually, closed suction drainage is advisable.

Sentinel node biopsy :

Sentinel node dissection is indicated for small primary tumorswith clinically negative axillary lymph nodes and no
prior axillarysurgery. Pregnancy or multicentric carcinomas are contraindications.Experience with the technique
after neoadjuvant chemotherapyis limited and the available studies suggest a high false-negativerate. Sentinel
node dissection in this circumstance should beconsidered investigational and be performed only under
investigationalprotocols.
For patients who require preoperative chemotherapy, sentinelnode biopsy can be performed prior to the initiation
of chemotherapy.In general, patients with metastases in sentinel nodes detectedin hematoxylin and eosin-stained
sections should undergo completeLevel I and II axillary dissection. Immunohistochemistry shouldnot be routinely
performed, as the significance of metastasesin sentinel nodes detected only by immunohistochemistry remainsto
be determined. Therapeutic decisions should be made on thebasis of metastases identified by hematoxylin and
eosin staining.

In experienced hands, this sentinel node dissection has beenshown to be extremely accurate in predicting
axillary statusand is likely to replace axillary lymph node dissection forwomen with tumor-free sentinel nodes.
Experience with this techniqueprior to abandoning axillary lymph node dissection is essential.Surgeons should
perform both sentinel node biopsy and axillarylymph node dissection until they are confident that the
procedurecan be performed with identification of sentinel nodes in atleast 90 percent of patients with a false-
negative rate of 10percent or less. For most surgeons, this requires 20 to 30 sentinelnode biopsies followed by
axillary dissections to determinean individual surgeons technical accuracy.40,41 LevelI and II axillary lymph
node dissection should be performedas standard therapy.

Sentinel node biopsy usually results in minimal morbidity; however,rehabilitation after axillary lymph node
dissection or sentinelnode biopsy is essential. Usually, patients after sentinel nodebiopsy require no formal
exercise to return to full function.Patients after axillary dissection should be given formal exercisetraining to
prevent a frozen shoulder. Use of shoulder immobilizationand arm slings or wraps should be avoided, as these
contributeto a frozen shoulder. If a patient does not achieve early recoveryof full shoulder function (by six to eight
weeks), physicaltherapy should be instituted to avoid permanent dysfunction.

ONCOPLASTIC SURGERY

Oncoplastic procedures often permit wide resection of tissue which increases the chance of tumour-free margins.
Furthermore, positive margins under these circumstances usually reflect extensive disease for which mastectomy
(rather than re-excision) is indicated. It has been suggested that the chance of local relapse could be reduced by
more aggressive approaches to BCS but there are currently no data on longer-term follow-up of these
oncoplastic procedures. Moreover, there is no information from clinical trials on the safety of BCS for invasive
tumours in excess of 4 cm . Though margin status and the presence or absence of an extensive in
situ component are the principle determinants of local recurrence, consistent associations have been found for
tumours >2 cm . For node-positive patients, tumour size exceeding 5 cm was the only risk factor for local
recurrence on multivariate analysis .Therefore, it is likely that the risk of relapse would remain high for larger
tumours despite adequate surgical clearance. Nonetheless, it may be possible to excise large areas of non-high-
grade ductal carcinoma in situ (DCIS; >4 cm) with clear margins and partially reconstruct the breast with
autologous tissue replacement. Age less than 35 years and family history of breast cancer are additional factors
that must be considered when selecting patients for either oncoplastic surgery with a high EPBVE or skin-sparing
mastectomy with whole-breast reconstruction (higher risk of local recurrence or de novo cancer risk). Though it
may not be feasible in routine clinical practice to formally estimate the EPBVE from radiological measurements of
tumour and breast size, magnetic resonance imaging assessment of all patients is advisable. This can confirm
unifocality or exclude multifocal disease involving different quadrants. Where imaging is equivocal and tumour
parameters are borderline for BCS, it may be preferable to undertake a two-stage procedure; initial 'wide' local
excision of tumour permits full histopathological evaluation with assessment of margins. A definitive oncoplastic
procedure can subsequently be carried out either 2-3 weeks later or following radiotherapy to the breast. A one-
stage procedure is optimal and avoids any technical difficulties relating to the sequelae of previous surgery and
radiotherapy (scarring, fibrosis). There are less likely to be problems with skin viability when completion
mastectomy is undertaken after simple excision of tumour compared with a more complex oncoplastic procedure
with parenchymal undermining and transposition.

87
There is a higher chance of wound infection and fat necrosis in patients who smoke, are obese (body mass index
>30), have large breasts or are diabetic, and these potential complications and their effect on further oncological
treatment should be fully discussed with the patient.

Techniques of oncoplastic surgery

Oncoplastic surgery in the context of partial breast reconstruction encompasses both volume replacement and
volume displacement techniques. The former import additional tissue in the form of a flap and attempt to
compensate for loss of volume from surgical ablation. By contrast, the latter rearrange the remaining breast
tissue using methods of glandular advancement which serve to re-distribute the parenchyma and minimise the
impact of wide local excision. In effect, the volume loss is absorbed over a wider area with concomitant re-
shaping of the breast. Volume displacement surgery is less extensive than for autologous tissue transfer and
there is no donor site morbidity. However, the reconstructed breast is of smaller overall volume and a
symmetrisation procedure on the contralateral side is often required. This applies particularly to therapeutic
mammoplasty where tumour excision is incorporated into a standard or modified reductional procedure.

Volume displacement represents the simplest option for partial breast reconstruction and is usually preferred over
techniques for volume replacement which involve more extensive surgery with harvesting of a myocutaneous or
subcutaneous flap. These flaps cannot subsequently be used for whole-breast reconstruction should the patient
develop local recurrence and require mastectomy. Volume displacement techniques are only possible in patients
with medium to large breasts, whereas replacement techniques are suited to small breasted women. The choice
of method is determined by both the breast volume and the size of the surgical cavity for infill.

Volume replacement techniques

The majority of these techniques use the latissimus dorsi muscle which can be harvested as either a
myocutaneous or myosubcutaneous flap . . The former incorporates an island of overlying skin which can be
used to replace any excised breast cutis. The benefit of partial breast reconstruction with volume replacement
in terms of both cosmesis and patient satisfaction was most evident for patients with small breasts. Three-
quarters of these women were judged to have excellent cosmetic results on combined subjective and objective
assessment compared to none of those with large breasts who underwent a similar method of volume
replacement.

Rainsbury's group described a modified version of the latissimus dorsi (LD) musculosubcutaneous flap which is
popularly known as the 'LD mini-flap' .The LD muscle was harvested with a laterally placed lazy-S
incision through which resection of breast and axillary tissue was simultaneously performed. No skin overlying
the LD muscle was removed, though subcutaneous fat could be employed to enhance tissue bulk if necessary.
The technique is best suited to tumours in the superior and central (2 cm deep to nipple) aspects of the breast .
Tumour bed biopsies with frozen section can reduce the chance of positive margins and permit immediate
mastectomy if a second set of biopsies after routine cavity re-excision are also positive.

Dixon and colleagues incorporated the LD mini-flap into a two-stage procedure with a 'delayed-immediate'
axillary dissection and partial breast reconstruction 5-10 days after initial tumour excision. Where re-excision was
indicated, this was performed at the same time and the flap harvested through an extended axillary incision .

The volume of tissue within a typical latissimus dorsi musculosubcutaneous flap is usually sufficient for partial
breast reconstruction, but adequate mobilisation is required to ensure there is an optimal length of muscle. It is
generally difficult to use an LD flap for volume replacement within the inferior quadrants of the breast. There is no
evidence for any significant atrophy with time and these radiolucent flaps do not interfere with follow-up imaging
of the ipsilateral breast. Variants of this basic flap have been reported which aim to reduce muscle disruption and
hence donor site morbidity.
thoraco-dorsal artery perforator (TDAP) flap--this pedicled flap harvests only the skin or
subcutaneous fat overlying the LD muscle;
intercostals artery perforator (ICAP) flap--the skin or fat overlying the lateral chest wall can
alternatively be supported by the intercostals artery perforator vessels;
muscle-sparing latissimus dorsi flap--this is mainly composed of subcutaneous adipose tissue.

Volume displacement techniques

Several options are available for volume displacement which constitutes a spectrum of techniques of varying
complexity . The common aim of volume displacement is to utilise the remaining breast tissue to fill the defect
resulting from extirpation of the tumour. As previously discussed, resections which lead to loss of >10-20% of
breast volume are likely to incur significant cosmetic detriment and to demand some form of 'infill' to create an
acceptable cosmetic outcome in the longer term. Displacement techniques re-shape the breast through
advancement, rotation or transposition of existing parenchyma and skin with a resultant decrease in overall
breast volume.

88
Simple breast tissue mobilisation

The cosmetic outcome after removal of a relatively small volume of tissue can be enhanced by simple
mobilisation of breast tissue adjacent to the surgical cavity. The extent of this mobilisation depends on the size of
the defect and may involve undermining the whole breast plate . Extensive mobilisation of breast tissue can
sometimes threaten the blood supply to both glandular tissue and skin. This can lead to post-operative necrosis
and secondary sepsis or can compromise flap viability in the event of future mastectomy.

Local tissue flaps

Grisotti described an advancement rotation flap for filling a central defect after removal of the nipple-areola
complex .This is a dermatoglandula flap based on an inferior pedicle and has a skin paddle which replaces the
nipple-areola complex and can be used to fashion a new areola immediately.

Breast reduction techniques and therapeutic mammoplasty

Over the past decade, several reports have emerged describing integration of local tumour excision with a
classical reduction mammoplasty procedure. Most of these cases involve patients with relatively large breasts
and/or who desire smaller breasts and have a tumour located in the zone of resection for a conventional Wise
pattern reduction mammoplasty [27-29]. This includes inferior pole tumours from the 3 to 9 o'clock positions
together with tumours immediately above the nipple-areola complex in medium to large breasts.

Informed consent

Both volume displacement and replacement techniques represent more complex and challenging surgery than
standard wide local excision where a variable amount of breast tissue is removed, but no formal attempt is made
to reconstruct the breast. Patients must be aware of the pattern of scarring which may be more extensive than
anticipated for a reductional procedure. Moreover, patients must be informed of any need for surgery to the
contralateral breast to achieve symmetrisation and the possibility of completion mastectomy in the event of
incomplete tumour excision. The latter may be particularly traumatic after bilateral oncoplastic surgery and the
patient will be faced with the prospect of whole-breast reconstruction. A woman may chose to have a normal-
sized breast with a localised defect rather than a nicely shaped, but smaller breast with concomitant scarring and
a contralateral breast reduction. Conversely, she may opt for a mastectomy with immediate breast reconstruction
rather than an attempt at breast conservation with oncoplastic techniques in order to minimise any chances of
recurrence or to avoid radiotherapy. Patients should be warned of possible delays to adjuvant treatment in the
event of any complications and be made aware of fat necrosis which can give rise to a worrisome lump in the
breast. Where volume replacement techniques are employed, significant donor site morbidity can occur with
seroma formation and even wound dehiscence.

TECHNIQUES OF IRRADIATION

A multidisciplinary approach is necessary for optimal breastconservation treatment. Radiation therapy should be
deliveredonly after evaluation of the mammography findings, the pathologyfindings, and the surgical procedures
performed on the patient.The optimal combination of surgery and irradiation to achievethe dual objectives of local
tumor control and preservationof cosmetic appearance varies from patient to patient. The optimalcombination is
determined by the extent, nature, and locationof the tumor, the patients breast size, and the patientsrelative
concerns about local recurrence and preservation ofcosmetic appearance. Close cooperation between radiation
oncologistsand medical oncologists also is important because irradiationand adjuvant chemotherapy require
integration if both treatmentmodalities are used.
Although controversy has existed concerning the need for deliveringan additional boost dose to the primary site,
,
thereis growing consensus about its utility Most recently,the EORTC has reported the favorable impact of boost
on localfailure rates.

FOLLOW-UP CARE

Follow-up assessment of the results of breast conservation treatmentemphasizes the cosmetic outcome as well
as the detection oflocal recurrence. Regular follow-up examination includes thefollowing goals:
1. Early detection of recurrent or new cancer,allowing timelyintervention.
2. Identification of any treatmentsequelae and appropriate interventionswhere indicated.
3. Providingthe individual practice with the database necessaryto optimizetreatment and compare
outcomes against nationalstandards.

Regular history and physical examination in conjunction withbreast imaging are the cornerstones of effective
follow-up care.Unfortunately, many patients perceive history and physical examinationto be less important as
reliable follow-up measures than sophisticatedmedical testing. A public education effort is needed to addressthis
problem.

89
The following evaluations should be performed by the physicianat cited intervals following the completion of
treatment:

Examinations and Mammography

History and Physical Examination

Local failure occurs at a constant rate from years two througheight post-treatment; therefore, examination
frequency shouldbe based on risk factors for both local and distant recurrence.

EXAMINATION FREQUENCY
Every three to six months, years one to three. This will varyfor patients receiving adjuvant chemotherapy
who need more frequentassessment during the course of their active treatment.
Everysix months, years four and five. Some investigators prefertocontinue semiannual examinations
through year eight becausethe rate of local recurrence is constant through that time interval.
Annually after year five. More frequent follow-up for patientsat exceptionally high risk may be needed.

Mammography

A goal of follow-up imaging of the treated breast is the earlyrecognition of tumor recurrence. To prevent
unnecessary biopsy,it is important to know that postoperative and irradiation changesoverlap with signs of
malignancy on a mammogram. The changesinclude masses (postoperative fluid collections and
scarring),edema, skin thickening, and calcifications. At times, these changes may be impossible to
distinguish. Post-surgicaland radiation edema, skin thickening, and postoperative fluidcollections will be
most marked in the first six months. Afterthe first six to 12 months, radiographic changes will slowlyresolve
and demonstrate stability within two years for mostpatients.

In order to interpret mammograms accurately and assess the directionof change, the current mammogram
must be compared in sequencewith preceding studies. The diagnostic radiologist can tailormammographic
studies of the treated breast to the surgical siteby using special mammographic views in addition to routine
mediolateraloblique and craniocaudal views. Magnification and spot compressioncan be used with any view
to increase detailed visualizationof the site of tumor excision and other areas. Magnificationmammography
is useful to classify calcifications morphologicallyand quantitate them. In some cases, a view with the x-ray
beamtangential to the scar and various other additional obliquitieswill be helpful to differentiate recurrent
tumor from postproceduralchanges.

Ultrasonography can characterize a postoperative mass, suchas a seroma, as fluid-filled rather than solid.
As these massesresolve and scars form; a spiculated soft-tissue density thatmimics tumor may be seen on
the mammogram. Additional radiographicprojections of the site of tumor removal will facilitate moreconfident
radiographic interpretations.

SCHEDULE OF IMAGING OF THE TREATED BREAST

1. Postoperative, pre-radiation therapy mam-mography is particularlyimportant after malignant

microcalcifications have been removedor if the adequacy of the resection is questioned.
Magnificationmammography can be useful in identifying or verifying possibleresidual malignant
calcifications.
2. A baseline mammogram forcomparison should be performed sixto nine months after tumorexcision and
completion of all therapies.
3. At least annuallythereafter or at more frequent intervals aswarranted by clinicalor radiographic findings.

SCHEDULE OF IMAGING OF THE CONTRALATERAL BREAST

Mammography should be performed annually according to the guidelinesendorsed by both the AmericanCollege
of Radiology and the AmericanCancer Society and with synchronization of surveillance mammographyof the
treated breast. More frequent intervals may be warrantedby clinical or radiographic findings. (The risk of cancer
isapproximately the same for both the treated and untreated breast.)

Evaluation of Sequelae

At the time of the first follow-up examination and seriallythereafter, the physician should evaluate the patient for
anytreatment-related toxicities. This evaluation should include:
1. Assessment of the overall cosmetic result. A four-point scoringsystem is recom-mended for
assessing the cosmetic result .

90
 2. Assessment of complications. Complications should be specifiedwith regard to symptomatology and
physical findings. The useof the Radiation Therapy Oncology Group (RTOG)/EORTC RadiationToxicity
Scoring Scheme is recommended for the grading of complications.
In addition, the simple measurement of arm circumference atfixed distances above and below the
olecranon is recommendedfor the evaluation and quantification of arm edema.
3. Patientevaluation of results. The patients evaluationof treatmentoutcomes in terms of psychological,
functional,and cosmeticconsequences should be taken into account in thefollow-up process.

Four-point Scoring System of Breast Cosmesis

Excellent
Treated breast almost identical to untreated breast.
Good
Minimaldifference between the treated and untreated breasts.
Fair
Obvious difference between the treated and untreated breasts.
Poor
Major functional and esthetic sequelae in the treated breast.

References

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2. Morris AD, Morris RD, Wilson JF, et al: Breast-conserving therapy vs mastectomy in early-stage breast cancer: A
meta-analysis of 10-year survival. Cancer J Sci Am 3:6-12, 1997
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of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol
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4. Fisher B, Anderson S, Redmond CK, et al. Reanalysis and results after 12 years of follow-up in a randomized
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in the treatment of Stage I and II breast cancer. N Engl J Med 1995;332:907911
6. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-
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7. Blichert-Toft M, Rose C, Anderson JA, et al. Danish randomized trial comparing breast conservation therapy with
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1992;11: 1925
8. Morrow M, Schmidt R, Hassett C. Patient selection for breast conservation with magnification mammography.
Surgery 1995;118:621626
9. Orel SG, Schnall MD: MR imaging of the breast for the detection, diagnosis, and staging of breast cancer.
Radiology 220:13-30, 2001
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11. Chen C, Orel SG, Harris E, et al: Outcome after treatment of patients with mammographically occult, magnetic
resonance imaging-detected breast cancer presenting with axillary lymphadenopathy. Clin Breast Cancer 5:72-77,
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12. . Baker DR: Magnetic resonance imaging of occult breast cancer. Clin Breast Cancer 1:66-67, 2000
13. Olson JA, Jr., Morris EA, Van Zee KJ, et al: Magnetic resonance imaging facilitates breast conservation for occult
breast cancer. Ann Surg Oncol 7:411-415, 2000
14. Davis PL, Julian TB, Staiger M, et al: Magnetic resonance imaging detection and wire localization of an occult
breast cancer. Breast Cancer Res Treat 32:327-330, 1994
15. Rodenko GN, Harms SE, Pruneda JM, et al: MR imaging in the management before surgery of lobular carcinoma
of the breast: Correlation with pathology. AJR Am J Roentgenol 167:1415-1419, 1996
16. Schelfout K, Van Goethem M, Kersschot E, et al: Preoperative breast MRI in patients with invasive lobular breast
cancer. Eur Radiol 14:1209-1216, 2004
17. Uematsu T, Sano M, Homma K, et al: Value of three-dimensional helical CT image-guided planning for made-to-
order lumpectomy in breast cancer patients. Breast J 10:33-37, 2004
18. Henry-Tillman R, Johnson A, Smith L, et al: Intraoperative ultrasound and other techniques to achieve negative
margins. Semin Surg Oncol 20:206-213, 2001
19. Rahusen FD, Bremers AJ, Fabry HF, et al: Ultrasound-guided lumpectomy of nonpalpable breast cancer versus
wire-guided resection: A randomized clinical trial. Ann Surg Oncol 4:994-998, 2002
20. BergWA, Gilbreath PL: Multicentric and multifocal cancer: Whole-breast US in preoperative evaluation. Radiology
214:59-66, 2000
21. Moon WK, Noh DY, Im JG: Multifocal, multicentric, and contralateral breast cancers: Bilateral whole-breast US in
the preoperative evaluation of patients. Radiology 224:569-576, 2002
22. Newman LA, Washington TA: New trends in breast conservation therapy. Surg Clin North Am 83:841-883, 2003
23. Hunt KK, Ames FC, Singletary SE, et al: Locally advanced noninflammatory breast cancer. Surg Clin North Am
76:393-410, 1996
24. Newman LA: Management of patients with locally advanced breast cancer. Curr Oncol Rep 6:53-61, 2004
25. Mauriac L, Durand M, Avril A, et al: Effects of primary chemotherapy in conservative treatment of breast cancer
patients with operable tumors larger than 3 cm. Results of a randomized trial in a single centre. Ann Oncol 2:347-
354, 1991

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26. Mauriac L, MacGrogan G, Avril A, et al: Neoadjuvant chemotherapy for operable breast carcinoma larger than 3
cm: A unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein
(IBBGS). Ann Oncol 10:47-52, 1999
27. Scholl SM, Asselain B, Palangie T, et al: Neoadjuvant chemotherapy in operable breast cancer. Eur J Cancer
27:1668-1671, 1991
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with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6.
Eur J Cancer 30A:645-652, 1994
29. Scholl SM, Pierga JY, Asselain B, et al: Breast tumour response to primary chemotherapy predicts local and
distant control as well as survival. Eur J Cancer 31A:1969-1975, 1995
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surgery for treatment of primary breast cancer. J Clin Oncol 13:547-552, 1995
31. Makris A, Powles TJ, Ashley SE, et al: A reduction in the requirements for mastectomy in a randomized trial of
neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 9:1179-1184, 1998
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breast carcinomas. Clin Cancer Res 3:593-600, 1997
33. Fisher B, Brown A, Mamounas E, et al: Effect of preoperative chemotherapy on local-regional disease in women
with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin
Oncol 15:2483-2493, 1997
34. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with
operable breast cancer. J Clin Oncol 16:2672-2685, 1998
35. Wolmark N, Wang J, Mamounas E, et al: Preoperative chemotherapy in patients with operable breast cancer:
Nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr:96-
102, 2001
36. Ring A, Webb A, Ashley S, et al: Is surgery necessary after complete clinical remission following neoadjuvant
chemotherapy for early breast cancer? J Clin Oncol 21:4540-4545, 2003
37. Newman LA, Buzdar AU, Singletary SE, et al: A prospective trial of preoperative chemotherapy in resectable
breast cancer: Predictors of breast-conservation therapy feasibility. Ann Surg Oncol 9:228-234, 2002
38. Mathieu MC, Rouzier R, Llombart-Cussac A, et al: The poor responsiveness of infiltrating lobular breast
carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer 40:342-351,
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39. Kurtz JM, Jacquemier J, Amalric R, et al: Breast-conserving therapy for macroscopically multiple cancers. Ann
Surg 212:38-44, 1990
40. Leopold KA, Recht A, Schnitt SJ, et al: Results of conservative surgery and radiation therapy for multiple
synchronous cancers of one breast. Int J Radiat Oncol Biol Phys 16:11-16, 1989
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ipsilateral breast cancers. Cancer 72:137-142, 1993
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surgical volume analysis. J Am Coll Surg 2001;193:593600

Locally Advanced Breast Cancer

P.N. Agarwal, Vivek Wadhawa

Locally advanced breast cancer (LABC) is defined by bulky primary breast tumors and/or extensive adenopathy.
This includes patients with T3 (>5 cm) or T4 tumors (chest wall fixation or skin ulceration and/or satellitosis) and
[1]
N2/N3 disease (matted axillary and/or internal mammary metastases) . Recent studies demonstrate that
prolonged survival can be achieved in patients with metastatic disease limited to the supraclavicular nodes after
[1], [2]
appropriate multimodality breast cancer treatment . As a result, American Joint Committee on Cancer
(AJCC) staging system now includes isolated supraclavicular metastases in the stage III/LABC disease category
[2]
. Five-year survival for stage III breast cancer is approximately 50%, compared with 87% for stage I. In India
60% of breast cancer present as LABC.

Diagnosis

Tissue Diagnosis

Establishing a tissue diagnosis is the initial priority on presentation of LABC. In many patients, core biopsy of the
tumor, either freehand or under ultrasound guidance, is diagnostic. Core needle is preferred over fine needle
aspiration, as cytology is insufficient to confirm lymphovascular invasion. Additionally, multiple cores should be
extracted both to confirm invasive cancer and to evaluate hormone receptor status and HER2/neu expression. A
negative or nondiagnostic needle biopsy with a clinically suspicious lesion is an indication to proceed to
diagnostic open biopsy; cases characterized by skin involvement may be amenable to punch biopsy. If matted,
fixed, axillary, or supraclavicular adenopathy is present, fine needle aspiration of the nodes should be performed
for staging.

92
Bilateral mammography

Prompt bilateral mammography in this setting is essential (except in known contraindications of BCT e.g.
inflammatory breast cancer, ulcerative lesions), regardless of patient age and date of her most recent study.
Diffuse, suspicious microcalcifications or multiple lesions in different quadrants indicate multicentric disease, and
[14]
are a contraindication to breast conservation therapy (BCT) . If BCT is a consideration, a microclip placed at the
primary tumor (biopsy site), under mammographic or ultrasound guidance, is essential before the initiation of
induction therapy, unless the primary tumor is associated with a cluster of microcalcifications. Up to 50% of
patients may have a complete clinical response, and an unmarked primary site eliminates the possibility of breast
preservation in these cases, as the lumpectomy site will no longer be adequately defined.

Breast and axillary ultrasound

Breast and axillary ultrasound frequently yield valuable information regarding the extent of disease. In particular,
[15], [16]
axillary ultrasound can be used for image-guided FNA ; ultrasound detection of apical axillary/infraclavicular
[17]
nodal metastases has been shown to provide important prognostic information . Unfortunately, ultrasound has
an approximately 20% false-negative rate, as metastases smaller than 5 mm in size are undetectable.

Metastatic Work up

A baseline bone scan, abdominal, pelvic and chest CT scans are recommended for detection of metastatic
disease. Directed radiographs to sites of new bone pain, or a head CT scan for new neurologic symptoms are
also appropriate in selected cases. The yield of a metastatic work-up in an asymptomatic, early breast cancer
[18]
patient is approximately 2% to 3%, but this risk rises to 30% in LABC . The most common sites of metastasis is
bones followed by lung, liver amd brain. The metastasis to bones may be osteoblastic or osteoclastic.

Therapeutic management

Neoadjuvant chemotherapy

Currently, optimal control is achieved with preoperative chemotherapy followed by surgery and radiation.
Preoperative versus postoperative chemotherapy have been directly compared in women with LABC and also in
women with early stage breast cancer. These prospective clinical trials have demonstrated overall survival
[6], [7], [8], [9], [10], [11],
equivalence for the two sequences, confirming the oncologic safety of the neoadjuvant approach
[12], [13]
. Since patients with LABC benefit from the tumor downstaging and improved resectability that can be
achieved with neoadjuvant chemotherapy, this sequence has become the preferred approach for patients with
bulky, locally advanced disease at time of diagnosis. Neoadjuvant chemotherapy offers several advantages
compared with traditional postoperative regimens. Invasive breast cancer patients have a significant risk of
harboring occult micrometastatic disease in distant organs.

Neoadjuvant chemotherapy allows for earlier exposure of these micrometastases to chemotherapeutic agents,
and an observed response to chemotherapy in the primary breast disease site indicates that the regimen has
effective antitumor activity.

Patients receiving preoperative chemotherapy should be reassessed after one or two cycles and again at the
completion of therapy to document response and explore surgical options. Repeat imaging may be useful at the
interim evaluation. If minimal or no response is observed after the initial cycles, a decision should be made to
either proceed with surgery or to cross over to a different systemic therapy. Surgery allows for a full pathologic
evaluation, facilitating decisions on adjuvant therapy. If an alternative regimen is selected, then reassessment
after two cycles of the crossover treatment is necessary. Follow-up imaging is essential after complete delivery of
neoadjuvant therapy for final preoperative surgical planning. Occasional patients that appeared to have a
unicentric cancer density at presentation will experience unmasking of extensive microcalcifications or
multicentric satellite tumors after chemotherapy response, and these findings may convert them to mandatory
mastectomy cases.

Subset analyses of the phase III studies reveal that patients who have a complete pathologic response (pCR)
have a statistically significant survival benefit, substantiating the concept that primary tumor response is a reliable
[4]
surrogate for chemotherapy effect on micrometastases. In the NSABP B-18 trial , patients with stage I to III
breast cancer randomized to receive preoperative doxorubicin and Cyclophosphamide and who experienced a
pCR had a 5-year overall survival of 86%, statistically superior to the outcome seen in all other study participants.
Predictors of a pCR include relatively smaller size primary breast tumors, estrogen receptor negativity, and high-
[5]
grade lesions .

Neoadjuvant chemotherapy regimen

Currently, doxorubicin-based chemotherapy is the most widely-studied induction regimen, and it results in at least
50% tumor shrinkage in more than 75% of cases. The NSABP B-27(1995-2000) protocol randomized patients

93
with resectable breast cancer to one of three neoadjuvant treatment arms: (1) doxorubicin and cyclophosphamide
alone; (2) doxorubicin, cyclophosphamide, and docetaxel; or (3) preoperative doxorubicin and cyclophosphamide
[23]
followed by postoperative docetaxel. Preliminary data reveal a pCR rate of 26% associated with the addition
of docetaxel to the preoperative regimen. Similarly, the University of Texas M.D. Anderson Cancer Center(2000)
[24]
has reported a pCR rate of nearly 30% in patients treated with preoperative doxorubicin, Cytoxan, 5-
fluorouracil, and weekly Taxol.

The Aberdeen trial(1996-1999) investigated whether the number of chemotherapy cycles is a stronger predictor
[25], [26]
of tumor response compared with chemotherapy type , demonstrating that the nature of the agent is more
important than the quantity. They also showed that poor responders may benefit from crossover to an alternative
regimen. Survival analyses at 3 years also suggest improved outcomes for patients on docetaxel plus
[26]
doxorubicin . Other neoadjuvant regimens currently being evaluated include trastuzumab, Navelbine,
capecitabine, and gemcitabine. Microarray technology and gene expression profiling are also being explored to
[29]
optimize selection of neoadjuvant therapy . In neoadjuvant chemotherapy all the cycles are given prior to
surgery but depending on the response surgery may be considered early and completion chemotherapy given
postoperatively There has been many combinations and schedule for chemotherapy a few recommended are
mentionedas follows.

FAC 5-FU 500mg/sqm IV day 1 and 8 Doxorubicin 50mg/sqm IV day Cyclophosphamide 500mg/sqm IV
day 1 Cycled every 21 days for 6 cycles
AC Doxorubicin 60mg/sqm IV day 1 Cyclophosphamide 600mg/sqm IV day 1 Cycled every 21 days for 4
cycles
AC followed by paclitaxel Doxorubicin 60mg/sqm IV day 1 Cyclophosphamide 600mg/sqm IV day 1
Cycled every 21 days for 4 cycles followed by paclitaxel 175mg/sqm 3hr IV infusion day 1 Cycled every
21 days for 4 cycles.

Neoadjuvant endocrine therapy

Neoadjuvant endocrine therapy for estrogen receptor-positive LABC also holds great promise. Three-to-four
months of therapy are preferred for an adequate response assessment, and preliminary studies suggest that
[27], [28]
aromatase inhibitors such as letrozole are more effective than tamoxifen . Presently it is always combined
with neoadjuvant chemotherapy

Monitoring response to neoadjuvant chemotherapy

A significant response to the primary chemotherapy regimen is observed in about 80% of cases; however,
accurate prediction of a pCR is challenging. Conventional modalities for assessing chemotherapy response,
including clinical examination, mammogram, and breast ultrasound, are incorrect in identifying pCR patients in
[3], [30]
nearly half of cases. The addition of imaging is clearly more useful than physical examination alone . Breast
[31], [32] [33] [34], [35]
MRI , positron emission tomography , and nuclear medicine sestamibi uptake scans have been
reported in small series as monitoring strategies with encouraging results but not yet routinely recommended.

Surgical : Breast conservation therapy and mastectomy

Treatment of the primary tumor is surgical. Treatment of the remainder of the breast tissue for control of occult
disease can be accomplished by either surgery or irradiation. The magnitude of the clinical response(i.e.
downstaging of tumour) to neoadjuvant chemotherapy in LABC prompted investigations of breast conservation
[19]
for selected patients. Singletary and colleagues conducted a feasibility study to evaluate the pathologic extent
of residual disease in 136 LABC patients treated with induction chemotherapy. Extensive scrutiny of the
postchemotherapy mastectomy specimens revealed that the residual tumor would have been amenable to
lumpectomy in approximately 25% of patients.
[11]
From this and other studies , several criteria for BCT in postneoadjuvant LABC have been adopted widely:
Patient desire for breast preservation
Absence of multicentric disease (tumors in different quadrants of the breast)
Absence of diffuse microcalcifications on mammogram
Absence of skin involvement consistent with inflammatory breast cancer
Residual tumor mass amenable to a margin-negative lumpectomy resection

Prospective, randomized controlled clinical trial data have confirmed acceptable rates of local control among
LABC patients undergoing breast-conserving surgery after neoadjuvant therapy. Several prospective,
randomized controlled trials of neoadjuvant versus adjuvant/postoperative chemotherapy have included cohorts
of patients with Stage III disease/LABC. Data from these studies have documented acceptably low rates of local
[20], [21]
recurrence in LABC patients undergoing breast-conserving surgery after neoadjuvant chemotherapy . The
NSABP B-18 investigators did note a trend toward higher local recurrence rates among patients requiring
preoperative downstaging in order to become lumpectomy eligible (15% versus 7% which is statistically
significant). This is not necessarily surprising, however, as postlumpectomy local recurrence is one manifestation

94
of aggressive tumor biology, and larger tumors are more likely to demonstrate aggressive behavior, even after
mastectomy. The margin for lumpectomy is kept at 1-1.5cmfrom postchemotherapy tumor edge. Postmastectomy
[22].
radiation (PMRT) is recommended for patients with T3 tumors because of this concept . Although women with
breast cancer are approached with the intention of offering breast-conserving therapy, there are situations in
which that is not possible. Contraindications to breast-conservation treatment include (1) presence of two or more
primary tumors in separate areas of the breast, (2) diffuse malignant-appearing microcalcifications, or (3) a
history of prior therapeutic irradiation to the breast that precludes full-breast irradiation for the present condition,
(4) Active collagen vascular disease. For women who are not well treated by breast-conserving therapy,
mastectomy is recommended.

Management of Regional Lymph Nodes

Today axillary lymph node metastases are considered a regional manifestation of metastatic breast cancer.
Axillary lymph nodes that are suspicious by palpation for tumor can be evaluated by FNA cytologic examination
when results will affect the order of therapeutic interventions. If axillary lymph nodes are matted or fixed (N2), the
disease has advanced beyond "early" breast cancer. When mobile axillary lymph nodes contain tumor, an axillary
dissection provides excellent local control of this axillary disease.This is only the surgical aspect of such control,
and there is a role for radiation and systemic therapy as well in controlling disease in the axilla. The primary
indication for axillary surgery today is the provision of pathologic staging. If the axillary lymph nodes are involved,
their removal accomplishes both goals: defining prognosis and diminishing the risk of subsequent axillary
recurrence. Presently, Axillary dissection is preferred modality for treatment of axillary lymph node in LABC.

Breast reconstruction

LABC traditionally has been perceived as a contraindication to immediate breast reconstruction (IBR), because of
concerns regarding adjuvant treatment delays and the cosmetic effects of PMRT to breast reconstruction.
[36]
Newman and colleagues noticed slightly prolonged interval for adjuvant chemotherapy among reconstructed
patients; this did not affect recurrence rates. IBR with implants, however, was associated with more radiation-
related complications; nearly half of the irradiated patients developed contractures or recurrent infections,
necessitating implant removal. Delayed reconstruction is therefore, usually preferred in LABC patients
undergoing mastectomy, because of the substantial likelihood that PMRT will be necessary, and the potential
damaging effects of radiating the reconstructed breast. Occasionally, LABC patients will require soft tissue
coverage of an extensive chest wall defect at mastectomy. In these cases, a latissimus dorsi flap is the most
common approach, as this flap is a technically straightforward and provides durable, radiation-tolerant coverage.
Breast reconstruction after local failure in the irradiated breast presents a unique challenge for the oncologic and
the reconstructive surgeon. The late effects of radiation are characterized clinically by a loss of skin elasticity,
fibrosis, and decreased blood supply. In a series of 680 consecutive patients who underwent TRAM flap breast
reconstruction, 108 had had previous irradiation, and no difference was found in flap survival in the two groups
[40]
.

Locoregional irradiation

The American Society of Clinical Oncology recommends PMRT for all patients who have four or more metastatic
axillary lymph nodes based upon axillary surgical findings at presentation (without neoadjuvant chemotherapy),
[37]
and that PMRT should be considered for all cases of LABC .

Patients who have at least four metastatic lymph nodes or 5 cm of residual disease in the breast after
chemotherapy clearly benefit from locoregional irradiation, and all lumpectomy patients require breast irradiation.
A conservative (and aggressive) approach would be to recommend radiation to all patients that present with
LABC, regardless of chemotherapy response. However, patients with little or no residual breast/axillary disease
after chemotherapy may not derive a significant benefit from regional nodal irradiation. Existing data are limited
regarding whether or not comprehensive irradiation is absolutely necessary to achieve optimal locoregional
control of disease in patients presenting with LABC, but in whom a substantial degree of downstaging occurred
with neoadjuvant chemotherapy.

The NSABP B-18 data suggest that surgical pathology indications for locoregional irradiation are the same for
patients that receive neoadjuvant chemotherapy and those that receive postoperative chemotherapy. In clinical
practice, the oncology team should review each patient in a multidisciplinary fashion, and discussions regarding
[38]
the complete multimodality management (including final radiation planning) should begin at presentation . For
whole breast irradiation IMRT is preffered with doses of 45-50 Gy in fraction of 1.8-2 Gy.all doses aregiven at
5doses per week regional irradiation of 50 Gy in fraction of 1.8-2 Gy.The ASCO guidelines for postmastectomy
radiation treatment state that postmastectomy radiation treatment is indicated when there are four or more
pathologically positive axillary lymph nodes and when the tumor is stage III (except for T3N0M0 lesions); the
need for postmastectomy radiation treatment is uncertain after neoadjuvant systemic chemotherapy, with one to
three pathologically positive axillary lymph nodes, for T3N0M0 tumors, for close or positive margins of resection,
or for positive lymph nodes associated with extracapsular extension.

95
Postoperative systemic therapy

Patients with hormone receptor-positive breast cancer should receive at least 5 years of either tamoxifen or an
aromatase inhibitor. Aromatase inhibitors should be given only to postmenopausal women, as these drugs do not
block estrogen production from functioning ovaries. Any woman of unknown menstrual status can have ovarian
function assessed by measurement of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
estradiol levels. The role of ovarian ablation/suppression for premenopausal, hormone receptor-positive breast
cancer patients is not yet defined. Tumors overexpressing HER2/neu also require treatment with adjuvant
[39], [40]
trastuzamab .

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reconstruction. Plast Reconstr Surg 1997;100:1153.

Management of the Axilla in Carcinoma Breast

Gaurav Agarwal, Sendhil Rajan

The legendary American surgeon William Halstead, who propagated the radical mastectomy for treatment of
breast cancer hypothesized that the involvement of the axillary lymph nodes in breast cancer are due to spread
of the tumour in an step-wise manner, where the nodes of the axilla act as an anatomical barrier, thereby
limiting the spread of cancer cells. According to this hypothesis, metastatic spread of breast cancer happens
chiefly via the lymphatic system. This contiguous theory is applied in the operation room- en-bloc removal of all
the nodes and fibro-fatty tissue of the axilla along with the primary tumour is based on this. Halsteds theory
th
lasted from the 1890s to the mid part of the 20 century.

However, studies have shown that up to 30% of patients, despite being axillary node-negative; will ultimately
present with distant disease. Also, a considerable number of breast cancer patients are recognized to have
systemic disease at the time of presentation, due to entry of tumour cells into the bloodstream during initial
stages of the neoplastic process.The above data was put forth by Bernard Fisher in his 1980 paper where he
considered breast cancer to be a systemic disease from its very onset, thus advocating systemic therapy in
nearly all patients. Samuel Hellman in 1994 presented his Spectrum theory, which stated breast cancer
presentation to be a spectrum- as a disease that always remains local through its course to one that, at its very
clinical onset, may be systemic in nature.

Today, the regional axillary lymph nodes although thought to be ineffective barriers for spread of tumour cells,
are still considered to be of vital biological and prognostic importance, and are yet to be superseded by newer
molecular prognostic indices. Axillary lymph-node dissection (ALND) has been an important part of surgical
management of breast cancer over more than a century now, and, besides its therapeutic potential, also provides
key prognostic data for to select patients for further adjuvant systemic therapies. The main factor affecting node
positivity is tumour size, although other features, such as tumour grade, histological type and lympho-vascular
invasion also play a part. Axillary node metastases also have clinical relevance as they may represent either
loco-regional relapse or distant disease by acting as a source for tertiary spread.

In patients with invasive breast cancer, management of the axilla has two critical goals:
1. Prognostic and Staging Goal: Does the metastatic spread extend to the axillary nodes? If yes- what is the
extent of the spread and number of metastatic lymph nodes? Is there any extra-nodal infiltration?
2. Therapeutic Goal: When axillary lymph node metastases are present, ALND aims for surgical extirpation of
all remaining metastatic disease from the axilla. Also, radiation to the axilla after surgical intervention is also
widely followed. Studies have shown that ALND (without/before post-operative radiation to axilla) results in
enhanced relapse-free survival. However, its role on overall survival is little less established.

97
Management of the axilla in patients with breast cancer has improved significantly in the recent decades, chiefly
due to better understanding of the biological models of lymphatic networks within the breast and patterns of
tumour dissemination. The NCI consensus statement of the past recommends that treatment of potentially
curable breast cancer should include level I and II ALND (see below). The position of routinely performed ALND
for the treatment of breast cancer, in the last decade or so, has been more closely scrutinized due to various
reasons. These include an increase in the detection of small, non-palpable lesions detected mammographically
having a low risk of nodal metastases, a greater knowledge regarding the complications following ALND, and the
present treatment paradigm of providing adjuvant chemotherapy to the majority of patients with breast cancers
>1.0 cm, regardless of axillary lymph node status.

Breast cancer shows heterogeneous patho-biology, therefore making any blanket axillary treatment unsuitable for
disease management. The surgical management of axilla needs to be customized individually to each patients
requirement and preference, as well as to the characteristics of the tumour. It should be in concurrence with local
treatment protocols and available facilities. Sentinel lymph node biopsy (SLNB) is now recognised as the
standard of care in most centres the world over and has revolutionized axillary management through the last
decade and a half. Nevertheless, there is still limited information regarding long-term outcomes, and there are
multiple variations in practice and inconsistencies in methodology. Other procedures like the four node biopsy
and axillary sampling are limited to certain centres, and have not gained acceptance in routine clinical practice. In
patients undergoing breast conserving therapy (BCT), axillary irradiation (AI) has been studied as a substitute for
ALND. However, more conclusive studies need to be done for this to be a recommendation.

This review will seek to outline the scientific basis, technical aspects and outcomes of the current axillary lymph
node management strategies in patients with invasive breast cancers.

Surgical and Applied Anatomy of the Axilla

The lymphatic system of the breast is constituted of a large and complex network of peri-ductal and peri-lobular
lymph vessels, which drain principally to the axillary nodes. There is a connection between the dermis and the
intra-parenchymal lymphatics (via the sub-areolar plexus), which explains the spread of cutaneous malignancies
and drainage of tracer agents to axillary nodes. Sappey's plexus are specialized lymphatic channels that are
present under the nipple and areola. There is uni-directional flow of lymph from the superficial to deep plexus and
from the sub-areolar plexus through the lymph vessels of the lactiferous ducts to the peri-lobular and deep sub-
cutaneous plexus.

SLN biopsy can be accomplished only with knowledge of the intricate lymphatic anatomy of the breast. Lymphatic
anatomy also determines the preferred sites for loco-regional spread of malignancy. The vast majority of breast
tumours metastasise to the axilla regardless of the site of primary tumor within the breast. The internal mammary
nodes constitute an alternative path for drainage of lymph from the central zone and medial breast quadrants.
However, exclusive involvement of the internal mammary nodes is seen in <10% of node-positive tumours and
clinical signs are rare. Considerable morbidity can result from surgical removal of these nodes, with no advantage
in overall survival. Currently, the clinical and pathological significance of involvement of internal mammary nodes
is uncertain at best.

The axilla is a pyramidal shaped area, medially bounded by the chest wall, laterally by the latissimus dorsi,
posteriorly by the sub-scapularis, superiorly by the axillary vein and inferiorly by the inter-digitation of the
latissimus dorsi and serratus anterior muscles. About 50 lymph nodes are present within the loose areolar fat of
the axilla, although this number is variable. Arbitary division of the lymph nodes of the axilla is as follows: Level I
nodes are those found lateral to the lateral border of the pectoralis minor muscle; Level II nodes are those in the
central axillary group, found under the pectoralis minor muscle; Level III include the sub-clavicular nodes medial
to the medial border of the pectoralis minor muscle. (Figure-1) Expirtation of these nodes requires either division
or retraction of the pectoralis minor, although dissecting between the two heads of the pectoralis major can also
accomplish this. The pectoralis minor is enclosed in the clavi-pectoral fascia, which extends laterally to fuse with
the areolar tissue of the axilla. One can divide the axillary fascia and expose the contents of the axilla by
dissection along the lateral border of the pectoralis minor.

The axilla contains many clinically important structures, which require preservation during dissection and removal
of the lymph nodes with the fatty areolar tissue of the axilla. Rotters nodes are the inter-pectoral lymph nodes
present between the two pectoralis muscles. They are usually seen on the posterior surface of the pectoralis
major, in close relation to the lateral pectoral nerve, which if injured, results in atrophy of the muscle. The inferior
lateral aspect of the pectoralis major muscle is innervated by the medial pectoral nerve, which should also be
carefully preserved. The second cutaneous inter-costo-brachial nerve runs in a mediallateral direction
approximately a centimetre inferior to the axillary vein. Running just posterior to the inter-costo-brachial nerve in
the second inter-costal space is the long thoracic nerve (of Bell), which innervates the serratus anterior
muscle. It should always be identified before proceeding with axillary dissection, at a site just lateral to the
serratus anterior muscle. Any surgical dissection anterior to the inter-costal nerves will safely preserve the long
thoracic nerve as the latter runs in a superiorinferior direction, and is always posterior to the inter-costal nerves

98
(which run in a mediallateral direction). Division of the long thoracic nerve results in winging of the scapula.
The thoraco-dorsal nerve innervating the latissimus dorsi, is first seen posterior to the lateral thoracic vein. It
then travels infero-laterally, passing over the sub-scapular muscle, with the sub-scapular vessels, entering the
latissimus dorsi muscle in its medial aspect. Dissection therefore should be done along the lateral or anterior
aspects of the latissimus dorsi to prevent thoracodorsal nerve injury.

Management of Axilla in Invasive Breast Cancer Patients

The single most important prognostic factor in patients with invasive breast cancer is the presence of axillary
lymph node metastases, and therefore evaluation of the axilla is of paramount importance. Patients who have
axillary nodal metastases without systemic metastases exhibit 40% poorer overall survival at 5 years, when
compared to patients who do not have axillary metastases. Also, the number of positive lymph nodes (>3) and
presence of extra-nodal spread into axillary soft tissue are recognized high-risk factors for loco-regional
recurrence and overall survival. An ideal plan of management of the axilla remains a controversial topic, and it is
currently formulated based on the tumor characteristics, presence of clinically (including radiologically) detected
lymphadenopathy, patients desire, availability of local infrastructure and medical facilities and individual institute
protocols and acceptability of various choices. Table-1 provides a list of several options for management of the
axilla in invasive breast cancer patients.

Table 1: Options for management of axilla in patients with Invasive Breast Cancers
A. Established options backed by sufficiently high quality scientific evidence:
1. Axillary lymph-node dissection level I and II for
(a) patients with palpable axillary lymphadenopathy
(b) patients with metastatic sentinel lymph node

2. Axillary lymph node dissection levels I, II and III in patients with enlarged level III nodes or bulky level I and II
nodes.
3. Sentinel Lymph node biopsy for patients with clinically (including radiologically) impalpable/ non-enlarged
axillary lymph nodes:
(a) Sentinel-lymph-node biopsy with dye and isotope
(b) Sentinel-lymph-node biopsy with isotope only
(c) Sentinel-lymph-node biopsy with dye only
Further management of axilla based on SLN pathology:
(i) ALND if SLN has metastatic deposits (including micro-metastases)
(ii)Avoidance of ALND if SLN has no metastatic deposits or have isolated tumor cells (sub-
micro-metastases) evident on immuno-histochemical studies.

B. Other options- NOT backed by sufficient scientific evidence/ limited evidence:

May be practiced in clinical trial setting, not recommended for routine clinical use
(a) Axillary lymph node sampling
(i) Blue-dye-assisted node sampling
(ii) Blind sampling- such as four node sampling
(b) Observation only
(c) Avoidance of ALND in patients with metastatic SLN (except in highly selected very low-risk patients,
as per ACOSOG Z0011 criteria)
(d) ALND in patients with Sub-micro-metastases (isolated tumor cells) in SLN
* While only well established procedures namely ALND and SLNB are mostly practiced, in certain specific groups
e.g. small (<1 cm) low grade tumours with favourable risk profile- axillary surgical procedures may be avoided.

The foremost intention of axillary surgery in patients of operable breast cancer is to stage the axilla. Independent
predictors of survival include number of lymph nodes and the level of lymph node involvement.

Staging options
a) Sentinel lymph node biopsy
b) Axillary node sampling
c) Axillary dissection

Sentinel Lymph Node Biopsy (SLNB)

The aims of sentinel lymph node biopsy are axillary staging and avoidance of unnecessary axillary dissection
leading to significant morbidity. The principle behind SLNB is that the sentinel lymph node(s) is the first (group) of
node(s) to drain the tumour bed. If the SLN is free of the tumour then the nodes at the further station are also
tumour free and an axillary dissection can be avoided with oncological safety. Historically, Sappey in 1980
injected mercury in the lymphatic channels of the breast and concluded that drainage to the axilla occurs via a
sub-areolar plexus although recent studies have doubted this. The tracer can be injected via the intradermal,
sub-areolar or peritumoral route. Because the skin has richer lymphatics than the parenchyma, it is almost
always possible to differentiate the sentinel from the other higher level nodes when the tracer is injected in the

99
skin. In the case of non-palpable breast lumps, the dye or tracer needs to be injected under image guidance.
Chapgar et al, in a review of 3961 patients,concluded that the rate of identification by intra-dermal or sub-areolar
injection was 99.3% & 95.6% respectively compared to 91.1 % of peri-tumoral injection.

Indications of SLNB
a) Operable early breast cancer (T1, T2)
b) Clinically node negative

Under Trial/Partial evidence:

a) Locally advanced breast cancer with complete or good partial response after neo-adjuvant
chemotherapy and clinically N0 stage
b) Patients with extensive DCIS undergoing mastectomy.

A patient with clinically-N0 axilla is explained the procedure and consent is obtained to subject her to a SLNB
followed by a possible axillary dissection in case SLNB is reported metastatic. SLNB is performed using a colour
(blue) dye, radio-pharmaceutical or a combination of both, which is the preferred method, with highest SLN
detection rate and lowest false negative rates. The different agents used for SLNB are:
Isosulphan blue (Lymphazurin) or Patent blue dye V or Methylene blue

m
99 Technetium- labelled albumin/ antimony/goldor sulphur colloid

Although the volume of dye used has been different in various studies with similar results, when using a radio-
pharmaceutical, usually 0.5 -6 ml of Tc labelled dye in saline is injected at the periphery of the tumour or the
previous excisional biopsy site directed by manual palpation or USG guidance or injected around the areola. The
gamma probe is then employed to identify the site of maximum radioactivity in the axilla. A small skin crease
incision is made at the point of maximum intensity and the axillary fat is dissected to reach to the point of the
maximum radioactivity, highlighted by maximum sound emitted by the device. When blue dye is used, 2 - 7.5 ml
of sterile isosulphan blue or methylene blue (more cost effective) is taken and injected just prior to surgical skin
preparation. If no radioactivity is encountered/radiopharmaceutical not used, then the skin is incised between the
pectoralis major and the latissimus dorsi over the lower part of the axilla, axillary fat is dissected to visualise the
blue channels defined by the dye (SLNB is always done before the procedure for the breast tumour). These
channels are traced upto the first node/group of nodes which is/are biopsied and sent for histo-pathological
examination. For each patient, the average yield is found to be more than one in most studies, highlighting the
fact that SLN is not a single node but regularly a group of nodes. The node(s) is then subjected to frozen section
or imprint cytology and if the node is positive for malignant deposit, a complete axillary dissection is carried out.
As only one or two lymph nodes are submitted for histology, the SLN can be subjected to a more detailed
pathological examination than routine nodal tissue, with multiple-step sections and immuno-histochemical
staining - Cytokeratin (CK) staining is another method employed for intra-operative evaluation of sentinel lymph
nodes.

One-step nucleic acid amplification (OSNA) is a recently introduced method for intra-operative evaluation of
sentinel lymph node status in breast cancer The principle behind OSNA is measurement of mRNA copy
numbers of CK 19 (CytoKeratin19) in the SLN sample, giving a rapid report. (A vast majority of breast cancers
express CK19, therefore it is preferred). In recent times, researchers have also investigated the possibility of
using spectral imaging (which refers to the formation of a multi-planar image where each pixel in the spatial
plane records reflected intensities from a range of spectral bands) to assess the SLN(s) of breast cancer patients
with an idea to ultimately develop an optical system that can categorize spectra of normal and metastatic tissue
in the visible and near infrared region, providing a report quickly.

Reduction of morbidity, especially arm lymphedema, is a main objective of SLNB. Most studies show lower rates
of morbidity after SLNB compared with ALND.There is an increasing trend toward omitting ALND altogether in
patients with micrometastatic nodal disease identified by SLNB, as shown by recent studies. The IBCSG 23-01
trial randomized patients with SLN micromets (<2 mm) and T1/T2 tumours to either completion ALND or no
further intervention to the axilla. There was no significant difference in OS or DFS for patients of either arm at a
median follow-up of 49 months.The recent ACOSOG Z-0011 trial addressed the need for completion ALND for
patients with EBC that were clinically node negative and had less than three positive SLNs; all patients
underwent breast irradiation. At a median follow-up of 6.3 years, there were no significant differences in survival
or loco-regional recurrence between the SLND plus ALND group versus the SLND alone group. The five-year
overall survival, five-year disease-free survival and recurrence rates in the ipsilateral axilla were all similar
between the two arms.The National Comprehensive Cancer Network (NCCN), however, has not changed its
guidelines and continues to recommend completion ALND for all women with positive sentinel nodes until
additional randomized trial results are available.Other recent studies have shown that SLNB is as accurate in
patients presenting with a T3 tumour and clinically negative axilla as in patients with EBC. Thus, many clinicians
do not recognize large breast tumours as a contraindication to SLN dissection, as long as the axilla is clinically
negative.

At SGPGIMS, Lucknow, the SLNB protocol consists of a combination of 1% w/v methylene blue dye and 99mTc-
99m
Antimony colloid, both of which are produced in-house, therefore limiting their costs. A dose of 40MBq of Tc-

100
Antimony colloid is injected sub-areolarly 12-24 hours prior to surgery. Later, a few minutes before incising the
skin, 1-2 ml sterile methylene blue is injected in the sub-areolar region. The hand held gamma probe draped in a
sterile glove (Neo-probe 2000, Ethicon) is then employed trans-dermally to search for the hot SLN in the axilla,
surface marking of which is then done. A small 1-2 cm skin crease incision, placed posterior to the pectoral fold in
the upper axilla or exactly over the marked SLN is then made. Streaks of blue lymphatics are sought for, and
when found are followed in a supero-medial direction to a blue SLN. The hand held gamma probe is then used to
trace the areas/ SLN with radio-tracer concentration (hot area), once the SLN (blue, and /or hot) is identified, it is
removed intact. Other hot areas if found, are explored and further SLNs are thereby identified and removed. All
the SLNs removed are sent to the pathologist for frozen section histopathology and/or imprint cytology in cold
saline. If the frozen section histology shows metastasis in one or more of SLNs- a formal Level I+II axillary
dissection is performed, utilizing and extending the SLNB incision by an extra 3-4 centimeters.

A validation study conducted at SGPGIMS Lucknow, on 120 patients with early breast cancer, revealed a SLN
identification rate of 96% and false negative rate of <4%, thereby now establishing the oncological safety of this
procedure for patients with early breast cancer. Another validation study in patients with impalpable axillary lymph
nodes after undergoing neoadjuvant chemotherapy is currently nearing completion. Preliminary results for this
group show poorer SLN identification rates and higher false negative rates compared to EBC patients undergoing
primary surgery.

Axillary Node Sampling

When the radiotracer and/or blue dye fails in SLN identification, axillary node sampling is done. It may also be
combined with the SLNB to increase the overall sensitivity. The largest nodes (a minimum of 4) are excised. In
patients with non-palpable Level I nodes, level II or III nodes are sampled. This technique therefore permits
identification of skip metastases in the axilla although such cases are relatively rare (5%). Most of the
SLN/lymphatic mapping studies have recognized the first draining node in level I, therefore level I node is most
frequently sampled.

Avoidance of ALND and any axillary surgical procedure

Any of the staging procedures of the axilla can be safely omitted in selected clinically node-negative patients
having small (1.0 cm) non high- grade (I and II) tumours, in elderly patients associated with co-morbidities, and
also in cases of localised non-palpable DCIS amenable to wide excision. ALND, however, is no longer an
acceptable staging procedure for clinically node-negative patients. Studies are underway in clinically node-
negative patients undergoing preoperative ultrasound-guided biopsy to identify axillary metastases and,
therefore, allowing ALND at the without conventional SLNB.

Axillary Lymph Node Dissection (ALND)

A formal complete ALND is warranted in cases of histologically proven positive axilla by FNAC (palpation guided
or US guided) or cases in which SLN or axillary sampling specimen is positive for metastases (3). It may also be
required additionally in variety of other situations, as listed below.

Indications for ALND

a) Axillary node metastasis proven by fine needle aspiration (FNA), core biopsy, or SLN biopsy
b) Validation trials of SLN biopsy (in which a planned backup ALND is done to establish the proportion of
false-negative results).
c) Failed SLN biopsy (even in expert hands, SLN mapping fails in a few percent of cases).
d) Clinically suspicious nodes palpated at the time of an otherwise successful SLN biopsy procedure
e) Inflammatory breast cancer (following neo-adjuvant
chemotherapy, SLN biopsy appears accurate for non-
inflammatory disease, but remains investigational for
inflammatory breast cancer)
f) Unavailability of SLN biopsy
g) Isolated loco-regional recurrence, either in the ipsi-lateral
axilla after SLN biopsy or in the contra-lateral axilla, with
no evidence of a contra-lateral breast primary.

Though still regarded as a beneficial procedure by conferring

better regional disease control, the overall survival advantage with
ALND has always been in doubt, since the Halsted era.A large
meta-analysis of about 3000 patients has shown a survival benefit
of 5.4% from ALND. However, many other studies have shown no
survival benefit from ALND. The prevalence of node positivity in
patients undergoing ALND mainly depends on the tumour size, Fig 1: Levels of axillary lymph nodes: I, II and
although other factors, such as tumour grade and type, lympho- III in relation to the pectoralis minor muscle
vascular invasion, are also relevant. and tendon.

101
Technique of ALND

Classification of ALND isdone based on the extent dissected: level I, level I+II, or level I+II+III (complete ALND).
Axillary nodal Levels I & II are routinely dissected out along with all fibro-fatty and lymphatic tissue. A minimum of
10 nodes need to be histo-pathologically examined for optimal axillary staging. When level III nodes are found to
be enlarged, and also in patients exhibiting bulky level II nodes, a complete level III dissection is performed. Skip
metastases, refers to disease limited to levels II to III, sparing level I, or limited to level III, sparing levels I-II. As
most of these skip metastases were found at level II (isolated level III disease is rare), most recommendations
favour a level I+II ALND as the standard procedure.

Incisions utilized for ALND may be separate from or in-continuity

withthe incision used for the breast procedure. If a separate
incision is employed, it is best made transversely,about two finger-
breadths below the axillary skin crease, gently curved to follow a
skin-line. The length should be adequate for good exposure, but
must not extend beyond the anterior pectoral border, where it
would be visible the incision may be posteriorly extended if
required. A contiguous incision is perfectly rational in patients
undergoing mastectomy without reconstruction or BCS and for
tumours present high up in the axillary tail. In both cases, SLNB is
done through the axillary end of the incision before the breast
procedure. The procedure of ALND involves dissection and
removal of all fibro-fatty and lymphatic tissue including the lymph Fig 2: Completely dissected axilla, showing
nodes from whole of levels I and II, and if indicated level III. The intact and skeletonized long thoracic nerve
extent of dissection is from the axillary vein superiorly, to second and thoraco-dorsal neuro-vascular bundle.
digitations of the serratus anterior muscle inferiorly, and from the The axillary vein is not skeletonized, leaving a
layer of fascia with it, in an attempt to prevent
anterior border of latissimus dorsi muscle laterally to the rib-cage edema of the arm.
and intercostals muscles medially, with the nerve to serratus
anterior as a guide to the medial limit. The important structures
that are needed to be preserved include the axillary vein, the long
thoracic nerve and the thoraco-dorsal neuro-vascular bundle (Figure-2). The axilla is closed with a suction drain
in-situ using interrupted or sub-cuticular sutures, and a compression dressing applied.

Complications of Axillary Node Dissection

The axillary component of breast cancer surgery is responsible for the majority of post-operative complications,
and minor problems are frequent. Seromas are commonly seen (in up to 30% of patients), particularly if the
axillary drain was removed prematurely. These are managed by aspiration, performed in the outpatient clinic.
Long term complications include numbness over the medial part of the arm, occurring if the inter-costo-brachial
nerve was sacrificed.

The most feared and potentially disabling complications include upper limb lymphedema and recurrent cellulitis.
The incidence of lymphedemacontrasts between 7-60% according to the methods used to assess the arm and
the interval between surgery and follow-up. Most recent studies have reported that, after axillary dissection or
axillary irradiation, the incidence of lymphedema is 15-20%; and that this complication occurs more frequently if
the patient received both surgery and irradiation.A rare sequel of lymphedema is upper extremity angiosarcoma,
known as Stewart-Treves syndrome. The type of ALND and use of axillary irradiation are the prime factors
associated with the lymphedema formation. Other minor factors include obesity, older patient and infection.
Lymphedema may even manifest years after the operation. Patients should always be advised to avoid arm
swelling and infection by taking precautions not to suffer cuts and scrapes on the operated side, to avoid
injections, blood-pressure monitoring, and IV sampling/access, to avoid constricting clothing and jewellery, etc. In
a study conducted by Warmuth in 1998, of a survey of 330 patients who were disease-free 2-5 years after
surgery for early-stage breast cancer, 35% reported numbness, 30% reported pain, 15% reported arm swelling,
and 8% reported limitation of arm movement. However,most patients had mild symptoms, not interfering
significantly with daily activity.

Summary

Management of the axilla is a fundamental aspect of treating a patient with invasive breast cancer. Optimal
management of the axilla in breast cancer patients has evolved greatly during the last century and particularly the
last two decades, and is continuously undergoing refinement. Today, staging of the axilla is dominated by SLNB,
which is now practiced all across the developed world, usually with the dual localisation technique; and is rapidly
gaining prominence in developing nations such as India. Other procedures for axillary staging, as well as
therapeutic procedures need to be carefully assessed with respect to individual risk and tailored to patient
preference. A custom-made methodology integrating the variety of options on the basis of risk and cost-benefit
ratio, together with the choice of the patient, will undoubtedly prove to be the most ideal practice. In todays
practice, ALND is indicated in patients with clinically (including radiologically) enlarged axillary nodes, in those

102
with metastatic SLN or detection of metastatic nodes on lymph node sampling, and where ever SLN biopsy is not
available or a SLN study has failed to detect the SLN. However, there are currently ongoing studies that
challenge even these indications for ALND. Whenever required, levels I & II axillary nodes are routinely dissected
out along with all fibro-fatty and lymphatic tissue of the axilla. A minimum of 16 lymph nodes need to be
examined by the pathologist for optimal axillary staging. In presence of enlarged nodes in level III, and in patients
with bulky levels II nodes, a complete level III dissection is also performed. Various complications such as
seroma, lymphedema and cellulitis can occur post-operatively and patient education for their prevention and
treatment is paramount to their management.

References

1. Ciesl L et al, Alternative sites of injection for sentinel lymph node biopsy in breast cancer, ANZ J Surg 2003; 73:
6004.
2. Chagpar A, Martin RC 3rd, Chao C, Wong SL, Edwards MJ, Tuttle T, McMasters KM. Arch Surg. 2004
Jun;139(6):614-8; discussion 618-20.
3. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al: A nomogram for predicting the likelihood of additional nodal
metastases in breast cancer patients with a positive sentinel node biopsy. Ann SurgOncol 10:1140-1151, 2003
4. Giuliano AE: Z0011: A randomized trial of axillary node dissection in women with clinical T1 or T2 N0 M0 breast
cancer who have a positive sentinel node. 2003.
5. Warmuth MA, Bowen G, Prosnitz LR et al. Complications of axillary lymph node dissection for carcinoma of the
breast: a report based on a patient survey. Cancer 1998; 83:1362-8.
6. John R Benson, G QuercidellaRovere, and the Axilla Management Consensus Group,Lancet Oncol 2007; 8: 331
48
7. Giuliano AE, Morrow M, Duggal S, Julian TB. Should ACOSOG Z0011 change practice with respect to axillary
lymph node dissection for a positive sentinel lymph node biopsy in breast cancer? ClinExp Metastasis. 2012
Oct;29(7):687-92. Epub 2012 Aug 29.
8. Galimberti V, Cole BF, Zurrida S, et al. [S3-1] Update of International Breast Cancer Study Group Trial 23-01 To
Compare Axillary Dissection Versus No Axillary Dissection in Patients with Clinically Node Negative Breast
Cancer and Micrometastases in the Sentinel Node. Lancet Oncology 2013 Jun;14(7):e254.
9. Chung MH, Ye W, Giuliano AE, Role for sentinel lymph node dissection in the management of large (>or = 5 cm)
invasive breast cancer. Ann SurgOncol. 2001;8(9):688
10. Cody HS. Axillary Dissection for Breast Cancer. Operatice Tech in General Surg 2006;1524-1540
11. Newman LA, Mamounas EP. Review of breast cnacer trials conducted by the national surgical adjuvant breast
project. Surg Clin N Am. 2007;87:279-305.
12. Pegolo E, Puppin C, Gerometta A, Damante G, Puglisi F, Di Loreto C. One-step nucleic acid amplification (OSNA)
for intraoperative evaluation of sentinel lymph node status in breast cancer: a comparative study between CK19
protein expression and CK19 mRNA level in primary tumors and lymph node metastasis. Virchows Arch. 2013
Jul;463(1):7-15
13. Jack D. O'Sullivan ; Paul R. Hoy ; Harvey N. Rutt, Spectral imaging as a potential tool for optical sentinel lymph
node biopsies, Clinical and Biomedical Spectroscopy and Imaging II, 80872J (June 15, 2011)
14. Bensen JR et al, Management of the axilla in women with breast cancerThe Breast (2007) 16, 130136
15. Cserni G. What is a positive sentinel lymph node in a breast cancer patient? A practical approach. The Breast
(2007) 16, 152160.
16. J E A Somner, J M J Dixon, J S J Thomas, Node retrieval in axillary lymph node dissections: recommendations
for minimum numbers to be confident about node negative status; J ClinPathol. 2004 August; 57(8): 845848
17. Diseases of the Breast by Harris PJ, 4th edition 2009; Lippincott Williams & Wilkins
18. Sabiston textbook of Surgery, 19th Edition 2012, Saunders.

Operative Procedures for Breast Cancer

Nikhil Talwar

History and Terminology

1,2
Radical and extended radical mastectomy :Going back to the late 1800s, the treatment of breast cancer was
characterized by either wide excision or simple mastectomy. These resulted in extremely high rates of local
recurrence and poor survival. In 1894, William Halsted proposed that breast cancer was a local disease that
spread by contiguous extension, and that more extensive resection would provide a better chance of disease
control (Halsteds Theory).
1
The original radical operation of Halstead radical mastectomy consisted of en bloc removal of the breast, the
overlying skin, both the pectoralis major and minor muscles, in continuity with the regional lymph nodes along the
axillary vein to the costoclavicular ligament (level I, II, and III nodes). The long thoracic nerve and the
thoracodorsal neurovascular bundle with the axillary contents were routinely resected. This procedure often
required a skin graft to close the large skin defect created. Extended radical mastectomy was a logical
extension to a Halsted radical mastectomy, which achieved more radical lymphatic clearance by excision of the
internal thoracic and supraclavicular nodes. An even more radical mastectomy was the super-radical

103
mastectomy that also included four parts: Breast and axillary contents, Internal mammary artery and vein with
internal mammary lymph node chain, upper mediastinal nodes and low supraclavicular nodes.

Modified Radical Mastectomy: Unfortunately, a large number of women continued to die of metastatic breast
cancer after radical mastectomy. Moreover, morbidity was increased without significant advantages in survival or
local control. In 1948, Patey and Dyson of the Middlesex Hospital, London, advocated a modified radical
mastectomy for the management of advanced operable breast cancer, explaining, "Until an effective general
agent for treatment of carcinoma of the breast is developed, a high proportion of these cases are doomed to die."
They preserved the pectoralis major muscle and the lateral pectoral nerve and sacrificed the pectoralis minor
muscle and medial pectoral nerve the to allow clearance of axillary lymph node levels I to III. Subsequently,
Madden advocated a modified radical mastectomy (MRM) that preserved both the pectoralis major and minor
muscles even though this approach prevented complete dissection of the apical (level III) axillary lymph nodes.
Scanlon modified the Patey procedure by dividing but not removing the pectoralis minor muscle, allowing
removal of level III nodes and preservation of the lateral pectoral nerves to the major muscle.

The procedure described by Auschincloss differs from the Patey procedure by not removing or dividing the
pectoralis minor muscle. This modification limits the complete removal of high axillary nodes but is justified by
Auchincloss, who calculated that only 2% of patients will potentially benefit by removal of the highest level nodes.
The Auchincloss mastectomy is the most popular form of MRM in the present era.

Several prospective randomized trials documented equivalent survival rates with MRM as compared to radical
mastectomy, with less morbidity. As a result of these data, the radical mastectomy has become an historical
footnote in the treatment of breast cancer.

Breast conserving surgery: The fact that less radical surgery did not affect survival made people question
whether Halsteds theory was correct; that breast cancer was not a local disease that spread contiguously, but
instead, systemic disease was ultimately the main determinant of survival. The question arose as to whether the
breast needed to be removed or could be preserved without compromising survival. There had been several
reports of breast cancer being treated by radiation alone, and there was evidence that radiation could eliminate
subclinical foci of disease. This allowed for the combination of limited surgery and radiation therapy as a method
of adequately treating breast cancer while avoiding mastectomy. The use of radiation therapy in conjunction with
surgery has allowed dramatic reductions in the extent of surgery required for local control of breast cancer, with a
large number of patients now eligible for breast-conserving surgery.
3,4,5
Breast-Conserving Surgery
The aim of local treatment of breast cancer is to achieve long-term local disease control with the minimum of
local morbidity. The major advantages of breast-conserving treatment (BCT) are:

Box 1: Major advantages of BCT

1. An acceptable cosmetic appearance
2. Lower levels of psychological morbidity
3. Equivalence in terms of disease outcome for BCT and mastectomy in selected patients

Box 2: Four critical elements in patient selection for BCT

1. History and physical examination
2. Mammographic evaluation
3. Histologic assessment of the resected breast specimen
4. Assessment of the patient's needs and expectations

Recent (i.e., usually within 3 months) preoperative mammographic evaluation is necessary to determine a
patient's eligibility for BCT. Mammographic evaluation defines the extent of a patient's disease, the presence or
absence of multicentricity, and other factors that might influence the treatment decision, and evaluates the
contralateral breast.

Indications of BCT
Clinically, solitary cancers measuring 4 cm or less, without signs of involvement of skin or chest wall, can usually
be managed by BCT. Many units consider tumors measuring 3 cm or less clinically as the ultimate size of a
tumor for a patient to be able to undergo BCT. Patients with tumors measuring clinically larger than 4 cm can be
treated by BCT if the patient has large breasts. Conversely, in a patient with small breasts, excision of even a 1-
cm tumor may produce an unacceptable cosmetic result.

Box 3:Indications for breast conserving surgery:

1. T1, T2 (<4 cm), N0, N1, M0
2. T2 >4 cm in large breasts
3. Single clinical and mammographic lesion

104
Absolute and Relative Contraindications to Breast-Conserving Therapy
In the selection of patients for BCT, there are some absolute and relative contraindications.

Absolute Contraindications
1. Pregnancy: Pregnancy is an absolute contraindication to the use of breast irradiation. However, in
many cases, it may be possible to perform BCS in the third trimester and treat the patient with irradiation
after delivery.
2. Multifocal/multicentric disease: Women with two or more primary tumors in separate quadrants of
the breast or with diffuse malignant-appearing microcalcifications on mammography are not considered
candidates for breast conservation treatment.
3. A history of prior therapeutic irradiation to the breast region: Such patients would require
retreatment to an excessively high total radiation dose to a significant volume is another absolute
contraindication.
4. Persistent positive margins after reasonable surgical attempts: The importance of a single focally
positive microscopic margin needs further study and may not be an absolute contraindication.
5. T4, N2, or M1 lesions
6. Patients who prefer mastectomy.

Relative Contraindications
1. A history of collagen vascular disease: Such patients tolerate irradiation poorly.
2. Tumor size: It is not an absolute contraindication to breast conservation treatment, although there is
little published experience in treating patients with tumor sizes greater than 4 to 5 cm. However, a
relative contraindication is the presence of a large tumor in a small breast in which an adequate
resection would result in significant cosmetic alteration.
3. Breast size: Treatment by irradiation of women with large or pendulous breasts is feasible if
reproducibility of patient setup can be ensured and the technical capability exists for 6 MV or greater
photon beam irradiation to obtain adequate dose homogeneity.
4. Women with a strong family history of breast cancer or BRCA1 and BRCA2 mutation carriers: Such
patients are at higher risk of a recurrent cancer or a new cancer in the same or opposite breast.

Nonmitigating Factors
There are certain clinical and pathologic features that should not prevent patients from being candidates for
breast conservation treatment. These features include the presence of clinically suspicious and mobile axillary
lymph nodes or microscopic tumor involvement in axillary nodes. Tumor location is not a factor in treatment
choice. Tumors in a superficial subareolar location may occasionally require the resection of the nipple/areolar
complex to achieve negative margins, but this does not have an impact on outcome.

Technique of BCT
Two breast-conservation surgical procedures have been extensively studied and described: quadrantectomy
and wide local excision. Quadrantectomy is based on the belief that the breast is organized into segments, with
each segment draining into its own major duct, and that invasive cancer spreads down the duct system toward
the nipple. The evidence is that both of these premises are incorrect. Studies have shown similar rates of local
recurrence in both quadrantectomy and wide local excision, providing margins of excision are clear.
Quadrantectomy is no longer advocated because it produces a significantly poorer cosmetic outcome than wide
local excision. The consensus view is that the majority of patients having BCT can be adequately treated
by wide local excision.

The majority of wide excisions of palpable and impalpable cancers are performed under general anesthesia. The
patient is given a dose of intravenous antibiotics at induction (1.2 g of co-amoxiclav or a cephalosporin).

Incisions: The aim of wide local excision is to remove all invasive and
any ductal carcinoma in situ with a 1-cm macroscopic margin of
normal surrounding breast tissue. If a subsequent mastectomy is
likely, the scar should be within the ellipse of skin, which would be
excised at mastectomy. It is also important to place the incision in a
position that will obtain the optimal cosmetic result (Fig. 1A,B,C).
Langer described the predominant orientation of collagen fibers in the
skin and around the breast, and these lines are essentially circular
(Fig. 1A). Kraisl later demonstrated that lines of maximum resting skin
tension run in a more transverse orientation across the breast (Fig.
1B). In general, scars that are parallel to both the lines of maximum
resting skin tension and to the orientation of collagen fibers produce
the best cosmetic incisions with least hypertrophy and keloid Fig. 1.The direction of Langer's lines (A) and the
formation.An incision to excise a cancer should be placed directly over lines of maximum resting skin tension in the
the lesion. Excessive tunneling is not recommended because this may breast (the so-called dynamic lines of Kraisl) (B)
compromise margins and make a reexcision for positive margins
unnecessarily difficult. Excising skin directly overlying a cancer is only

105
necessary if the carcinoma is very superficial and/or Fig. 1 (C):Planning the
the skin is tethered. lumpectomy incision. Skin
incisions should be placed
within the Langers lines
Wide local excision: After making the skin incision,
when possible. Closer to the
the skin and subcutaneous fat are dissected off the
areola, circumareolar
breast tissue. The skin flaps should be elevated 1 to 2 incisions are appropriate, but
cm beyond the edge of the cancer (Fig. 2A). Normal excessive tunneling should be
breast tissue should be excised at least 1 cm beyond avoided. In the lower
the limit of the palpable mass. Having divided breast hemisphere of the breast,
tissue beyond the edge of the cancer, the deep aspect radial incisions can be
of the tumor can be palpated and dissection through considered, because these
the breast tissue is continued down to the pectoral result in less distortion of the
fascia and the breast tissue containing the cancer is nipple-areolar complex.
lifted off the fascia. It is not necessary to excise
pectoral fascia unless it is tethered to the tumor. Once
assured that an adequate biopsy has been performed,
a tissue-marking clip should be placed at the site of the biopsy so that the
area can be easily targeted in the future in case the lesion requires re-
excision.

Wound Closure: After excision, hemostasis should be achieved to avoid a

hematoma. Drains are not necessary after surgery. Once hemostasis is
achieved, surgical clips should be placed within the lumpectomy cavity in
the six anatomic locations (anterior, posterior, medial, lateral, superior,
inferior). This helps in the planning of the radiation therapy. The surgeon
should also never try to simply reapproximate the breast tissue. Sutures
should not be placed in the breast parenchyma to close the cavity. The
lumpectomy cavity will fill with seroma and fibrin, and ultimately fibrous
tissue, which maintains the normal, rounded contour of the breast. The
incision should be reapproximated with absorbable deep dermal sutures
followed by a subcuticular stitch or tissue adhesive. Fig. 2A: Finger of non-dominant
hand is placed over palpable cancer
Immediately after excision, the specimen is immediately orientated prior to and breast tissue is divided beyond
submission to the pathologist with sutures, ligaclips, or metal markers (Fig. the fingertips
2B).
6
Wire-Localized Lumpectomy
With the increased use of screening mammography, many cancers are
diagnosed by means of a stereotactic core biopsy of a mammographic
abnormality. In these cases, a wire-localized lumpectomy will be necessary.
Localization involves placing a rigid introducer needle with a flexible hooked
wire inside of it at the site of the abnormality using either biplanar
mammography or ultrasound.
3,4
Reexcision Lumpectomy
Reexcision lumpectomy should be performed in any patient with unknown or
positive margins. It is also strongly recommended in patients with close
margins, approximately 2 to 3 mm. Reexcision is necessary in one fourth to one
third of lumpectomies. Failure to reexcise close or positive margins stands a
high chance of leaving residual disease and increases local recurrence rates.
Fig. 2B: The lumpectomy specimen
The standard approach to a reexcision lumpectomy is to remove the entire should be oriented in three planes so
cavity. An ellipse of skin is drawn around the previous skin incision so that the that the pathologist can identify
previous scar is removed with the specimen. Skin flaps are then raised. The close or positive margins.
previous cavity is usually readily palpable, and the approach to the reexcision is
similar to that of a wide local excision. It is important not to violate the cavity
because this complicates the inking and evaluation of the new margins.
7,8
Axillary Surgery in Patients Undergoing Breast Conserving Surgery
The two main aims of axillary surgery in patients with operable breast cancer are to stage the axilla and to treat
any axillary disease. The presence or absence of axillary lymph node involvement is the single best predictor of
survival in patients with breast cancer, and important treatment decisions are based on it. The number of involved
lymph nodes and the level of lymph node involvement are independent predictors of survival of patients with
breast cancer.

Options for staging axillary disease include: (a) Sentinel lymph node biopsy, (b) Axillary node sampling, and (c)
Axillary dissection

106
Box 4: Indications for sentinel lymph node biopsy (SNLB)or axillary node sampling
1. Operable breast cancer (T1, T2)
2. Clinically node-negative patients

Box 5: Contraindications for sentinel lymph node biopsy or axillary node sampling
1. Palpable lymphadenopathy
2. Prior axillary surgery
3. Chemotherapy or radiation therapy
4. Multifocal breast cancer

Box 6: Indications for axillary dissection

1. Preoperative diagnosis of axillary node metastasis
2. Positive SLN
3. Failed SLN biopsy or a recent inadequate ALND
4. Clinically suspicious nodes identified at surgery
5. Non availability of equipment for SLN biopsy

Technique of Sentinel lymph node biopsy

The combination of intraoperative gamma probe detection of radioactive colloid and intraoperative visualization of
isosulfan blue dye is more accurate than the use of either agent alone. On the day prior to surgery, or on the
morning of surgery, using a 25-gauge needle, 0.5 mCi of 0.2-micron technetium-99 sulfur colloid in a volume of
0.2 to 0.5 mL is injected (three to four separate injections) at the cancer site or subdermally. Subsequently, in the
operating room, 4 mL of isosulfan blue dye is injected in a similar fashion, but with an additional 1 mL injected
between the cancer site and the overlying skin. For nonpalpable cancers, the injection is guided by either
intraoperative ultrasound or by a localization wire that is placed preoperatively under ultrasound or stereotactic
guidance. Women are told preoperatively that the isosulfan blue dye injection will impart a change to the color of
their urine and that there is a very small risk of allergic reaction to the dye (1 in 10,000). The use of radioactive
colloid is safe and radiation exposure is very low.

A hand-held gamma counter is then employed transcutaneously to identify the location of the sentinel lymph
node. A 3- to 4-cm incision is made in line with that used for an axillary dissection, which is a curved transverse
incision in the lower axilla just below the hairline. After dissecting through the subcutaneous tissue and identifying
the lateral border of the pectoralis muscles, the clavipectoral fascia is divided to gain exposure to the axillary
contents. The gamma counter is employed to pinpoint the location of the sentinel lymph node. As the dissection
continues, the signal from the probe increases in intensity as the sentinel lymph node is approached. The
sentinel lymph node also is identified by visualization of isosulfan blue dye in the afferent lymph vessel and in the
lymph node itself. Before removing the sentinel lymph node, a 10-second in vivo radioactivity count is obtained.
After removal of the sentinel lymph node, a 10-second ex vivo radioactive count is obtained, and the lymph node
is then sent to pathology for either permanent or frozen section analysis. When necessary, a search is made for a
second sentinel lymph node. This procedure is repeated until residual radioactivity in the surgical bed is less that
10% of the 10-second ex vivo count of the most radioactive sentinel lymph node.

Complications associated with Sentinel Lymph Node Biopsy

Surgical Complications: As with any incision, the SLN biopsy can be associated with bleeding
(hematoma) and wound infection, although both of these are rare complications. Seroma formation after
SLN biopsy can occur and is readily treatable by needle aspiration. Other complications of SLN biopsy are
similar to those seen in ALND, including neurosensory disturbances, and lymphedema. Although it is
rare, and certainly less common than with ALND, it is a mistake to believe that SLN biopsy completely avoids
the risk of lymphedema. Lymphedema rates have been described in as many of 5% to 7% of SLN biopsy
procedures.
Technical Complications: Inability to find the sentinel node is a relatively rare occurrence. A meta-
analysis of data on SLN biopsy from 69 studies, reveals overall identification rate of 96% and overall false
negative rate of 8.4%. Given the importance of the axillary nodal status on guiding adjuvant therapy
decisions and the potential benefit of removing nodal disease early, if a SLN is not identified, a level I and II
axillary lymph node dissection should be performed. A rare, but serious, risk of sentinel node biopsy is the
potential allergic reaction to isosulfan blue or patent blue dye.

Technique of axillary lymph node dissection

A curvilinear incision is made just inferior to the hair-bearing area, extending from just posterior to the pectoralis
major muscle and just anterior to the latissimus dorsi muscle (Fig. 3A). A lazy S incision is an alternative, placed
between the pectoralis major and latissimusdorsi muscles (Fig. 3B). An anterior axillary fold incision can also be
used (Fig. 3C). The skin incision is deepened through the superficial fascia and skin flaps are developed deep to
this superficial fascia.

107
The medial dissection is begun by using skin hooks to
elevate the superior, medial, and inferior skin flaps and
dissecting in the plane between the subcutaneous fat and
axillary fat. Dissection continues with the aid of gentle
retraction with a swab. The lateral border of the pectoralis
major muscle is easily palpable and dissection should
continue to it.The first step is to raise superior and inferior
skin flaps. The incision should be carried straight down to
just above the axillary fascia and then flaps created. Once
the flaps are raised, the next step is to identify three
landmarks; the pectoralis major and minor muscles, the
axillary vein, and the latissimusdorsi muscle (Fig. 4B). With
the pectoralis major muscle retracted medially, the pectoralis
minor muscle is exposed, and the investing fascia can be
opened in a similar manner. During the exposure of the Fig. 3: Incisions for axillary dissection. A: Skin crease
muscles, it is important to identify and preserve the medial incision distal to the hair-bearing skin of the axilla. B:
pectoral neurovascular bundle. The latissimusdorsi muscle Lazy S incision placed between pectoralis major and
should be exposed to the point where the axillary vein latissimusdorsi muscles. C: Anterior axillary fold incision
crosses it. During this dissection, the lateral aspect of the (dashed line) placed parallel and posterior to lateral
intercostobrachial nerves will be encountered. Preserving border of the pectoralis major muscle.
these nerves, although adding time to the procedure, will
avoid numbness of the upper inner arm.Finally, the axillary
vein is exposed. The vein is often encountered during the exposure of the muscles. It is important not to dis- sect
superior to the level of the axillary vein because an injury to the brachial plexus can be one of the most
debilitating complications.

The dissection is greatly facilitated by retracting the axillary contents caudally. As the fat is dissected from the
vein, small superficial branches of the axillary vein are divided and ligated with 3-0 silk sutures. As the vein is
cleared laterally to medially, the next step is to identify the thoracodorsal bundle. (Fig. 4C). Once the entire
bundle is identified, the fibrofatty tissue can be cleared from the neurovascular structures so that they may be
seen entering the latissimusdorsi muscle.

As the thoracodorsal vein is cleared, a branch is noted heading toward the chest wall. This crossing branch can
often provide a clue to the location of the long thoracic nerve. Some surgeons will routinely follow this branch to
the serratus anterior at this point in the dissection to identify the long thoracic. Others identify the long thoracic
after the dissection of the level II nodes.

Fig. 4B: Superior and inferior flaps are raised, and the
pectoralis major, latissimusdorsi, and axillary vein are
Fig. 4A: Levels I to III of the axillary lymph identified.
nodes.

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For a level I and II dissection, the pectoralis minor muscle must be raised to allow access to the level II nodes.
This is greatly facilitated by rotation of the arm medially. The exposure of the axillary vein can then be continued
under the pectoralis minor muscle with inclusion of this fibrofatty tissue with the specimen. The axillary contents
are now dissected from medial to lateral off of the serratus anterior muscle. During this portion of the dissection,

Fig. 4D: After completion of the axillary dissection, the relationship of

Fig. 4C: The thoracodorsal neurovascular bundle is seen laterally.
Near the axillary vein, the thoraco- dorsal nerve is more medial
than the artery and vein.
the nerves can be seen. The intercostobrachial nerve can be identified
and preserved. The long thoracic nerve is identified slightly lateral to
the serratus anterior, in the encapsulating fascia. The long thoracic
nerve is in the same anteroposterior plane as the thoracodorsal
nerve, so knowing where the thoracodorsal nerve is will help the
surgeon identify the long thoracic.

the medial aspect of the intercostobrachialnerve is identified, and the entire nerve can be freed from the
specimen if the decision was made to preserve it. The long thoracic nerve is also identified (Fig. 4D). Knowing
where the thoracodorsal nerve is will help the surgeon identify the long thoracic. The crossing branch of the
thoracodorsal vein will serve the same purpose. The most common mistake is to look for the nerve directly on the
serratus anterior, thus actually retracting the nerve into the specimen. Once identified, it is cleaned off along its
length. With both nerves visualized, the tissue between the nerves may be clamped at the inferior margin of the
vein and suture ligated. The tissue may now be dissected free from the muscle. The nerves should be visualized
throughout this portion of the dissection.

Once the specimen is removed, hemostasis is assured and a closed suction catheter is placed through a
separate incision lower on the chest wall. The drain is secured with a suture and attached to a suction reservoir.
The wound is closed with absorbable subcutaneous sutures and the skin reapproximated.

Complications after ALND are discussed under complications of modified radical mastectomy.
4,5,6,9
Modified Radical Mastectomy
A modified radical mastectomy removes all breast tissue, the nipple-areola complex, necessary skin, and the
level I and II axillary lymph nodes.

After the induction of general anesthesia, the patient is positioned supine with the arm abducted to 90 degrees on
an armboard. The arm is not secured to the armboard for the MRM so that it may be brought into the operative
field during surgery. The chest, axilla, and entire arm are prepared and draped in sterile fashion. The prepared
area should extend sufficiently beyond the breast so that the landmarks can be easily identified: across the
midline, to the costal margin, the base of the neck, and laterally to the operating room table, including around the
shoulder. The forearm and hand are draped in a towel secured with a bandage.

Incisions
The standard incision for a mastectomy is an elliptical skin incision including both the nipple-areolar complex and
the previous biopsy incision. The ellipse may be oriented either transversely or obliquely. The choice of incision
must be based on the size of the breast, body habitus of the patient, and size and location of the tumor (or biopsy
cavity). Care should be taken to make the ellipse wide enough that redundant skin is avoided, including dog-ears,
but not so wide that the closure is excessively tight. It is not necessary to extend the incisions further into the
axilla; a complete axillary dissection can be performed through the standard incisions. Undue tension may lead to
vascular compromise of the flaps.

There are several options for how this ellipse is oriented. The classic Stewart incision results in a transverse
scar (Fig. 5). It should begin at the lateral margin of the sternum and end at the anterior margin of the

109
latissimusdorsi. It is not necessary to extend the incisions further into the axilla; a complete axillary dissection can
be performed through the standard incisions. The Stewart incision may be modified to lie obliquely, so the final
incision extends superiorly at the lateral margin.

Fig. 5: The classic Stewart elliptical skin incision for central and Fig. 6:The modified Stewart oblique elliptical skin incision for
subareolar breast cancers. The medial extent of the incision is the inner quadrant breast cancers. The medial extent of the incision
ipsilateral margin of the sternum, while the lateral extent overlies often extends to the midsternum
the anterior margin of the latissimus dorsi muscle. The incision
incorporates the nipple-areola complex and skin overlying the
breast cancer en bloc with skin margins that lie 1 to 2 cm from the
cephalad and caudad extents of the cancer.

The other popular incision is the Orr oblique incision. As opposed to the modified Stewart incision, which
extends slightly superiorly in the lateral margin, the Orr incision is an oblique incision (Fig. 6). This approach is
ideal for upper, outer quadrant incisions but, as with the Stewart incision, can be used for most tumors. Incisions
appropriate for cancers occupying various locations in the breast are shown in Figures 5, 6, 7,8, 9, 10, 11. The
elliptical incision of the breast skin incorporates the nipple-areola complex and skin overlying the breast cancer
en bloc with skin margins that lie 1 to 2 cm from the cephalad and caudad extents of the cancer.

Raising of skin flaps

Skin flaps are developed using cautery or scalpel and extend to the boundaries of dissection for the modified
radical mastectomy, which are: (a) the anterior margin of the latissimus dorsi muscle laterally, (b) the lateral
border of the sternum medially, (c) the clavicle superiorly, and (d) the superior extent of rectus sheath inferiorly
(Fig. 11).

The skin incision is then made with a scalpel, dividing the skin and superficial fascia just until the breast tissue is
evident. Several superficial veins need to be cauterized. Once the skin incision is completed, the superior flap is
raised. The skin edges are elevated at a right angle to the chest wall to adequately expose the superficial fascia
(Fig. 12). The appropriate dissection plane for skin flap elevation is deep to the subcutaneous vasculature and
superficial to the vessels of the breast parenchyma. The surgeon elevates the skin flap with consistent thickness
to avoid creation of devascularized subcutaneous tissues. If cautery is used, it should not be maintained in one
position for too long a period of time to avoid thermal injury to the flap.

110
 Fig 7: The classic Orr oblique elliptical skin incision for cancer of Fig. 8: Variation of the Orr oblique elliptical incision for
the upper outer quadrant of the breast. The incision, which is lower inner quadrant and lower midline (6 o'clock) breast
directed cephalad toward the ipsilateral axilla, incorporates the cancers.
nipple-areola complex and skin overlying the breast cancer en
bloc with skin margins that lie 1 to 2 cm from the cephalad and
caudad extents of the cancer.

Elevation of the breast parenchyma

Once the skin flaps are developed, the breast parenchyma and pectoralis major fascia are elevated from the
underlying pectoralis major muscle in a plane parallel with the muscle bundles as they course from their medial
origin (ribs 2 to 6) to their lateral insertion on the humerus (Fig. 13). Perforating vessels from the lateral thoracic
or anterior intercostal arteries, which are end arteries that supply the pectoralis major and minor muscles and
breast parenchyma, are regularly encountered and cauterized. Elevation of the breast parenchyma and pectoralis
major fascia is continued laterally until the lateral edge of the pectoralis major muscle and the underlying
pectoralis minor muscle are exposed.

The laterally placed neurovascular bundle in which the medial pectoral nerve innervates the pectoralis major and
minor muscles. If possible, this nerve is preserved to prevent atrophy of the lateral head of the pectoralis major, a
significant cosmetic and functional defect.

Axillary Dissection
As the breast is removed from the lateral border of the pectoralis major muscle, the space between the pectoralis
major and minor muscle can be developed so that palpation of the interpectoral (Rotters) nodes can be
undertaken (Fig. 14). Some surgeons only remove this tissue when palpable nodes are detected; other surgeons
routinely include the fibroareolar tissue in the interpectoral space, which can be swept laterally and included with
the specimen. However, excessive dissection in this area can lead to injury of the lateral pectoral nerve and is
unlikely to be of added benefit if grossly involved nodes are not present. The investing fascia of the axillary space
is sharply divided (Fig. 14), the pectoralis minor muscle is defined, and lymph nodes, which may lie between the
pectoralis muscles (Rotter nodes), are cleared. As the axillary lymph node dissection proceeds, the loose areolar
tissue of the lateral axillary space is elevated with identification of the lateral extent of the axillary vein in its
course anterior and caudad to the brachial plexus and axillary artery (the axillary contents can also be removed in
a medial to lateral direction). The investing layer of the axillary vein is dissected sharply, with dissection allowing
complete visualization of the anterior and ventral surfaces of the vein. Ligation and division of intervening venous
tributaries is performed. Dissection continues medially on the anteroventral surface of the axillary vein, and the
loose areolar tissue at the juncture of the axillary vein with the anterior margin of the latissimusdorsi muscle is
swept inferomedially to include the lateral group of axillary lymph nodes (level I, see Fig. 15). The
intercostobrachial nerves are visualized, and course through the level II axillary lymph nodes that lie below the
axillary vein. Generally, no attempt is made to salvage the superior trunk and branches of the intercostobrachial
nerve.

111
 Fig. 9 (Left): Oblique elliptical skin incision for upper inner
quadrant breast cancers. The medial extent of the incision
often extends to the midsternum. The cephalad skin flap,
which is subsequently developed, must provide exposure to
the axilla for axillary lymph node dissection.

Fig. 10 (Above): Oblique elliptical skin incision for lower

outer quadrant breast cancers.

Fig. 11: Vertical elliptical skin incision for high-lying,

midline (12 o'clock), or infraclavicular breast cancers.
The lateral skin flap, which is subsequently developed,
must provide exposure to the axilla for axillary lymph
node dissection.

112
The thoracodorsal artery and vein are preserved- they are located deep in the axillary space and are invested
with loose areolar tissue and the axillary lymph nodes of the lateral and subscapular groups (Figs. 15, and 16).
The thoracodorsal nerve originates from the posterior cord medial to the thoracodorsal artery and vein and is
visualized and protected along its variable inferolateral course en route to its innervation of the latissimus dorsi
muscle.

The lateral axillary lymph node group (Fig. 15) is retracted inferomedially and anterior to the thoracodorsal
neurovascular bundle and dissected en bloc with the subscapular group of axillary lymph nodes (level I), which
are medially located between the thoracodorsal nerve and the lateral chest wall. Dissection of the posterior
contents of the axillary space exposes the posterior boundary of the axilla, allowing visualization of the heads of
the teres major muscle laterally and the subscapularis muscle medially.

Fig. 12: Initiation of the modified radical mastectomy. Fig. 13: Elevation of the breast and pectoralis major fascia off of
Development of skin flaps. the underlying muscle. Dissection should proceed superior to
inferior and medial to lateral.

Dissection then proceeds medially with extirpation of the central axillary lymph node groups (level II). A level III
dissection is generally considered unnecessary (unless there is grossly apparent disease present in the
axillary apex) because skip metastases to level III only occur in 2% to 3% of cases and due to increased
incidence of lymphedema. The surgeon continues the dissection en bloc to avoid separation of nodal groups
and disruption of lymphatic vessels in the axilla.

Fig. 14: Exposure of the pectoralis minor muscle and incision of the investing fascia of the axilla.

113
 Fig. 15.Axillary lymph node dissection (Patey modification).

Fig. 16: The completed axillary lymph node dissection. In this illustration, the pectoralis minor muscle has been resected (Patey
modification).The medial and lateral pectoral nerves, the thoracodorsal neurovascular bundle, and the long thoracic nerve are preserved.

With medial dissection, the surgeon encounters the chest wall deep in the medial axillary space and is able to
identify and preserve the long thoracic nerve (of Bell), which is constant in its location, anterior to the
subscapularis muscle, and is closely applied to the investing fascial compartment of the chest wall. The long
thoracic nerve is dissected along its course to where it innervates the serratus anterior muscle (Figs. 14, 15, 16).

114
Damage to the nerve causes permanent disability with a winged scapula deformity. When level III
lymphadenopathy is present, a Patey modification of the modified radical mastectomy may be employed
(Figs. 15 and 16). As dissection proceeds medially along the lateral margin of the pectoralis major muscle,
abduction of the shoulder and extension of the arm along with finger dissection at the lateral margin of the
pectoralis major muscle allows visualization of the insertion of the pectoralis minor muscle on the coracoid
process of the scapula. The Patey modification involves division of the tendinous portion of the pectoralis minor
muscle near its insertion on the coracoid process with or without removal of the muscle, which permits access to
the apical axillary lymph nodes (level III).

Closure
Once the axillary lymph node dissection is complete, the resection specimen is sent for histologic examination
and for immunohistochemistry (ER, PR, Her2-neu). The surgical bed is irrigated with normal saline to evacuate
residual tissue, blood clots, and serum. Bleeding points are identified and cauterized or ligated. Just prior to
closure, two closed-suction drains are typically placed through two different stab incisions inferiorly (Fig. 16). The
laterally placed drain is positioned in the axillary space approximately 2 cm inferior to the axillary vein on the
ventral surface of the latissimus dorsi muscle to provide drainage of the axilla. The medially placed drain is
positioned under the skin flaps. Both drains are secured to the skin with a 2-0 silk suture and are connected to
the suction reservoir. The wound is closed with 3-0 or with 4-0 nylon suture.

Postoperative Care
Wound dressings are removed after 24 to 48 hours. The silastic catheters remain in place until drainage
becomes serous or serosanguineous in character and decreases to less than 30 mL per 24 hours for a 48-hour
period. Generally, the catheters are removed between postoperative days 5 and 7, but, when necessary for
continued high-volume drainage, can remain until postoperative day 10. Range-of-motion shoulder exercises
begin 24 hours after surgery.
2,10
Total Mastectomy and Prophylactic Mastectomy
The term total mastectomy refers to the removal of the entire breast, with the same limits of dissection as
described for the modified radical mastectomy. Care must be taken to remove the axillary tail of Spence, and
therefore identification of the latissimus dorsi muscle is important. Bot pectoral muscles and the axillary nodes
are preserved. The indications for total mastectomy include the patients with DCIS who elect mastectomy,
patients undergoing prophylactic mastectomy, patients in whom a recurrence develops in the breast after a BCS
that had included ALND, and patients with metastatic disease who are undergoing toilet mastectomy for local
control of the primary tumor.

Prophylactic mastectomy continues to be indicated as an option

for patients at high risk of developing breast cancer, including
known gene mutation carriers of BRCA1 or BRCA2, strong family
history of multiple first-degree relatives, or successive generation of
breast or ovarian cancer and high-risk lesions such as atypical
ductal hyperplasia and lobular carcinoma in situ. This decision
should be made with the assistance of a multidisciplinary team and
includes a thorough discussion of alternative such as close
surveillance and risk-reduction techniques.
10
Skin Sparing Mastectomy
This alternative to a simple total mastectomy for breast cancer can
be used when immediate reconstruction is planned, and usually
results in a better cosmetic appearance. A total mastectomy is
performed through a circumareolar incision. The nipple and areola
are excised with the rest of the breast, but the breast skin is Fig. 17: Skin sparing mastectomy incisions: varying
preserved as an envelope, which receives an immediate
incisions used in skin sparing mastectomy. The
reconstruction.
incision is in part determined by areas of previous
Complications of Breast Surgery biopsy. The goal is to minimize area of scar on the
Wound complications are typically minor and frequently managed skin envelope by incorporating biopsy incisions
on an outpatient basis, but can occur in up to 30% of cases. These
include flap necrosis, breast infections, seromas, and
hematomas. Very rarely, more serious complications can occur. Flap necrosis and epidermolysis occurs in 18-
30% of all mastectomies. Deep venous thrombosis and pulmonary embolism (PE) are potential complications of
any major surgery. Pneumothorax has been described as a result of wire localization or inadvertently deep
dissection. Brachial plexopathy may occur related to a stretch injury of a malpositioned patient.

Major Complications of Axillary Lymph Node Dissection

Seroma, Infection, Paresthesia, Chronic pain, Shoulder immobility, Axillary vein thrombosis, Thoracodorsal nerve
injury, Long thoracic nerve injury (winged scapula), Brachial plexopathy, Arm lymphedema, Breast lymphedema.

115
Box 7: Anatomic Complications of the Modified Radical Mastectomy
Vascular Injury
The first and second perforating vessels are too large for cautery. They are ligated.
The axillary vein, if torn, is repaired. Ligation may cause chronic edema.
Nerve Injury
Intercostobrachial nerve When cut, circumscribed numbness of the medial aspect of
the ipsilateral upper arm results.
Long thoracic nerve If cut, a winged scapuladeformity results
Medial and lateral thoracic nerves If cut, the pectoralis muscles atrophy.
Thoracodorsal nerve If cut, internal rotation and abduction of the shoulder are
weakened.

Lymphedema
The most significant complication of an ALND is lymphedema of the upper extremity. Approximately 10% to 30%
of patients who have an ALND will experience lymphedema.

Box 8: risk factors for lymphedema among patients undergoing axillary surgery
Extent of surgery: increased risk after level I,II,III dissection compared to level I,II dissection
Radiation
Infection
Regional recurrence
Inflammatory diseases (rheumatoid
arthritis, chronic dermatitis)
Venous obstruction
Obesity
Air travel

Box 9: Risk factors for lymphedema among patients undergoing axillary surgery
Use the opposite arm for intravenous catheters, blood draws, injections, or blood pressure
measurements.
Avoid cuts, scratches, or burns to the hand and arm by wearing long sleeves and/or gloves
when doing cooking, gardening, household projects, etc.
Do not wear tight or constricting jewelry or clothing.
Wear a compression sleeve on the arm when lymphedema manifests
Advice to maintain an ideal body weight.

Breast Reconstruction
Breast reconstruction may be performed as immediate reconstruction, that is, the same day as mastectomy, or
as delayed reconstruction, months or years later. Immediate reconstruction has the advantages of preserving the
maximum amount of breast skin for use in reconstruction, combining the recovery period for both procedures,
and avoiding a period of time without reconstruction. Immediate reconstruction does not have a detrimental effect
on long-term survival or local recurrence rates. Reconstruction may be delayed in patients who might require
postmastectomy radiation therapy and is usually delayed in patients with locally advanced cancer.
Reconstruction options include tissue expander and implant reconstructions and autologous tissue
reconstructions, most often with latissimusdorsi flaps, transverse rectus abdominis muscle (TRAM) flaps, and
more recently, muscle-preserving
perforator abdominal flaps.

Latissimus dorsi
musculocutaneous flap
This is the most widely used method
of breast reconstruction following
mastectomy. After completion of the
mastectomy and any axillary
clearance, the patient is turned on her
side and a suitably sized ellipse of
skin marked overlying the latissimus
dorsi muscle. The paddle is placed
sufficiently posteriorly to afford
adequate length to the flap (Fig. 18A).
The skin is incised, leaving it attached
to the underlying muscle. The skin and
fascia are dissected off the muscle
proximal and distal to the skin ellipse,
and the muscle freed on its deep
Fig. 18: The latissimus dorsi flap
116
surface, prior to dividing its posterior
attachment. It may then be elevated as a
flap based on the branches of the
subscapular vessels. Dissection is carried
along the flap pedicle until it can be rotated
and passed subcutaneously round to fill the
breast defect (Fig. 18B). The flap is then
rotated through the axilla to the anterior
defect. Ideally, the muscle should be
denervated to avoid future painful
contractions. The donor site is closed over
suction drains and the patient returned to
the supine position. The latissimus dorsi
muscle forms the tissue replacement for
the excised breast, and its overlying ellipse
of skin is sutured to the upper and lower
mastectomy flaps.

Alternative flaps
Although pedicled transverse rectus Fig. 19: The transverse rectus abdominis myocutaneous flap rotation. A,
abdominis myocutaneous (TRAM) flaps Contralateral technique. B, Ipsilateral technique.
based on the internal thoracic artery have a
somewhat perilous blood supply, free
TRAM flaps, or free deep inferior epigastric artery perforator (DIEP) flaps, based on the inferior epigastric artery
are increasingly employed where microsurgical skills are available. These are preferred by some surgeons to
latissimusdorsi flaps. A free superior gluteal artery perforator flap is another alternative.

References

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Breast 2003;12:163.
9. Bland KI, Beenken SW. Modified Radical Mastectomy with Immediate or Delayed Breast Reconstruction. In:
Fischer, Josef E (eds): Mastery of Surgery. 5th ed. Lippincott Williams & Wilkins; 2007:530-544.
10. Tuttle TM, HabermanEB, Grund EH et al. Increasing use of contralateral prophylactic mastectomy for breast
cancer patients: a trend toward more aggressive surgical treatment. J Clin Oncol 2007;25(33):5203309.

Growth for the sake of growth is the ideology of the cancer cells
~ Edward Abbey Comprehending Nature.

Metastatic breast cancer (A Surgeons approach)

Ajit Sinha

Introduction
Cancer incidence is generally expressed as age adjusted or age standardized rate according to the world
standard population per 100,000 persons.

In female, breast cancer continues to be the most frequent cause of cancer death (15% 40,290) preceded only
[1]
by lung cancer (26% 71,660) and the most frequently diagnosed cancer. This can be attributed to improvement
in imaging and diagnostics, coupled with advancement in treatment strategies over the recent years.

117
Among females, breast cancer and cervical cancer are the leading sites of cancer in 18 out of 25 population
2]
based cancer registry PBCR[

Metastatic breast cancer (MBC) ie; stage IV breast cancer is defined as the spread of tumor beyond the breast,
chest wall and regional lymph nodes to other sites of the body. So any T, Any N and M 1 constitute a metastatic
disease. Approximate 50% of patient with breast cancer develop distant metastasis. Tumor dissemination can
occur via-direct extension through chest wall, through blood and lymphatic. Common sites includes bone, lung,
[3]
liver, chest wall, brain and distant lymph nodes. Symptoms are related to the site and extend of the tumor.

While strategies for treatment of primary tumor has markedly improved, no significant cure is available for MBC
and current treatment strategies focus mainly on symptom control and minimization of adverse effects to improve
[4]
disease free survival (DFS) and good quality of life.

Systemic therapy is the treatment of choice and surgery in a breast cancer with distant metastasis is indicated
only to prevent local complications-ulceration and fungation. Though it is generally accepted that local therapy
provides no survival advantage once metastasis has occurred, infact tumor excision may further stimulate the
growth of metastasis, various RCTs however suggests that surgery of primary tumor can actually improve
[5]
survival in a patient with only bony metastasis.

Natural History of Breast Cancer

th
At approximately 20 cell doubling, breast cancer cells acquire their own blood supply (neovascularization),
thereafter may spread into systemic venous blood to seed into distant sites such as pulmonary circulation via
axillary and intercostal veins or via batson plexus into the vertebral column. Successful implantation of the
metastatic foci from breast cancer occurs after primary cancer exceeds 0.5 cm in diameter.

Management of the breast cancer is based on the understanding of the tumor natural history. Three viewpoints
have been proposed on the basis of various hypotheses concerning the tumor biology.
[6]
1. Contiguous Theory spread from one source by Dr. William Halsted.
Halsteadian theory proposed that breast cancer begins strictly as a local disease and that
tumor cells spread overtime in a contiguous manner through lymphatics and that even distant
metastasis are the result of direct extension of local involvement. This theory dictated on the
aggressive local therapy for control of disease on the breast chest wall and regional lymph
nodes and provided justification for radical breast surgery.

2. The Systemic Theory or Alternative Theory By Dr. Bernard Fisher.

Fisher postulated that breast cancer is a systemic disease and that operable breast cancer has
distant micro metastasis at its very early stage. Hence variation in local treatment would not
effect survival; since it is the presence of the micro metastasis that determines the final
outcome.
His theory had a therapeutic implication on the management of breast cancer by introduction of
[7]
adjuvant systemic treatment and part of surgery replaced radiation for locoregional control.

3. The Spectrum Theory-By Dr. Hellman.

This hypothesis synthesized the aspect of the previous two theories; that breast cancer is a
spectrum of proclivities ranging from a disease that remain localized throughout its course to
one that is systemic when it is first detectable. Dr. Hellman suggested that metastasis is a
function of the tumor growth and progression and lymph node involvement indicates more
malignant potential.

4. Recent Concepts
Metastatic potential is an inherent , genetically predetermined property that is expressed very early by
tumor cells
Tumor cells are programmed to metastasize to a certain site in the presence of a favourable
environment.
Surgical removal of a primary tumor may reverse tumor induced immunosuppressant and restores both
T and B cells immunity
Self seed theory self seeding of the tumor cells occur at the primary site or other distant sites;
[8]
which supports complete excision of the primary
Biologic hypothesis- surgical removal of the primary tumor in a woman with MBC may confer a growth
advantage on distant metastasis.

Clinical Presentation of a MBC

A patient may present as a MBC or develop a systemic recurrence after treatment of an apparently localized
breast cancer. Most common sites of metastasis in order of frequency are- bone, lung, pleura, soft tissue and
liver. Symptoms are related to the location and extend of the tumor.

118
 Hormone receptor positive tumors are more likely to spread to bone as an initial site of metastasis; while
hormone receptor negative or HER 2 positive tumors are more likely to recur initially in viscera.

[10]
Lobular carcinoma more likely to metastasize to the pleura and abdomen compared to ductal carcinoma

Triple Negative breast cancer (TNBC)

Those patients whose tumor are negative for all the three biomarkers ER, PR, HER 2 are referred to as triple
negative and have increased risk of multiple visceral and brain metastasis and have poorer prognosis.
Chemotherapy is the mainstay of treatment for these patients
OMBC- Oligometastatic breast cancer is a subset of MBC with limited number and sites of metastasis and
constitutes as high as 20% of all MBC. There is increasing evidence that there is a potential advantage of
removing the primary tumor in OMBC by eliminating a potential source for further metastatic seeding,
restoration of immune competence and reduction in chemo resistance by reducing the number of clones.

Stage IV NED
Approx 1-10% of women with MBC have a metastatic of disease as an isolated lesion. These groups of patients
are known as Stage IV no evidence of disease (NED) and have relatively poorer prognosis due to early
metastasis at distant sites.

Diagnostic Approach for MBC

Staging evaluation includes:

Triple assessment ( thorough clinical examination , Imaging and histopathological examination)
Tissue diagnosis-
NCCN Panel recommends that metastatic disease at presentation or first recurrence of disease should be
biopsied for histological assessment of the biomarkers which will allow selection of appropriate treatment. As
discordance between the receptor status of primary and recurrent diseases has been reported in 7.2 % -
31% for ER and 0.7-11% for HER2, Reassessment is therefore mandatory. This discrepancy may be related
to change in the biology of the disease, differential effect of prior treatment on clonal subset, tumor
heterogeneity or imperfect accuracy of assay (NCCN guidelines 2015)
Metastatic work up and diagnostic radiographs of chest , CT of abdomen , bone scan and radiograph of the
long bones or weight bearing area that are painful or appear abnormal on bone scan
FDG-PET scan is helpful in situation where the standard imaging results are equivocal or suspicious.
Extensive evaluation to identify metastatic disease is not required in asymptomatic patients with Stage I and
II breast cancer because of low likelihood of metastasis. But in stage III breast cancer occult metastasis is
found in 20% of cases and staging studies are recommended.

Prognostic Factors in MBC-

The likelihood of response to therapy in a MBC is dependent on

Tumor biology (grade, ER/PR , HER 2 status)
Cancer related symptoms
Sites of recurrence
Number of the sites of recurrences
Performance status of the patient
Prior adjuvant therapy
Period of disease free interval

[10]
Prior therapy for metastatic disease

Patients who have received less therapy, experienced longer disease free interval since initial diagnosis, soft
tissue or bone metastasis, fewer symptoms, better performance status are more likely to experience longer
[10]
survival

Patients whose tumor is negative for ER/PR, HER receptors referred to as triple negative breast cancers have
relatively poorer prognoses.

Metachronous breast cancer have more frequent relapse rate and distant metastasis and better response to
chemotherapy in case of relapse as compared to synchronous breast cancer .

Management of MBC
MBC is considered as incurable disease and therefore treatment is mainly palliative. Systemic therapy is the
treatment of choice and removal of metastatic lesion is suggested only in selected patients .
A treatment goal in patients with MBC includes:
Prolongation of life
Control of tumor burden
Reduction in cancer related symptoms or complication
Improvement of quality of life and function

119
Various treatment options are:

1. Endocrine therapy
Patients with hormone receptor status positive tumors with minimal symptoms and limited visceral involvement
are candidates for initial treatment with endocrine therapy alone. ASCO guidelines suggest that Endocrine
therapy should be offered as the standard first line treatment for patients with hormone receptor positive MBC,
except in cases of immediate life threatening disease or when patient has developed resistance to endocrine
therapy. Sequential single agent chemotherapy rather than combination therapy is preferred, however
combination regimen must be considered for immediate life threatening disease as metastatic disease can
progress rapidly if there is no response to a single agent. No single agent has demonstrated superiority in
treatment of MBC and treatment selection must be based on previous therapy, differential toxicity, co- morbid
[12]
conditions and patients preference. First line Endocrine therapy is associated with 8-12 months of tumor
control. TAMOXIFEN is the standard endocrine therapy for hormone receptor positive tumors and causes
[10]
estrogen suppression and achieve response rate of 50% in ER positive MBC. Tamoxifen flare can occur in 5-
10% of the patients within days or weeks of therapy; characterized by intensification of bone pain, transient tumor
progression, hypocalcaemia, and must be distinguished from over tumor progression. It usually subsides in 4-6
weeks. Side effect of Tamoxifen includes hot flashes, increased risk of thrombosis , uterine bleeding,
endometrial cancer. For pre-menopausal women with metastatic disease, initial treatment is ovarian
suppression with selective ER modulator Tamoxifen.

Endocrine Therapy in Pre-Menopausal Women

1. Selective ER modulator : Tamoxifen
2. Ovarian ablation or suppression
LHRH agonist- Goserelin , Leuprolide
Progestin- Megestrol acetate
Androgen- Fluoxy mesterone
High dose estrogen Ethinyl estradiol
Surgical or Radio therapeutic Oophorectomy

Endocrine Therapy in Post-Menopausal Women

Options include-
1. Non steroidal Aromatase inhibitor- Anastrozole , Letrozole
2. Steroidal Aromatase inhibitor Exemestane
3. Selective ER modulator Tamoxifen
4. ER down Regulator Anti-Estrogen ; Fulvestrant
5. Progestin Megestrol acetate
6. High dose Estrogen Ethinyl estradiol

Post menopausal women with MBC , who are anti-estrogen nave OR who are on > 1 year of estrogen therapy,
options includes - Aromatase inhibitors , Selective ER modulators, ER down regulator (Fulvestrant ) . Whereas
post menopausal women with MBC , who have received prior Tamoxifen therapy in an adjuvant settings OR are
within 1 year of anti estrogen therapy , Aromatase inhibitors are the preferred options.

Resistance to endocrine therapy can develop in women with hormone receptor positive status. This is due to
activation of mammalian target of rapamycin ie; mTOR signal transduction pathway. In such cases Aromatase
Inhibitors AIs + inhibitors of mTOR (eg; Everolimus) are recommended.

Both pre and post menopausal women with hormone responsive breast cancer, benefit from sequential use of
endocrine therapy at disease progression.

2. Chemotherapy in MBC
Cytotoxic chemotherapy is the mainstay of treatment for MBC irrespective of hormone receptor status. It can
be used in women with hormone receptor status negative tumors, with symptomatic visceral metastasis or
hormone receptor status positive tumors refractory to endocrine therapy.
Due to its substantial side effects; the benefit must be weighed against the toxicities and treatment must be
interrupted in patients who shows significant response or palliation and reintroduced when there is tumor
progression or recrudescence of symptoms.

There is no optimal single first line Chemotherapy and treatment option must be based on efficacy of prior
treatment, risk of life threatening disease, relative toxicity, performance status co morbid conditions and patients
preference.

Recommendations by ASCO for Chemotherapy and Targeted therapy

Sequential single agent CT is preferred in a MBC, as it facilitates better understanding of the response and
less toxicity. However combination regimen is considered for patients with immediate life threatening disease
as the metastatic disease progresses rapidly if there is no response.

120
 ERIBULIN a mitotic spindle inhibitor is used in MBC who have previously received at least 2
Chemotherapy regimen (Anthracyclines and taxanes)
In PHASE III RCT Addition of BEVACIZUMAB with PACLITAXEL with has demonstrated improved
[13]
response rate and progression free survival rate (PFS ) but not overall survival (O.S)
However the unique side effect of Bevacizumab is - increased risk of hypertension and thromboembolism
and there is no specific marker for tumors that are likely to benefit from antiangiogenic therapy

Single Agents
Anthracyclines Doxorubicin, Epirubicin
Taxanes Paclitaxel , Docetaxel
Anti-metabolites (5FU )- Capecitabine , Gemcitabine
Mitotic spindle inhibitors Eribulin , Vinorelbine
Platinum salts- Cisplatin, Carboplatin
Others Cyclophosphamide , Etoposide

Combination Regimen
CAF Cyclophosphamide ,Adriamycin, 5 FU
FEC- 5FU , Epirubicin, Cyclophosphamide
AC Adriamycin, Cyclophosphamide
EC- Epirubicin , Cyclophosphamide
CMF- Cyclophosphamide, Methotrexate , 5 FU
GT- Gemcitabine , Paclitaxel
Paxlitaxel, Bevacixumab.

3. Anti-HER2 therapy
It is a treatment targeted against Human epidermal growth factor 2 receptor, a protein that is over expressed by
certain type of aggressive breast tumors (20-25%).

The NCCN panel recommends selecting patients with HER -2 targeted therapies if the tumors are positive for
HER-2 by ISH (in situ hybridization) or 3+ve by ICH (immunohistochemistry)

TRASTUZUMAB is used as first line anti-HER2 therapy. When added to chemotherapy in HER2- positive
tumors, trastuzumab showed synergistic effect and improve response rate 7 times to progression as well as over
all survival rate.

Cardiomyopathy is a well known side effect of trastuzumab, hence concurrent administration with Anthracyclines
must be avoided.

LAPATINIB - second line anti-her 2 therapy for patient with tumor progressing despite Trastuzumab therapy. It is
a dual kinase inhibitor that targets both HER2 and EGFR tyrosine kinase.

PERTUZUMAB another humanized monoclonal antibody that binds to a domain of the HER2 saperately from
trastuzumab . it is assumed to overcome the limitations of trastuzumab

Preferred First Line Regimen for HER 2 positive tumors

Pertuzumab + Trastuzumab+ Docetaxel
Pertuzumab +Trastuzumab + Paclitaxel
Other regimen- Trastuzumab +Paclitaxel +Carboplatin
Trastuzumab +Docetaxel
Trastuzumab +Capecitabine

Regimen for Trastuzumab Exposed HER 2 Positive Diseases

Ado- Trastuzumab Emtansine (T-DM1 )
Lapatinib +Capecitabine
Lapatinib +Trastuzumab

Role of Surgery and Radiotherapy in MBC with Intact Primary

Role of surgery in MBC is very limited. Women with MBC with intact primary tumor are primarily treated with
systemic therapy and surgery is considered only for palliation of symptoms or complication such as ; fungation ,
skin ulceration, bleeding etc and done only when complete local clearance of the tumor may be obtained and
other sites of disease are not immediately life threatening. Radiation therapy is an alternative option.

Several studies suggested that surgical removal of primary breast cancer in MBC actually improves survival if
[14]
performed with negative surgical margins, esp. in patients with only bone metastasis. It was suggested that
the total tumor burden play a central role in survival and that the primary tumor can be considered as a another
metastatic site, therefore removal of the primary tumor could be considered as a part of multi modality strategy to

121
prevent further metastasizing of cancer cells. This is consistent with the recent studies that suggest a strong
correlation between the level of circulating tumor cells CTCs and prognosis of MBC.

However in a clinical trial presented at 2013 San Antonio Breast cancer Symposium, It was suggested that ,
patient with MBC may not benefit from surgery and radiation after chemotherapy ; as such treatment may
facilitate growth of metastatic disease and concluded that such treatment may be reserved only for palliation of
[15]
symptoms.

MANAGEMENT OF SITE SPECIFIC METASTASIS

Bone Metastasis
Skeletal related events like pathological fracture, bone pain, cord compression, hypercalcemia can occur in a
MBC with bone metastasis.

According to NCCN guidelines,

Iv BIPHOSPHONATE Pamidronate 90 mg or Zolidronic acid 4 mg can be given in combination with oral
Calcium and Vitamin D3 supplementation. If expected survival is 3 months or longer and Serum Creatinine is
below 3.0 mg/dl and can be given in lytic bone metastasis in addition to Chemotherapy OR Endocrine therapy
A monoclonal activity against RANK ligand of osteoclast; Denosumab -120 mg can also be given every 4 week.
While those with impending bone fracture or pathological fracture surgical stabilization or external beam RT
may be required

Brain Metastasis
nd
Breast cancer is the 2 most common source of brain metastasis being preceeded only by lung cancer with an
incidence of approx 10-15% among patients with MBC.
Data from a large population study shows that brain is most frequently the first site of relapse in patient treated
[16]
with Trastuzumab in HER2 receptor positive tumors, whether in adjuvant or metastatic settings. Assumed to
be due to the role of chemokines- CXCR4 , which is found to be up regulated in the HER2 receptor positive
tumors and have emerged as a main challenge affecting the morbidity and mortality of patient with HER2
receptor positive MBC.

WBRT remains the standard of care and is associated with short term tumor regression and clinical improvement
in MBC with brain metastasis with survival ranging from 3-6 months
Combining WBRT + Trastuzumab has a good response rate.
In patients refractory to WBRT + Trastuzumab, LAPATINIB + CAPECITABINE can be given; however, pulmonary
[17]
embolism could be a dose limiting toxicity
Stereotatic Radio surgery (SRS) - is a minimally invasive and well tolerated by patients who are not surgical
candidate. It is emerging as a new modality of management for brain metastasis so that patient can be spared
from upfront WBRT whenever feasible.

Breast cancer liver metastasis (BCLM)-

Radiofrequency ablation (RFA)
Hepatic resection , if Ro resection is feasible and no extra hepatic metastasis present
Regional Chemotherapy
Regional Radiotherapy

Pulmonary metastasis
VATS or conventional Resection

Malignant pleural effusion-

VATS and Talcum pleurodesis
Chemical pleurodesis- Talcum slurry, bleomycin, mitoxantrone, povidone iodine
Continuous pleural drainage
Local antibody therapy- Catumaxomab

Soft tissue metastasis

Local Radiotherapy

Lepto-meningeal disease
WBRT / Intrathecal chemotherapy with methotrexate or cytarabine.

MONITORING OF METASTATIC DISEASE

Monitoring the treatment of MBC involves a wide array of assessments. Determine the effectiveness of the
treatment and the acceptability of toxicity. It takes into account
complete clinical examination

122
 laboratory tests
radiographic imaging
functional imaging
tumor biomarkers

Results of these assessments are classified as Response; continued response to treatment; stable disease;
uncertainty regarding disease status; or progression of disease.

The NCCN Panel recommends widely accepted criteria such as RECIST or WHO criteria for reporting response,
stability, and progression of disease. Frequency of monitoring can be reduced in patients who have long term
[18]
stable disease.

References

1. American Cancer Society; cancer facts and figures 2015 @ 2015 American Cancer Society.Inc
2. ICMR, National Cancer Registry Programme. Three year report of population based cancer registry PBCR; 2009-
2011
National cancer registry programme (ICMR 2013, Bangalore)
3. Principles and practice of Oncology; DaVita Hellman and Rosenbergs. Ninth edition
4. Bernard Marty C, Cardoso F, Piccart MJ. Facts and controversies in systemic treatment of MBC. Oncologist 2004;
9: 617-632.
5. Elisabetta Rapiti, Helena M, George V. Complete excision of primary tumor improves survival in patient with
Metastatic breast cancer at diagnosis. J.Clin Oncol 24; 2743-2749@ 2006 by American society of clin oncol.
6. Rinaa S.Punglia, M.P.H. Monica Morrow, Eric P. Winer. N.Engl Journal of medicine 2007; 356: 2399-2405.
7. J. Formos ; Med asso 2004;103(8): 579-598.
8. Frank et al. Int J.Radiation Oncology. Biol. phy 2008. Future oncology 2015; 11
9. ASCO post 2013. San Antonio Breast cancer symposium
10. Devita , Hellman and Rosenbergs . Principle and practice of oncology. Ninth edition
11. Clinicopathological features in bilateral breast cancer . Asian pac J Cancer prev 2012; 13: 4571-4575.
12. Chemotherapy and targeted therapy for women with HER2 negative metastatic breast cancer . American society
of clinical oncology. Ann H. Partridge, R Bryan Rumble; Lisa A Carey
13. Kathy muler; MD ; Mous Wang PhD, Julie Gralow ,MD. Paclitaxel plus Bevacizumab versus Paclitaxel alone for
MBC N.Eng J of Med. 2007; 357: 2666-2676.
14. Elisabetta Rapiti ,Helena M,George Vlastos. Complete excision of primary breast tumor improves survival in
patient with MBC at diagnosis. J Clin.Oncol.24;2743-2749@ 2006 ,ASCO
15. Surgical removal of primary tumor and axillary LN in women with MBC at firs presentation. A RCT. Rajendra
Badwe, MD. @2013 San Antonio Breast cancer syumposium.
16. Yin W, Jiang Y, Shen Z, Shaw Z. Trastuzumab in the adjuvant treatment of HER2 positive early breast cancer. A
meta analysis of RCT. 2011
17. Capecitabine therapy of CNS metastasis form breast cancer. J.Neurooncol. 2007; 85(2): 223-227.
18. NCCN Guidelines ; inc .2015.

Role of Radiotherapy in breast cancer

Kishore Singh

With advent of multidisciplinary approach for the management of breast cancer, the survival has gone up, the
local recurrence and distant metastasis gone down. Surgery, radiotherapy, chemotherapy, hormone therapy are
the different modalities used for treatment. In the past Keynes G practiced BCS in 1937. Mc Whirter changed it to
Total Mastectomy & RT in 1955. Now there is again trend of BCS & RT (NIH Consensus 1992). BCS & RT
together is called as Breast conservation therapy. Recent met analysis at 20 year with PORT for early stage
rd
disease showed 2/3 decrease in LR with clear effect on total mortality (all node positives, but degree of benefit
for 1-3 nodes positive is less clear).

Now the question arises, as the breast cancer is a systemic disease, what is the need for a local treatment
modality like RT after surgery? Answer given by a landmark EBCTCG trial 2000, initial local control obtained by
RT increase breast cancer specific and overall survival rates (Lancet 2005; 366:2087-2106). Among the 25 000
women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks
were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were
446% versus 495% (absolute reduction 50%, SE 08, 2p_000001). Surgery is good for removal of gross
disease but leaves behind subclinical disease, whereas radiotherapy is superior in controlling the subclinical
disease. Therefore combining two results in improved local control and reflected in better overall survival rates.

Now the next important question is who are the patient groups to be subjected to adjuvant radiotherapy? There is
consensus that PMRT should be considered when risk of LRF is greater than 20%, such as for patients with four

123
or more positive axillary lymph nodes, primary tumour size 5 cm or more (T3), T4 disease and positive/very close
margin. Some studies suggest other factors as risks of local recurrence such as age less than 40 years,
histological grade 3 tumours, presence of lymphovascular invasion, less than 6 nodes removed at axillary
dissection and significant nodal extracapsular spread (> 2 mm). The merit of PMRT, however, in this group of
patients is not known. When breast conservation therapy is planned, RT to tumour bed is mandatory irrespective
of tumour size.

RT is to be started within 8 months of surgery and within 6 weeks of last chemotherapy cycle. To be started early
if high risk of local recurrence or microscopic residual disease, or else it can be started after the completion of
adjuvant chemotherapy.

Table- 1: Classification of risk groups.

Low risk ER / PR ve
& N0
& T1
&G1
& Age >35 years
& LVI 0
& Her 2 neu Negative
Intermediate risk ER / PR + ve
& N0
& T >1
&G2-3
& Age <35 years
& N + (1-3 LN)
& Her 2 neu Negative
High risk 1. N + (>3 LN)
Or
2. N + (1-3 LN) & LVI +
Or
3. Her 2 neu Positive

It can be delivered using conventional or conformal (IMRT, 3D- CRT) techniques. RT is contraindicated if there is
past history of chest wall irradiation, collagen vascular disease and during pregnancy.

Newer technique of RT for early breast cancer

RT substantially reduces the risk of local recurrence following breast conserving surgery.

PARTIAL BREAST IRRADIATION (PBI) - 75% of recurrences appear in 1st 5 yrs at or near original tumor site
(represent original tumor). Usually done by shorter treatment time with high dose per fraction (Hypofractionation);
often called as Accelerated Partial Breast Irradiation (APBI)

Advantage Compared to Whole Breast Irradiation: Accelerated treatment (Shorter Single day to 1 week), better
combination with chemotherapy and decrease overall cost of therapy; reduced treatment volume might reduce
risk of long term complications.

ASTRO's Accelerated Partial-Breast Irradiation Consensus Statement was used to classify patients with invasive
breast cancer as suitable for brachytherapy (34.7%), cautionary (17.6%), or unsuitable (35.2%); 12.5% of
patients were unclassified.
Basis of APBI:
1. New disease development is not controlled by whole breast RT, PORT impact at the site of initial
disease only
2. Documented under utilization of BCT
3. Time, cost and convenience of BCT
4. Potentially Acute and Chronic Toxicity
5. QOL
6. Eliminate schedule problem with CT
7. Potential to outcome ( delays to local therapy)

Technique Aim of coverage tumor bed with 1cm margin

TM TM
- PBI (Brachytherapy) through SAVI , Contura
TM
- MammoSite Radiation therapy system (RTS)
TM
- TARGIT IORT
- Protons

124
Cosmetic: Good to excellent >80%; decline with time in first 3 yrs, then stable until 7 yrs. Outcome is related to
tumor size, location, breast size, body weight, dose and tech of RT and extent of resection. (Recht A. Oncology
1999; 4:23-30).

Poor Cosmetic outcome if :

Small breast and large tumor
Associated with nipple discharge or sub capsular location
Multi centric
Extensive micro calcification on mammography - LF
Coexisting medical condition Collagen vascular disease
Unterminated pregnancy
Extensive Intraductal component 35% failure, these patients have significant residual disease.
Age young (<35yrs), associated with recurrence 21% Vs 10%

ASTRO- Choosing wisely

Dont initiate whole breast radiotherapy as a part of breast conservation therapy in women age 50 with early-
stage invasive breast cancer without considering shorter treatment schedules.

Conclusion
Radiotherapy is an integral modality for treatment of breast cancer. May it be an adjuvant modality still its role
cant be underestimated. So it is necessary to understand the indication and timings of radiotherapy during the
course of breast cancer treatment.

Approach to a patient with breast disease

Geeta Kadayaprath

Clinical
The commonest presentation of a patient with breast disease, accounting for more than 50% of all complaints
pertaining to the breast, is a lump. While most of these lumps are likely to be benign, it is the responsibility of the
clinician to allay the fears of the patient and be certain that the lump is not malignant. The presence of a lump
should never be taken lightly if the patient is young or if the lump feels right or if there is no family history or is
found in a male patient.

The dictum should always be Triple Assessment. No effort should be spared to correlate clinical, radiological
and pathological findings to finally arrive at a diagnosis.

Besides a lump, the other complaints could be pain in the breast, nipple discharge, palpable lump in the armpit,
nipple retraction or changes in the skin of the breast etc.

One could also dwell upon the menstrual history, previous surgeries, hormonal use, family history, treatment
history etc. for additional clues

History
A detailed history followed by thorough examination is an important exercise and puts one on the right path to
establishing a diagnosis. One can use a template, such as shown below, to get a comprehensive history without
missing out on vital points

Physical Examination
A complete clinical breast examination (CBE) includes an assessment of both breasts and the chest, axillae, and
regional lymphatics. In premenopausal women, CBE is best done a week after menses, when breast tissue is
least engorged. With the patient in an upright position, the breasts are inspected, looking for asymmetry, nipple
discharge, obvious masses, and skin changes, such as dimpling, inflammation, rashes, and unilateral nipple
.
retraction or inversion

With the patient supine and one arm raised, palpate the breast tissue on the raised-arm side in the superficial,
intermediate, and deep tissue planes (i.e., the triple touch technique); axilla; supraclavicular area; neck; and
chest wall, assessing the size, texture, and location of any masses.It is important to note the size of the masses
for future reference. A pictoral record is always helpful.Now,inspect the areola-nipple complex for any discharge.
CBE sensitivity can be improved by longer duration (i.e., five to 10 minutes) and increased precision (i.e., using a
systematic pattern, varying palpation pressure, and using three finger pads and circular motions)
Benign masses generally cause no skin change and are smooth, soft to firm, and mobile, with well-defined
margins.

125
 HISTORY AND EXAMINATION Performa

NAME: AGE/SEX: ID NO:

Lump in the breast Y/N Right/Left Duration- days/ weeks/ months/ years

Discharge from the nipple Y/N Spontaneous/ Expressed Colour- clear/ greenish/ milky/ bloody

Skin changes Y/N Discolouration /Dimpling/ Tethering/ Peau-de-orange/redness

Lump in the armpit Y/N Lump in the neck Y/N

Loss of appetite Y/N Loss of weight Y/N

Menarche - years

LMP - __/__/__ Premenopausal/ Perimenopausal /Postmenopausal

Married/ single

Age at first childbirth No. of children

Breast fed 1) Y/N Duration-

2) Y/N Duration-
3) Y/N Duration-

Use of oral contraceptives/ hormonal therapy Y/N

Previous surgery in breast Y/N Biopsy/ HPE- Y/N

Description-----------------------

Family history of breast or ovarian cancer or any other cancer Y/N If Y, then specify

H/O hypertension/ DM/ COPD/ Asthma/ thyroid disorder/CAD controlled/ uncontrolled

Treatment

Other significant history

Investigations done outside-

Diffuse, symmetric thickening, which is common in the upper outer quadrants, may indicate fibro-cystic changes.
Malignant masses generally are hard, immobile, and fixed to surrounding skin and soft tissue, with poorly defined
or irregular margins.However, mobile or nonfixed masses can be cancerous.

Infections such as mastitis and cellulitis tend to be erythematous, tender, and warm to the touch; they may be
more circumscribed if an abscess has formed. Similar symptoms may occur in patients with inflammatory breast
cancer. Therefore, caution should be used in assessing patients with suspected breast infections.
Digital palpation of the breast is effective in detecting masses and can help determine whether a mass is benign
or malignant.CBE can detect up to 44 percent of cancers, up to 29 percent of which would not have been
detected by mammography.Despite its accuracy, CBE alone is not adequate for definitive diagnosis of breast
cancer. Further evaluation, including follow-up examinations, imaging, and tissue sampling, is required in all
patients with breast masses

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 EXAMINATION

Right Breast Left Breast

Size of the lump-------------cms Size of the lump-------------cms

Distance from areolar margin-------------------cms Distance from areolar margin-------------------cms

Quadrant- UOQ/UIQ/LIQ/LOQ Quadrant- UOQ/UIQ/LIQ/LOQ

Skin-- dimpling/ tethering/ ulceration/ peau de orange/ Skin-- dimpling/ tethering/ ulceration/ peau de
redness orange/ redness

Fixity to muscle- Y/N Fixity to muscle- Y/N

Fixity to chest wall Y/N Fixity to chest wall Y/N

Nipple areola complex---Normal/ eczematous/ Nipple areola complex---Normal/ eczematous/

retracted/ ulcerated/ discharge retracted/ ulcerated/ discharge

Scar of previous surgery- Y/N Scar of previous surgery- Y/N

Axilla Lymph nodes present/ absent Axilla Lymph nodes present/ absent
Size- Size-
Number Number
Fixity Fixity

Supraclavicular lymphadenopathy-present/ absent Supraclavicular lymphadenopathy-present/ absent

Impression- Benign breast disease/ carcinoma Impression- Benign breast disease/ carcinoma
breast breast

Performance Score

GENERAL PHYSICAL EXAMINATION

SYSTEMIC EXAMINATION Respiratory System

CVS
CNS
Abdomen, P/V, P/R

In certain situations where there is no well- defined lump, only a vague nodularity or thickening of breast tissue,
one must compare it with the opposite side. If one is not happy with the findings and is unable to make much
headway after investigations, it may be worthwhile to do the next possible investigation or call the patient back for
an early follow up after 2-3 months.

Symptoms other than a lump

Mastalgia- Mastalgia is a very common presentation in the clinic. Premenstrual aggravation is usual. 70% of
mastalgias respond to reassurance alone while 10% of the remaining 30% require medical intervention.
Mastalgia as the first presenting symptom of cancer is rare with only 5-8% doing so.

Nipple Discharge- A single duct, spontaneous, serous or sanguineous, persistent discharge needs to be
investigated. In a young patient less than 30 years with no radiological or cytological proof, a period of
observation of 4-6 weeks may be undertaken. In women over the age the age of 45 years, it is best to go ahead
with surgery- microdochectomy or major duct excision.

Mastitis- Mastitis may present as a lump or diffuse area of erythema and edema and will have to be
differentiated from an inflammatory carcinoma. After thorough clinical examination, radiological investigations and
core biopsy, one will need to distinguish between acute mastitis, chronic granulomatous and non granulomatous
mastitis. The treatment for each situation is very different.

Special Situations- In patients presenting with repeated excoriation of unilateral nipple or areola with discharge
from the surface, healing and a repeat of such symptoms should be evaluated for Pagets Disease.

127
In young women with lumps, which have shown a significant increase in size, should be evaluated with a core
biopsy to rule out phyllodes tumour. Many a time, a core biopsy may also not be able to provide a definite
answer, wherein one should go ahead and excise the lump with adequate margins.

TRIPLE ASSESSMENT

Involves subjecting patient to clinical examination, radiological and pathology.

Radiology primarily involves mammograms, ultrasound of the breast and MR mammogram while pathology
involves cytopathology (FNAC) or histopathology (core biopsy or incisional biopsy or excisional biopsy).
.
The triple test is the combination of results from CBE, imaging, and tissue sampling When the three assessments
are performed adequately and produce concordant results, the triple test diagnostic accuracy approaches 100
.
percent Discordant results or results that cannot be evaluated may indicate the need for excisional biopsy.

The Triple Test Score (TTS) was developed to help physicians interpret discordant triple test results.A three-point
scale is used to score each component of the triple test (1 = benign, 2 = suspicious, 3 = malignant). A TTS of 3 or
4 is consistent with a benign lesion; a TTS of 6 or more indicates possible malignancy that may require surgical
intervention. Excisional biopsy is recommended in patients with a TTS of 5 to obtain a definitive diagnosis.

References
1. Campbell HS, Fletcher SW, Pilgrim CA, Morgan TM, Lin S. Improving physicians and nurses clinical breast
examination: a randomized controlled trial. Am J Prev Med. 1991;7:18.
2. Baines CJ, Miller AB. Mammography versus clinical examination of the breasts. J Natl Cancer Inst
Monogr.1997;(22):1259.
3. Kolb TM, Lichy J, Newhouse JH. Comparison of the performance of screening mammography, physical
examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient
evaluations. Radiology. 2002;225:16575.

Radiology in Breast Disease

Richa Bansal

Mammography
All women 30 years old or older presenting with a breast mass should have mammography performed. Patients
who present with a palpable mass should undergo a diagnostic mammogram in which additional views of the
area in question are performed. Spot compression views and magnification views for concomitant calcifications
are recommended. The lump on the mammogram should be categorised as benign or suspicious of malignancy
according to the BIRADS descriptors and further imaging with ultrasound should be performed.

A BI-RADS designation of 4c or 5 should alert the pathologist that a malignant diagnosis is strongly suspected
and that further evaluation of the specimen (and possible rebiopsy) is needed if the biopsy is initially interpreted
as benign)

Mammographic features of breast cancer There are two general categories of mammographic findings
suggestive of a breast cancer: soft tissue masses and clustered microcalcifications.

Soft tissue mass/architectural distortion The most specific mammographic feature of malignancy is a
spiculated soft tissue mass; Approximately one-third of noncalcified cancers appear as spiculated masses, 25
percent as irregularly outlined masses, 25 percent as less specific round, oval or lobulated masses, less than 10
percent as well-defined round, oval, or lobulated masses, and 5 percent as areas of architectural distortion of
dense tissue without an obvious mass.

Clustered microcalcifications Clustered microcalcifications are calcium particles of various size and shape
measuring between 0.1 to 1 mm in diameter and numbering more than four to five per cubic centimeter.
Microcalcifications are seen in approximately 60 percent of cancers detected mammographically . Histologically,
these represent intraductal calcifications in areas of necrotic tumor or calcifications within mucin-secreting tumors
such as the cribriform or micropapillary subtype of intraductal cancer.

Calcifications that are not suspicious for malignancy and considered benign include vascular and skin
calcifications, rim-like calcifications, large coarse calcifications, and smooth round or oval calcifications.

Thus, mammographic findings such as masses and calcifications can be stratified by suspicion for malignancy,
and the BI-RADS 4a, 4b, and 4c categories are helpful in alerting the referring physicians, the pathologists, and
surgeons to the underlying risk of malignancy.

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 Typical BIRADs 5 lesion on
mammogram

Typical BIRADs 2 lesion on Benign calcifications

mammogram

Suspicious calcifications

129
In typically malignant lesions, attempt should be made to identify multi-focal or multi-centric disease although in
dense glandular breasts it may be a challenge. In such cases MRI helps in identifying the extent of the disease in
the same breast as well assessing the contralateral breast .

In the setting of a palpable breast mass, mammography is 82% to 94% sensitive and 55% to 84% specific for
detecting breast cancer. The sensitivity and specificity of diagnostic mammograms declined with breast density,
younger age, and mammographic examination. Dense breasts can limit the sensitivity of mammography both for
detection of breast cancers and for delineating disease extent. Younger women may present with large tumors
prior to the age at which screening is usually recommended. Accordingly, when women present with a suspicious
new mass, diagnostic mammograms should be part of the initial workup, despite young age or having had a
negative routine screening mammogram.

BIRADS Classification

Ultrasound of the Breast

Ultrasonography is often considered the diagnostic test of choice in patients <30 years old,because the density of
breast tissue in younger women limits the sensitivity of mammography.The false-negative rate for mammography
has been reported as high as 52% in patients <35 years old with a palpable malignant breast mass.In addition,
ultrasound is routinely available in the outpatient setting and is a ready extension of the physical exam.
Ultrasound helps in identifying whether the palpable lesion is cystic or solid. It can also distinguish between
simple or complex cyst architecture.Simple cysts are fluid-filled lesions that present as smooth, round, well-
demarcated, and anechoic and can be kept under follow up in an asymptomatic patient. Complex cysts and solid
lesions require further evaluation as in the algorithm below. Elastography has been proposed as a potential
adjunct to ultrasonography.

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 Complex cyst on Ultrasound

Elastography appearance of
Benign lesion

Elastography appearance of
malignant lesion

Ultrasound Algorithm

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Ultrasonography of the axilla may also be performed to evaluate lymphadenopathy, and abnormal lymph nodes
biopsied.

MRI

Current National Comprehensive Cancer Network (NCCN) guidelines recommend MRI be 'considered' in patients
with newly diagnosed breast cancer to evaluate extent of disease and screen the contralateral breast, especially
in the setting of mammographically occult disease.

Indications of Breast MRI in Diagnosed Cases of Breast Cancer

In patients where the clinical extent of disease is larger than what is appreciated by mammography
(particularly in the setting of dense breasts which lower the sensitivity of mammography).
For invasive cancers that are contiguous to the chest wall and not completely included on mammographic
projections, MRI may be necessary to assess posterior tumor extension and pectoralis fascia or muscle
involvement if that will determine a change in surgical approach or the use of neoadjuvant therapy
For patients with axillary nodal metastases and a clinically occult primary tumor, breast MRI can facilitate the
identification of occult breast cancer
For women with Pagets disease of the breast who have a negative physical examination and mammogram,
breast MRI can define the extent of disease and aid in treatment planning
In women with locally advanced breast cancer who are being considered for upfront (neoadjuvant) systemic
therapy, breast MRI may be used to define the extent of disease, and potential for breast conserving
therapy.
For women with very high risk for contralateral disease (for example, because of an inherited predisposing
condition, or prior chest wall irradiation).
For women who are planning extensive reconstructive surgery, breast MRI may be used to identify occult
contralateral cancers.

Women should be informed of the risks and benefits of preoperative breast MRI. The limits of the accuracy of
MRI should be discussed with patients, so that they understand the need for biopsy of MRI detected lesions
before definitive surgery. Breast MRI should be performed with a dedicated breast coil by expert breast imaging
radiologists in institutions that have the capability to perform MRI guided needle biopsy and/or wire localization of
the findings.

Surgical decisions should not be based on MRI findings alone. MRI findings alone should not be used to change
surgical planning and conversion from breast conservation to mastectomy. All suspicious findings onMRI require
pathologic confirmation.

Newer Imaging Techniques in Breast

Digital mammography
Digital breast tomosynthesis
CAD
Contrast enhanced Mammography
Positron Emission mammography.

References

1. Silverstein MJ, Recht A, Lagios MD, et al. Special report: Consensus conference III. Image-detected breast
cancer: state-of-the-art diagnosis and treatment. J Am Coll Surg 2009; 209:504.
2. Lehman CD, DeMartini W, Anderson BO, Edge SB. Indications for breast MRI in the patient with newly diagnosed
breast cancer. J Natl Compr Canc Netw 2009; 7:193.
3. Warner E, Causer PA, Wong JW, et al. Improvement in DCIS detection rates by MRI over time in a high-risk breast
screening study. Breast J 2011; 17:9.
4. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology.
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on April 01, 2014).

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Algorithm for Imaging of Breast Mass In Women <30 Yrs Age

133
Algorithm for Imaging of Breast Mass in Women > 30 Yrs Age

134
 Biopsy Algorithm of Solid Lesions of Breast

Approach to breast disease: Pathologists Perspective

Anuj Khurana

Diseases of the mammary gland can be broadly classified as

Non neoplastic
Neoplastic (Tumor)

Non neoplastic: Includes

Inflammatory lesions:
Abscess (+/- lactational breast)
Mastitis (infective- bacterial), idiopathic granulomatous/lobular mastitis or secondary to mycobacterial
infection)

The nonneoplastic non-inflammatory lesions:

Fat necrosis
Duct ectasia
Spectrum of fibrocystic disease and fibroadenomatoid mastopathy.

Neoplastic conditions:
Benign clinical course
Fibroadenoma
Phyllodes (benign)

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 Nipple adenoma
Intraductal papilloma

Intermediate/Indeterminate
Borderline Phyllodes
Stromal sarcomas

Malignant
Carcinoma in situ (DCIS/LCIS)
Infiltrating Carcinoma (Most common) including the various subtypes
Pure /Primary sarcomas like malignant phyllodes, spindle sarcomas.

Based on clinical assessment and radiological evaluation patients with breast lump undergo various diagnostic
procedures, which are subsequently evaluated by a pathologist.

Pathological evaluation of a breast lump:

Cytological Diagnosis
Nipple fluid cytology: Presence / Absence of atypical cells
Fine Needle Aspiration (FNA)

Cytological classification of breast aspirates:

Categorised from C1 to C5
C1: Inadequate
C2: Benign
C3: Atypical; probably benign
C4: Suspicious for malignancy
C5: Malignant

Many a times, FNA cytology findings dictate the subsequent surgical procedure.

Intraoperative Evaluation by Frozen Section technique

Depending upon the degree of clinical suspicion, radiological findings and initial cytological or histopathological
results, the patient undergoes surgical procedure and specimen is sent for histopathogical examination; which
eventually decides the future management. In a clinically suspicious lesion with ambiguous patology, frozen
section technique may be adopted to provide intraoperative diagnosis and subsequent management

Histopathological Diagnosis
Most of the surgical specimens received for pathological evaluation:
I. Needle core biopsies

II. Excision specimens:

1) Unoriented (done for benign lesions like fibroadenoma/fibrocystic disease)

2) Oriented (marked with sutures/ink/J wire localised)

-Phyllodes
-Cytologically inconclusive but radiologically suspicious lesion (BIRAD III/IV)
-Suspicious micro calcification on routine mammography

III. Wide Local excision/ Breast Conservative Surgery

(Margin assessment +/- Primary diagnosis)- Intraoperative assessment

IV. Modified Radical Mastectomy

(+/- Sentinal node biopsy)

Specimen Handling and processing

Irrespective of nature of surgical specimen, adequate tissue fixation and proper tissue processing are imperative
for optimal pathological reporting

Importance of Tissue fixation.

Improper fixation can lead to:
- Suboptimal tissue details
- Erroneous interpretation of hormonal receptors.

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Contents of the histopathology report:

Gross findings
Core needle biopsy:
Number and size of the submitted cores
Consideration of small size of the specimen: Inked by a special dye (So as to be identified throughout the journey
from fixation till sectioning

Unoriented specimens:
Three dimensional measurements
Comment on:
- Integrity (Single piece or multifragmented)
- Outer surface (Capsulated/Unencapsulated)

Oriented specimen: (Including WLE/ BCS)

Three dimensional measurements
Keeping in view of the Side (Left /Right): The prosector re-orients the specimen w.r.t sutures.
Comment on overlying skin (if present)
Protocol followed: Outer / Capsular surface is inked

The cut section findings are recorded:

- Presence of Lesion/ tumor
- Appearance
- Size
- Margins of lesion: Infiltrative/ Circumscribed
- Gross distances from margins are recorded.

Modified radical mastectomies:

- Three dimensional measurements
- Skin dimensions
- Axillary tissue: Size
- Appearance of skin: Any cutaneous changes like peau d orange, fungation or any previous scar/ suture.
- Nipple: Retracted/ Unremarkable
- The posterior surface/ base is inked ( formed by fascia or by pectoralis muscle)
- The inked surface is sliced serially at a gap of 1.0cm each.
Advantages of slicing:
- Adequate fixation of the tissue.
- Identification of multifocal lesions apart from the main tumor

Tumor is identified {Size ( pT size), lesional margins}

Distance from the inked base is noted.

Representative sections taken:

Tumor (Number of sections depending upon the size of tumor)
Surrounding breast
Nipple
Overlying skin
Base /Inked posterior surface
Axillary nodes:
Size of the largest lymphnode (Grossly involved/not involved)

Microscopic Findings:
Histological type:
Conventional IDC
Special histological subtypes
Lobular/ Mucinous/Tubular/ Medullary/ Metaplastic

Histological Grade:
Based on Nottingham histological grade (Based on modified Scarff Bloom Richardson grading) - I, II or
III
Three parameters
Tubule formation
Nuclear pleomorphism
Mitotic count

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Other Parameters:
Presence or absence of DCIS
Grade/ Pattern of DCIS
Concept of EIC
Lymphovascular Invasion
Nipple Areola- Involvement by pagetoid spread or not
Overlying skin: Involved
Deep surgical margin: Status
If post therapy:
Presence or absence of residual tumor
Microscopic largest contiguous focus (determines ypT size)

Axillary Nodes:
Number
Number of positive nodes
Extracapsular extension: Present/ Absent
Largest involved node
Concept of isolated tumor cells/ micrometastases.

Final Report should include Pathological TNM stage

Immunohistochemistry (Theranostic tool)

-ER PR profiling (Allred scoring)
-Her 2 neu status (As per ASCO/CAP guidelines)
-Ki67 proliferation index

Other uses of IHC:

Identification of special histological subtypes (e.g lobular, metaplastic)
Detection of low volume disease /residual disease or isolated tumor cells.

Incorporate Her 2 neu by FISH ( if IHC for Her2 was borderline)

Summary and Recommendations

The majority of breast cancers are diagnosed as a result of an abnormal mammogram, but the majority of
mammographic findings represent benign tissue.
Triple assessment is the cornerstone to diagnosing breast disease especially malignancies
While FNAC can provide the diagnosis in a large majority, it is recommended to go for an ultrasound guided
core biopsy to improve the accuracy as well as distinguish between invasive carcinoma and DCIS as also for
receptor studies prior to neoadjuvant chemotherapy
Cystic lesions that resolve after aspiration do not need to be evaluated further unless they recur
A clinically suspicious mass should be biopsied, regardless of imaging findings.
Women who have an abnormal screening mammogram need further diagnostic evaluation with special views
and/or targeted ultrasonography to determine the need for tissue sampling or biopsy.
The American College of Radiology (ACR) BI-RADS (Breast Imaging Reporting and Data System) final
diagnostic assessment categories indicate the relative likelihood of a normal, benign, or malignant diagnosis
and standardize both the reporting of mammographic findings and the recommendations for further
management.
Ultrasound (US) examination of the breast is used to differentiate between solid and cystic masses and to
provide guidance for interventional procedures.
Breast MRI is highly sensitive, and can identify foci of cancer that are not evident on physical examination,
mammogram, or ultrasound. Although breast MRI is not recommended as a routine component of the
diagnostic evaluation of breast cancer but it should be considered in above mentioned circumstances.
Suspicious lesions seen on MRI must be biopsied to confirm diagnosis before planning definitive surgery.
Diagnostic algorithms can provide useful guidelines for the work up of a suspicious finding on breast imaging
or breast examination.
In the patient with a suspicious mammographic abnormality or palpable breast mass, the obligatory
diagnostic technique is biopsy which should preferably be image guided.
Excisional biopsies should be performed on lesions, which are clinically suspicious and ambiguous on
imaging, FNA or core biopsy

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 Hand Infections

Jainendra K. Arora

Introduction
Closed-space hand infections have been considered traditionally as an important concern and have been treated
as an emergency. Despite modern diagnostic methods, surgical treatment advances and the evolution of newer
antibiotics, hand infections remain a therapeutic challenge. Even those authors advocating an evident decrease
in the ratio of hand infections, underline the necessity of treatment of infected hands to be treated by experienced
staff.

Soft tissue anatomy of the hand: considerations relevant to infection

The differences between the palmar and dorsal structures may explain the different pathways of extension and
the different clinical signs of infection between the two sides of the hand. The palmar skin is thicker than the
dorsal and is anchored to the underlying structures. It contains many sweat glands but no hair follicles or
sebaceous glands, whereas the tough palmar fascia represents a thick and resistant fibrous tissue layer. Both
skin and fascia hinder the horizontal spread of pus and even edema to the palm. Pus is rather oriented to the
deeper palmar structures while edema is always more prominent at the dorsum of the hand. In the deeper
structures of the hand the anatomic relationships are established, but variations cannot be excluded.

Pathways of pus spread

The true anatomic communications represent pathways of decreased resistance for the spreading pus However,
in the late stages of purulent infections direct spread into the surrounding tissues through liquefactive necrosis is
anticipated.

Table 1: Pathways of pus spread.

From Through To
Index flexor tendon sheath 1. Proximal edge Thenar space (vice versa)
2. Lubrical channel
Middle and ring flexor tendon 1. Proximal edge Midpalmar space (vice versa)
sheath
2. Lubrical channel
Web space Lubrical channel Deep palmar spaces (vice versa)
Flexor policis longus tendon Proximal edge Radial bursa (vice versa)
sheath
Small finger flexor tendon sheath 1. Proximal edge 1. Ulnar bursa (vice vesa)
2. Lubrical channel 2. Midpalmar space
Ulnar bursa 1. Radial edge 1. Midpalmar space (vice versa)
2. Communication distal to the wrist 2. Radial bursa (viceversa)
3. Proximal edge 3. Parona's space of wrist
Radial bursa 1. Ulnar edge 1. Thenar space (vice versa)
2. Proximal edge 2. Parona's space of wrist
Hand dorsal subaponeurotic Narrow connection at MCP level Finger dorsal subaponeurotic spaces
space

Pathophysiology
In all closed spaces of the hand, accumulation of purulent material is raising the pressure, compromising the
blood flow, and causing ischemia and necrosis. These conditions are further aggravating the infection,
establishing a vicious circle. Direct inoculation (epithelium lysis), spread from the adjacent necrotic tissues or
through the lymphatic pathway, could result in the establishment of hand infections.

Pathogens
Gram positive cocci and especially S. aureus and -Hemolytic-Streptococcus group A (pyogenes) are usually
involved. This is the result of skin flora inoculation during injury.S. aureus is reported to range from 30 to 80% of
positive cultures although it has been shown that this percentage is decreasing while mixed gram positive and
gram negative hand infections are increasing. An emerging pathogen is the S. aureus that carries the PVL gene;
it is usually community-acquired and leads to necrotic lesions. At least 3 sets of cultures should be ordered, each
one including cultures for bacteria, mycobacteria and fungi. Gram stain provides important information. While
cultures are often negative, recent advances in the detection and identification of bacterial pathogens by
molecular methods greatly facilitate the diagnosis and expedite the initiation of treatment.

Empirical antibiotic treatment is mandatory, while waiting for the culture results, taking into consideration the
hospital flora and the local spread of community-acquired methicillin resistant S. aureus (CA-MRSA). The
introduction of antibiotics was a great progress in the early treatment of hand infections and led to the reduction
of devastating complications such as amputations.

139
Host type and infection
In immunocompromised patients (underlying malignancy and immunosuppressive disease) or patients receiving
steroids and anti-tumor necrosis factors, closed-space hand infections present subtly and a high rate of morbidity
must be expected if treatment is delayed. Temperature elevation, localized tenderness and erythema are
indications for hospitalization while broad spectrum antibiotics and debridement are needed. Discoloration,
fluctuation, drainage or, even worse, hypotension were found to be late signs.Polymicrobial infections and mixed
infections are likely to occur in these patients, including gram negative bacteria and/or anaerobes and
appropriate antibiotics must be administered. The same principles apply to patients with diabetes mellitus,
intravenous use of drugs and in human bite and crush injuries, as well as in injuries in highly contaminated
environments

Diagnosis
Because of the deep location of closed space accumulations the typical signs infection are often absent.
Throbbing pain, edema and restricted finger motion are the most common sings and symptoms, while specific
clinical signs such as Kanavel's signs (septic tenosyn-ovitis) may be obtained in cases of infections in closed
spaces. Finally, systemic signs of infection are usually absent. Apart of a complete laboratory testing (complete
blood count, ESR, CRP), imaging studies such as radiographs and ultrasound are helpful in the diagnosis of
concomitant skeletal involvement or deep space collections. Culture samples must be obtained before the
administration of antibiotics; Gram stain, antibiotic resistance phenotypes, detection of the mecA gene, and
molecular typing of the isolates must be requested from the microbiology departments.

Cellulitis
Cellulitis is characterized by a nonpurulent diffuse spreading of inflammation characterized by erythema, warmth,
pain, swelling, and induration. Skin breakdown is a frequent cause, but often no inciting factor is identified. Group
-hemolytic Streptococcus is the most common offending pathogen and causes a more diffuse spread of
infection. S. aureusis the second most common offending pathogen and will cause a more localized cellulitis. The
diagnosis of cellulitis is clinical. Septic arthritis, osteomyelitis, an abscess, a deep-space infection, and
necrotizing fasciitis are severe infectious processes that may initially mimic cellulitis. These must be ruled out
appropriately before initiating treatment, and serial exams should be conducted to ensure proper diagnosis.
Treatment of cellulitis consists of elevation, splint immobilization, and antibiotics that cover both Streptococcus
and Staphylococcus. Intravenous antibiotics are usually initiated for patients with severe comorbidities and those
who fail to improve on oral antibiotics after 24 to 48 hours. Failure to improve after 24 hours indicates a need to
search for an underlying abscess or other infectious cause.

Abscess
An abscess will present much like cellulitis, but they are two clinically separate entities. The defining difference is
an area of fluctuance. Skin-puncturing trauma is the most common cause. S. aureusis the most common
pathogen, followed by Streptococcus. Treatment consists of incision and drainage with appropriate dbridement,
wound cultures, wound packing, elevation, immobilization, and antibiotics. The packing should be removed in 12
to 24 hours or sooner if there is clinical concern, and warm soapy water soaks with fresh packing should be
initiated. Most should be allowed to heal second- arily. Delayed primary closure should only be performed after
repeat washouts for larger wounds where complete infection has been achieved.

Felon
Felon is an infection of the pulp of the distal phalanx , a subcutaneous abscess of the fingertip and is most
commonly caused by penetrating trauma It is usually a primary infection caused by an unnoticed injury in more
than 50% of cases . Many authors advocate secondary infection from the extension of a severe or neglected
infection around the nail as tissue liquefactive necrosis favors the spread to the surrounding tissues, although the
anatomical course of the lymphatics does not support this opinion.4

S. aureus is the most common pathogen. The fingertip contains multiple septa con- necting the distal phalanx to
the skin. These septa are poorly compliant, and presence of an abscess will increase pressure and lead to
severe pain and tissue death. The typical signs of acute inflammation are present. The initial sticking pain in the
distal phalanx transforms to throbbing severe pain, while the initial tenseness of the pulp is replaced by an
induration and later by a fluctuating boggy mass. Due to presence of septa, pus or edema have no means of free
egress and therefore occlude the blood supply and result in necrosis of the pulp and distal phalange. At the first
stage necrosis can spare the epiphysis and distal interphalangeal (DIP) joint, but in neglected cases spontaneous
expulsion of the necrotic tissue is expected. At this stage the finger pulp is a bluish insensitive pus bag with
asinus opening by the nail side. Usually there are no systemic signs of infection.

A lateral incision is preferable since the transverse dissection of the radiating columns of fat and connective
tissue results in more efficient drainage and wound closure is by secondary intention. A longitudinal incision over
the area of greatest fluctuance is the safest procedure when incision and drainage is required. Many other
procedures, including hockey-stick or fish-mouth shaped incisions, are no longer recommended because of injury
to neurovascular structure.

Attention should be drawn to avoid exposure of the healthy DIP joint or the flexor tendon sheath through a

140
proximally extended incision. The treatment of coexisting osteomyelitis of the distal phalanx depends on the
amount of bone involvement and includes resection of the involved bone or even amputation.

Surgical drainage of the finger pulp performed too early, at the stage of a more diffuse inflammation, that some
authors call an early felon, could be an unnecessary and even harmful procedure over a cellulitis, causing diffuse
pain and tenderness throughout the whole finger. Imaging modalities (e.g. ultrasound) can help the differential
diagnosis by detecting fluid accumulations. . The wound is irrigated and packed, with warm soapy water soaks
and packing changes initiated within 24 hours and performed two to three times daily until secondarily healed.
Antibiotic coverage should cover for Staphylococcus and Streptococcus species.

Decrease of pain sometimes signals an aggravation of the felon as the necrotic process destroys the septa and
therefore offers a temporary relief.

Paronychia
Paronychia is an infection beneath the nail fold. The nail plate can be viewed as an invagination into the dorsal
skin extending down to the distal phalanx periosteum. Predisposing factors include anything that causes nail
trauma, such as manicures, artificial nails, or nail biting. The infection may spread around the nail plate from one
side to the other, or it may extend into the pulp and result in a felon. An acute paronychia is usually caused by S.
aureus or Streptococcalspecies. Patients report pain, erythema, swelling, and possibly purulent drainage involv-
ing the periungual tissue. Treatment consists of warm water soaks and oral antibiotics if diagnosed early. If
purulence or fluctuance is present, then a freer elevator or 18-gauge needle can be passed along the involved
nail fold to decompress the collection (Fig. ). If the infection involves the eponychial fold, a small proximally based
flap of eponychium is created by using a scalpel, followed by irrigation and packing. The nail plate must be
removed if the infection extends beneath the nail plate. Packing is kept in place for 24 to 48 hours, followed by
warm water soaks and local wound care. Usually, the wound cannot be repacked once the dressing is removed.A
chronic paronychia is most commonly caused by Candida species and is most often found in patients who
perform jobs involving the submersion of their hands in water or other moist environments. These develop into
thickened nails with callus-like formation along the nail folds and may occasionally become red and inflamed.
They do not respond to antibiotic treatment, and nail plate removal with marsupializa- tion of the skin proximal to
the eponychial fold will allow the wound to heal secondarily. The environmental factors leading to the chronic
paronychia must also be corrected in order for treatment to be successful.All hand infections other than cellulitis
will require surgical management. Clinical examination, particularly noting the area of greatest tenderness and/or
inflammation, is the single most useful diagnostic tool to purulence requiring drainage.

Osteomyelitis
Osteomyelitis in the hand usually occurs due to an open fracture with significant soft tissue injury. The presence
of infected hardware, peripheral vascular disease, diabetes, and alcohol or drugabuse are also predisposing
factors. Presentation includes persistent or recurrent swelling with pain, erythema, and possible drainage. It will
take 2 to 3 weeks for periosteal reaction and osteopenia to be detected on radiographs. Bone scans and MRI are
useful modalities to aid in diagnosis. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have
low specificity but are useful for monitoring the progress of treatment, with CRP being more reliable. Treatment
consists of antibiotics alone in the early stage as long as there is favorable response. All necrotic bone and soft
tissue, if present, must be dbrided. Initial intravenous antibiotic therapy should cover S. aureus, the most
common pathogen, and should then be adjusted according to bone cultures. Antibiotic therapy is continued for 4
to 6 weeks once the patient clinically improves and there is no further need for dbridement. For osteomyelitis in
the setting of an acute fracture with internal fixation in place, the hardware should be left in place as long as it is
stable and the fracture has not yet healed. If the hardware is unstable, it must be replaced. An external fixation
device may be useful in this setting. If osteomyelitis occurs in a healed fracture, all hardware and necrotic bone
and soft tissue must be removed.

Pyogenic Arthritis
Infection of a joint will progress quickly to severe cartilage and bony destruction if not addressed quickly. Direct
trauma and local spread of an infection are the most common causes. Hematogenous spread occurs most
commonly in patients who are immunocompromised. S. aureusis the most common pathogen, followed by
Streptococcus species. Neisseria gonorrhoeaeis the most common cause of atraumatic septic arthritis in an adult
less than 30 years of age. Presentation includes exacerbation of pain with any joint movement, severe pain on
axial load, swelling,erythema, and tenderness. Radiographs may show a foreign body or fracture, with widened
joint space early in the process and decreased joint space late in the process due to destruction. Joint aspiration
with cell count, Gram stain, and culture is used to secure the diagnosis. Treatment of nongonococcal septic
arthritis includes open arthrotomy, irrigation, dbridement, and packing the joint or leaving a drain in place.
Intravenous antibi- otics are continued until there is clinical improvement, followed by 2 to 4 weeks of additional
oral or intravenous antibiotics. Gonococcal septic arthritis is usually treated nonoperatively. Intravenous
ceftriaxone is first-line therapy. Joint aspiration may be used to obtain cultures and decrease joint pressure .

Necrotizing Infections
Necrotizing soft tissue infections occur when the immune system is unable to contain an infection, leading to
extensive spread with death of all involved tissues. This is different from an abscess, which forms when a

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functioning immune system is able to wall off the infectious focus. Necrotizing infections can result in loss of
limb or life, even with prompt medical care.

Bacteria spread along the fascial layer, resulting in the death of soft tissues, which is in part due to the extensive
blood vessel thrombosis that occurs. An inciting event is not always identified. Immunocompromised patients and
those who abuse drugs or alcohol are at greater risk, with intravenous drug users having the highest increased
risk. The infection can by mono- -hemolytic Streptococcus being the most
c -hemolytic Strep- tococcus, S. aureus, and anaerobes. Prompt clinical
diagnosis and treatment are the most important factors for salvaging limbs and saving life. Patients will present
with pain out of proportion with findings. Appearance of skin may range from normal to erythematous or maroon
with edema, induration, and blistering. Crepitus may occur if a gas-forming organism is involved. Dirty dishwater
fluid may be encountered as a scant grayish fluid, but often there is little to no discharge. There may be no
appreciable leukocytosis. The infection can progress rapidly and can lead to septic shock and disseminated
intravascular coagulation. Radiographs may reveal gas formation, but they must not delay emergent dbridement
once the diagnosis is suspected. Intravenous antibiotics should be started immediately to cover gram-positive,
gram-negative, and anaerobic bacteria. Patients will require multiple dbridements, and the spread of infection is
normally wider than expected based on initial assessment.

Necrotizing myositis, or myonecrosis, is usually caused by Clostridium perfringensdue to heavily contaminated

wounds. Unlike necrotizing fasciitis, muscle is universally involved and found to be necrotic. Treatment includes
emergent dbridement of all necrotic tissue along with empirical intravenous antibiotics.

Wet gangrene is most common in diabetics with renal failure and an arteriovenous shunt. It is usually
polymicrobial. Patients will present with a necrotic digit that is purulent and very malodorous, with rapidly evolving
pain, swelling, skin discoloration, and systemic collapse. Emergent treatment is the same as for other necrotizing
infections, and amputation of the involved digit or extremity must often be performed.

Tenosynovitis/bursitis
Flexor tenosynovitis (FTS) is a severe pathophysiologic state causing disruption of normal flexor tendon function
in the hand. A variety of etiologies are responsible for this process. Most acute cases of FTS are due to purulent
infection. FTS also can occur secondary to chronic inflammation as a result of diabetes, RA, crystalline
deposition, overuse syndromes, amyloidosis, psoriatic arthritis, systemic lupus erythematosus, and sarcoidosis.

The primary mechanism of infectious FTS usually is penetrating trauma. Most infections are caused by skin flora,
including both Staphylococcus and Streptococcus species. Bacteria involved vary by etiology of the infection: bite
wounds (Pasteurella multocidacat, E. corrodenshuman); diabetic patients (Bacteroides, Fusobacterium,
Haemophilus species, gram-negative organisms); hematogenous spread (Mycobacte- rium tuberculosis, N.
gonorrhoeae); or water-related punctures (Vibrio vulnificus, Mycobacterium marinum). Infection in any of the
fingers may spread proximally into the wrist, carpal tunnel, and forearm, also known as Paronas space.

Suppurative FTS has the ability to rapidly destroy a fingers functional capacity and is considered a surgical
emergency. Suppurative FTS results from bacteria multiplying in the closed space of the flexor tendon sheath
and culture-rich synovial fluid medium causing migration of inflammatory cells and subsequent swelling. The
inflammatory reaction within the closed tendon sheath quickly erodes the paratenon, leading to adhesions and
scarring, as well as increase in pressures within the tendon sheath that may lead to ischemia. The ultimate
consequences are tendon necrosis, disruption of the tendon sheath, and digital contracture.

Patients with infectious FTS present with pain, redness, and fever . Physical examination reveals Kanavels
cardinal signs of flexor tendon sheath infection: finger held in slight flexion, fusiform swelling, tenderness along
the flexor tendon sheath, and pain over the flexor sheath with passive extension of the digit.Kanavels signs may
be absent in patients who are immunocompromised, have early manifestations of infection, have recently
received antibiotics, or have a chronic, indolent infection.

If a patient presents with suspected infectious FTS, empiric intravenous antibiotics should be initiated. Prompt
medical therapy in early cases may prevent the need for surgical drainage. For healthy individuals, empiric
antibiotic therapy should cover Staphylococcus and Streptococcus. For immunocompromised patients (including
diabetics) or infections associated with bite wounds, empiric treatment should include coverage of gram- negative
organisms as well.

Adjuncts to antibiotics include splint immobilization (intrinsic plus position preferred) and elevation until infection
is under control. Hand rehabilitation (i.e., range-of-motion exercises and edema control) should be initiated once
pain and inflammation are under control.

If medical treatment alone is attempted, then initial inpatient observation is indicated. Surgical intervention is
necessary if no obvious improvement has occurred within 12 to 24 hours.

Several surgical approaches can be used to drain infectious FTS. The method used is based on the extent of the

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infection. Michon developed a classification scheme that can be useful in guiding surgical treatment drainage of
a stage II FTS. A Brunner incision allows better initial exposure but may yield difficulties with tendon coverage if
skin necrosis occurs. A 16-gauge catheter or 5-French pediatric feeding tube then is inserted into the tendon
sheath through the proximal incision. The sheath is copiously irrigated with normal saline. Avoid excessive fluid
extravasation into the soft tissue, because the resulting increase in tissue pressure can lead to necrosis of the
digit. The catheter is removed after irrigation. The incisions are left open. Some surgeons prefer a continuous
irrigation technique for a period of 24 to 48 hours. The catheter is sewn in place, and a small drain is placed at
the distal incision site. Continuous or intermittent irrigation every 2 to 4 hours with sterile saline can then be
performed through the indwelling catheter.In severe or aggravating infections, drainage through a wide or limited
approach, in a bloodless field, is necessary. The wide approach is either lateral or palmar (zig-zag) whereas the
limited consists of two small incisions over the two edges (A1 and A5 pulleys) of the infected sheath. Surgeons
advocating the limited approach claim a better final range of motion, while others believe that a limited approach
should be used in less severe cases, although there are no level I studies comparing the type of incision. All
authors agree that intra-operative irrigation is useful or at least of no harm. In addition, many authors advocate
that post-operative sheath irrigation until the resolution of the acute inflammation. The irrigating solution consists
of normal saline without antibiotics.

After surgery, an intrinsic plus splint is applied, the hand is elevated, and the appropriate empiric antibiotic
coverage is instituted while awaiting culture results. The hand is reexamined the following day. Drains are
removed before discharge from the hospital. The wounds are left open to heal by secondary intention. In severe
cases, repeat irrigation and operative dbridement may be required.

Antibiotic therapy is guided by culture results as well as clinical improvement. Once there is no further need for
debridement, a 7- to 14-day course of oral antibiotics is generally prescribed

Ulnar bursitis is often difficult to be diagnosed due to its deep location. It is characterized by the development of
hand edema, especially upon the dorsum. A general fullness is seen in the palm, but the palmar concavity is not
lost at first. The wall of the bursa often becomes necrotic before the extensive formation of exudate, and this
permits the trespass of the accumulation to the surrounding closed spaces. There is exquisite tenderness and the
wrist becomes fixed, whereas the little finger and sometimes the ring finger show tenderness to palpation and
pain on passive extension. Extension to the radial bursa is observed up to 85% of cases.

Radial bursitis is diagnosed by the swelling and tenderness in the thenar eminence and along the radial bursa.
The treatment in cases of purulent accumulation consists of surgical drainage, debridement of abscesses through
a palmar incision over the infected area followed by intraoperative irrigation with normal saline. Care should be
taken not to injure the branch of the median nerve, which supplies the thenar muscles as it passes across the
radial bursa, approximately 1 cm distal to the transverse ligament of the wrist.

In both tenosynovitis and bursitis the surgical wounds can be closed by secondary intention unless there is
continuous postoperative irrigation.Passive assisted and active exercises to restore range of motion start with the
remission of acute inflammation and after the removal of postoperative irrigation system (after 2448 hours).
However Nemotoet al. in 1991 suggested mobilization to start even if the irrigation system is in place and
advocates the use of the system for a week postoperatively.

In the presence of multiple painful fingers, careful evaluation will reveal the infected one from its marked painful
rigidity.

Decrease of tenderness to a considerable degree does not necessarily mean a definite improvement; it may be
only a temporary relief due to the rupture of the infected sheath at its proximal edge and therefore of extension of
the pus to more proximal structures. Differential diagnosis should include acute bleeding into the tendon sheath
in patients under anticoagulation therapy and also tenosynovitis developing in 2/3 of patients with gonococcal
infection.

Michons stages of suppurative flexor tenosynovitis and appropriate treatment

Stage Findings Treatment
Increased fluid in sheath, mainly a serous
I Catheter irrigation
exudate
Minimal invasive drainage indwelling catheter
II Purulent fluid, granulomatous synovium
irrigation
Necrosis of the tendon, pulleys, or tendon
III Ext open debridement+/- amputation
sheath

Paron's Space potential space between FPL tendon, FDP tendons, & pronator quadratusis known as the
subtendinous space of the wrist or Parona's space;pus in FPL sheath can ascend in the radial bursa and
eventually rupture into this space; pus in little finger sheath can ascend in ulnar bursae & rupture into Paron's
space; pus from thenar abscess or midpalmar abscess may rupture into Parona's space; if pus from either the
radial or ulnar bursae ruptures into Parona's space, it can be drained by the same incision used for releasing pus

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from the proximal end of the ulnar bursae

Deep space infections of the hand

These are infections of the midpalmar space, the thenar space and compartment, the hypothenar space and
compartment and the subaponeurotic space of the dorsum of the hand. They are either a primary infections via
direct bacterial inoculation or secondary infections through extension from adjacent tendon synovium/bursae or
fascial spaces. An aggressive treatment may prevent devastating complications from the adjacent sheaths,
nerves, bones and joints. Close observation and antibiotics are always necessary. Drainage, debrideament and
intraoperative irrigation are the subsequent steps, whereas the decision for continuous postoperative irrigation is
based on intraoperative findings. The wound can be closed later or by secondary intention if continuous
postoperative irrigation is not used. Rehabilitation with passive assisted or active range of motion exercises
begins after the remission of the acute inflammation.

In a mid-palmar infection the concavity of the palm is usually lost. There is an exquisite tenderness over the
infected area which is pallid and sometimes red. Fingers are held rigidly flexed, with decreasing rigidity from the
little to the index finger. However, finger rigidity in case of mid-palmar infections is less severe than the rigidity of
septic tenosynovitis. There is usually a pitting edema in the remaining palm (over the thenar) and at the dorsum
of the hand, while in the case of pus extension along the lubrical channel, swelling of the web space is also
observed. The midpalmar space is drained and debrided through a palmar incision (transverse, longitudinal or
along one of the lubrical channels) taking care to avoid injury of the neurovascular bundle or contamination of the
surrounding tissues (the ulnar bursa in particular).

In thenar compartment and thenar space infections a painful swelling of the thenar eminence is observed. The
concavity of the palm is lost and often soft edema on the dorsum of the hand is present. The 1st metacarpal and
the thumb are abducted and distal phalanx flexion becomes more marked. In extensive infections, a double
incision over the volar and dorsal side is necessary for drainage of the infected spaces/compartments.
In hypothenar compartment and space infections the abscess is more localized. There is often limited swelling in
the palm but always painful swelling of the hypothenar eminence. The incision is located over the hypothenar
with care to avoid injury to the neurovascular bundle.

In subaponeurotic space infections the dorsal edema is more soft and the ischemia of the skin less severe than in
cases of subcutaneous pus accumulation. Attempts of finger extension may be limited by pain. The dorsal
incisions for the drainage of the subaponeurotic space are longitudinal, over the 2nd and between 4th5th
metacarpals.

Because of the intimate relationship of the midpalmar and the thenar spaces, any infection persisting for more
than 48 hours extends in the majority of cases to the adjacent space. When both spaces are involved, a
considerable abscess is formed under the flexor tendons.

Web space infections

These are either primary infections from direct inoculation or secondary extending from the adjacent anatomical
structures. The diagnosis is clinical and based on an abscess forming at the distal edge of the palm separating
the adjacent fingers.

This is a subfascial infection of a web space and is usually caused by skin trauma that becomes infected; it often
occurs in laborers. The adherence of the palmar web space skin to the palmar fascia prevents lateral spread, so
the infection courses dorsally, resulting in both palmar web space tenderness and dorsal web space swelling and
tenderness. The attachment of the palmar fascia to the skin results to the spread of the pus into the dorsal
subcutaneous space with the typical picture of a collar-button abscessThe adjacent fingers will be held in
abduction with pain on adduction. Surgical treatment includes drainage of the often multi-loculated abscess,
through a palmar and/or a dorsal incision. The incision should never cross the edge of the web to avoid the
formation of dysfunctional scars.The web is a significant crossroad in hand infections.

Treatment
In deep space hand infections apart of antibiotic coverage and immobilization with hand elevation, the surgical
incision and drainage of all potentially communicating spaces and compartments is mandatory, along with
intraoperative irrigation and sometimes, continuous postoperative irrigation. Parameters such as the pathway of
inoculation, the environment where the initial injury occurred and above all the underlying condition of the host
must be taken into consideration for a radical and successful treatment. Finally, postoperative hand therapy must
be initiated as soon as the acute signs of infections subside.

Antibiotic treatment is usually initiated with penicillinase-resistant penicillin or cephalosporins. The oral empiric
antibiotic treatment expected to be effective against suspected CA-MRSA infections includes ciprofloxacin,
clindamycin, rifampin, tetracyclines, and TMP-trimethoprim/sulfamethoxazole. For more serious infections,
intravenous vancomycin is recommended. Alternative intravenous therapies include daptomycin, gentamicin, and
line-zolid. In crush injuries, injuries in highly contaminated environments or in immunocompromised hosts, gram
negative bacteria and/or anaerobes are suspected.

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Antibiotics are usually required for 7 to 10 days unless complications arise.The route of administration is
intravenous for all cases that require hospitalization, until the remission of the acute signs of infection.
Subsequently an oral regimen could be administered.

Specific approaches will be presented for the different types of closed-space infections. In all cases a bloodless
field is imperative for the evaluation of all potentially infected closed-spaces and for the drainage through safe
anatomical paths. Special attention must be given to the avoidance of use of Ershmarch bandage so as to limit
the spread of infection. Simple elevation of the hand and forearm is usually adequate for a bloodless field.

Venous ulcers

Vivek Agrawal, Ashesh Jha

1
Venous ulcer or stasis ulcer accounts for 80% of the lower extremity ulceration . Venous ulcers are difficult to
treat owing to its chronicity and high recurrence rate , which ranges from54% to 78% 2.Studies have shown that
an estimated 5% to 8% of the world population suffers from the venous disease and approximately 1% develops
3 4 5 6 7 8
venous ulcers . Venous ulcers most commonly occur in women & elderly persons . Advancing age ,
obesity , previous leg injuries, deep venous thrombosis & phlebitis are the risk factors that have been described
9
with venous ulceration . Nonhealing ulcers can be complicated by cellulitis, osteomyelitis, & malignant
transformation. Although the overall prevalence of venous ulcers are low but the refractory nature of these ulcers
& complications associated with these ulcers increases the morbidity & mortality of the patients and adversely
impact the quality of life 10 11 .

Pathophysiology
The pathophysiology of venous ulcer is not completely understood , however venous incompetence & associated
venous hypertension are thought to be the primary predisposing factors for ulcer formation. Therefore it is
imperative to know the venous anatomy of the lower limb to understand the overall effect of the venous
incompetence and venous hypertension on the development of chronic venous insufficiency and venous
ulceration. The venous system of the lower extremity comprises of three components: the superficial veins ,
perforator veins & deep veins . The deep veins lay within the muscle of the lower extremity , whereas the
superficial vein lie above the fascia overlying the muscles. The perforators or communicating veins connects the
superficial and the deep systems. The superficial veins are low pressure systems whereas the deep veins are
high-pressure systems. All three venous system have one way valve , which only open towards the deep venous
system and in normal circumstances, prevent reflux of blood .During ambulation, as the calf muscle contracts ,
the deep veins are compressed ,thus propelling blood proximally towards the heart. With brief rise in pressure ,
the valve of the all three system close preventing retrograde flow of blood 12 13 14 15 16 . As the calf muscle relaxes ,
the deep veins empty thus allowing a drop in pressure. The venous valve open during this phase, allowing the
blood to flow from the superficial veins through the communicating veins to the deep venous system 17 . In
17
patients with venous insufficiency, this series of events does not occur .

Venous hypertension , a sustained elevation of ambulatory pressure, is the hallmark of venous disease and may
be caused by an abnormal calf muscle pump. An abnormal calf muscle pump may occur due to incompetent
18
veins or valves of the lower extremities , muscular dysfunction , limited mobility or combination of the three
19
.Vein incompetence may be acquired or congenital often due to absence or dysfunction of valves . Contraction
of the calf muscle ,specifically the gastronemicus and the soleus muscle empty the intramuscular deep veins and
20
decrease the volume of venous blood present in the lower extremity . Anatomically, the plantar venous plexus
of the foot has a smaller vessel diameter than does the outflow tract of the posterior tibial deep veins, thus adding
the cephalad flow of venous blood. Compression of the plantar plexus is assisted by ambulation thereby
decreasing the strain on calf muscle pump. Venous ulcer may occur in some of these patient who lack the benefit
of the calf muscle pump and the plantar plexus that facilitate the movement of blood back to the heart.

Erect ambulatory patients who lack proper compensation of the venous system develop venous pooling near the
ankle. Increased venous pressure with concomitant reduced differential between the arteriolar and the venular
21
side of the capillary bed may trap leukocytes in post capillary venules . These leukocytes may activate and
release proteolytic enzymes , which leads to the formation of free radicals which may lead to local tissue damage
21 22
. Activated leukocytes also can release various cytokines such as tumor necrosis factor(TNF) & Interleukin
1(IL 1).In addition to leukocyte activation, margination of white cells can act as diffusion barrier to oxygen and
nutrients necessary for tissue survival 23 . Venous blood pooling in the lower limb increases the capillary
intraluminal pressure leading to stretching of the interendothelial pores with subsequent increase in the capillary
permeability and edema formation. Additionally macromolecules such as fibrinogen and alfa-macroglobulin may
leak into the dermis through the dilated capillary pores 23 . Alpha-macroglobulin may bind growth factors such as
24
TNF & transforming growth factor beta(TGFb),which are required for wound repair . Entrapment of these

145
growth factors may make them unavailable for the tissue repair. Fibrionogen leaking into the dermis leads to the
formation and deposition of fibrin cuff around the dermal blood vessels, which also may act as an additional
diffusion barrier to oxygen and nutrients 23 .

Recently, it also has been proposed that arterio-venous(AV) shunting may play a role in the pathogenesis of
venous ulcers 20 .This theory is supported by presence of elevated oxygen content of the venous blood,
premature venous filling, increased blood flow in the skin of legs on angiography,and decreased capillary density
in leg skin in patients with venous insufficiency possibly representing hypoperfusion of nutritive capillaries.

Clinical examination & Diagnosis

History
The patients history provides important information necessary for the differentiation of the types of ulcers that
develop in the lower extremity. The following symptoms are common to the most venous disorder & focused
question to elaborate these symptoms may provide the essential information for defining the etiology of ulcer
formation.
Aching
Swelling
Distended superficial veins
Bleeding
Skin discolouration
Ulceration
Restless leg syndrome
History of past DVT
History suggestive of Pelvic pathology
Family history

Most of the patients usually describe an increase in symptoms with prolonged standing. They deny pain but
acknowledge a more subtle dull ache or fatigue. Often these symptoms have been present for many years and
have been attributed to age or other factors. The symptoms are typically less noticeable in the morning but get
worse throughout the day are often exacerbated in women by menstrual cycle. Nighttime cramping and restless
legs also may be due to venous disease and often are noticeable after a particular long or active day. Patients
often experience itching in the lower leg which may be accompanied by stasis dermatitis or the other features of
chronic venous insufficiency. Many of these symptoms are significantly or completely relieved with treatment of
the superficial venous reflux.

Physical examination
A complete physical examination must always be performed . In addition attention should be directed towards the
involved extremitys circumference, edema, Skin changes, color , temperature, pulse as well as the location, size
and appearance of the ulcer.

Differential diagnosis of leg ulcer:

The differential diagnosis of leg ulcers are endless. Common causes of leg ulcers are as follows.
1) Vascular
- Arterial
- Venous
- Lymphatic
2) Vasculitis
- Periarteritisnodosa
- Rheumatoid arthritis
- Lupus erythematosus
- Hypertension
- Hematological Sickle cell anemia, Thalassemia , Polycythemia vera
3) Metabolic disorders :
- Diabetes mellitus
- Pyoderma gangrenosum
4) Tumors
- Squamous cell carcinoma
- Mycosis fungoides
5) Miscellaneous
- Drugs
- Factitial
Arterial ulcers
Arterial occlusive disease is a frequent cause of lower extremity ulcerations. These are located on the distal end
of the extremities. The ulcer appear as punched-out lesion. These ulcers are painful and the signs of chronic
ischemia are present in the involved extremity.

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Venous ulcers
On physical examination, venous ulcers are commonly irregular in shape and shallow. Granulation tissue and
fibrin are often present in the ulcer base. These ulcers are commonly located above the medial malleolus Other
findings include lower extremity varicosities; edema; venous dermatitis associated with hyperpigmentation ,
hemosiderosis or hemoglobin deposition in the skin; and lipodermatosclerosis associated with thickening and
fibrosis of normal adipose tissue under skin. A clinical severity score based on the CEAP (clinical, etiology,
anatomy, and pathophysiology) classification system can guide the assessment of chronic venous disorders. The
highest CEAP severity score is applied to patients with ulcers that are active, chronic (greater than three months
duration, and especially greater than 12 months duration), and large (larger than 6 cm in diameter) . Poor
prognostic factors for venous ulcers include large size and prolonged duration .

Vasculitis ulcers
Ulcer formation secondary to vasculitis falls in broad category of diseases including polyarteritisnodusa,
hypersensitivity angitis ,Wegeners granulomatosis & necrotizing vasculitis*. The important points in making the
diagnosis are the history, laboratory testing and a biopsy to document the presence of vasculitis.These ulcer
appear primarily on the lower extremity from the midcalf to the dorsum of the foot.These lesion also have a
punched-out appearance with gangrenous central tissue. They can be unilateral or bilateral and are frequently
painful.

Hematologic ulcers

Sickle cell anemia : Ulceration occurs in approximately 75% of patients with sickle cell anemia. The
pathophysiology of this process involves a lowered oxygen tension and pH in areas of stasis in the distal portion
of lower extremities. The shape is usually round or oval and they are very refractory to healing.
Thalassemia : The presence of ulceration with thalassemia is not common. The mechanism for tissue damage is
probably inadequate tissue oxygenation.These ulcer appear similar to those of patients with sickle cell anemia.
Polycythemia Vera : Ulcer formation in this group of patients most likely has a dual origin. Either the increased
viscosity of the blood results in venous thrombosis ,valvular incompetence and venous ulceration,or local hypoxia
occurs at the capillary level and causes tissue damage.

Metabolic Leg ulcers

Diabetes Mellitus
The etiology of ulcer formation in patient with diabetes is multifactorial .Microangiopathy , sensory neuropathy &
infections predisposes these patients to ulcer formation. There are a number of rare cuases of ulcers in the lower
extremities of diabetes , including necrobiosis lipoidicadiabeticorum, diabetic dermopathy ,and bullae
diabeticorum.

Pyoderma Gangrenosum
It presents as an acute necrotizing ulcer predominantly on the lower extremities. Pyoderma gangrenosum
frequently produces an irregular ulcer with a necrotic base. This skin lesion begin as a deep-seated painful
nodule or as a superficial hemorrhagic pustule either de novo or after minimal trauma. This lesion was once
pathognomonic for ulcerative colitis but has been observed in many other conditions.

Tumors causing ulcers

Squamous cell carcinoma : These lesions occurs most commonly on sunexposed areas of the face neck and
extremities. The ulcers are shallow with a raised and everted border and never heals. When a chronic leg ulcers
of any etiology has been present for a long period and not healing,squamous cell carcinoma should be
considered.

Mycosis Fungoides : This is the most common type of lymphoma affecting the skin.There are three stages of
presentation: patch,plaque and tumor. Ulceration occurs secondary to necrosis of the tumor.

Miscellaneous causes of leg ulcer

Medications : Bromide and iodide compound can produce skin lesion.These ulcers usually occur on the anterior
surface of the tibia and are extremely painful.

Radiation : Ionizing radiation to the lower extremities in doses above 10 Gy may cause acute dermatitis which
can ulcerate 6 to 8 weeks following the acute reaction.

Decubitus ulcers: They are seen frequently in bedridden patients secondary to neurologic causes or general
debilitation.The lesion occur from prolonged pressure to a small surface area, on the lower extremity primarily the
malleoli and heels.

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Diagnostic studies
The clinical diagnosis may be supported by further diagnostic testing as indicted, specially if other diagnoses are
being considered in differential.

Vascular studies
The initial evaluation of a venous ulcer should rule out concurrent arterial disease. Using a standard a
sphygmomanometer , the clinician can determine an ankle to brachial pressure index (ABPI).If the patient has an
ABPI between 0.5 to 0.8 ,it indicates that there may be concurrent arterial disease and venous disease. If the
26
ABPI is less than 0.5,the ulcer is more likely to be arterial in origin .

Duplex Ultrasound
It is often the initial choice for patient evaluation because it is widely available and easy to use. With this
technique one can delineate vascular architecture , site of venous reflux and status of deep venous system. For
venous evaluation patient is examined in the standing position , compression of the calf by manual pressure
produces a systolic flow of blood in the anterograde direction. After the release of the calf muscle, a patient with
valvular incompetence will demonstrate retrograde flow in the vein being evaluated.*Despite the widespread use
of this technique , considerable skill is necessary for a thorough evaluation of the deep veins.Functional testing
such as Plethysmography can be a complementary method alongside ultrasound to evaluate the calf muscle
27 28
dysfunction .

Invasive Techniques
The gold standard for defining the patients venous anatomy and demonstrating reflux is venography. In
ascending venography , the patient is upright while a tourniquet is applied above or below the knee. Contrast dye
is introduced,and if the dye is seen distal to the tourniquet , the patient is assumed to have venous reflux. In
descending venography ,the patient is placed in supine position and the contrast is injected into the common
femoral vein. The patient is then tilted downward , and the level to which the contrast dye leaks is observed.A
leak below the level of knee considered significant for reflux.

A comparison between various invasive and noninvasive techniques were performed by Mantonis group. They
found continuous wave Doppler and ambulatory strain guage plethysmography are of little value in the work up of
patients with deep venous insufficiency.They suggested colour duplex ultrasound should be used as a first line
29
diagnostic tool , with ascending phlebography used only when the triple ultrasound is inconclusive .

Radiological studies
Magnetic resonance imaging is becoming more popular as a diagnostic tool in the evaluation of these patients.
Magnetic resonance venography can show occluded vessels and alteration of blood flow, in addition they may
display subcutaneous fibrosis and infiltration of extrafascial spaces 30.

Biopsy & Tissue culture

These investigations are rarely warranted in the cases of classical venous ulcer. However in certain cases biopsy
can be performed to rule out malignant transformation. Although tissue culture has been considered as gold
standard in the assessment of wound infection, recent studies have shown a culture swab to be equivalent in the
31
initial evaluation of bacterial wound infection .

Therapy

General principles
The core principles for management of venous ulcerations are
1) Clean wound base
2) Compression
3) Surgical interventions/procedures
4) Medications

The clean ulcer

The aim of wound care is to provide an optimum environment for healing. A clean ulcer with healthy appearing
granulation tissue at its base is considered as the best environment for healing. It may be achieved by applying
the following methods
- Debridement :
- Treating infection:
- Wound care : Dressings,Topical agents

Compression
Compression is undoubtedly one of the most important factors in the healing of venous ulcer 32.Compression not
only supplements the pumping action of the calf muscle but also increases tissue pressure to reverse the
33
gradient between the capillaries and intravascular space , thus leading to reduction in tissue edema .It is
important to rule out concomitant arterial disease before initiating compression therapy.

148
Compression therapy should be performed in two consecutive phases. The first treatment phase is
decompression phase, which should take place at the time of active leg ulcer. The goal of this phase to reduce
edema and promote wound healing. For decompression phase three types of compression may be utilized : 1)
inelastic compression bandage ,2) multi-layered elastic bandage, 3) mechanical compression using intermittent
34
pneumatic compression boots .

Inelastic compression bandages provide limited pressure at rest, but high pressure with activity. The prototype of
inelastic bandage is the Unna boot, a moist, zinc oxide impregnated paste bandage that hardens to an inelastic
form. Unna boots require frequent reapplication because they do not accommodate for changes in leg volume as
edema subsides and they have limited absorptive capacity for highly exudative wounds. The multi-layered elastic
bandage system is comprised of a cotton or wool layer for absorption of exudates , one or two elastic wraps, and
self-adherent wrap that maintains the bandage in place. Multi-layered elastic bandage exert continuous pressure
(40-45 mmHg at the ankle) at rest and with activity. They require less frequent reapplication than inelastic
bandages because they have the ability to conform to the lower extremity better and have superior absorptive
capacity for highly exudative wounds. The disadvantage to multi-layered inelastic compression bandage is that
they require a certain degree of expertise for adequate application. Mechanical compression is reserved for
patient who are unable to ambulate and for those who fail to respond to standard compression therapy.

Pictures of Unna boot

Triple layer compression bandage

For the second phase or maintenance phase, which occurs after wound healing, elastic graduated compression
stockings are used to control venous HTN and prevent ulcer recurrence.
Surgical intervention/procedure

The main objective of surgical treatment in these patients are to achieve ablation of the hydrostatic forces of axial
reflux (i.e disconnection of SFJ , SPJ & stripping) and removal of hydrodynamic forces of perforator venous
reflux. Various studies have shown that no more than 15% of patient have isolated deep venous reflux , whereas
53% of patients have isolated superficial reflux35.Patients with reflux in the superficial and perforating veins are
more amenable to surgical treatment and may actually have clinical cure after surgery. The surgical intervention
may help to reduce venous reflux, hasten healing, and prevent ulcer recurrence. Venous insufficiency may be
taken care of surgically by saphenous vein ablation, subfascial endoscopic surgery for the interruption of the
perforating veins; stenting for treatment of iliac vein obstruction and removal of incompetent superficial veins with
36 37 38
phlebectomy, stripping, sclerotherapy, or laser therapy . Surgical management has been shown to achieve
an ulcer healing rate of 88 percent, with only a 13 percent recurrence rate over 10 months 39. There should be an
early evaluation for possible surgical intervention however the superiority of surgery over medical management
has never been proved 40.By repairing or eliminating or repairing venous incompetence one can reduce the risk of
recurrent venous ulceration 41. Subfascial endoscopic perforator vein surgery has been described for treatment of
42
venous ulceration with proven incompetent perforators .

149
Available surgical options are:
A. Saphenofemoral Junction Ligation

Saphenofemoral junction ligation alone, sometimes referred to as a Trendelenburgs procedure, is associated

with a high rate of recurrence of varices. Recent research has shown that it is necessary to remove the
saphenous vein to ensure that as much venous reflux as possible is eliminated.

A few sound principles:

1. In a patient of normal build the SFJ lies directly beneath the groin crease; in the obese it lies above. An incision
made below the crease is likely to be too low.
2. Do not divide any vein until the SFJ has been unequivocally identified.
3. Beware of the superficial external pudendal artery that usually passes between GSV and CFV but passes
superficial to the GSV in 5% of cases.
4. Follow and divide all tributaries (Superficial circumflex iliac, superficial inferior epigastric, superficial external
pudendal) beyond secondary branch points. Failure to do so leaves a network of superficial veins connecting the
veins of the thigh with those of the perineum, the lower abdominal wall and the iliac region. These cross-groin
connections are a frequent cause of recurrence.
5. Ligate the GSV deep to all tributaries flush with the CFV.
6. Divide the deep external pudendal vein as it comes off the CFV
7. Retract the lower margin of the wound to identify and ligate the posteromedial thigh branch that often joints the
GSV high in the thigh. Failure to do so increases the risk of haematoma formation after stripping above the
bandage, as well as medial thigh recurrence. A high anterolateral branch should be dealt with similarly.

B. Stripping

Several randomized trials have clearly shown that routinely stripping the GSV reduces the risk of recurrence
developing through the Hunterian perforating veins and to remove a vein in the thigh which is difficult to treat later
by sclerotherapy. Stripping markedly reduces the risk of recurrence by:

1. Disconnecting the thigh perforators and saphenous tributaries

2. Preventing any neovascularisation arising from the saphenous stump reconnecting with the GSV.

Perhaps the most common problem with conventional stripping of the GSV has been that of saphenous nerve
damage. Stripping the vein either to or from the ankle has long been recognized as carrying a significant risk of
this unpleasant complication. It is interesting to speculate on the mechanism of saphenous nerve damage when
the vein has been stripped only as far as the knee. Trauma within the femoral triangle is one possibility.
Inadvertent passage of the stripper out of the LSV and through the fascia lata is another. For this reason, and
because the main GSV below this level is rarely varicose, many now recommend stripping to the knee. The GSV
should be stripped to approximately one hands breadth below the knee. At this level the below knee perforator
(Boyd) would have been crossed but the saphenous nerve would not yet have joined the vein. Also, important
perforating veins below the knee are a part of the posterior arch circulation and not the great saphenous vein.

Alternatives to stripping
New venous surgical techniques have been developed in an effort to reduce the number and size of lower-
extremity incisions and hematomas, to eliminate postoperative discoloration, and to reduce the recuperation time.

Radio frequency (RF) ablation: The intervention employs radiofrequency (RF) energy mediated heating of the
vein wall to destroy the intima and denature collagen in the media with resulting fibrous occlusion of the vein.24
the Closure system (VNUS Medical Technologies Inc., San Jose, CA) consists of a bipolar heat generator and
collapsible catheter electrodes suitable for use in veins ranging from 2 to 12 mm in diameter. The procedure is
usually performed under conscious sedation and local anesthesia in an outpatient setting. The catheter is
preferably introduced into the saphenous vein at the knee percutneously under ultrasound (US) guidance or
through a small incision and direct exposure of the vein. The position of the catheter at the saphenofemoral
junction is confirmed by US. Local tumescent anesthetic is instilled in the subcutaneous tissues superficial to the
vein under US guidance. The vein wall temperature is allowed to equilibrate at 85Cafter turning on the circuit
and graduated withdrawal of the catheter is performed at a rate of 3 cm/min. The heating is controlled by
monitoring temperature and impedance of the vein wall via a feedback system. Veins up to 12 mm in diameter
are treated. The mechanics of the surgical procedure are relatively straight forward with a few caveats. The
treated vein should be relatively straight, free of severe tortuosity or thrombus and without aneurysm.
Contraindications include a post phlebitic vein that cannot be accessed, a mega saphenous vein (>12 mm), and
significant dilation of the proximal saphenous vein with an aneurysmal SFJ.

Endovenous laser therapy: Endovenous laser therapy (EVLT) is similar to RF ablation, but laser energy is used
for ablation of the saphenous vein.25 The procedure is faster and easier to perform than RF ablation and there is

150
no size limitation of the saphenous vein that can be treated. Both the 810-nm and the 940-nm diode lasers are
effective in inducing thrombotic vessel occlusion. Laser-induced indirect local heat injury of the inner vein wall by
steam bubbles originating from boiling blood is proposed as the pathophysiological mechanism of action of EVLT.
This causes collagen contraction and endothelial damage. The result is thickening of the vein wall and
contraction or thrombosis of the lumen.

The use of diode laser energy to ablate the saphenous vein is a method that obviates the need for general
anaesthesia and is associated with less pain than traditional surgical stripping of the great saphenous vein. This
procedure can be performed in an office based setting using local anaesthesia following preoperative
assessment with duplex ultrasound.

Foam Sclerotherapy: An increasing number of authors have recently reported successful injection of
incompetent GSV with 3% polidocanol in the form of foam.26 The foam is generated by mixing liquid and air in a
standardized procedure of forward and backward movements within a close double-syringe system. The GSV is
punctured directly under US guidance, and the foam injected. Results are verified by serial post treatment duplex
examinations

C. Saphenopopliteal Ligation

Some surgeons advocate routine stripping of the short saphenous vein should be disconnected and never
stripped. The short saphenous vein operation should be carried out first, if a long saphenous vein operation is to
be performed under the same anaesthetic.

Failure to mark the SPJ preoperatively will lead to a misplaced incision in a significant number of cases that will
necessitate further blind incisions or abandonment of the procedure. Clinical examination and hand held Doppler
are not reliable. Insist on a duplex ultrasound.

D. Ligation of the Lower Leg Perforating Veins

Surgery for these veins is usually required in patients with lipodermatosclerosis or ulceration. The presence of
incompetent perforators in patients with advanced CVI (clinical classes 4 to 6) is an indication for surgical
treatment in a fit patient. Whereas open perforator ligation is done only in those with healed ulceration, a clean,
granulating open ulcer is not a contraindication for subfascial endoscopic perforator vein surgery (SEPS).

Subfascial ligation of the medial communicating veins (Lintons operation): In view of considerable wound
complications associated with Lintons radical operation of subfascial ligation, which included long medial,
anterolateral, and posterolateral calf incisions, it was soon abandoned and he advocated only a long medial
incision from the ankle to the knee to interrupt all medial and posterior perforating veins53 A long vertical incision
is made through the skin and subcutaneous fat down to the deep fascia, approximately 1 cm behind the
subcutaneous posterior border of the tibia. Any subcutaneous veins that are divided are ligated. The deep fascia
is incised in the same line as the skin incision and is held open gently with a self-retaining retractor. As the
subfascial space is opened, leashes of communicating vessels can be seen passing from the posterior tibial
vessels between the muscles to the undersurface of the deep fascia. These vessels are isolated, divided and
ligated. When all the communicating veins have been ligated, the deep fascia and skin are carefully
approximately. The disadvantage of Linton procedure is that the lateral perforating veins can not be taken care by
this procedure.

Extrafascial ligation of perforators (Cocketts procedure): This operation is not commonly employed today.
The aim of surgery is to clear all the extrafascial enlarged veins and to divide perforating veins. However, the
perforating veins may be difficult to accurately locate in this plane and the dissection tends to be traumatic
because of adherence of subcutaneous fat and connective tissue to the fascia due venous ulcer and
lipodermatosclerosis and associated with a higher incidence of skin necrosis.

Posterior approach (Robs procedure): This is done if the perforators on the lateral side are also to be ligated.
The incision is a posterior subfascial one and the perforators on both the sides are ligated and divided. This
procedure offers advantage in the fact that the incision is away from the areas of ulceration and thus results in
good healing.

Subfascial endoscopic perforator surgery (SEPS): The major drawback of open procedure was a high
incidence of wound complications. Edwards in 1976 designed a device called the phlebotome to ablate the
incompetent perforators from sites remote from the diseased skin. The phlebotome is inserted through a medial
incision just distal to the knee, deep to the fascia, and advanced to the level of the medial malleolus. Resistance
is felt as perforators are engaged and subsequently disrupted with the leading edge. Hauer28 introduced the
endoscopic technique for division of perforating veins in 1985. His work was soon followed by other investigators
in Europe, who used different types of endoscopes or mediastinoscopes to perform the surgery with direct vision
through a single incision made in the proximal calf.

151
The use of laparoscopic instruments was described by ODonnell, who infused saline beneath the fascia to
facilitate the visualization and dissection of the subfascial plane. In Australia, Conrad29 began using carbon
dioxide insufflation in 1993 and published a report on his first seven patients in 1994. This technique, the two
port technique, employs one port for the camera and a separate port for instrumentation, thereby making it
easier to work in the limited subfascial space. All perforators encountered are divided either with the harmonic
scalpel or electrocautery or sharply between clips. The surgeons apply metal clips to the perforating vein before
the transection or simply use electrocautery to cauterize the veins. However, the use of metal clip in a potentially
infected wound with chronic unhealthy skin and ulcer may not be desirable. The repeated movement in and out of
the operative field to reload metal clips can be time consuming when multiple perforators are found. On the other
hand, the application of electrocautery in the limited subfascial space may cause inadvertent damage to the
surrounding soft tissue by the electrical currents. The production of smoke during dissection by electrocautery
may obscure the operative field, and intermittent evacuation of smoke is needed. The ultrasonic scalpel uses
precise ultrasonic vibration to coagulate and transect the vessels in a smoke-free environment.30,31 It has been
widely used in different areas, both in laparoscopic and open surgery. The scalpel vibrates at a rate of
55000times/sec. This mechanical action results in protein denaturation and the formation of coagulum, which
seals off blood vessels. The same action causes vaporization of cells resulting tissue fragmentation. This dual
action makes dissection quicker resulting in decreased operating time.

Complications
1. Major venous damage: Deep veins can be damaged during varicose veins surgery through attempts to control
bleeding and misidentification of anatomy. Complete division of the common femoral vein is estimated to occur
once in every 10,000 varicose veins operations.
2. Arterial damage.
3. Nerve damage. Popliteal dissection, stripping and distal avulsions may result in damage to the divisions of the
sciatic nerve (usually the common peroneal nerve), saphenous and sural nerve.
4. Haematoma. This is the commonest cause of discomfort after varicose veins and can be minimized by
operating the patient in the head-down position, careful hemostasis, and evacuation of all clots from the stripper
tunnel and use of a tourniquet.
5. Venous thromboembolism.
6. Necrosis of the wound edges: this is the most common and troublesome complication of both the subfascial
and extrafascial operations. It appears to occur more frequently after the extrafascial operation

E. Elimination of Residual Varicosities

Sclerotherapy: The aim of injection sclerotherapy is to place a small volume of sclerosant in the lumen of a vein
empty of blood, and then appose the walls of that vein with appropriate compression. The vein fibroses and gets
closed without the formation of clot. The sclerosant must remain localized within the segment of vein to be
treated. The vein must be kept empty of blood both during and after the injection. Patients should be mobilized
immediately afterwards and be encouraged to walk on a daily basis. This measure allows symptoms and signs of
allergic reactions to appear and be treated. The comfort of elastic compression can be evaluated, and the deep
venous circulation is stimulated and any sclerosant that has entered from the superficial injection is flushed.
Immobility is a relative contraindication to sclerotherapy.

Indications of sclerotherapy:
1. Telangiectasia
2. Reticular varicosities and reticular veins
3. Isolated varicosities
4. Below knee varicosities
5. Recurrent varicosities

Contraindications:
1. Presence of arterial occlusive disease
2. Patient immobility
3. Hypersensitivity to the drug
4. Acute thrombophlebitis
5. Huge varicosities with large communications to deep veins

Technique:
1. The patient is examined standing and varices are marked with an indelible pen.
2. A number of 2ml syringes fitted with 26 gauge needles are filled with 0.5 ml of sclerosant. Maximum volume
that can be given during one treatment is around 10 ml of sclerosant.
3. The skin is cleaned and venepunctures are made at 5 cm intervals along the course of each vein.
4. The patient lies down, veins are transfixed and the needle is slowly withdrawn. As soon as the blood appears
in the vein, the vein is emptied and the sclerosant is injected into the empty vein.
5. Cotton wool balls are placed and fixed with micropore tape.

152
6. When all injections have been completed, crepe bandages are applied and the patient is encouraged to
walk.
7. Compression bandages are worn for 3 weeks. After this period the legs are carefully inspected and
untreated varices or failed injection sites are re-injected.

Complications
The complications of injection sclerotherapy include:
1. Anaphylaxis.
2. Allergic reactions. Typically symptoms include urticaria, peri-orbital and oral swelling, bronchospasm and
migraine.
3. Ulceration. Ulceration follows extravascular injection. Commonly it is due to arterial occlusion caused by
sclerosant reaching a terminal arteriole. Another cause is reactive vasospasm because of a large volume of
injection. Treatment is symptomatic. Unless the ulcer is obviously infected (rare) antibiotics have no role.
4. Arterial injection. This is a serious complication that is accompanied by severe pain distal to the injection site.
The most vulnerable artery appears to be the posterior tibial artery at the ankle. Treatment includes
analgesia, cooling of the foot, and infusion of heparin and dextran.
5. Pigmentation. Pigmentation is due to the deposition of haemosiderin, often following superficial
thrombophlebitis. Most commonly seen in those treated with sodium tetradecylsulphate and hypertonic
saline and least common with polidocanol.
6. Superficial thrombophlebitis. This occurs when clot remains in the lumen of the sclerosed vein and is largely
due to inadequate compression. Localisedhaematoma is particularly painful and may be eased by aspiration
with a needle or scalpel under local anaesthesia.
7. Deep venous thrombosis. The risk is reduced by careful patient selection and by advising patients to walk
immediately after injection treatment and thereafter on a regular basis each day.
8. Nerve damage. Can occur due to approximate injection and/or pressure from bandaging.
9. Telangiectatic matting: or neoangiogenesis is the new appearance of red telangiectasias in a site of prior
sclerotherapy. It is believed to be a complex process in which new vessels grow in response to endothelial
growth factors or platelet-derived growth factors. Prevention is best achieved through use of dilute solutions
and in small volume

Skin Grafts and Flaps

Skin grafts and flaps have been used for the management of chronic ulcerations. They should only be applied to
a clean, uninfected ulceration with an adequate vascular supply. It has been suggested that the benefit of skin
grafts are the transplanted cells, which can secrete growth factors and other products that might enhance
healing. Full-thickness or split-thickness grafts can be used. Allogeneic (cultured) keratinocytes also may be used
but can be expensive. There is increasing interest in tissue-engineered skin. Graft skin (Apligraf) is a bilayered
skin equivalent that includes dermal and epidermal components and is manufactured by harvesting neonatal
foreskins and extracting both keratinocytes and fibroblasts that are then cultured separately to create the
epidermal and dermal components. Graftskin has been approved by the Food and Drug Administration (FDA) for
use in diabetic neuropathic ulcerations and venous ulcerations. Dermagraft is comprised of human fibroblasts on
a bioabsorbable scaffold; studies indicate that this product also may be useful for venous ulcerations.

Prevention of recurrence
The cornerstone of prevention of recurrence of venous ulceration is compression 38.A Cochrane review cited
circumstantial evidence for the benefit of compression as a whole ,and referred to evidence that high
compression is superior to moderate compression for the prevention of recurrence. Patient education is
important in the prevention of recurrences as well.

Oral agents for the treatment of venous ulcers

Pentoxifylline is xanthine derivative that is thought to treat occlusive disease by decreasing blood viscosity with
approval by the FDA for the treatment of claudication 39.In a systemic review of clinical trials , it has been found to
be helpful in treating venous ulcers and has been recommended as an adjunctive treatment 40.

Zinc was popularized as a topical treatment for leg ulcers during the past century , and one study found it helpful
for arterial and venous ulcers 41.Although it might have a mild antimicrobial effect , there is no evidence that zinc
can improve wound healing 41.It is argued that although Unna boots(made with zinc paste) are used in the
treatment of venous ulcers , they may be effective because of compressive effect and not because of the
42
composition of the plaster .A metaanalysis did not find sufficient evidence that oral zinc sulfate could improve
the wound healing of venous ulcers 43.

Diuretic treatment of peripheral edema caused by CVI is a temporizing measure that does not address the true
physiological problem 44.In the treatment of venous ulcers, however they may occasionally found to be useful to
acutely decrease the volume of leg edema.

Oral micronized purified flavonoid fraction modulates leukocytes adhesion and prevent endothelial damage and it
45
may also promote healing of venous ulcer .

153
Aspirin & Iloprost are also used as an adjunct to compression therapy, however there are insufficient data to
recommend their routine use.

Adjunctive management/ Advanced / Investigational Techniques

Several supplemental techniques have tried or are under investigation. The topical application of Simulium
vittatum erythema protein extracted from black flies may locally increase blood flow to aid in wound
46 47
healing .Topical autologous platelets have no significant adjuvant effect on healing of chronic venous ulcers
48
. Platelet derived growth factors , however have become popular in wound care centre,and have been shown to
49 50 51
be helpful in diabetic ,neuropathic ,decubitus ulcers. However the role of PGDF in chronic venous ulcer is
52
inconclusive .Recombinant PDGF.BB (Becaplermin) has been approved by the FDA for use in diabetic foot
ulcers.* and a recombinant GCSF product (Filgastrim) is proven to be effective as a subcutaneous injection for
the treatment of infected diabetic foot ulcers.*At this time,none of these treatments have been comprehensively
studied for the treatment of venous ulcers.
Further clinical studies are needed to elucidate the role growth factors may play in venous ulcers.*

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Database Syst Rev. 2000;(2): CD001733; PMID: 10796661]. Cochrane Database of Systematic
Reviews2002:CD001733
46. Brandrup F, Menne T, Agren MS, et al: A randomized trial of two occlusive dressings in the treatment of leg
ulcers. ActaDermVenereol 1990;70:231-5.
47. Margolis DJ, Berlin JA, Strom BL: Which venous leg ulcers will heal with limb compression bandages? Am J Med
2000;109:15-9.
48. Wilkinson EA, Hawke CI: Does oral zinc aid the healing of chronic leg ulcers? A systematic literature review [see
comment]. Arch Dermatol 1998;134:1556-60.
49. Felix W: MedikamentoseTherapiebeivenosenDurchblutungsstorungen des Beines. Hautarzt 1979;30:198-201.
50. Coleridge Smith PD: From skin disorders to venous leg ulcers: path physiology and efficacy of Daflon 500 mg in
ulcer healing [see comment]. Angiology 54:S45-S50, 2003 (suppl 1)
51. Cupp MS, Ribeiro JM, Champagne DE, et al: Analyses of cDNA and recombinant protein for a potent vasoactive
protein in saliva of a blood-feeding black fly, Simuliumvittatum. J ExpBiol 1998;201:1553-61.
52. Senet P, Bon FX, Benbunan M, et al: Randomized trial and local biological effect of autologous platelets used as
adjuvant therapy for chronic venous leg ulcers [see comment]. J VascSurg 2003;38:1342-48.
53. Weed B, Davis M, Felty C, et al: Autologous platelet lysate product versus placebo in patients with chronic leg
ulcerations: a pilot study using a randomized, double-blind, crossover trial. Wounds 2004;16:273-82..
54. Smiell JM, Wieman TJ, Steed DL, et al: Efficacy and safety of becaplermin (recombinant human platelet-derived
growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four
randomized studies. Wound Repair Regen 1999;7:335-46.
55. Wieman TJ, Smiell JM, Su Y: Efficacy and safety of a topical gel formulation of recombinant human platelet-
derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III
randomized placebo-controlled double-blind study. Diabetes Care 1998;21:822-27.
56. Mustoe TA, Cutler NR, Allman RM, et al: A phase II study to evaluate recombinant platelet-derived growth factor-
BB in the treatment of stage 3 and 4 pressure ulcers. Arch Surg 1994;129:213-19.
57. Vasques R, Marien BJ, Gram C, Goodwin DG, Menzoian JO, Raffetto JD. Proliferative capacity of venous ulcer
wound fibroblast in the presence of Platelet-derived growth factor. Vasc.Endovascular Surg.2004 Jul-
Aug;38(4):355-60
58. Gough A, Clapperton M, Rolando N, et al: Randomised placebo controlled trial of granulocyte-colony stimulating
factor in diabetic foot infection. Lancet 1997;350:855-9.
59. Banta MN, Eaglstein WH, Kirsner RS: Healing of refractory sinus tracts by dermal matrix injection with Cymetra.
DermatolSurg 2003;29: 863-6.

The Thoracic Outlet Syndrome

Sabyasachi Bal

Thoracic outlet syndrome is not the name of a single entity, but rather a collective title for a variety of conditions
attributed to compression of these neurovascular structures as they traverse the thoracic outlet.The thoracic
outlet is bordered by the scalene muscles, first rib, and clavicle. Neurovascular structures pass from the neck and
thorax into the axilla through this space. Thoracic outlet syndrome remains one of the most controversial clinical
entities in medicine.

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Epidemiology

The wide variability of symptoms and signs in patients with thoracic outlet syndrome and the lack of an objective
confirmatory test for the diagnosis makes correctly identifying patients with thoracic outlet syndrome difficult.
Therefore, determining its exact incidence remains elusive; estimates range from 3-80 cases per 1000
population. Thoracic outlet syndrome is more common in women, particularly those with poor muscular
development, poor posture, or both.

Functional anatomy

The neurovascular bundle courses through 3 spaces, or triangles, as it exits the neck to reach the axilla and
proximal arm. All 3 spaces can be the source of compression of the various components of the neurovascular
bundle, including the brachial plexus and the subclavian vessels. These spaces are small at rest and become
even smaller with certain arm maneuvers, such as abduction and external rotation. [13, 14] This can aid in the
diagnosis of thoracic outlet syndrome and forms the basis for provocative testing,

The first space is the interscalene triangle. It is bordered by the anterior scalene muscle, the middle scalene
muscle, and the upper border of the first rib. This space contains the trunks of the brachial plexus and subclavian
artery. The interscalene triangle is the most common site for neural compression, vascular compression, or both.

The second space is the costoclavicular triangle, which is bordered by the clavicle, first rib, and scapula and
contains the subclavian artery and vein and the brachial nerves.

The third and final space is beneath the coracoid process just deep to the pectoralis minor tendon; it is referred to
as the subcoracoid space.

Sport Specific Biomechanics

Thoracic outlet syndrome is most often seen in patients who engage in repetitive motions that place the shoulder
at the extreme of abduction and external rotation. An example of such activity is swimming, especially with the
freestyle stroke, butterfly stroke, and backstroke. When a swimmer reports tightness and pain around the
shoulder, neck, and clavicle as his or her hand enters the water, thoracic outlet syndrome should be suspected.

In addition to swimmers, other athletes affected by thoracic outlet syndrome include water polo, baseball, and
tennis players and athletes in any other activity that places repetitive stress on the shoulder at the extremes of
abduction and external rotation. These individuals may present with neurologic and arterial or venous symptoms.
Venous thoracic outlet syndrome most commonly develops in young male athletes in whom the upper extremity
musculature is overdeveloped as a result of work or physical conditioning. Baseball players, whose sport requires
repetitive throwing motions, are at increased risk for arterial thoracic outlet syndrome in their dominant arm.

Presentation

The initial presentation of thoracic outlet syndrome is dependent on whether the compression is primarily
vascular, neurogenic, or a combination of both. It is also dependent on the underlying continuum of
histopathologic changes noted with chronic nerve compression, ranging from intermittent to constant debilitating
symptoms. Three symptomatic patterns emerge; these are vascular, true neurogenic, and disputed or
nonspecific-type thoracic outlet syndrome.

Vascular thoracic outlet syndrome is rare and can involve the subclavian artery or vein. Both forms of vascular
thoracic outlet syndrome tend to occur in young patients who perform vigorous overhead arm activity such as
throwing. With venous obstruction (if secondary to thrombosis, Paget-von Schrtter syndrome), patients may
present with upper extremity swelling, venous distention, or diffuse arm or hand pain (including the forearm).

With arterial obstruction, patients may report color changes of their affected upper extremity, claudication, or
diffuse arm or hand pain (including the forearm). Because of arterial collateral blood flow, the iinitial symptoms
tend to be mild, with arm ache and fatigue, particularly after overhead activity. Patients typically seek medical
evaluation after ischemic events (eg, ulceration, gangrene, absent pulses) occur.
Neurogenic thoracic outlet syndrome involves compression of the brachial plexus. Similar to vascular thoracic
outlet syndrome, a pure neurogenic presentation is also rare. Patients present with painless atrophy of the
intrinsic muscles of the hand, and athletes may report difficulty grasping a racket or ball as a result of intrinsic
muscle weakness. They may also report sensory loss or paresthesias. Pain is often reported but is not as
dramatic as in the nonspecific-type thoracic outlet syndrome. Again, neurogenic thoracic outlet syndrome tends
to affect individuals who perform overhead arm activities.

The disputed or nonspecific-type thoracic outlet syndrome refers to a large group of patients with unexplained
pain in the arm, scapular region, and cervical region. Typically, their symptoms begin after a traumatic event (eg,

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motor vehicle accident). Much debate surrounds this diagnosis, with certain providers believing the disorder is
underdiagnosed and others believing it is overdiagnosed.

The clinical examination

The examination should begin with an assessment of the patients posture. A slumped posture of the shoulders
and upper back and a poked-forward position of the head and neck are comfortable but potentially damaging for
the scapular and neck muscles and are thought to contribute to the susceptibility for thoracic outlet syndrome.

The symmetry of both arms should be evaluated. Cervical active range-of-motion assessment and the Spurling
test (ie, patients head is placed in extension and lateral flexion, with axial compression applied by the examiner
to the patients head in an effort to recreate radicular pain) should be performed. Active and passive range of
motion of both shoulders should be examined. A careful neurovascular examination of both upper extremities is
needed, taking care to remember that the muscles and nerves supplied by the lower brachial plexus are most
commonly affected.

Vascular thoracic outlet syndrome has different examination signs depending on whether the venous or arterial
vessels are affected. With venous compression, patients often present with edema and cyanosis of the upper
extremity. They may also have distended veins in the shoulder or chest. With arterial compression, patients often
present with pallor, a weak or absent pulse, and coolness of the upper extremity. Decreased blood pressure
greater than 20 mm Hg in the affected arm compared with the contralateral arm is sometimes noted and is a
reliable indicator of arterial involvement. Rarely, small infarcts are noted in the hands and fingers, which are due
to embolization.

The classic finding in a person with neurogenic thoracic outlet syndrome is the Gilliatt-Sumner hand. This
physical examination finding includes atrophy of the abductor pollicis brevis with lesser involvement of the
interossei and hypothenar muscles. Patients may also have decreased sensation that follows the ulnar nerve
distribution because the lower trunks of the brachial plexus are usually more involved than the upper trunks.

Patients with disputed or nonspecific-type thoracic outlet syndrome tend to have diffuse upper extremity pain with
guarding. Examination tends to be difficult and findings nonfocal. Weakness and decreased sensation tend to be
unreliable signs that are difficult to quantify.

Because of the variability of the structures involved in thoracic outlet syndrome, many provocative maneuvers
have been described to aid in diagnosis. They include the Adson maneuver, Wright test, and Roos stress test.
Note, however, that these tests have high rates of false-positive and false-negative results.

The Adson maneuver is performed by positioning the tested shoulder in slight abduction and extension. Then, the
patient extends his or her neck and turns the head toward this affected shoulder. The patient inhales while the
examiner simultaneously palpates the ipsilateral radial pulse. If the pulse diminishes or the patient has
paresthesias, the test result is considered positive as long as this maneuver does not cause symptoms on the
asymptomatic contralateral side.

The Wright test is performed by progressively hyperabducting and externally rotating the patients affected arm
while assessing the ipsilateral radial pulse. Again, the test result is considered positive if the pulse diminishes or
paresthesias develop.

The Roos stress test is performed with the patient positioning both of his or her shoulders in abduction and
external rotation of 90 with elbow flexion at 90. The patient then opens and closes his or her hands for several
minutes. Reproduction of symptoms or a sensation of heaviness or fatigue is considered a positive test result.

Causes

Causes of thoracic outlet syndrome can be divided into bony and soft-tissue factors. Bony factors include
abnormalities such as anomalous cervical ribs, hypoplastic first thoracic ribs, and exostoses of the first rib or
clavicle.[17, 18] The rate of anomalous cervical ribs is considered to be 0.17-0.74% in the general population, and
the rate of rudimentary first ribs is 0.29-0.76%.

Soft-tissue factors include congenital anomalies such as anomalous fibrous muscular bands near the brachial
plexus and hypertrophic muscles in athletes and weight lifters. Space-occupying lesions (eg, tumors, cysts) and
inflammatory processes also occur in the soft tissues and can cause thoracic outlet syndrome.

Trauma or mechanical stress to the neck, shoulders, or upper extremities can lead to thoracic outlet syndrome. In
fact, a combination of neck trauma and anatomic predisposition (ie, cervical rib) is considered the main etiology
of thoracic outlet syndrome. Posttraumatic conditions such as hematoma, myositis ossificans, and scar formation
can be important variables, as can a droopy shoulder secondary to trapezius muscle weakness. Thoracic outlet
syndrome can be secondary to malunion of a clavicle fracture.

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Interestingly, multiple points of compression may be present as the peripheral nerves descend from the thoracic
outlet to the hand (simultaneous thoracic outlet syndrome and ulnar nerve compression at the elbow or carpal
tunnel syndrome in the wrist). This has been referred to as double-or multiple-crush syndrome.

Diagnosis

In thoracic outlet syndrome with vascular compromise or nerve compression, with resultant atrophy of the
intrinsic hand muscles, the diagnosis is not controversial and specific tests can confirm the diagnosis. However,
no infallible clinical tests, laboratory tests, radiographic tests, or electrical studies establish the diagnosis of
thoracic outlet syndrome syndrome in patients with disputed or nonspecific-type thoracic outlet syndrome. Many
tests are available to refine the differential diagnosis and confirm or exclude other potential conditions (see
Differentials and Other Problems to Be Considered).

To exclude systemic disease and inflammation, a few simple blood tests may refine the differential diagnosis for
thoracic outlet syndrome, including a blood glucose level, complete blood cell (CBC) count, erythrocyte
sedimentation rate (ESR), basic metabolic panel, thyrotropin level, and rheumatologic workup, if indicated.

Imaging

Radiography
Cervical spine and upper thoracic spine radiographs may demonstrate bony abnormalities. Chest, shoulder, and
clavicle radiographs may also identify bony abnormalities.

Computed tomography (CT) scanning and magnetic resonance imaging (MRI)

CT scanning and MRI are more useful for identifying other conditions that might cause similar symptoms, rather
than for establishing the diagnosis of thoracic outlet syndrome.

Magnetic resonance angiography (MRA)

MRA can be useful for the diagnosis of arterial vascular thoracic outlet syndrome.

Venography and duplex scanning

Venography and duplex scanning (ie, ultrasonography combined with Doppler velocity waveforms) are used to
assist in the diagnosis of subclavian vein compression (thrombosis). These tests can be performed dynamically
with positions that recreate the tension placed on the thoracic outlet during certain motions such as abduction
and external rotation.

Other Tests
Electrodiagnostic studies can be helpful for classic cases of neurogenic thoracic outlet syndrome and therefore
can be useful when the results are positive. However, many symptoms are intermittent in neurogenic thoracic
outlet syndrome; therefore, negative test results do not rule out this diagnosis. Electrodiagnostic testing can also
be helpful in diagnosing other neuromuscular disorders.

Nerve conduction velocity has been used for the diagnosis of thoracic outlet syndrome as defined by a reduction
to less than 85 m/s of either the ulnar or median nerves across the thoracic outlet and was found to corroborate
the clinical diagnosis. A nerve conduction velocity of less than 60 m/s was considered an indication for surgery.
However, as with many aspects of thoracic outlet syndrome, this remains controversial and has not been
universally accepted.

Somatosensory evoked potentials are equally controversial, with some studies favoring their use and others not.

Electromyography may be helpful in confirming the presence or absence of a specific alternative diagnosis.

Management

Surgery in cases of thoracic outlet syndrome is indicated for acute vascular insufficiency and progressive
neurologic dysfunction. For subclavian venous thrombosis, treatment addresses 3 problems: the clot, the
extrinsic compression, and the intrinsic damage to the vein. Thrombolysis with urokinase is the most commonly
recommended treatment, with continued anticoagulation for several months. The timing of surgical
decompression is debated, but surgical decompression is needed for long-term improvement. Patients with acute
ischemia of the upper extremity require prompt diagnosis and surgical treatment.

All other patients should receive nonoperative treatment that includes relative rest, nonsteroidal anti-inflammatory
medications (NSAIDs), cervicoscapular strengthening exercises, and modalities such as
ultrasound, transcutaneous nerve stimulation, and biofeedback. Conservative care has been shown to be
successful in most patients. In those patients in whom pain is refractory to conservative care, surgery should be
considered.

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Physical Therapy
Physical therapy that addresses postural abnormalities and muscle imbalance relieves symptoms in most
patients with thoracic outlet syndrome by relieving pressure on the thoracic outlet. This is based on 3 potential
effects of abnormal static or repetitive postures and positions.

First, increased pressure directly around nerves at various entrapment points or increased tension on nerves
creates chronic nerve compression. Second, certain postures maintain muscles in abnormally shortened
positions, resulting in a new length. When these adapted muscles are stretched, pain occurs. Third, abnormal
posture results in some muscles being stretched and others being shortened to new lengths, resulting in both
being placed at a mechanical disadvantage and leading to muscle imbalance. This is the basis for physical
therapy.

Although, many conservative protocols for physical therapy are described, few outcome studies have been
published. The few studies available demonstrate positive outcomes for most patients.

Patient treatment includes several components that address the brachial plexus nerve compression and muscle
imbalance in the cervicoscapular region. Key points emphasized in treatment begin with education. Postural
correction focuses on positions of most risk and least risk for compression, with integration into the patient's
activities of daily living at work, home, and sleep. For example, patients should avoid overhead arm positions
while sleeping. Postural and position correction can be aided by wrist splints, elbow pads, soft neck rolls for
nighttime use, and lumbar supports for sitting. In addition, the impact of body habitus and general physical
conditioning should be evaluated and discussed (ie, obesity, breast hypertrophy).

Physiotherapy focuses on pain control and range of motion with specific stretching exercises. Stretching should
begin with short, tight muscles (ie, upper trapezius, levator scapulae, scalenes, sternocleidomastoid, pectoralis
major, pectoralis minor, suboccipitalis) and should not be aggressive. Once pain control and cervical motion are
regained, strengthening exercises of the lower scapular stabilizers are begun, as is an aerobic conditioning
program. The importance of patient compliance should not be overlooked.

Surgical Intervention

Little argument exists for the surgical treatment of a patient with severe compression or compromise of the
subclavian vein or artery. However, less severe cases are more controversial. Likewise, patients with atrophy of
the intrinsic muscles of the hand secondary to thoracic outlet syndrome with no distal sites of compression need
surgical intervention.

Because of the high prevalence of surgical complications and variable reports of success, many surgeons offer
surgery to patients with disputed or nonspecific-type thoracic outlet syndrome only as a last resort after prolonged
conservative management and a detailed discussion regarding the risks and complications of surgery. Potential
complications from surgery can include pneumothorax, injury to the subclavian artery or vein, injury to the
brachial plexus and long thoracic nerve, apical hematoma, intercostobrachial nerve injury, and injury to the
thoracic duct.

The surgical approach used varies and may be specialty dependent, with the transaxillary approach preferred by
many thoracic and vascular surgeons and the anterior supraclavicular approach favored by most neurosurgeons.
Both approaches allow for first rib removal and part or total scalene muscle removal.

Success rates for surgery vary dramatically in the literature. One review of 47 patients with thoracic outlet
syndrome revealed 75% lower plexus and 50% upper plexus compressions remained asymptomatic at 4.6 years.
Morbidity in this study involved 17% of patients and was most frequently the result of incisional pain. However,
not all studies have been so impressive. One retrospective analysis of patients with nonspecific neurogenic
thoracic outlet syndrome demonstrated work disability at 1 year after surgery in 60% of patients. At 4.8 years of
follow-up, 72.5% patients were limited in activities.

This has led many surgeons to agree with Wood et al, who empathically stated in 1988 that some errors always
occur in diagnosis, and, therefore, surgery should be advised "on a basis of exclusion and with great
reservation." This is especially true for disputed or nonspecific-type thoracic outlet syndrome.
Postoperative physical therapy is essential for strengthening and range of motion.

Rehabilitation

Physical Therapy
Continued regular stretching of the muscles around the cervical girdle (eg, scalene, pectoralis major and minor,
trapezius, levator scapulae, and sternocleidomastoid muscles) is essential.

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Recommended exercises for thoracic outlet syndrome include neck stretching, abdominal breathing, and postural
exercises. Ineffective therapies include shoulder shrugs (useful for prevention), weight lifting, and neck traction.
Exercises should be performed at home at least twice a day.

Medical Issues/Complications

Patients may require continued postoperative anticoagulation with warfarin.

To help prevent recurrence of thoracic outlet syndrome, the patient should avoid sleeping with his or her
arms in an overhead position.

Primary Hyperparathyroidism

Sunil Chumber, Pratyusha Priyadarshini

Introduction

Parathyroid gland was first identified by Sir Richard Owen during the autopsy of Indian Rhinoceros in 1850. In
1879, Ivar Viktor Sandstorm, named parathyroid glands in human as Glandulae Parathyroideae and he also
described tetany in post thyroidectomy patient. Felix Mandl performed first planned successful parathyroidectomy
for carcinoma of parathyroid in 1925.

Parathyroid glands are four in number and located on the posterosuperior surface of thyroid. However in 13%
they are supernumerary (more than or equal to five) and in 3% they are lesser in number. A normal parathyroid
gland measures 5-7 mm in size and weighs 15-40mg. Inferior parathyroid glands and the thymus are derived
embryologically from third branchial pouches, while superior parathyroid glands arise from third branchial pouch
along with the thyroid.

Hyperparathyroidism is the third most common endocrine disorder after diabetes mellitus and thyroid disease. It
is three times more prevalent in women and also its incidence increases with age. Primary hyperparathyroidism
(PHPT) is frankly elevated or inappropriately normal parathormone levels in the presence of hypercalcemia. It is
the most common cause of hypercalcemia. Most common cause of primary hyperparathyroidism is parathyroid
adenoma in 80-85% of cases. Remaining 15-20% of cases are due to multiglandular parathyroid hyperplasia
which are mostly associated with MEN1 or MEN2a. Parathyroid carcinoma is rare and accounts for <1% of cases
of primary hyperparathyroidism. Diagnosis and management of parathyroid disease has changed radically in the
past two decades.

Clinical presentation

Patients with hyperparathyroidism have been known to present with classic pentad of symptoms (kidney stones,
painful bones, abdominal groans, psychic moans and fatigue overtones). In western countries due to routine
screening of serum calcium, more and more patients are diagnosed in asymptomatic or pauci-symptomatic
stage. However, the clinical presentation in our country has not changed much over the decades. In our
experience of more than 300 primary hyperparathyroidism, 95% of patients were symptomatic at presentation
and multisystem involvement is rule rather than exception. Skeletal system is most common involved system in
approximately 70% of patients. Bone disease may present as osteopenia, osteoporosis, bone deformities, brown
tumors, increased fragility, delayed healing of fractures and multiple fractures. Next common organ to get
involved is kidney in approximately 30-40% of patients. Kidney involvement may present with nephrolithiasis,
nephrocalcinosis, hypercalciuria, chronic renal insufficiency,nephrogenic diabetes insipidus,thirst,polydipsia and
polyuria. Gastrointestinal involvement is present in 25-30% of patients, with peptic ulcer disease being most
common manifestation and pancreatitis present in 5% of our patients. Central nervous system involvement is
often underreported (10% in our series) because most of the symptoms are very subjective and can be elicited
only on detailed questioning. Myopathy is another common clinical manifestation and proximal muscle groups are
more frequently involved. Most of the patients have no palpable disease however, in patients with large adenoma
neck lump may become palpable.

Investigations

Biochemical Studies
The diagnosis of PHPT is established with the presence of an elevated serum calcium and intact PTH level.
Patients with PHPT also have decreased serum phosphate and elevated 24-hour urinary calcium concentrations.
Elevated levels of alkaline phosphatase are found in approximately 60-70 % of patients with PHPT and are
indicative of high-turnover bone disease. Alkaline phosphatase levels are markedly elevated in patients with

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severe bone disease; however in patients with isolated renal disease they may be normal. These patients are
prone to develop postoperative hypocalcemia due to bone hunger.

Few patients may present with normocalcemic PHPT due to vitamin D deficiency, a low serum albumin, or a low
normal blood calcium set point. Normocalcemic PHPT is more prevalent in our country (approximately 25% in our
series). These patients have increased total PTH levels with or without increased blood ionized calcium levels.

Radiologic Tests
In patients with PHPT, characteristic bone lesions are present on radiograph. Subperiosteal resorption is virtually
pathognomonic for hyperparathyroidism and is typically seen at the radial aspect of the middle phalanx of the
index and middle fingers.Bone mineral densitometry studies using dual-energy absorptiometry are being
increasingly used to assess the effects of PHPT on bone. Abdominal ultrasound examination is used selectively
to document renal stones.

Preoperative Localization Tests

It has become routine to localize hyperfunctioning parathyroid glands before parathyroidectomy. Localization
studies have permitted surgeons to perform more limited operation. The predominant imaging techniques for
preoperative localization of parathyroid adenomas are ultrasonography and 99mTc-sestamibi scintigraphy.
Numerous studies done to compare these techniques suggest similar sensitivities and specificities for detection
of solitary adenoma. Reported sensitivities for the detection of solitary parathyroid adenomas by ultrasonography
range from 72% to 89%. Sonography has the advantage of being more specific regarding the site of an adenoma
in relation to the thyroid gland. In our series ultrasonography was performed in 65% patients and its sensitivity
was 86% and it was accurate in localizing the culprit lesion in 77% of patients. Sestamibi with 99mTc is the most
commonly used radiotracer for imaging the hyperfunctioning parathyroid glands and has been extensively studied
in the setting of primary hyperparathyroidism . Sensitivity of parathyroid scintigraphy has been reported to range
from 80-100% and it clearly has an advantage in the detection of ectopic glands, particularly in the mediastinum .
Sensitivity of sestamibi scan in our series was 93% and it was more sensitive for ectopic lesions as compared to
ultrasonography (94% versus 44%). A preoperative approach combining both sonography and scintigraphy has
been shown to predict more accurately the presence and location of solitary adenomas than either technique
alone. At our centre combining both the modalities for localization increased the sensitivity to 97%.

Single-photon emission CT is now being used increasingly as it has been shown to be superior to other nuclear
medicinebased imaging. It is more sensitive than sestamibi scan and has got better image acquisition,
specifically it can indicate whether an adenoma is located in the anterior or posterior mediastinum
(aortopulmonary window), thus enabling the surgeon to modify the operative approach accordingly.

CT and MRI scans are less sensitive than sestamibi scans, but are helpful in localizing large paraesophageal and
mediastinal glands. More recently, four-dimensional CT (4D-CT) has shown utility in parathyroid localization. This
technique incorporates the perfusion of contrast in hyperfunctioning parathyroid tissue over time, thus providing
functional information in addition to the anatomic information provided by conventional three-dimensional CT
imaging.

Management

Surgery is the mainstay of treatment for PHPT and requires successful localization and excision of the abnormal
gland(s). The surgical approach to patients with primary hyperparathyroidism has evolved since the first
successful parathyroidectomy performed by Felix Mandl in 1925. Since then, bilateral neck exploration with
resection of enlarged parathyroid glands has been the gold standard operation performed for this disease.
Conventional neck exploration is conducted through a standard transverse skin crease neck incision. An attempt
is made to identify all the 4 glands and excision of abnormal gland is done with or without biopsy of normal gland.
It has more than 95% cure rate and minimal morbidity in the hands of an experienced endocrine surgeon.
However, since 80-90% of primary HPTH cases are due to a single parathyroid adenoma, the need for bilateral
neck explorations have been questioned and it lead to evolution of unilateral approaches termed minimally
invasive parathyroidectomies. Various types of minimally invasive procedures available are minimally invasive
radioguided parathyroidectomy (Norman et al), minimally invasive parathyroidectomy with intraoperative PTH
assay (Irvin et al), video-assisted and endoscopic parathyroidectomy. The prerequisite for all of them is
successful preoperative localization with nuclear scan and/or ultrasonogaphy of neck. Open minimally invasive/
focused parathyroidectomy comprises of reduced skin lesion placed on the side of localization, division of strap
muscles, identification of the abnormal parathyroid gland and ligation of its vascular supply and excision. In this
approach only abnormal gland is excised and no attempt is made to identify other glands. Bergenfelz et al
compared bilateral versus unilateral neck exploration for primary HPTH in the first prospective randomized trial
and reported that there was no difference in cure rates or complications between patients in the two groups.

In our series, minimally invasive parathyroid surgery was performed in overall 58% of our patients, however after
year 2000, 76% of surgeries were carried out by minimally invasive approach. At our centre, for all patients
diagnosed with primary hyperparathyroidism, two localizing investigations preferably USG and sestamibi scan
are ordered. In patients with no evidence of familial disease and concomitant thyroid pathology, if findings of both

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the investigations are concordant, an open minimally invasive parathyroidectomy without introperative PTH assay
or frozen section is performed. In remainder of our patients conventional neck exploration is the procedure of
choice. Cure rates for minimally invasive surgery and conventional neck exploration in our series were 97.7% and
98.5% respectively which includes the reoperative cases in both groups. There was no mortality in whole series
and only one patient had transient paresis of unilateral recurrent laryngeal nerve which recovered completely.

For patients undergoing reoperative parathyroid surgery a comprehensive preoperative work up is must before
venturing into the surgery. Operative records of previous surgery, localization studies and previous histopatholgy
should be reviewed extensively. For patients operated outside, the surgeon who had performed the initial surgery
preferably should be contacted. If needed fresh localization studies should be ordered. Intra operative infusion of
methylene blue dye has been found to be very useful in facilitating the localization of gland in reoperative
surgery.

Most of our patients will develop hypocalcemia after successful surgery due to hungry bone syndrome. All the
patients will require calcium and vitamin D supplementation for 3 to 6 months after surgery which can be
gradually tapered down. Patients are called for regular follow up at 6 monthly interval and serum calcium and
intact PTH level are monitored. Outcome after parathyroid surgery is excellent, most of the patients report
improvement in bone pain, elevation of mood and sense of well being immediately after surgery. In the long term,
the healing of fractures is accelerated and bone mineral density improves after surgery and most of the sequelae
of the disease are reversed.

Conclusion

The diagnosis of PHPT is based on the presence of elevated serum calcium and intact PTH level. Most of our
patients present with classical symptoms of PHPT. The most common pathology for PHPT is single adenoma
and surgery is the mainstay of treatment for PHPT. The surgical management of primary hyperparathyroidism
has evolved significantly over the past few decades mainly due to improved preoperative localization of
parathyroid adenomas. Ultrasonography and nuclear scintigraphy successfully localize the adenoma in 85-95%
of patients with PHPT. Minimally invasive parathyroidectomy has replaced conventional bilateral neck exploration
in patients with a localized adenoma on preoperative imaging. In carefully selected patients, the minimally
invasive technique provides cure rates comparable to the traditional bilateral approach. Conventional neck
exploration is reserved for patients who have familial disease, concomitant thyroid pathology, discordant or
nonlocalized lesion. Despite improvement in imaging modalities and surgical technique, a good parathyroid
surgeon is must to ensure successful parathyroid surgery. The old dictum that for parathyroid surgery the only
localization which is needed is to locate a good parathyroid surgeon will always remain relevant.

References

1. Textbook of Endocrine Surgery (eds Orlo H. Clark Quan-Yang Duh and Electron Kebebew) pp 365-371 Elsevier
Saunders, Philadelphia, PA.
2. Endocrine Surgery: Principles and Practice (eds Hubbard J, Inabnet WB, Lo C-Y) pp 267-278 Springer, London
3. The Parathyroids, Basic and Clinical Concepts (1994),pp. 531551. Raven,New York.

Surgery for Hereditary MEN-related tumors

Amit Agarwal, NavneetTripathi, Roma Pradhan

Introduction

MEN syndromes have been well characterized in the past 10 to 15 years following identification of their molecular
underpinnings. Genetic testing plays an indispensable role in clinical management of these tumours in children
and adults. MEN 1 probably has the widest pleiotropy of any hereditary cancer syndrome whereas MEN2 is
notable for remarkably precise genotype-phenotype correlations at the level of the codon that determines timing
of surgical intervention.Surgeons have to recognize these syndromes and use a multidisciplinary approach for
early and presymptomatic diagnosis, reduction of morbidity and mortality and avoidance of surgical
misadventures.

Multiple Endocrine Neoplasia (MEN) definition

These are familial conditions with tumors involving two or more endocrine glands in index case & family
members.Prevalence of MEN2 is 1 in 35000 and of MEN1- is 1 in 20-40,000. They follow autosomal dominant
inheritance with important implications for family members

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MEN1
st
In MEN 1 syndrome, proband is affected by at least 2 out of 3 major MEN 1 related tumors & 1 degree relative
with 1 major lesion.
Endocrine major lesions % Minor lesions associated %

Primary hyperparathyroidism 95 Foregut carcinoid 2

Thymic, bronchial 10
GIT

Entero-Pancreatic tumors 40-80 Adrenal cortex NF 25

Gastrinomas 50 Lipomas 30
Insulinomas 10 Facial angiofibromas 85
NF- PP 20 Thyroid tumors 25
Glucagonoma, VIPomas, Somatostatinoma 2 Pheochromocytoma <1
Ependymoma 1

Anterior Pituitary tumor 15-90

Prolactinoma 60
GH+PRL, GH,NF 20
ACTH, TSH 2-5

MEN 1 mutations, in about 50% cases cause truncation of meninresulting in loss of function. At least 10 % cases
have de novo mutations. There is no evident genotype - phenotype correlation in MEN1. MEN 1 has high
penetrance rates with more than 50 % expressing by 20 years and more than 95 % by 40 years

Clinical situations requiring consideration for MEN 1 are :

Hyperparathyroidism in young age (< 55 years)
Multiglandular / recurrent HPT in absence of renal disease
Any classic MEN 1 lesion and family h/o associated lesions
Any MEN 1 lesion & adrenal incidentaloma
All patients with pancreaticoduodenal tumors
All patients with bronchial/ thymic carcinoids

In the absence of treatment, endocrine tumors are associated with an earlier mortality in patients with MEN1.
Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by the age of 50
years and the cause of death in 50-70% of patients with MEN1 is usually a malignant tumor process or sequelae
of the disease.

Treatment of MEN1

Management is generally similar to that for the respective tumors occurring in non-MEN1 patients. However, the
treatment outcomes are not as successful as those in non-MEN1 patients. MEN1 associated tumors with
exception of pituitary tumors are usually multiple, thereby making it difficult to achieve a successful surgical cure.
Occult metastatic disease is more prevalent in MEN1 patient with metastasis in about 50% cases. MEN1
associated tumors may be larger, more aggressive and more resistant to treatment.

Hyperparathyroidism in MEN1
It is the most common endocrinopathy in MEN 1 with 100 % penetrance by age 50 years. MEN1 constitutes
about 2-4% of all cases of PHPT. MEN1 associated hypercalcaemia is usually mild and hypercalcemic crisis is
rare. Age of onset is earlier at 20-25 years with no sexual preponderance.

Surgery is the definitive treatment. All four glands are usually involved having asymmetrical hyperplasia.
Parathyroid carcinoma in MEN setting is rare. There is controversy regarding optimal surgery i.e sub-total versus
total parathyroidectomy with autotransplantation. After subtotal parathyroidectomy, problems of recurrent or
persistent hypercalcemia occur in 40%-60% of patients within 10 years. Permanent hypocalcemia occur in 10-
30% of patients. Patients who underwent Total parathyroidectomy with autotransplantation may also have
Persistent disease due to supernumerary parathyroid glands. In case of recurrence, transplanted parathyroid
tissue in forearm can be removed.

Open bilateral exploration is recommended in such patients and there is no role of minimally invasive
parathyroidectomy. Resections less than sub-total parathyroidectomy are associated with unacceptably high
frequency of persistent or recurrent disease.There is a trend toward using sub-total parathyroidectomy instead of
total because of concerns about a higher rate of post-operative hypoparathyroidsim. In addition, a thymectomy
should routinely be performed in these patients. Intraoperative parathormone assay is helpful in documenting

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curative PTH fall and completeness of surgery. Calcimimetics are indicated post failed surgery as well as in
patients in whom surgery is contra-indicated.

Pancreatic Islet tumors/Insulinoma

Pancreas of patients with MEN1 is characterized by the presence of multiple small endocrine tumors (upto 5 mm
in diameter), known as microadenomatosis distributed throughout the pancreas. These are often accompanied by
1 or more macrotumors (>5mm), some of which may be functionally active. If left behind, they could grow and
become symptomatic, explaining the relapse rate observed in MEN1. Pancreatic islet tumours can be associated
with gastrinoma in 10% cases and the two tumors may arise at different times. Furthermore, the question of
potential malignancy is also to be considered (8.55%). Localization of insulinomas is difficult on imaging and may
require regionalization with intra-arterial calcium stimulation test

Surgery is the optimal treatment for insulinomas. There is wide range of extent of surgery:
Enucleation of a single tumor
Distal/partial pancreatectomy
Sub-total pancreatectomy
Excision of all macroscopic pancreatic tumors with enucleation of nodules in the remaining pancreas

The best surgical approach for patients with insulinomas in the setting of MEN-1 is controversial . Because these
patients are more likely to have multiple and malignant neoplasms, some advocate subtotal pancreatectomy to
the level of the portal vein along with enucleation of lesions from the pancreatic head. However, whether more
extensive pancreatic resection has an impact on the overall survival of these patients is unknown. Not all patients
with MEN-1 have aggressive disease, and such an approach cannot be definitively advocated unless one can
identify the subset of patients with specific MEN-1 mutations or pathologic features that are most likely to benefit
from radical surgery. Given that redo pancreatic surgery in large volume centers has low morbidity, a reoperation
policy for patients with MEN-1 and recurrent insulinoma remains an alternative option to initial subtotal
pancreatectomy

Gastrinoma

Role of surgery in treating MEN1- associated gastrinomas is controversial. There is considerable debate
regarding the extent of surgery: aggressive resection versus conservative surgery. Surgical procedure depends
on the location of tumour in pancreas, duodenum, lymph nodes or liver. Long term prognosis is associated with
tumor size and presence of hepatic metastases ( 25-40% of patients with tumor more than 4 cm develop hepatic
metastasis). Overall survival in tumors less than 2cm is 100% at 15 years and 52% at 15 year in metastatic
disease. Goals of treatment is to control gastric acid hypersecretion, reduce the risk of distant metastatic disease
and improve survival. Some studies have shown that resection of localized gastrinomas often did not require
extended surgical resection and were associated with excellent long-term outcomes. Others have shown that
aggressive resection surgery based on accurate localization was useful for biochemical cure of gastrinoma in
patients with MEN 1.

Non-functioning pNETs

Identification of these tumours is important as malignant pNETs are now reported to be the commonest cause of
death in MEN1. These tumors are now the most common pNETs in MEN1 setting. Non functioningtumours are
associated with worse prognosis than functioning tumors. Treatment of these tumours is controversial. Surgical
resection can be offered for tumors more than 2 cm. For tumors less than 1cm, if there is significant growth or
doubling of tumor size over 3-6 month interval then surgical resection is indicated.

Carcinoid tumors

Carcinoids can be located in the bronchi, GIT, pancreas or thymus. Male patients with history of cigarette
smoking have a higher risk for development of thymic carcinoids. The course of thymic carcinoids in MEN1
appears to be particularly aggressive. The presence of thymic tumors is associated with a significantly increased
risk of death in patients with MEN1 (hazard ratio, 4.29, median survival is 9.5 years). Surgical removal of
carcinoids, if resectable, is the treatment of choice.

Adrenocortical tumors

Incidence of asymptomatic adrenocortical tumors is 20-73% in MEN patients. Primary hyperaldosteronism and
ACTH independent cushings syndrome are also common.
Surgery for non-functioning adrenal tumors is indicated in (i)Size > 4cm; (ii) have atypical or suspicious
radiological features; (iii) show significant measurable growth over a 6-month interval

Thyroid tumors

Thyroid tumors comprising adenomas, colloid goiters, and carcinomas have been reported to occur in more than

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25% of patients with MEN1 syndrome. Treatment is similar to that for non-MEN1 patients

MEN 2A

MEN 2A syndrome is defined as the presence of medullary thyroid cancer,pheochromocytoma and PHPT
associated with a germline RET mutation. In a patient with one or two of the clinical features of MEN 2A, the only
way to be certain of a diagnosis of MEN 2A is to identify a RET mutation or identify the clinical features of MEN
2A in other first-degree relatives. In the absence of an autosomal dominant familial inheritance pattern or RET
mutation, at least two of the classical clinical features of MEN 2A are required to make a clinical diagnosis of
MEN 2A. In the presence of a germline RET mutation and in the absence of any clinical features, that individual
is said to be at risk for the clinical features of MEN 2A, and appropriate management should ensue.

Medullary thyroid carcinoma in MEN 2A

Hereditary MTC occurs at younger age than sporadic MTC and associated with C cell hyperplasia, multifocal and
frequently bilateral tumours. About 50% of index patients with MEN2 present with locally advanced disease with
regional lymph node metastasis. Previous investigation for pheochromocytoma is mandatory to avoid the
potential risk of hypertensive crisis during surgery for MTC, since pheochromocytoma occurs in about 50% of
MEN patients. Also, hyperparathyroidism needs to be investigated, since it affects 20-30% of MEN2A.
MEN2 RET codon mutations Level of risk of Age before which
subtype development & prophylactic thyroidectomy
aggressiveness of MTC recommended

MEN2A/FMTC 768,790,791,804,891 1(lowest risk) 5-10 yrs

MEN2A/FMTC 609,611,618,620,630,634 2(intermediate risk) 5yrs

MEN2B 883,918,922 3(highest risk) 6 mo

MEN2 patients with clinically detected MTC should be subjected to total thyroidectomy with bilateral central
compartmental with or without lateral neck compartmental dissection. High priority must be given to preserving
parathyroid function during surgery for hereditary MTC. Normal parathyroid glands should be left in-situ with an
adequate vascular pedicle. Prophylactic treatment of HPT is not usually recommended. Accidentally resected or
devascularized glands must be immediately autografted to a heterotropic site in the neck or forearm in patients
with MEN2A, especially with 634 mutation.

Role of prophylactic thyroidectomy for carriers of MEN2

Bilateral and multicentric MTC is the most common cause of death in patients with MEN2A. MTC follows
anorderly pattern of development, from C-cell hyperplasia to microscopic MTC to a visible focus. Another
important finding was of an age-dependent progression of early MTC specific to the RET codon. This resulted in
codon directed prophylactic surgery. There is enough evidence now to show that total thyroidectomy that is
performed before MTC develops or spreads beyond the gland is currently the only curative treatment modality.

In older MEN 2A series, where treatment was initiated after the identification of a thyroid nodule, MTC progressed
and showed 15-20% of cancer mortality. Early prophylactic thyroidectomy may have lowered the mortality from
hereditary MTC to less than 5%, well below the cancer mortality in MEN1.A three level risk stratification has been
adopted for prophylactic thyroidectomy, generally as close as possible to earliest reported age of onset of each
genotype. For highest risk group ( codon 918,883 mutations) , including MEN2B carriers, prophylactic
thyroidectomy should be done within first year of life, preferably by age of 6 months.

Parathyroid surgery in MEN2A

HPT is generally diagnosed at or after thyroidectomy in MEN 2 kindreds. It tends to be milder, more often
asymptomatic and caused by a single enlarged parathyroid gland. A germline mutation at codon 634 has the
highest association with development of HPT in a given MEN2A family. There is a collective conclusion that a
less aggressive resection of only enlarged glands may be sufficient with fewer complications in terms of
hypoparathyroidism. Surgery has evolved from aggressive conventional exploration of all 4 glands to focused
MIP with low rates of persistent/recurrent disease and minimal complications.

Pheochromocytoma in MEN2A
Pheochromocytomas are most frequent with mutations in codons 634 and 918. MEN2 associated
pheochromocytomas are diagnosed at an early age. Screening for pheochromocytoma is recommended from
age of 5-7 years especially for codon 634 carriers. MEN2 pheochromocytomas are often bilateral and multifocal.
Pheochromocytomas in MEN2 are rarely extraadrenal (<1%) and malignant (3-4%). They may be accompanied
by diffuse and/or nodular hyperplasia of the surrounding and contralateral adrenal medulla. Surgical options
include unilateral / bilateral total adrenalectomy and partial/cortical sparing adrenalectomy. There is little

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controversy whether to go for routine unilateral adrenalectomy versus bilateral adrenalectomy in apparent
unilateral pheochromocytoma in MEN2 setting.

B/L Pheochromocytoma develop in 35-50% of MEN2 patients. Risk of recurrent contralateral pheochromocytoma
is about 30% during 5 years and 50% during 11 years of follow up. 25% of patients following b/ladrenalectomy
require hospitalization for adrenal insufficiency. Bilateral resection reserved for patients with family history of
malignant PCC. For bilateral adrenalectomy or subsequent operation of the contralateral gland after prior
adrenalectomy, an adrenal cortical sparing adrenalectomy is generally recommended. Recurrence has been
reported in 10-20% of patients on long term follow up.

Indication for Extent of neck dissection Management of devascularized

surgery parathyroid glands

Prophylactic Central neck dissection(CCLND) RET mutation consistent with

thyroidectomy in based on RET mutation, age, serum, MEN2A:cryopreserve/ autograft in forearm
MEN2A / FMTC calcitonin, USG

Prophylactic CCLND routine, lateral based on age, Autograft in neck

thyroidectomy in calcitonin, USG
MEN2B

Therapeutic Level1 RET mutation: CCLND routine RET mutation consistent with
thyroidectomy in Level2 RET mutation: CCLND routine, MEN2A:cryopreserve/autograft in forearm
MEN2A/FMTC lateral based on age, calcitonin, USG RET mutation consistent with FMTC:
autograft in neck

Therapeutic CCLND+B/L MRND Autograft in neck

thyroidectomy in
MEN2B

Therapeutic CCLND+ I/L MRLND Autograft in neck

thyroidectomy in
Sporadic MTC

MEN2B

MTC in MEN2B
The most distinctive feature of MTC in the setting of MEN2B is the ominous potential for early metastases (50%).

In gene mutation carriers surgical recommendations

Prophylactic total thyroidectomy with CCLND by the age of 6 months
Homolateral LN exploration (2 compartments) in cases with macroscopic evidence of carcinoma at
surgery
Bilateral lymphadenectomy ( 3 compartments) in cases with evident LN metastasis
Mediastinal lymphadenectomy ( 4 compartments) is added in cases with imaging evidence of
mediastinal LN

Pheochromocytoma arises in 50% of individuals affected with MEN2B. 50% patients have bilateral involvement
as hyperplasia precedes development of PCC. Spectrum of adrenal involvement includes nodular/diffuse
hyperplasia, multiple small pheochromocytoma and thickening of entire adrenal medulla.

Treatment options
For unilateral disease:
Unilateral total adrenalectomy with close FUP
Bilateral total adrenalectomy

For Bilateral disease:

Bilateral total adrenalectomy
Unilateral total and C/L adrenal sparing surgery
Bilateral adrenal sparing surgery

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 Carcinoid tumors

Manoj Andley

Introduction
Carcinoid tumors are rare, slow-growing neoplasms of neuroendocrine origin generally asymptomatic (incidental
finding) but minority develop metastatic disease. They cause carcinoid syndrome (flushing, diarrhea, valvular
heart disease) if they metastasise to liver or if primary tumor is not in gastrointestinal tract. Also called as
Neuroendocrine Tumor (NET), Gastroenteropancreatic NET, Malignant Carcinoid, Neuroendocrine Carcinoma,
Neoplasm of uncertain or unknown behavior of Oral cavity, Digestive organs, or Female genital organs.

DEFINITIONS

Carcinoid syndrome:
Clinical syndrome resulting from bioactive secretions of functional tumors. Less than 10% of carcinoid tumor
cases develop carcinoid syndrome.
Findings associated with carcinoid syndrome are:
Cutaneous flushing, mostly in face, neck, and upper chest
Watery & explosive diarrhea
Palpitations
Wheezing
Valvular heart disease

TYPES
Traditional classification by embryonic origins:
Foregut carcinoids (respiratory tract, stomach, duodenum, biliary system, pancreas)
Midgut carcinoids (jejunum, ileum, appendix, cecum, proximal colon)
Hindgut carcinoids (distal colon, rectum)

WHO classification of Gastroenteropancreatic neuroendocrine tumor (NET) based on malignant

potential:
Well-differentiated endocrine tumor (proliferation index [PI] < 2%)
Well-differentiated endocrine carcinoma (PI 2%-15%)
Poorly differentiated endocrine carcinoma (PI > 15%)
Mixed exocrine-endocrine tumors
Tumor-like lesions

Classification by presentation:
Nonfunctioning - presenting as tumor mass.
Functioning - presenting as carcinoid syndrome due to secretion of bioactive substances.
Features of carcinoid syndrome
o Characterized by flushing (pale, purplish, or red), diarrhea (watery and explosive),
bronchoconstriction, tachycardia or hypotension, telangiectasia, and right-sided heart disease
or failure.
o Bioactive secretions include Serotonin, Corticotrophin, Histamine, Dopamine, Substance P,
Neurotensin, Prostaglandins, Kallikrein, and Tachykinins.
o Symptoms can be precipitated by exertion, eating, or drinking (especially tyramine-containing
foods and ethanol).

Classification by site and subtype:

Lungs and Bronchi (Cell of origin: Epithelial Endocrine Cell)
1. Typical carcinoid (well-differentiated NET)
a. Histologic features - minor cellular atypia
b. Mitoses rare, usually indolent
c. May secrete corticotropin, rarely secretes serotonin

2. Atypical carcinoid (well-differentiated neuroendocrine carcinoma)

a. Histologic features - cellular atypia, increased mitoses, areas of necrosis
b. Usually aggressive
c. high incidence of metastases

Stomach (Cell of origin: Enterochromaffin-like cell)

1. Chronic atrophic gastritis type A-associated carcinoid tumor:
a. Well differentiated
b. Noninvasive

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 c. Indolent
d. Often multiple
e. Not associated with carcinoid syndrome

2. Carcinoid tumor associated with Zollinger-Ellison syndrome or Multiple Endocrine Neoplasia 1:

a. Well differentiated
b. Noninvasive
c. Indolent
d. Often multiple
e. Not associated with carcinoid syndrome

3. Sporadic Carcinoid tumor:

a. Well differentiated
b. Often invasive
c. May be aggressive
d. High incidence of metastases
e. Associated with atypical carcinoid syndrome (flushing mediated by histamine)

Small Bowel (Cell of origin: Epithelial Endocrine Cell)

a. Usually well differentiated
b. Contains serotonin and substance P
c. Often multiple, usually in ileum
d. Associated with carcinoid syndrome

Appendix (Cell of origin: Subepithelial Endocrine Cell)

a. Usually well differentiated
b. Contains serotonin and substance P
c. Usually indolent

Colon (Cell of origin: Epithelial Endocrine Cell)

a. Usually well differentiated
b. Contains serotonin and substance P
c. Usually right-sided
d. Often presents at late stage

Rectum (Cell of origin: Epithelial Endocrine Cell)

a. Usually well differentiated
b. Contains serotonin and substance P
c. Carcinoid syndrome rare

Frequency of organs involved: 5,468 cases identified by National Cancer Institute (NCI) from 1973 to 1991 and
2,837 cases registered in prior NCI programs
a. 73.7% in gastrointestinal tract
18.9% appendix
15.4% ileum
11.4% rectum
4.2% cecum
3.2% stomach
2% duodenum
1.9% jejunum
1.2% rectosigmoid
1% ascending colon
Other sites with < 1% frequency - Meckel's diverticulum, ileocecum, hepatic flexure of colon,
transverse colon, splenic flexure of colon, descending colon, sigmoid colon, nonspecified colon,
nonspecified intestine, liver, gallbladder, nonspecified biliary tract, pancreas, nonspecified digestive
tract
b. 25.1% respiratory system (trachea, bronchi, lung)
c. 0.56% reproductive system
d. 0.52% ovary, 0.04% cervix, 0.6% unspecified site

EPIDEMIOLOGY
Approximate age at presentation dependent on tumor site:
a. Appendix - age 40-50 years
b. Lungs, bronchi, and trachea - age 50 years
c. Rectum - age 60 years
d. Small intestine - age 60-70 years

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 e. Stomach - age 60-70 years
f. Colon - age 70 years

Possible risk factors:

Saturated fat intake may be associated with risk for carcinoid tumor of small intestine.
Gastric carcinoid reported in 1 patient who had used long-term omeprazole but causation not shown.

Associated conditions:
13% overall rate of associated noncarcinoid neoplasms (based on series of 8,305 carcinoid tumors).
Associated conditions reported in retrospective review of 36 patients with gastric carcinoid (11% of
whom had carcinoid syndrome)
67% had atrophic gastritis
58% had pernicious anemia
39% had hypothyroidism
19% had diabetes
6% had adrenocortical insufficiency
6% had hyperparathyroidism
Zollinger-Ellison syndrome also associated with gastric carcinoid tumors Multiple Endocrine Neoplasia I
Possible association with sarcoidosis (report of 7 cases and discussion can be found in Mayo Clinic Proc 1997

ETIOLOGY AND PATHOGENESIS

Causes
Carcinoid tumors originate in cells of neuroendocrine system.
Carcinoid syndrome caused by secretion of bioactive substances by tumors.
Metastases to lungs and liver

Pathogenesis:
Carcinoid syndrome occurs when neuroendocrine cells of carcinoid tumor secrete bioactive substances.
Most common substance is serotonin (5-hydroxytryptamine) degradation product of serotonin, 5-
hydroxyindoleacetic acid (5-HIAA), when released in circulation leads to:
o Increased gastric motility (by exciting smooth muscle) bronchoconstriction (by exciting smooth
muscle) platelet aggregation.
o Vasoconstriction or dilation.
o Increased production of serotonin and 5-HIAA may lead to tryptophan deficiency and
subsequent reduced niacin synthesis which may result in pellagra
Bioactive substances secreted may include many amines and peptides including serotonin, histamine,
dopamine, substance P, corticotrophin (ACTH), neurotensin, tachykinins, and kallikrein.

HISTORY AND PHYSICAL EXAMINATION

History:
Usually asymptomatic
If present, symptoms vary by tumor site:
Pulmonary carcinoids (well-differentiated pulmonary neuroendocrine tumors):
o Recurrent pneumonia, cough, hemoptysis, chest pain.
o Symptoms of Cushing syndrome with ectopic ACTH syndrome symptoms of acromegaly with
ectopic secretion of growth hormone- releasing factor
Gastric carcinoid tumors:
o Abdominal pain and symptoms of pernicious anemia in patients with chronic atrophic gastritis type A.
o Abdominal pain, diarrhea (gastric hypersecretion), and gastrointestinal bleeding in patients with
Zollinger-Ellison syndrome.
o Flushing in histamine-mediated atypical carcinoid syndrome, primarily in patients with sporadic
gastric carcinoids.
Tumors of small intestine:
o Abdominal pain
o Small bowel obstruction
Appendiceal tumors:
o < 10% patients symptomatic
o Carcinoid syndrome has been reported in patients with liver metastases
Tumors of colon:
o Pain
o Anorexia
o Weight loss
Rectal tumors:
o 50% patients asymptomatic
o rectal bleeding constipation
o pain

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 Carcinoid Heart Disease may present with symptoms of right heart failure (possibly due to inactivation of
vasoactive substances by lungs)
Symptoms associated with carcinoid syndrome
o Classic syndrome occurs in < 10%
o Episodic cutaneous flushing, mostly in face, neck, and upper chest
o Watery, explosive diarrhea
o Palpitations

Physical examination
General physical: Carcinoid tumors usually found incidentally during surgeries for other conditions, so typically
not associated with physical findings.
Skin: cutaneous flushing, cyanosis, telangiectasia can be seen with carcinoid syndrome
Cardiac: findings with carcinoid heart disease may include(2) tachycardia, hypotension and murmurs
Lungs: wheeze may occur with pulmonary disease
Abdomen: hepatomegaly may be seen with liver metastases

DIAGNOSIS AND STAGING

Making the diagnosis

Nonfunctioning tumors often detected incidentally
Diagnosis of carcinoid syndrome based on consistent symptoms plus objective findings, such as
o elevated biologic markers: e.g. Urinary 5-hydroxyindoleacetic acid (5-HIAA) or Plasma
Chromogranin A
o neuroendocrine origin identified on histology

Biomarkers of carcinoid tumor

1. 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA): 5-HIAA is a metabolite of 5-
hydroxytryptamine (serotonin). Normal range 3-15 mg/24 hours. Avoid serotonin-rich foods 48 hours
prior to urine collection (bananas, avocados, plums, eggplant, tomatoes, plantains, pineapples,
cantaloupe, hickory nuts/pecans, dates, grapefruit, honeydew, kiwis, walnuts).
a. urinary 5-HIAA levels may be falsely lowered by levodopa.
b. elevated 5-HIAA or serotonin levels in 24-hour urine collection reported in 75% of patients with
carcinoid tumors, 4% of 50 patients with solid noncarcinoid tumors, 0 of 55 patients with
suspected carcinoid syndrome (flushing but no carcinoid tumor).
2. Plasma Chromogranin A (CgA)
a. CgA levels > 130 mcg/L associated with 62.9% sensitivity and 98.4% specificity for
gastroenteropancreatic endocrine tumors.
b. Elevated CgA levels reported in 80% of carcinoid tumors and 7% non- neuroendocrine tumors.
c. CgA levels 100-1,000 times normal reported in classical midgutneuroendocrine tumors.

Imaging studies

Computed Tomography
Characteristic appearance of infiltrated carcinoids on CT
Spiculated with stellate pattern.
Mass lesions.
Evidence of calcification and fibrosis.
Can detect mucosal thickening, submucosal mass, and luminal narrowing.
76%-100% detection rates reported for carcinoid tumors with CT.

Magnetic resonance imaging (MRI)

Not routinely used for carcinoid tumors but may be useful if other imaging studies conflicting or
unhelpful.
67%-81% detection rates reported for carcinoid tumors with MRI.
May detect pulmonary lesions not seen well on CT
o Bronchial carcinoids have high T2-weighted signal intensity
o Short tau inversion recovery (STIR) (T2-weighted sequence with fat suppression) can
distinguish between small masses and vasculature.

Ultrasound
Endoscopic ultrasound sensitive for tumors in pancreatic head, duodenal wall, local lymph nodes. Can be used to
distinguish nonfunctioning NET from adenocarcinoma based on:
High vascularity
Abundant color Doppler signal
Pulsatile or wave pattern
Endoscopic ultrasound may detect and localize gastroenteropancreatic neuroendocrine tumors.

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Small bowel enteroclysis
Used to diagnose small bowel midgut carcinoids.
Large volume of contrast introduced via tube in distal duodenum.
Provides luminal view of small bowel.
May not detect primary tumor, mesenteric nodes or masses, liver metastases.
Multidetector computed tomographic (CT) enteroclysis may have high sensitivity and specificity for small
bowel lesions.

Biopsy and pathology

Histologic pattern of typical carcinoid:

o Classified as well-differentiated neuroendocrine tumor
o Small cells with regular, well-rounded nuclei
o 5 generally accepted growth patterns
Insular
Trabecular
Glandular
Undifferentiated
Mixed

Histologic pattern of atypical carcinoid also called anaplastic carcinoid:

o Well-differentiated or poorly differentiated neuroendocrine tumor
o Increased nuclear atypia higher mitotic activity
o Areas of necrosis

STAGING

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MANAGEMENT

For non-metastatic disease

For jejunum/ilium/colon
Bowel resection with regional lymphadenectomy is recommended.
Perform examination of entire bowel as multiple lesions may be present.
Assess proximity to or involvement of superior mesenteric artery and superior mesenteric vein.
Consider prophylatic cholecystectomy if future treatment with octreotide is possible.

For duodenum, appropriate treatment options include

endoscopic resection
transduodenal local excision with or without lymph node sampling pancreatoduodenectomy (6)

For appendix
For nonmetastaticappendiceal carcinoids 2 cm, appendectomy recommended
For appendiceal carcinoids > 2 cm or incomplete resection, appropriate treatment options include re-
exploration or right hemicolectomy (6)

For rectal carcinoids

2 cm, transanal or endoscopic resection recommended
> 2 cm, low anterior resection or abdominoperineal resection are appropriate treatment options (6)

For stomach
If hypergastrinemic patient with solitary or multiple tumors 2 cm, appropriate treatment options include
expectant management
endoscopic resection with biopsy of tumor and adjacent mucosa
somatostatin analogues in patients with Zollinger-Ellison syndrome
octreotide LAR 20-30 mg monthly intramuscular
lanreotide 120 mg monthly subcutaneous
If hypergastrinemic patient with solitary or multiple tumors > 2 cm, endoscopic resection is recommended,
surgical resection in some cases (6)
If normal gastrin
Radical gastric resection with lymph node removal is recommended consider endoscopic or wedge resection for
tumors 2 cm (6).

For lung
Lobectomy or other anatomic resection plus mediastinal lymph node dissection or sampling
recommended (6)
Resection recommended if incomplete resection, consider radiation therapy with or without
chemotherapy (6)

Treatment of unresectable locoregional disease or distant metastatic disease

If asymptomatic with low tumor burden, appropriate treatment options include(6)

Observation by performing tumor marker analysis and imaging studies every 3-12 months
octreotide or lanreotide
If locally symptomatic, consider resection of primary tumor

If tumor burden is clinically significant, treat with octreotide or lanreotide

If carcinoid syndrome, appropriate treatment options include octreotide or lanreotide

Octreotide (short-acting form 100-500 mcg 3 times daily, or long- acting form 10-30 mg [up to 60 mg]
every 4 weeks) reported to relieve symptoms of carcinoid syndrome in patients with metastatic carcinoid
tumors
Lanreotide (60-120 mg every 4 weeks) and octreotide may be equally effective in reducing symptoms of
carcinoid syndrome
Echocardiogram if patient has signs or symptoms of heart disease or if planning surgery

Treatment of progressive locoregional unresectable or metastatic disease that fails to respond to above
treatment
Octreotide or lanreotide recommended (6)

Consider any of the following options hepatic regional therapy, including

Hepatic artery chemoembolization; reported to provide symptom palliation for median 13 months
Radiofrequency ablation for neuroendocrine liver metastases; reported to provide symptom palliation for
mean 11 months

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 Cytoreductive hepatic resection for functioning metastatic neuroendocrine tumors reported to be safe
and effective in selected patients (6)
Everolimus 10 mg/day plus interferon alfa-2b.

Diet
Avoid identified precipitating factors for carcinoid syndrome(3) like alcohol
Catecholamines, chocolate coffee, cheese.

PROGNOSIS

References

1. van der Lely AJ, de Herder WW. Carcinoid syndrome: diagnosis and medical management. Arq Bras
EndocrinolMetabol. 2005;49(5):850-60.
2. Robertson RG, Geiger WJ, Davis NB.Carcinoid tumors. Am Fam Physician. 2006;74(3):429-34.
3. Maroun J, Kocha W, Kvols L, et al. Guidelines for the diagnosis and management of carcinoid tumours. Part 1:
The gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group.CurrOncol.
2006;13(2):67-76.
4. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340(11):858- 68.
5. Kaltsas G, Rockall A, Papadogias D, Reznek R, Grossman AB. Recent advances in radiological and radionuclide
imaging and therapy of neuroendocrine tumours. Eur J Endocrinol. 2004;151(1):15-27.
6. Kulke MH, Shah MH, Benson AB, et al. Neuroendocrine Tumors. Version 1.2015. In: National Comprehensive
Cancer Network (NCCN) Clinical Practice Guidelines in Oncology.

Paraneoplastic syndrome

Jitendra Kumar

In addition to local tissue invasion and metastasis, neoplastic cells can produce a variety of peptides (e.g.-
hormones or cytokines ) that that can stimulate hormonal, hematologic, dermatologic, or neurologic responses.
Even tumor tissue itself can induce immunologic responses. All these systemic response can produce wide
varieties of signs and symptoms and termed as paraneoplastic syndrome. However, almost every type of
malignancy has the potential to produce it but tumors of neuroendocrine origin, such as small cell lung carcinoma
(SCLC) and carcinoids, produce a wide array of peptide hormones and are common causes of paraneoplastic
syndromes.

Definition:
Paraneoplastic syndromes refer to the disorders that accompany benign or malignant tumors but are not directly
related to mass effects or invasion.(1)

or

Paraneoplastic syndromes are a group of clinical disorders associated with malignant diseases that are not
directly related to the physical effects of the primary or metastatic tumor.(2)

In nutshell the syndromes may be due to

1. tumor production of substances that directly or indirectly cause distant symptoms,
2. depletion of normal substances that leads to a paraneoplastic manifestation, or
3. host response to the tumor that results in the syndrome

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The paraneoplastic syndrome may be the first sign of a malignancy, and its recognition may be critical for early
cancer detection. Careful studies of the prevalence of paraneoplastic syndromes indicate that they are more
common than is generally appreciated. Consequently, atypical clinical manifestations in a patient with cancer
should prompt consideration of a paraneoplastic syndrome.

Paraneoplastic syndromes may parallel the underlying malignancy, and successful treatment of the tumor leads
to disappearance of the syndrome. However, many paraneoplastic syndromes, especially those of an immune or
neurologic etiology, do not predictably resolve with treatment of the underlying malignancy. In some situations,
the underlying disease cannot be treated, but the symptoms and complications of the paraneoplastic syndrome
can be successfully managed. Proteins secreted in paraneoplastic syndromes may be used as tumor markers.

Paraneoplastic syndromes are usually divided in to the following categories:

Endocrine
Hematologic
Cutaneous
Neurologic/Neuromuscular
Rheumatologic
Renal
Gastrointestinal

Endocrine

Hormones can be produced from eutopic or ectopic sources. Eutopic refers to the expression of a hormone from
its normal tissue of origin, whereas ectopic refers to hormone production from an atypical tissue source. For
example, adrenocorticotropic hormone (ACTH) is expressed eutopically by the corticotrope cells of the anterior
pituitary but it can be expressed ectopically in SCLC.

Ectopic Adrenocorticotropic Hormone Syndrome

Ectopic ACTH production accounts for 1020% of Cushing's syndrome.
Tumors Associated with Ectopic Adrenocorticotropic Hormone (In order of frequency)
Small cell lung carcinoma (Most common cause >50%.
Thymic carcinomas (15%).
Bronchial carcinoid (10%).
Pancreas (islet cell tumors) (10%).
Other carcinoids (5%.)
Pheochromocytoma (2%).
Others:
Medullary cancer of the thyroid
Adenocarcinoma ,etc

The differential diagnosis of a patient with hypercortisolism includes Cushing's disease, adrenal dysfunction,
ectopic ACTH production, and corticotropin-releasing hormone (CRH) overproduction. Pituitary overproduction
(Cushing's disease) is the cause of disease in over 55% of patients, followed in frequency by adrenal
dysfunction, ectopic ACTH production (occurring in 11% to 25%), and CRH overproduction, which is quite rare.

Clinical Manifestations
Signs and symptoms of classic hypercortisolism include truncal obesity, purple striae, hypertension, fatigue,
moon facies, buffalo hump, weakness, depression, amenorrhea, hirsutism, decreased libido, osteopenia,
osteoporosis, impaired wound healing, impaired glucose tolerance diabetes, easy bruising, and edema. In
contrast, ectopic ACTH production from SCLC causes myopathy with weakness, muscle wasting, weight loss,
hyperpigmentation, and hypokalemia. Carcinoid tumors that secrete ectopic ACTH may cause signs and
symptoms that overlap those of pituitary-dependent Cushing's disease and paraneoplastic ACTH overproduction

Diagnosis
laboratory findings include a baseline serum cortisol level greater than 29 g/dL (to convert to nmol/L, multiply by
27.588), a urinary free cortisol level greater than 47 g/24 h, and a midnight adrenocorticotropic hormone level
greater than 100 ng/L.13

Failure to respond to high-dose dexamethasone suppression distinguishes ectopic (ie, paraneoplastic) Cushing
syndrome from a pituitary source. For the high-dose dexamethasone suppression test, 2 mg of dexamethasone
is given orally every 6 hours for 72 hours, and levels of urine 17-hydroxycorticosteroid (an inactive product
resulting from cortisol breakdown) are measured at 9 am and midnight of days 2 and 3 of the test. The
suppression test is considered positive if 17-hydroxycorticosteroid levels are reduced by 50% or more.

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Once the diagnosis of ectopic ACTH production has been established, localization is the most important aspect
of therapy. Imaging studies, including computed tomography (CT), magnetic resonance imaging, and
somatostatin receptor scintigraphy (ie, octreotide scan), are then used to locate the primary tumor.

Treatment
Surgery is the treatment of choice in patients with early stage tumors producing Cushing's syndrome because it
can completely alleviate symptoms. Although bilateral adrenal removal is effective in treating Cushing's
syndrome, the patient must have lifelong glucocorticoid and mineralocorticoid replacement.
Medical therapy with ketoconazole (200400 mg PO bid), metyrapone (250500 mg PO every 6 h), mitotane (3
6 g PO in four divided doses, tapered to maintain low cortisol production), or other agents that block steroid
synthesis or action is often the most practical strategy for Because of its rapid onset of action and favorable
toxicity profile, ketoconazole has evolved as the therapy of choice for ectopic ACTH. Primary suppression of
ACTH production can be accomplished by cytotoxic chemotherapy for the primary malignancy or octreotide
suppression of ACTH release.

Syndrome of Inappropriate Antidiuretic Hormone Production

Tumors with neuroendocrine features, such as SCLC and carcinoids, are the most common sources of ectopic
vasopressin production, but it also occurs in other forms of lung cancer and with central nervous system (CNS)
lesions, head and neck cancer, and genitourinary, gastrointestinal, and ovarian cancers.
Compensatory mechanisms, such as decreased thirst, suppression of aldosterone, and production of atrial
natriuretic peptide (ANP), may mitigate the development of hyponatremia in patients who produce excessive
vasopressin.

Clinical Manifestations
Most patients with ectopic vasopressin secretion are asymptomatic and are identified because of the presence of
hyponatremia on routine chemistry testing. Symptoms may include weakness, lethargy, nausea, confusion,
depressed mental status, and seizures. The severity of symptoms reflects the rapidity of onset as well as the
extent of hyponatremia. Hyponatremia usually develops slowly but may be exacerbated by the administration of
IV fluids or the institution of new medications. Thirst is typically suppressed.

Diagnosis
Hyponatremia and reduced serum osmolality occur in the setting of an inappropriately normal or increased urine
osmolality. Urine sodium excretion is normal or increased unless volume depletion is present. Other causes of
hyponatremia should be excluded, including renal, adrenal, or thyroid insufficiency. Physiologic sources of
vasopressin stimulation (CNS lesions, pulmonary disease, nausea), adaptive circulatory mechanisms
(hypotension, heart failure, hepatic cirrhosis), and medications, including many chemotherapeutic agents, should
also be considered as possible causes of hyponatremia. Vasopressin assay is not usually necessary to make the
diagnosis.

Treatment
As with any syndrome associated with ectopic hormone production, treating the underlying disease is the most
effective means of controlling SIADH. Chemotherapy treatment of the associated SCLC is generally associated
with improvement in the syndrome.

Fluid restriction to less than urine output, plus insensible losses, is often sufficient to partially correct
hyponatremia. Salt tablets or saline are not helpful unless volume depletion is also present. Demeclocycline
(150300 mg orally three to four times daily) can be used to inhibit vasopressin action on the renal distal tubule
but its onset of action is relatively slow (12 weeks). Conivaptan, a nonpeptide V2-receptor antagonist, can be
administered either PO (20120 mg bid) or IV (1040 mg), and is particularly effective when used in combination
with fluid restriction in euvolemic hyponatremia.

Severe hyponatremia (Na < 115 meq/L) or mental status changes may require treatment with hypertonic (3%) or
normal saline infusion together with furosemide, to enhance free water clearance. The rate of sodium correction
should be slow (0.51 meq/L per h) to prevent rapid fluid shifts and the possible development of central pontine
myelinolysis.

Hypercalcemia

There are 4 principal mechanisms of hypercalcemia in cancer patients. Secretion of parathyroid hormone (PTH)-
related protein (PTHrP) by tumor cellsknown as humoral hypercalcemia of malignancyaccounts for 80% of
cases and occurs most commonly with squamous cell tumors. Another 20% of cases arise directly from osteolytic
activity at sites of skeletal metastases. Breast cancer, multiple myeloma, and lymphomas commonly cause
hypercalcemia via this mechanism.9 Rarely, hypercalcemia may result from tumor secretion of vitamin D, which
has been described in association with certain lymphomas, or from ectopic tumor secretion of PTH.9

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Clinical Manifestations
The clinical features of hypercalcemia include nausea, vomiting, lethargy, nephrolithiasis, renal failure, and coma.

Diagnosis
In patients with malignancy-associated hypercalcemia, typical laboratory findings include an elevated calcium
level, a low-to-normal PTH level, and often a high PTHrP level.

Treatment
As with SIADH, the optimal approach to paraneoplastic hypercalcemia is treatment of the underlying tumor. Other
important measures are removal of excess calcium in the diet, medications, or IV solutions.

Oral phosphorus (e.g., 250 mg Neutra-Phos 34 times daily) should be given until serum phosphorus is >1.0
mmol/L (>3 mg/dL Bisphosphonates such as pamidronate (3090 mg IV), zolendronate (48 mg IV), or
etidronate (7.5 mg/kg per day PO for 37 consecutive days) can reduce serum calcium within 12 days and
suppress calcium release for several weeks. Bisphosphonate infusions can be repeated or oral bisphosphonates
can be used for chronic treatment. Dialysis should be considered in severe hypercalcemia when saline hydration
and bisphosphonate treatments are not possible or are too slow in onset.

Hypocalcemia
Tumors associated with bone metastases such as breast, prostate, and lung cancers can lead to hypocalcemia.
Patients with hypocalcemia and osteoblastic metastases have increased skeletal avidity for calcium, thus
implicating the rapid deposition of calcium in bone as the cause of hypocalcemia. Hypocalcemia can also occur in
patients whose tumors secrete calcitonin (i.e., medullary carcinoma of the thyroid and, rarely, breast cancer,
colorectal cancer, SCLC, and carcinoid).

Clinical manifestations
In many cases it is asymptomatic; however, it can occasionally lead to the development of significant symptoms
secondary to neuromuscular irritability and cardiovascular changes. These symptoms include peripheral and
perioral paraesthesia, cramps, tetany, seizures, bronchospasm, laryngospasm, anxiety, confusion, cardiac
arrhythmias, and congestive cardiac failure. In severe cases, hypocalcemia can be life threatening, especially if it
remains unrecognized and untreated.

Oncogenous Osteomalacia

Tumor-induced or oncogenousosteomalacia is a rare paraneoplastic syndrome characterized by osteomalacia

with hypophosphatemia, hyperphosphaturia, and undetectable or inappropriately low circulating concentrations of
1,25-dihydroxyvitamin D3.

Mean age at diagnosis is approximately 35 years. Patients typically present with bone pain, phosphaturia, renal
glycosuria, hypophosphatemia, normocalcemia with normal parathyroid hormone function, low levels of 1,25-
dihydroxyvitamin D3, and increased alkaline phosphatase levels. The majority of neoplasms causing this
syndrome are benign, but the syndrome has also been described with carcinoma of the lung, multiple myeloma,
and prostate cancer

The definitive therapy is removal of the tumor, if possible, which leads to clinical and biochemical cure.
Otherwise, treatment requires large doses of vitamin D and phosphate.

Hypoglycemia

Mesenchymal tumors, hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other
large tumors have been reported to produce excessive amounts of insulin-like growth factor type II (IGF-II)
precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin-like actions.
The diagnosis is made by documenting low serum glucose and suppressed insulin levels in association with
symptoms of hypoglycemia.

Treatment of the underlying malignancy, if possible, may reduce the predisposition to hypoglycemia. Frequent
meals and IV glucose, especially during sleep or fasting, are often necessary to prevent hypoglycemia.
Glucagon, GH, and glucocorticoids have also been used to enhance glucose production.

HEMATOLOGIC

Erythrocytosis
The most common solid tumor leading to erythrocytosis is renal cell carcinoma then is hepatoma. Other tumors
leading to erythrocytosis include Wilms tumor, hemangiomas, cerebellar hemangioblastoma, sarcomas, uterine
fibroids, adrenal tumors, and pheochromocytomas. Ectopic production of erythropoietin by cancer cells causes
most paraneoplastic erythrocytosis.

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It is important to rule out other causes of erythrocytosis, even in the presence of a tumor. Erythropoietin can be
measured in the blood when it is suspected that it is overproduced secondary to a tumor.
Paraneoplastic erythrocytosis rarely requires specific therapy other than control of the underlying neoplasm and
occasional phlebotomy when required.

Anemia
Normochromic, normocytic anemia of cancer is a common paraneoplastic syndrome, characterized by low serum
iron levels, normal or increased ferritin levels, normal iron stores, and a low serum erythropoietin level.
Paraneoplastic pure red cell aplasia is most commonly associated with thymoma.

Granulocytosis
Neoplasms most commonly associated with granulocytosis include Hodgkin's lymphoma, lymphoma, and a
variety of solid tumors, including gastric, lung, pancreatic, and brain cancers and malignant melanoma.
Paraneoplastic granulocytosis does not require treatment. The granulocytosis resolves when the underlying
cancer is treated.

Granulocytopenia
Rarely, tumors may produce a factor that suppresses granulopoiesis by interfering with any number of growth
factors. The preferred therapy for severe granulocytopenia is direct stimulation with growth factors, including
granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor.

Eosinophilia
Eosinophilia is commonly associated with Hodgkin's lymphoma and mycosis fungoides and is rarely associated
with other lymphomas and solid tumors.
Definitive treatment is directed at the underlying malignancy. In most patients who develop shortness of breath
related to eosinophilia, symptoms resolve with the use of oral or inhaled glucocorticoids.

Thrombocytosis
Thrombocytosis is present in 40% of patients with lung and gastrointestinal cancers, 20% of patients with breast,
endometrial, and ovarian cancers, and 10% of patients with lymphoma. Patients with thrombocytosis are more
likely to have advanced-stage disease and have a poorer prognosis than patients without thrombocytosis.
Paraneoplastic thrombocytosis does not require treatment.
Thrombocytopenia
A syndrome similar to idiopathic thrombocytopenic purpura is commonly seen in lymphoid malignancies including
CLL and lymphomas, as well as Hodgkin's lymphoma. Rarely, solid tumors such as lung, breast, and GI cancers
have been associated with a similar syndrome. These patients may have bleeding, petechiae, and purpura and
may respond to high-dose prednisone, splenectomy, or both. As is typical of nonparaneoplastic idiopathic
thrombocytopenic purpura, patients have adequate or increased megakaryocytes in the bone marrow and do not
respond to transfusion of platelets.

Thrombophlebitis
Patients with cancer have a hypercoagulable state. Deep venous thrombosis and pulmonary embolism are the
most common thrombotic conditions in patients with cancer. Migratory or recurrent thrombophlebitis may be the
initial manifestation of cancer.
The most common cancers associated with thromboembolic episodes include lung, pancreatic, gastrointestinal,
breast, ovarian, and genitourinary cancers, lymphomas, and brain tumors.

Coagulopathies
Acquired von Willebrand factor is seen in plasma cell dyscrasias, gastric and adrenal carcinomas, leukemias, and
lymphomas.
When possible, successful treatment of the underlying malignancy associated with acquired von Willebrand
factor can lead to resolution of the bleeding diathesis.

CUTANEOUS MANIFESTATIONS OF CANCER

Paraneoplastic dermatoses are a heterogeneous group of clinical manifestations that may have a benign
appearance. They are the second most common paraneoplastic syndrome, only behind endocrine syndromes.

Curths criteria for the diagnosis of cutaneous paraneoplastic syndromes

1) Both conditions began simultaneously (neoplasia and paraneoplasia)
2) Development of a parallel course. ( Treatment of the neoplasia results in regression of the skin lesion;
recurrence of the neoplasia implies recurrence of the skin lesion.)
3) The skin lesion is not associated with a genetic syndrome.
4) There is a specific type of neoplasia that occurs with paraneoplasia.
5) The dermatosis is rare in the general population
6) There is a high frequency of association between both conditions

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Association of dermatoses with systemic neoplasias
Dermatosis Associated neoplasia
Acanthosis NigricansMaligna Abdominal adenocarcinomas (gastric neoplasia)
Acquired Pachydermatoglyphia Gastric and pulmonary carcinoma
Erythema gyratumrepens Pulmonary, esophageal and breast
Bazex paraneoplastic acrocheratosis Aerodigestive tract (oral cavity,
larynx, pharynx, trachea, esophagus and lung)
Acquired hypertrichosis lanuginose Colorectal, pulmonary and breast
Necrolytic migratory erythema Glucagonoma
Leser-Trlat Sign Gastric and colorectal
Paraneoplastic pemphigus Non-Hodgkin lymphoma, chronic lymphocytic
leukemia, Castlemans disease, thymoma
Pityriasis rotunda Hepatocellular carcinoma, gastric and esophageal
carcinoma, prostate cancer, chronic lymphocytic
leukemia and multiple myeloma
Dermatomyositis Ovarian carcinoma, bronchogenic adenocarcinoma
Palmoplantar keratoderma Esophageal Carcinoma
Pyoderma gangrenosum Myelodysplastic syndrome, myeloma, leukemia
Sweet syndrome Acutemyelogenous leukemia, myelodysplastic
syndrome

NEUROLOGIC MANIFESTATIONS OF CANCER

Neurologic diseases are defined as paraneoplastic when they occur in increased frequency in patients with
cancer and are not related to a direct effect of tumor, infection, metabolic abnormalities, or toxicity of therapy. In
response to a developing cancer, a patient produces tumor-directed antibodies known as onconeural antibodies.
Because of antigenic similarity, these onconeural antibodies and associated onconeural antigen-specific T
lymphocytes inadvertently attack components of the nervous system as well. In contrast to paraneoplastic
endocrine syndromes, PNS are detected before cancer is diagnosed in 80% of cases. Because tumor cells
themselves do not directly produce the causative agents of PNS, and because onconeural antibodies may cause
permanent damage, successful cancer treatment does not necessarily result in neurologic improvement.
Immunosuppressive therapy is a mainstay of PNS treatment, but success is variable.

Onconeural antibodies are classified according to 3 main categories:

(1) those that are molecularly well characterized with a strong cancer association (anti-amphiphysin, anti-CV2
[CRMP5], anti-Hu [ANNA-1], anti-Ma2, anti-recoverin, anti-Ri [ANNA-2], anti-Yo [PCA-1]);
(2) those that are partially characterized (ANNA-3, anti-mGluR1, anti-Tr, anti-Zic4, PCA-2); or
(3) those occurring in both cancer- and noncancer-associated syndromes (anti-acetylcholine receptor [AchR],
antinicotinic AchR, anti-VGCC, anti-VGKC) (27N)

Limbic encephalitis

Clinical feature
Mood changes, hallucinations, memory loss, seizures, and less commonly hypo- thalamic symptoms
(hyperthermia, somnolence, endo crine dysfunction); onset over days to months.
Associated antibodies: anti-Hu (typically with small cell lung cancer) ; anti-Ma2 (typically testicular cancer); anti-
CRMP5 (anti-CV2); anti-amphiphysin

Diagnosis
EEG: epileptic foci in temporal lobe(s); focal or generalized slow activity; FDG-PET: increased metabolism in
temporal lobe(ss); MRI: hyperintensity in medial temporal lobe(s); CSF analysis: pleocytosis elevated protein,
elevated IgG, oligoclonal band.
Associated cancers:SCLC (~40%-50% of LE patients.), testicular germ-cell (~20% of LE patients), breast (~8%
of LE patients),thymoma, teratoma, Hodgkin lymphoma .

Treatment options
IVIG, 400-1000 mg/d to total 2-3 g; Methylprednisolone, up to 1 g/d IV Prednisone, 1 mg/kg per day orally,
Plasma exchange, Cyclophosphamide, ~2 mg/kg/d orally, Rituximab, 375 mg/m2IV per dose.

Paraneoplastic cerebellar degeneration

Clinical feature
Ataxia, diplopia, cerebellar dysphagia, dysarthria; prodrome of dizziness, nausea, vomiting. Associated
antibodies:Anti-Yo antibodies in patients with breast and gynecologic cancers and anti-Tr antibodies in patients
with Hodgkin's lymphoma are the two paraneoplastic antibodies typically associated with prominent or pure
cerebellar degeneration.

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Diagnosis
FDG-PET: Increase metabolism (early stage) and then decreased metabolism( late stage) in cerebellum.
MRI: cerebellar atrophy ( late stage).
Associated cancers:
SCLC, Gynecologic, Hodgkin lymphoma and Breast.

Treatment options
IVIG, 400-1000 mg/d to total 2-3 g; Methylprednisolone, up to 1 g/d IV Prednisone, 1 mg/kg per day orally,
Plasma exchange, Cyclophosphamide, ~2 mg/kg/d orally, Rituximab, 375 mg/m2IV per dose.

Lambert-eaton myasthenia syndrome (LEMS)

In approximately 60% of patients with Lambert-Eaton myasthenic syndrome, the disorder is associated with an
underlying cancer, usually SCLC.182,205(D) Proximal weakness is a common presenting complaint, but bulbar
symptoms are uncommon. In most patients, Lambert-Eaton myasthenic syndrome is not a pure motor syndrome.
Paresthesias are frequently reported206; and patients may report dry mouth or erectile dysfunction.
Characteristic electrophysiologic abnormalities include augmentation of the compound motor action potential with
repetitive stimulation. Most patients with Lambert-Eaton myasthenic syndrome benefit from plasmapheresis and
immunosuppressive therapy. Drugs that increase presynaptic acetylcholine release may also decrease
symptoms; for example, 3,4-diaminopyridine.

Subacute Sensory Neuronopathy and Encephalomyeloneuritis

This is most frequently associated with SCLC. Others are breast and hodgkins lymphoma. Diagnosis of SSN-
EMN and documentation of anti-Hu antibody should lead to the search for an SCLC. The disorder progresses
relentlessly over days to weeks, and sensory nerve action potentials are lost. The cerebrospinal fluid (CSF)
usually demonstrates increased protein concentration and a lymphocytic pleocytosis, and in SSN associated with
anti-Hu antibody, the dorsal root ganglia show lymphocytic infiltration and loss of neurons. Most cases of SSN
are associated with other autoimmune disorders rather than with cancer, and anti-Hu antibodies are absent.
Treatment of the underlying SCLC may ameliorate signs of neurological dysfunction, and treatment of Hodgkin's
lymphoma with chemotherapy was followed by clinical improvement in one patient. Immunosuppression may
produce at least transient disease stabilization even in patients who did not receive treatment for the underlying
tumor.

Autonomic Neuropathy
A pure paraneoplastic autonomic neuropathy is rare, but approximately 25% of patients with anti-Hu syndrome
and SSN-EMN have autonomic dysfunction.114 (DThe disorder is usually associated with SCLC and
autoantibodies that react with neurons in the myenteric plexus. GI dysmotility is usually a core complaint, with
orthostatic hypotension, hypoventilation, sleep apnea, and cardiac dysrhythmias being variably present.
Treatment of the underlying tumor and/or immunosuppression is usually unable to reverse neurologic
dysfunction, but may stabilize disease.

Paraneoplastic Visual Syndromes

This group of disorders involves the retina and, less frequently, the uvea and optic nerves.The most commonly
associated tumor is SCLC. Melanoma-associated retinopathy affects patients with metastatic cutaneous
melanoma. Patients develop the acute onset of night blindness and shimmering, flickering, or pulsating
photopsias that often progress to visual loss. The ERG demonstrates reduction in the b-wave amplitude.
Paraneoplastic optic neuritis and uveitis are very uncommon and can develop in association with
encephalomyelitis. Some patients with paraneoplastic uveitis harbor anti-CV2/CRMP5 antibodies.
Paraneoplastic retinopathies usually fail to improve with treatment, although rare responses to glucocorticoids,
plasma exchange, and IVIg have been reported.

Paraneoplastic Stiff-Person Syndrome

This disorder is characterized by progressive muscle rigidity, stiffness, and painful spasms triggered by auditory,
sensory, or emotional stimuli. Rigidity mainly involves the lower trunk and legs, but it can affect the upper
extremities and neck. Symptoms improve with sleep and general anesthetics. Electrophysiologic studies
demonstrate continuous motor unit activity. Antibodies associated with the stiff-person syndrome target proteins
[glutamic acid decarboxylase (GAD), amphiphysin] involved in the function of inhibitory synapses utilizing -
aminobutyric acid (GABA) or glycine as neurotransmitters. Paraneoplastic stiff-person syndrome and
amphiphysin antibodies are often related to breast cancer. Optimal treatment of stiff-person syndrome requires
therapy of the underlying tumor, glucocorticoids, and symptomatic use of drugs that enhance GABA-ergic
transmission (diazepam, baclofen, sodium valproate, tiagabine, vigabatrin).

RHEUMATOLOGIC MANIFESTATION
Paraneoplastic arthropathies arise as rheumatic polyarthritis or polymyalgia, particularly in patients with
myelomas; lymphomas; acute leukemia; malignant histiocytosis; and tumors of the colon, pancreas, prostate, and
CNS. Hypertrophic osteoarthropathy may be observed in patients with lung cancers, pleural mesothelioma, or
phrenic neurilemmoma. Scleroderma may precede direct evidence of tumor. The widespread form is typical of

179
malignancies of the breast, uterus, and lung (both alveolar and bronchial forms). The localized form is
characteristic of carcinoids and lung tumors (bronchoalveolar forms). Systemic lupus erythematosus (SLE) may
develop in patients with lymphomas or cancers of the lung, breast, or gonads. Secondary amyloidosis of the
connective tissues is a rare presentation in patients with myeloma, renal carcinoma, and lymphomas.

Hypertrophic Osteoarthropathy
Hypertrophic osteoarthropathy is characterized by periostosis and subperiosteal new bone formation along the
shaft of long bones and the phalanges (digital clubbing), joint swelling, and pain.100,112(N) The symptoms of
paraneoplastic hypertrophic osteoarthropathy may resolve with successful cancer therapy. Other treatment
options include bisphosphonates, opiate analgesics, nonsteroidal anti-inflammatory drugs, and localized palliative
radiation.

RENAL SYNDROMES
Membranous nephropathy has been clearly associated with malignancy. Although the majority of cases are
idiopathic, in the elderly as many as 22% may be associated with cancer. Various forms of malignancy have
been described in patients with membranous nephropathy. The most common has been carcinomas of the lung,
colon, and stomach. Hypokalemic nephropathy, which is characterized by urinary potassium leakage of more
than 20 mEq per 24 hours, may develop in patients with tumors that secrete adrenocorticotropic hormone
(ACTH) or ACTH-like substances. It occurs in 50% of individuals with ACTH-secreting tumors of the lung (ie,
small cell lung cancer. Nephrotic syndrome is observed, although infrequently, in patients who have Hodgkin
lymphoma (HL); non-Hodgkin lymphoma (NHL); leukemias; melanomas; or malignancies of lung, thyroid, colon,
breast, ovary, or pancreatic head.

GASTROINTESTINAL SYNDROMES
Watery diarrhea accompanied by an electrolyte imbalance leads to asthenia, confusion, and exhaustion. These
problems are typical of patients with proctosigmoid tumors (both benign and malignant) and of medullary thyroid
carcinomas (MTCs) that produce several prostaglandins (PGs; especially PG E2 and F2) that lead to
malabsorption and, consequently, unavailability of nutrients.

CONCLUSION
As the number of patients with cancer grows, and as these patients live longer, the incidence of paraneoplastic
syndromes will likely increase. These conditions affect the presentation, clinical course, and treatment of cancer.
As a result of recent diagnostic and therapeutic advances, many paraneoplastic syndromes are currently well
defined, have a clear pathogenesis, and have effective treatment options. The ability to recognize and treat
paraneoplastic syndromes may have a substantial effect on clinical outcomes, ranging from earlier cancer
diagnosis, to improved quality of life, to increased delivery of tumor-directed therapy. Furthermore, ongoing
research into these disorders may shed light on mechanisms of tumor development, maintenance, and
proliferation.

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Ann Neurol 1992;31:268.
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2004 Sep. 31(9):1854-7. [Medline].
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ComprCancNetw. 2006 Jul. 4(6):631-8. [Medline].
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119(6):526-8. [Medline].

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 Approach to a Patient with Thyroid swelling

Anjali Mishra, Chandan Kumar Jha, Niraj Kumari, Zafar Neyaz

I. Epidemiology

Thyroid nodules are discovered by palpation in 3%-7%, ultrasonography (USG) in 20%-76% and during autopsy
in 50-65% of the general population. The incidence of thyroid nodule has been correlated with various risk factors
mainly iodine nutrition of the population, age, gender, therapeutic and environmental radiation. According to the
available estimates, in India about 71 million people suffer from Goiter or other iodine deficiency disorders. The
incidence of goiter in sub- Himalayan region of India continues to be high despite an active National Goiter
control Programme (NGCP). According to conventional definition goiter is an enlarged thyroid but what the exact
cut off of enlargement is not well- defined. So far as thyroid nodule is concerned the American Thyroid
Association defines a thyroid nodule as a discrete lesion within the thyroid gland that is radiologically distinct
from the surrounding thyroid parenchyma.

Main Causes of Thyroid Swelling

1. Colloid Nodule
2. Follicular adenoma
3. Multinodular goiter
4. Graves disease
5. Thyroid Cyst
6. Primary thyroid malignancy: Papillary thyroid carcinoma (PTC), Follicular thyroid carcinoma (FTC),
Poorly differentiated thyroid carcinoma (PDTC), Medullary Thyroid Carcinoma (MTC), Anaplastic thyroid
carcinoma (ATC), Thyroid lymphoma
7. Metastases to thyroid from primary malignancy of bronchus, breast, and colon etc.
8. Thyroiditis
a. Immunologically mediated
b. Infective
9. Lymphangioma, Hemangioma or hamartoma
10. Physiological e.g. Puberty, pregnancy

II. Clinical Evaluation

There are many causes of thyroid swelling or enlargement. The evaluation of thyroid swelling is chiefly focused
on excluding presence of thyroid malignancy and dysfunction. Other things to rule out are presence of potential
respiratory compromise and other nodules. Thyroid incidentalomas measuring < 1 cm in size dont warrant
further evaluation unless there is high suspicion of malignancy based on imaging findings. Clinical examination is
not very accurate in assessing a thyroid swelling. A comprehensive evaluation consists of detailed history of
present history, past history, family history and clinical examination. Depending upon patients habitus and
swelling characteristics Pizzilos, Laheys or Criles methods are employed. Majority of nodules measuring < 1 cm
in size are not palpable and some >1cm in diameter may also be not palpable. Up to two-third of patients with
multiple thyroid nodules >1cm in diameter can be misclassified as having solitary or no nodules based on clinical
examination. Physical examination is an unreliable detection method for small cervical lymph node metastases
from thyroid cancer and detects only large lymph nodes; even intraoperative palpation will only detect about two-
third of lymph node metastases.

Features of Malignant Nodule/Swelling

As is evident thyroid nodules are fairly common in population however majority of nodules are benign. The
incidence of malignancy ranges from 5-15% in different clinical scenario. Non-palpable nodules have similar risk
of being malignant as those palpable. Clinical examination is not very accurate in predicting malignancy in a
thyroid nodule. However, the following features heighten the suspicion for malignancy should be noted.
1. Extremes of age < 14 years or > 70 years
2. Male gender
3. History of head and neck irradiation
4. Family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasis Type-2 (MEN-2),
papillary thyroid carcinoma (PTC) or associated syndromes
5. Growing nodule
6. Hoarseness of voice, dyspnea and dysphagia
7. Firm or hard consistency
8. Fixed nodule
9. Associated cervical lymphadenopathy
Out of all the above mentioned findings 100% positive predictive value for malignancy has been reported
only with palpable lymphadenopathy of > 1cm and vocal cord immobility on laryngoscopy examination (not
voice change).

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 10. Thyroid nodules detected on FDG-PET examination

Features of Thyrotoxicosis
The most common causes of thyrotoxicosis include Graves disease (GD), toxic multinodular goiter (TMNG), and
toxic adenoma (TA). All patients with known or suspected hyperthyroidism should undergo a comprehensive
history and physical examination, including measurement of pulse rate, blood pressure, respiratory rate, and
body weight. In addition, thyroid size; presence or absence of thyroid tenderness, symmetry, and nodularity;
pulmonary, cardiac, and neuromuscular function; and presence or absence of peripheral edema, eye signs, or
pretibial myxedema should be assessed.

III. Laboratory evaluation

Serum thyrotropin (TSH) is the most useful test in initial evaluation in majority of patients. However,
measurement of free thyroxine (fT4) and thyroninine (fT3) should be done as initial screening if patients present
with sign or symptoms of thyroid dysfunction. Patients with low TSH levels are less likely to have thyroid
malignancy whereas those with elevated TSH or high level values are more likely to harbor malignancy. If TSH
levels are deranged fT4 and T3 are measured to confirm the diagnosis of clinical hyper or hypothyroidism.
Patients with suppressed TSH level need thyroid scan to establish the cause of thyrotoxicosis. Measurement of
thyroid peroxidase antibodies (TPOAb) supports the diagnosis of immunologically mediated thyroid disorders.
Thyroid stimulating immunoglobulins (TSI), thyrotropin binding- inhibitor immunoglobulins (TBII) measurement is
not routinely recommended. Laboratory test should be interpreted with caution as certain physical conditions and
drugs intake can influence the levels of thyroid hormones and TSH. Not all high values for T4 and T3, and not all
suppressed TSH levels, are associated with hyperthyroidism. Estrogen administration or pregnancy raises the
thyroxine-binding globulin level and results in high total T4 and T3 levels on but normal fT4 and T3 estimates and
a normal result on sensitive TSH assay. Euthyroidhyperthyroxinemia may also be attributable to other abnormal
binding proteins, including albumin and prealbumin. Similarly, thyroid hormone resistance states can cause
increased serum T4 levels without hyperthyroidism. Administration of corticosteroids, severe illness, and pituitary
dysfunction can be associated with a suppressed TSH level in the absence of hyperthyroidism. Some patients
have elevated serum TSH concentrations (immunologically active and biologically inactive TSH) despite the
presence of central hypothyroidism. Using serum fT4 alone as a diagnostic test of hypothyroidism detects clinical
hypothyroidism but it cannot detect subclinical hypothyroidism. Also, low fT4 alone is not sufficient to make the
diagnosis of central or primary hypothyroidism. The combination of serum TSH and fT4 is the most accurate test
for detecting central as well as primary hypothyroidism. Addition of serum fT4 to TSH costs more than the single
test, but the accuracy of the test may eventually turns out to be more cost-effective in certain situations e.g. it
avoids frequent repeat testing.

Serum thyroglobulin (Tg) level is raised in many thyroid conditions, therefore, pre-operative estimation of serum
Tg is not recommended as it is not contributory to the diagnosis making and does not influence management.
Routine measurement of serum calcitonin (Ct) though advocated by few is not generally recommended because
of poor yield of MTC. Serum Ct, though, should be measured in patients who have a family history of MTC,
MEN2, pheochromocytoma or when the fine needle aspiration result suggests MTC. Serum CEA measurement is
done is diagnosed cases of MTC.

IV. Ultrasonography (USG)

A thyroid ultrasound is required as part of the evaluation for any nodule suspected on physical examination.Many
nodules suspected on the basis of physical examination are not confirmed upon ultrasound examination. USG
frequently changes the management of patients with known or presumed thyroid nodules.

Thyroid USG: Objectives of evaluation

1. Confirmation of presence of nodule or enlargement
2. Solitary (STN) versus Multiple (MNG)
3. Characterization of nodule to assess the presence of malignancy
4. Extra-thyroidal recurrence
5. Presence of lymphadenopathy and characterization of lymph nodes
6. Guide Fine needle aspiration

USG should not be used as screening modality in general population. However, it is recommended to be used as
screening of thyroid cancer in certain high- risk group patients eg: familial thyroid cancer, history of radiation
exposure, FDG avid thyroid incidentalomas. USG generally does not contribute to the diagnosis of thyrotoxicosis.
However, in special situation where radio-nuclide scan is contraindicated e.g .pregnancy or breast feeding an
increased vascularity demonstrable on color Doppler may help in establishing the diagnosis.

USG prediction of malignancy

Cancer risk does not differ among solitary and multiple nodules. Nodule size is not predictive of malignancy.
Following features are indicative of presence of malignancy.
1. Hypoechoic solid nodule

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 2. Round or more wider than taller nodule
3. Loss of peripheral halo and irregular margins
4. Presence of microcalcifications
5. Chaotic intra-nodular vascularity
6. Complex nodules
7. Extra-thyroidal invasion
8. Presence of cervical lymphadenopathy
9. Features of cervical lymph nodes: enlargement, rounded shape, absent hilum, cystic nature, micro-
calcifications and chaotic hypervascularity.

The specificities of ultrasound features and color Doppler finding for cancer are as follows: microcalcifications-85-
95%, irregular/indistinct nodule margins- 83-85%, chaotic intra-nodular vascularity 81%. The corresponding
sensitivities are: microcalcifications-29-59.2%, irregular/indistinct nodule margins- 55.1-77.5%, chaotic
intranodular vascularity 74.2%

In low-risk patients, most nodules <1 to 1.5cm should be followed without further intervention. Following
sonographic identification of a thyroid nodule >1 to 1.5cm in diameter, euthyroid patients should be referred for
consideration of FNA. Reading et al found four classic patterns of nodules that did not require biopsy: small (< 1
cm) colloid-filled cystic nodules; a nodule with a honeycomb appearance consisting of internal cystic spaces
with thin echogenic walls; a large predominantly cystic nodule; and diffuse multiple small hypoechoic
nodules with intervening echogenic bands, which are indicative of Hashimotos thyroiditis. USG guided FNAC of
a nodule < I cm in size is generally not recommended unless there are associated high- risk feature eg:
microcalcifications, history of neck irradiation, or a young patient with complex or predominantly cystic lesions as
some PTCs may be cystic.

USG guided fine needle aspiration cytology (FNAC)

USG-FNA is becoming increasingly popular because of the increased precision and ability to guide the biopsy
needle to the desired location in real time. In one study, 8.7% of aspirates guided via palpation were inadequate,
whereas only 3.5% were inadequate for those obtained with ultrasound-guidance. If the patient has multiple
nodules or a prior thyroid ultrasound was nondiagnostic, only ultrasound should be employed for guidance.
Indications for USG-FNAC are: non diagnostic palpation guided FNAC, complex nodule if cystic component is
more than 25-50%, palpable small nodule (<1.5cm), posteriorly placed nodules, impalpable incidentalomas, and
abnormal cervical nodes. To avoid the inappropriate use of US-FNA it is essential to determine which thyroid
lesions are at risk of malignancy on the basis of USG characteristics. In the presence of two or more thyroid
nodules >1 cm, those with a suspicious sonographic appearance should be aspirated preferentially. If none of the
nodules has a suspicious sonographic appearance and multiple sonographically similar coalescent nodules with
no intervening normal parenchyma are present, the likelihood of malignancy is low and it is reasonable to
aspirate the largest nodules only.

USG Elastography
Elastography has recently been applied in the diagnostic approach to nodular thyroid disease and has shown a
high sensitivity and specificity in selected patients. Larger prospective studies are needed to establish the
diagnostic accuracy of this technique.

V. Thyroid Scintigraphy

Thyroid nodule patients with low serum TSH concentration need scintigraphy to assess the presence of
autonomous nodule(s). FNAC is not necessary for hot nodules. A technetium 99mTc pertechnetate, 123I or131scan
can be performed and directly compared to the USG images to determine functionality of each nodule. FNAC
should then be considered only for those isofunctioning or nonfunctioning nodules, among which those with
suspicious sonographic features should be aspirated preferentially. A radioactive iodine uptake in patients with
Gravess disease is only performed when the clinical presentation of thyrotoxicosis is not diagnostic. 99mTcO4 is
less expensive; more readily available; and allows more rapid examination, however, technetium is trapped but
not organified (risk of false-positive images); activity in esophagus or vascular structures can be misleading; poor
image quality when uptake is low. Use of 123-I is associated with better visualization of retrosternal thyroid tissue;
better images when thyroid uptake is low; real iodine clearance of the thyroid may be measured instead of only
uptake, however it is costlier and more cumbersome to perform.

Indications of Scintigraphy
1. Thyroid nodules with suppressed TSH
2. To distinguish low-uptake from high-uptake thyrotoxicosis
3. Diagnosis of ectopic thyroid tissue
4. In follicular neoplasms to identify a functioning cellular adenoma which is more likely to be benign.
5. To determine eligibility for radioiodine therapy

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VI. Other imaging techniques

MRI and CT are not recommended for routine use as they are rarely diagnostic of malignancy in nodular thyroid
disease. However in cases of large, fixed and retrosternal goiters, these imaging are useful in assessing the size,
extent of retrosternal extension and relationship of the goiter with surrounding vital structures in neck and
superior mediastinum. X- ray neck AP and lateral view help in assessing tracheal deviation and narrowing. CECT
of thorax abdomen and bone scan are done in select cases of MTC. FDG-PET is not recommended for routine
pre-operative imaging.

VII. Fine needle aspiration biopsy (FNAC)

FNA can decrease the need for surgical thyroidectomy by 30% to 50% while increasing the diagnostic yield of
surgery. It is the most accurate test for determining malignancy pre-operatively. Routine FNA is not
recommended for sub-centimeter nodules. In the presence of two or more thyroid nodules >1 cm, those with a
suspicious sonographic appearance should be aspirated preferentially. If none of the nodules has a suspicious
sonographic appearance and multiple sonographically similar coalescent nodules with no intervening normal
parenchyma are present the likelihood of malignancy is low and it is reasonable to aspirate the largest nodules
only. In MNG, up to four nodules >1cm may require aspiration to accurately detect all cases of thyroid cancer. In
autoimmune thyroid diseases, such as Graves' disease and Hashimoto's thyroiditis, a dominant localized
abnormality in the thyroid gland is an indication for FNA.

The results of FNAC are very sensitive for the differential diagnosis of benign and malignant nodules, although
there are limitations: inadequate samples and follicular neoplasia. The reported sensitivity, specificity, positive
predictive value, false- negative rate and false positive rate for FNAC vary from 65-98, 72-100, 50-96, 1-11, and
0-7% respectively in different series. Nondiagnostic biopsies are those that fail to meet specified criteria for
cytologic adequacy that have been previously established (the presence of at least six follicular cell groups, each
containing 1015 cells derived from at least two aspirates of a nodule). After an initial nondiagnostic cytology
result, repeat FNA with US guidance will yield a diagnostic cytology specimen in 75% of solid nodules and 50%
of cystic nodules. Therefore, such biopsies need to be repeated using US guidance and, if available, on-site
cytologic evaluation, which may substantially increase cytology specimen adequacy. However, up to 7% of
nodules continue to yield nondiagnostic cytology results despite repeated biopsies and may be malignant at the
time of surgery. Approximately 60% to 70% of FNA samples will prove benign, 5% of samples will return positive
for malignancy and 15% to 25% of aspirations will be adequate though diagnostically indeterminate (Follicular or
Hurthle cell neoplasm). There are different systems of reporting the FNAC results. Apart from non-diagnostic or
inadequate the results can generally be grouped as benign, malignant, indeterminate and suspicious. Recently
National Cancer Institute (NCI) has adopted the Bethesda system for reporting thyroid cytopathology, which
consists of six diagnostic categories: Non-diagnostic or unsatisfactory, Benign, Follicular lesion, Follicular
neoplasm Suspicious for malignancy, Malignant.The chances of a nodule being proven malignant after surgery
vary among different category of FNAC diagnosis. In case of non-diagnostic: 1-4%, benign: 0-3%, follicular
lesion: 5-15%, follicular neoplasm: 15-30%, suspicios for malignancy: 60-75%; and malignant: 97-99%.

Palpation guided fine needle aspiration

Palpation-guidance is reasonable for certain patients in whom ultrasound has validated the presence of a true
thyroid nodule. The nodule must also be easily identified via palpation and should only be performed on solid
nodules (<25% cystic) in patients with normal neck anatomy. Indications for USG guidance for FNA are
discussed under USG section.

Role of Immunocytochemical/ histochemical markers

Various protein and genetic markers have been investigated to achieve definite diagnosis in cases with
ideterminate aspirates. No single tumor marker is available to reliably distinguish benign from malignant thyroid
tumors. Various markers tested include BRAF, RET-PTC, RAS, or PAX8/PPAR genes, Galectin 3, thyroid
peroxidase, HBME-1, and Telomerase. More recently genomic analysis of aspiration material for multiple genes
seems to hold some promise. A group led by McMillan and Kebebew have developed 96-gene arrays, one such
array having a sensitivity of 91% and specificity of 95% in distinguishing benign from malignant tumors. Currently
some commercially available molecular diagnostic tests are available in international market but each of these
has its limitation regarding sensitivity and specificity.

Thyroglobulin in fine needle aspiration of cervical lymph nodes

FNA-Tg sensitivity was reported to be 84% in one study and increased FNA sensitivity from 76% to 92%

VIII. Preoperative Considerations/Investigations

Thyroid dysfunction should be under control with medical treatment so as not to precipitate thyroid or
myxoedematoud crisis. A proper airway assessment is must in cases of large, infiltrative and retrosternal goiters.
X- ray neck AP and lateral view help the Anaesthetist in assessing tracheal deviation and narrowing. Apart from
other blood test required for surgery under general anaesthesia a serum calcium measurement is helpful
particularly if total thyroidectomy is planned.

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Vocal Cord examination
Pre- operative laryngeal examination in the form of direct or indirect laryngoscopy is increasingly being carried
out routinely. Vocal cord palsy can be present in normal population (2-3%) patients without significant vocal
symptoms and preoperative voice symptoms are not a reliable indicator of recurrent laryngeal nerve (RLN)
function. Since, many factors are responsible for post-thyroidectomy voice change a pre-operative laryngeal
examination also has medico-legal implications. And as mentioned earlier RLN palsy is a good predictor of
invasive thyroid carcinoma.

*As Per American Thyroid Association Guidelines 2009 (Ref.2)

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Selected References

1) National Institute of Health and Family Welfare (2003). National Iodine Deficiency Disorders Control Program:
National Health Program Series 5, p. 99. New Delhi: Department of Communication, National Institute of Health
and Family Welfare
2) Cooper DS, Doherty GM, Haugen BR, et al: Revised American Thyroid Association management guidelines for
patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19:1167
3) GharibH, Papini E Paschke R et al. American Association of Clinical Endocrinologists, Associazione Medici
Endocrinologi, and European Thyroid Association Medical Guide lines for Clinical Practice for the Diagnosis and
Management of Thyroid Nodules. Endocrine Practice 2010; 16:11
4) BahnRS, Henry BB, Cooper D et al. Hyperthyroidism and other causes of thyrotoxicosis: Management
guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists.
Endocrine Practice 2010; 17(Suppl 1): 1
5) GharibH,Papini E .Thyroid nodules: Clinical importance, Assessment and Treatment. EndocrinolMetabClin N Am
2007; 36: 707
6) Brander A, Viikinkoski P, Tuuhea J., et al: Clinical versus Ultrasound Examination of the Thyroid Gland in
Common Clinical Practice. J ClinUltrasound1992; 20: 37
7) Reading CC, Charboneau JW, Hay ID, Sebo TJ. Sonography of thyroid nodules: a classic pattern diagnostic
approach. Ultrasound Q 2005; 21:157 165
8) Danese D, Sciacchitano S, Farsetti A, et al: Diagnostic accuracy of conventional versus sonography-guided fine-
needle aspiration biopsy of thyroid nodules. Thyroid1998; 8:15
9) Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J ClinPathol2009;132:658
10) Bartolazzi A., Gasbarri A., Papotti M., et al: Application of an immunodiagnostic method for improving
preoperative diagnosis of nodular thyroid lesions. Lancet 2001; 357:164.
11) Maruta J., Hashimoto H., Yamashita H., et al: Immunostaining of galectin-3 and CD44v6 using fine-needle
aspiration for distinguishing follicular carcinoma from adenoma. DiagnCytopathol 2004; 31:392
12) Kebebew E, Peng M, Reiff E et al. Diagnostic and extent of disease multigene assay for malignant thyroid
neoplasms. Cancer 2006; 106(12):2592-7
13) Bacuzzi A, Dionigi G, Bosco Ad, et al. Anaesthesia for thyroid surgery: Perioperative management. International
J Surg 2008; 6:S82S85
14) Duick DS. Overview of molecular biomarkers for enhancing the management of cytologically indeterminate
thyroid nodules and thyroid cancer. EndocrPract. 2012 Jul-Aug;18(4):611-615

Cystic Lesions of the Pancreas

Pancreatic cysts are challenging lesions to diagnose and to treat. Determining which of the five most common
diagnosespancreatic pseudocyst, serous cystic neoplasm (SCN), solid pseudopapillary neoplasm (SPN),
mucinous cystic neoplasm (MCN), and intraductal mucinous papillary neoplasm (IPMN)is likely the correct one
requires the careful integration of many historical, radiographic, laboratory, and other factors, and management is
markedly different depending on the type of cystic lesion of the pancreas. Pseudocysts are generally
distinguishable based on historical, clinical and radiographic characteristics, and among the others, the most
important differentiation is between the mucin-producing MCN and IPMN (high risk for cancer) versus the serous
SCN and SPN (low risk for cancer). EUS with FNA and cyst-fluid analysis will continue to play an important role
in diagnosis. Among mucinous lesions, those that require treatment (resection currently) are any MCN, any MD
IPMN, and BD IPMN larger than 3cm, symptomatic, or with an associated mass, with the understanding that
SCN or pseudocysts may be removed inadvertently due to diagnostic inaccuracy, and that a certain proportion of
SPN will indeed be malignant at the time of removal. The role of ethanol ablation is under investigation as an
alternative to resection in selected patients.

Introduction
Pancreatic cysts are common in the general population. The reported incidence of asymptomatic cysts varies
widely, largely due to differences in study design, ranging between 0.7% and 24.3%. The lowest estimate comes
from a study employing both single- and multidetector CT scanners and relying on original dictated reports as
opposed to rereview of images [1], while the highest estimates come from autopsy studies and studies including
both symptomatic and asymptomatic patients . The incidence of truly asymptomatic cysts in the general
population is approximately 2.6%. In large series of pancreatic cysts, most (71%) cysts are largely asymptomatic
and range from benign to premalignant to malignant cysts. The most useful first dichotomy in the long differential
diagnosis (Table 1) of pancreatic cysts is their classification as either neoplastic or nonneoplastic. Nonneoplastic
cysts include pseudocysts, retention cysts, and duplication cysts, whereas neoplastic cysts are further broadly
classified as mucinous and nonmucinous cysts. The more commonand more commonly malignantmucinous
neoplasms include primarily intraductal papillary mucinous neoplasm (IMPN) and mucinous cystic neoplasms
(MCN), while nonmucinous neoplastic cysts include primarily serous cystic neoplasm (SCN), solid
pseudopapillary neoplasm (SPN), and usually solid neoplasms with degenerative cystic changes. Whereas most
serous cystic neoplasms are not malignant, intraductal papillary mucinous neoplasms and mucinous cystic
neoplasms can harbor an associated invasive carcinoma and should be treated as having malignant potential.

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 Table 1: Differential diagnosis of pancreatic cysts.
Nonneoplastic lesions Neoplastic lesions
IPMN
Pseudocysts MCN
SCN
Syndromes causing multiple cysts SPN
(i) Autosomal dominant polycystic disease
(ii) Cystic fibrosis

Infectious cysts Cystic variants of solid tumors

(i) Hydatid cysts (i) Cystic teratoma
(ii) Abscess (ii) Cystic ductal adenocarcinoma
(iii) Cystic neuroendocrine tumor
(iv) Cystic acinar cell carcinoma
Lymphoepithelial cysts (v) Cystic metastases
Congenital epithelial cysts
Duplication cysts
Retention cysts

Differentiating among these cysts is challenging, and a variety of modalitiesincluding imaging, cytology, and
cyst fluid analysisare useful. The management of pancreatic cystic lesions continues to evolve. The purpose of
this paper is to review the current approaches to the diagnosis and management of pancreatic cystic lesions.

Nonneoplastic Pancreatic Cysts

Pseudocysts are defined as a collection of pancreatic fluid enclosed by a wall of nonepithelialized granulation
tissue. Pancreatic pseudocyst). They are caused by the abnormal release of pancreatic enzymes into the tissues
that might result from pancreatic duct disruption related to pancreatitis or trauma. In the absence of a history of
pancreatitis or trauma, this diagnosis should be considered very unlikely.
Retention cysts, duplication cysts, and other rare nonneoplastic cysts of the pancreas (Table 1) can be difficult to
distinguish from more common lesions, and therefore clinical, laboratory, and radiographic characteristics guide
the decision to treat or to observe, as discussed below.

Neoplastic Pancreatic Cysts

The most important distinction among neoplastic cysts is the categorization of mucinous versus nonmucinous.
The most common nonmucinous neoplastic cysts are SCN and SPN, while the most common mucinous lesions
include IPMN and MCN.

SCNs represent approximately 7%36% of all cystic neoplasms and are present in middle-aged females, evenly
distributed throughout the pancreas, and characterized grossly by a microcystic appearance and a central stellate
scar that often corresponds radiographically with a pattern of central sunburst calcification on CT imaging. They
grow slowly, and their potential for malignancy is extremely low, but when these cysts are greater than 4cm or
causing symptoms, surgical resection is recommended.

Serous cystic neoplasm: (a) CT and (b) EUS images both showing the central starburst calcification pattern
characteristic of serous cystic neoplasms.

Previously known by the eponymous terms Hamoudi tumor or Franz tumor, SPNs are typically benign mixed
solid/cystic tumors that are associated with young age (median 3238 years) and female gender (84%89%).
Grossly, they are often filled with bloody or necrotic debris and radiographically have a similarly mixed solid/cystic
appearance, with calcifications commonly seen. SPNs are now considered potentially malignant, and 10% to
15% of patients have or ultimately develop metastases.

Solid pseudopapillary neoplasm: (a) Typical CT and (b) EUS appearance of solid and cystic components.

Cystic variants of solid tumors are some of the many rare cystic lesions that may also be present in the pancreas.
For example, ductal adenocarcinoma, acinar adenocarcinoma, and neuroendocrine tumors all may undergo
cystic degeneration and may present as primarily cystic lesions (Table 1). In a recent study of over 1,400 cystic
lesions of the pancreas, 7% were cystic pancreatic neuroendocrine tumors and 14% were adenocarcinomas with
cystic degeneration.

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 Fluid characteristics of pancreatic cystic lesions

Previously known as mucin-producing tumor and mucinous ductal ectasia, IPMN is a grossly visible (typically
1.0cm) intraductal epithelial neoplasm composed of mucin-producing cells. IPMNs may arise from either the
main pancreatic duct (MD IPMN), branch ducts (BD IPMN), or both (Figures. IPMN is most common in elderly
patients, males more than females, and located in the head of the pancreas more often than the tail. The
malignant potential is variable, depending predominantly on the location of the IPMN: the percentage of IPMNs
found after resection to harbor a malignancy (invasive carcinoma or carcinoma in situ) ranges in various studies
from 6% to 46% for BD IPMN and from 49% to 92% for MD IPMNs. If carcinoma develops within an IPMN,
survival depends on the subtype: colloid adenocarcinomas are associated with a more favorable survival than
tubular adenocarcinomas, which are associated with a 5-year survival rate not statistically different from
conventional, non-IPMN-related pancreatic ductal adenocarcinoma.

In contradistinction to IPMN, MCNs do not involve the duct system and have an associated ovarian-type of
stroma. MCNs also have a strong female predominance and are found almost exclusively in the body and tail of
the pancreas. MCNs are typically macrocystic (>2cm), spheroid, solitary, and associated with a normal
pancreatic duct with which there is no communication. In a recent, large, two-institution series, approximately
11% were invasive.

Mucinous cystic neoplasm. (a) Typical CT and (b) EUS appearance of a well-rounded hypodense and anechoic,
respectively, pancreatic cyst in the tail of the gland of a female patient.

Diagnostic Modalities
The two noninvasive imaging modalities which have been most frequently used to evaluate pancreatic cysts are
computed tomography (CT) and magnetic resonance imaging (MRI). Pancreas-protocol CT scan (with the IV
contrast bolus timed for both arterial and venous phases and typically with water as the oral contrast to minimize
artifacts arising from denser contrast media) has become the preferred modality to evaluate the pancreas due to
its ease, relatively low expense, and diagnostic accuracy. However, some authors have argued that MRI with
magnetic resonance cholangiopancreatography (MRCP) is the best noninvasive method for identifying the
presence or absence of communication between pancreatic cysts and the pancreatic ductal system. While
MRI/MRCP has the clear advantage over CT of not involving the use of ionizing radiation, it lacks the ability to
sample cyst fluid for analysis, which, as discussed below, can help distinguish between high-risk mucinous and
low-risk nonmucinous cysts.

Endoscopic retrograde cholangiopancreatography (ERCP) has been useful in cases of IPMN especially when
combined with pancreatoscopy and/or intraductal ultrasound. Hara et al. found that lesions protruding more than
4mm into the pancreatic duct were malignant in 88% of cases. ERCP, although more invasive than MRCP, is
very useful in defining the communication of the cyst with the main pancreatic duct and provides another method
for tissue acquisition. Due to its associated risk of pancreatitis, however, and the improving quality of MRCP, its
role has become limited in favor of endoscopic ultrasound (EUS).

EUS with fine-needle aspiration (FNA) has been extensively studied in the detection, diagnosis, and treatment of
pancreatic cysts. The diagnostic accuracy of EUS morphology alone is widely variable with the largest
prospective study reporting an accuracy of 50% for identification of macrocystic septations or adjacent mass.
FNA increases the sensitivity of EUS by allowing for cyst fluid analysis and cytology to further differentiate
mucinous cysts, serous cysts, and pseudocysts. Columnar epithelial cells which stain for mucin are characteristic
of MCN and IPMN, whereas cuboidal cells which stain for glycogen are associated with serous cystadenomas. A
recent study by Rogart et al. showed that EUS with FNA and cyst wall puncture (passing the needle repeatedly
through the far wall of the cyst to obtain wall epithelium for cytology after simple aspiration of cyst fluid) increased
the cytologic yield by 37% compared to simple FNA with fluid analysis alone. The increased diagnostic
capabilities of EUS/FNA compared with noninvasive modalities must be balanced, however, with the associated
risks, including pancreatitis and hemorrhage. In general EUS/FNA is associated with a favorable risk/benefit ratio,
as evidenced by several large studies including several hundred patients suffering no major complications. In
addition to being used to evaluate cystic lesions of the pancreas found by other modalities, EUS/FNA is also

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potentially useful as a screening modality in individuals deemed to have 10-fold increased risk of harboring a
pancreatic cancer, such as those with 3 relatives with pancreas cancer in the same lineage.

While imaging modalities provide morphologic characteristics of the lesions, it is the fluid analysis and tumor-
marker levels that ultimately classify a cyst as of high or low risk for malignancy. Cyst fluid amylase level is
elevated in pseudocysts and IPMNs. IPMNs have elevated amylase levels because, by definition, they involve
the pancreatic duct system. By contrast, SCNs and MCNs, because they do not communicate with the pancreatic
duct system, typically have lower amylase levels. Carcinoembryonic antigen (CEA) level is the most studied and
widely used tumor marker in differentiating mucinous from nonmucinous lesions. Although no cutoff level is
universally agreed upon, a cyst-fluid CEA level <30ng/mL has a sensitivity of 79% and specificity of 73% in
differentiating nonmucinous from mucinous lesions. In the Cooperative Pancreatic Cyst Study, a higher cut-off
(192ng/mL) was found to be optimal, with a sensitivity of 73%, a specificity of 84%, and an accuracy of 79% for
diagnosing nonmucinous from mucinous lesions. Although CEA has been found to have the highest accuracy
among cyst fluid analyses in distinguishing mucinous from nonmucinous cysts, other tumor markers have also
been predictive. For instance, in the same Cooperative Study, cyst fluid CA19-9 levels had a sensitivity of 68%, a
specificity of 62%, and an accuracy of 66% (P = 0.004) with a cutoff value of 2900U/mL for differentiating
nonmucinous from mucinous lesions; corresponding numbers for CA72-4 were 80%, 61%, and 72% (P = 0.001).
The demographic, historical, radiographic, gross, and cyst fluid analysis characteristics described above are
summarized in Table 2.
Table 2: Distinguishing features of pancreatic cystic lesions
Typical
IPMN MCN SCN PSEUDO SPN LEC cNET cPDAC
characteristics
Middle- Middle-
Age group Elderly Middle Any Young Elderly Elderly
elderly Elderly
>50% 95% >50% 80%90% >50%
Gender >50% male 80% male 50% each
male female female female male
Asx; Asx;
Asx; pain; Asx; Fxnl; Asx; pain;
History pain; Pain; Asx; VHL Pancreatitis Asx
nausea MEN jaundice
jaundice nausea
% of all cysts*** 17%40% 9%28% 7%36% 1%19% 1%13% <2% <8% 13%16%

Head in
Location in Body/Tail
70%; Anywhere Anywhere Anywhere Peripheral Anywhere Anywhere
pancreas in 95%
multifocal
Shape Ovoid Spheroid Ovoid Spheroid Ovoid Ovoid Spheroid Variable
Uni- or Oligo- or Oligo- or
Locularity Any Uni- Oligo- Uni- Any
oligo- multi- Multi-
Duct com-
Common No No Common No No No Some
munication
Central
Calcification No No No Some No Some No
sunburst

Opaque, Opaque,
Viscous, Viscous, Thin, Nonmuc.,
Cyst fluid bloody/ bloody/
clear, clear, clear, crystalline Nonmuc. Thin
appearance necrotic necrotic
muc. muc. nonmuc. debris
debris debris
High
+ +
CEA/Mucin**
High Ca19-9
High amylase + +

Poorly
cohesive
Columnar, No Gland-
Epithelium Columnar Cuboidal cells with Squamoid Uniform
papillary epithelium forming
nuclear
grooves
Sometimes Sometimes
Stroma Fibrotic Ovarian Fibrotic Fibrotic Lymphoid Fibrotic
hyalinized hyalinized
Abbreviations: IPMN: intraductal papillary mucinous neoplasm; MCN: mucinous cystic neoplasm; SC: serous
cystadenoma; PSEUDO: pancreatic pseudocyst; SPN: solid-pseudopapillary neoplasm; LEC: lymphoepithelial

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cyst; cNET: cystic neuroendocrine tumor; cPDAC: pancreatic ductal adenocarcinoma with cystic degeneration;
VHL: von Hippel-Lindau disease; muc.: mucinous; Nonmuc: nonmucinous; Asx: asymptomatic; Fxnl: functional.

Emerging Modalities
Loss-of-heterozygosity studies and DNA mutational analysis of cyst fluid have shown that the presence of a point
mutation in the KRAS gene is 96% specific in detecting a mucinous neoplasm, and when there is a KRAS gene
point mutation coupled with allelic loss at selected markers, there is a 96% specificity in detecting malignancy
(invasive versus in situ carcinoma not specified). However, this study has been rightfully criticized for harboring a
selection bias resulting from the exclusion of nonoperated patients from cyst fluid DNA analysis. Furthermore,
there is poor correlation between cysts with high CEA levels and those with KRAS point mutations and allelic
loss. There are a number of other biomarkers that are currently under evaluation to predict risk in pancreatic
cysts.

Confocal laser endomicroscopy (CLE) is an exciting emerging diagnostic modality that employs a low-power
laser to illuminate tissue with subsequent detection light reflected from the tissue through a small probe (pCLE) or
needle (nCLE). It is confocal because both illumination and collection systems are aligned in the same focal
plane. While largely still experimental, nCLE has been used successfully in a porcine model to collect real-time,
in vivo pancreatic images at histologic resolutions and of acceptable image quality.

Management

Nonneoplastic Cysts
Initially, the management of pseudocysts is conservative since as many as 60% may completely resolve
spontaneously within a year. As such, surveillance is the first-line therapy for noninfected pancreatic pseudocysts
and may be done with US, CT, or MRI. Pseudocysts that either cause severe symptoms or are large and
refractory to surveillance should be drained percutaneously, endoscopically, or surgically. The disadvantages of
percutaneous drainage include risk of infection, fistula formation, and a low rate (21%) of resolution. Open and
laparoscopic internal surgical managementincluding internal and external drainage as well as resectionis
effective, but is associated with 12%35% complication rate, including hemorrhage, infection, and fistulae, and a
mortality rate of 1%. Endoscopic drainage has been reported to achieve a similarly high success rate but with
lower rates of complications, including bleeding, infection, perforation, and mild pancreatitis, which is generally
self-limited. Endoscopic drainage has therefore become the preferred modality for draining cysts which have a
mature wall and are within 1cm of the gastrointestinal lumen. In a recent large retrospective study by Ahn et al.,
single-step EUS-guided transmural drainage and stent placement was effective in 89% of patients with complete
drainage, with an overall recurrence rate of 12% and minor complications in 11% of patients.

Unlike pancreatic pseudocysts, which are typically identifiable as such based on historical, clinical, laboratory,
and radiographic information, other nonneoplastic cysts such as duplication cysts, retention cysts, congenital
epithelial cysts, and lymphoepithelial cysts are rarer, and not easily diagnosed preoperatively. As such, they are
typically subjected to the various diagnostic modalities described above in an effort to classify them correctly as
low-risk versus high-risk cysts and they are treated or surveilled accordingly.

Neoplastic Cysts

Indications for Resection

In the absence of randomized controlled data to guide treatment recommendations, the Sendai International
Consensus Guidelines, first published online in 2005 by the International Association of Pancreatology, identified
several factors as relative indications for resection of IPMN. These include a main-duct component, diameter
>3cm, any solid component, and the presence of symptoms attributable to the cyst, such as abdominal pain,
weight loss, and pancreatitis (Table 2). Rapid rate of growth of the cyst and young age (such that life-long
surveillance would be prohibitively burdensome for the patient) may be considered relative indications outside the
Sendai Guidelines. Resection recommended as the mainstay of treatment for lesions thought to have increased
the potential for harboring significant dysplasia or an associated invasive carcinoma, and indeed it is the only
potentially curative option for such lesions.

Unlike a cystic lesion thought to be IPMN, which may be observed or resected, depending on the above-
mentioned risk factors, any lesion thought to be MCN should be resected until data are available to better stratify
these patients, if such data ever exist.

Regarding the serous lesions SCN and SPN, all lesions known to be SCN may be left in place and all those
known to be SPN should be resected. In reality, however, a given cystic lesion of the pancreas is not generally
known to be one or the other with sufficient certainty, even despite all of the above-discussed diagnostic
modalities. Therefore, each pancreatologist and patient must together carefully weigh the risks and benefits of
resection and surveillance on a case-by-case basis (see Surveillance, below).

The chief difficulty is, of course, the fact that the only way to achieve a definitive diagnosis in many cases of
pancreatic cysts is to remove the cyst and subject it to pathologic evaluation. Although pancreatectomy is

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curative in most cases of cystic lesions of the pancreas, it is associated with a perioperative morbidity rate of 30
60% and a mortality rate ranging from <1% to 2%. In addition to complications associated with any operation in
general, such as bleeding and infection, complications specific to the resection of pancreatic lesions include
pancreatic or biliary fistula, delayed gastric emptying, and pancreatic insufficiency, both exocrine and endocrine.

Cyst Ablation

In an effort to avoid a more invasive treatment and the associated complications, pancreatic cyst ablation has
been suggested both as an experimental approach to treatment for pancreatic cysts in general and for treatment
of those patients specifically deemed unfit or at a too high risk for a major operation (Figure 1).

Figure 1: Pancreatic cyst therapeutic algorithm.aAlso considered are nonimaging findings such as symptoms
attributable to the cyst, rapid growth, and young age. bSurveillance may be performed initially at close intervals
(e.g., 3mo),

Although less commonly employed than resection, pancreatic cyst ablation is an increasingly studied modality,
typically using EUS to guide injection of alcohol or other ablative agents into the cyst cavity. Ethanol has the
advantages of being safe, inexpensive, readily available, and having the potential to rapidly ablate the entire cyst
wall epithelium. A 2005 pilot study using escalating doses (5% to 80%) of ethanol for 3- to 5-minute lavage
showed histological evidence of epithelial ablation in resected cysts. Patients reported no symptoms at 2 hours,
72 hours, and 612 months following the procedure, with no complications detected, although theoretical
complications include acute pancreatitis, hemorrhage, intoxication, and abdominal pain.

In an effort to assess effectiveness as well as to further assess safety, DeWitt et al. compared ethanol ablation to
saline lavage in a randomized controlled trial including 42 ethanol-lavaged and 17 saline-lavaged patients.
Ethanol lavage resulted in greater decrease in pancreatic cyst size (43%), compared with saline (11%), with
similar safety profile. Four patients underwent resection after lavage of mucinous cysts (2 who decided to drop
out after lack of response (one to saline and one to ethanol) and 2 whose cyst fluid had atypical cells), and
histology of resected pancreata showed IPMNs in 3 and MCN in 1 patient; not surprisingly, there was more
extensive ablation (50% to 100% of cyst epithelium) in the ethanol group than the saline group (0%). Resolution
by CT imaging was seen in 33% (12 of 36 cysts lavaged with saline alone, ethanol alone, saline then ethanol,
ethanol then ethanol.

Subsequent studies of EUS with ethanol ablation have expanded the field to include ablation of septated cysts
(successful), the addition of paclitaxil to increase ablative capacity of the lavage (62% of patients had complete
resolution), and longer (2 years) followup of ablated patients (no recurrence during second year). Although these
preliminary data suggested that ethanol ablation is safe and feasible, prospective randomized trials with longer
followup in more patients comparing ablation with resection are needed.

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 Management of commonly encountered cystic lesions of the pancreas

Follow-up guidelines are based on Sendai criteria

Surveillance
Patients too unfit to undergo resection or whose cysts do not meet the above-mentioned Sendai criteria for
treatment may undergo surveillance (Figure 1). Indeed, not only a patient's physiologic fitness for resection but
also a patient's goals must be considered. To this end, the Markov modeling and nomograms have been used in
a recent study to assist patients with small asymptomatic BD IPMNs with decision making regarding the risks and
benefits of resection versus surveillance. The decision to resect or to surveil depended on the patient's age and
comorbidities, the size of the cyst, and whether the patient values quality or quantity of life more; that is, overall
survival versus quality-adjusted survival: those valuing primarily survival, irrespective of quality of life, would
benefit most from resection of lesions >2cm. However, for patients valuing quality of life over longevity, a 3-cm
threshold for resection would be more appropriate.

Summary
The diagnosis and management of cystic lesions of the pancreas is challenging and continues to evolve. The five
most common diagnoses are pseudocysts, SCN, SPN, MCN, and IPMN. Pseudocysts are generally
distinguishable based on historical, clinical, and radiographic characteristics, leaving the most important
differentiation being between the mucin-producing (often malignant or premalignant), MCN and IPMN, and the
serous (generally benign), SCN and SPN, cysts. EUS and FNA with cyst-fluid analysis have an increasingly
important role in diagnosis. Among mucinous lesions, those that require treatment (resection currently) are any
MCN, any MD IPMN, and BD IPMN larger than 3cm, symptomatic, or with an associated mass. In the future,
ethanol ablation may well supplant resection or at least provide an alternative treatment in selected patients.

Gastrointestinal Stromal Tumors

Nikhil Talwar, Rigved Gupta

INTRODUCTION
Gastrointestinal Stromal Tumors (GISTs) are rare tumors that usually originate from mesenchymal tissue of
gastrointestinal tract or occasionally from intra-abdominal tissues. They arise from Interstitial cells of Cajal, the
1
pacemaker cells of GI tract. They constitute less than 1% of all GI tumors, yet they are the commonest GI
1
mesenchymal tumors.

Also called
GIST, gastrointestinal stromal sarcoma, gastric leiomyoblastoma. 2, 3

Sites
Common locations: stomach (50%-60%) and small intestine (30%-35%)1

192
Rarer sites: colon and rectum (about 5%), esophagus (< 1%), retroperitoneum (< 5%), omentum and mesentery
1,2
(< 5%).

EPIDEMIOLOGY
Males and females are equally affected, and greater than 80% of patients with GIST are > 50 years old (median
age 63 years).1
1
GISTs are rare in pediatric patients, and in patients < 20 years old, they appear almost exclusively in females.

Incidence/Prevalence
Global prevalence of GIST is 130 per million. 2
Annual incidence ranges from 10 to 22 per million (10 per million in Europe to 16-22 per million in Korea and
2
Hong Kong).

ETIOLOGY AND PATHOGENESIS

Causes
Most cases of GIST are sporadic and have no risk factors. 1
75%-80% of gastrointestinal stromal tumors have mutations in KIT receptor tyrosine kinase (CD117), and
additional 10% have mutations in related platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine
1
kinase.
1
Familial GIST is caused by heritable mutations in KIT (exons 8, 11, 13, and 17) and exon 12 of PDGFRA. These
patients are at high risk of developing gastric or small-bowel GIST and present at earlier age than sporadic
1
GIST.

Associated conditions
Carney triad - rare tumor syndrome in girls and young women resulting in gastrointestinal stromal tumor,
paraganglioma and pulmonary chondroma. 2
Carney-Stratakis syndrome: Germ-line mutations of succinate dehydrogenase leading to co-occurrence of
2
gastrointestinal stromal cancer (GIST) and paraganglioma.

Pathogenesis
Tumors probably originate in interstitial cells of Cajal (or their precursor stem cells) located in myenteric plexus.
Depending on locus, mutations in KIT and PDGFRA result in either unregulated receptor dimerization or
unregulated tyrosine kinase activity (more rare). 1,2

CLINICAL FEATURES
History: Most common symptoms are abdominal pain, blood in stools, and anemia1
Other symptoms may include dyspepsia, fatigue, nausea and vomiting, constipation or diarrhea. About 25%
1
asymptomatic and discovered incidentally.
1
Clinical examination: Tumors are often palpable on abdominal examination.
Metastases may cause abdominal pain, bleeding, or symptoms of bowel obstruction. 1

DIAGNOSIS AND STAGING

Most patients with GIST have suggestive symptoms or palpable tumor, but 25% cases are identified incidentally
2,3
during imaging for other disorders. Making a diagnosis of GIST requires a high degree clinical suspicion.
Diagnosis should be suspected in a large abdominal mass seen arising from the bowel in absence of symptoms
of obstruction.2,3

Investigations
Initial evaluation and staging of all patients should include imaging with abdominal computed tomography (CT)
with contrast or magnetic resonance imaging (MRI).
18F-fluoro-deoxyglucose positron emission tomography (PET) should be considered to assess baseline tumor
activity prior to medical therapy.
Although not essential in all cases, biopsy is standard for diagnosis and is required prior to initiation of
preoperative medical therapy and in patients with gastric GISTs < 2 cm (0.8 inch), endoscopic ultrasound-guided
4
FNAC recommended.
4
Mutational testing for KIT and PDGFRA mutations should be done before initiating medical therapy.

Computed Tomography (CT)

Contrast-enhanced CT is preferred imaging technique for diagnosis, staging, monitoring response to therapy, and
follow-up.4 It shows greater anatomic detail than positron emission tomography (PET). 4
On the basis of CT findings, GISTs, GISTS can be divided into small (< 5 cm), intermediate (5-10 cm), and large
(>10 cm) tumors. Small GISTs are sharply demarcated, homogeneous masses, mainly exhibiting intraluminal
4
growth patterns.

193
Intermediate GISTs are characterized by irregular shape, heterogeneous density, an intraluminal and
4
extraluminal growth pattern, and signs of biological aggression, including adjacent organ infiltration.
Large GISTs feature irregular margins, heterogeneous densities, locally aggressive behavior, and distant and
peritoneal metastases.4

Magnetic Resonance Imaging (MRI)

MRI seems to be as sensitive as CT & is considered as an alternative to CT, especially for rectal GISTs where
4
MRI provides better staging information.

Positron Emission Tomography (PET)

PET detects changes in tumor metabolism that may precede changes in tumor morphology. PET may be used to
clarify ambiguous or equivocal findings on CT or MRI, but is not a substitute for CT. It can be useful for early
3,4
detection of tumor response to imatinib.

Endoscopic Ultrasound and guided FNA

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of primary site is preferred over percutaneous
image guidance due to reduced risk of tumor hemorrhage and intra-abdominal dissemination of neoplastic cells.
1,2
EUS is also indicated for small (< 2cm) incidentally detected lesions to differentiate high risk & low risk tumors
which aids in further management. High risk features on EUS include irregular extra-luminal borders,
1,2
heterogeneous echo patterns, presence of cystic spaces and echogenic foci.

Biopsy
Although biopsy may provide the definitive diagnosis, however a preoperative biopsy is not recommended for
resectable lesions with characteristic CT findings, since biopsy may cause hemorrhage and tumor seeding. 2,3
Biopsy is recommended before starting medical therapy either in neoadjuvant setting or for metastatic disease.
Percutaneous biopsy may be done for confirmation of metastatic disease. It is also indicated when diagnosis is in
doubt or an alternate diagnosis (such as lymphoma) is being considered. 3

Immunohistochemistry
Overlap of morphology with many other tumor types necessitates immunochemical staining to aid in differential
diagnosis.
CD117 (an epitope of KIT) and anoctamin (ANO1 or DOG1) are the most sensitive and specific markers for
GIST. In contrast, desmoids, scwannomas (S-100-positive, KIT-negative), leiomyomas and leiomyosarcomas do
not. In GISTs, CD 117 appears diffusely in the cytoplasm in a punctate or Golgi-like pattern.
CD34 results are positive in approximately 60% GISTs.
Additional markers may include CD34 antigen, smooth muscle actin, desmin, S100 (rules out melanoma)and
cytokeratins.1,2

Staging systems
4
American Joint Committee on Cancer (AJCC) staging for gastrointestinal stromal cancer (GIST) :
- Primary tumor (T)
TX - primary tumor cannot be assessed
T0 - no evidence of primary tumor
T1 - tumor 2 cm
T2 - tumor > 2 cm but 5 cm
T3 - tumor > 5 cm but 10 cm
T4 - tumor > 10 cm in greatest dimension
- Regional lymph nodes (N)
N0 - no regional lymph node metastasis (if regional node status unknown, use N0, not NX)
N1 - regional lymph node metastasis
- Distant metastasis (M)
M0 - no distant metastasis (no pathologic M0; use clinical M to complete stage group)
M1 - distant metastasis
Stage T N M Mitotic Rate
Stage IA T1 or T2 N0 M0 Low
Stage IB T3 N0 M0 Low
Stage II T1 N0 M0 High
T2 N0 M0 High
T4 N0 M0 Low
Stage IIIA T3 N0 M0 High
Stage IIIB T4 N0 M0 High
Stage IV Any T N1 M0 Any rate
Any T Any N M1 Any rate

194
TREATMENT

Surgery and procedures

Surgical resection is primary treatment for localized GIST. 5 Goal is complete resection of the tumor, avoiding
tumor rupture, and achieving negative margins. Segmental or wedge resection may be appropriate for obtaining
negative margins. Unlike adenocarcinomas, wide resection margins are not recommended since GISTs tend to
2,5
grow out from the organ rather than intramural spread. The preferred resection margin is 10 mm.Therefore,
gastric tumors rarely require total gastrectomy; a partial gastrectomy or even wedge resection is adequate with
2,4
lower morbidity & similar prognosis. Similarly, a segmental resection is adequate for small bowel GISTs.

Maintaining pseudocapsule and preventing spillage are both essential. Avoid endoscopic excision in esophagus
2
or stomach as R0 section may be difficult to achieve. Lymphadenectomy is not routinely required due to rarity of
nodal metastases. Local involvement of adjacent organs should be treated with en bloc resection; however multi-
visceral resections should be avoided. If such a morbid resection is necessary, neoadjuvant therapy should be
2,3
considered.

For small gastric GIST, <2cm, surgery is indicated if there are high risk features on EUS, presence of ulceration
and bleeding or increase in size on follow up. In absence of these features, such lesions are managed
4
conservatively with endoscopic surveillance every 6-12 months.

Laparoscopic Surgery
Laparoscopic surgery may be considered for GISTs located favorably (anterior wall of stomach, jejunum, and
ileum). Laparoscopic excision should follow oncologic principles of GIST resection (preserving pseudocapsule
and preventing tumor spillage).5 Laparoscopic approach for larger tumors appears safe in several case series but
caution is advised due to risk of rupture. Plastic bag should be used when removing resected specimens from
abdominal cavity to prevent spillage.5

Based on systematic review of 22 observational studies comparing laparoscopic vs. open resection in 1,166
patients with GISTs, it was concluded that laparoscopic resection was associated with lower risk of complications
compared to open resection in patients with gastrointestinal stromal tumors.5

Medications
Imatinib mesylate
Imatinib (Gleevec TM) is small molecule tyrosine kinase inhibitor. 2 Also known as STI-571, imatinib first received
attention as an inhibitor of the BCR-ABL fusion protein, which induces uncontrolled tyrosine kinase activity in
3
CML.

Indications for initiating therapy with Imatinib include:

1. Primary treatment with imatinib recommended in patients with unresectable, recurrent, or metastatic disease.
2. Postoperatively, recommended as an option for patients with
a) complete resection and no prior imatinib treatment and intermediate or high recurrence risk
b) complete resection and prior imatinib treatment
c) persistent, gross residual disease, regardless of prior imatinib treatment
3. Progressive disease- at either same dose as used previously (400mg/day) or with dose escalation to 800
mg/day as tolerated.
4. Patients with resectable gastrointestinal stromal cancer (GIST) with significant risk of morbidity.

Dosing: 400 mg/day orally is standard dose. Increased 800 mg/day dose is a recommended option for patients
with KIT exon 9 mutation or tumor progression. 2,4

Duration: Since rapid disease progression occurs after Imatinib is stopped, therefore lifelong therapy is
recommended until disease progression or Imatinib intolerance.

Adverse effects: The most common adverse effects include edema, nausea, diarrhea, malaise and fatigue.
Rarely myelosuppression, hemorrhage, elevated transaminases & cardiotoxicity may be seen. 2
Imatinib does not appear effective for treating advanced PDGFRA D842V-mutant GISTs. Pre-operative imatinib
is reported to reduce tumor size for improved resectability and surgical outcome in patients with unresectable or
4
high surgical risk GIST, but this has not been subjected to a systematic review.

Reported treatment benefit rates for imatinib based on mutational profile of tumor are
4
- 90% of patients with KIT exon 11 mutation
- 50% of patients with KIT exon 9 mutation (likelihood improves with higher 800 mg daily dose) 4
- 0%-45% in patients without KIT or PDGFRA mutations

Sunitinib
TM
Sunitinib (Sutent ) is multikinase inhibitor that targets several tyrosine kinase inhibitors (including VEGF and
2,3
PGDF) implicated in tumor growth, pathologic angiogenesis and metastatic progression.

195
Indications include:
1. disease progression in patients receiving imatinib,
2. intolerance to imatinib.

Recommended doses include 50 mg/day orally for 4 weeks followed by 2 weeks off or 37.5 mg/day orally without
4
interruption.

Regorafenib
Regorafenib (StivargaTM) is FDA approved to treat patients with advanced gastrointestinal stromal tumors that
cannot be surgically removed and no longer respond to imatinib and sunitinib. 4
4
Regorafenib is also recommended third-line therapy for patients after progression on imatinib and sunitinib.
Dose: 160 mg/day orally for 21 days of each 28 day cycle.

Radiation therapy
Radiation does not have a role in treatment of GIST. Several case reports have shown successful treatment of
abdominal metastases has been reported with cumulative dose 30-50 Gy delivered in 2-3 Gy/day fractions.3
Liver metastases has been reported to be treated with brachytherapy using yttrium 90 (90Y) microspheres. 3

FOLLOW UP

In case of completely resected localized disease, recommended surveillance includes:

- history and physical examination every 3-6 months for 5 years then annually
- abdominal CT every 3-6 months for 3-5 years then annually
If recurrence is diagnosed, consider treatment for primary unresectable or metastatic disease. 4

In persistent metastatic disease or persistent gross residual disease after surgery, recommended
surveillance includes history and physical and abdominal CT every 3-6 months.4
If disease is progressive, medical management of progressive disease is started.

In small GIST (<2cm) with no high-risk features on endoscopic ultrasound, endoscopic surveillance is carried out
4
at 6-12 month intervals.

References
1. Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumor. Lancet. 2013;382 (9896):973-83
2. European Society for Medical Oncology (ESMO)/European Sarcoma Network Working Group. Gastrointestinal
stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct;23
Suppl 7:49-55.
3. Kirsch R, Gao ZH, Riddell R. Gastrointestinal stromal tumors: diagnostic challenges and practical approach to
differential diagnosis. Adv Anat Pathol. 2007;14(4):261-85
4. von Mehren M, Randall RL, Boles S, et al. Soft Tissue Sarcoma. Version 1.2015. In: National Comprehensive Cancer
Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines). NCCN 2015 Feb from NCCN website.
5. Chen QL, Pan Y, Cai JQ, Wu D, Chen K, Mou YP. Laparoscopic versus open resection for gastric gastrointestinal
stromal tumors: an updated systematic review and meta-analysis. World J Surg Oncol 2014;12:206. doi: 10.1186/1477-
7819-12-206.

Motility disorders of oesophagus

Anubhav Vindal, Sachin Mittal

Oesophageal motility disorders run on a continuum from hypomotile to hypermotile dysfunction, with intermediate
types in between. Motility disorders of the oesophagus can be primary or secondary. Primary oesophageal
motility disorders fall into one of five types: achalasia cardia, diffuse oesophageal spasm (DES), nutcracker
oesophagus, hypertensive lower oesophageal sphincter (LES), and ineffective oesophageal motility.
Secondarymotor disorders of the oesophagus result from progression of systemic diseases such as collagen
vascular and neuromuscular diseases and cause disorders, reflecting a spectrum of various stages of destruction
of oesophageal motor function. Clinical presentation of primaryand secondary oesophageal motility disorders
may be similar. A careful assessment is therefore needed to ensure an accurate diagnosis and appropriate
treatment plan.

1. Achalasia Cardia
The literal meaning of the term achalasia is failure to relax and it is the best understood of all the oesophageal
motility disorders. It is mainly seen in young women and middle-aged men and women with an annual incidence
1
of 6/1,000,000 population. Its pathogenesis is an idiopathic or infectious neurogenic degeneration. Severe
emotional stress, trauma, drastic weight reduction, and Chagas disease (parasitic infection with Trypanosoma
cruzi) can sometime be causative factors. Whatever the cause, the muscle of the oesophagus and LES are

196
affected in this disease. Destruction of the nerves to the LES is considerd to be the primary pathology and it is
believed that the degeneration of the neuromuscular function of the body of the oesophagus is secondary. This
degeneration causes hypertension of the LES with an increase in its pressure, and non relaxation of the LES on
swallowing. This in turn causes pressurization of the oesophagus ando esophageal dilatation with loss of
progressive peristalsis over time.

Vigorous achalasia, a variant of classic achlasia, presents with dysphagia. In this variety, the LES is
hypertensive and fails to relax, as seen in achalasia, with simultaneous and nonperistaltic contractions of
oesophageal body, but the amplitude of contractions is normal or high, which is inconsistent with classic
achalasia. It may represent the early phase of achlasia which may not have abnormalities in the oesophageal
body and may go on to develop abnormal oesophageal body contractions in later stages.

Achalasia is considered to be a premalignantcondition of the oesophagus with an 8% risk of malignancy.

Constant mucosal irritation induces squamous metaplasia. Accordingly squamous cell carcinoma is the most
common variant of malignancy in the lower third of the oesophagus in patients with achalasia. Adenocarcinoma is
common in the middle third of the oesophagus above the air fluid level, as the irritative effect on the mucosa is
absent.2

Symptoms
The classic triad of achlasia consists of dysphagia, regurgitation of undigested foul smelling food, and weight
loss. However, heartburn, postprandial choking, and nocturnal coughing are also commonly seen. Dysphagia
begins with liquids and progresses to solids. The eating is slow, labourious and large volumes of water is used
to help wash the food down into the stomach. Pressure build up by water leads to retrosternal chest pain which
can be severe until the LES opens, providing relief from the pain. With progression of the disease, regurgitation
of undigested, foul-smelling food is common. Aspiration pneumonia, lung abscess, and bronchiectasis are
frequent sequelae of long-standing achalasia. Patients usually seek medical attention in advanced stages of the
disease.

Diagnosis
The diagnosis of achalasia is made from an oesophagogram and a motility study.

On oesophagogram, a dilated oesophagus with a distal narrowing referred to as the classic birds beak
appearance of the barium-filled oesophagus, is seen. (Fig 1) Other findings can be a sphincter spasm, delayed
emptying through the LES and dilatation of the oesophageal body. A lack of peristaltic waves in the body and
failure of relaxation of the LES is hallmark of this disease. Lack of a gastric air bubble is a common finding as the
tight LES does not allow air to pass easily into the stomach. In advanced stage of the disease, massive
oesophageal dilation, tortuosity, and a sigmoidal oesophagus (megaesophagus) are seen. (Fig 2) 2

Figure 1 - Bird Beak appearance Figure 2 - Megaoesophagus

Adapted fom Maish SM. Esophagus. In: Townsend MC, Beauchamp DR, Evers MB, Mattox LK, eds. Sabiston
text book of surgery. 19e. Philadelphia: Elseveir Saunders; 2012:1027 - 8.

Manometry is the gold standard test for diagnosis and helps to eliminate other potential oesophageal motility
disorders. In typical achalasia, the manometry tracings show five classic findings - two of which are abnormalities
of the LES and three, of the oesophageal body.

LES
Hypertensive (pressure >35 mm Hg)
Failure to relax with deglutition
BODY
Pressurisation of the oesophagus
Simultaneous mirrored contraction with loss of progressive
peristalsis
Low amplitude waveforms

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These five findings provide a diagnosis of achalasia. Endoscopy contributes little to the diagnosis of achalasia. It
evaluates the mucosa for evidence of oesophagitis or cancer.

Treatment
There are surgical and nonsurgical treatment options for achlasia, all of which are directed toward relieving the
obstruction caused by the LES. As none of these target the problem of decreased motility in the oesophageal
body, they are all palliative treatments.

Non Surgical
MEDICAL ENDOSCOPIC
(Mainly effective in early phase)
Sublingual nitroglycerine Bougie dilatation (54 F)
Calcium channel blockers Balloon dilatation
Injection botulinum

Surgical
Laparoscopic modified Hellers myotomy is the procedure of choice and offers superior results with less trauma
3
than balloon dilatation. It can be done open or with video or robotic assistance. The decision to perform an
antireflux procedure remains controversial. Antireflux procedures like Toupet or Dor can be added to restore a
barrier to reflux and decrease post operative symptoms after myotomy. This is more effective in patients whose
4
oesophageal clearance is greatly impaired. Oesophagectomy is considered in any symptomatic patient with
tortuous oesophagus (megaoesophagus), sigmoid oesophagus, failure of more than one myotomy, or an
undilatable reflux stricture. Oesophageal resection can be considered in end stage achlasia as it also eliminates
the risk of carcinoma. A transhiatal oesophagectomy withor without preservation of the vagus nerve offers a
good long-term result.5

Results
Results of medical, endoscopic and surgical procedures indicate surgery as the safest and most effective
treatment of achalasia. Studies of laparoscopic versus open myotomy have shown superior results with a
minimally invasive technique. Shorter length of stay, less pain, and excellent relief of dysphagia with an improved
heartburn score are seen with a laparoscopic approach. Laparoscopic myotomy is effective even after treatment
2
with botulinum toxin or balloon dilatation or with a massively dilated oesophagus.

2. Diffuse oesophageal spasm (DES)

Diffuse oesophageal spasm (DES) is a poorly understood oesophageal hypermotility disorder. Although its
presentation is similar to achalasia, it is five times less common than the latter. It is seen mostly in women and is
often found in patients with multiple complaints. The cause is unclear but basic pathology is related to a motor
abnormality of the lower third of the oesophageal body. There is muscular hypertrophy and degeneration of the
branches of the vagus nerve in the oesophagus which results in repetitive, simultaneous, high amplitude
oesophageal contractions.

Symptoms
The clinical presentation of DES is typically that of chest pain and dysphagia which may mimic those of angina.
There is feeling of squeezing pressure in the chest that may radiate to the jaw, arms, and upper back. The
symptoms are often aggravated during emotional stress. Regurgitation of oesophageal contents and saliva is
common, but acid reflux is not. Other functional gastrointestinal complaints, such as irritable bowel syndrome and
pyloric spasm, may accompany DES, whereas gallstones, peptic ulcer disease, and pancreatitis, all may trigger
DES.

Diagnosis
The diagnosis of DES is made by oesophagography and manometric studies. Oesophagogram shows cork screw
oesophagus or pseudodiverticulosis due to presence of tertiary contractions which indicates advanced disease.
(Fig 3)

Figure 3 - Cork screw oesophagus Adapted fom Maish SM. Esophagus. In: Townsend MC,
Beauchamp DR, Evers MB, Mattox LK, eds. Sabiston text book of surgery. 19e. Philadelphia: Elseveir Saunders; 2012:1031.

198
Manometry findings in DES are simultaneous multipeaked contractions of high amplitude (>120 mm Hg) or of
long duration (>2.5 seconds) occuring after more than 10% of wet swallows. An ambulatory motility record has a
sensitivity of 90% and a specificity of 100% based on an identified set of abnormalities. 2

Treatment
The mainstay of treatment for DES is nonsurgical, and pharmacologic or endoscopic intervention is preferred.
Surgery is reserved for patients with recurrent incapacitating episodes of dysphagia and chest pain who do not
respond to medical treatment. Evaluation for psychiatric conditions with their control, and reassurance of the
oesophageal nature of the chest pain, is often therapeutic in itself. For dysphagia elimination of trigger foods or
drinks from the diet is beneficial. For reflux, acid suppression medications are helpful. Peppermint may provide
temporary symptomatic relief. 6Bougie dilatation of the eosophagus up to 50 or 60 Fr provides relief for severe
dysphagia. Surgery is indicated for patients with incapacitating chestpain or dysphagia with failed medical and
endoscopic therapy, or in the presence of a pulsion diverticulum of the thoracic oesophagus. A long
oesophagomyotomy is performed through a left thoracotomy or a left Video assisted thoracic surgery (VATS) with
oesophageal manometry guiding the extent of the myotomy. The proximal extent should be high enough to
encompass the entire length of the segment with abnormal motility, as determined by manometric measurement,
with the distal extent extended down onto the LES. A Dor fundoplication can be added to prevent healing of the
myotomy site and to provide reflux protection.

3. Nutcracker oesophagus

Nutcracker oesophagus is the most common hypermotility disorder and is also known as super squeeze
oesophagus. It is described as an oesophagus with hypertensive peristalsis or high-amplitude peristaltic
contractions, and has equal gender predilection. It is associated with a hypertrophic musculature that results in
high-amplitude contractions of the oesophagus and is the most painful of all oesophageal motility disorders.

Symptoms
Presentation is similar to DES with chest pain and dysphagia. Odynophagia is also noted, but regurgitation and
reflux are uncommon.

Diagnosis
An oesophagogram may or may not reveal any abnormalities.

The gold standard of diagnosis is the subjective complaint of chest pain with simultaneous objective evidence of
peristaltic oesophageal contractions 2 standard deviations above the normal values on manometric tracings.
Amplitudes higher than 400 mm Hg are common. The LES pressure is normal and relaxation occurs with each
wet swallow. Ambulatory monitoring can help distinguish this disorder from DES. This differentiation is important
as patients with DES can be helped with an oesophagomyotomy, but surgery is of questionable value in patients
with a nutcracker oesophagus.

Treatment
The treatment of nutcracker oesophagus is essentially medical. In acute episodes calcium channel blockers,
nitrates, and antispasmodics may offer temporary relief. Bougie dilatation also has no long-term benefits. Patients
are counselled to avoid caffeine, cold, and hot foods.

4. Hypertensive LES

Hypertensive LES described by Code and colleagueswas first observed in patients presenting with dysphagia,
chest pain and manometric findings of an elevated LES. 7 Although the symptoms mimick achalasia, the
manometric findings are not consistent with achalasia. The LES pressure is above normal and relaxation though
incomplete, may not be consistently abnormal. The motility of the oesophageal body may be hyperperistaltic or
normal.

Symptoms and Diagnosis

The presentation in this disorder is with chest pain or dysphagia but acid reflux and regurgitation are experienced
less commonly. Manometry is diagnostic and demonstrates elevated LES pressure (>26 mm Hg) along with a
normal relaxation of the LES. About 50% of the time, peristalsis in the oesophageal body is normal. An
oesophagogram may show narrowing at the gastro oesophageal junction.

Treatment
Both endoscopic and surgical interventions can be done. Botulinum toxin injections alleviate symptoms
temporarily and hydrostatic balloon dilatation may provide long term symptomatic relief. Surgery is indicated for
patients who fail endoscopic treatments and those with significant symptoms. A laparoscopic modified Hellers
oesophagomyotomy is the operation of choice. In patients with a normal oesophageal motility, a partial antireflux
procedure (Dor or Toupet fundoplication) is added.

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5. Ineffective oesophageal motility (IEM)

First recognized as a separate disturbance by Castell in 2000,it is a contraction abnormality of the distal
oesophagus and is usually associated with gastro oesophageal reflux disease (GERD).8 It may be secondary to
an inflammatory injury of the oesophageal body because of increased exposure to gastric contents. Dampened
motility of the oesophageal body leads to poor acid clearance in the lower oesophagus. It is considered to be
irreversible if altered motility is present.

Symptoms and Diagnosis

The symptoms of IEM are mixed but the usual presentation is with symptoms of reflux and dysphagia. Heartburn,
chest pain, and regurgitation are noted. Diagnosis is made by manometry. IEM is characterized by a contraction
abnormality of the distal oesophagus in which the total of the number of low amplitude contractions (<30 mm Hg)
plus non transmitted contractions exceed 30% of wet swallows.

Treatment
The best treatment of IEM is prevention, which is associated with effective treatment of GERD.

6. Nonspecific oesophageal motor disorders (NEMs)

Nonspecific oesophageal motor (NEM) disorders include patients with manometric findings that do not fit into one
of the five classic patterns. It proves that oesophageal motility disorders are a spectrum of abnormalities that
reflect various stages of destruction of oesophageal motor function. The pathogenesis of NEM is multifaceted.
Several collagen vascular disorders like scleroderma, dermatomyositis, polymyositis and lupus erythematous
affect the neuromuscular oesophageal architecture, resulting in poor oesophageal motility.

Symptoms and Diagnosis

Chest pain and dysphagia are common and patients tend to experience more reflux symptoms and regurgitation
than patients with other defined disorders. Diagnostic tests include barium esophagography and manometric
studies. Oesophagography is helpful to rule out disorders with defined abnormalities and identifies abnormal
oesophageal body contractions as well as abnormalities of the LES.

On manometry LES can be normal or hypertensive, but incomplete relaxation (residual >5 mm Hg) is noted.
Contractions of the oesophageal body follow one or more of the following patterns: nontransmitted, triple-peaked,
retrograde, low-amplitude (<35 mm Hg), or prolonged duration (>6 seconds). Patients with scleroderma have
low-amplitude simultaneous contractions of the oesophageal body, similar to those seen with achalasia, but the
2
LES is noted to have normal or low pressure.

Treatment
Treatment of NEM is difficult because a primary diagnosis is missing. Those with a collagen vascular or
neuromuscular disorder are treated for their primary medical condition, which often results in improved
oesophageal motility. For those whose underlying condition remains undiagnosed, combination therapy,
including medications and endoscopic interventions, can be applied, as guided by the existing manometric
findings.
VIGROUS HYPERTENSIVE NUTCRAKER
FEATURES NORMAL ACHALASIA DES IEM NEMs
ACHALASIA LES ESOPHAGUS
Dysphagia
Chest Pain Dysphagia
Chest Dysphagia Dysphagia Dysphagia Dysphagia
Symptoms NONE Dysphagia Heart Burn
Pressure Chest Pain Chest Pain Pain
Chest Pain
Regurgitation
Barium Bird Beak Super Slow Transit Slow Transit
Distal
Oesophago- Normal Dilated Abnormal Corkscrew squeeze Incomplete Incomplete
Obstruction
gram Oesophagus emptying emptying
Patulous Hyper Hyper
Endoscopy Normal Normal Normal Non Specific Non Specific
Oesophagus Peristalsis Peristalsis
LES 15-25 mm Hypertensive Normal or Hypertensive Normal or Normal or
Normal Normal
Pressure Hg > 26 mm Hg Hypertensive > 26 mm Hg elevated low
Incomplete Incomplete
LES Follows Residual Partial or Residual
Normal Normal Normal Normal
Relaxation swallowing pressure > 5 Absent pressure
mm > 5 mm Hg
Hypertensive
Amplitude Decreased Decreased Decreased
50-120 MM Normal Normal Normal >180 mm Hg
Pressure < 40 mm Hg <30 mm Hg <35 mm Hg
>400 mm Hg
Non
Simultaneo Non
Contraction Simultaneous Simultaneous transmitted
Progressive Normal us Long > 6 sec transmitted
Wave Mirrorred Repetitive >20%
Repetitive >30%
Triple peaked
Hypertensive
Peristalsis Normal None None Normal None Abnormal Abnormal
Peristalsis

200
References

1. Park W, Vaezi MF: Cause and pathogenesis of achalasia: The current understanding. Am J Gastroenterol. 2005;
100:14041414.
2. Maish SM. Esophagus. In: Townsend MC, Beauchamp DR, Evers MB, Mattox LK, eds. Sabiston text book of
surgery (19e) Philadelphia: Elseveir Saunders. 2012; 1025-1032.
3. Moawad FJ, Wong RK: Modern management of achalasia. Curr Opin Gastroenterol. 2010; 26:384388.
4. St Peter SD, Swain JM: Achalasia: A comprehensive review. Surg Laparosc Endosc Percutan Tech. 2003; 13:22740.
5. Banki F, Mason RJ, DeMeester SR, et al: Vagal-sparing esophagectomy: A more physiologic alternative. Ann
Surg. 2002; 236:324335.
6. Tutuian R, Castell DO: Review article: Oesophageal spasmdiagnosis and management. Aliment Pharmacol
Ther. 2006; 23:13931402.
7. Code CF, Schlegel JF, Kelley ML, Jr, et al: Hypertensive gastroesophageal sphincter. Proc Staff Meet Mayo Clin.
1960; 35:391399.
8. Blonski W, Vela M, Safder A, et al: Revised criterion for diagnosis of ineffective esophageal motility is associated
with more frequent dysphagia and greater bolus transit abnormalities. Am J Gastroenterol. 2008; 103: 699704.

Short bowel syndrome

Deepak Ghuliani, Abhinav Agrihari

Short bowel syndrome (SBS) is a complex condition and remains one of the most challenging problems in
surgical practice with significant morbidity and mortality. It is characterized by a short small intestine length which
is inadequate to digest and/or absorb nutrients for normal growth, development, and maintaining normal
homeostasis. The inadequate intestinal length either due to congenital absence or following extensive bowel
resection results in an intestinal failure leading to significant protein energy , fluid, electrolyte and micronutrient
imbalances requiring specialized medical and nutritional support .Patients with SBS present with diverse
derangements in the initial disease with a complex array of secondary problems .A multidisciplinary approach,
conscientious decision making and timely judicious planning can be crucial in improving the quality and quantity
of life of these patients.

ETIOLOGY
The causes of short bowel syndrome may be congenital or acquird.15% of adult patients undergoing intestinal
resections are likely to develop short bowel syndrome.75% cases of SBS occur because of single massive
intestinal resection while 25% result from multiple sequential resections.

Table 1. etiology of SBS

Congenital Acquired Functional/ Physiological
Necrotising enterocolitis Mesenteric vascular accidents Proximal diverting stoma
Intestinal atresia Trauma- loss of intestinal vascularity Enteropathies
Midgut volvulus Post-traumatic mesenteric Lymphangiectasis
thrombosis
Gastroschisis Radiationl enteritis Pseudo-obstruction
Long segment Hirschsprungs Crohns disease
Meconium ileus Malignancy
True congenital short gut

PATHOPHYSIOLOGY
As a consequence of massive intestinal resection there is loss of absorptive surface area and increase in
intestinal transit resulting in malabsorption of macro, micro nutrients , electrolytes and water. Small intestine has
a large functional reserve and about 50% of small bowel resection is well tolerated. SBS develops when less than
1/3rd (<200cm) of small intestine has been left behind. The extent of malabsorption is not only determined by
length of the residual intestine but also on the specific parts of bowel resected, their site specific transport cells
and adequacy of the adaptive process in the of intestine left.

SBS can be divided into three anatomic subtypes

Type I :Small bowel resection with a high output end jejunostomy
Type II: Small bowel resection with partial colonic resection and a enterocolic(jejunocolic) anastamosis.
Type III: Small bowel resection with enteroenteric anastmoses(jejunoileal)and an intact colon.

Type II is the most commonly encountered in clinical practice while Type III is the most tolerated subtype with
maximum adaptive potential. The important factors associated with outcome of short bowel syndrome include the
length and function of small intestine (<40 cm or< 10% of gestational age), the presence or absence of ileoceacal
valve and colon in continuity, the nature of primary disorder, presence of residual underlying disease and age of
the patient.

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Jejunal resections are better tolerated than ileal resections as ileum has a greater adaptive capacity. Extensive
ileal resections lead to an inability to absorb dietary fluid and jejunal secretions along with the loss of absorption
of vitamin B12, bile salts and fatty acids. Besides the disruption of enterohepatic circulation and passage of
unabsorbed bile salts in colon stimulates colonic secretion and motility with further worsening of the symptoms.

Presence of colon is always beneficial in patients of SBS as the colon absorbs water, electrolytes and fatty acids,
slows intestinal transit and stimulates the adaptive response in small intestine. Peptide YY(PYY) hormone
produced in terminal ileum and proximal colon is responsible for jejunal-ileal-colonic brake which slows down the
intestinal transit in response to fat intake. Besides ,the fermentation of mal absorbed carbohydrates by colonic
bacteria to short chain fatty acids and their subsequent absorption in the colon provides an additional source of
energy upto 1000 kcal(4.2MJ).A rapid gastric emptying and increased intestinal transit due to impaired release of
Glucagon like peptide1(GLP1),Glucagon like peptide2(GLP2 )and PYY in patients with proximal jejunostomy
compromises the gastric phase of digestion and nutrient mal absorption. Rapid intestinal transit affects the
enterocyte nutrient contact time thereby decreasing the segmental absorption.

Adaptation
Adaptation is a compensatory mechanism by the residual small bowel after massive bowel resection and plays a
crucial role in management of these patients .There are both structural and functional changes in the small bowel
during the adaptive process. The structural process is characterized by increase in absorptive surface area with
enhanced digestive and enzymatic activity. It involves hyperplasia of the mucosal epithelium with and increase in
the crypt cell proliferation , villous height and crypt depth . This results in elongation and dilatation of small bowel
with an overall increase in the functioning absorptive surface area with increase in microvillous enzyme activity
and absorptive capacity per unit length of intestine for nutrient absorption. During functional adaptation there is a
slowing of the bowel transit which allows an increased contact time for absorption to occur.

The intestinal adaptation depends upon number of factors like extent and site of intestinal loss or dysfunction,
function of the remnant small bowel and associated digestive organs, presence of icv, terminal ileum and colon
and amount of time that has elapsed since bowel resection. The adaptive process starts as early as within 12 to
24 hours of resection and continues for 1 to 2 years. Younger the patient more pronounced is the adaptive
response. It is more marked in infants who have a growth potential .The remaining intestine lengthens to a
greater degree after a resection of the proximal small bowel when compared to the resection of the distal portion.
Ileum is more adept at adaptation, and attains morphological features of jejunum with taller villi and deeper
crypts. The length of the residual bowel is the prime determinant of the adaptive response. The adaptive
response is effective enough to allow full enteral nutrition even after a 70-80% of the small bowel mass has been
removed. The best results occur when the ileocaecal valve remains intact. Loss of IC valve almost doubles the
minimum length of residual bowel required for successful adaptation. Minimum length required for eventual
successful adaptation has been reported to be 40cm without an intact IC valve, and 25cm in the presence of an
intact IC valve.

Mechanisms and Mediators of adaptation

Although the precise mechanisms or signals triggering the adaptive response are not clear , the major factors
influencing this process include the exposure of small intestinal mucosa to enteral nutrients and trophic effects of
various growth factors and hormones.
1. Intra luminal nutrients: The presence of specific intra luminal nutrients can play a vital role in the adaptive
process. Reversal of gut mucosal atrophy consequent to prolonged parenteral nutrition(PN) and starvation
has been seen with initiation of enteral feeds. Enteral feeds act as stimulators of intestinal mucosal
maintenance. Mucosal hyperplasia stimulation by direct contact with epithelial cells, stimulation of trophic
gastrointestinal hormone secretion, peristalsis, increased mucosal blood flow and production of pancreato
biliary secretions contribute to the effects of enteral feeds in adaptive response. Complex nutrients trigger a
better response, the so-called functional workload hypothesis . Long-chain and unsaturated fatty acids are
specially trophic to intestinal mucosa. Soluble fibre( pectin, guar gum)and carbohydrates slow the gastric
emptying and overall bowel transit producing a mild anti diarrhoeal effect. Glutamine has been reported to
prevent mucosal atrophy and shown to be vital for the proliferative effects of endogenous growth factors, but
there are no large studies at present showing beneficial effects of glutamine.

2. GastrointestinalSecretions: Endogenous pancreatico biliary secretions have been found to be trophic to the
gut mucosa. Bile alone has been shown to stimulate RNA and DNA synthesis in bowel mucosa, and the
effect is potentiated by pancreatic secretions. Somatostatin used to decrease the fecal volume loss, acts by
diminishing the output of pancreatic secretions, also blunts the adaptive process.

3. Hormones and growth factors: The neurohormonal mediators like Enteroglucagon, Peptide YY, glucagon like
peptide1 and 2, are produced by the terminal ileum and have been found to play a role in the adaptive
response. These extracellular growth factors trigger polyamine synthesis in crypt cells which induces
increased DNA synthesis and mitotic activity. The administration of growth hormone has shown to improvise
the fluid and electrolyte absorption and nutrient transport in human GIT. Most convincing evidence has been
gathered so far for epidermal growth factor and its receptor .

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Clinical Sequelae of SBS
Loss of a significant length of small bowel results in interrelated physiological events as a result of decreased
small intestinal mucosal absorptive cell mass. Nutritional and metabolic effects ensue from diminished
intraluminal digestive capacity and rapid intestinal transit leading to an excessive loss of fluids, nutrients,
electrolytes and bile salts.

The important clinical sequlae include :

1. Malnutrition: Malabsorption of essential and nonessential nutrients, fluids, and electrolytes, leads to
diminished body stores and subclinical and eventually clinical deficiencies . The patient becomes cachexic
with time. Decreased output of brush border disaccharidases results in carbohydrate malaborption producing
reducing substances in the stools.
2. Bile salt malabsorption resulting from extensive ileal resections produces diarrhea, steatorrhea, and loss of
fat soluble vitamins. This also leads to depletion of bile acid pool which cant be compensated even with
increased hepatic synthesis. Loss of ileocaecal valve permits the reflux of colonic bacteria into small bowel
and increased bacterial counts in small bowel lumen. Adaptive process may lead to dilated dysfunctional
loops with poor motility susceptible to bacterial overgrowth. The endotoxins damage the mucosa, affect
motility, deconjugate the bile salts and further aggravate stasis. Bacterial translocation can further enhance
endotoxin shock, septicemia and bowel necrosis.

3. Diarrhea: inadequate absorptive surface leads to excessive volume loss and diarrhea. There is a rapid
intestinal transit across a shortened length. Gastric hyper secretion, seen with proximal and midgut
resections complicates the initial phase in SBS(2). Increased secretions and excessive salt load thus
secreted, compounds the diarrhea. Mal absorbed fats and carbohydrates pass into the colon and are
fermented by colonic bacteria into volatile short chain and hydroxylated fatty acids which also contribute to
diarrhea. Loss of cholecystokinin and secretin secondary to loss of enteroendocrine cell mass leads to
impaired gallbladder motility, decreased bile secretion and pancreatic secretions.

4. Vitamin and trace element deficiency: Deficiency of fat soluble vitamins can occur. Rickets is a known
complication. Vitamin B12 deficiency can result due to loss of ileal absorptive surface and also due to
excessive consumption in bacterial overgrowth.

MANAGEMENT
Management of SBS is complex and requires multi disciplinary dedicated intestinal rehabilitation teams

Medical management
The medical management comprises of the following:
1. Acute phase management
2. Nutritional support
3. Control of diarrhea
4. Management OF complications

ACUTE PHASE MANAGEMENT

The initial management in these patients primarily includes intense post operative and supportive care to
enhance the survival potential. This includes achievement of haemodynamic stability, control and treatment of
sepsis, maintenance of the fluid and electrolyte balance and nutritional support in the form of total parenteral
nutrition. Extensive small bowel resection is associated with transient hypergastenemia and acid hypersecretion
due to loss of negative feedback mechanisms. H2 blockers and PPI are given i.v to counter the
hypergasternemia induced gastric acid hypersecretion. This limits the volume losses, prevents impairment in the
function of digestive enzymes and peptic complications. In this phase, the treatment focuses on the replacement
of fluids and electrolytes as the patient is at risk for dehydration, sodium imbalance and metabolic acidosis.

Nutritional support
This should begin promptly, either by parentral or enteral route. Central venous lines are placed after the sepsis
is cleared. Ongoing fluid losses are calculated and can be either added in TPN solution or given by a second line
so that the TPN formulation is stable and does not require daily adjustments. After a stable state is reached, the
TPN is cycled so that the patient has significant periods of each day off the line. This allows for mobility and
appears to reduce the incidence and severity of PN associated cholestasis. Enteral feeding is started once the
patient is haemodynamically stable and the bowel function has returned. The enteral nutrition is started with the
aim of maximizing intestinal adaptation, attempting to discontinue PN and prevent complications associated with
underlying disease and TPN. Gradual introduction of enteral feeds is done as rapid introduction may exacerbate
the secretory diarrhea with its attendant fluid losses. Elemental formulas are used initially to facilitate digestion
and absorption and also to decrease the incidence of allergic reactions. Many hypoallergenic formulas are
available. These contain extensively hydrolysed proteins and thus they have very low antigenicity, and are thus
well tolerated. In contrast to adults, tolerance of fats is better in children, and they do not do well on calorie dense
high carbohydrate formulas. Thus pediatric formulas have 40-50% calories derived from fats. Long chain fats
have a higher calorie density and are better stimulators of adaptation, but medium chain fats are more easily
absorbed. The carbohydrates are generally well absorbed except for lactulose. They are digested rapidly and

203
produce a high osmotic load. Proteins in the formula are better provided in a hydrolysed partially digested forms.
But even complex proteins are well tolerated and protein malabsorption is rarely a problem in SBS.

Feeds are initiated as a dilute infusion in a continuous tube feeding pattern. Initially concentration is advanced at
low volume rates, finally reaching around 1cal//ml. Once the final rates are achieved at low volumes, enteral rates
are advanced and parentral rates are decreased isocalorically over 1-3days. Tolerance to enteral feed is judged
by testing for reducing sugars in the stools and monitoring volume and consistency of stools. As fat
malabsorption is not osmotically significant and protein malabsorption is rarely seen, advancement of feeding is
based on above criteria which monitor carbohydrate malabsorption only.

Patients with extensive terminal and distal ileal resections have a significant bile salt and fat malabsorption due to
loss of enterohepatic circulation leading to malnutrition, steatorrohea and deficiency of fat soluble vitamins A,D E
K. Administration of synthetic conjugated bile acid cholylsarcosine can improve the fat absorbtion. Since water
soluble vitamins are absorbed in entire bowel ,the deficiency of these vitamins except for vitamin B12 is usually
not seen in patients of SBS. Vitamin B12 absorption needs and intact stomach for intrinsic factor and intact
terminal ileum to absorb this intrinsic factor-vitmain B12 complex. Therefore the vitaminB12 levels should be
monitored and if abnormal, it should be replaced monthly. Adequate supplement doses of vitamin A, D and E
should be added to the diet. Vitamin K should be given IV every week. Deficiency of trace elements like zinc,
copper and seleneium, is common in these patients and may lead to epithelial and mesenchymal dysfunction
along with immunodeficiency. Active enteral or parenteral replacement of these elements becomes essential

Appropriate enteral feeding devices are selected based upon the duration of expected adaptation interval,
etiology of SBS and motility of residual bowel. Nasogastric tube feeding is indicated when the expected duration
of tube feeds will be less than 3-4months. Gastrostomy feedings are usually ideal for the long term feeds and for
continuous drip in feeds. Jejunostomy tubes are indicated in patients with poor GI motility or in those who dont
tolerate gastrostomy feeds. After the patient is stabilized, and the acute phase is over, therapies targeted at
promoting adaptation may be started.

The adaptation phase occurs over the next 1-2 years during which majority of functional and structural changes
would take place . This is followed by a maintainence phase with the goals of providing adequate caloric nutrition,
preventing any complications and providing a definitive medical therapy for underlying disease like the crohns
disease . Long term parenteral nutrition can lead to mechanical, septic and metabolic complications including
catheter related complications, venous thrombosis and parenteral nutrition associated liver disease. End stage
liver disease develops in 15% of adult patients on long term PN. The 1 and 5 year survival rates of patients on
PN varies from 91 TO 97%and 62 to 86% in adults and 97% and 89% in children. The morbidity and expense
associated with PN makes it important to maximize the enteral feeding for long term survival of these patients
with the ultimate aim of achieving enteral autonomy.

The diet of these patients has to be individualized and continuously modified as the ability to absorb nutrients
improves with the adaptation of residual intestine. A hyperphagic diet is advised as these patients absorb only
rd rd
1/3 to 2/3 as much energy as a normal individual. The dietary intake should be increased by 50% and this
increased quantity is best tolerated when taken as 5-6 meals spread over 24 hours. The fluid and macronutrients
in the diet have to be planned according to the remaining bowel anatomy. In patients without presence of colon
administration of ORS helps in improving water and sodium absorption in proximal small bowel. Use of ORS is
not critical in patients with an intact colon if dietary sodium is sufficient. In patients with colon in continuity with the
residual small bowel complex carbohydrates including starch, non starch polysaccrides and soluble fibre in diet is
preferred. The presence of complex carbohydrates in the diet reduces the osmotic load and exerts a positive
effect on the adaptive process. Since These complex macronutrients are not absorbed in small bowel they pass
undigested to colon where they are fermented to short chain fatty acids by the colonic bacteria. The fat in the diet
should be restricted to 20-30% of total daily calorie intake in patients with an intact colon to limit steatorrhoea.

CONTROL OF DIARRHEA
Diarrhea in a patient of SBS results from multiple causes, the causative factor should be identified and therapy
instituted accordingly. Gastric hypersecretion complicates the acute phase of adaptation by augmenting diarrhea.
Histamine-2 receptor blockers are useful in reducing water and sodium losses related to hypergastrinemia .In
addition to the dietary changes long term use of anti motility and anti secretory agents may be required to control
fluid losses in stools. These agents predominantly reduce the intestinal motility but may also reduce intestinal
secretions to some extent. Loperamide 4-6 mg 4 times daily, Diphenoxylate 2.5-5mg 4 times daily, codeine
phosphate 15-60 mg 2-4 times daily and tincture of opium 0.6 ml(2.5)mg 2-4 times daily can be used successfully
to reduce intestinal motility but must be weaned off early due to the addictive potential of these agents. Use of
anti-motility drugs increases the risk of bacterial overgrowth. It causes pain, fever, sudden increase in diarrhea
with foul smelling stools and can retard the process of adaptation. Somatostatin and its long acting synthetic
analogue Octreotid may be useful in short term treatment of refractory diarrhea and massive fluid losses
especially in patients of type I subtype of short bowel syndrome with a proximal jejunostomy. Octreotide reduces
the gastric secretion, slows the intestinal transit and increases sodium and water absorbtion. But its use can
produce important side effects like inhibition of intestinal adaptive process, cholelithiasis and exacerbation of
steatorrhoea due to decrease in pancreatic exocrine functionAddition of 2% pectin to the diet improves the

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consistency of the stools and prolongs the intestinal transit and thus helps in adaptation. Management of diarrhea
also includes the prevention and treatment of troublesome perineal rash. Emollient oils like coconut oil and zinc
oxide paste can be used in early stage while 10% mixture of cholestyramine powder in a suspension of aquaphor
base helps bind the excess bile acids which potentiate the rash.

COMPLICATIONS

Metabolic
Metabolic complications are quite common in SBS due to diarrhea with massive fluid and electrolyte losses.
Continuous use of enteral feeds, reduction in osmolarity of enteral feeds using a low carbohydrate and a high fat
diet or diluting feeds can be helpful. Hypocalcemia can be seen due to poor absorbtion, binding to the
unabsorbed intraluminal fatsand vitamin D deficiency .Hypocalcemia and hypomagnesaemia are common in
patients on PN and need a aggressive replacement.

Small bowel bacterial overgrowth

A common and treatable complication of SBS is small bowel bacterial overgrowth (SBBO) which is defined as a
significant increase in the number of bacteria in upper GI Tract leading to development of symptoms..This usually
occurs due to anatomical factors like absence of ileoceacal valve, presence of fistulas, strictures or blind loops,
loss of gut associated lymphoid tissue, malnutrition and immunodeficiency. Bacterial overgrowth produces
inflammation of intestinal epithelium, villous atrophy and increase in bile acid deconjugation leading to nutrient
malabsorption.
Another consequence of SBBO in patients with intact colon is D-lactic acidosis which occurs due to fermentation
of simple sugars by these enteric bacteria .Patients present with ataxia, delirium and seizures.A definitive
diagnosis of SBBO can be established by culture of the upper small bowel and gastric fluid obtained after
aspiration. Glucose hydrogen breath test which measures the hydrogen produced by luminal bacteria from
metabolism of carbohydrates in the intestinal lumen.

Treatment includes broad spectrum antibiotics covering both aerobic and anaerobic bacteria with a reduction
intake of oral carbohydrates. Since the cause associated with SBBO persists periodic treatment with antibiotics
every 7-14 days every month may be needed. The anti motility agents should be stopped and surgical correction
of underlying anatomical defects like strictures, fistulas or dysmotile segments should be considered.

Complications of Parenteral nutrition

Chronic PN use can lead to several mechanical, septic and metabolic complications.
Most devastating and frequent complication is the sepsis that is associated with central venous lines. Meticulous
care of central catheters with regular dressings in aseptic manner, frequent cultures, flushing with urokinase and
antibiotic instillation (antibiotic lock technique) can all be helpful in preventing CVP line related sepsis.One thirds
of mortalities in a series of patients of SBS was due to central venous catheter related sepsis. Staphylococcus,
fungi and gram negative bacteria are the common causative organisms.

Liver disease commonly ensues in patients requiring long term PN. Previously known as parenteral nutrition
associated liver disease(PNALD)this complication is now commonly known as Intestinal failure-associated liver
disease.(IFALD) .It is seen in 40- 60% of infants and 15-40% of adults requiring long term PN.15% of patients
who receive PN for more than 1 year will develop end stage liver disease resulting in 100% mortality within 2
years. The contributory factors include prematurity, lack of enteral feeding, systemic or portal endotoxemia,
amino acid imbalance, carbohydrate overloading, abnormal fat metabolism and presence of phytosterols in
intravenous fat emulsions. Hepatic steatosis, intrahepatic cholestasis and cholelithiasis are the common
pathological features seen. To prevent this complication at least 20-30% of daily calorie intake should be through
enteral routes thereby promoting the enterohepatic circulation and stimulating the release of GI hormones. SBBO
be promptly treated sepsis should be prevented and the amino acid composition of PN should include the
essential amino acid, Taurine.

Renal stones
60% of patients with SBS have hyperoxaluria and can develop the calcium oxalate stones in kidney. In patients
with distal small bowel resections with fat malabsorbtion the dietary calcium binds to free fatty acids allowing free
oxalate to be absorbed in the colon. Treatment includes the restriction of oxalate rich foods and supplementation
of oral calcium.

Cholelithiasis
30% of patients with SBS develop chholelithiasis. Disruption of enterohepatic circulation, increased colonic bile
salts and gall bladder stasis due to long term PN are the contributory factors. Risk of gall stones increases with a
small (<120 cm) intestinal length, absence of terminal ileum and increased dependence on PN. The risk of
cholelithiasis can be reduced by increasing calorie intake enterally, administering cholecystokinin in PN
dependent patients and a prophylactic cholecystectomy.

Surgical Management
Surgical management may be indicated in patients

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 Who fail to achieve independence from PN
Develop hepatic complications of long term PN
Have recurrent episodes of central line sepsis
Have developed complications like bacterial overgrowth and intestinal stasis

The main objective of surgical treatment is enteral autonomy either by increasing the intestinal transit
time or by increasing the function absorptive capacity and surface area of the bowel.

Broadly the surgeries are divided into two broad categories

Autologous intestinal reconstruction surgery(AIRS)
Intestinal transplantation

Factors which influence the choice of operative treatment are

a. Length, location and caliber of the remnant bowel
b. Underlying bowel function
c. Age of the patient and associated co morbid conditions if any

Prior to surgery a contrast study must be done to assess the length, caliber and motility of remaining bowel. A
liver biopsy is also mandatory preoperatively to see the extent of PN associated cholestasis and differentiate
liver fibrosis from end stage liver disease. A prophylactic cholecystectomy is advisable as patients with terminal
ileal resection and long term PN carry a risk of developing cholelithiasis.

Autologous intestinal reconstruction surgery

1. Improve intestinal function and motility(Maximise the intestinal remanant)

Surgical management of SBS begins at the initial operation itself. Viability of the bowel should be carefully
assessed and tissue even if marginally viable should be preserved. Mechanical small bowel obstruction due to
adhesions from previous surgeries should be treated by adhesionlysis and benign strictures repaired by
stricturoplasty. Chronic fistulas and perforations should be managed with serosal patch repair if
appropriate.Resection if necessary should involve short segments even if requires multiple anastamosis. To
maximize the functional bowel length avoid formation of blind loops end to end anasatmosis are preferred. Any
bowel loop if bypassed during any previous surgery should be tried to be recruited into continuity during
reoperation.

2. Resoration of GI continuity
Stoma closure not only increases the mucosal absorptive surface area and also facilitates the adaptive response
in the residual bowel. Bringing the colon in continuity affects the stool volume and also improves carbohydrate
absorption.

TECHNIQUES FOR IMPROVING INTESTINAL MOTILITY AND PROLONGING TRANSIT

After extensive small bowel resection there is increase in the caliber of residual bowel. These dilated segments
of bowel become dysmotile and predispose to stasis bacterial overgrowth, bacterial translocation, enteritis and
malabsorption. The function of these dysmotile segments may be improved by tapering and plication of the small
intestine. One of the procedures for achieving this is tapering enteroplasty. This entails partial resection of the
anti mesenteric border of the dilated intestine to reduce the diameter of the intestinal loop. An important
disadvantage of this procedure is the loss of some absorbtive surface which is already limited in these patients.
Thus , this procedure should be avoided in patients with already borderline short small intestine. In Intestinal
plication a part of dilated bowel loop is inverted in the small bowel lumen and secured by seromuscular sutures.
This procedure salvages absorptive area and at the same time narrows the dysfunctional lumen. But the inverted
bowel can lead to bowel obstruction and there may be repeat dilatation and dysmotility due to suture line failure.

Many procedures like reveresed intestinal segments, intestinal valves , colonic interposition pacing, denervation,
recircu lating bowel loops have been tried to increase the intestinal transit time. But no large studies are available
in literature evaluating the outcome of reversed intestinal segments, intestinal valves , colonic interposition. Since
these procedures are usually performed in adaptation phase it becomes difficult to ascertain that improvement in
nutritional status is due to the surgery or normal adaptive mechanism.

Reversed intestinal segments: The placement of antiperistaltic intestinal segment is one of the oldest
procedures described to prolong the intestinal transit. A segment of small bowel is placed in a direction opposite
to that of the normal peristalsis. This induces reverse peristalsis and prolongs intestinal transit by disrupting the
intrinsic nerve plexus and slowing down the myoelectrical activity. The ideal length of reversed intestinal segment
should be<=10cm in adults and 3 cm in children and should be created as distal in small intestinal remnant as
possible. Anastamotic leaks and transient bowel obstruction can be some important complications. Clinical
improvement has been reported in upto 80% of patients in whom an antiperistaltic segment is used

Colonic transposition: Interposing a colonic segment in the remnant small intestine in either an isoperistaltic or
antipersitaltic fashion will retard intestinal motility due to inherent slow peristaltic activity of the large bowel.

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Besides, the interposed colonic segments also absorb water, electrolytes and nutrients. Isoperistaltic segments
are placed in proximal bowel and antiperistaltic segments are placed in distal locations. The effects are
inconsistent but many patients have reported successful outcome. Stasis is a necessary side effect of these
procedures. The experience with colonic interposition has seen primarily in paediatric patients.

Intestinal Valves: The purpose of creating intestinal valves surgically is to simulate the ileocaecal valve function,
to slow down the transit and to prevent bacterial back wash into proximal valve. Intestinal valve causes dilation
and hypertrophy of the proximal intestine and may serve as a first step to intestinal lengthening procedures (16).

Intussuscepted nipple valves are the most commonly used valves. The valve is constructed like a Brooke
ileostomy and preferably at the ileocolonic junction, with about 8cm of intestine.

A prosthetic valve made of PTFE requires only 3cm of native intestine for its construction.made by placing a
prosthetic band 1cm wide around the intestine and then intussuscepting the intestine over the band
reterogradely.

Construction of the appropriate diameter and length of the valve is difficult as this varies with the age of the
patients, growth rate, diameter of the intestine and motility. The result of these valves has been variable.
Potential complications include, obstruction due to too tight valve, no benefit due to too loose a valve, erosion of
the prosthesis into the lumen of small intestine and obstruction due to dislodgement and tissue reaction.
.
PROCEDURES FOR INCREASING ABSORBTIVE SURFACE AREA: SMALL BOWEL LENGTHENING
PROCEDURES

Longitudinal intestinal lengthening procedure ( LILT,Bianchi procedure): This was first described by Bianchi
in 1980 and was first applied clinically by Boeckman and Traylor in 1981. This procedure is based on the
anatomical observation of peculiar blood supply of small intestine. Intestinal vasculature divides within the two
mesenteric leaves into end arteries which alternate to each side of intestine. By dividing the bowel longitudinally
between the two mesenteric leaves at a relatively avascular plane midway between the mesenteric vessels, two
parallel vascularised loops of half the diameter as the original one, can be obtained. The hemi segments are
rolled into tubes either by manual suturing or by stapler and are anastamosed isoperistaltically to each other. The
reduction in bowel diameter improves the problems of ineffective peristalsis and stasis while an increased bowel
length prolongs transit time especially in the early post operative period . This procedure is recommended in
refractory short bowel syndrome with dilated small bowel loops. But this procedure may not prolong survival in
the setting of liver failure. Patients with an obviously short bowel length who may not adapt on medical
management should be offered this procedure early when liver dysfunction has not set in yet. This procedure is
not recommended in inflammatory bowel disease, chronic vascular occlusions and chronic infections, as all these
conditions have an abnormal and unreliable vascularity. Successful adaptation to full enteral feeds has been
reported in 45-70% of the patients who underwent this procedure for refractory SBS. Factors associated with
better outcome were more than 40cm of residual small intestine, presence of ileocaecal valve, presence of colon
and treatable liver dysfunction. Complications have been reported in 20% of patients and include leakage, fistula
formation, stenosis due to inadequate vascularity. Loss of hemiloop due to vascular insult has also been seen but
infrequent. Most of the mortality and morbidity was due to liver dysfunction.

Serial transverse enteroplasty procedure (STEP): Kim et al were first to describe the STEP procedure in
aporcine model in 2003.and performed the first steo procedure later in the same year in a 2 year old boy.It is a
novel technique during which linear cutting stapler is applied from alternating and opposite directions along the
mesenteric border of intestine to incompletely staple and divide the dilated intestine. This produces tapering of
intestine in a zig zag pattern which results in nutrients being channeled through a narrower but longer intestine..
The final bowel length can be increased by greater than 100% of the original length. In comparison to LILT ,
STEP is technically less demanding and allows better preservation of the mesenteric blood supply. STEP can be
used as a primary intestinal legthening procedure or may be done after a successful LILT if there is repeat
dilatation of the bowel. Like LILT H post lengthening dilation may occur, which can lead to bacterial overgrowth
and malabsorption.

Transverse bowel lengthening (Kimuras procedure): Kimura et al described the concept of isolated bowel
segment in 1990s and the first human report was published in 1993. It consists of creating an alternate blood
supply on the antimesentric surface of the small intestine and then dividing the intestine in two parallel loops in

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the transverse plane, isolating one loop on the new blood supply. The procedure is performed in 2 stages. In the
first stage a strip of serosa is removed from the antimesentric bowel wall and this loop is anastomosed to a
portion of the abdominal wall or liver that has been stripped off its peritoneal covering. With time collaterals
develop and at 8-12weeks the bowel is transversely divided into 2 loops . This technique is used in when a
conventional LILT cannot be done due to foreshortened mesentery like in duodenum. Random nature of the
blood supply from the vascular adhesions portends a higher risk of ischemic bowel loss. Thus this usually is not
the first line option for bowel lengthening in these patients with already a limited intestinal reserve. Further
abdominal surgery is very difficult after this and thus it is offered as a final lengthening option and
cholecystectomy is done alongwith it.

Sequential intestinal lengthening: a combination of transverse and longitudinal bowel lengthening has been
proposed. Initially a nipple valve was used to dilate the bowel, then dilated loop was divided horizontally and
vertically at the same time into 3 segments which were rolled into tubes. The nipple valve was resected and
isoperistaltic anastomosis was done .

INTESTINAL TRANSPLANTATION
Small bowel transplantation is the final treatment option once the adaptive process has been completed and
results of AIRS and intestinal lengthening procedures are unsatisfactory. The indications include worsening liver
failure, recurrent severe sepsis, loss of central venous access and inability to achieve more than 50% of caloric
requirements enterally if associated with growth failure. Several variations exist for small bowel transplants. The
composite liver-small bowel allograft involves the liver, duodenum, pancreas and small intestine. Of late, colonic
segments too have been included in patients who have lost their colon to increase the post transplant absorptive
capacity. Other variations include small bowel pancreas or isolated small bowel allograft. In the isolated small
bowel graft intestine from ligament of trietz to ileoceac al junction is transplanted with the vascular pedicle based
on donor superior mesenteric aretery and portal vein.. Results are not as good as solid organ transplantation.
Vascular anastomoses need to be performed according to the state of the graft and the recipient. The portal route
is the first choice when possible. A two stage gut reconstruction could decrease the incidence of complications
(23). Generally, a cadaveric graft is used after ABO matching and virology screening.. Postoperative
immunosupression is mainly based on tacrolimus and steroids, while azathioprine, cyclophosphamide and
mycophenolate mofetil are useful in episodes of rejection. The lack of biochemical markers (like serum creatinine
in renal transplant) makes it difficult to assess the post transplant function. Assessment is based on clinical
findings of stool frequency, volume, consistency, and repeated endoscopies and mucosal biopsies. . Acute
rejection is reported in 56 to 79 % of patients with isolated small bowel transplant. Large amounts of gut
associated lymphoid tissue, donor dendritic cells and macrophages makes small bowel transplant , a highly
immunogenic one. The risk of acute rejection is lower in combined liver- small bowel transplants(71%) in
comparison to isolated small bowel transplants.(79%)

Chronic rejection is the most common cause of graft loss after second year. The incidence of chronic rejection is
10% and is five times more common in isolated small intestinal transplant. Retransplant after graft failure has
been reported in 6.8% of patients. Sepsis, dysmotility, and post operative gastrointestinal lymphoproliferative
disease are the other common complications

Prognosis
The mortality rate for SBS has remained stable after a substantial decrease was seen with the introduction of
TPN in early 80s. Mortality rates range from 17-22% and the most common causes are sepsis and hepatic
failure. In children, SBS can lead to developmental delay in around 10-15%. Treatment of SBS is very expensive,
more for developing countries. The shorter the segment, and higher the cost of managing short bowel syndrome.

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A multidisciplinary intestinal rehabilitation has been found to decrease the liver failure related mortality due to
early referral and increased survival to transplant.

Parasitic infestations of liver

Sushanto Neogi

HEPATIC AMOEBIASIS (AMOEBIC LIVER ABSCESS ALA)

Entaboeba hystolitica is a protozoa Sarcodina that infects 1-5% of world population and average 5% of the
affected individuals suffer from amoebic liver abscess. The incidence is more common in tropics with poor
sanitation.1

Genesis of hepatic ameobiaisis

Amobic liver abscess occurs as sequelae to amoebic infestation of large intestine where the cysts have
developed into trophozoites. The trophozoites of E. hystolitica are carried as emboli by the radicles of portal vein
from the base of ulcer in large intestine. Once established in liver, they multiply and proceed to carry on their
cytolytic actions. These cause obstruction to the circulation and cause thrombosis of the portal sinusoids,
resulting in necrosis. At first, the necrotic material consists of solid slough and later the center liquefies by the
cytolytic action and the liquefaction extends radially. A fairly large sized abscess forms by coalition of these
military abscesses.

Gross appearance- abscesses are usually single and located in the postero- superior part of liver and can be of
various sizes.the absceess are reddish brown in colour with semifluid or groumous consistency.

Microscopic appearance- the margin of liverabscess shows three zones from centre to periphery.
Central zone of cytolysed granular material with no amoebae.
Intermediate zone of degenerated liver cells, few leucocytes, connective tissue, red blood celss and few
trophozoites.
Peripheral zone of congested capillaries with varying degree of necrosed liver cells. The amoebae are
seen multiplying and invading healthy tissue.

The pus in liver abscess is a mixture of sloughed liver tissue and blood. It is chocolate brown in colour and thick
in consistency and called anchovy- sauce pus.2

Clinical features
Pain is the earliest manifestation which starts in the right upper abdomen usually because of capsule stretching
and can also be referred to the tip of right shoulder when the under surface of diaphragm is irritated. A dry cough
may also be present. Presentations because of complications of liver abscess are based where the rupture is
occurring.
Fever is a constant symptom and can start as mild grade, later becomes quotidian and hectic because of
pyrogenic effect of necrosed liver cells.
Jaundice is an unusual manifestation and can be because of associated amebic hepatitis or pressure effect of
biliary channels by a large abscess.
Examination reveals a tender hepatomegaly. The liver dullness may extend upwards. The basal air entry may be
less because of either collapse of right lung base or by right sided pleural effusion.
Left lobe liver abscess are known for pericardial rupture and fill present with features of pericardial effusion or
1
tamponade.

Course and termination

It may heal up spontaneously leaving an encysted mass, the contents of which are fibrosed or calcified.
The liver abscess can have following sequelae:

Right sided abscess may rupture:

a. Externally- rupture through the skin is one of the most natural forms of termination. The skin may be
secondarily infected with the trophic forms of E. hystolitica, forming granuloma cutis.
b. Into lungs- anchovy sauce pus comes in expectoration giving rise to symptom of hemoptysis.
Microscopically, liver cells and trophozoites may be recognized.
c. Into right pleural space- leading to empyema thoracis.
d. Subdiaphraghmatic abscess
e. Into peritoneal cavity to produce localized or generalized peritonitis.

Left sided liver abscess may ruture into:

a. Stomach- hemetemesis of anchovy sauce pus
b. Pericardial cavity- tamponade or purulent pericarditis with a high mortality.
c. Externally through the parities in the central abdomen

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 d. Left pleural effusion- uncommon

Inferior surface abscess may rupture in

a. colon or duodenum causing malena or hematochezia
b. peritoneal cavity- peritonitis

Posterior surface abscess may cause inferior vena cava obstruction by extrinsic pressure or thrombosis, or
2
very rarely rupture into IVC which is uniformly fatal.

Investigations 3

Laboratory studies
1. Leucocytosis seen in 75% of cases.
2. Hyperbilirubinemia is seen in less than 10% of cases.in acute phase, apartate aminotransferase (AST) are
high, but with chronicity the alkaline phospahatase levels increase in 70% of cases.
3. Stool examination- since only 30 to 40% of ALA have concomitant intestinal amebiasis, and in endemic
areas, stools may be positive even when patients do not have ALA ,therefore the tests may not sensitive
enough.
4. Stool antigen tests are available but sensitivity poor, require fresh stools and are positive only in first 7 days
before antibody response sets in.
5. Enzyme linked Imunosorbent Assay- EIA has now largely replaced indirect hemagglutination (IHA) testing
and counter immunoelectrophoresis (CIE) testing. EIA is relatively simple and easy to perform, rapid,
inexpensive, and more sensitive.The EIA test detects antibodies specific for E histolytica in approximately
95% of patients with extraintestinal amebiasis, in 70% of patients with active intestinal infection. The EIA
serology findings revert to negative in 6-12 months following eradication of infection. Even in highly endemic
areas, fewer than 10% of patients who are asymptomatic have positive amebic serology findings.Initial
negative test results may appear in as many as 10% of patients with amebic liver abscess. Under these
circumstances, order repeat serology testing in 1 week. This test result will usually be positive.4
6. Serum antigen detection- E histolytica galactose lectin antigen is detectable by enzyme-linked
immunosorbent assay (ELISA) in at least 75% of serum samples obtained from patients with amebic liver
abscess. Studies reported an antigen seropositivity of 96% with a reversal rate of 82% after 1 week of
treatment with metronidazole. This test may be useful for patients who present acutely, before an antibody
response occurs. The sample needs to be obtained before starting the treatment, as the treatment leads to
rapid antigen loss. This test can be used for rapid diagnosis in highly endemic areas, where serology can be
misleading, but it is not widely available.4
[21]
7. Rapid antigen and antibody tests are currently being evaluated and seem very promising.
8. Plain chest or abdominal films may show elevation and limitation of motion of the right diaphragm, basilar
atelectasis, and right pleural effusion or gas within the abscess cavity.
9. Ultrasonography- Ultrasonography is the preferable initial diagnostic test. It is rapid, inexpensive, and is
only slightly less sensitive than CT scan (75-80% sensitivity vs 88-95% for CT scan). The lesions tend to be
round or oval, with well-defined margins, and hypoechoic.
10. Computed tomography scanning- CT scanning is sensitive but the findings are not specific. The abscess
typically appears low density with smooth margins and a contrast-enhancing peripheral rim. The use of
injected contrast may differentiate hepatic abscesses from vascular tumors. 5

CT scan of the abdomen with IV and oral contrast is shown. The cavity is thick-walled with low attenuation center and contrast-
enhanced periphery.

CT scan cannot differentiate amebic liver abscess from pyogenic liver abscess other than by number.
11. Magnetic resonance imaging- MRI is sensitive, but the findings are not specific. This imaging modality
.5
provides information comparable with less expensive imaging procedures
12. Nuclear imaging studies- Technetium-99m liver scanning is useful for differentiating an amebic liver
abscess from a pyogenic abscess; however, it is not used as a first-line test. Because amebic liver

210
 abscesses do not contain leukocytes, they appear as cold lesions on hepatic nuclear scanning, with a typical
hot halo or a rim of radioactivity surrounding the abscess. In contrast, pyogenic liver abscesses contain
leukocytes and, therefore, typically appear as hot lesions on nuclear scanning. 5

Treatment
Most uncomplicated amebic liver abscesses can be treated successfully with amebicidal drug therapy alone. We
use tissue amebicides to eradicate the invasive trophozoite forms in the liver. After completion of treatment with
tissue amebicides, luminal amebicides are administered for eradication of the asymptomatic colonization state.
Failure to use luminal agents can lead to relapse of infection in approximately 10% of patients.In general,
metronidazole, tinidazole, emetine, and dehydroemetine are active in invaded tissues; chloroquine is active only
in the liver; tetracycline acts on the bowel wall; and diloxanide furoate, paromomycin, and iodoquinol are luminal
agents only.

Metronidazole- is the drug of choice and is given in the dose of 750 mg three times a day for 10 days is curative
in 90% of ALA.Metronidazole enters the protozoa by passive diffusion and is converted to reactive cytotoxic
nitroradicals by reduced ferredoxin or flavodoxin. Tinidazole, another nitroimidazolehas been approved for the
treatment of amebic liver abscess and invasive amebiasis.

Chloroquine phosphate may be substituted or added in the event of failure of resolution of clinical symptoms
with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole.
Chloroquine has the disadvantage of being associated with higher relapse rates than nitroimidazoles. Adverse
effects include gastrointestinal upset, headache, dizziness, and blurred vision. Retinopathy does not occur at the
dose used for amebic liver abscess.
Emetine or dehydroemetine has a direct lethal action on the trophozoites of E histolytica. These agents are
very toxic and, therefore, should be used only as a second-line therapy. Their toxicity includes cardiac
arrhythmias, precordial pain, muscle weakness, vomiting, and diarrhea. Dehydroemetine is less toxic than
emetine.

Luminal agents
Diloxanide furoate is free of major adverse effects. The most common adverse effect is flatulence and
occasional gastrointestinal upset.
Iodoquinol (diiodohydroxyquin) rarely causes abdominal pain, diarrhea, or rash. A structurally related
diiodohydroxyquin caused subacute myelopticoneuropathy and is obsolete now.
Paromomycin may occasionally cause nausea, abdominal cramps, or diarrhea, it is the preferred luminal
amebicidal.1,5

Surgery

Surgical intervention in form of ultrasound guided therapeutic aspiration of amebic liver abscess in the following
situations:
a. High risk of abscess rupture, as defined by cavity size greater than 5 cm;
b. Left lobe liver abscess, which is associated with higher mortality and frequency of peritoneal leak or
rupture into the pericardium;
c. Failure to observe a clinical medical response to therapy within 5-7 days.

In endemic areas, because of the late presentation and the existence of multiple abscesses, as many as 50% of
patients may require aspiration. In case of large abscess where the volume is calculated to be approximately
more than 500ml, catheter drainage may be preferred over needle aspiration.

Open surgical drainage incidence has reduced over the years, but when the abscess is inaccessible to needle
drainage or a response to therapy has not occurred in 5-7 days, this may be required. Secondly, required in case
of peritonitis because of ruptured liver abscess. .

Follow up
Follow-up ultrasonography or CT scan is unnecessary after resolution of symptoms and signs because the
radiological resolution may take several months to years. 1,5

HYDATID LIVER DISEASE (Family-Taeniidae: Genus- Echinococcus)

Causative agent Echinococcus granulose (synonym: Taenia echinococcus)

Epidemiology
It is most commonly found in those countries where sheep and cattle raising is important industry and there is a
close interaction between man, sheep and dogs. Man harbours the larval form and not the adult worm which is
6
seen in intestine of dog and other canine animals.

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Life cycle
The worm passes its life cycle in two hosts.
1. Definitive host- dogs, wolf, fox and jackal. The adult worm lives in the small intestine of these
animals and discharge large number of eggs in their feces.
2. Intermediate hosts. Sheep, pig, cattle, horse, goat and man. The larval stage is passed here and
gives rise to hydatid cyst.

The discharged eggs are swallowed by the intermediate hosts, sheep and domestic animals while grazing and
also by man (particularly children) due to intimate handling of dogs. In the duodenum, the hexacanth embryos are
hatched. They bore their way through the intestinal wall and enter the portal system and carried to liver, where
they are arrested in the sinusoidal capillaries (liver- first filter). A few of the embryos may enter the pulmonary
circulation and filter out in lungs (lung- second filter). A few embryos may pass the pulmonary capillaries and
enter the systemic circulation and lodge in various organs.

These embryos then form a hydatid cyst, the young embryo being transformed into a hollow bladder (hydatis-
drop of water). From the inner side of cyst, brood capsule with number of scolices develop. A hydatid cyst
developing from a single egg may contain thousands of scolices. These fertile hydatids when ingested by dog are
capable of growing into adult worms in 6-7 weeks time, thus completing the cycle. Since, dogs have no access to
7
human hydatid cyst; the life cycle comes to an end in humans.

Man is infected either by direct contact (handling, fondling) with infected dogs, or by consuming uncooked
vegetables contaminated with canine faeces. Infection is usually acquired in childhood but disease manifests in
adulthood.

Evolution of hydatid cyst. The cyst wall secreted by the embryo consists of 2 layers:
1. Outer Cuticular layer (Ectocyst)- It is a laminated hyaline membrane, having a thickness up to 1mm. to the
naked eye, the ectocyst has the appearance of the white of a hard-boiled egg. It is elastic and when incised
or ruptured, it curls on itself, exposing the inner layer containing the brood capsules and daughter cysts.
2. Inner or Germinal layer (Endocyst)- It is cellular and consists of a number of nuclei embedded in a
protoplasmic mass. It is very thin and measures 22 to 25 m in thickness. It is a vital layer of the cyst and
gives rise to brood capsules with scolices and secretes the hydatid fluid and also responsible for formation of
7
the outer layer.

Endogenous daughter cyst formation in hydatid cysts is the result of growth over many years and is seen in
man. The daughter cysts develop inside the mother cyst and may arise from the detached fragment of the
germinal layer or drom t he regressive changes of the young brood capsule and scolex bud.

Reaction of the host: An active cellular reaction consisting of monocytes (macrophages), giant cells and
eosinophils develop aroung the parasite. A large number of parasites may be destroyed by the phagocytic activity
of these cells. Whenever, the embryo escape, the inflammatory cells are replaced by fibroblasts and
neoangiogenesis, which transforms into fibrous tissue. This forms a fibrous layer and is known as pericyst. It
merges into the surrounding healthy tissue and derives nutrition through it. In an old cyst, the pericyst may
become calcified and the parasite dies.

The organ most commonly involved are liver (first filter), lungs (second filter). After this it enters into systemic
7
circulation and can involve any organ.

Clinical features
Many hydatid cysts remain asymptomatic, even into advanced age. The parasite load, the site, and the size of
the cysts determine the degree of symptoms. Symptoms can be produced by mass effect or cyst complications.
Symptoms due to pressure usually take a long time to manifest, except when they occur in the brain or the eyes.
Most symptomatic cysts are larger than 5 cm in diameter. Organs affected by E granulosus are the liver (63%),
lungs (25%), muscles (5%), bones (3%), kidneys (2%), brain (1%), and spleen (1%).
Pressure effects are initially vague. They may include nonspecific pain, cough, low-grade fever, and the
sensation of abdominal fullness.

In the liver, the pressure effect of the cyst can produce symptoms of obstructive jaundice and abdominal pain.
With biliary rupture, the classic triad of biliary colic, jaundice, and urticaria is observed. Cholangitis can also
develop. Passage of hydatid membranes in the emesis (hydatid emesia) and passage of membranes in the
stools (hydatid enterica) may occur rarely.

Involvement of the lungs produces chronic cough, dyspnea, pleuritic chest pain, and hemoptysis. Expectoration
of cyst membranes and fluid is observed with intrabronchial rupture.

Headache, dizziness, and a decreased level of consciousness may signify cerebral involvement. Specific
7
neurologic deficits may occur depending on the location of the cyst in the brain.

212
Clinical examination
1. Fever may be a feature of cyst rupture and leak either in peritoneal cavity or intestine may be a feature of
superadded infection
2. Tachycardia and hypotension or pleura because of anaphylaxis.
3. Lungs: Decreased breath sounds over the affected area are signs of airway obstruction with consolidation of
the affected segment, lobule, lobe, or the whole lung.
4. Abdomen: tender heaptomegaly or an asymptomatic abdominal lump may be a feature.
5. Splenomegaly may be a feature of splenic echinoccocus or portal hypertension.
6. Extremities
a. Bone involvement can result in tenderness over the affected area and, rarely, a palpable mass.
b. Muscle involvement is usually characterized by a palpable mass.
7. Brain
a. Findings from the neurologic examination are nonspecific and depend on the area of the brain
involved.
b. They range from very mild to full coma and cerebral herniation.
8. Eyes: abnormal findings from the ophthalmologic examination include decreased visual acuity, blindness,
and exophthalmos.7

Laboratory investigation
1. Eosinophilia is present in 25% of cases.
2. Serum bilirubin and alkaline phosphatase may be elevated in jaundiced patients or into intrabiliary
rupture.
3. Serological tests have variable results.
a. The indirect hemagglutination test and the enzyme-linked immunosorbent assay (ELISA) have a
sensitivity of 80% overall (90% in hepatic echinococcosis, 40% in pulmonary echinococcosis) and
are the initial screening tests of choice.
b. Immunodiffusion and immunoelectrophoresis demonstrate antibodies to antigen 5 and provide
specific confirmation of reactivity.
8
c. The ELISA test is useful in follow-up to detect recurrence.

Radiological investigations

Plain films- The findings from plain films of the chest, abdomen, or any other involved site are, at best,
nonspecific and mostly non revealing. A thin rim of calcification delineating a cyst is suggestive of an
echinococcal cyst.The water-lily sign is seen in hydatid infections when there is detachment of the endocyst
membrane which results in floating membranes within the pericyst that mimic the appearance of a water lily. It is
classically described on plain films (mainly chest x-ray) when the collapsed membranes are calcified but may be
seen on ultrasound and CT. 8

Water lily sign

Ultrasound
Ultrasonography helps in the diagnosis of hydatid cysts when the daughter cysts and hydatid sand are
demonstrated. The accuracy of ultrasound can be as good as 98% in expert hands. Ultrasound findings have
been classied by various methods. Of them, The World Health Organization 2001 classification of hepatic
hydatid cysts is a useful for assessing stage of a hepatic hydatid cyst on ultrasound and to decide on
appropriate management for it depending on the stage of cyst.
CL - unilocular anechoic cystic lesion without any internal echoes and septations
CE 1 - uniformly anechoic cyst with fine echoes settled in it representing hydatid sand
CE 2 -cyst with multiple septations giving it multivesicular appearance or rossette appearance or honey
comb appearance with unilocular mother cyst .This stage is the active stage of the cyst .
CE 3 -unilocular cyst with daughter cysts with detached laminated membranes appearing as water lily
sign. This is the transitional stage of the cyst .
CE 4 -mixed hypo and hyperechoic contents with absent daughter cysts, these contents give an
appearance of ball of wool sign indicating the degenerative nature of the cyst .
CE 5 -arch like thick partially or completely calcified wall .This stage of cyst is inactive and infertile. 9

213
 Ultrasound image with Gharbi I type of cyst or CL cyst (WHO classification)

Another simpler claasification on ultrasound findings is also in use and is known as Gharbi classification of
hydatid cysts 9
Type Description
I Pure fluid collection
II Fluid collection with a detached membrane
III Fluid collection with multiple septa and/or daughter cysts
IV Hyperechoic with high internal echoes
V Cyst with reflecting calcified thick wall

CT scan

CT scan has an accuracy of 98% and the sensitivity to demonstrate the daughter cysts.
It is the best test for the differentiation of hydatid from amebic and pyogenic cysts in the liver.
Fluid density cyst, with frequent peripheral focal areas of calcification. Septation and daughter cysts may be
visualised. Fluid is of variable density depending on the amount of proteinaceous debris. May also show
hyperdense internal septa representing a spoke wheel pattern within a cyst. 10

MRI 10
Images show the cysts adequately, but MRI offers no real advantage over CT scan.
T1: mixed low signal (depending on the amount of proteinacous cellular debris)
T1 C+ (Gd): the walls and septae enhance
T2: mixed high signal (depending on the amount of proteinacous cellular debris), septae and daughter
cysts are well visualized.

MRI T2 image MRI T2 image

Treatment
1. Medical Management- indications are:
a. Primary liver or lung cysts which are inoperable because of location
b. Multiple cysts either in one organ or in multiple organs
c. Peritoneal cysts

214
2. Contraindication of medical management:
a. Early pregnancy
b. Bone marrow suppression
c. Chronic liver disease
d. Large cyst with risk of rupture
e. Calcified cysts
f. Bone marrow cysts do not respond to drugs

3. Drugs used are benizimidazoles-

a. Albendazole- 10-15mg/Kg /day for 1month with a 14 days interval. The total duration is 3-6
months, with no further increase in the incidence of adverse effects if this period is prolonged.
Albendazole has been found ineffective in the treatment of primary liver cysts in patients who are
[5]
surgical candidates.
b. Mebendazole is also administered for 3-6 months orally in dosages of 40-50 mg/kg/d.
c. Weekly use of praziquantel, an isoquinoline derivative, at a dose of 40 mg/kg/wk, especially in
cases in which intraoperative spillage has occurred, is also sometimes used.
d. Patients have to be monitored for side effects on long term benizimidazoles, with complete blood
counts and liver function test every 4 weekly.
rd rd
e. Responses to the tune of 100% in 1/3 of patients , with 50% reduction in another 1/3 of patients
rd 10,11
and no response in remaining 1/3 of patients is reported.

4. PAIR
The Puncture Aspiration Injection Reaspiration (PAIR) technique is performed using either ultrasound or CT
guidance, involves aspiration of the cyst contents via a special cannula, followed by injection of a scolicidal agent
for at least 15 minutes, and then reaspiration of the cystic contents. This is repeated until the return is clear. The
cyst is then filled with isotonic sodium chloride solution. Perioperative treatment with a benzimidazole is
mandatory (4 days prior to the procedure and 1-3 months after).
The PAIR technique can be performed on liver, bone, and kidney cysts but should not be performed on lung and
brain cysts. The cysts should be larger than 5 cm in diameter and type I or II according to the Gharbi ultrasound
classification of liver cysts. PAIR can be performed on type III cysts as long as it is not a honeycomb cyst.

Indications:
a. Inoperable patients
b. patients refusing surgery
c. patients with multiple cysts in segment I, II, and III of the liver
d. relapse after surgery or chemotherapy

Contraindications:
a. Early pregnancy
b. lung cysts
c. inaccessible cysts
d. superficially located cysts (risk of spillage)
e. type II honeycomb cysts, type IV cysts, and cysts communicating with the biliary tree (risk of
sclerosing cholangitis from the scolecoidal agent).

Outcome: The reduced cost and shorter hospital stay associated with PAIR compared to surgery make it
desirable. The risk of spillage and anaphylaxis is considerable, especially in superficially located cysts, and
transhepatic puncture is recommended. Sclerosing cholangitis (chemical) and biliary fistulas are other risks.
Experience is still limited, but early reports are supportive of this technique if the indications are followed. 10.11

Surgical Procedure
Indications of surgery are:
a. Large liver cysts with multiple daughter cysts
b. superficially located single liver cysts that may rupture (traumatically or spontaneously)
c. liver cysts with biliary tree communication or pressure effects on vital organs or structures
d. infected cysts
12
e. cysts in lungs, brain, kidneys, eyes, bones, and all other organs are indications for surgery.

Contraindications
1. General contraindications to surgical procedures (eg, extremes of age, pregnancy, severe preexisting
medical conditions)
2. multiple cysts in multiple organs; cysts that are difficult to access; dead cysts; calcified cysts; and very
small cysts.

Choice of surgical technique

a. Radical surgery (total pericystectomy or partial affected organ resection, if possible)
b. conservative surgery (open cystectomy)

215
 c. tube drainage of infected and communicating cysts are choices for surgical technique. The more radical
the procedure, the lower the risk of relapses but the higher the risk of complications. Patient care must be
individualized accordingly.

Description of surgical procedure

The basic steps of the procedure are eradication of the parasite by mechanical removal, sterilization of the cyst
cavity by injection of a scolicidal agent, and protection of the surrounding tissues and cavities.
20% saline, 3% hydrogen peroxide, 1.5% cetrimide-0.15% chlorhexidine (10% Savlon), 95% ethyl alcohol, 10%
polyvinylpirrolidone-iodine are the scolicidal agents used. Scoleces sprayed on sponges soaked in 20% saline,
95% ethyl alcohol, Betadine and 3% hydrogen peroxide were killed after 15 minutes. Sponges work not only as a
mechanical barrier but also as a chemical one if the agent is chosen correctly. 10% Formalin was one of the
agents used earlier but not in use now a days as the risk of sclerosing cholangitis if there is a biliary
communication.. A report by Ochieng'-Mitula and Burt in 1996 on the injection of ivermectin in the hydatid cysts of
infected gerbils revealed severely damaged cysts with no viable protoscoleces. 13

At surgery, the exact location of the cyst is identified and correlated with the radiologic findings. The surrounding
tissues are protected by covering them with cetrimide-soaked pads. The cyst is then evacuated using a strong
suction device, and cetrimide is injected into the cavity. This procedure is repeated until the return is completely
clear. Cetrimide is instilled and allowed to sit for 10 minutes, after which it is evacuated, and the cavity is irrigated
with isotonic sodium chloride solution. This ensures both mechanical and chemical evacuation and destruction of
all cyst contents. During this process, care is taken to ensure no spillage occurs to prevent seeding and
secondary infestation.

The cavity is then filled with isotonic sodium chloride solution and closed. Rarely, omentum is needed to fill the
cavity. The cyst fluid is inspected for bile staining at the end of the evacuation and irrigation process. The inside
of the cyst is inspected, and any bile duct communication is sutured. In case of infected cysts with biliary
communication, closed suction drainage is required. Regardless of whether an open or laparoscopic approach is
chosen, these basic principles must be followed in order to ensure the safety of the procedure. 12,13

Appropriate surgical treatment of hydatid cysts of the liver depends on communication of the cyst and the bile
duct. If the cyst is localized peripherally, total cystectomy or hepatic resection is recommended because of the
low rate of recurrence. However, partial cystectomy and omentoplasty are the most frequently used operations
for intraparenchymal hydatid cysts.Omentoplasty has been advocated for its absorptive capacity of residual fluid
in the cystic cavity. It has also been hypothesized to stimulate macrophage migration into the operated area.
Fluid accumulation and recurrence also can be prevented by using a capitonnage technique. Here the remaining
walls of the cavity were brought together with a series of purse-string or mattress sutures starting from the bottom
and working outward, but it is important to remember that capitonnage carries with it the risk of injuring major
ducts or vessels passing just outside the pericystic layer. Ariogul and co-workers have shown that the introflexion
method suturing the outer surface layers of the cyst to each other or to the bottom of the cavity to keep the cyst
walls folded 4 is a simple, safe, and effective means of closing the cystic cavity. Although pericystectomy and
hepatectomy have low recurrence rates, these operations are very radical and are preferred in superficial and
exophytic hydatid cysts and in cysts originating from Echinococcus alveolaris.
Patients who have jaundice or a history of cholangitis, elevated liver enzymes, and dilatation or debris in major
bile ducts should be assessed for main bile duct contamination. If the bile ducts are evaluated with ERCP before
surgery, it is not necessary to perform main duct exploration. Kayaalp and co-workers have shown that hydatid
cysts lying around the hilus of the liver had a higher biliary communication rate (48%) than did peripherally
14
located cysts (27%).
In case of large biliary communication is detected at surgery, Common Bile Duct exploration, removal of daughter
cysts from the ducts, closure of the abnormal opening and closure of CBD over a T- tube is preferable. Surgeons
have also done a Roux- en Y cystojejunostomy between the pericystic opening and jejunum, where CBD
exploration is technically difficult. 15

OTHER PARASITIC INFESTATIONS

Schistosomiasis (Is a Platyhelinith Trematode- Common Species- S mansonii, S japonicum)

Epidemiology: seen in Africa, Central and South America, Eastern Asia, uncommon in India.

Life Cycle: Cercariae enyters the skin of swimmers when they enter contaminated water. They change to
schistosomules. These penetrate the lymphatics and then in to circulation. They then travel to lungs and from
there to liver. In liver they go to portal vein branches and mature into adults. They then lay eggs afetr 30 days
which enter the intestine and then evacuated in stools, the eggs enter snails in contaminated water where they
develop into cercariae. This completes the life cycle.

In humans liver, inflammatory hepatomegaly is common in childhood. In adults, hepatomegaly because of

periportal fibrosis is seen in 5-10% of individuals after years of infection. Granulomas and fibrosis cause
presinosoidal portal hypertension, but liver function is usualy preserved as blood flow is maintained.

216
 16
Treatment-praziquintal is the drug of choice and single treatment cure rates are 60 to 75%.

Malaria ( Plasmodium vivax, ovale, malariae, falciparum) vector Anopheles mosquito

Epidemiology- in tropical developing countries, more than 500 million febrile illnesses and are than 2.5 million
deaths annually. Upto 50% of world population is at risk. Most severe cases occur in children and pregnant
women.

Life cycle- anopheles mosquito transmit malaria by injecting sporozoites into human hosts. Sporozooites invade
hepatocytes an develop into schizonts. The infected hepatocytes rupture to release merozoites that invade into
erythrocytes. Growth and development of these merozoites into RBC results in waves of invasion every 48 or 72
hours depending on the species of plasmodium. Some forms may remain latent in hepatocytes as hypnozoites
which later can develop recurrences.

Signs and symptoms- fever develops 2-4 weeks after mosquito bite depending upon the species of
plasmodium. Presentation is fever with chills and rigors with night sweats, myalgias and arthragias. The fever
last for few hours and the recurrence of fever occurs according to the species involved.
Examination shows tender hepatospelomegaly.

Laboratory investigations

1. Anemia, microcytic type, low hematocrit is seen.

2. Leucocytosis and thrombocytopenia is seen.
3. Peripheral blood smear- Geimsa stained thick and thin smear if positive is confirmatory.
4. serology- is available which have a 96% sensitivity.

Treatment- antimalrials have been developed based on the isolated or suspected species of Plasmodium.17

Fasciola (F hepatica, F gigantic)(Is a Platyhelminth trematode)

Epidemiology- Intermediate host is snail and definitive host is herbivore. Infestation occurs after injestion of
water cress. Eggs open to release metacercaria that burrows through duodenum , then peritoneum, Glissons
capsule into liver and then to biliary tree and gall bladder. Adult parasite form in 3-4 months and release eggs in
to bile and then intestine.

Clinical features- in acute phase, fever and dyspepsia are the main features. Severe diarrhea and jaundice is
also the presentation. Tender hepatomegaly and splenomegaly is common.
Investigations show eosinophilia and hyperbilirubinemia and elevated liver enzymes.
Chronic phase present with gall stone and common bile duct stones.

Diagnosis
1. ova and cyst examination of stool or duodenal aspirate.
2. ELISA serology is diagnostic.
3. ERCP may show parasite and which might require removal.

Treatment
Bithionol 30-50mg/Kg alternate day for 10 doses is drug of choice.
ERCP and surgery for parasite or stones is required. 18

Chonorchiasis sinensis (Are Platyhelminth trematode)

Epidemiology-Reservoir- cats and dogs

Intermediate host- fresh water snail and fish

Life cycle- water is contaminate with eggs which then operculate into miracidia. Miracidia is eaten by snails and
then change to sporocyte and then to redia.
Redia mature into cercaria and these are relased in water then penetrate the skin of fish and transform into eggs
and then to metacercaria.
Humans eat fish. Metacercaria excyst inside duodenum and penetrate the wall to enter the gall bladder, biliary
tree and pancreatic duct. Here they mature into adults and lay eggs in 4 weeks.

Clinical features
Acute phase- can present as fever, diarrhea, tender hepatomegaly and jaundice.
In chronic cases- severe infestation cause intrahepatic and extrahepatic bilary obstructioin.may have repetitive
cholangitis. Cholecystitis may also develop. Later secondary bilairy cirrhosis may develop. Patient may develop
Oriental Cholangiohepatitis with formation of intraductal stricture and stones and recurrent cholangitis

217
Diagnosis-
1. Stool and duodenal aspirate may show cysts.
2. Serum Immonoblot for C sinensis show 92% sensitivity.

Treatment
19
Praziquintal 75mg/Kg divided in 3 doses for single day.

References

1. Sharma MP, Ahuja V. amoebic liver abscess. JIACM 2003;4:107-11.

th
2. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:14-34..
3. Sharma MP, Ahuja V. Management of amebic liver abscess. Arch Med Res 2000;31:4-5
4. Restrepo MI, Restrepo Z, Elsa Villareal CL. Diagnostic tests for amoebic liver abscess: comparison of enzyme-
linked immunosorbent assay (ELISA) and counterimmunoelectrophoresis (CIE). Rev Soc Bras Med Trop. 1996;
29:27-32.
5. Blessmann J, Binh HD, Hung DM. Treatment of amoebic liver abscess with metronidazole alone or in combination
with ultrasound-guided needle aspiration: a comparative, prospective and randomized study.Trop Med Int Health.
2003; 8:1030-4.
6. Torgerson PR. The emergence of echinococcosis in central Asia. Parasitology. 2013;10. 1-7.
th
7. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:121-127.
8. Filippou D, Tselepis D, Filippou G, Papadopoulos V. Advances in liver echinococcosis: diagnosis and
treatment. Clin Gastroenterol Hepatol. 2007 ; 5:152-9.
9. Guidelines for treatment of cystic and alveolar echinococcosis in humans. WHO Informal Working Group on
Echinococcosis. Bull World Health Organ. 1996;74:231-42.
10. Sayek I, Tirnaksiz MB, Dogan R. Cystic hydatid disease: current trends in diagnosis and management.Surg
Today. 2004;34:98796
11. De Diego J, Lecumberii FJ,Franquet T, Ostiz S. computed tomography in hepatic echinococcosis. AJR Am J
Roentgenol. 1982;139: 699-702.
12. Dziri C, Paquet JC, Hay JM, Fingerhut A, Msika S, Zeitoun G, et al. Omentoplasty in the prevention of deep
abdominal complications after surgery for hydatid disease of the liver: a multicenter, prospective, randomized
trial. French Associations for Surgical Research. J Am Coll Surg. 1999;188:2819.
13. Ochieng'-Mitula PJ, Burt MD. The effects of ivermectin on the hydatid cyst of Echinococcus granulosus after
direct injection at laparotomy. J Parasitol. 1996; 82:155-7.
14. Vignote ML, Mino G, de la Mata M, de Dios JF, Gomez F. Endoscopic sphincterotomy in hepatic hydatid disease
open to the biliary tree. Br J Surg. 1990;77:301
15. Kayaalp C, Bostanci B, Yol S, Akoglu M. Distribution of hydatid cysts into the liver with reference to cystobiliary
communications and cavity-related complications. Am J Surg. 2003;185:1759
th
16. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:137-42.
th
17. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:71-83.
th
18. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:146-8.
th
19. Chatterjee KD. IN: Parasitology. 12 ed . Calcutta, India:Chatterjee Medical Publishers.1981:151-3.

Sub-diaphragmatic abscesses

C.B. Singh, Suresh R.

INTRODUCTION
Collection of pus or infected peritoneal fluid in one of the subphrenic spaces is called subphrenic or
subdiaphragmatic abscess. It is often accompanied by infection of the pleural cavity. Sometimes subphrenic
infection is not accompanied by suppuration and presents as cellulitis of the subphrenic space. This cellulitis may
resolve completely or proceed to the formation of an abscess.

The first reported account of subphrenic abscess was given by Ochsner and Graves, in I933 who reported
1
that about 70% of subphrenic infections subside spontaneously and about 30% proceed to suppuration. It was
common to find a localized empyema in some patients with a subphrenic abscess . It is believed that the infection
spreads from the peritoneum to the pleura via the diaphragmatic lymph vessels.The pathology and surgical
importance of sub phrenic infection cannot be fully understood without a thorough appreciation of the anatomy of
the subphrenic space.

ANATOMY
The subphrenic space is defined as being that portion of the abdomen which lies between the diaphragm above
and the transverse colon and mesocolon below. The space is divided into two parts by the liver-- the supra-
hepatic and infra-hepatic portions.The supra-hepatic portion is divided into right and left sides by the falciform
ligament of the liver. The right side is itself divided into an anterior and posterior space by the right lateral
ligament of the liver.

218
The left lateral ligament of the liver runs very close to the posterior margin of the left lobe of the liver so that it
does not divide the left suprahepatic area but forms the posterior part of the boundary between the supra- and
infra-hepatic parts on the left side. There is, therefore, only one supra-hepatic space on the left side, In addition
there is one small extra-peritoneal space in the supra-hepatic part, namely the bare area of the liver, between the
leaves of the lateral and falciform ligaments. The supra-hepatic portion of the subphrenic area therefore contains
two intra-peritoneal spaces on the right and one on the left and one small extra-peritoneal space. These spaces
are usually referred to as the right superior anterior subphrenic space, the right superior posterior subphrenic
space, the left superior subphrenic space and the bare area of the liver.

The infra-hepatic portion is divided into right and left parts by the free edge of the lesser omentum and the
descending part of the duodenum. There is only one space on the right in the infra-hepatic region, but on the left
there are two spaces, an anterior one and a posterior one, being separated from each other by the stomach and
the lesser omentum. All the infra-hepatic spaces are intra-peritoneal, there is no extraperitoneal space below the
liver. These spaces are usually referred to as the right inferior subphrenic space, which is the same as the
hepatorenocolic pouch of Morrison; the left inferior anterior subphrenic space, often called the perigastric space;
and the left inferior posterior subphrenic space, also referred to as the omental bursa or lesser sac of the
peritoneum. From the surgical point of view the space most commonly infected, and therefore the most important,
is the right superior posterior space(28.8%), and is difficult to access both for diagnosis and drainage. 2

ETIOLOGY
The cause of subphrenic infection is any infective process occurring in the peritoneal cavity (88%).About 6 per
cent abscesses are blood borne , 3 per cent result from extension from the thorax and the remainder are due to a
variety of rare causes. Of the causes of abdominal suppuration, most reports mention appendicular infective
diseases as source in about 30 per cent of all subphrenic infections , another 30 per cent from perforations of the
duodenum or stomach and I2 per cent patients have liver and biliary passages as the source . The remainder of
infections come from kidney, pancreas or following trauma . 1

The subphrenic region infected occur by the following routes :

1. Direct extension: This is by direct spread of infection from contiguous organs, such as perforated
lesion from stomach or duodenum(29%) and infection of the liver and gall bladder(12%).
2. Distant extension: The commonest cause of infection of the subphrenic region is spread from infective
condition of appendix(30%) . Distant infection in pelvis can also be the source. The infection probably
spreads mainly by means of retro-peritoneal cellulitis or by retroperitoneal lymphangitis in other cases.
Distant intra-peritoneal focus cai of infection can also infect the subphrenic region by direct intra-
peritonen also drainage into subphrenic space especially in supine posture.

3. Rupture into the subphrenic space: can occur from adjoining abscess into one of the subphrenic
spaces , as in case of ruptured liver abscess.

4. Extension from the thorax: This is not a common source of subphrenic infection, although it certainly
does occur (3%). It is probable because of retrograde lymphatic extension rather than directly through
the diaphragm.
5. Blood stream: In these cases the subphrenic infection is a metastatic infection following septicaemia or
pyaemia.

6. Direct implantation: The organisms can get implanted directly in the subphrenic region following
3
traumatic injury (3%) like missiles, aspirating needles during empyema aspiration.

BACTERIOLOGY
The majority of abscesses show polymicrobial infection . Gram negative bacteria are predominantly seen . They
include E. coli (41.6%); Aerobacter aerogenes (23.3%); Proteus, (20%); and Pseudomonas (8.3%). In recent
years, Pseudomonashas become one of the most frequently cultured bacteria. Gram positive organisms like
Staphylococci and Streptococci are also cultured frequently these days and are commonly resistant to the
4
available antibiotics.

CLINICAL FEATURES AND DIAGNOSIS

The presence of a subphrenic infection can usually be diagnosed if the possibility of its existence is kept well in
mind. Thus the aphorism: pus nowhere, pus somewhere pus under the diaphragm .The average time
from the onset of the abdominal suppuration to the suspicion of the presence of subphrenic infection has been
reported to be 15 days. Any patient having had an antecedent abdominal operation or inflammatory process of
abdomen if exhibits an unexplained temperature elevation should be suspected of having a subphrenic abscess.
Patients complaint of pain or discomfort in upper abdominal or over lower ribs posteriorly with fever and
tachycardia.

On physical examination abdominal distention , abdominal guarding and rigidity. The most useful and constant
physical sign is some limitation of movement of affected lower chest wall during respiration .There is usually
abnormal auscultatory findings over lower chest wall , mostly consisting of rales and dullness due to limitation of

219
diaphragmatic movement on the affected side. Apparent increase in the liver dullness may be noticed. There may
be signs of a basal pleural effusion, on the affected side or basal lobular pulmonary atelectasis.

The initial evaluation should include a history, physical examination, laboratory tests, plain roentgenograms of the
chest and abdomen, and appropriate cultures . There is leukocytosis and erythrocyte sedimentation rate is
elevated in 50% of cases.1,4

INVESTIGATION

Chest X-Ray
The most useful aid to diagnosis is the use of X-rays taken in the anterior-posterior and lateral planes. The most
constant X-ray finding is of raised diaphragm on the affected side, obliteration of the costo-phrenic angle and
decreased range of movement on respiration. It may be possible to see an air-fluid level in subphrenic abscess
cavity either due to gas from from hollow viscus perforation or due to presence of gas-forming organisms within
the abscess.
A barium filled stomach may show indentation by the abscess. Diagnostic aspiration is mentioned only to be
condemned, as there is a very great risk that the infection will be spread along the needle track to result in an
empyema or spread to other parts of the peritoneum. 5

Ultrasonography
Ultrasonography is a non invasive relatively sensitive and useful tool for diagnosing an intra-abdominal abscess
including sub phrenic abscess with accuracy rate of 72% to 90%. 6 Ultrasonography can be a bedside diagnostic
tool in very ill patients and otherwise also. It is less accurate than computed tomography (CT), less capable of
detecting small abscesses. The utility of ultrasonography may be affected adversely by the size of the patient or
the presence of excessive bowel gas, surgical wounds, dressings, drains, and ostomies that may prevent
imaging of all areas of the abdomen and pelvis.7

Computed Tomography (CT)

7
CECT abdomen provides high anatomic resolution and has greater accuracy rate of 91% to 96% . It allows
better visualization of the retroperitoneum, lesser sac, and pelvis. Contrast enhancement may help to differentiate
between a loop of intestine and a fluid collection.

Scintigraphy
Radioactive gallium(Ga67 citrate) and Indium (In111) labeled leukocytes can be used for scintigraphy with
sensitivity of 86% only.8 Labeled leukocytes only accumulate in sites of active infection or inflammation.

Complication

The most common complications (50%) of subphrenic infections are those affecting the pleura and lung
immediately above the part of the diaphragm which is overlying the area of infection. The raising and immobility
of the diaphragm results in a high incidence of basal lobular atelectasis of the lung on the affected side, and the
atelactatic lung not infrequently becomes infected and results in broncho-pneumonia, which itself may give rise to
a lung abscess.

Pleural effusions develop not infrequently owing to inflammation of the pleura which can develop into empyema .
The other complications are comparatively rare and consist mainly of hepatic abscess, septicaemia and pyaemia.
In very rare cases a subphrenico-pleuro-
bronchial fistula may develop.3

Treatment

Effective management of sub diaphragmatic abscess requires both appropriate antibiotic therapy and surgical
drainage.

Initial therapy should consist of broad-spectrum antibiotics until culture and antibiotic sensitivity results are
available. As the pathogens are frequently similar to those involved in secondary peritonitis, it is rational to direct
initial therapy against Bacteroides fragilis and the Enterobacteriaceae. The antimicrobial regimen can be
selectively revised once the causative pathogens have been identified in culture.

Previously, the most commonly used therapy was an aminoglycoside combined with either clindamycin or
9
metronidazole . However, based on in vitro studies, imipenem and aminoglycosides, though less efficacious
against B. fragilis,and Piperacillin/ tazobactam as monotherapy, is effective for treating patients with an intra-
abdominal abscess because of the coverage of anaerobes in addition to broadspectrum gram-positive and gram
negative coverage.10 Piperacillin/tazobactam also penetrates well into abdominal tissues and works well at a low
11
pH. Addition of anaerobic coverage by metronidazole and clindamycin is also required.

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Surgical Drainage

Once suppuration has occurred, resolution will only take place in rare cases on medical management, and
surgical drainage of the abscess must be undertaken. Surgical drainage can be either percutaneous drainage or
by surgical approach.

Nowadays treatment of choice for subdiaphragmatic abscess by percutaneous drainage(PCD) using USG,
fluoroscopic or CT guided method. It can be either intercostal or subcostal approach, the latter has lesser
complication rate. In some cases, an intercostal path may be a safer route to drain certain collections because it
avoids bowel and avoids a longer and potentially more damaging path through the abdomen. 12

Surgical drainage of a subphrenic abscess was the modality of choice in earlier days. As the percutaneous
drainage either by insertion of needle or by indwelling a catheter is associated with high sucess rate and less
complication with ease of conducting this procedure under local anaesthesia ,it has become preferred method of
drainage .Incomplete drainage can occur in difficult locations and thickened collection contents. In these scenario
surgical approach is warranted. It can be either trans-thoracic or trans-abdominal, and in either case the
approach can be trans-serous or extra-serous. Any form of trans-serous approach is to be condemned as this will
result in infection of the serous cavity traversed in a high proportion of cases, giving rise to an empyema or
peritonitis. Drainage must, therefore, be carried out by an extra-serous route.
1
Ochsner and Graves had described the method of retro peritoneal, extra-serous approach to a subphrenic
abscess through the bed of the I2th rib. The right superior posterior subphrenic abscess and right inferior sub
phrenic abscess can be approached via this method . Under paravertebral block analgesia and with the patient
lying on the unaffected side on either a kidney rest or sandbag placed in the lumbar region . An incision is made
over and parallel to the twelfth rib. The entire twelfth rib is resected subperiosteally, care being taken not to injure
the pleura .The erector spinae mass of muscles is retracted medially and a transverse incision is made at the
level of the spinous process of the first lumbar vertebra. It is importalnt that this incision through the bed of the rib
be made transversely at this level and not parallel to the rib, to avoid injury to pleura. This incision passes
through the bed of the twelth rib and the attachlment of the diaphragn, after the diaphragm has been incised, the
renal fascia is encountered. This is continuous above and anteriorly with the posterior parietal peritoneum. By
means of the finger the peritoneum is peeled from the undersurface of the diaphragm until the abscess cavity is
reached. By plunging the finger through the abscess wall the abscess may be drained without contaminating the
pleural or peritoneal cavity.

Abscesses located in the right anterior superior, the right inferior, the left anterior inferior, and the left superior
spaces can be drained extraperitoneally through the anterior abdominal wall via anterior approach. An incision
just beneath the parallel to the costal margin is made through the flat abdominal muscles and transversalis fascia
down to the anterior parietal peritoneum. Similarly as in the retroperitonieal operation the parietal peritoneumn is
separated from the unidersurface of the diaphragm by means of the index finger.The peritoneum is mobilized
upward until the abscess cavity is reached. The cavity is opened extraperitoneally through the abscess wall
which is intimately adherent to the mobilized parietal peritoneum.

Figure showing the transverse incision made through the resected bed of the twelfth rib. It is important that this incision does
not parallel the original skin incision.

References

1. Ochsner A, Graves AM. Subphrenic abscess: An analysis of 3,372 collected and personal cases. Ann Surg.1933
Dec;98(6):961-90.
2. Boyd DP. The anatomy and pathology of the subphrenic spaces. Surg Clin North Am.1958 Jun;38(3): 619-26.
3. Birt AB. Subphrenic infection. Postgrad Med J.1953 May;29(331): 242-7.

221
4. Roberts EA, Nealon TF. Subphrenic abscess: Comparison between operative and antibiotic management. Ann
Surg. 1974 Aug;180(2): 209-12.
5. Johnson TH. Chest roentgen findings of subdiaphragmatic abscess with antibiotic therapy. Am J Roentgenol
Radium Ther Nucl Med. 1968 Nov;104(3):584-9.
6. McGahan JP, Anderson MW, Walter JP. Portable real-time sonographic and needle guidance systems for
aspiration and drainage. Am J Roentgenol 1986 Dec;147(6): 1242-6.
7. Filly RA. Annual oration: Detection of abdominal abscesses. A combined approach employing ultrasonography,
computed tomography and gallium-67 scanning. J Can Assoc Radiol 1979 Dec;30(4):20210.
8. Knochel JQ, Koehler PR, Lee TG et al. Diagnosis of abdominal abscesses with computed tomography,
ultrasound, and 111In leukocyte scans. Radiology. 1980 Nov;137(2):425 32.
9. Eklund AE, Nord CE. A randomized multicenter trialof piperacillin/tazobactam versus imipenem/cilastatin in the
treatment of severe intra-abdominal infections. J Antimicrob Chemother 1993Jan;31(suppl A): 7985.
10. Polk HC Jr, Fink MP, Laverdiere M, et al. Prospective randomized study of piperacillin/tazobactam therapy of
surgically treated intra-abdominal infection. Am Surg 1993Sep;59(9):598 605.
11. Wistanley TG, Wilcox MH, Spencer RC. Effect of pH on antibiotics used to treat anaerobic infection. J Antimicrob
Chemother 1992 May;29(5):5945.
12. Preece SR, Nelson RC, Bashir MR, et al. Safety of an Intercostal Approach for Imaging-Guided Percutaneous
Drainage of Subdiaphragmatic Abscesses. Am J Roentgenol 2014 Jun;202(6):1349-54.

Ischemic Bowel Disease

Sundeep Saluja, Harsh Shah

Ischemic bowel disease occurs when the perfusion to the intestine fails to meet the normal metabolic
requirement. Based on the duration of ischemia, it can be categorized as either acute ischemia (hours to days) or
chronic ischemia(months to years).

History
In 1950, Klass1 performed the first embolectomy for mesenteric ischaemia. The patient died in post-operative
period due to heart failure and the postmortem examination revealed the normal bowel. Ende(1958) 2 described
3 4
the non-occlusive mesenteric ischaemia as a variety of acute mesenteric ischemia. Boley & Clark first described
angiographic finding for mesenteric ischemia in 1970s.

Mesenteric circulation

Anatomy
Three major visceral arteries- celiac, superior mesenteric & inferior mesenteric provide blood supply to abdominal
organs. The coeliac artery arises at the level of L1 vertebra just below diaphragm. The median arcuate ligament
lies just above while the superior border of pancreas just below the artery. The superior mesenteric artery arises
few cms below coeliac trunk behind neck of pancreas. It lies superior to uncinate process and 3rd part of
duodenum. The inferior mesenteric artery arises at level of L3 vertebra 3-4 cm proximal of aortic bifurcation.
The splanchnic circulation is characterized by a vast network of collateral blood vessels, which provides
substantial protection from ischemia or infarction in settings of segmental vascular occlusion. The major collateral
connections are:
The celiac axis and the SMA, which communicate principally through the junction of the superior and inferior
pancreaticoduodenal arteries.
The SMA and IMA, which communicate through several pathways. The middle colic and left colic arteries
primarily anastomose through the marginal artery of Drummond, which runs along the mesentery of the
splenic flexure of the colon and the arc of Riolan.
Collateralization between the IMA and systemic circulation, which occurs in the rectum, as the superior rectal
(hemorrhoidal) vessels merge with the middle rectal vessels from the internal iliac arteries.

Physiology
Changes in the resistance of mesenteric arterioles account for wide fluctuations in splanchnic blood flow during
fasting and postprandial state, which can range from 10 to 35 percent of cardiac output respectively. Numerous
control mechanisms contribute to the regulation of mesenteric vascular tone and are responsive to varying
conditions such as the postprandial state or systemic hypotension. Intrinsic autoregulation of blood flow by the
splanchnic vessels is thought to occur in response to acute reductions in perfusion pressure. Proposed
mechanisms that result in the preservation of tissue perfusion include direct arteriolar smooth muscle relaxation
and a metabolic response to adenosine and other metabolites of mucosal ischemia 5.Neural and hormonal
mechanisms contribute to the extrinsic control of intestinal blood flow. These include the sympathetic nervous
system, the renin-angiotensin axis, and vasopressin, which is released from the pituitary gland.

Acute Mesenteric Ischaemia

AMI is a rapidly progressive and morbid condition that leads to intestinal infarction.

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Etiology

Cause Incidence
Acute arterial embolus 40-50%
Acute arterial thrombosis 20-30%
Non-occlusive mesenteric ischaemia (NOMI) 20%
Acute venous thrombosis 10%

Acute arterial occlusion in the form of embolus or thrombus is the most common cause of acute mesenteric
ischaemia. Emboli usually arise from left atrium (atrial fibrillation), left ventricle (ventricular aneurysm, post
myocardial infarction, cardimyopathies), heart valves (bacterial endocarditis) or aneurysm of the aorta.
Thrombotic occlusion of mesenteric vessels is the next most common cause, which is superimposed on pre-
existing atherosclerotic mesenteric vascular disease. NOMI, as the name suggests, lacks themechanical
component & affects mesenteric arterioles, which are maintained in the state of spasm. Mesenteric venous
thrombosis usually affects younger individuals & accounts for 10% of cases of mesenteric ischaemia.

Acute Arterial Occlusion (Embolism & Thrombosis)

SMA is the largest caliber mesenteric vessel withnarrow takeoff angle from aorta (45-degree).This makes it the
most commonly affected vessel for emboli. IMA is rarely affected due to its small caliber. Emboli usually lodge
distal to the origin of middle colic, causing small bowel ischemia, sparing transverse colon & ascending colon.
Approx. 20% of emboli are multiple. The middle segment of the jejunum is most often involved in the ischemic
process, as it is most distant from the collateral circulation of the celiac and inferior mesenteric arteries.

Arterial thrombosis is the next most common cause for AMI. It constitute for 20-30% of cases. Patients usually
have preexisting atherosclerotic plaques in many of the visceral vessels. Hypercoagulatibilty syndromes can also
predispose to acute visceral artery thrombosis. The affected part is usually at the origin of vessel from the aorta
therefore it causes ischemia to more part of the bowel and carries higher mortality (77%) compared to embolic
occlusion (54%)

Figure 1 Narrow angle of origin & wide caliber of SMA makes it most susceptible to emboli (Left),
Emboli lodge past the origin of middle colic artery (Right)

Symptoms & signs

Pain may be absent in the initial phase. Most commonly sudden onset crampy abdominal pain in an elderly
individual, with or without peritoneal signs should raise the suspicion of mesenteric ischaemia. Symptoms are
usually out of proportion to clinical findings. Patients are usually in an agitated or anxious state. History of
hypertension, myocardial infarction or stroke, are notable clues to suspect the diagnosis. Blood in stools is a sign
of mucosal ischaemia, which could be present 30-40% cases. Diarrhoea is usually due to intestinal smooth
muscle spasm (i.e. failure of relaxation) secondary to impaired energy supply, as ATPs are required for smooth
muscle relaxation. On examination bowel sounds may be hyperactive in early phase while it may absent in late
phase of illness. Abdomen may be soft in some cases. Presence guarding and rigidity are suggestive of
peritonitis and is usually a late sign. Cardiovascular system examination may reveal atrial tachyarrhythmias,
murmur or signs of failure thereby providing clue to predisposing condition precipitating the acute event.

Investigations

The Laboratory parameters are usually non-specific. Leukocytosis & raised amylase levels are the common
abnormalities noted in these patients. Elevated lactate &metabolic acidosis on arterial blood gas analysis may
point towards the diagnosis of mesenteric ischaemia.

223
Plain X-ray films may reveal thumb printing or free air under diaphragm. Duplex ultrasound has a limited role in
acute setting. Obesity, bowel gases & experience of the operator are the important limiting factors.The flow
velocity and resistance index of splanchnic arteries and their vessel wall and end organ vascularity are the
important parameters assessed. The important findings include transmural hemorrhage, inflammation and
necrotic thickening of the bowel wall. The asymmetrical bowel wall with associated ileus, ascites and free air
could suggest AMI. CT angiography (CTA) is the investigation of choice in this setting. CTAwill show the site of
vascular occlusion, state of the mesenteric vessels & degree of bowel ischaemia.It has got a sensitivity of 96%
and a specificity of 94%.The lack of enhancement of bowel wall, presence of pneumatosis intestinalis and gas in
the portal venous system or free intraperitoneal airare suggestive of bowel gangrene. Disadvantages of CT
include contrast nephrotoxicity, hypersensitivity reaction and underestimation of stenosis in presence of
calcification at the origin of the vessel.
The conventional angiography is the gold standard for the diagnosis of mesenteric ischaemia. Antero-posterior
and lateral views along with selective catheterization of main visceral arteries are performed to get a complete
picture. However, its use is as a diagnostic tool is limited in the present era of high resolution CT scan. It is now
used while contemplating stent placement.

Treatment

Once the diagnosis of acute arterial occlusion is made, prompt institution of treatment is must. Fluid resuscitation,
hemodynamic stabilization, correction of metabolic acidosis & electrolyte abnormalitiesarethe basic tenet of initial
treatment.
Patients presenting with signs and symptoms of AMI require urgent abdominal exploration, assessment of bowel
viability, and revascularization.SMA emboli typically lodge distal to its origin, therefore the middle colic artery and
ileocolic branches may remain patent. Thus, the pattern of bowel necrosis following embolus may be less
extensive and usually spare the proximal jejunum and transverse colon from ischemic insult. Acute thrombosis
usually occurs at the orifice of the SMA. A more extensive pattern of hypoperfusion and necrosis is present in
these patients.
Surgical embolectomy & thrombolytic therapy are treatment options for embolic disease. Surgical thrombectomy,
vascular bypass procedures & stenting are options for acute mesenteric thrombosis.

SMA embolectomy: Transverse arteriotomy is placed distal to the area of block. Appropriately sized balloon-
tipped embolectomy catheter is passed proximally & distally to clear embolus. Arteriotomy is closed with fine
prolene sutures. SMA pulses are felt and the small bowel is examined carefully for areas of persistent ischemia,
which are resected. Intraoperative duplex ultrasonography or woods lamp examination can assist in identifying
thepersistently ischemic segments. 500-1000 mg (1-2 ampoules) of flurosecein dye is injected, bowel is
evaluated under wood's Lamp. Patchy uptake of dye suggestthat bowel resection is required.A "second-look"
laparotomy within the next 24 to 48 hours may be necessary to resect additional ischemic or gangrenous bowel.
If there is associated flow limiting atherosclerotic plaque then arteriotomy is converted to longitudinal
endarterectomy. Patch angioplasty with autologous vein graft is used for revascularization.

Embolus Thrombus

SMA pulsation Usually Present Absent

Duodenum & proximal jejunum Usually Spared Involved

Thrombolytic therapy:It can be considered in patients who can undergo angiography within eight hours of the
onset of abdominal pain and who do not have clinical evidence of bowel infarction. Urokinase has shown some
good results in few reports6.

SMA thrombectomy/surgical bypass: Described in detail in chronic mesenteric ischemia.

Hybrid procedures
Option for such patients is bowel resection first followed by percutaneous aortography & antegrade stent
placement. Retrograde mesenteric stenting has also been recently described with good results.

Follow-up
Lifelong anti-platelet therapy (e.g. aspirin, clopidogrel) will be continued.

Post-operative course
Mortality from acute mesenteric ischaemia ranges from 60-70%. Most common cause of death is sepsis.
Survivors usually end up in short bowel syndrome.Mortality remains high despite successful surgical
revascularization especially due ischemic reperfusion intestinal injury. 30-day mortality is reported around 50-
70%. The age >70, renal insufficiency, metabolic acidosis, symptom duration and need for second look
laparotomy are associated with poor outcome.

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Non-occlusive Mesenteric Ischaemia (NOMI)

NOMI is defined as impaired intestinal perfusion in absence of thromboembolic occlusion. It is a sympathetically

mediated mesenteric vasospasm in response to shock, sepsis or myocardial infarction, which results in
mesenteric hypoperfusion. Usually seen in critically ill ICU patients with known risk factors for atherosclerosis.
Few drugs e.g. alpha-agonists, digoxin, vasopressin etc. may also cause mesenteric ischaemia by similar
mechanism.
It has an insidious onset unlike AMI secondary to thromboembolic disorders. Clinical picture may resemble
cholecystitis, duodenal ulcer or infectious colitis. Pain may be absent in 25% of cases.
Based on a study cohort it was suggested that when three out four features described below when present in
patient undergoing cardiovascular surgery or dialysis are diagnostic of NOMI. a) Ileus with abdominal pain or
nausea b)requirement of catecholamine treatment c)episode of hypotension d)slow elevation of
transaminases.CT scan in such cases reveals vasospasm of mesenteric vessels without any evidence of
occlusion or stenosis suggestive of NOMI. Prostaglandin E1 infusion (0.01-0.02 ug/kg/min) for 5 days resulted in
improvement 7/9 patients and avoided need for angiography and papaverine catheter placement.
Narrowing of multiple SMA branches, impaired filling of intramural vessels, string of lake appearance of runoff
vessels are typical features seen on the conventional angiography.
The Goal of treatment is to optimize bowel perfusion by maximizing cardiac output & reversing vessel spasm.
Vasospasm can be overcome by direct catheter delivery of papaverine (30-60mg/hour). Systemic anticoagulation
is also started. Presence of peritonitis merits exploration.Therapeutic success can be gauged by resolution of
abdominal pain & reversal of changes seen on angiography. There is no need for long-term follow-up. 30-day
mortality with NOMI is reported around 80%.

Mesenteric Venous Thrombosis (MVT)

MVT can be either primary or secondary to intra-abdominal pathologies. SMV is the most commonly involved
vein.

Primary causes
Inherited coagulopathies
o Factor V Leiden mutation (Most common)
o Protein C and protein S deficiencies
o Antithrombin III deficiency)
Acquired Coagulopathies
o Paroxysmal nocturnal hemoglobinuria
o Myeloproliferative disorders
o Polycythemia vera

Secondary causes
Post-op (Post-splenectomy)
Abdominal trauma
Intraabdominal inflammatory states (pancreatitis, IBD)
Malignancy (colonic, pancreatic)
Cirrhosis with portal hypertension

Theoretically, primary & secondary causes can be differentiated on the basis of the fact that venous thrombosis
starts from smaller venules in procoagulant states & then progresses to larger veins while in secondary etiologies
larger veins are affected first.

MVT impairs venous return from the bowel, which leads to bowel wall edema & exudation of fluid from bowel
serosa into the peritoneal cavity. Ascites (may be haemorrhagic) is not an uncommon finding. Arterial inflow is
impaired secondary to mesenteric venous hypertension & bowel ischaemia ensues.
Signs & symptoms are similar to arterial occlusion but can have an insidious onset and course. Past or family
history of venous thrombosis or pulmonary embolism may be present7. Fever, abdominal distension and bloody
stools are most common symptoms. Presence of ascites with abdominal distension are among the important
findings on examination.

MDCT is the investigation of choice. The mainstay of treatment is the prevention of clot propagation by
anticoagulant therapy (Heparin/LMWH). The bolus dose of heparin is followed by continuous infusion while
maintaining APPT between 50-70 seconds. Intravenous antibiotics are administered to decrease bacterial
translocation. Aggressive fluid therapy, nasogastric decompression and bowel rest are other cornerstones of
conservative management.

Presence of peritonitis mandates laparotomy & removal of gangrenous bowel. Resection margins should not
have thrombosed veins. Attempts at thrombectomy or catheter directed lytic therapy is not recommended as they

225
are associated with higher mortality when compared to anticoagulant therapy 8. After recovery, procoagulant
work-up is advised. Life long anticoagulation will be necessary if no secondary causes are found.

Chronic Mesenteric Ischaemia

Prevalence of >50% of stenosis of at least one mesenteric vessel is seen in 6-10% of elderly Americans9. Due to
presence of extensive collateral circulation, occlusion of at least 2 mesenteric vessels is required to produce
symptoms.

Etiology

Atherosclerosis(98%)
Median Arcuate ligament syndrome
Fibromuscular dysplasia
Aortic dissection
Isolated SMA dissection
Takayasus arteritis
Giant cell arteritis
Polyarteritis nodosa

Pathophysiology

The postprandial rise in splanchnic blood flow reaches its peak at 1 hour after meals. Small bowel & pancreas
demonstrates major increase in blood flow as compared to stomach & colon. Fat is the most potent stimulant
followed by protein & carbohydrates. When there is stenosis of celiac & SMA, there is failure of postprandial
hyperemic response.

Signs & symptoms

The most common symptom is postprandial crampy abdominal pain, located in epigastrium, occurring 15-45
minutes after meal, lasting for 1-3 hours & is termed as intestinal angina. Patients develop food fear, as food
brings the pain. Therefore, weight loss and symptoms of malnutrition are common. The patients are commonly in
elderly age group, have a long smoking history.History of hypertension, myocardial infarction, stroke &
intermittent claudication could provide clue to cause for mesenteric ischemia. Bruit may be auscultated in
epigastrium. Laboratory tests will reveal hypoalbuminemia.

Investigations

UGI endoscopy, colonoscopy, CT scan etc. will be required to rule out intra-abdominal malignancy which is an
important differential diagnosis. It is not uncommon to find gastric ulcer in these patients as they have history of
long term NSAIDs intake.

Ultrasound Doppler is the first line investigation for patients suspected to have CMI. Duplex ultrasound
assessesthe flow velocity and resistance index along with vessel wall morphology and end organ vascularity. It
has a high sensitivity (90%) & negative predictive value (95%) 10. Doppler frequency of 2-5 MHz & insonation
angle of 45-70 degree is most accurate in assessing these patients. IMA is a difficult vessel for evaluation. High
flow velocity, post-stenotic dilatation, turbulent flow, reversal of flow in Common Hepatic Artery in celiac stenosis
are to be noted on Doppler. A fasting peak systolic velocity 275 cm/spredicts a 70% or greater stenosis with a
11
sensitivity of 92 % and a specificity of 96% . The lack of flow or peak systolic velocity (PSV) in SMA >275cm/sec
or no flow or PSV >200 cm/sec are reliable indicator >70% stenosis of vessel with a sensitivity of 92% and
87%for SMA and coeliac artery respectively.

CT angiography is the investigation of choice. Identifies significant vascular stenosis with very high sensitivity
(96%) & specificity (94%)12. Also excludes any other intra-abdominal pathology. MR angiography is equally
sensitive, useful in patients with contrast allergy & renal failure, however, requires longer time for image
acquisition.

Conventional angiography is the traditional gold standard for diagnosis. However, presently its role is limited for
therapeutic purpose only. Lateral views are essential. Findings include orificial stenosis, well-developed
collateralsand aneurysm of pancreato-duodenal arteries.

Indications for Intervention

All symptomatic patients

Asymptomatic patients with significant stenosis(>70%) of all three major visceral vessels 13

226
Mesenteric Revascularization

Antegrade
Bypass
Surgical Retrograde
Mesenteric
Revascularization Endarterectomy
Endovascular

Endovascular Treatment

It is usually the first choice. Access can be obtained via femoral or brachial artery. Brachial approach is preferred
for selective catheterization SMA since it has an acute downward angle at its origin while femoral artery approach
is useful for coeliac artery stenting

Femoral artery approach Brachial artery approach

Lower incidence of vascular injury Higher
Closer to target artery Distant
Vector forces are opposite to the angle of origin of mesenteric vessels Favorable
Higher maximal sheath size Limited
No risk of carotid embolization Risk present

SMA first, followed by celiac artery, both are revascularized in the same sitting. Systemic heparinization is done
at the initiation of the procedure. Balloon angioplasty + stenting is the procedure of choice. Balloon expandable
stents are preferred over self-expanding stents due to their superior radial force & controlled deployment.
Patients can be orally allowed at 4 hours post-procedure. Patients are followed-up with duplex ultrasound at 6-
monthly intervals. Antiplatelet agents (clopidogrel/aspirin)are continued for life long, if no contraindication exists.
Coeliac artery stenosis secondary to median arcuate ligament should be treated by laparoscopic lysis of ligament
as first line of treatment. If the patient does not improve then endovascular balloon angioplasty with stenting
should be planned.

Limitations of endovascular treatment

Restenosis & re-intervention rate is high(10-20%)

Risk of distal embolization
Access site hematoma
Arterial dissection
Contrast nephropathy
Vessel perforation

Open Surgical Revascularization

Patient selection
Younger,good risk patient, with lesion anatomy unsuitable for endovascular treatment (i.e. complete occlusion,
long segment (>2cm) SMA stenosis, flush aortic stenosis) or those with recurrent or refractory stenosis after
endovascular treatment are suitable candidates.Pre-operative cardiac evaluation is mandatory. Parenteral
nutrition may be considered in severely malnourished. Bowel preparation should not be given as it may
precipitate acute ischaemia.The choice of procedure depends upon the judgment and experience of the surgeon.

Bypass Grafting
Revascularization of SMA & celiac is the goal. IMA is optional 14. Synthetic grafts (ePTFE, dacron) are preferred
over autogenous grafts (femoral vein, saphenous vein) due to their higher long-term patency15. The comparison
between antegrade and retrograde bypass is shown in table below.

Antegrade bypass Retrograde bypass

Prograde flow with reduced turbulence Higher turbulence
Lesser likelihood of graft kinking Higher graft kinking rate
Need for supraceliac aortic clamping Risk of No such risk
renal failure & paraplegia

227
Technical details
After gaining access to peritoneal cavity, supraceliac aorta is exposed. Side biting clamp is applied. Graft is
tunneled through retropancreatic region between supraceliac aorta & SMA, usually end to side. Celiac
revascularization can be end to end or end to side, at the level of trifurcation or distal to it, respectively.
Retrograde bypass is indicated in following situations: Inaccessible supraceliac aorta (due to prior surgery),
severe cardiac disease that contraindicates supraceliac aortic clamping & need for simultaneous infrarenal aortic
& mesenteric revascularization.

Trans-aortic Endarterectomy

Indications
Concomitant renal ostia stenosis
Prior abdominal surgery/radiation
Perforated viscus

Procedure
Approach is retroperitoneal. Trap-door incision is placed over aorta after application of clamps. Diseased intima
with plaque separated from vessel wall to open-up origin of mesenteric vessels. Separate incision over SMA &
celiac may be necessary for plaques extending further beyond the origin of vessels. Divided intimal ends may be
fixed to vessel wall by fine prolene sutures to prevent aortic dissection. Renal arteries can be dealt with in the
same sitting.

Post-operative course
May be complicated by multi-organ failure either due to reperfusion injury or graft thrombosis. Diarrhoea may
occur due to disruption of periarterial neural plexus. Patients will require parenteral nutritional support.

Outcomes
Though, surgical revascularization procedures have shown better long-term results, but endovascular therapy is
to be offered first, due to its lower morbidity & mortality 16,17.
Advanced age, existing cardiac disease, hypertension and presence of disease in other vessels is associated
with poor outcome

Surgical bypass Endovascular

Clinical success 90% 80%
Morbidity 30% 15%
Mortality 8% 3%
Hospital stay 13-21 days 1-3 days
Primary patency rate 80% at 5 yrs 70% at 1 yr
Assisted primary patency rate 90% at 5 yrs 85% at 1 yr
Survival 70% at 5 yrs 70% at 5 yr

References

1. Klass AA: Embolectomy in acute mesenteric occlusion. Ann Surg 134:913-917, 1951
2. Ende, Norman. "Infarction of the bowel in cardiac failure." New England Journal of Medicine 258.18 (1958): 879-
881.
3. Boley SJ, Brandt LJ: Selective mesenteric vasodilators. A future role in acute mesenteric ischemia?
Gastroenterology 91:247-249, 1986
4. Clark RA, Gallant TE: Acute mesenteric ischemia: Angiographic spectrum. AJR Am J Roentgenol 142:555-562,
1984
5. Boley, SJ, Frieber, W, Winslow, PR, et al. Circulatory responses to acute reduction of superior mesenteric arterial
flow. Physiologist 1969; 12:180
6. Schoots IG, Levi MM, Reekers JA, et al. Thrombolytic therapy for acute superior mesenteric artery occlusion. J
VascInterv Radiol 2005; 16:317.
7. Harward TR, Green D, Bergan JJ, et al. Mesenteric venous thrombosis. J Vasc Surg 1989; 9:328
8. Morasch MD: Mesenteric venous thrombosis: Current concepts in diagnosis and treatment. In Pearce WH,
Matsumura JS, Yao JST, editors: Trends in vascular surgery. Chicago, 2002, Precept Press, p 473.
9. Wilson DB, Mostafavi K, Craven TE, et al: Clinical course of mesenteric artery stenosis in elderly americans. Arch
Intern Med 2006; 166:2095-2100.
10. Zwolak RM, Fillinger MF, Walsh DB, et al: Mesenteric and celiac duplex scanning: a validation study. J Vasc Surg
1998;27:1078-1087
11. Moneta GL, Lee RW, Yeager RA, et al: Mesenteric duplex scanning: a blinded prospective study. J Vasc Surg
1993; 17:79-84.
12. Shih MC, Hagspiel KD: CTA and MRA in mesenteric ischemia: part 1, Role in diagnosis and differential diagnosis.
AJR Am J Roentgenol 2007; 188:452-461.
13. Thomas JH, Blake K, Pierce GE, et al: The clinical course of asymptomatic mesenteric arterial stenosis. J Vasc
Surg 1998; 27:840-844.
14. Park WM, Cherry Jr KJ, Chua HK, et al: Current results of open revascularization for chronic mesenteric
ischemia: a standard for comparison. J Vasc Surg 2002; 35:853-859.

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15. Kihara TK, Blebea J, Anderson KM, et al: Risk factors and outcomes following revascularization for
chronicmesenteric ischemia. Ann Vasc Surg 1999; 13:37-44.
16. Atkins MDet al: Surgical revascularization versus endovascular therapy for chronic mesenteric ischemia: a
comparative experience. J Vasc Surg 2007; 45:1162-1171.
17. Tallarita T et al. Patient survival after open & endovascular revascularization for CMI. J vasc Surg. 2013
Mar;57(3):747-55.

Abdominal compartment syndrome

Shaji Thomas

Intra-abdominal hypertension has a prevalence of at least 50% in the critically ill population and has been
identified as an independent risk factor for death. Yet, many of the members of the critical care team do not
assess for intra-abdominal hypertension and are unaware of the consequences of untreated intra-abdominal
hypertension. These consequences can be abdominal compartment syndrome, multisystem organ failure, and
death.

Definitions

Intra-abdominal Pressure (IAP)

IAP is the steady-state pressure within the abdominal cavity. In healthy persons, IAP is 0 to 5 mm Hg and varies
inversely with intrathoracic pressure during normal breathing. Various factors, such as coughing, sneezing, and
loud singing, can cause IAP to increase drastically for short periods and then return easily to baseline. IAP is also
increased in persons who are morbidly obese, have chronic ascites, or are pregnant. In these chronic forms, the
increase develops slowly and the body adjusts to the change. Patients with chronically increased IAP do not
experience the systemic effects of IAH. The mean IAP in critically ill adults is approximately 5 to 7 mm Hg.

Intra-abdominal Hypertension (IAH)

IAH is a sustained or repeated pathological elevation of IAP of 12 mm Hg or greater.

Abdominal Perfusion Pressure (APP)

Abdominal perfusion pressure is a measure of the relative adequacy of abdominal blood flow. APP is calculated
by subtracting the IAP from the mean arterial pressure (MAP): MAP-IAP=APP. The APP in patients with IAH or
ACS should be maintained at 60 mm Hg or higher.

Abdominal Compartment Syndrome (ACS)

ACS is a sustained IAP greater than 20 mm Hg (with or without an APP <60 mm Hg) associated with new organ
dysfunction or failure.

Causes of ACS

Conditions that cause ACS are categorized as primary (surgical), secondary (medical), and recurrent.
Primary conditions are ones that need surgical or interventional radiological treatment. Secondary conditions
are due to medical causes that do not require surgery or radiological intervention as an initial therapy. Recurrent
conditions are ones in which ACS redevelops after surgical or medical treatment of primary or secondary causes
of ACS.

Table 1. Risk factors for intra-abdominal hypertension and abdominal compartment syndrome

Diminished abdominal wall compliance Capillary leak/fluid resuscitation

Abdominal surgery Acidosis
Major trauma Damage control laparotomy
Major burns Hypothermia
Prone positioning Increased APACHE-II or SOFA score
Massive fluid resuscitation or positive fluid balance
Increased intra-luminal contents Polytransfusion
Gastroparesis/gastric distention/ileus
Ileus Others/miscellaneous
Colonic pseudo-obstruction Age
Volvulus Bacteremia
Coagulopathy
Increased intra-abdominal contents Increased head of bed angle
Acute pancreatitis Massive incisional hernia repair
Distended abdomen Mechanical ventilation

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Hemoperitoneum/pneumoperitoneum or intra-peritoneal Obesity or increased body mass index
fluid collections PEEP > 10
Intra-abdominal infection/abscess Peritonitis
Intra-abdominal or retroperitoneal tumors Pneumonia
Laparoscopy with excessive insufflation pressures Sepsis
Liver dysfunction/cirrhosis with ascites Shock or hypotension
Peritoneal dialysis

Pathophysiological effects of IAH and ACS

The abdominal compartment contains solid organs, hollow organs, fluid, gas, solids, and adipose tissue. When a
condition arises that persistently increases pressure in the abdominal cavity to 12 mm Hg or greater, not only the
gut but all major body systems can be affected, and the effects can lead to multisystem organ failure and death.

Gastrointestinal System
The effect of IAH on the splanchnic organs leads to diminished gut perfusion. The consequences of this change
lead to ischemia, acidosis of the mucosal bed, capillary leak, intestinal edema, and translocation of gut bacteria,
and sepsis.
Patients with IAH are also at high risk for stress ulcers because of the loss of the mucosal barrier.
Distention of the abdominal wall by IAH leads to decreased compliance of the wall, further compounding the IAH.
The decreased blood flow leads to poor healing and possible dehiscence of abdominal surgical wounds.
Persistent pressures as low as 10 mm Hg can decrease hepatic perfusion and impair liver function.

Renal System
IAH leads to impaired renal function. The renal impairment, as indicated by an elevated serum level of creatinine,
may not appear until 2 to 3 days after the incident of IAH.

Pulmonary System
As the abdomen distends with intestinal gas, fluid, or edematous organs, the diaphragm is pushed upward,
impinging on the thoracic cavity. Approximately 50% of the IAP is dispersed across the diaphragm and affects
respiration and ventilation. Pulmonary dysfunction may be one of the earliest signs of ACS.

Cardiovascular System
The increased intrathoracic pressure compresses the heart and major vessels, causing a tamponade-like picture,
especially with the higher grades of IAH. Central venous pressures (CVPs) and pulmonary artery wedge
pressures (PAWPs) are fictitiously elevated because of the effects of IAH.
Compression of the inferior vena cava causes a decrease in venous return to the heart, affecting preload and
causing a decrease in cardiac output.
IAH also causes pressure on the femoral veins. This pressure increases venous stasis and the development of
deep vein thrombosis. When the IAH is resolved, the risk of pulmonary emboli increases.

Measuring intra-abdominal pressure

The gold standard of indirect measurement is measurement via a urinary bladder catheter. Either a transducer
technique or a manometer technique can be used.
This method may be contraindicated in patients who have bladder surgery or trauma and may not be reliable in
patients who have neurogenic bladder.

Transducer technique
The indwelling Foleys catheter drainage tube is connected by a three-way stopcock to a pressure tubing and
transducer. Instill 25 ml of sterile saline solution into the bladder and connect to the transducer to obtain the
pressure readings.

Manometer technique
The manometer technique is similar to the method of measuring CVP with a fluid column. The patient should
have a urinary catheter in place; the only equipment needed is a centimeter ruler. This technique is called the U-
tube technique.
Obtain a centimeter ruler.
Position the patient supine with the head of the bed flat.
The patient should be quiet, not agitated, restless, coughing, or talking. Ensure that abdominal muscle
contractions are absent.
Raise the urinary catheter above the patient, allowing a U-shaped loop to develop.
Level the connection site (the zero level) where the catheter meets the drainage tubing in line with the
symphysis pubis.
The urine in the tubing should fluctuate with respirations.

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 Allow the fluid column to settle, and using the centimeter ruler, measure from the zero connection site to the
meniscus of the fluid column.
Convert from centimeters of water to millimeters of mercury (1.00 cm H 2O = 0.74 mm Hg).
When measurement is completed, reposition patient to appropriate position for patients condition.

The clinical validation with the U-tube technique is poor, and the method is recommended primarily for screening.

Screening and Monitoring

The 2004 International ACS Consensus Conference defined risk factors for IAH/ACS as:
1. diminished abdominal wall compliance, typically after abdominal surgery with tight fascial closure,
especially in patients with a high body mass index (>30 kg/m2), after incisional hernia repair and after
abdominal burns;
2. increased intraluminal contents, for example, gastro-intestinal paresis or obstruction;
3. increased intraperitoneal or retroperitoneal contents, abdominal organ injury or pathology, as damage
control surgery for trauma with packing, pelvic ring disruption with retroperitoneal hematoma,
hemoperitoneum from non-operative treatment of organ injury, pancreatitis and other causes of
abdominal sepsis or abdominal aortic aneurysm repair;
4. capillary leak, as it occurs in the setting of systemic inflammation and/or massive fluid/blood
resuscitation of more than 5 liters of crystalloids/ colloids or more than 10 packed red blood cells within
24 hours. In all these cases, IAH is the result of tissue and bowel wall edema.

Any patient admitted to a critical care unit or in whom new organ failure develops should be screened for risk
factors for IAH and ACS. If a patient has at least 2 of the risk factors, a baseline IAP measurement should be
obtained.

Perhaps, initially the U-tube method could be used as a screening tool, and then once the IAP is greater than 12
mm Hg for 2 consecutive measurements, a more reliable measuring device should be used. Patients at risk for
IAH or ACS should have IAP measured at least every 4 to 6 hours. Patients with unstable hemodynamic status
and patients with rapidly deteriorating organ dysfunction should have IAP measured hourly. IAP measurements
can be discontinued once the condition causing IAH has resolved and the IAP has remained at 10 to 12 mm Hg
or less for 24 to 48 hours.

Management

Once IAH has been detected in a susceptible patient, the goal is to decrease the IAP to 15 mm Hg or less,
maintain the APP at 60 mm Hg or greater, and prevent ACS.
Initial treatment of ACS is always non-operative due to the significant morbidity associated with opening the
abdomen. The following strategies are suggested as part of the World Society for the Abdominal Compartment
Syndrome guidelines:
1. improvement of abdominal wall compliance with sedation, analgesia, neuromuscular blockade and a
supine body position;

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 2. evacuation of intraluminal contents by, for example, gastro-colonic decompression with tubes or
endoscopy and prokinetic agents such as erythromycin, metoclopramide or neostigmine;
3. evacuation of intra-abdominal contents using percutaneous catheter decompression with intraperitoneal
fluid or blood removal;
4. correct positive fluid balance with diuretics or extracorporeal techniques and hypertonic or colloid-based
resuscitation protocols; and
5. should all these measures fail, surgical techniques with a negative pressure dressing to relieve IAH
should be considered, always taking into consideration the benefit-to-risk ratio.

There is no consensus regarding the indications for surgical treatment of ACS, and a critical threshold value of
IAP cannot be applied to decision making. Clinical experience suggests that surgery should be indicated for an
IAP consistently higher than 30 mmHg or an abdominal perfusion pressure (APP) lower than 50 mmHg
associated with ongoing organ failure refractory to medical treatment.

For primary ACS, the best choice for surgical decompression is obviously to re-open the existing recent
abdominal incision. For secondary ACS and in general for patients without recent operations, there are several
options. A midline vertical incision is the most commonly used method, however for some cases, a bilateral
subcostal incision is preferable. For example, in acute necrotizing pancreatitis, the subcostal approach
ameliorates exposure of the pancreas, facilitates a necrosectomy and allows for selective open treatment of the
supramesocolic and paracolic regions. Another option is a subcutaneous vertical linea alba incision, which
leaves the peritoneum intact and has less complications and a significant advantage for nursing during the acute
phase.

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Surgical decompression produces a prompt decrease in IAP, which is often reduced by 50%, but its effects on
organ function and survival are still debated. The impression is that reducing the IAP is useful for improving the
physiology in critically ill patients with ACS or those at risk for IAH, but the outcomes are principally related to the
evolution of the underlying illness.

Table 2. Final 2013 WSACS consensus management statements

(World Society of the Abdominal Compartment Syndrome)
Recommendations
1. We recommend measuring IAP when any known risk factor for IAH/ACS is present in a critically ill or injured patient [GRADE
1C]
2. Studies should adopt the trans-bladder technique as the standard IAP measurement technique [not GRADED]
3. We recommend use of protocolized monitoring and management of IAP versus not [GRADE 1C]
4. We recommend efforts and/or protocols to avoid sustained IAH as compared to inattention to IAP among critically ill or
injured patients [GRADE 1C]
5. We recommend decompressive laparotomy in cases of overt ACS compared to strategies that do not use decompressive
laparotomy in critically ill adults with ACS [GRADE 1D]
6. We recommend that among ICU patients with open abdominal wounds, conscious and/or protocolized efforts be made to
obtain an early or at least same-hospital-stay abdominal fascial closure [GRADE 1D]
7. We recommend that among critically ill/injured patients with open abdominal wounds, strategies utilizing negative pressure
wound therapy should be used versus not [GRADE 1C]

Suggestions
1. We suggest that clinicians ensure that critically ill or injured patients receive optimal pain and anxiety relief [GRADE 2D]
2. We suggest brief trials of neuromuscular blockade as a temporizing measure in the treatment of IAH/ACS [GRADE 2D]
3. We suggest that the potential contribution of body position to elevated IAP be considered among patients with, or at risk of,
IAH or ACS [GRADE 2D]
4. We suggest liberal use of enteral decompression with nasogastric or rectal tubes when the stomach or colon are dilated in
the presence of IAH/ACS [GRADE 1D]
5. We suggest that neostigmine be used for the treatment of established colonic ileus not responding to other simple measures
and associated with IAH [GRADE 2D]
6. We suggest using a protocol to try and avoid a positive cumulative fluid balance in the critically ill or injured patient with, or at
risk of, IAH/ACS after the acute resuscitation has been completed and the inciting issues have been addressed [GRADE 2C]
7. We suggest use of an enhanced ratio of plasma/packed red blood cells for resuscitation of massive hemorrhage versus low
or no attention to plasma/packed red blood cell ratios [GRADE 2D]
8. We suggest use of PCD to remove fluid (in the setting of obvious intraperitoneal fluid) in those with IAH/ACS when this is
technically possible compared to doing nothing [GRADE 2C]. We also suggest using PCD to remove fluid (in the setting of
obvious intraperitoneal fluid) in those with IAH/ACS when this is technically possible compared to immediate decompressive
laparotomy as this may alleviate the need for decompressive laparotomy [GRADE 2D]
9. We suggest that patients undergoing laparotomy for trauma suffering from physiologic exhaustion be treated with the
prophylactic use of the open abdomen versus intraoperative abdominal fascial closure and expectant IAP management
[GRADE 2D]
10. We suggest not to routinely utilize the open abdomen for patients with severe intraperitoneal contamination undergoing
emergency laparotomy for intra-abdominal sepsis unless IAH is a specific concern [GRADE 2B]
11. We suggest that bioprosthetic meshes should not be routinely used in the early closure of the open abdomen compared to
alternative strategies [GRADE 2D]

No recommendations
1. We could make no recommendation regarding use of abdominal perfusion pressure in the resuscitation or management of
the critically ill or injured
2. We could make no recommendation regarding use of diuretics to mobilize fluids in hemodynamically stable patients with IAH
after the acute resuscitation has been completed and the inciting issues have been addressed
3. We could make no recommendation regarding the use of renal replacement therapies to mobilize fluid in hemodynamically
stable patients with IAH after the acute resuscitation has been completed and the inciting issues have been addressed
4. We could make no recommendation regarding the administration of albumin versus not, to mobilize fluid in hemodynamically
stable patients with IAH after acute resuscitation has been completed and the inciting issues have been addressed
5. We could make no recommendation regarding the prophylactic use of the open abdomen in non-trauma acute care surgery
patients with physiologic exhaustion versus intraoperative abdominal fascial closure and expectant IAP management
6. We could make no recommendation regarding use of an acute component separation technique versus not to facilitate
earlier abdominal fascial closure

References / Suggested reading

1. Kirkpatrick AW, Roberts DJ, De Waele J, et al. Intra-abdominal hypertension and the abdominal compartment
syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the
Abdominal Compartment Syndrome. Intensive Care Med. 2013 Jul;39(7):1190-206. doi: 10.1007/s00134-013-2906-z.
Epub 2013 May 15.
2. Lee RK. Intra-abdominal hypertension and abdominal compartment syndrome: a comprehensive overview. Crit
Care Nurse. 2012 Feb;32(1):19-31. doi: 10.4037/ccn2012662.
3. Chiara O, Cimbanassi S, Boati S, Bassi G. Surgical management of abdominal compartment syndrome. Minerva
Anestesiol. 2011 Apr;77(4):457-62.

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 Approach to a patient with obstructive jaundice

P K Mishra, Arvind PS, P Narang

Introduction
Jaundice (icterus) (derived from French word jaune meaning yellow) refers to excess bile pigment in the serum
and tissues leading to yellowish discoloration of skin, mucus membrane and sclera.

Jaundice may result from

1. Increased production of bilirubin,
2. Impaired hepatocyte uptake of bilirubin,
3. Impaired conjugation of bilirubin,
4. Impaired transport or excretion of bilirubin into the bile canaliculus,
5. obstruction of the intrahepatic or extrahepatic biliary tree

The medical jaundice is usually associated with either excess production, impaired hepatic uptake, conjugation
or excretion of bilirubin into bile canaliculi. Surgical jaundice also known as obstructivejaundice is due to the
conditions causing the obstruction of the major biliary passages.

The evaluation and management of the patient with biliary obstruction is a common problem facing the general
surgeon.

PATHOPHYSIOLOGY OF OBSTRUCTIVE JAUNDICE

The pathophysiologic effects of obstructive jaundice are due to two mechanisms. 1) due to absence of bile
constituents in the intestines (bile salts, bilirubinderivatives and lipids) 2)due to their overflow into the systemic
circulation. Absence of bile salts in the intestines can produce steatorrhea and malabsorption, leading to
deficiencies of fat-soluble vitamins (particularly A, K, and D);Vitamin K deficiency causes prolonged prothrombin
time.Vitamin D and Calcium malabsorption can cause osteoporosis or osteomalacia. Stools are pale as less
bilirubin derived pigments (urobilinogen) reaches the intestine. As conjugated bilirubin is water soluble it is
excreted in the urine and urine becomes dark in obstructive jaundice. Pruritus is usually associated with high
levels of circulating bile salts.

Common causes of Biliary Tract Obstruction

Type I Type II Type III TypeIV
Complete Obstruction Intermittent Chronic Incomplete Segmental Obstruction
Obstruction Obstruction
Tumors of the head of Choledocholithiasis Strictures of the Traumatic
the pancreas (most common) common bile duct Intrahepatic stones
Cholangiocarcinoma Periampullary tumors Congenital Sclerosing cholangitis
Common bile duct Duodenal diverticula Traumatic (iatrogenic) Cholangiocarcinoma
ligation Choledochal cyst Sclerosing cholangitis
Parenchymal liver Polycystic liver disease Post radiotherapy
tumors (primary or Biliary parasites Stenosis of biliary-
secondary) Haemobilia enteric anastomosis
Chronic pancreatitis
Cystic fibrosis
Sphincter of Oddi
stenosis

Diagnostic Approach to Jaundice

1. History, Physical examination, and Screening laboratory studies
2. Differential diagnosis
3. Specialized tests
4. Strategy for treatment or further testing

HISTORY AND PHYSICAL EXAMINATION

For the surgeon the most important question while evaluating apatient with jaundice is whether the patient has
medical or surgical jaundice.A careful history, clinical examination and basic laboratory test and its careful
1
interpretation can accurately diagnose the condition in 75%of cases.

Important points to remember while evaluating a patient with obstructive jaundice are:
Patients with biliary tract obstruction due to malignancy usually have painless progressive jaundice,
whereas patients with an acute attack of pain or a long history of intermittent episodes of jaundice
accompanied by pain frequently have gallstone disease.

234
 Intermittent jaundice with pain, chills and fever (Charcots Triad) is seen more commonly in
choledocholithiasis (stone may block and then get passed away or due to ball valve effect)than in
malignancy.
Painless progressive jaundice is typically associated with malignant biliary obstructions like
carcinoma of head of pancreas, periampullary carcinoma, carcinoma of neck of gall bladder or
hilarcholangiocarcinoma (Klatskintumor) whereas fluctuating jaundice may be seen in small
periampullarytumor (due to sloughing of the tumor causing transient melena).
Obstructive jaundice is associated with high colored (cola
colored) urine due to presence of conjugated bilirubin filtered by kidney into the urine from the blood.
Jaundice associated with hemolyticanemia is not associated with such high colored urine (acholuric
jaundice) due to presence predominantly of unconjugated bilirubin in serum which is not filtered by the
kidneys.
Severe pruritus in these patients; scratch marks all over the body and the associated shining nails may
be seen in many patients.
Significant loss of weight and anorexia are usually seen in malignant causes of jaundice.
Jaundice unaccompanied by pain, and especially if the gallbladder is palpable, almost always indicates
malignancy (Courvoisiers law).
Malignant disease affecting the hepatic ducts at the biliary confluence in the hilus of the liver often
presents with jaundice, but in such instances, the gallbladder is usually not palpable.
Itching can be an initial feature of biliary obstruction, but in prolonged cholestasis, itching may occur in
association with partial biliary obstruction and significantly in primary biliary cirrhosis.
Back pain usually indicates a pancreatic lesion; chronic pancreatitis and tumors of the pancreas can
manifest in this manner. Patients with chronic pancreatitis occasionally are seen with jaundice,
especially during an acute-on-chronic attack, and the jaundice may be accompanied by symptoms
of endocrine and exocrine deficiency (diabetes, steatorrhea, malabsorption).
Presence of left supra-clavicular lymph nodal mass along with jaundice indicates advanced
biliary-pancreatic tract malignancy or associated liver metastasis.
Abdomen examination may be unremarkable in many cases of obstructive jaundice.
Distended gallbladder may be palpable in malignant biliary obstructions at or below the level
of cystic duct insertion into bile duct but not in benign causes like choledocholithiasis (Courvoisiers rule)
Presence of splenomegaly in a jaundiced patient may be due
to hemolyticanemia, portal hypertension, infiltrative diseases, recurrent cholangitis, secondary biliary
cirrhosis, SMV or splenic vein thrombosis.
Ascites in these patients may be pointer toward advanced malignancy or chronic liver disease
with portal hypertension.
Jaundice in a severely malnourished patient may be due tounderlying malignancy like
carcinoma of gallbladder, head of pancreas, extensive liver metastasis or may indicate an advanced
decompensated chronic liver disease.

INITIAL LABORATORY STUDIES

Essential laboratory studies in the patient with jaundice include serum total bilirubin, alkaline
phosphatase, ALT, and AST levels, a complete blood count, and the prothrombin time.

In a jaundiced patient, a predominant increase in (hepatic) alkaline phosphatase activity relative to levels of
the serum aminotransferases suggests the possibility of biliary tract obstruction. An increase in serum
alkaline phosphatase activity, however, also may reflect release of alkaline phosphataseisoenzymes
fromextrahepatictissues. Therefore, other more specific markers, such as gamma glutamyltranspeptidase (GGT),
or 5-nucleotidase (or alternatively, alkaline phosphatase isoenzymes), are measured to confirm the hepatobiliary
origin of an elevated serum alkaline phosphatase level when other liver biochemical test results (e.g., total
bilirubin, ALT, AST) are normal. Intrahepatic cholestatic disorders can produce an identical biochemical picture.
Predominant elevation of serum aminotransferase activity (AST,ALT) in comparison with alkaline phosphatase
activity suggests that jaundice is the result of intrinsic hepatocellular disease. However, in acute biliary
obstruction, these enzymes may be raised up to 20 times normal even before significant increase in
serum alkaline phosphates. These enzymes are also raised in cholangitis.

A complete blood count provides complementary information concerning the cause of jaundice. Leukocytosis
may be a clue to the presence of biliary tract obstruction or other inflammatory disorder that may be associated
with cholestasis. The presence of anemia leaves open the possibility that a hemolytic disorder is responsible for
bilirubin overload.Thrombocytopenia is a characteristic finding in cirrhosis and appears to result from reduced
platelet production from decreased hepatocyte synthesis of thrombopoietin or from increased platelet
consumption from splenic sequestrationassociated with portal hypertension.

Prolongation of the prothrombin time (and an associated increase in the international normalized ratio,
INR) can result from impaired hepatic synthesis of these proteins and from deficiency of vitamin K, which is
required as a cofactor for essential posttranslational modification of factors II, VII, IX, and X.

235
Tumor markers like CA 19-9, CEA and CA-125 are usually elevated in pancreatic cancers, cholangiocarcinoma
and peri-ampullary cancers, but they are non specific and may be elevated in other benign diseases of the
hepatobiliary tree2.

IMAGING STUDIES
Selection of the appropriate imaging study depends on the likelihood of bile duct obstruction and the
diagnostic accuracy, cost, complication rate, and availability of each test, especially if therapeutic intervention
at the time of the study is anticipated.

The goals of imaging include

1. Confirm the presence of obstructive jaundice
2. To determine the severity and the level of obstruction
3. Staging malignant disease
4. Guiding therapy with image based assistance.

IMAGING MODALITIES FOR THE BILIARY SYSTEM

Ultrasound (US)
US is generallyreadily available in most medical institutions and should be the first
imaging modality used when assessing patients with suspected biliary disease. US
is a relatively inexpensive, non-invasive imaging modality used to confirm the
presence of biliary ductal dilation. US accurately predicts the level of biliary
obstruction in the majority of cases (92%), but it is less accurate in suggesting
the correct cause (71%).3Ultrasound will also show presence of ascites, portal
hypertension, lymph nodal enlargement and liver infiltration. Coupled with Doppler it
may give valuable information regarding status of portal vein, superior mesenteric
vein (SMV) and hepatic arteries. This is especially important in malignancies and
bile duct injuries.The major disadvantages are that the procedure is operator-dependent and interpretation may
be difficult in obese patients or patients with overlying bowel gas.In patients with cirrhosis and other conditions
associated with poorly compliant hepatic parenchyma, such as primary sclerosing cholangitis, intrahepatic
ducts may not dilate with biliary obstruction.

Computed Tomography
In many institutions, the initial non-invasive imaging modality of choice for
patients with suspected biliary obstruction is CT, specifically, helical CT
scanning. With the advent of multi-detector CT scanners, imaging of the
entire biliary tract can be performed in a single breath hold allowing for
shorter scan durations and the acquisition of volumetric data, which can
subsequently be reconstructed at very thin sections. This is especially
helpful when scanning paediatric or critically ill patients. The disadvantages
include (1) the requirement for intravenous contrast administration (not
always possible in patients with renal dysfunction), (2) use of ionizing
radiation, and (3) additional cost as compared to US. CT is less operator
dependent than US. Thus, it is reproducible, and studies are easily compared. It
is therefore important for followup after biliary surgical or interventional procedures.

Magnetic Resonance Cholangiopancreatography

When accurately performed MRCP has, in many institutions, replaced
conventional ERCP and PTC. Although more expensive than US or CT,
MRCP is considered an accurate, non-invasive technique for evaluation of
the biliary tract. MRCP has a high sensitivity and specificity in demonstrating
biliary tract stone disease, allowing visualization of stones as small as 2 mm in
4
size. MRCP is also useful in the evaluation of congenital disorders, benign
and malignant biliary strictures, and for patients with failed or incomplete ERCP
or PTC.5,6This is a valuable non-invasive means to visualize the biliary tree
before therapeutic intervention or surgery. 7

Endoscopic Retrograde Cholangiopancreatography

Endoscopic retrogradecholangiopancreatography (ERCP) permits direct
visualization of the biliary tree. ERCP is more invasive than ultrasonography and
CT. The procedure involves passage of an endoscope into the duodenum,
introduction of a catheter into the ampulla of Vater,and injection of contrast
medium into the bile duct; sedation and analgesia are necessary. ERCP is
highly accurate in the diagnosis of biliary obstruction, with sensitivitiesof 89%
to 98% and specificities of 89% to 100%.

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In addition to providing radiographic images, ERCP permits biopsy and brushings for cytology of distal biliary
and periampullary lesions. Moreover, if a focal cause of biliary obstruction is identified (e.g.,
choledocholithiasis, biliarystricture), manoeuvres to relieve obstruction (e.g., sphincterotomy, stone extraction,
stricture dilation, stent placement) can be performed during the same session.

Acquisition of biopsy specimens and therapeutic interventions via ERCP are limited largely to lesions
distal to the bifurcation of the right and left hepatic bile ducts. The technical success rate of ERCP is higher
than 90%; the technique fails when the ampulla of Vater cannot be cannulated, as may be the case in patients
with prior abdominal surgery and altered anatomy (e.g., gastric bypass, choledochojejunostomy). Rates of
morbidity and mortality from untoward events, such as respiratory depression, aspiration, bleeding, perforation,
cholangitis, and pancreatitis, are 3% and 0.2%, respectively, in patients undergoing ERCP.These rates are
higher when interventional procedures are carried out.

Percutaneous Transhepatic Cholangiography

Percutaneous transhepatic cholangiography (THC) is a procedure that
complements ERCP. Sensitivity and specificity rates of percutaneous THC for
the diagnosis of biliary tract obstruction are 98% to 100% and 89% to 100%,
respectively, and are comparable with those for ERCP.

Like ERCP, interventional procedures, such as balloon dilation and stent

placement, can be performed at the time of percutaneous THC to relieve
focal obstructions of the biliary tree.

Percutaneous THC is potentially technicallyadvantageous when the level of

biliary obstruction is proximal to the common hepatic duct or altered
anatomy precludes ERCP. (Percutaneous THC may be technically challenging in the absence of dilatation of
the intrahepatic bile ducts; in this situation, multiple passes may be required, and visualization of the biliary
tree may be unsuccessful in up to 10% of attempts.Rates of morbidity and mortality as a result of bleeding,
perforation, and cholangitis are 3% and 0.2%, respectively, in patients undergoing percutaneous THC.
Percutaneous THC is more invasive than abdominal USG and CT.

Endoscopic Ultrasonography
Endoscopic ultrasonography (EUS) can also detect obstruction of the bile duct and major intrahepatic bile ducts,
with a sensitivity and specificity comparable with those of MRCP.EUS has the potential advantage of permitting
biopsy of suspected malignant lesions, and under appropriate circumstances, the operator can proceed directly
to ERCP for definitive biliary decompression. The risk of diagnostic EUS is comparable with that of diagnostic
upper endoscopy; when needle biopsy is used, the mortality rate is approximately 0.1%. EUS may be most useful
incircumstances in which the patient is thought to be at high risk for complications of ERCP or percutaneous
THC.

Nuclear Imaging Studies

Nuclear scintigraphy of the biliary tree, although helpful in the diagnosis of cholecystitis, is not sufficiently
sensitive tojustify its routine use in the diagnostic evaluation of jaundice.A suspected traumatic injury to the
biliary system may be confirmed using nuclear medicine scintigraphy (e.g., technetium-99m
diisopropyliminodiacetic acid [DISIDA] scan). In addition to confirming the presence of bile duct injury (i.e.,
leak), the technique may also prove useful in confirming the presence of gallbladder disease, biliary
obstruction, and so forth. It is rarely used in routine practice.

THERAPEUTIC APPROACHES
In the patient with obstruction of the bile ducts, therapy is typically directed at the cause ofobstruction.
Interventional endoscopic or radiologic approaches include sphincterotomy, balloon dilation of focal strictures,
and placement of drains or stents; the alternatives are surgical. The therapeutic strategy chosen will depend, in
part,on the location and likely cause of the obstructing lesion. It is beyond the purview of this chapter to go into
the details of all aspects of the therapeutic strategy. Malignant lesions should undergo resection after determining
resectability.

Focal intrahepatic strictures may be amenable to an interventional radiologic approach, whereas lesions distal to
the bifurcation of the hepatic ducts may be more suitably managed endoscopically (e.g., sphincterotomy for
choledocholithiasis); mass lesions may require surgery.
In many institutions, after initial clinical, laboratory, and imaging evaluations, ERCP is generally the first
minimally invasive procedure performed in patients withknown biliary disease. This is especially true for
patients with non-dilated biliary ducts (e.g., patients with a suspected bile duct injury, such as a leak after
surgery, or with sclerosing cholangitis, etc.)

In general, ERCP should be used in patients when

1. Intrahepatic bile ducts are nondilated.

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 2. The patient has an absolute contraindication to PTC/PBD (i.e., a coagulopathy that cannot be
corrected).
3. The patient has a relative contraindication to PTC/PBD (i.e. ascites, polycystic liver disease, etc.). PTC
(often followed by PBD) should be performed:
o When ERCP fails and the patient is symptomatic (e.g., obstruction with sepsis, etc.).
o When the patient has had a prior biliary-enteric anastomosis.
o If surgical resection of a tumor at the biliary confluence is planned, PBD (often bilateral) is
performed to relieve symptoms (i.e., to drain obstructed and potentially infected bile). In some
centers, it is felt that the presurgical placement of percutaneously placed biliary drainage
catheter(s) facilitates intraoperative biliary reconstruction and aids in the surgical creation of a
biliary-enteric anastomosis(es).
o In those patients who are not surgical candidates and who have known malignant
tumors at the biliary confluence, bilateral PTC/PBD will allow palliative endoprosthesis
placement.

Preoperative Drainage
Preoperative drainage is required in patients where liver resections are contemplated. Preoperative drainage in
lower end blocks is debated. Several prospective randomized studies have shown that the routine use of
preoperative biliary drainage does not reduce operative morbidity or mortality in patients with obstructive
jaundice with lower end blocks. It is associated with higher incidence of infectious complications. Indications for
preoperative drainage are as below

Indications:
1. Cholangitis
2. Before chemotherapy
3. Advanced malnutrition
Besides these most surgeons use preoperative drainage at bilirubin levels above 15 mg%.

Pre operative preparation in obstructive jaundice

1. Maintenance of adequate hydration and urine output
2. Adequate nutrition
3. Inj.Vit K to correct coagulation abnormalities
4. Pre operative biliary drainage as discussed earlier
In addition to the specific treatments outlined, cholestatic disorders may lead to impaired absorption of fat-soluble
vitamins (A, D, E, and K), and supplementation is recommended.

References

1. Lidofsky SD. Jaundice. In: Feldman M, Friedman LS, Brandt LJ (Eds). Sleisanger&Fordtrans Gastrointestinal and
Liver Disease, 9th edition. 2010. pp. 323-35
2. Malhi H, Gores GJ, Malhi H, Gores GJ. Review article: the modern diagnosis and therapy of cholangiocarcinoma.
[Review] [78 refs]. Alimentary Pharmacology & Therapeutics 2006; 23(9):1287-1296.
3. Laing FC, Jeffrey RB Jr, Wing VW, et al: Biliary dilatation: Defining the level and cause by real-time US.
Radiology160:39, 1986
4. Yeh BM, Liu PS, Soto JA, et al: MR imaging and CT of the biliary tract. Radiographics29:1669, 2009
5. Fulcher AS, Turner MA: Benign diseases of the biliary tract: Evaluation with MR cholangiography. Semin
Ultrasound CT MR20:294, 1999.
6. Hekimoglu K, Ustundag Y, Dusak A, et al: MRCP vs ERCP in the evaluation of biliary pathologies: Review of
current literature. J Dig Dis9:162, 2008
7. Levy AD: Noninvasive imaging approach to patients with suspected hepatobiliary disease. Tech VascInterv
Radiol4:132, 2001

Diagnostic Laparoscopy

Anurag Mishra

Introduction
Diagnostic laparoscopy has been in the armamentarium of the gynecological surgeon for many years.
Recognized more than 30 years ago by gynecologists as a useful technique for evaluating pelvic pathology,
diagnostic laparoscopy now is one of the most frequently performed gynecological procedures. However, the
general surgeons have only recently embraced diagnostic laparoscopy. The use of laparoscopy in the diagnosis
of abdominal diseases has rapidly expanded over the last few years. Surgeons are now expanding the role of the
laparoscope to include preoperative staging of a wide range of cancers, post-treatment or second-look
laparoscopy for numerous malignancies, liver disease, and ascites. The numbers of treatment options available
through the laparoscope are also increasing rapidly.

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Increasingly, surgeons are using laparoscopic techniques outside the operating room to help evaluate the patient
with an unknown intraperitoneal process. Diagnostic laparoscopy has also been used in the trauma ward,
emergency room, intensive care unit, and even the out patient departments. Therapeutic laparoscopy is also
becoming more common in these settings as surgeons become more versatile with its use. In this era,
laparoscopy is taken out of the operating room to the patients bedside.

History
In 1901 Kelling, a surgeon from Dresden, performed the first successful laparoscopy in a dogbefore the
Seventy-third Congress of German Naturalists and Physicians. He anesthetized an area of the
abdominal wall and introduced a puncture needle through which room air (filtered by sterile cotton) was
injected into the peritoneal cavity to produce a pneumoperitoneum. He then introduced a larger trocar
and introduced a Nitze cystoscope through it. Through a second trocar site, he inserted a probe to
manipulate the contents of the abdominal cavity. A more detailed report was to follow but was never
published.
In 1910, Jacobaeus described the technique in humans afflicted with ascites. After experimenting on 20
cadavers with a trocar he invented, he performed laparoscopy on 17 patients with ascites and
thoracoscopy on 2 patients with empyema. He did not introduce air through a separate needle, as did
Kelling, instead insufflating air through the original trocar.He advocated the technique as an early
diagnostic tool for malignancy.
Orndoff presented the first large-scale series of diagnostic laparoscopy in humans, in 1920. He
described 42 cases of peritoneoscopy in the Journal of Radiology.He described the then novel
pyramidal trocar blade and utilized fluoroscopy to decrease visceral injury during trocar insertion.
Ruddock, in 1937, demonstrated the efficacy and safety of diagnostic laparoscopy with a report of 500
patients without a single mortality,Since the founding work of these and other pioneers, diagnostic
laparoscopy has slowly evolved into an invaluable tool for the diagnosis of intra-abdominal and pelvic
disease.

Indications
Acute Right Lower Quadrant Abdominal Pain: Although not traditionally considered an indication for
laparoscopy, the increasing use of laparoscopic appendectomy has liberalized the laparoscopic
evaluation of right lower quadrant pain. Laparoscopy helps diagnose the problem and, in most
instances, the treatment can be carried out using the laparoscopic technique. The situation of the female
with right lower quadrant (RLQ) pain is especially well suited to differentiation and treatment through the
laparoscope. The wide differential diagnosis and high negative appendectomy rate have led many to
adopt diagnostic appendectomy in virtually all females with RLQ pain who would otherwise undergo
appendectomy.

Chronic abdominal/pelvic pain:One of the most frustrating problems for both patient and surgeon is
chronic abdominal pain. In some cases, a barrage of tests leaves both surgeon and patient with no
understanding of the etiology. Admittedly, a large number of these patients will ultimately not have any
identifiable organic disease; however, when all noninvasive tests have failed to detect any disease
process, diagnostic laparoscopy should be considered as a final step to rule out organic disease. In one
prospective study by Wood and Cuschieri, 30% of patients with unexplained abdominal pain had
significant pathology, including unsuspected malignancy.

Infertility:A standard part of the workup for infertility has included diagnostic laparoscopy. The fimbria,
tubes, uterus, and ovaries can be evaluated and the presence of scarring or other abnormalities that
might increase infertility documented. This examination is usually combined with chromotubation, often
using indigo-carmine dye to assess patency of the fallopian tubes. The failure of dye to pass freely may
indicate intratubal pathology, which may contribute to a patients inability to conceive.

Evaluation of an abdominal mass: The presence of an abdominal mass that cannot be adequately
characterized by noninvasive and semi-invasive methods (e.g., US, CT, MRI, flexible endoscopy) may
be readily visualized and identified by diagnostic laparoscopy and biopsy.Not only can the diagnosis
with histology be made using this technique, but the true extent, including involvement of adjacent
structures, of the mass can also be established.

Liver disease: Diagnostic laparoscopy with laparoscopic biopsy is indicated for cirrhotic patients when
a standard biopsy is not diagnostic or is undesirable (e.g., small liver, large- volume ascites).Patients
with advanced liver disease may be more prone to hemorrhage following biopsy. However, during
laparoscopy, directed hemostasis can be applied to any bleeding biopsy site using electrocautery or
other hemostatic technique.

Liver tumors:Evaluation of primary or secondary hepatic malignancies may be improved with

laparoscopyas 80% to 90% of these lesions are at the surface of the liver and two- thirds of the livers
surface can be visualized with the laparoscope. Laparoscopic biopsy is particularly helpful when hepatic

239
 neoplasm is suspected and blind percutaneous biopsy is negative. When surgical resection is a
therapeutic option, laparoscopy may reveal small (less than 2cm) satellite lesions that might not be
detected using other modalities.

Ascites: When the etiology of ascites remains elusive; laparoscopy may prove helpful, especially when
the ascites are secondary to tuberculosis or carcinomatosis.

Tumor staging: Laparoscopy can be useful in helping to stage several malignancies, including
lymphoma, pancreatic,gastric, and esophageal cancer.

Second-look post-treatment evaluation: Several authors have espoused the utility of laparoscopy to
detect occult disease post-treatment with chemotherapy or radiotherapy.This added information has
allowed clinicians to alter a patients treatment protocol in attempts to eradicate the residual disease.

Sepsis
Unexplained Acidosis
Clinical, laboratory, or radiologic suspicion for an intra-abdominal process without a clear diagnosis
Fever and/or leukocytosis in an obtunded or sedated patient not explained by another identifiable
problem such as pneumonia, catheter sepsis, urosepsis
Unexplained abdominal distension
Equivocal evidence of fascial penetration on local stab wound exploration
Questionably tangential gunshot wound and with potential fascial penetration
Miscellaneous Other indications in which laparoscopy may prove useful include fever of unknown
origin, critically ill patients with suspected abdominal pathology, obscure gastrointestinal bleeding,
trauma, and second look after reconstruction/ resection for mesenteric ischemia.

Contraindications
Absolute Contraindications
o Known Ruptured Diaphragm: Insufflation of the abdomen of patients with diaphragmatic
ruptures may lead to tension pneumothorax and consequent hemodynamic and respiratory
deterioration. Utilizing alternatives to pneumoperitoneum can eliminate these adverse effects.
o Hemodynamic InstabilityA patient who is so severely sick or injured that hemodynamic
reserves are exhausted should not undergo laparoscopy to find the source of the problem. The
added hemodynamic changes induced by pneumoperitoneum along with the increased delay
invoked by laparoscopy are unacceptable in a hemodynamically compromised patient. An
expeditious laparotomy and correction of the problem should be performed without delay.

Relative Contraindications
o Previous abdominal surgery,
o Morbid obesity,
o Irreducible external hernia,
o Lack of technical or staffing support,
o Immediately postoperative
o Tense, distended abdomen.
o Mechanical or Paralytic Ileus
o Uncorrected Coagulopathy
o Generalized Peritonitis
o Severe Cardiopulmonary Disease
o Large Hiatal Hernia Large hiatal hernias
o Abdominal Wall Infection

Instrumentation
Diagnostic laparoscopy requires few instruments. It is important for the surgeon to be familiar with these
instruments and their availability. For safe DL, the basic instruments include a 0 or angled laparoscope, monitor,
two trocars, manipulating instruments, a light source and cord, insufflator with appropriate tubing, and often a
syringe or suction setup. These instruments should be stored on one portable cart that can be easily accessed
and transported to the location where it is needed. More recently, mini-laparoscopic instruments have become
increasingly popular, especially in the office or trauma bay. These instruments are 1 to 2 mm in size, fit through
specialized miniports, and can even be placed under local anesthesia. An additional advantage of the mini-
instruments is that the trocars can easily be repositioned multiple times with minimal morbidity to the patient.

Telescope
The quality of the visual image is of utmost importance to the laproscopic surgeon. These scopes are available in
0, 30, and 45 lenses. The 45 scope provides the most versatility as it allows one to see around corners and
underneath structures. Diagnostic laparoscopists must be familiar with its use and manipulation. A 0 scope is
sufficient to provide the surgeon with adequate information pertaining to further care of the patient.

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In addition to having different angles, the scopes now come in different sizes. The most commonly used scope is
the 10-mm scope; 5-mm and 2-mm scopes are available that provide an image that is similar but not equal to that
of a 10-mm scope. Smaller instruments allow for fewer anesthesias and less discomfort to the patient. As optics
move toward digitalization, the images from the smaller scopes will improve.

Camera
The camera is as important as the telescope. Three- chip cameras are recommended, although a single-chip
camera can be used at the loss of significant resolution. The cameras are designed to fit with the different size
scopes. The cameras are also improving in resolution as digital technology advances.

Monitor
The monitor screen allows a two-dimensional projection of the image so that all who are involved in the
procedure can see what the surgeon is seeing. The monitor is the third piece in the image circuit following the
scope and camera. All three components must provide adequate resolution so the surgeon can effectively
operate under clear visualization. The monitors come in different sizes and with different resolutions. The screen
must be at least 10 in. in diameter so that it can be observed comfortably from a distance of 3 to 4 feet. A high-
resolution monitor is preferred to make the image as accurate as possible. The quality of the picture on the
screen is important, particularly when assessing patients for intestinal ischemia. A slight aberrance in the quality
or coloring of the picture can lead to a misdiagnosis. Additionally, the monitor allows for teaching and can be
used to videotape the case or capture still photos for documentation on the chart.

Trocars
For DL, generally only two trocars are required. One 2-, 5-, 10-, or 12-mm port is used for introduction of the
scope, depending on its diameter. Another 2- or 5-mm trocar is used as a blunt-tipped manipulating instrument.

Light Source
Traditionally, a bright light source such as a xenon 300V light is necessary to transmit light through the camera to
provide adequate visualization in the abdomen. One must also have a light cord to connect the source to the
scope.

Insufflator
One can use the Veress needle (in the virgin abdomen) or the Hasson trocar (surgeons preference, or in patients
who have undergone previous surgery) to provide access to the abdominal cavity for peritoneal insufflation. CO 2
insufflation is the gas of choice for DL. Virtually any system can be used to obtain a intra-abdominal pressure of
12 to 15 mmHg. However, patients who are awake during the procedure better tolerate lower pressures of 8 to 10
mmHg and usually provide adequate visualization.

Laparoscopic Instruments
A limited number of laparoscopic instruments are desirable but not all are necessary; these can be 5-mm or 2-
mm instruments. The instruments one might need include blunt-tipped, atraumatic grasping forceps, blunt
probes, biopsy forceps, peanuts or Kittners, and biopsy needles. It also may be helpful to have an instrument
for suction, In general, instrumentation that is disposable may be easier to maintain and stock.

Anesthesia
General or local anesthesia can be used. Less insufflation combined with local anesthesia can be used in
patients with a contraindication to general anesthesia or if the procedure is being performed as an outpatient.

Laparoscopic Technique
The preferred initial entry site into the peritoneal cavity is the umbilicus. The Veress needle or Hasson technique
can be used, depending on the history of previous surgery or the preference of the surgeon. Once the abdomen
is insufflated, the scope is inserted. Inspection of the abdomen is carried out in an orderly fashion. All four
quadrants are inspected to look for any gross abnormalities. The presence of fluid is sought in the pelvis and in
the right and left paracolic gutters. If fluid is found, it is aspirated and sent for Gram stain and culture. A second
trocar is ideally placed below the right costal margin (or in an area free of intraperitoneal adhesions) under direct
visualization lateral to the rectus sheath for careful manipulation of intra-abdominal structures.
It is helpful if the patient table or bed used for the procedure can be placed in Trendelenburg or reverse
Trendelenburg and rotated from side to side to use gravity so one can easily see all organs. If the patient is
awake, the surgeon can ask the patient to move from side to side to further visualize the right and left paracolic
gutters.

It does not matter where in the abdomen one begins exploration as long as inspection is done systematically.
One of the most common causes of intra-abdominal pathology in the intensive care patient is acalculous
cholecystitis.The gallbladder should be carefully inspected and lifted by placing a blunt instrument under the
gallbladder or gingerly grasping it with atraumatic graspers so as not to injure the organ; this allows some tactile
sense to determine if the gallbladder is distended or edematous. Additionally, one should inspect the liver, a
portion of the duodenum, and the stomach. Next, the right lower quadrant, the appendix, and the cecum are

241
visualized. It is sometimes helpful to rotate the patient to the left to more adequately view these structures. The
patient can then be flattened and placed in Trendelenburg position to view the pelvic structures. If one is
evaluating the pelvis, it is helpful for the patient to have an empty bladder, especially at the time of trocar
placement, which can be achieved by having the patient void prior to the procedure or by placing a Foley
catheter. The camera is slowly moved around the peritoneal cavity to allow thorough inspection of all quadrants.
The small bowel, colon, spleen, and stomach should be visualized. If necessary to run the small bowel, a third
trocar is placed. The ileocecal valve is identified and the small bowel is inspected carefully by progressing
proximally to the ligament of Treitz. Using this technique, the retroperitoneal structures cannot be inspected
completely; one should keep this in mind.

At the end of the procedure, the abdomen should be completely desufflated to minimize postoperative shoulder
pain. The trocars are removed, and the scope site and any incisions greater than 5mm should be closed at the
level of the fascia. The skin can be approximated using staples or sutures.

Laparoscopy in the Trauma Patient

The use of diagnostic laparoscopy in the trauma population is controversial. Concern regarding the use of
laparoscopy in trauma revolves around the equipment costs, availability, setup time, and potential complications
of pneumoperitoneum including gas embolus and pneumothorax. Initially, laparoscopy required general
anesthesia and the use of an operating room. With the advent of mini-laparoscopic instruments, this procedure
can be performed in the trauma bay under local anesthesia by a skilled operator. Thus, the procedure is not
much more invasive than a diagnostic peritoneal lavage.Diagnostic peritoneal lavage (DPL) is the gold standard
diagnostic modality for intra-abdominal trauma, although computed tomography (CI) scan and ultrasound are
becoming increasingly popular. DPL is limited, however, because it is nonspecific and cannot identify the type of
injury or degree of injury to organs. The indications for diagnostic laparoscopy in trauma are similar to the
indications for a DPL, including Glasgow Coma score of 13 or less neurological deficit, equivocal abdominal
examination, unexplained episodic hypotension (systolic BP < 90), factors precluding reliable and timely follow-up
examination, or equivocal fascial penetrance in penetrating trauma.A nontherapeutic laparotomy rate as high as
20% has been reported following a positive DPL.If a patient has a positive DPL, laparoscopy can be used as an
adjunct to define the injury as one that is minor and can be managed nonoperatively versus one that requires
exploratory laparotomy. Thus, the number of nontherapeutic laparotomies can be reduced. The same holds true
for the patient who has positive or equivocal findings on a CT. Laparoscopy can detect a diaphragmatic injury
that would not be seen on CT scan or by DPL.One may be able to identify a hollow viscus injury that may not
have been clearly recognized on CT or by DPL. The utility of DL applies to both blunt and penetrating trauma.

A word of caution: one must recognize the limitations of laparoscopy in evaluating the retroperitoneum. Another
diagnostic modality is necessary to evaluate this space. Computed abdominal and pelvic tomogram is the gold
standard.

DL is helpful but cannot replace laparotomy in the trauma situation. However, it may aid in identifying those
patients who have positive findings on CT, ultrasound (US), or DPL but can be spared a nontherapeutic
laparotomy. Gazzaniga et al. published a series of 37 trauma patients who underwent emergency diagnostic
laparoscopy. Nontherapeutic laparotomy was avoided in 10 (42%) of 24 patients with blunt trauma.In a
prospective analysis of 182 diagnostic laparoscopies performed in hemodynamically stable trauma patients with
equivocal abdominal exams, negative laparotomies were avoided in a large group of patients with stab wounds,
gunshot wounds, and blunt trauma on the basis of laparoscopic findings.A large retrospective multicenter series
on the use of laparoscopy in penetrating trauma reported avoidance of laparotomy in 54.3% of patients based on
laparoscopic findings; 26 patients also had therapeutic procedures performed laparoscopically. The avoidance of
laparotomy in a patient may lead to a quicker recovery.17

Laparoscopy in the Emergency Room

Diagnostic laparoscopy can be helpful in the emergency room setting for a young woman with right lower
quadrant pain, to rule out appendicitis in an equivocal exam, to rule out intestinal ischemia, and sometimes to
evaluate an acute abdomen. This procedure can be diagnostic and therapeutic.
A limiting factor in the use of DL in the emergency department is the availability of equipment and skilled
personnel. Ultimately, exploratory laparotomy remains the gold standard.

The literature on the use of laparoscopy for the outpatient with the acute abdomen is sparse. One interesting
paper worthy of note reviews the use of laparoscopy in the pregnant patient with an acute abdomen at a single
institution. Laparoscopy identified 34 patients with symptomatic biliary disease, 5 with appendicitis, and the rest
with bowel obstruction or pelvic mass. Twenty-three patients required surgical intervention during their
pregnancy, of which 15 were done laparoscopically. Women were operated during all trimesters with no
morbidity.DL can also be helpful in the non-pregnant patient in diagnosing appendicitis versus a gynecological
process.

Laparoscopy in the Intensive Care Unit

The critically ill patient can be a diagnostic challenge to the surgeon when called upon to rule out an intra-
abdominal process. Intra-abdominal complications in the critically ill are not very common, but when they do

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occur, they are associated with high morbidity and mortality. There are very few reports describing the use of
diagnostic laparoscopy in this population. Those who have used DL in the ICU have found it to be very useful in
terms of high diagnostic value with minimal morbidity. Often these are patients with multisystem organ failure,
and little help is provided by history and physical examination. Open exploration provides high risk with unknown
gain to the patient. The scenario is often the following: A patient is admitted to the intensive care unit after
coronary artery bypass grafting or myocardial infarction with a rocky hospital course. Then, the patient develops
fever of unknown origin, abdominal distension of unknown etiology, or unexplained acidosis. They appear to have
slight abdominal tenderness on physical exam; however, due to sedation or their illness, they are depressed
neurologically and are unable to provide one with a reliable exam. The differential diagnosis includes
cholecystitis, appendicitis, and intestinal ischemia (Table 1). The key to helping these patients who are so
critically ill is to make the diagnosis of an intra-abdominal process as early as possible in its course. In the ICU
population, there is usually a delay in the decision to operate for several reasons, including reluctance to operate
in the absence of a definite diagnosis, fear of the harmful physiological effects of a negative laparotomy,
unrealistic faith in antimicrobial therapy, and a delay in carrying out special diagnostic investigations.DL provides
one with a minimally invasive way to accurately and quickly diagnose or rule out an intra-abdominal process.
Because DL is minimally invasive, it allows one to avoid all delays and proceed with treating the patient in a
timely fashion.

A thorough review of the literature reveals very little published experience with diagnostic laparoscopy in critically
ill patients. The groups that have evaluated DL in critically ill patients have found it to be a useful diagnostic
technique, which the patients tolerated well.

Table 1: Differential diagnosis of abdominal process in critically ill patients necessitating diagnostic
laparoscopy.
Acalculous/calculous cholecystitis
Gangrenous bowel
Bowel/mesenteric ischemia
Perforate diverticulitis
Perforated peptic ulcer
Other perforated viscus
Acute appendicitis
Pancreatitis
Bowel obstruction
Intra-abdominal hemorrhage

Brandt et al. have presented two studies on this topic. One reviews 9 trauma patients who are in the ICU setting
and are suspected of having acalculous cholecystitis. Four patients had positive studies, and 5 patients had
negative studies, which spared them a nontherapeutic laparotomy.In the study of medical/surgical patients in the
ICU, 25 patients underwent DL with 12 positive and 13 negative laparoscopic explorations. In this study,
laparoscopic findings led to a change in management in 9 patients, earlier exploration in 4 patients, and
avoidance of laparotomy in 5 patients. DL led to a change in therapy 40% of the time.Bender and Talamini also
evaluated the role of DL in ICU patients, noting that DL provided a surgeon the ability to accurately make a
diagnosis without any unnecessary diagnostic delays.Thus, DL can be useful in diagnosing intra-abdominal
processes in critically ill patients. However, one must realize the limitations of this diagnostic modality. The
benefits of DL are that a definitive diagnosis can be established at the bedside and that some patients are spared
a nontherapeutic laparotomy and its associated sequelae.

Laparoscopy in the out patient department

In the OPD setting, laparoscopy is currently primarily performed by gynecologists. The procedure is usually
performed using mini-laparoscopic instruments under local anesthesia. Patients tolerate the procedure well, and,
in cases of undiagnosed abdominal pain, the patient can direct the surgeon to the point of maximal pain or
tenderness.OPD DL has been described as useful in evaluating patients for carcinomatosis, endometriosis,
chronic pelvic pain, and ovarian cancer. Some groups have shown this to be very helpful in diagnosis of various
pelvic processes outside the operating room setting. Office-based sterilization has become commonplace.
Schnepper reported 810 sterilizations attempted in the office under local anesthesia with 808 successes. The
only complication was wound infection in 3 patients.

Comparison of Diagnostic Laparoscopy to Other Diagnostic Modalities (Table 2)

Brandt et al. retrospectively reviewed the accuracy of DL compared to CT scan, ultrasound, and MRI (Table). Not
all patients had all the diagnostic studies. Results by DL were compared to findings at exploratory laparotomy or
autopsy. Overall, DL is 96% sensitive, according to this review.In Table, the advantages of DL are compared to
the other diagnostic modalities.The gold standard remains laparotomy, but because DL appears to be equally
effective in a trained persons hands, the minimally invasive technique is the less morbid diagnostic test for the
patient.

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Walsh et al. prospectively compared DL to DPL in accuracy of diagnosis and time of procedure. In comparison to
diagnostic peritoneal lavage, DL was superior in providing a diagnosis and defining the need for further
exploration. Laparoscopy required an average of 19min and DPL took 14min. Therefore, in experienced hands,
laparoscopy can provide an accurate diagnosis in a timely fashion.

Table 2: Different diagnostic modalities to evaluate the abdomen.

Investigations Advantages Disadvantages
Diagnostic Inexpensive Invasive
peritoneal Easy to perform Nonspecific
lavage Expeditious Cannot identify type of injury
Transportable Cannot identify severity of injury
Few complications Not reliable for diphragm or retroperitoneal injuries
Sensitivity >95% High false-positive rate
Determines character of fluid High nontherapeutic laparotomy rate
Computed Noninvasive Expensive
tomography Localizes site of injury Need skilled technician
Best for solid organ injuries Time consuming
Best for retroperitoneal injuries Availability
May miss bowel injuries
Ultrasonography Noninvasive Less sensitive than CT
Easy to perform Large learning curve
Expeditious Availability
Transportable
May miss bowel injuries
Cannot localize injury
Unreliable in obese patients
Diagnostic Accurately localizes injury Expensive
laparsocopy Demonstrates active bleeding Invasive
Localizes source of bleeding Time consuming
Best for diaphragm injuries May miss retroperitoneal injuries
Can be therapeutic May need anesthesia
Decreases nontherapeutic Gas embolism
laparotomies (about 25%) Tension pneumothorax if diaphragm injury present
Difficult to quantify blood volume

Complications

Complications

General Specific

During Procedure
Due to
Pnuemoperitoneum
Due to any
surgery or
Anaesthesia
During Access

Veress Needle Insertion: The viscera that is most likely to be injured during Veress needle insertion is
the small bowel. The incidence of bowel injury is suspected to be greater than that reported. Due to the
small needle size and the proximity of any injury to the eventual camera site, these injuries may not be
noticed intraoperatively. Indeed, because of the small size of the needle, some of these injuries may
resolve without need for repair. Loffer and Pent reported a rate of visceral perforation at 0.67 in
1000,and Mintz reported a rate of perforations specifically associated with Veress needle insertion of
0.05 in 1000.Querleu et al. quoted a rate of 0.4 per 1000 cases of visceral injury,and roughly half of
visceral injuries were diagnosed during the laparoscopic procedure.

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 Trocar Injuries: Devastating complications of trocar (i.e., major vessel or visceral injury) should only
occur with blind insertion either directly or after creation of pneumoperitoneum with a Veress needle.
The rates of vessel injury directly related to trocar insertion were reported by Mintz at 0.18 per 1000, and
Bergqvist and Bergqvist reported a rate of 0.01 per 1000. Bowel injuries are also a problem with trocar
insertion. The rates of visceral injury caused specifically by the trocar were reported by Mintz at 0.26.
Nuzzo et al. reported that the highest rate of complications is associated with the insertion of the Veress
needle and trocar.They presented data from nine major studies of laparoscopic cholecystectomy
between 1991 and 1996 involving more than 160,000 patients. They concluded that the 0.05% to 0.2%
mortality rate was due to Veress needle or trocar insertion. At least half of the visceral injuries (0.1%
0.4% total) were also related to the Veress needle or trocar. Overall, the incidence of bowel and
vascular complications due to the Veress needle technique is between 0.63 and 0.8 per 1000.

Hasson Insertion: Although considered by many surgeons as considerably more safe than Veress
needle insertion, the Hasson technique, published by Hasson in 1971,may also cause specific
complications. Hasson described his method for open insertion of the trocar, thereby (1) guaranteeing
pneumoperitoneum and (2) avoiding the dangers described of blind trocar insertion. By dissecting down
to and suturing to the fascia, the peritoneum is exposed, and safe placement of a blunt trocar is
facilitated. Perone confirmed the usefulness of this technique in 585 patients, of whom 173 (29.5%) had
undergone previous abdominal surgery and, therefore, had the potential of viscera adjacent to the
anterior abdominal wall.No major complications (major vascular injury or bowel injury) were reported.
Lafullarde et al. also reported their experience with the Hasson technique.In 802 laparoscopies, they
reported no major vascular or visceral injuries.

Procedural Injuries: Injuries during the procedure are varied and numerous. Injuries to the vascular,
alimentary, and urinary systems are the most common and occur from a number of mechanisms: direct
cut or puncture; thermal injury secondary to cautery; crush injury from graspers; and traction injuries.
Injury to solid organs can also occur from similar mechanisms. Much attention has been placed on
potential cautery injury, both primary and secondary from arcing or poor instrument insulation. However,
according to Levy et al. many of the injuries formerly ascribed to cautery burn may be related to the
insertion of trocars.

Pneumoperitoneum Complications: Carbon dioxide (CO2) is the gas most commonly used to
establish pneumoperitoneum. Pneumoperitoneum with CO 2 induces several well characterized
physiological responses.

o CO2 Absorption: As the rate of absorption of CO2 across the peritoneum overcomes the ability
of the respiratory and the buffer systems to compensate, the patients PaCO 2 rises; this is
reflected in the end-tidal CO2, which should be measured in every patient. In patients with
limited respiratory reserve, the PaCO 2 may be measured directly with arterial blood gas
measurements intraoperatively.
o Arrhythmia:Up to 20% of patients experience cardiac arrhythmias from the CO 2
pneumoperitoneum.The most common dysrhythmias are tachycardia, premature ventricular
contraction, and bradycardia; most are transient and do not lead to clinical instability.
o Cardiac Output: Stroke volume, and subsequently cardiac output, may be diminished by
severe hypercarbia, particularly with high intrabdominal pressures or high altitudes. The high
intrabdominal pressures may result from insufflator malfunction or incomplete muscular
paralysis.
o Hypotension is thought to result from a combination of myocardial depression from acidosis
and decreased venous return secondary to venous compression.
o Gas Embolism:Carbon dioxide is a diffusible gas. As a result, when small amounts of CO 2
enter the bloodstream either from absorption from the peritoneal surface or from direct injection
into the circulation, minimal physiological consequences result. However, when larger amounts
of CO2 enter the vasculature, a gas embolism syndrome and potential fatality result.
Fortunately, the incidence of gas embolism during laparoscopy is rare, between 1 and 4 per
65,000 laparoscopies.Unexplained hypotension, change in cardiac rhythm, new heart murmur,
and increased end-tidal CO2 suggest CO2 embolism. Hypoxia, pulmonary hypertension, and
right ventricle obstruction may result, which may lead to right ventricular failure. Treatment
consists of immediate release of pneumoperitoneum, positioning the patient in the head down,
left-side down position, aspirating the right ventricle through a central line, and increasing FiO 2
to 100%.
o Pulmonary Complications:During laparoscopy, several respiratory changes result, most of
which are caused by either the absorption of carbon dioxide or pressure from the
pneumoperitoneum. Both functional residual capacity (FRC) and forced expiratory volume
(FEV) decrease as much as 23%.Atelectasis is present post-laparoscopy in as many as 50% of
patients. Pressure and stretching of the diaphragm causing diaphragmatic dysfunction is now

245
 implicated as a possible cause.

In the hand of the experienced laparoscopic surgeon, the complication rate and the mortality rate should be quite
low. One review of more than 46,000 cases reported a mortality rate of 0.054%, which compares favorably with
the mortality rate of other invasive interventions.

The application of laparoscopic technique has revolutionized the role of the laparoscope in general surgery and
led to the rapid application of laparoscopic techniques to a wide range of general surgical problems. The result is
that diagnostic laparoscopy is quickly replacing diagnostic laparotomy for many disease processes and patient
presentations.
Table 3: Indications for conversion to open procedure.
1. Complication not amenable to laparoscopic control/repair
Massive bleeding
Complex enterotomies
Cystotomy
Ureter injurye.
Other organ injury that cannot be assessed adequately
2. Lack of visualization
Bloody field
Anatomic details unclear
Retraction problems
Exposure difficulties
3. Instrumentation problems
Obese patient presenting trocar and instrument length problems
Instrument angle

Conclusion
When called upon to evaluate a critically ill patient, a patient with abdominal pain in the office, patients with
equivocal abdominal findings in the emergency department, or patients suffering abdominal trauma, a surgeon
must appropriately select from the diagnostic tools available to quickly and accurately evaluate the patient.
Diagnostic laparoscopy provides a minimally invasive method to determine the presence of an intra-abdominal
process effectively and accurately. The patient is subjected to minimal morbidity with a precise diagnosis in most
cases.

As technology advances, imaging is improving, and 2- mm scopes have resolution approaching that of 10-mm
scopes. Placing a mini-laparoscope is similar to a needle biopsy through the abdominal wall. DL with the
standard-size laparoscopic instruments currently available is minimally invasive when compared to the alternative
of exploratory laparotomy. DL allows avoidance of multiple diagnostic tests that can be expensive, lack
sensitivity, and are not therapeutic. Furthermore, this procedure can be performed at the bedside in the trauma
bay, emergency department, intensive care unit, or office.

Another advantage of DL is that it is very cost effective. DL is performed efficiently provided one has the proper
equipment and well-trained personnel. DL allows the avoidance of several less sensitive but more expensive
radiologic tests. DL can be shown to be cost-effective when considering the ability to make a rapid and accurate
diagnosis that allows early intervention while avoiding other diagnostic studies and unnecessary laparotomy.
Additionally, it is well known that hospital stay after laparoscopy is often shorter than after laparotomy.

Unfortunately, there are also some disadvantages to this diagnostic modality, particularly in the intensive care
unit. These patients are already very sick and often expected to have poor outcomes regardless of the
intervention. Nontherapeutic laparotomies can be avoided in this population with DL. DL is accurate, but thus far
has not been shown to improve the overall survival or outcome of these patients. Additionally, not all institutions
have the resources available to evaluate the patient with DL. Furthermore, DL is an invasive procedure with
inherent potentially serious complications.

In conclusion, laparoscopy can be used in several settings outside the operating room. The procedure is most
often diagnostic and occasionally can be therapeutic. In the diagnostic capacity, laparoscopy can be very helpful
when the findings are positive. One should always interpret negative findings with caution even though DL is
quite specific. As laparoscopic instruments become smaller and technology more portable, these procedures may
become increasingly applicable. Laparoscopy should be used whenever indicated with the expectation of having
accurate results in a timely fashion.

Further Reading and References

1. Davis CJ, Filipi CJ. A history of endoscopic surgery. In: Arregui ME, et al. (eds) Principles of Laparoscopic
Surgery: Basic and Advanced Techniques. New York: Spinger-Verlag, 1995.

246
2. Khaitan L, et al. Diagnostic laparoscopy outside of the operating room. Semin Laparosc Surg 1999;6(1):3240.
3. Guidelines for diagnostic laparoscopy. Society of American Gastrointestinal Endoscopic Surgeons (SAGES).
Surg Endosc 1993;7(4):3678.
4. DiamondMP.AManualofClinicalLaparoscopy.NewYork: Parthenon, 1998.
5. Khaitan L. Bedside Laproscopy. In:MacFadyen BV, et al. (eds) Laparoscopic Surgery of the Abdomen. New York:
Spinger-Verlag, 2003.
6. McMahon RL. Principles of Diagnostic Laparoscopy. In: MacFadyen BV, et al. (eds) Laparoscopic Surgery of the
Abdomen. New York: Spinger-Verlag, 2003.
7. Conlon KC, Toomey D. Diagnostic Laparoscopy. In: Fischer JE, et al. (eds) Mastery of Surgery. London:
Lippincott Williams & Wilkins, 2007.

Ergonomics in laparoscopic surgery

R. S. Mohil, Sharmistha Bhattacharyya

It was a landmark in the history of surgery when in 1901, Kelling [1] introduced a visualising scope for the first
time in the peritoneum of a dog. However, it took another eight decades for a perfected laparoscopic technique to
be implemented, when in 1987, for the first time, Mouret [2] performed a successful laparoscopic
cholecystectomy.

Along with the advances came the drawbacks. The drawbacks are majorly twofold. In the firstly the surgeon
experiences the ill effects from the surgery, and secondly, the patient is the victim. There have been multiple
reports of carpal tunnel syndrome, eyestrain and cervical spondylosis.[3] Reports of thenar neuropathy have
arisen due to use of awkward thumb grips in case of laparoscopic pistol-grip instruments.[4]

Patients too have been found to be experiencing a lot of inconvenience with greater post-operative pain at port
sites and other complications. Simple application of understanding of the physics and functioning of the whole
event can help avoiding mistakes leading to these poor outcomes.

Herein we understand the principle of Ergonomics applicable to the field of laparoscopy as much as any other
surgical expertise.

WHAT IS ERGONOMICS?
The term ergonomics is derived from the Greek words "ergon" meaning work and "nomos" meaning natural laws
or arrangement. Ergonomics is "the scientific study of people at work, in terms of equipment design, workplace
layout, the working environment, safety, productivity, and training". Ergonomics is based on anatomy, physiology,
psychology, and engineering, combined in a systems approach.

The term was formally defined in 1949. In simple words, it is the science of best suiting the worker to his job, or to
make the setting and surroundings favourable for the laparoscopic surgeon. The importance of ergonomics in the
setting of laparoscopy cannot be over-emphasised. Studies have shown that correct ergonomics can reduce
suturing time.[5] Pressure-related chronic pain among surgeons has been shown to be relieved by the use of
ergonomically designed products.[6]

Ergonomic challenges during laparoscopy

At the outset it is helpful to identify the potential problematic areas in the practice of minimal access surgery that
pose unique ergonomic difficulties not faced by non-laparoscopic surgeons.

a) Lack of tactile sensation: While learning the skills associated with open surgical procedures, as residents, we
are trained to "see" with our hands as well as our eyes. We train our hands towards achieving this dual job in an
attempt to reach the level of dexterity required to be competent. This constitutes the tactile feedback which is
conspicuously lacking when one transitions from performing open procedures to laparoscopic surgeries. The long
graspers manoeuvered through the trocars get substituted for the surgeon's hands and this definitely reduces the
efficiency and increases the time of the dissection.[7]

b) Decreased degree of freedom of movement: Open surgery has a high degree of freedom and surgeons work
in line with visual axis. There is a three-dimensional direct vision and direct tactile feedback. While during
laparoscopic surgery there is a two-dimensional vision and loss of depth perception to some extent. Current
handheld laparoscopic instruments offer only 4 degrees-of-freedom of movement (rotation, up/down angulation,
left/right angulation, in/out movement). Additionally, there is fulcrum effect with tremor enhancement. [8].
According to Struges, Wright and Falk, an increase in degree of freedom from 4 to 6 increases dexterity by a
factor of 1.5.[9]

c) Decoupling of the visual (monitor) and motor axes: Visual orientation changes with the loss of depth
perception due to indirect visual input and also the loss of peripheral binocular vision caused by the limited

247
viewing spectrum offered. One of the most significant cognitive challenges for the general surgeon in his
transformation into a laparoscopic surgeon is to overcome the spatial separation of the axis of vision and the axis
of the physical aspect of the procedure. The surgeon does not get a chance to directly look at the instruments or
his hands and also at the field of surgery at the same time. He has to learn to adapt to the difficulty of combining
the two functions into the same-channelled approach in order to dexterously manipulate the tissues without direct
contact. Studies have shown that working in separate coordinate systems decreases performance, leading to
higher rates of error in the procedure.[10]

d) Assumption of relatively static posture during major part of the procedure which, ergonomically speaking,
contributes to the inefficiency. Great concentration and skill is required for performing the complex laparoscopic
surgeries. Hence, it has been observed that the operating surgeon assumes a more static posture during
laparoscopic procedures compared to erstwhile open approach. These static postures have been demonstrated
to be more disabling and harmful than dynamic postures are since muscles and tendons build up lactic acid and
toxins when held for prolonged periods in same postures.[11-13]

Sensorial ergonomics (manipulations and visualisation) improve precision, dexterity, and confidence, while
physical ergonomics provide comfort for surgeon (Figure 1). Together, these two elements of ergonomics
increased safety, have better outcome and reduce the stress.[14]

Figure 1: The surgeons mental and physical reserve during laparoscopic surgery is significantly reduced compared to open
surgery.

e) More Clutter Due to increase in the number of equipments, tubes and cables in the operating room [15] it
creates physical hazards for traffic in the operating room. The multitude of tubes and cables creates a spaghetti
of connections in the operating field that decreases the efficiency of instrument handling, positioning, and
exchanges [16]. Using a ceiling-mounted boom system can make the floor clutter free.

f) Dark Room The operating room lights being turned off during laparoscopic surgery rest of the team must work
in relative darkness. This increases the risk of choosing the wrong instruments and of collision hazards.

ERGONOMICS CONCEPTS IN OT
The goal of proper posture is comfort, efficiency of movement and minimisation of the risk of musculoskeletal
injuries to the operator. The surgeons neck and back should be maintained in a comfortable and upright position
facing forward. To achieve this ideal posture following factors are important.
1. The height of the operating table
2. Position of the visual display (Monitor)
3. Foot pedal location
4. Port placement
5. Related to Instrumentation
6. Surgeon and team position
7. Technical advancements

1. Operating Table height:

As in open surgery ergonomically the angle between the lower and upper arm should be between 90 to 120
degrees or in simple terms at or slightly below the elbow level. The height of the table should be adjusted so as to
achieve this goal. As the laparoscopic instruments are longer and the table is also tilted much more than
conventional surgery, this may require table to be lowered substantially. If this ideal position is not achieved then
body unconsciously compensates it by raising the ipsilateral. This cause shoulder and neck strain if the surgery is
prolonged. If required surgeon need to stand on an elevated platform if its not possible to lower the table below
a certain point. [17] (Figure 2)

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2. Monitor position
The best view for laparoscopy is achieved with the monitor image at or within 15- 40 degrees below the
horizontal plane of the eye.[18, 19] resulting in least neck strain. Standard LCD monitors placed on a low cart
separate from the operating room equipment may be used for best results. It is not advisable to have a "chin-up"
arrangement on the part of the surgeon.[20] Ceiling mounted monitors, large high definition monitors, monitors
with flexible boom, head mounted displays, projection system all have helped in achieving this goal. The second
monitor is essential in operations where surgeons change their ports and positions, and also for assistants to
reduce strain on their neck. (Figure 2)

3. Foot pedal location:

Foot pedals are commonly used during laparoscopic surgery to activate instruments such as the cautery,
ultrasonic shears, bipolar device, or other tissue welding/dividing instruments. Foot pedals, which are often poorly
positioned, demand awkward and unnatural postures and should be avoided in favor of hand controls when
possible. Pedals should be placed near the foot and aligned in the same direction as the instruments, toward the
target quadrant and the principal laparoscopic monitor. Such positioning will permit the surgeon to activate the
pedal without twisting their body or leg. If the surgeon is standing on a lifting platform, the pedal must be placed
at the same level off the ground. A pedal with a built-in foot rest is preferable so the surgeon does not have to
hold their foot in the air or move it back and forth on the floor. If there are two pedals (for different devices), the
surgeon must be careful not to confuse them in the darkness. (Figure 2)

Figure 2: Key elements of the ergonomic laparoscopic surgeon.

4. Port placements
There is a need to know some angles for better understanding of port placement. The three angles i.e.
Manipulation Azimuth and Elevation angles are depicted in Figure 3.

There is no uniform consensus about port placements for advanced laparoscopic procedures. To facilitate
smooth instrument manipulation along with adequate visualisation during laparoscopy, usually trocars are placed
in triangular fashion This is termed as triangulation (Figure 4) in which target organ is placed 1520 cm from the
centre port (used for placing the optical trocar). Generally, the two remaining trocars are placed in the same 15
20 cm arc at 57 cm on either side of the optical trocars. This allows the instruments to work at a 6090
angle[21] with the target tissue and avoids problems of long handle due to too far or too near placement of ports.
Additional retracting ports can be placed in the same arc but more laterally.

Figure 3: The various angles in Laparoscopic surgery

When optical trocar is placed as one of the lateral port trocar, it is called as sectorisation (Figure 4). This is
usually done during appendicectomy when 10 mm trocar is placed in subumbilical region as optical trocar. Two

249
other trocars are placed below these trocars laterally. Sectoring of instruments requires a greater degree of
understanding and experience of the laparoscopic view and significantly different hand-eye coordination. Hence
this should be avoided by beginners.

Manipulation angle should be between 45-75 , Azimuth between 30-45 and elevation around 60.
Manipulation angles below 45 or above 75 are accompanied by increased difficulty and degraded performance
with increased workload by the deltoid and trapezius as well as that of the dominant arm extensor and flexor
groups. [22-24]. Task efficiency was reported be better with equal azimuth angles. Achieving equal azimuth
angles (between scope and instruments) may be difficult in many practical situations, but in principle, azimuth
inequality should be avoided because it degrades task efficiency.

There exists a direct correlation between the manipulation and the elevation angles (Figure 3 ). Wide
manipulation angles necessitate wide elevation angles for optimal performance and task efficiency. When a 30
manipulation angle is imposed by the anatomy or build of the patient, the elevation angle should be also 30 as
this combination carries the shortest execution time.

Figure 4: Port placement to achieve Traingulation - Laparoscopic Fundoplication & Sectorisation in Laparoscopic
Appendicectomy

Another factor that one should consider during trocar placement is that the instrument length. Length is limited so
if trocar is too far from the desired position one has to push abdominal wall towards target organ to gain a few
centimeters. This not only makes these movements less precise but also causes strain on the fingers and hand
muscles. Similarly, if the angle between the target and instrument if too wide or obtuse, manipulation of curved
instrument is very difficult

5. Related to Instrumentation
Equipment related challenges are a major factor in laparoscopic surgery. Nearly half of the 1.3 million instrument-
related injuries that occur in US hospitals each year could be due to poor instrument design.[25]
a. Limited view : While performing minimal access surgery, the surgeon is typically viewing a two-
dimensional video image of the operating field on a television video screen placed at a certain distance
of 48 feet away from the surgeon's eye. Even with the best quality monitoring equipment, the quality
and resolution detail of the image are not comparable with direct visualisation. Binocular depth cues are
also lost and the resolution and quality of the image are less than that with direct viewing [26]. Also
important is the loss of peripheral vision that makes efficient navigation of the larger surgical workspace
(inside the body and outside) more difficult [27]. Surgeons also do not control the direction of view with
their eyes and now must move the laparoscope via a trained assistant or an electromechnical control
device. On the positive side, the 15x magnification and wide-angle view of the optical system lens can
often provide a very detailed view of normally hard-to-see internal anatomy.
b. Use of angulated scopes can help achieve better view of the anatomy in difficult situation. Normally zero
and a 30 scopes are used but more angulation can be used but need orientation on the part of the
surgeon due to limited view of the field. (Figure 5)

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 Figure 5: View and orientation from a zero degree (above) and thirty degree (below) scope.

c. Less Efficient Instruments: Laparoscopic instruments are constrained to work through small ports 3 to
10 mm in size. This results in more complex internal mechanical linkages that decrease the efficient
transmission of force from the surgeons hand to the instrument tip. A typical disposable laparoscopic
grasper transmits the force of the surgeons hand from the handle to the tip with a ratio of only 1:3, in
contrast to a 3:1 ratio with a hemostat [28]. The surgeon must therefore work about 6 times as hard to
accomplish the same grasping task with the laparoscopic instrument [29]. This increase in force
magnifies other problems, such as poor handle design, handles too big for small-handed surgeons, and
other problems.
d. Improperly designed shapes of instruments cause strain on functional areas of the hand Mattern and
Waller[30]. Handle have been designed based on ergonomic criteria. This multifunctional handle fits
only one hand and like a pistol handle. It rests continuously in the half-closed hand, similar to the ''basic
position'' of the resting hand (between the ring and little fingers). The thenar performing an encircling
grip. The longitudinal axis of the instrument is an extension of the forearm's rotation axis. This allows
pronation and supination to be transferred directly to the instrument effector.
e. Limited Instrument Mobility: Laparoscopic technique requires the use of fixed-position entry ports that
limit the surgeon's ability to adjust instrument position and angle to the task at hand. Improperly placed
ports can make an entire operation much more difficult to execute.
f. Instrument exchanges during laparoscopic surgery are laborious and distracting to the surgeon, thus
placing a premium on minimizing exchanges and using multifunction instruments. The latter, when
poorly designed, can be even more difficult to use. For all the above reasons, laparoscopic instruments
are less able to support the surgeons needs than are open surgery instruments. Moreover, these
laparoscopic instruments are generally available in one standard size and hence surgeons of all heights,
builds, and hand sizes work with same ones and the efficacy suffers somewhere along the way.
g. Intracorporeal suturing techniques is the skill-related factors which have a profound impact on the
outcome. These problems are a result of the necessity to suture in odd port positions in the absence of
triangulation, suturing at odd angles to the tissue, suturing in the retroperitoneum and maintaining
tension in continuous suturing while using less efficient instruments. All the above problems associated
with this skillful field of expertise are the specific challenges which laparoscopy presents.

6) OT position of Surgeon and team American or EuropeanLaparoscopic cholecystectomy can be performed in

two different positions; standing on the left side of patients (preferred by Americans) or by standing between the
legs (preferred by Europeans). Both the positions are convenient but it is usually surgeon's preference or habit of
getting adjusted to the position.

SINGLE PORT LAPAROSCOPY

Single port laparoscopy has changed the concept of triangulation. The instruments often cross each other,
making the procedure "counter-counterintuitive". Steerable endoscopes, bent and articulating instrumentation,
magnetic anchorage and guidance systems as well as flexible robotics have been developed to overcome these
difficulties .

ROLE OF ROBOTIC SURGERY

Robotic surgery is ergonomically advantageous as it has 7 degrees of freedom as compared to laparoscopic
hand surgery. This helps one to access deeper areas in abdomen such as oesophagus, pancreas and
retroperitoneum. It also allows placements of ports in shorter arc without instrument interference.

251
TECHNOLOGICAL ADVANCES

HD monitors
In laparoscopic surgery a significant benefit of 16:9 HD monitors would be that the images offer a natural,
panoramic view. In humans, the horizontal field of view is wider than our vertical field of view. For surgeons, this
wider, natural view is less fatiguing during procedures. Additionally, during laparoscopic surgery as surgeons are
viewing full-screen endoscopic images, trocars and hand instruments that normally approach the surgical area
laterally is visible earlier with a 16:9 monitor than they are able to on the 4:3 or 5:4 monitor.

3D laparoscopy
The main advantage is accurate depth perception which is very important for surgeries requiring suturing and a
complex procedure. 3D visualization of depth perception can shorten the learning curve for the surgeons who
used to rely on their experience. The clear image of full HD(1080P) can benefit surgeons who are looking for
small vessels and veins in the organ

The combinations of increased technological complexity along with poorly adapted equipment have led to
increased complaints of surgeon fatigue and discomfort during laparoscopic surgery. Neck pain and spondylosis
has been observed to be a recurring complaint among surgeons in high-volume centres.[31] The other physical
constraints reported are cervical spondylitis, shoulder pain due to abduction of shoulder (chicken wing scapula)
during laparoscopy termed as "laparoscopic shoulder" is frequently seen. Others being backache, hand finger
joint pain, tenosynovitis, burning eyes, stress exhaustion, and hand muscle injury.[32,33]

Better ergonomic integration and understanding ergonomics can reduce physical strain and make the life of
surgeon comfortable in the operating. The reason for the inability of ergonomics to be applied optimally in the
field of laparoscopy are manifold some of which includes : lack of complete awareness among surgeons,
communication gap between surgeons and intrument designers, inadequate knowledge of the potential problems
for the users and the contradictory expert advice which reduces the credibility of ergonomics as a science.

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23. Manasnayakorn S, Cuschieri A, Hanna GB. Ideal manipulation angle and instrument length in hand-
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Troubleshooting Equipment and Procedural Difficulty in Laparoscopic Surgery

Deborshi Sharma, Swati Sattawan

INTRODUCTION
Laparoscopic surgical procedures are becoming common across a broad spectrum of surgical specialties.
However, the introduction of sophisticatedtechnical equipment in laparoscopic surgery has made the
surgicalenvironment more complex. New problems are created due to manmachine interactions during high-
tech operations, thereby increasing the risk of errors or incidents leading to potential adverse events.Technical
problems also cause an increase in operating theatre timeand therefore increase the cost of operative
procedures.Operating rooms are complex environments, which can be over-whelming; however, well-established
protocols, such as the surgicalsafety checklist have measurably reduced (peri)operative risks. 1,2An observational
study by Verdaasdonk et al.who investigated the incidence of technical equipment problemsduring laparoscopic
cholecystectomies revealed that technical failure orinstrument problems can occur in up to 87% of
laparoscopies.The authors concluded that improvement and standardization ofequipment in combination with the
preoperative usage of a checklistwill help to prevent laparoscopy associated problems. 3,4 Given the multitude of
potential sources for equipment failure, a systematic approach to equipment troubleshooting is key. In this
section, we discuss some of the most common equipment problems that the surgeon may experience in the
operating room and offer a methodical approach to address these issues.

LAPAROSCOPIC INSTRUMENTS
General considerations include the size of the operating room, location of doors, outlets for electrical and
anesthetic equipment, and the procedure to be performed. Time spent in positioning the equipment and operating
table is well spent. An equipment checklist helps to ensure that all items are available and minimizes delays once
the patient has arrived in the operating room. Most of the equipment and instruments listed here will be needed
for operative laparoscopy.

a. Anesthesia equipment
b. Electric operating table with remote control if available
c. Two video monitors
d. Suction irrigator
e. Electrosurgical unit, with grounding pad equipped with current
f. monitoring system
g. Ultrasonically activated scissors, scalpel, or other specialized unit
h. if needed
i. Laparoscopic equipment, generally housed in a cart on wheels:
i. Light source
ii. Insufflator
iii. Videocassette recorder (VCR), other recording system, tapes

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 iv. Color printer (optional)
v. Monitor on articulating arm
vi. Camera-processor unit
h. C-arm x-ray unit (if cholangiography is planned) with remotemonitor
i. Mayo stand or table with the following laparoscopic instrumentation:
i. #11, #15 scalpel blades and handles
ii. Towel clips
iii. Veress needle or Hasson cannula
iv. Gas insufflation tubes with micropore filter, if desired
v. Fiberoptic cable to connect laparoscope with light source
vi. Video camera with cord
vii. Cords to connect laparoscopic instruments to the electrosurgical unit, with various adapters for all
instrumentsneeded
viii. 6-in. curved hemostatic forceps
ix. Small retractors (Army-Navy or similar pattern) for umbilical
x. Trocar cannulae (size and numbers depend on the plannedoperation, with extras available in case of
accidental contamination)
xi. Laparoscopic instruments
xii. Monopolar electrocautery dissection tools
L-shaped hook
Spade-type dissector/coagulator
xiii. Ultrasonically activated scalpel (optional)

Laparoscope and camera

The purpose of the laparoscope and camera unit is to transmit high-quality images from the surgical field to the
signal processing unit, which relays the images to the video monitor. Traditional laparoscopes have two separate
channels. One channel contains a series of glass rods (known as the hopkins rod lens system that transmit
images from the surgical field to the eyepiece of the laparoscope. 5 The second channel contains light fibers,
which transmit light from an external source to the surgical field. Laparoscopes may be straight or angled at the
tip. Straight (0 ) laparoscopes offer a view of whatever lies directly ahead of the laparoscope, whereas angled
(e.g., 30 or 45 ) scopes allow the surgeon to look around structures by rotating the scope. Typically,
laparoscopes are either 5 or 10 mm in diameter and are usually 25 to 30 cm in length. Smaller diameter
laparoscopes, such as 3 mm scopes, are also available, although they tend to be less durable. To transmit
images from the laparoscope to the signal processing unit, a camera is attached to the eyepiece via a coupler. 6

Light source and cable

One of the early limitations of laparoscopic surgery was the need to place the light source in the surgical field,
often at the distal end of the laparoscope. Several types of light sources are used during minimally invasive
procedures today. Halogen (150 watt), metal halide (50 to 270 watt), xenon (300 watt), and, more recently, light-
emitting diodes ( LEDs) are all high-intensity light sources capable of producing quality images on a video
monitor. One of their main differences is their life span. Halogen and metal halide light sources typically last
several hundred hours, whereas xenon bulbs may last up to 500 hours. Despite their classic label as cold light
sources, each of these light sources generates a substantial amount of heat. Temperatures at the tip of the
laparo scope ranged from 140 to 212 F. Evidence of small bowel injury occurred after only 5 seconds of direct
contact between the laparoscope and the bowel.

Camera control unit or signal processing unit

The purpose of the signal processing unit is to transmit the signal from the camera to a variety of end devices,
including printers, recording devices, and, most importantly, the video monitor.

Video monitor
Most traditional video monitors used in the or will accept input from three types of analog signals: composite,
Y/C(super video) and RGB(red, green, blue). However, evenwith the use of RGB signals, the resolution
7
provided by traditional cathode ray tube monitors is somewhat limited (typ-ically 600 lines or less). For enhanced
resolution, including high-definition formats, digital monitors that accept DVI(Digital video interface) and
SDI(serial digital interface) digital signals may be used with high-definition video cameras. These flat-panel
digital monitors, which are alsocapable of accepting analog signals, are often ceiling-mounted displays that are
capable of providing more than 1,000 lines of resolution (nearly twice the resolution of a typical television
image).7

Insufflator and gas supply

The creation of pneumoperitoneum is one of the essential steps of laparoscopic surgery because it distends the
abdominal wall and significantly enhances visualization of intraabdominal structures. One of the first physicians
to insufflate the abdomen was Dr.George Kelling, a german surgeon who is also credited with performing the
8
first laparoscopic procedure in 1901. Interestingly, improved intraabdominal visualization was not one of his
primary goals. Rather, he wanted to arrest gastrointestinal bleeding by injecting large amounts of air into the
9
peritoneal cavity to create extremely high intra-abdominal pressures (50 to 100 mm hg). Shortly thereafter, a

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swedish internist named Hans Christian Jacobaeus used a trocar with a bulb and a one-way valve to manually
insufflate air into the abdomen. He referred to this new procedure as Laparoscopy. Carbon dioxide is currently
the most commonly used gas during insufflation. It is odorless, nonflammable, and highly soluble in blood, which
reduces the likelihood of air embolisms. Although clinically significant hypercarbiaand acidemia can occur,
particularly in patients with cardio-pulmonary comorbidities, most patients tolerate carbon dioxide
pneumoperitoneum without any adverse effects. Although the amount of gas needed to create adequate
pneumoperitoneum varies according to patient size, abdominal wall compliance, and degree of gas leakage,
several liters of carbon dioxide are usually adequate. To maintain pneumoperitoneum throughout a case,
substantially more gas is needed. one report estimated that an average laparoscopic colectomy requires
approximately 110 to 180 l of carbon dioxide. 10

Insufflators alternate between injecting gas every 2 to 3 seconds and monitoring the intra-abdominal pressure. To
address the concern of introduction of infection, insufflation filters composed of mesh with 0.1- to 0.3-micron
pores have been developed. The literature surrounding the effectiveness of these filters is limited. One study
11
published in 1989 reported that rust, dust, and metal filings could be detected on insufflator filters. Another found
12
that the use of a 0.3-micron filter reduced microbial colonization of gas cylinders and insufflators. Given the
theoretical possibilities of contamination and disease transmission, insufflation filters are commonly used today.

Laparoscopic trocars
There are a wide variety of commercially available laparoscopic trocars, with their own specific characteristics. In
general, trocars consist of two different components. The head of the trocar includes a diaphragm to prevent
leakage of gas around the inserted instruments and a port for insufflation. The shaft is the portion that is inserted
through the abdominal wall into the abdominal cavity and can vary in both length and diameter to accommodate
patients with larger abdominal walls and instruments of various sizes. Additionally, all trocars come with an
obturator, which inserts through both the head and the shaft to facilitate introduction of the trocar through the
abdominal wall. The end of the obturator can be bladed (cutting trocar) or non-bladed (noncutting
trocar).Trocar placement is done by either Open method via using Hasson's cannula which was first described in
197413 or by direct puncture method using veress needle.

Laparoscopic Hand Instruments

Nearly all instruments are designed such that the shaft will rotate through 360 of rotation while keeping the
handles stationary. The handles come in a variety of sizes and grip styles and should be trialed to find a set that
provides both comfort and proper ergonomics. Additionally, a variety of ratcheting and locking mechanisms are
available. There are a variety of instruments commercially available, designed for laparoscopic dissection like
Maryland dissector, Babcock grasper, allis grasper, laparoscopic biopsy forceps, needle drivers, scissors,
staplers, clip appliers, probes, sponges, and retractors .

Laparoscopic energy sources

The energy sources used to obtain hemostasis in laparoscopic surgery are similar to those employed in open
surgery. Monopolar, bipolar, and ultrasonic energy sources all come in forms suitable for use in laparoscopic
cases. Bipolar and ultrasonic energy sources have significantly decreased operative times for more complex
laparoscopic cases as larger vessels can now be controlled with these instruments. The problem with this
equipment is direct coupling and capacitative coupling. Ultrasonic shears use mechanical energy rather than
electrical current to seal vessels and divide tissue. The most commonly used devices are the harmonic ACE. It
requires a generator that produces an electrical signal, which in turn is converted into a mechanical vibration at a
frequency of 55,500 hz.

Troubleshooting the difficulties in laparoscopic Surgery

The mostcommon error sources responsible for image quality and technicalproblems in laparoscopic surgery that
should be kept in mind whilefacing an intra-operative technical problem are:
(1) Scope
(2) Operator
(3) Image capture device
(4) Camera head
(5) Light
(6) Cables
(7) Camera console
(8) Monitor

The use of checklists provides a reliable way of dealing with technical problems, but checklists have to be user-
friendly and applicable in the daily routine.In general, all elements of the image chain consisting of
scope,camera head including camera cable, light guide and light source,camera processor, cables and monitor
need to be checked to findthe error source as each component is equally responsible forproducing the picture
and the image produced is only as good as theweakest link. The checklist developed by SAGES(Society of
American Gastrointestinal and Endoscopic Surgeons) and AORN(Association of Perioperative and Registered
Nurses) to aid operating roompersonnel in the preparation of equipment and other duties unique to laparoscopic
14
surgery cases has been shown in table(1).

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Table (1): Minimal Invasive Surgery(MIS) Checklist
1. Pre-patient entry: A. Circulating nurse duties
Parameter Actions
Surgeon preference card Reviewed
OR Table position Correct orientation and weight capacity
Bean bag mattress(if indicated)
Table accessories(eg.leg support, footboard as indicated.
Positioned for fluoroscopy if indicated.
Power sources Connected and linked to all devices
CO2 insufflator Check CO2 volume, pressure and flow
Back up cylinder and accessories in place, Filter for CO 2 unit or
tubing.
Video monitors Position per procedure
Test pattern present
Suction/Irrigation Cannister set
Irrigation and pressure bag available.
Alarms Turned on and audible
Video Documentation Recording media available and operational(DVD, print etc.)

B. Scrub Person Duties

Parameter Actions
Reusable Instruments Check movement handles, all screws present
Check sealing caps
Instrument vents closed
Check cautery insulation
Veress needle Check plunger/spring action
Flush needle and stopcock, saline solution available
Hasson cannula Check valves, plunger and seals
Trocars/Ports Check appropriate size/type
Close stopcocks
Laparoscope Size and type per preference
Check lens clarity
Anti-fog solution or warmed saline for lens cleansing

2. After Patient entry

Parameter Actions
Patient Position Secured to OR table, safety strap on
Pressure sites padded
Arms out or tucked per procedure
Sequential compression device On and connected to device
Electrosurgical unit Ground pad applied
Foot controls Positioned for surgeons access
Power sources (camera, Turned on(on standby)
insufflators, light source, monitor,
cautery, ultrsonics, bipolar)
Miscellaneous Foley catheter(if indicated)
Naso or orogastric tube (bougies if indicated)
Antibiotics Given as indicated

3. After Preparation and Drape

Parameter Actions
Electrosurgical unit Cautery cords connected to unit
Monopolar cautery Tip protected
Ultrasonic or bipolar device Connected to unit
Activated test performed
Line connections Camera cord
Light source(on standby)
CO2 tubing (connected and flushed)
Suction/ Irrigation(Suction turned on)
Smoke evacuation filter connected
Local anaesthetic Syringe labelled and filled with anaesthetic of choice, needle
connected
Fluoroscopy case Mix and dilute contrast appropriately and label
Clear tubing, syringe, catheter of air bubbles, label syringes

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Laparoscopic procedures are inherently complex. Many things can go wrong. The surgeon must be sufficiently
familiar with the equipment to troubleshoot and solve problems. Although few studies have measured the
frequency, etiology, cost, or clinical impact of laparoscopic equipment misuse and malfunction, equipment
problems during laparoscopic surgery are quite common. Fifty-five percent of these incidents were the result of
equipment malfunction related to an equipment defect, improper device setting, or faulty connection. another
study that examined 62 laparoscopic cases concluded that at least one equipment failure occurred in 42% of
15
cases. Human error contributed to nearly half of these failures. Table (2) gives an outline of the common
16
problems, their cause, and suggested solutions.
TABLE(2)
Problem Cause Solution
1. Poor insufflations/loss Carbon dioxide tank empty Change tank
of pneumoperitoneum Open accessory port stopcock(s) Inspect all accessory ports-close
Leak in sealing cap or stopcock stopcock(s)
Excessive suctioning Change cap or cannula
Instrument cleaning channel screw Allow abdomen to reinsufflate
cap missing Replace screw cap
Loose connection of insufflators Tighten connection
tubing at source or at port Replace or secure sutures
Hasson stay sutures loose
2. Excessive pressure Veress needle or cannula tip not in Reinsert needle or cannula
required for free peritoneal cavity Inspect full length of tubing,
insufflations(initial or Occlusion of tubing(kinking,table replace with proper size as
subsequent) wheel, inadequate size tubing, etc.) necessary.
Port stopcock turned off Assure stopcock is opened
Patient is high More muscle relaxant
3. Inadequate Loose connection at source or at Adjust connector
lighting(partial/complete scope Go to "automatic"
loss) Light is on "manual-minimum" Replace bulb
Bulb is turned on Replace light cable
Fibreoptics are damaged Reposition instruments, or switch
Automated iris adjusting to bright to "manual
reflection from instrument Readjust setting
Monitor brightness turned down
4.Lighting too bright Light is on "manual maximum" Go to "automatic"
"Boost" on light source activated Deactivate"boost"
Monitor brightness turned up Readjust setting
5. No picture on Camera control unit or other Make sure all power sources are
monitor(s) components(VCR, printer, light plugged in turned on
source, monitor) not on Cable should run from"video out"
Cable connector between camera on camera control unit to"video in"
control unit and/or monitors not on primary monitor; use
attached properly compatible cables for camera unit
and light source
Cable should run from "video out
on primary monitor to "video in"
on secondary monitor
6. Poor quality picture Condensation on lens of cold scope Gently wipe lens on viscera; use
a) Fogging, haze entering warm abdomen antifog solution, or warm water; it
is preferred not to wipe the lens
on viscera or the end of the
telescope may get hot; gently
wiping on liver or uterine surface
is preferrble
Detach camera from scope (or
Condensation on scope eyepiece, camera from coupler), inspect and
camera lens, coupler lens clean lens as needed
Use compressed air to dry out
Moisture in camera cable connecting moisture (don't use cotton tip
plug applicators on multiprong plug)
Replace video cable between
monitors
Poor cable shielding Reattach video cable at each
b) Flickering monitor
electrical Insecure connection of video cable
interference between monitors
Adjust camera focus ring

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 c) Blurring, Incorrect focus Inspect scope and camera,
Distortion replace as needed
Cracked lens, internal moisture

7. Inadequate Occlusion of tubing(kinking, blood Inspect full length of tubing; if

suction/irrigation clot, etc.) necessary, detach from
instrument and flush tubing with
sterile saline
Occlusion of valves in Detach tubing, flush device with
suction/irrigator device sterile saline
Not attached to wall suction Inspect and secure suction
canister connectors, wall source
connector
Irrigation fluid container not Inspect compressed gas source,
pressurised connector, pressure dial setting

8. Absent/ Inadequate Patient not grounded properly Assure adequate patient

cauterisation grounding pad contact, and pad
cable- electrosurgical unit
connection
Connection between electrosurgical Inspect both connecting points
unit and pencil not secure
Foot pedal or hand switch not Make connection
connected to electrosurgical unit

CONCLUSION
In conclusion, the introduction of checklists provides a reliable way of dealing with technical problems. The
problem with checklists, however, is that laparoscopic systems are often different and more generic processes
may not solve user-specific problems. Nonetheless, this is an attempt to build on the idea of the surgical safety
checklist and may well encourage further similar checklists to be developed, which can be augmented and
improved as time goes on or experience demonstrates.

As laparoscopic procedures continue to increase in frequency and complexity, it will become progressively more
important to be mindful of the advantages and disadvantages of the various techniques available so that surgery
can be tailored to individual patients. The simple troubleshooting maneuvers we reviewed above will ideally help
keep these procedures flowing smoothly and safely. Although surgeons must have intricate knowledge of their
laparoscopic instrumentation, it is equally important for the other members of the surgical team to be familiar with
both the equipment and the myriad potential problems that can arise during these procedures. When all members
of the surgical team can work together to quickly overcome any equipment issues during minimally invasive
cases, or efficiency will improve and better outcomes can be anticipated.

References

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3. Verdaasdonk EG, Stassen LP, van der Elst M, Karsten TM, Dankelman J.Problems with technical equipment during
laparoscopic surgery. An observational study.Surg.Endosc.2007; 21: 2759.
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of endoscopic and laparoscopic surgery.philadelphia: lippincott, Williams, and Wilkins; 2008. p. 3447.
8. Harrell AG , Heniford BT. Minimally invasive abdominal surgery: lux et veritas past, present, and future. Am J surg
2005;190:23943.
9. Litynski GS. laparoscopythe early attempts: spotlighting Georg Kelling and Hans Christian Jacobaeus. Jsls
1997;1: 835)
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colonic surgery: a double-blinded randomized con-trolled trial. ann surg 2010;251:102433.
11. Ott D. Contamination via gynecologic endoscopy insufflation. J Gynecol Surg 1989;5:2058
12. Ott de. Microbial colonization of laparoscopic gas delivery systems: a qualitative analysis. Jsls 1997;1:3259.)
13. Hasson HM. open laparoscopy: a report of 150 cases.J reprod. Med 1974;12:2348)
14. Society of american gastrointestinal and endoscopic surgeons. laproscopy
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content/uploads/troubleshooting.pdf?c27c83.
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16. The SAGES Manual Fundamentals of Laparoscopy, Thoracoscopy, and GI Endoscopy, Second Edition;Carol E.H.
Scott-Conner; Chapter1. Equipment Setup and Troubleshooting;Mohan C. Airan.page 11-15

Current status of Laparoscopy for abdominal Malignancies

As surgeons have become familiar with laparoscopic techniques for benign disease, the potential value of
laparoscopy in the management of malignant disease has been increasingly recognized. The general acceptance
of such benefits over laparotomy has resulted in the application of laparoscopic techniques to many other
procedures, benign and malignant. Initially usage of diagnostic laparoscopy was limited in malignancy due to
concerns over its adequacy. In the 1970s, several series demonstrated the ability of laparoscopy to diagnose
occult metastases and thus sparing several patients of morbidity due to laparotomy.Meanwhile, fears of
jeopardizing oncologic surgical principles with the laparoscopic approach have abated. Successful treatments of
malignant colon,stomach,adrenal,and pancreatic endocrine tumorshave all been described. Although associated
with steeper learning curves than comparable open procedures, laparoscopic cancer resectionswhen
performed by experienced surgeonscan provide adequate surgical margins and lymph node dissection with
minimal tumor handling. Much attention has been paid to port site recurrence following laparoscopic colectomy,
which has been reported to have an incidence as high as 1.6%.This uncommon phenomenon has been attributed
to spillage of tumor cells in the growth-conducive environment of CO2 pneumoperitoneumand may be minimized
through avoidance of unnecessary manipulation of the tumor as well as improved specimen handling. Indeed, a
more recent series reported the incidence of port site recurrence to be 0.8%; in comparison, wound recurrence
following open colectomy occurs in 0.6% of cases.Animal studies have suggested that the preserved immune
function after the less invasive laparoscopic approach may actually result in decreased propensity for tumors to
spread.

The increasing availability of preoperative therapies for certain localized tumors has made accurate diagnosis
and staging more important than ever. The presence of metastatic disease is a contraindication for aggressive
therapy in most patients. Computed tomography (CT) is the primary modality for staging of most gastrointestinal
(GI) malignancies. Although continuously improving, CT cannot routinely detect liver lesions smaller than 0.5cm
and is notoriously insensitive for peritoneal disease. For certain tumors, angiography, endoscopic ultrasound
(EUS), magnetic resonance imaging (MRI), and positron emission tomography (PET) may be valuable in
combination with CT but, as individual imaging studies, remain inferior to CT scanning alone.

Laparoscopic staging may offer the opportunity to visualize small-volume metastatic deposits, detect cytological
peritoneal spread, and, together with adjuncts such as laparoscopic ultrasound, accurately determine tumor
resectability. Biopsies may safely be performed of indeterminate liver lesions, suspicious lymph nodes, and, in
some situations, the primary tumor. When neoadjuvant therapy is intended, laparoscopic exploration may further
allow for placement of enteral feeding access or performance of fertility-sparing procedures. In the event that
metastatic disease is encountered, laparoscopic palliative procedures can potentially be performed.

Staging laparoscopy alone can be performed with very low morbidity, often with same-day discharge. At our
institution, pneumoperitoneum is established using an open technique, and a 30 angled laparoscope is
introduced. Two 5-mm trocars are placed in the right upper quadrant (Fig. 1); these may be exchanged for 10-
mm trocars if a feeding jejunostomy or gastrojejunostomy is subsequently performed. A systematic, 360
inspection of the abdomen is performed, beginning with the liver and including the peritoneum, omentum, and
entire bowel mesentery. A more extensive examination can be per- formed by entering the lesser sac by incising
the gastro- hepatic omentum. Biopsies are obtained of any suspicious lesions and sent for pathological
examination. Biopsy of the primary tumor is generally avoided because of the theoretical risk of intraperitoneal
dissemination. If no visible evidence of metastasis is present, 1 to 2 liters of saline are instilled, then collected for
peritoneal cytology. Complications related to trocar placement and pneumoperitoneum are possible, as with any
laparoscopic procedure, but the collective mortality for series in the literature approaches zero. Furthermore,
although laparoscopy is usually done under general anesthesia, at least one center has reported successful
performance of (one trocar) staging laparoscopy under local anesthesia.

Laparoscopy in malignant disease has thus expanded from a laparotomy-sparing procedure for patients with
advanced disease to a sensitive staging tool for patients with potentially curable disease. Like any staging
modality, laparoscopic staging is most appropriately utilized when its outcome will affect management. The
decision thus is affected by institutional factors such as the avail- ability of neoadjuvant therapies and the quality
of radiographic imaging. The need for operative palliation as well as the comfort level of the individual surgeon
with laparoscopic palliative procedures may also enter into this equation. The potential roles of laparoscopic
staging in the management of specific malignancies are discussed in the sections that follow.

259
Figure 1. Placement of ports for laparoscopic staging.

Pancreatic Cancer
The potential value of laparoscopic staging is perhaps most appreciated for pancreatic cancer. More than 30% of
patients with pancreatic cancer present with metastatic disease. Only 10% to 15% of patients with pancreatic
cancer have tumors that are amenable to curative resection at the time of diagnosis. The remaining patients
(approximately 50%) are considered unresectable because of local tumor invasion. Thus, despite improvement in
the morbidity and mortality of pancreatic resection, the overall long-term survival for patients with pancreatic
cancer remains less than 5%.The appeal of avoiding unnecessary laparotomy, which is associated with
increased morbidity and mortality and with decreased quality of life,in patients with incurable disease is obvious.

Still, many patients are found to be unresectable on exploration following preoperative staging with state-of- the-
art imaging modalities. Dynamic, contrast-enhanced CT is the most widely utilized technique, and numerous
studies over the years have tracked its accuracy. In 1990, Warshaw et al. published a series in which CT
predicted unresectablity with greater than 90% accuracy but correctly predicted resectability in only 45%.CT
failed to identify small liver metastases in 26% of patients and vascular invasion in 26%. In several subsequent
studies, CT has predicted resectability with 57% to 88% accuracy.Despite improvements in the technology, CT
remains limited in its ability to detect and characterize small metastatic foci and in its sensitivity for vascular
invasion. When performed in patients with resectable disease by CT, angiography improved the ability to predict
resectability from 60% to 77% but was associated with a false-positive rate of 14%.Endoscopic ultrasound
marginally improved the ability to predict resectability but also has a tendency to overstage tumors, particularly
those of large size.MRI has not been shown to offer any additional staging information over CT.PET has yet to
find a role in the routine staging of pancreatic cancer.In summary, angiography is used selectively at most
centers, and endoscopic ultrasound has established a role mainly in the diagnosis of small pancreatic tumors.

Laparoscopic staging has been pursued as a means to visualize small-volume metastatic disease below the
resolution of CT. Several series have addressed the value of laparoscopic staging in patients with
radiographically localized disease before laparotomy for attempted resection. In two of the largest and most
recent series, Fernandez-del Castillo et al.and Conlon et al.identified distant metastases in 24% and 19% of
laparoscopically staged patients, respectively. These rates are somewhat lower than those of earlier series,
perhaps because of interval improvements in CT resolution versus changes in the patient population.
Subsequent resectability rates for patients with no evidence of unresectability by laparoscopy range from 37% to
91%. In most of these series, laparoscopy was performed for the purposes of excluding extrapancreatic spread of
disease. In two of these studies, negative laparoscopy was followed by laparoscopic ultrasoundor angiographyto
evaluate for evidence of local tumor invasion, improving the actual resectability rate to 79% and 75%,
respectively. The patients in the Duke series predominately showed locally advanced tumors on preoperative
imaging studies with not unexpectedly higher rates of unresectability both on laparoscopy and on subsequent
laparotomy.In contrast, Conlon et al. at Memorial Sloan-Kettering (MSK) utilized a more extensive laparoscopic
evaluation, including inspection of the lesser sac, which yielded an additional 9% of patients with vascular
invasion as the sole reason for unresectability. The sub- sequent resectability rate in this series, which included
some benign and malignant periampullary tumors other than pancreatic adenocarinoma, was 91%.

Standard laparoscopy lacks the tactile sensation and three-dimensional quality of open exploration. Laparoscopic
ultrasound (LUS) has been proposed as an adjunct to standard laparoscopy to improve its capability to determine
locoregional invasion, particularly retropancreatic vascular involvement. Early experience suggested that
additional information could be obtained with LUS over laparoscopy alone.John et al.demonstrated that LUS had
a positive predictive value for resectability of 79% as compared to 46% for standard laparoscopy. These results
have been corroborated by subsequent seriesas well as by a recent update of John et al.s experience.In the
lattermost study, LUS was prospectively compared to transabdominal US, CT, and angiography; LUS was most

260
reliable for determining overall resectability, with a positive predictive value of 68% and a negative predictive
value of 97%. In all these series, the additional value of LUS over laparoscopy alone was greatest for
assessment of local resectability although LUS detected intraparenchymal liver metastases missed by
laparoscopy alone in up to 9% of patients.In the MSK experience, LUS was most useful for the 14% of patients
with equivocal findings, such as possible vascular or nodal involvement; LUS merely confirmed the findings of
their standard extended laparoscopy in patients thought to be resectable or unresectable.These studies, taken
together, suggest that LUS may prove valuable in at least selected cases.

Another adjunct to laparoscopy worthy of mention is peritoneal lavage for cytology. The peritoneum is the second
most common site of extranodal disease, following the liver. Laparoscopy alone can detect the almost 20% of
patients with gross intra-abdominal spread. However, in the Massachusetts General Hospital experience,
peritoneal cytology will be positive in another 8% of patients without other evidence of spread.These patients
have an outcome that is not significantly better than patients with visible metastases. Peritoneal lavage for
cytology is a simple, inexpensive study that may be performed at the time of laparoscopy. As the results
generally require more than a day for specimen preparation and pathological review, peritoneal lavage is
optimally performed in situations in which the patient is not intended for immediate laparotomy.

A second domain of laparoscopic staging is in the screening of patients with radiographically localized disease for
preoperative (neoadjuvant) therapy. It is generally accepted that complete surgical resection is necessary for
long-term survival. In fact, patients with positive margins demonstrate survivals similar to those treated with
chemoradiation alone.High rates of positive margins, nodal metastases, and local recurrence under- score the
locally aggressive nature of this disease.Post- operative (adjuvant) chemoradiation following resection has been
shown to increase survival from 11 to 12 months over resection alone and is considered standard of care at most
centers.

However, as many as 25% of patients do not receive intended postoperative therapy due to complications or
prolonged recovery.Therefore, in addition to the theoretical benefit of tumor downstaging, the advantages of
preoperative (neoadjuvant) therapy include the assurance that chemoradiation will be received by all patients and
at a time when oxygen delivery to the tumor is the greatest.

Series from several centers including our own have demonstrated that neoadjuvant therapy is feasible and is not
associated with increased morbidity or mortality.Although radiographic responses are modest compared to those
for rectal and esophageal cancers, significant histological responses have been seen. Complete pathological
responses occur only rarely, but neoadjuvant therapy has been associated with lower rates of local recurrence
and, in our experience, lower rates of positive margins and nodes (unpublished observations). Furthermore,
commonly used neoadjuvant regimens5-fluorouracil- (5-FU-) based chemotherapy combined with EBRTare
standard palliative regimens for unresectable patients that have been shown to increase survival in this group
from 6 to 10 months over chemotherapy alone.Combined chemotherapy and EBRT are not, however, standard
therapy for patients with metastatic disease.

Proponents of neoadjuvant therapy, therefore, utilize staging laparoscopy not only to prevent patients with occult
metastatic disease from undergoing unnecessary laparotomy but also to avoid the time, cost, and morbidity of
unnecessarily aggressive chemo-radiation. Many surgeons also routinely or selectively place feeding jejunostomy
tubes at the time of laparoscopy in patients considered candidates for neoadjuvant therapy. Few studies have
specifically examined the role of laparoscopy in the selection of patients for neoadjuvant therapy. The sensitivity
of CT scanning for small-volume metastatic disease remains the critical factor for deter- mining the value of
laparoscopy. In our experience, more than 20% of patients with radiographically localized disease are determined
to have gross or microscopic disease (liver 14%, peritoneal 5%, peritoneal cytology 5%) on laparoscopy that
disqualifies them from receiving preoperative chemo-radiation. This number, as would be expected, is
comparable to those published for series in which laparoscopic staging was performed before laparotomy for
attempted resection. LUS is not employed at our institution, as all patients with localized tumors are considered
for neoadjuvant therapy, regard- less of local resectability. Patients without evidence of metastatic disease on
laparoscopy undergo Hickman catheter and feeding jejunostomy tube placement as well as peritoneal lavage for
cytology in the same setting. Patients with localized disease following laparoscopy receive preoperative chemo-
radiation, after which they are restaged by CT. Although the routine placement of enteral feeding access has not
significantly influenced the subsequent morbidity or mortality of resection, the selective placement in nutritionally
challenged patients may improve tolerance of neoadjuvant therapy.

Regardless of whether surgeons adopt preoperative or postoperative chemo-radiation, most advocate staging
laparoscopy before formal laparotomy. The laparotomy- sparing benefit of laparoscopic staging is diminished,
however, if a patient requires subsequent laparotomy for palliation. Historically, staging was performed at the
time of laparotomy. If the patient was found to be unresectable, prophylactic biliary and gastric bypass was
performed. This practice was supported by reported incidences of biliary and gastro-duodenal obstruction as high
as 70% and 25% in patients with unresected pancreatic cancer.With advanced laparoscopic techniques,
laparoscopic gastrojejunostomy can be performed if necessary. In addition, although laparoscopic cholecysto-
jejunostomy can be performed, endoscopic stenting can provide excellent biliary palliation with lower early
morbidity, as has been shown in several randomized trials in the 1980s.Metallic expandable stents can now offer

261
longer patencythan their small, plastic, but easily removable predecessors. In addition, successful endoscopic
palliation of malignant duodenal obstruction has been reported by several institutions.Espat et al. reported a
series of 155 patients with laparoscopically staged unresectable disease who did not undergo prophylactic
surgical bypass.Many of these patients under- went endoscopic biliary decompression, but only 2% of patients
required subsequent laparotomy for palliation. The median survival of these patients was approximately 6
months; none received chemo-radiation. Whether newer therapies will increase the demand for surgical palliation
by increasing survival or decrease the demand by improving local tumor control is unclear.

Gastric Cancer
As is pancreatic cancer, gastric cancer in the United States is often advanced on presentation. At least 25% of
patients have metastatic disease at the time of diagnosis, and more than 60% are stage III or IV.Overall 5-year
survival is only 14%, compared to 45% in Japan. Resection is necessary for long-term survival, and local
recurrence is common, even after complete resection. Unlike pancreatic cancer, however, the treatment of
gastric cancer has traditionally included surgical resection, even for patients with metastatic disease.
Preoperative staging for the patient diagnosed with gastric cancer may have included at most a CT scan,
followed by laparotomy for complete staging and subtotal or total gastrectomy.

However, the availability of multimodality therapies as well as laparoscopic approaches to palliation and even
resection of gastric cancer have increased the importance of accurate preoperative staging. Although the best
radiologic modality for hepatic metastases, CT scanning has serious limitations for tumor (T) and nodal (N)
staging. CT understages a large percentage of primary tumors while overstaging others; CT is neither sensitive
nor specific for nodal disease.Endoscopic ultrasound has, therefore, emerged as the imaging study of choice for
loco-regional staging. EUS has an 86% concordance with pathologic T stage and is highly predictive of local
recurrence, less than 20% for T1 or T2 and greater than 75% for T3 or T4 disease.Although better than CT, the
accuracy of EUS for nodal staging ranges from only 60% to 80%.While the ability of current generation CT to
detect hepatic lesions continues to improve, the accurate identification of small-volume metastatic disease and
important for gastric cancerdistant (N2) nodal disease remains elusive.

Although not as extensively studied as for pancreatic cancer, the ability of laparoscopy to identify occult
metastatic disease not detected by high-quality CT scanning has been examined in a number of recent series.
Laparoscopic staging is most valuable for metastatic disease (M stage), which was identified in 24% to 37% of
patients with radiographically localized disease. The prevalence of liver metastases in these series is quite
variable, in part because of the inclusion of patients with metastases on CT in one seriesand to the restricted use
of CT in another.The sensitivity of laparoscopy in general is higher for peritoneal (69%94%) than for hepatic
metastases (33%100%), although the prevalence of the liver as the sole site of metastasis is low compared to
pancreatic cancer. The identification of nodal metastases by laparoscopic appearance alone was not very
sensitive,although nodal disease is not an absolute contraindication to resection at some centers. When
therapeutically relevant, nodal stage sensitivity may be improved with laparoscopic lymph node sampling.

Following from the success of EUS in predicting local recurrence and from experience with pancreatic and
hepatobiliary tumors, laparoscopic ultrasound has been pro- posed to further improve the detection of hepatic
and nodal disease.LUS may eventually even approach or surpass the accuracy of EUS for T staging. Published
experience with LUS in gastric cancer is limited, but early series in the literature suggest that LUS provides excel-
lent imaging of the primary tumor.

More than 80% of patients without evidence of metastatic disease by laparoscopy proceeded to resection in
these series. At least one-third were spared laparotomy. Furthermore, for all patients in these series with
laparoscopically staged metastatic disease who did not undergo palliative resection, less than 1% required
subsequent laparotomy for palliation. The majority of these patients can be adequately palliated through
advances in nonsurgical therapies such as radiation, chemotherapy, enteral nutrition, and endoscopic laser and
stenting. These patients, whose mean life expectancy is approximately 6 months, benefit from the avoidance of
gastrectomy with significantly decreased length of hospital stay.

Laparoscopic staging is thus recommended for patients in whom the presence of metastatic disease will affect
either the surgical approach or the patients candidacy for preoperative multimodality therapy. Where it is
routinely used, EUS may occupy a key role in this algorithm. For patients with small tumors by EUS, the risk of
metastasis is sufficiently low that the yield of laparoscopy is probably not high enough to warrant its routine use.
Thus, for the majority of surgeons who perform open gastric resection, patients who are T1 or T2N0 by EUS may
proceed directly to laparotomy. However, at centers where laparoscopic gastrectomy is practiced, patients with
small tumors by EUS may be appropriate for laparoscopic exploration followed by resection. Although a number
of groups have published experience with this procedure,laparoscopic resection is less common than for other
abdominal malignancies, perhaps due to the steep learning curve and low volume of cases.

Laparoscopic staging may have more widespread value for patients with large tumors. For the asymptomatic
patient with locally advanced disease, the identification of metastatic disease may allow the patient to avoid
laparotomy altogether. The symptomatic patient with metastatic disease may be a candidate for laparoscopic
palliation, such as gastrojejunostomy of partial gastrectomy. Locally advanced patients without metastatic

262
disease may be offered preoperative (neoadjuvant) chemotherapy with one of several multidrug regimens at
many centers. Response rates of up to 70% have been demonstrated, leading to complete resectability in almost
50% of patients with previously unresectable tumors.It is for this group that accurate staging is perhaps most
important, as patients with occult metastatic disease may be subjected to the side effects of these often toxic
chemotherapy regimens. Significant overstaging or understaging of patients within the context of experimental
protocols will also falsely affect our assessment of treatment results.

The role of laparoscopy in the management of tumors of the esophagus and gastro-esophageal (GE) junction
deserves mention. Advances in nonsurgical palliation, such as endoscopic stenting, radiation, and photodynamic
therapy, have diminished the need for palliative resection. In three recent series, laparoscopy detected distant
metastases in fewer than 10% of patients with adenocarcinoma of the esophagus or GE junction and in no
patients with squamous carcinoma of the esophagus.The addition of laparoscopic ultrasound in two of these
series improved sensitivity to between 70% and 90%, particularly improving the detection of celiac
lymphoadenopathy.The yield for occult metastases is still low compared to that for the other malignancies dis-
cussed in this chapter. For patients who are candidates for neoadjuvant therapies, however, staging laparoscopy
may identify those patients with unsuspected metastases as well as provide an opportunity for obtaining enteral
feeding access before multimodality therapy.

Colorectal Cancer
As the majority of patients with colorectal cancer will require resection for either cure or palliation, complete
staging can generally be performed at the time of resection. For patients undergoing laparotomy, this is
accomplished with nearly 100% sensitivity through direct visualization, palpation, and biopsy of suspicious
lesions. Rectal cancer patients who are candidates for local procedures are reliant on nonoperative staging,
utilizing EUS for regional nodal disease and CT for distant metastasis. The limitations of CT scanning for
detecting liver metastases are generalizable. Therefore, staging laparoscopy will theoretically yield a significant
percent- age of patients with metastases not detected by CT. However, unless the patient is a candidate for
neoadjuvant therapy of a locally advanced tumor, the presence of metastases is not going to affect the operative
approach. The role of laparoscopy in the staging of patients with rectal cancer for neoadjuvant therapy has not
been extensively studied. A recent paper from MSK reported a series of 14 patients with near-obstructing rectal
cancer who underwent staging laparoscopy.Four patients (29%) had unsuspected peritoneal metastases and
were managed without further surgery. The remaining 10 patients underwent laparoscopic diversion followed by
chemo-radiation and subsequent resection. This small series illustrates the potential value of this strategy for
patients with locally advanced tumors.

Laparoscopic colon resection, on the other hand, has received much attention in the literature. Concerns about
port site recurrence and long operative times initially hindered its acceptance. A rapidly growing number of
studies have suggested that laparoscopic resection is technically feasible, oncologically adequate, and
associated with shorter hospitalization, quicker recovery, and less pain. A prospective, randomized trial is
currently in progress to definitively prove these benefits.A potential pitfall of laparoscopic resection is the loss of
sensitivity for liver and nodal metastasis afforded by laparotomy. Laparoscopic ultrasound has been proposed as
an adjunct to laparoscopic resection and was shown to have a sensitivity of 100% for liver and 94% for nodal
metastases, compared to 75% and 6%, respectively, for laparoscopy alone.

Perhaps the most obvious role for laparoscopic staging in the management of colorectal cancer is its role in the
assessment of liver metastases. It is clear that the complete resection of colorectal metastases to liver confers a
survival benefit and even long-term survival in a minority of patients.The consensus on what is resectable has
evolved from small, single-lobe lesions to essentially any technically feasible resection(s) that leave an adequate
hepatic remnant. Nevertheless, as many as 40% selected for surgery are found unresectable at laparotomy. The
goals of preoperative staging are, therefore, very similar to those for primary hepatic malignancies, and most
studies of LUS for liver tumors have included both primary and metastatic lesions.A key difference is that, for
metastatic lesions, as many as two-thirds of patients are found to be unresectable because of extrahepatic
disease such as local recurrence, nodal metastases, or peritoneal implants, whereas only one-third are due to
underestimated intrahepatic extent.Laparoscopy allows for identification of extrahepatic disease, while LUS
examines the liver for evidence of technical unresectability, as discussed next for primary liver tumors. When
specifically studied in 47 patients under evaluation for resection of colorectal metastases, laparoscopy alone
identified 13% as unresectable, with half due to multifocality and half due to peritoneal metastasis; LUS identified
another 25% as unresectable for reasons of multifocality, location precluding resection, and misdiagnosis.Of the
patients who subsequently underwent laparotomy, 79% underwent resection, whereas 75% of patients with
unresectable disease were spared laparotomy. LUS may thus be as valuable for metastatic liver tumors as for
primary tumors.

Hepatobiliary Cancer
As for pancreatic, gastric, and colon cancer, surgery is still the mainstay of therapy for primary malignancies of
the liver and biliary tree. For hepatocellular carcinoma (HCC), the most common primary malignancy, only 20%
are resectable at the time of diagnosis, and local recurrence develops in approximately one-half of patients after
curative resection.HCC is locally aggressive with frequent vascular invasion and formation of satellite lesions.
Even if technically feasible, hepatectomy often leaves the cirrhotic patient with insufficient hepatic reserve.

263
Intrahepatic cholangiocarcinoma, the second most common primary liver malignancy, is also characterized by
extensive local disease and regional lymph node involvement at presentation. Gallbladder cancer is rarely
diagnosed preoperatively but is usually an incidental finding at laparotomy or on pathological examination
following cholecystectomy. The early onset of biliary obstruction associated with hilar and distal
cholangiocarcinoma often allows more timely diagnosis and greater resectability. Distal cholangiocarcinoma is
more similar to, although less aggressive than, pancreatic adenocarcinoma in its propensity for vascular and
nodal involvement. Therefore, this discussion focuses on the staging of primary hepatic and proximal biliary
malignancies, for which imaging of hepatic anatomy is crucial.

Unlike the other GI malignancies discussed, surgery is rarely necessary for palliation of liver tumors, either
primary or metastatic. Nonresectional therapies, such as percutaneous ethanol injection (PEI) and transcatheter
arterial chemoembolization (TACE) achieve satisfactory local recurrence rates, which, for small tumors, are not
significantly different than those for resection.Cryotherapy, frequently utilized for metastatic liver tumors, has
been shown in at least one series to have benefit for HCC as well.Effective and less invasive palliation is
available for many patients with unresectable disease. Therefore, laparotomy to confirm unresectability often
entails unnecessary expense and morbidity without additional benefit.

Despite the increasing quantity and quality of radio- logic imaging modalities, many surgical explorations
encounter unresectable tumors due to unsuspected spread or multifocality. CT and US remain the primary
imaging modalities.Intravenous contrast improves the sensitivity of CT, and numerous enhancement techniques
exist, such as dual-phase imaging, delayed scanning, and arterial portography. Arterial portography (CTAP) has
been shown to be more than 90% sensitive for the detection of metastatic liver lesions.Spiral CT is less invasive
and allows for dual-phase imaging but is less sensitive.In addition to the limitations of resolution inherent to CT,
the cirrhotic liver is prone to pseudolesions as a result of laminar flow perfusion defects and focal fatty deposits,
resulting in a high false-positive rate.US provides useful vascular information such as anatomy, flow, and patency
but is highly operator dependent and generally less sensitive than CT. MRI may help in the differentiation of
hemangiomata and in the detection of lesions less than 1 cm, but its role is not yet well defined.None of these
imaging studies is sensitive for the detection of nodal and small-volume peritoneal disease.

The exact number and size of lesions as well as their relationships to vascular and biliary structures are crucial
for deciding whether and how much to resect. Although preoperative imaging may identify some patients as
unresectable, laparotomy with intraoperative ultrasound (IOUS) has become the gold standard for the
determination of resectability. Concomitant cirrhosis can be determined by inspection. Suspicious nodal and
peritoneal lesions can be confirmed by biopsy. Direct contact with the liver surface allows visualization of lesions
as small as 3 to 5mm.Doppler imaging can localize vascular structures and identify tumor thrombi. With
sensitivity as high as 98%,IOUS accurately delineates anatomy and yields information that results in a change in
the operative procedure in almost 50% of patients.

Laparoscopy may obviate the need for laparotomy in some patients through more accurate diagnosis and
staging. The preoperative diagnosis of liver tumors is not always certain preoperatively; laparoscopy may yield
extrahepatic primary sites in as many as one-third of patients thought to have primary liver tumors.Although the
incidence of extrahepatic dissemination is lower for primary than for metastatic liver tumors, diagnostic
laparoscopy can identify the small percentage of patients with unsuspected peritoneal metastases. Laparoscopy
alone can also detect evidence of unresectability, such as unsuspected cirrhosis or bilobar disease, that
precludes further examination or laparotomy, in almost 10% of patients.

The introduction of ultrasound to diagnostic laparoscopy in the early 1980s was, therefore, an ideal combination
for the staging of liver tumors. Studies early in the past decade validated the idea that LUS, when performed in
patients with potentially resectable liver lesions by a variety of imaging modalities, may spare a significant
number of patients laparotomy.As already mentioned, most recent studies of LUS for liver tumors have included
both primary and metastatic tumors; one of these series also included several benign lesions. In the only series
specifically examining HCC,laparotomy was avoided because of definite, evidence of unresectability in 16% of
patients undergoing laparoscopic ultrasound (LUS); 88% of patients who underwent laparotomy following LUS
were resected compared to 68% of a nonrandomized control group. LUS was less accurate for tumors greater
than 10 cm and was least sensitive, in general, for tumor thrombi and invasion of adjacent organs.

Although the sensitivity of LUS compared favorably to open contact US in an in vitro model of hepatic
lesions,laparotomy with IOUS remains the gold standard. Technical refinements in laparoscopic ultrasound
transducers may gradually overcome the differences in sensitivity. Meanwhile, for patients with radiographically
resectable tumors, the ability to avoid laparotomy in 15% to 20% of patients following LUS warrants consideration
of this strategy.

Conclusion
Laparoscopy is a useful tool for both staging and treatment of many GI malignancies. It is cost-effective and
widely available. As technical advances continue, laparoscopic procedures both for staging and treatment should
take on an even greater role in the management of these malignancies.

264
 Robot assisted radical prostatectomy

Ketankumar Rupala, Varun Mittal, Gagan Gautam

Prostate cancer is the second most common cancer in men with estimated lifetime risk of 16.72% and 2.57% risk
[1]
of death. Various genetic and environmental factors may be responsible for development of prostate cancer as
shown in table 1.

Risk factors Protective factors

Increasing age (median age 68 years) 5 Alfa Reductase inhibitors
White and African descent Vitamin E
Family history (2 fold increased risk) Selenium
Genetic factors NSAID
Proliferative inflammatory atrophy (PIA) Green Tea
Androgen and estrogen Soy
High dietary fat lycopene
Table 1: Risk and protective factors for carcinoma prostate.

Clinical features
Prostate cancer rarely leads to any symptom at an early stage. Majority of patients of prostate cancer are
diagnosed on PSA screening or during evaluation of lower urinary tract symptoms (LUTS). Locally advanced and
metastatic disease, usually present with obstructive LUTS, or metastatic symptoms like bone pain, pathologic
fracture or lower limb edema.

Investigations
Early detection can be done by screening with both PSA and DRE, but currently value of PSA screening is
controversial so, men who present for periodic health examination should be provided option of PSA test for
[2, 3]
screening. American urological association recommends PSA based annual screening in men, beginning at
age of 55 years with life expectancy of more than 10 years and even earlier for a high risk man (positive family
history and/or African American decent. The AUA recommends that beginning at age 55, men engage in shared
decision making with their physician about whether to undergo PSA screening. The AUA doesn't recommend
routine PSA screening for men over age 70, or for any man with less than a 10-to-15 year life expectancy. [4] Gray
scale transrectal ultrasound (TRUS) guided standard 12 core biopsy of prostate is method of choice for
diagnosis. Rarely transperineal approach may be required in case of a congenital anomaly of the anus or prior
surgical extirpation such as abdominoperineal resection.

Pathology
On pathology, more than 95% prostatic carcinomas are adenocarcinoma. 85% cases arise from peripheral zone
and 70% cases show bilateral involvement. [5] Extraprostatic extension mainly occurs posteriorly or
posterolaterally and commonly in seminal vesicles and later in bladder and rectum. Distant spread occurs to
lymph nodes and bones and and later in the course of the disease to lungs and liver. [6]
Histological grading is reported in terms of Gleason scoring system, calculated on basis of dominant histological
grades ranging from grade 1 (well differentiated) to grade 5 (poorly differentiated). Gleason score is derived by
addition of primary (most prevalent pattern) and secondary grade (2nd most prevalent pattern). Recently, free
PSA, free PSA to total PSA ratio, PSA density, doubling time (PSA-DT) and PSA velocity helps in diagnosis of
[7, 8]
cases with PSA value between 4-10 ng/ml.

Staging
Local and distant staging is done with magnetic resonance imaging (MRI) or computerized tomography (CT)
scan, bone scan and Prostate-specific Membrane Antigen (PMSA) based positron emission tomography (PET)
Scan, table 2.

T - Primary tumor
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Clinically inapparent tumor not palpable or visible by imaging
T1a Tumor incidental histological finding in 5% or less of tissue resected
T1b Tumor incidental histological finding in more than 5% of tissue resected
T1c Tumor identified by needle biopsy (e.g. because of elevated prostate-specific antigen (PSA)
level)
T2 Tumor confined within the prostate
T2a Tumor involves one half of one lobe or less
T2b Tumor involves more than half of one lobe, but not both lobes
T2c Tumor involves both lobes
T3 Tumor extends through the prostatic capsule
T3a Extracapsular extension (unilateral or bilateral) including microscopic bladder neck involvement

265
 T3b Tumor invades seminal vesicle(s)
T4 Tumor is fixed or invades adjacent structures other than seminal vesicles: external sphincter, rectum,
levator muscles, and/or pelvic wall
N - Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M - Distant metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Non-regional lymph node(s)
M1b Bone(s)
M1c Other site(s)
[9]
Table 2: Tumor node metastasis (TNM) staging 2010, American Joint Committee on Cancer (AJCC)

Treatment
[10]
Treatment modality depends on risk category. Most commonly used is DAmico classification, table 3, 4.

Risk categories
Low risk Intermediate risk High risk
D Amico PSA < 10 ng / mL PSA 10-20 ng /mL PSA > 20 ng / mL any PSA
and GS < 7 or GS 7 or GS > 7 any GS cT3-4
and cT1-2a or cT2b or cT2c or cN+
Localized Locally advanced

Low risk Active Surveillance(Regular Life expectancy of more than 10 years

follow-up with DRE, PSA and
repeat biopsies with curative
intent)
Watchful waiting(Refers to Life expectancy of less than 10 years and not eligible for local
conservative management, curative treatment
until the development of local
or distant symptoms with
palliative intent)
Radical prostatectomy Life expectancy more than 10years
Radiotherapy Not fit/willing for surgery and with good IPSS (minimal LUTS) and
Prostate <50gm, dose 74-78 Gray
Intermediate Watchful waiting Life expectancy less than 10 years and not eligible for local curative
risk treatment
Radical prostatectomy Life expectancy more than 10years, Extended pelvic
lymphadenectomy (EPLND) should be performed if the estimated
risk for positive lymph nodes exceeds 5%.
Radiotherapy Total dose should be 76-78 Gray, in combination with short-term
Androgen deprivation therapy (ADT) (4-6 months).
Androgen suppression No role in asymptomatic patients. Should only be used in patients
monotherapy with significant local symptoms who are not eligible for curative
treatment.
High risk Watchful waiting Life expectancy less than 10 years and not eligible for local curative
treatment
Radical prostatectomy High risk localized and a life expectancy of > 10 yr, RP should be
offered in a multimodality setting.
High risk locally advanced and a life expectancy of > 10 yr, RP
can be offered in a multimodality setting.
Radiotherapy Must be given in combination with
long-term ADT (2-3 yr is recommended).
Androgen suppression Reserved for those unwilling or unable to receive
monotherapy any form of local treatment and either symptomatic
or asymptomatic with a PSA-DT < 12 months and a
PSA > 50 ng/mL and a poorly differentiated tumor.
[11]
Table 4: Treatment modalities for carcinoma prostate as per risk categories.

Radical prostatectomy
The surgical treatment of prostate cancer consists of radical prostatectomy, which involves removal of entire
prostate gland between urethra and bladder and removal of both seminal vesicles with goal of negative margins.

266
Bilateral extended pelvic lymph node dissection is often done along with it, especially in cases with intermediate
or high-risk prostate cancer. Radical prostatectomy provides overall and cancer specific survival benefit in
patients with localized prostate cancer. [12] Surgical advancement has decreased complication rates and improved
cancer cure rates. Traditional open radical retropubic prostatectomy (RRP) is being replaced by laparoscopic and
robot assisted radical prostatectomy (RARP). RARP has displaced RRP as the gold standard approach for
clinically localized ca prostate in western countries as well as in India. Recently systematic review of literature
has compared the results of RRP vs. RARP. RARP offers many potential oncological and functional benefits as
[13]
compared to traditional open surgery.

RARP is the most recent advancement in surgical treatment of prostate cancer. The robotic surgical system
enhances the surgeons technical abilities and improves outcomes. First documented use of robot assisted
[14]
surgical procedure occurred in 1985 for a neurosurgical procedure. In urology, first radical prostatectomy using
[15]
Da Vinci System was performed in Europe in 2000.

Robotic system provides advantage of stereoscopic view with 3D vision and 10 fold magnification. Due to seven
degrees of freedom, Endowrist instrument technology precisely replicates the skilled movement of surgeon and
improves ergonomics. Further, movements are scaled up to 3:1 and hence large movements of the master
controls are manifested as micro-movements of the robotic instruments. Thus, robotic system enhances vision,
[13]
dexterity and precision, which ultimately removes cancerous tissue more precisely and reduces complications.

Robot assisted radical prostatectomy

Surgical Technique of RARP has been well established now. Standardized technique of RARP has been
[16]
described by Detroit group, USA.

Indications
Established indications of RARP are:
1. Primary treatment in localized prostate carcinoma with life expectancy more than 10 years
2. Part of multimodality treatment in locally advanced cancer.
3. Salvage therapy (after failed radiation therapy for prostate cancer).

Contraindications
Absolute and relative contraindications to RARP are given in table 5.

Absolute Relative
Uncorrectable bleeding diathesis History of peritonitis or prior pelvic or complex lower
abdominal surgery
Contraindication to general anesthesia Large median lobe
Large prostate
Morbid obesity
Table 5: Absolute and relative contraindications to RARP

Pre-operative preparation
Standard pre-operative preparation includes withholding of anticoagulant, taking clear liquid diet for 2 days prior
[17]
to surgery and proctoclysis enema one night before surgery.

Specific patient positioning and surgical team: Procedure is done under general anesthesia in steep
Trendelenburg with low lithotomy or split leg position. Port placement is usually done as shown in the figure,
using anterior superior iliac spine, umbilicus and pubic symphysis as surface anatomical landmarks. Robot
docking can be done in between the legs or from side, figure 1 a, b, c.

The patient is placed supine

Tableflexed at the level of the hips
Legs areslightly abducted to allow
for docking of theda Vinci surgical
cart between legs of thepatient.
Legs are padded andsecurely fixed
to the table
Patient restson his shoulders on a
specially designedsoft cushioned
pillow to prevent nervecompression
injuries at the shoulder girdle
Abdomen and genitals are
scrubbed, and a Foley catheter is
inserted, figure 1a.

267
Figure 1a: Patient position in RARP

The assistant sits on the right side

and the scrub nurse on the left side
of the patient.

Flat screen monitors are placed on

both sides of the patient, figure 1b.

Figure 1b: Patient, surgeon and assistant position in RARP

Port placement in RARP:

Camera port (12 mm) is placed lateral to the

umbilicus on the left side or in a midline supra-
umbilical position.
Two robotic ports (8 mm) are placed pararectally
on the left and on the right side 10 cm lateral and
slightly more caudal to the camera port.
A 5-mm assistant port (for suction/irrigation) is
placed midway between the camera port and the
right robotic port.
A 12-mm assistant port is placed 3 cm from the
iliac crest and slightly caudal to the right robotic
port.
This port allows introduction of needles and clip
appliers.
An 8-mm robotic port for the fourth arm is
introduced in a mirror-like manner to the 12-mm
assistant port on the left side.
Final position of the ports shows a semicircular
arrangement, figure 1c.
Figure 1c: Port placement in RARP

Robotic parts and instruments

The Da Vinci System consists of a surgeons console usually in the same room as the patient, and a patient-side
cart with four interactive robotic arms controlled from the console. Three of the arms are used for holding working
instruments such as monopolar scissors, bipolar fenestrated forceps, and prograsp forceps or needle drivers.
The surgeon uses the consoles master controls to maneuver the patient-side carts robotic arms. The
instruments jointed-wrist design exceeds the natural range of motion of the human hand; motion scaling and
tremor reduction further interpret and refine the surgeons hand movements. Robot always requires a human
operator.

Surgical steps in RARP

[18]
Surgical steps in RARP are well illustrated in figure 2(a, b, c, d , e , f) and figure 3(a, b , c , d).

Creation of pneumoperitoneum by Veress needle though 12mm periumbilical incision

Bilateral extended pelvic lymph node dissection,
Dissection of seminal vesicles and vas deferens, Approach may be posterior (if done initially) or anterior (if done
once bladder neck is transected) (figure 2a,b)
Bladder drop to expose Retzius space (figure 2c)
Incision of endopelvic fascia bilaterally (figure 2d,e)

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 Dorsal venous complex control (figure 2f)
Bladder neck transaction (figure 3a)
Incision of Denonvilliers fascia and separation of prostate from the rectum
Control of lateral vascular pedicle and preservation of neurovascular bundle (figure 3b)
Apical dissection and urethral transaction (figure 3c)
Vesicourethral anastomosis (figure 3d)
Drain placement in pelvic cavity
Specimen retrieval through camera port
Port closure

Post-operative care
Early ambulation and chest physiotherapy are the key elements in the post operative period. Drain is removed on
first or second post operative day depending upon the output. Patient is discharged usually in 48 to 72 hours.
Per urethral catheter is removed after 7-10 days. Cystogram may be done before removal of per urethral catheter
to check for integrity of anastomosis.

Figure 2: (a, b, c, d, e, f) Figure 3: (a, b, c, d)

Complications
In the era of RARP the overall complication rate has decreased as compared to conventional (RRP) and (6.6%
vs 10.3%). [19]

Early complications Late complications

Bleeding Urethral/anastomotic strictures
Injury to the surrounding structures such as rectum and Inguinal/ Port site hernia
small bowel, bladder, ureter, nerves and vessels.
Anastomotic leak
Thromboembolic and cardiovascular events
Urinary tract infections
Wound infections
Lymphocele

Advantages of robotic assisted radical prostatectomy

The minimal invasive surgical benefits of RARP have lead to better outcome as compared to RRP. Significantly
less blood loss during RARP is due to better visualization of the dorsal venous complex and the tamponade
effect provided by the pneumoperitoneum. Important concerns after radical prostatectomy are its functional and
oncological outcome. As Da Vinci system provide improved visualization and dexterity as compared to open
surgery, there is likely to be a better preservation of the constituents of the urinary sphincter complex and
neurovascular bundle, leading to superior continence and sexual function recovery over RRP. RARP versus RRP
is associated with a lower incidence of positive surgical margin rate for intermediate- and high-risk prostate
carcinoma and lesser need of additional cancer therapy after surgery. Although the robust long term data are
lacking for RARP, the short term data as below is convincingly in favor of RARP.

Advantages of RARP over RRP

Overall complication rate is low (6.6% 10.3%). [19]
Minimal blood loss due to tamponade effect of pneumoperitoneum and magnified 3D vision (745.3 ml Vs
188ml). [12]
Improved urinary continence. (>95% vs. 80-90%). [12, 20]
[12, 20]
Speedy potency recovery. (75-85% vs. 60-80%).
[12]
Lower incidence of rectal injury, ureteral and bladder injuries.
[12]
Less pain, early mobilization, reduced risk of thromboembolic event, shorter hospital stay.

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 Lower risk of wound infection (2.8% Vs 0.7%). [12]
Better oncological outcomes with low margin positivity rates (13.6% Vs. 18.3%) and lesser need for
adjuvant therapy (4.5% Vs. 6.2%)[20, 21]
Aesthetically better in terms of small scar

Disadvantages
Higher cost
Lack of tactile sensations.
Need for specifically trained personnel

In view of above, Robotic surgery systems have disseminated rapidly throughout the world, especially in the field
of urology. For prostate cancer treatment, the proportion of prostatectomies performed robotically has risen from
[22]
8% in 2003 to more than 80% recently in the west. Robotic surgery is now gaining increased acceptance in
India as well, as revealed by an annual more than 44% rise in the number of procedures performed in India (in
[23]
contrast to ~21% rise worldwide). The benefits of robotic surgery have made it a leading choice for the
treatment of patients with prostate cancer.

References

1. Shahab AA, Soebadi DM, Djatisoesanto W, Hardjowijoto S, Soetojo S, Hakim L. Prostate-specific antigen and
prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer.
Prostate Int. 2013; 1: 2330.
rd
2. Andriole GL, Crawford ED, Grubb RL 3 , Buys SS, Chia D, Church TR, et al. Prostate cancer screening in the
randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of
follow-up. JNCI 2012; 104: 125.
3. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V et al. Prostate-cancer mortality at 11 years
of follow-up. N Engl J Med. 2012; 366:981-90
4. Carter HB, Albertsen PC, Barry MJ, Etzioni R, Freedland SJ, Greene KL et al. Early detection of prostate cancer:
AUA Guideline. J Urol. 2013; 190:419-26.
5. McNeal JE, Redwine EA, Freiha FS, Stamey TA. Zonal distribution of prostatic adenocarcinoma. Correlation with
histologic pattern and direction of spread. Am J Surg Pathol. 1988;12:897-906
6. Hess KR, Varadhachary GR, Taylor SH, Wei W, Raber MN, Lenzi R et al. Metastatic patterns in
adenocarcinoma.Cancer. 2006; 106:1624-33.
7. Vickers AJ, Savage C, O'Brien MF, and Lilja H. Systematic review of pretreatment prostate-specific antigen
velocity and doubling time as predictors for prostate cancer. J Clin Oncol 2009; 27:398-403.
8. Stephan C, Lein M, Jung K, Schnorr D, Loening SA. The influence of prostate volume on the ratio of free to total
prostate specific antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia. Cancer
1997; 79:104-9.
9. Cheng L, Montironi R, Bostwick DG, Lopez-Beltran A, Berney DM. Staging of prostate cancer. Histopathology.
2012; 60:87-117
10. Cooperberg MR. Prostate cancer risk assessment: choosing the sharpest tool in the shed. Cancer, 2008. 113:
3062-6
11. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T et al EAU guidelines on prostate
cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014; 65:124-
37.
12. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, et al. Cancer survival in Europe 1999-2007
by country and age: results of EUROCARE--5-a population-based study. Lancet Oncol 2014; 15:23- 34.
13. Tewari A, Sooriakumaran P, Bloch DA, Seshadri-Kreaden U, Hebert AE, Wiklund P. Positive surgical margin and
perioperative complication rates of primary surgical treatments for prostate cancer: a systematic review and
meta-analysis comparing retropubic, laparoscopic, and robotic prostatectomy. Eur Urol. 2012; 62:1-15.
14. Anthony R L, Andres E C, Jaydev P D, William C M. Robotic Surgery, A Current Perspective. Ann Surg. 2004; 239;
1421.
15. Erik M, Omer K, Justin V and David H. Trends in urology gynecology and sexual health. Robotic prostatectomy:
where are we now? 2007; 13; 29-34.
16. El-Hakim A, and Tewari A. Robotic Prostatectomy -- A Review. Med Gen Med. 2004; 6: 20.
17. Ficarra V, Novara G, Fracalanza S, D'Elia C, Secco S, Iafrate M et.al. A prospective, non-randomized trial
comparing robot-assisted laparoscopic and retropubic radical prostatectomy in one European institution. BJU
Int. 2009; 104:534-9.
18. Jens-Uwe Stolzenburg, Alan McNeill and Evangelos N. Liatsikos.Nerve-sparing endoscopic extraperitoneal
radical prostatectomy. Surgical Atlas, BJU int. 2008; 909-28.
19. Gonzalgo ML, Pavlovich CP, Trock BJ, Link RE, Sullivan W, Su LM. Classification and trends of perioperative
morbidities following laparoscopic radical prostatectomy. J Urol.2005; 174:13539.
20. Patel VR, Coelho RF, Chauhan S, Orvieto MA, Palmer KJ, Rocco B,et al. Continence, potency and oncological
outcomes after robotic-assisted radical prostatectomy: early trifecta results of a high-volume surgeon. BJU
Int. 2010; 106:696-702.
21. Hu CJ, Gandaglia G, Karakiewicz LP, Nguyen LP, Trinh Q,Shih YT et al. Comparative Effectiveness of Robot -
assisted Versus Open Radical Prostatectomy Cancer Control, Eur Urol. 2014; 66: 66672
22. Kolata G. Results unproven, robotic surgery wins converts. New York Times. February 14, 2010:A1.
23. Jain S,Gautam G. Robotics in urologic oncology. J Minim Access Surg. 2015; 11: 4044.

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 Retrograde Intrarenal Surgery

Atul Goswami

Retrograde intrarenal surgery or flexible ureterorenoscopy is a technique whereby all areas of the renal
pelvicalyceal system and ureter can be approached in a minimally invasive manner. With advances in optical
technology, miniaturization of scopes, advent of digital flexible ureteroscopes, incorporation of active deflection,
introduction of sophisticated flexible instruments as well as the development of holmium laser which can be
directed via flexible laser fibres and has soft tissue as well as lithotripsy applications , RIRS now occupies a
prominent place in a urologist's armamentarium.

Indications for RIRS

Established indications:
Diagnostic
Evaluation and Location of hematuria .
Evaluation and localization of positive urine cytology .
Evaluation of filling defects seen on contact studies.
Surveillance following endoscopically managed upper tract TCC.

Therapeutic applications.
Endoscopic Lithotripsy/stone retrieval
Inferior calyceal calculi <1cm.
Renal stones < 2cm elsewhere in collecting system
Upper Ureteric stones <2cm
Retrograde endopyelotomy for ureteropelvic junction obstruction .
Endoscopic managemtn of upper tract TCC.
Retrieval of foreign bodies (e.g. forgotten stents in upper tract.)

Evolving indications
Endoscopic lithotripsy for inferior calyceal stones >1cm, stones elsewhere in the collecting system >2 cm, and
ureteric stones >2cm.

Technique of RIRS
General anesthesia is preferable for RIRS. The patient is positioned in the lithotomy position throughout the
procedure. This is advantageous in patients with morbid obesity, respiratory compromise and cardiac
compromise in that prone position as required in PCNL is avoided, as also the potential pleural and lung
complications associated with supracostal punctures in PCNL. The ureteric orifice is then dilated and an access
sheath is placed. This facilitates repeated passage of the flexible ureteroscope as well as keeps the intrapelvic
pressure during the procedure low. The flexible ureteroscope is then introduced, and under direct vision, laser
lithotripsy or retrieval of stones with nitinol baskets can be done with the laser fibre or the basket being
introduced through the working channel of the flexible ureterscope . A double J stent is generally placed at the
conclusion of the procedure.

RIRS for treatment of upper ureteric and renal calculi-our experience

Total Patients operated : 358
Total units operated : 467
Bilateral procedures in the same sitting : 109
No. of units operated Stone clearance rate Stone clearance rate
after 1st session after 2nd session
Stone <1 cm 298 97.97% 100%
Stone 1-2 cm 132 90.9% 100%
Stone >2cm 37 66.67% 95.83%

Average Hospital Stay : 1.9 Days

Minor Complications : 4.8%
Major Complications : None

To conclude, with continuing advances in instrument, optical, digital and laser technology as well as increasing
expertise of operators , RIRS is rapidly becoming the technique of choices for procedures in the upper urinary
tract with comparable success rate to more invasive procedures like PCNL without the attendant complications.

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 Gastroesophageal reflux disease

Randeep Wadhawan, Hemanth Kumar

INTRODUCTION
Gastro Esophageal Reflux Disease (GERD) is a common chronic disorder of the upper Gastro-Intestinal Tract
(GIT) having an impact on both quality of life and economic burden. There is also evidence of this disorder being
a pre-disposing cause for barrets esophagus and adenocarcinoma of esophagus.

DEFINITION
In accordance with the Montreal consensus, GERD is defined as A condition which develops when the reflux of
stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation constitute
the characteristic symptoms of GERD.Heartburn is defined as a burning sensation in the retrosternal area while
regurgitation is defined as the perception of flow of refluxed gastric contents into the mouth or hypopharynx.

EPIDEMIOLOGY
In western countries, GERD is presently the most common upper GIT disease with a symptomatic prevalence in
10-20 % of the population. Though the prevalence of this disease is lower in Asians, the incidence is gradually
increasing due to change in lifestyle like obesity, changes in sleeping pattern and aging population.

CLASSIFICATION
Based on the definition, GERD can be classified into
1. Esophageal syndrome
2. Extra-esophageal syndrome, this being subdivided into established association and proposed
association

It can also be classified on the basis of endoscopy findings into

A) Esophageal mucosal damage (erosive esophagitis and barrets esophagus)
B) No mucosal damage (non erosive reflux disease, NERD)
NERD patients have been sub-classified into 3 types on the basis of the results of 24-hour pH evaluation

Type 1: Patients who demonstrate an abnormal acid exposure time in a manner similar to those with erosive
esophagitis
Type 2: Patients with a normal acid exposure time, but with symptoms and reflux events that are significantly
correlated, suggesting acid hypersensitivity. This is also referred to as the hypersensitive esophagus.
Type 3: Patients with typical reflux symptoms, but normal pH studies, and no correlation between symptoms and
acid exposure. Within this group are 2 subgroups; namely: - those who respond to proton pump inhibitor
therapy and those who do not respond.

AETIOLOGY
The various risk factors include
a) Genetic- difference in incidences among the various population.
b) Esophagitis is seen more in male sex
c) Obesity is likely to increase GERD by 2.5 times
d) Habits- like Alcohol, cigarette, coffee, cola consumption
e) Hiatus hernia- is associated with incompetent LES, defective peristalsis, more severe mucosal damage,
and increased acid exposure leading to GERD and Esophagitis.
f) Associated with systemic disease like chronic obstructive airway disease, connective tissue disease
especially scleroderma.

272
 g) Associated with use of certain Drugs and hormonal products- like anti cholinergics, benzodiazepines,
calcium channel blockers, dopamine, nicotine, nitrates, theophylline, estrogen, progesterone, glucagon,
and some prostaglandins
h) Association with pregnancy

PATHOPHYSIOLOGY
In GERD, the transient relaxation of lower esophageal sphincter (LES), which is otherwise a normal
phenomenon, occur more frequently. This is because of the presence of higher intracellular calcium levels in the
resting LES compared with nonsphincteric esophageal muscle.

The esophagus, LES, and stomach can be likened to a simple plumbing circuit. The esophagus functions as an
anterograde pump, the LES as a valve, and the stomach as a reservoir. The abnormalities that contribute to
GERD can stem from any component of the system. A dysfunctional LES allows reflux of large amounts of
gastric juice. Delayed gastric emptying can increase volume and pressure in the reservoir until the valve
mechanism is overwhelmed, leading to GERD.

Other defects of the LES that may contribute to GERD include a chronically hypotensive LES and the effects of a
hiatal hernia.In the presence of a hiatal hernia, the LES may migrate proximally into the chest and lose its
abdominal high-pressure zone (HPZ), or the length of the HPZ may decrease. The diaphragmatic hiatus may be
widened by a large hernia, which impairs the ability of the crura to function as an external sphincter.

DIAGNOSIS
The Society of American Gastrointestinal Endoscopic surgeons (SAGES) Practice Guidelines stipulates that the
diagnosis of GERD can be confirmed if at least one of the following conditions exists:
A mucosal break seen on endoscopy in a patient with typical symptoms,
Barretts esophagus on biopsy, a peptic stricture in the absence of malignancy, or
Positive pH-metry

Clinical Presentation : Symptoms include heartburn and regurgitation as the characteristic presentation.
Vomiting, gastrointestinal bleeding, anemia, abdominal mass, unexplained weight loss, and progressive
dysphagia indicate complication.

Endoscopy: Endoscopy has a high specificity but low sensitivity as over 60% of patients with GERD actually
have NERD. Newer imaging procedures like high-resolution magnification endoscopy, chromoendoscopy,
narrow-band imaging, and confocal endomicroscopy may shed more light on cases that were hitherto classified
as NERD. In Proton Pump Inhibitor (PPI) Test, favored by the Asia-Pacific Consensus on the management of
GERD, a short trial of PPI to determine if the patient is going to have symptom relief is carried out. Significant
symptom improvement suggests GERD.

Manometry : In patients with persistent reflux symptoms despite PPI therapy and normal findings on endoscopy
a further evaluation with manometry is indicated to identify alternative diagnosis, such as motor esophageal
abnormalities. Manometry helps to analyze the function and the peristaltic activity of the body of the esophagus
and the LES prior to antireflux surgery. It is mainly used to establish the diagnosis of dysphagia in cases in which
a mechanical obstruction (e.g., stricture) cannot be found. It is also indicated for the preoperative assessment of
candidates for antireflux surgery, to exclude achalasia or ineffective peristalsis. Moreover, manometry serves to
localize the LES for subsequent pH monitoring for documentation of abnormal esophageal acid exposure.

pH Montoring : Patients with NERD who do not respond to medications are best evaluated by ambulatory pH
monitoring. Ambulatory esophageal pH monitoring is based upon the duration of time the intraesophageal pH is
less than 4, with normal defined as less than 4% over a 24-hour period.
This test allows the physician to quantify the number and duration of reflux episodes, differentiate between
upright and supine reflux, and correlate these events with subjective symptoms.

Esophageal impedance pH monitoring is a very promising technique. Multichannel intraluminal impedance

monitoring with pH sensor (MII-pH) can detect all types of reflux (acidic, weakly acidic, and weakly alkaline). This
test measures the resistance of electrical conductivity of the esophageal content, thus detecting any change of
esophageal pH due to the presence of liquid or gas reflux.

TREATMENT
The goals of treatment include relief of symptoms, healing of esophagitis, prevention of recurrence, and
prevention of complications. The principles of treatment include lifestyle modifications and control of gastric acid
secretion using drugs or surgical treatment with corrective antireflux surgery.

Lifestyle/Dietary Modifications: These are considered the first line of treatment. They include weight loss (for
patients who are overweight); avoiding alcohol, chocolate, citrus juice, tomato-based products, peppermint,
coffee, and onion. Other measures include avoiding large meals, decreasing fat intake, cessation of smoking,

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elevation of head of the bed, and avoiding recumbency for 3 hours postprandial. Pregnant women who have
GERD should be offered lifestyle modification as first-line therapy.

Antacids/Alginates : These are effective in symptom relief and should be taken after each meal and at bed
time.

Acid Suppressive Therapy: Currently, acid suppressive therapy forms the mainstay of GERD treatment.
Histamine 2 receptor antagonists (H2RAs) used for the treatment of milder forms of the disease and for on-
demand therapy, especially for nocturnal symptoms.

Proton pump inhibitors (PPI) are the most potent type of acid suppressants. Clinical experience shows that 20
30% of patients with GERD continue to have persistent reflux symptoms even while taking PPI daily.
Prokinetic agents are somewhat effective but only in patients with mild symptoms; Randomized controlled trials
provide moderate-quality evidence that prokinetic drugs improve symptoms in patients with reflux esophagitis and
low-quality evidence that they have impact on endoscopic healing.

Role of Surgery: Indications for Surgery

(1) Failed medical management (inadequate symptom control, severe regurgitation not controlled with acid
suppression, or medication side effects).
(2) Patients who opt for surgery despite successful medical management (due to quality of life
considerations, life-long need for medication intake, expense of medication etc.)
(3) Complications of GERD (Barretts esophagus, peptic stricture).
(4) Extraesophageal manifestations (asthma, hoarseness, cough, chest pain, and aspiration).
(5) Hiatal hernia with GERD

Over the past 50 years, surgery for GERD has evolved from an open to a laparoscopic procedure. The surgical
treatment of GERD is fundoplication,

Fundoplication : Fundoplication can involve a

-Complete wrap (360 degrees) (Nissens)
-Partial wrap (varying degrees) which may be
a) Anterior (Dor)
b) Posterior (Toupet) wrap 270 degrees.

Fundoplication are performed laparoscopically .The advantages of laparoscopic procedure include shorter
hospital stay, less pain, quicker return to work, fewer incidence of incisional hernias and fewer defective wraps at
follow-up endoscopy.

The most common procedure is Nissen fundoplication which is a complete (360 degrees) wrap of stomach. This
procedure is done under general anesthesia. A 300 reverse trendlenberg position is preferred. Steps of the
procedure include crural dissection, circumferential dissection of the esophagus, fundic mobilization, crural
closure with non absorbable sutures, wrap around the lower esophagus covering at least 3cms of the lower
esophagus, suturing of the wrap with non absorbable sutures and fixing of wrap to the right crus. Laparoscopic
Nissen fundoplication have shown to produce excellent symptom relief (87% to 97%),normalisation of acid
reflux>85% and patient satisfaction of > 95%.

In a Dor (anterior) fundoplication, the fundus is laid over the lower esophagus. Dor fundoplication is now
preferred as wrap after a hellers cardiomyotomy for Achalasia Cardia as it provides a cover for the exposed
mucosa as well as reduces reflux symptoms,

In Toupet (posterior) fundoplication, the fundus is wrapped around the back of the esophagus.
The Toupet procedure is a variant of the Nissen's wrap and involves a 270 posterior wrap in an attempt to
lessen the likelihood of postoperative dysphagia. Partial fundoplication causes fewer unwanted post-operative
effects but provides a less reliable and longstanding anti-reflux procedure.

Complications of fundoplication include persistent dysphagia, inability to belch and vomit, epigastric fullness,
bloating and postprandial pain, temporary swallowing discomfort, and sometimes intense flatus (known as the
syndrome of gas bloat).

Endoluminal fundoplication is a new, modified version of open or laparoscopic fundoplication which accesses the
stomach through the mouth, thereby eliminating the need for incisions.

CONCLUSION
Aspects of GERD have undergone tremendous innovations in the last two decades. There have been innovations
in the definition, classification, diagnosis, clinical course, and management of GERD. Nonerosive reflux disease
(NERD) is the variant of GERD that affects over 60% of patients with GERD and it is not only more
heterogeneous than erosive esophagitis but has a different pathophysiology and response to standard medical

274
therapy. Because GERD is a chronic, relapsing disease, patients have to be managed with either long-term
medical treatment or surgery after a thorough analysis of the pros and cons of each modality. The coming years
would further determine how effective and successful the newer methods and innovations be, with a better
understanding of the disease process.

Stapled Haemorrhoidopexy

PN Agarwal, Anurag Mishra

INTRODUCTION
1
Hemorrhoids are one of the commonest afflictions of mankind from time immemorial. It is said that 40 percent of
population have symptoms due to hemorrhoids at some time of their lives, a price possibly man has had to pay
following the evolution of his erect posture. 2 The treatment of hemorrhoids dates back to antiquity for the two
chief symptoms of bleeding and protrusion. The methods of treatment date back to the Babylonian era,
Hippocrates described the treatment by, cautery, which must have been extremely painful in the pre-anaesthetic
3
era. This has been mentioned in Sushruta Samhita of the ancient Indian medicine. At present a wide variety of
treatment is available for hemorrhoidal disease, ranging from advice on diet and bowel habit, through a number
of non-operative methods of mucosal fixation and widening of the anus, to a host of different techniques of
excision of the internal anal vascular cushions and the external vascular channels. The choice of method
depends on the severity and type of the symptoms, on the degree of prolapse and on the expertise of the
operator and equipment available.

About 40% of the patients suffering from hemorrhoids require surgery. 4 Conventional hemorrhoidectomy is a
commonly performed operation for hemorrhoids, it has good results but is a very painful procedure resulting in a
hospital stay for four to ten days and time off work for two to six weeks. 5 The patient also faces the complications
of hemorrhage immediate, reactionary or secondary, urinary retention, and late complications tike stenosis or
incontinence. In search of a surgical technique to treat the common condition of hemorrhoids, stapler has been
introduced for hemorrhoidectomy. Stapled hemorrhoidectomy has come up as a new and promising procedure
causing minimal post-operative pain, early discharge and quick return to work.

The technique of stapling for hemorrhoids was initially presented by Donald Peck. 6 from San Jose, CA
approximately fourteen years ago in which the hemorrhoidal tissue was removed by application of two
circumferential purse string sutures and subsequent firing of a circular stapler. However, this technique was
standardized in 1993 by Dr. Antonio Longo at the University of Palermo. 6

By means of a circling stapling gun, a low rectal mucosal resection and mucosal mucosal anastomosis act to
remove redundant rectal mucosa above the hemorrhoids, correcting the previous down ward displacement of the
anal cushions and interrupting the vessels in the submucosal plane. Unlike excision ligation techniques the
external hemorrhoidal components are not dealt with directly, these are observed to regress in the early post
operative period, eventually forming radial cutaneous folds. When questioned most patients thought the external
component was considerably resolved. No attempt should be made to excise the cutaneous component.
Residual external hemorrhoidal skin taps that could not be entirely drawn into the anus shrivel and become
asymptomatic.

Indications of Stapled hemorrhoidectomy:

Prolapsing hemorrhoids requiring manual reduction (Grade III);
Uncomplicated hemorrhoids, irreducible by the patient but reducible at surgery (Grade IV);
Selected prolapsing hemorrhoids with spontaneous reduction (Grade II);
Failure to alleviate hemorrhoidal symptoms by other methods
Contra-indications:
Abscess;
Gangrene;
Anal stenosis;
Full-thickness rectal prolapse.

PATIENT PREPARATION AND ANAESTHESIA

Patient is admitted on the day of surgery in morning. Patient preparation included administration of laxative night
before the operation. Patient is kept nil orally a night before surgery. A single intravenous dose of Inj.
Ciprofloxacin 200 mg and Inj. Metronidazole 500 mg on shifting to the operating room is administered. The
procedure can be performed under saddle block or general anaesthesia. Regional anaesthesia is preferred as it
facilitates early ambulation and discharge.

Stapler PPH set (PPH) is checked for its contents. It should consist of :
1. 33 mm Ethicon Endosurgery circular stapler (HCS)

275
 2. Circular Anal Dilator (CAD)
3. Purse string suture anoscope (PSA)
4. Suture Threader (ST)

POSITIONING OF PATIENT
Patient is positioned in a standard lithotomy position, with surgeon sitting in between patient legs.

OPERATIVE PROCEDURE
The anal verge is held by three atraumatic forceps at the three points and the anoderm is slightly
everted. Such a manoeuvre facilitates the introduction of Circular anal dilator (CAD) after lubrication with
jelly. The introduction of the CAD causes the reduction of the prolapse of the anoderm and parts of the
anal mucous membrane.
After removing the obturator, the prolapsed mucous membrane falls into the lumen of the CAD. As it is
transparent, the CAD allows visualisation of the dentate line. The CAD should be fixed to the perineal
skin through the four windows with silk suture on a cutting needle. CAD can be cut from the sides to
accommodate for the ischial tuberosities esp. in thin patients in whom it is difficult to introduce.
All remaining prolapsing tissues should be pushed back with atraumatic forceps through the windows of
the CAD.
The purse string suture anoscope (PSA) is now introduced through the CAD.
The suture is taken 4-5 cm above the dentate line with 2-0 polypropylene (on a 26-mm curved, round-
bodied needle), the distance to be increased in proportion to the degree of prolapse.
The purse string is initiated at 3 oclock position, moving in clockwise direction and including mucosa
and submucosa. By rotating the PSA, it will be possible to complete a purse string suture around the
entire anal circumference.
The PSA will cover 2700 of the circumference and expose a 900 window to work on. The 900 window
must first visualise the 3 oclock position, which is the beginning point of the purse string suture. On
completion of the purse string both ends of the suture will be at 3 oclock.
The PSA is now introduced to visualise the 9 oclock window and a second simple stitch with the same
suture material is placed at 9 oclock at the level of purse string. This is to ensure equal pull down of
mucosa into the hollow stapler along its entire circumference. In women, the posterior vaginal wall is
checked to prevent entrapment.
The hemorrhoidal circular stapler (HCS) is opened to its maximum position. Its head is lubricated,
introduced and positioned proximal to the purse string. The purse string is then tightened with a single
throw.
With the help of the suture threader (ST) both ends of the purse string suture are pulled through the 3-0
clock hole of the HCS. The suture threads at 9 oclock are pulled through the 9 oclock hole. A simple
throw on the two sets of threads or clamping the two sets of threads to an artery forceps allows
moderate traction on the purse string. This simple manoeuvre draws the prolapsed mucous membrane
into the casing of HCS.
The instrument is then tightened adequately by clockwise rotation till the orange indicator reaches as
close as possible to the distal end of the green firing zone. It is then fired.
Keeping the HCS in the closed position for 20 seconds before and after firing acts as a tamponade,
which promotes hemostasis.
The stapler is opened completely by anticlockwise rotation of the dial till it comes out of the anus.
Occasionally, this manoeuvre can be hampered by the pinching of mucous membrane between the
stapler head and the upper edge of CAD. In such cases, it is easier to extract the CAD and HCS
simultaneously by cutting the stay sutures that fix the CAD.
Finally the staple line is always examined using the PSA for any spurter and, if present, hemostatic
sutures are taken with 3-0 Vicryl.
Unlike excision-ligation techniques, the external hemorrhoidal components are not dealt with directly.
These are known to regress in the postoperative period. No attempt is made to excise the cutaneous
component (probably because it will result in postoperative pain similar to conventional techniques and
he whole purpose of using stapled procedure is nullified).

Precautions
1. The muscular wall should not be included in the purse string suture.
2. In female patients, before the stapler is fired, vaginal mucosa must be checked to ensure it is not tenting
into the housing of the stapler.
3. Just before firing, the 4 cm mark on HCS should be in line with or inside the CAD at anal verge.

POST OPERATIVE CARE

Following drugs were administered to the patient:
Inj. Ciprofloxacin 200 mg i.v. 12 hourly
Inj. Metronidazole 500 mg i.v. 8 hourly
Inj. Diclofenac 75 mg i.m. stat and then SOS

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The patient was allowed oral sips 2-4 hours after surgery and was allowed fully orally 6 hours after surgery if no
nausea or vomiting was noted.
The patient was encouraged to micturate when he/she had bladder sensation. They were seated on bed and
ambulated 5-6 hours after surgery. Local examination was done to look for any evidence of pad soakage /
bleeding.

The patients are discharged once they fulfilled the discharge criteria usually the next morning.

On discharge, patients are advised the following treatment:

1. Sitz bath
2. Tab. Ciprofloxacin 500 mg 1 bid for 5 days
3. Tab. Metronidazole 400 mg 1 tds for 5 days
4. Tab. Diclofenac Sodium 50 mg SOS
5. Syrup Cremaffin 4 tsf HS to be taken if constipated.

References
th
1. Goligher JC. In Surgery of the Anus, Rectum and Colon. Haemorrhoids or piles. 5 Ed. Bailliere Tindall
London 1992; Pg 98-149.
2. Hawley PR. Haemorrhoids. In Rec Adv Surg no. 8 Ed. Selwyn Taylor. Churchill Livingstone Edinburg and
London 1973; Pg 235-56.
3. Eastman PF and Applebaum IA. Critical evaluation of internal haemorrhoidal ligation as an outpatient
procedure. Amer J Proctol 1969;201-9.
4. Turell R. In Diseases of the colon and anorectum Ed. R Turell. Philadeplphia and London, Saunders 1960; Pg
888.
5. Seow Choen F. Stapled haemorrhoidectomy: pain or gain. Br J Surg 2001;88:1-3.
6. Longo A. Treatment of haemorrhoids disease by reduction of mucosa and haemorrhoid prolapsed with
th
circular suturing device: a new procedure. Proceedings of the 6 World Congress of Endoscopic Surgery
1998: pp777-784.

Laparoscopic cholecystectomy

Lovenish Bains, A K Sarda

INTRODUCTION
The laparoscopic revolution in general surgery began between 1985 and 1987, whenlaparoscopic
cholecystectomy was introduced. The development of the technique toperform a cholecystectomy by laparoscopy
was the beginning of a radical changethat, in a few years, involved general surgeons all over the
world.Laparoscopic cholecystectomy (LC) has become the standard of care for patients requiring the removal of
the gallbladder.A National Institutes of Health consensus statement in 1992 stated that laparoscopic
cholecystectomy provides a safe and effective treatment for most patients with symptomatic gallstones and has
become the treatment of choice for many patients.

LC is now the gold standard treatment of symptomatic gallstones and is the commonest operation performed
laparoscopically world-wide.The initial driving force behind the rapid development of laparoscopic
cholecystectomy was patient demand. Laparoscopic cholecystectomy has been more instrumental in ushering in
the laparoscopic age far more than any other procedure.Laparoscopic cholecystectomy decreases postoperative
pain, decreases the need for postoperative analgesia, shortens the hospital stay from 1 week to less than 24
hours, and returns the patient to full activity within 1 week. Laparoscopic cholecystectomy also provides improved
cosmesis and improved patient satisfaction as compared with open cholecystectomy.

However, a significant increase in the incidence of bile duct injury was noted more than that occurring in the era
of open cholecystectomy reaching up to 0.5% and injuries were more commonly reported early in each surgeons
experience. Issues like poor surgical technique, lack of understanding of how injuries occur, surgeon resistance
to convert to open surgery, inadequate visualization, inflammation, aberrant anatomy, and misidentification of the
ducts or other technical errors are key risk factors for the development of injuries and a debilitating sequelae of
bile duct injury leading to significant morbidity and cost. Bile duct injury rates have increased since the
introduction of laparoscopic cholecystectomy, occurring in about 3 per 1,000 procedures performed.Population-
based studies have reported a significant increase of iatrogenic bile duct injury incidence following LC, compared
to open technique, ranging from 0.3 % to 1%.

Henceforth it is essential to understand the technique for a safe cholecystectomy

SAGES (Society of American Gastrointestinal and Endoscopic Surgeons) has also launched The SAGES Safety
in Cholecystectomy Task Force, aiming to establish a universal culture of safety in laparoscopic

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cholecystectomy. The SAGES Safe Cholecystectomy Program has identified 6 strategies that a surgeons can
employ to adopt a universal culture of safety for cholecystectomy and to minimize the risk of bile duct injury.

INDICATIONS
The indications for laparoscopic operations on the gallbladder and biliary tree have not changedsince the 1992
National Institutes of Health Consensus Development Conference Statement onGallstones and Laparoscopic
Cholecystectomy.Most patients with symptomatic gallstones are candidates for laparoscopic cholecystectomy,
ifthey are able to tolerate general anaesthesia and have no serious cardiopulmonary diseases or other co-morbid
conditions that preclude operation.Symptomatic gall stones causing biliary colic, acute cholecystitis, mucocoele,
gallstone pancreatitis, cholecystitis and its complications like empyema gall bladder, gall bladder perforation,
gangrenous cholecystitis.

Cholecystectomy is not indicated in most patients with asymptomatic (silent) gallstones, because only 2-3% of
these patients go on to become symptomatic each year.In 2012 Duncan and Riall reviewed the evidence-based
current surgical practice for calculous gallbladder diseases and concluded that prophylactic laparoscopic
cholecystectomy for asymptomatic gallstone patients is still not recommended. Nevertheless, according to the
conclusion of 2009 Cochrane Review on LC in silent stones, there is no RCT or high-level studies which offer
scientific evidence to refuse LC to asymptomatic gallbladder stone patients. Till such data and evidence are
available, surgeons and patients together would take a decision depending on their assessment of individual
risks and choices. There MAY be a case for suggesting preventive cholecystectomy in a young (20s or 30s)
patient with large gall stones in northern India but, as of today, there is no data or evidence to support it.Patients
who are immunocompromised, are awaiting organ transplantation, or have chronic hemolytic conditions (sickle
cell anemia) are at higher risk for the development of complications and should be treated irrespective of the
presence or absence of symptoms.

Additional reasons to consider laparoscopic cholecystectomy include the following:

Calculi greater than 3 cm in diameter, particularly in individuals in geographic regions with a high
prevalence of gallbladder cancer
Non-functioning gallbladder; biliary dyskinesia
Calcified (porcelain) gallbladder
Gallbladder polyp larger than 10 mm or showing a rapid increase in size
Gallbladder trauma
Anomalous junction of the pancreatic and biliary duct
Life expectancy >20 years
Questionable Indication- Patient living in an area remote from medical facilities
Indications include but are not limited to symptomatic cholelithiasis, biliary dyskinesia, acute
cholecystitis, and complications related to common bile duct stones including pancreatitis with few
relative or absolute contraindications.(Level II, Grade A).
Relative contra-indications are untreated coagulopathy, lack of equipment, lack of surgeon expertise,
hostile abdomen,advanced cirrhosis/liver failure, and suspected gallbladder cancer.(Level II, Grade A).

PRE OPERATIVE ANTIBIOTIC PROPHYLLAXIS

A recent meta-analysis of randomizedcontrolled trials concluded prophylactic antibiotics do not prevent infections
in low risk patientsundergoing laparoscopic cholecystectomy, while the usefulness of prophylaxis in high
riskpatients (age > 60 years, the presence of diabetes, acute colic within 30 days of operation,jaundice, acute
cholecystitis, or cholangitis) remains uncertain. The latestrandomized, prospective study included in the above
mentioned meta-analysis showed no difference in thepostoperative wound infection rate, although the control
group had a 1.5% infection rate and theantibiotic group had a 0.7% infection rate.

The current status is:

Antibiotics are not required in low risk patients undergoing laparoscopiccholecystectomy. (Level I, Grade
A).
Antibiotics may reduce the incidence of wound infection in high risk patients (age > 60years, the
presence of diabetes, acute colic within 30 days of operation, jaundice, acutecholecystitis, or
cholangitis). (Level I, Grade B).
If given, they should be limited to a single preoperative dose given within one hour ofskin incision. (Level
II, Grade A).

PATIENT POSTIONING
There are two basic room set-ups for performinglaparoscopic biliary tract surgery. The first is the standard supine
position with the surgeonstanding at the patients left and monitors at the head of the table (American approach).
The second iswith the patient in stirrups the surgeon standing between the legs (European Approach).Some
surgeons tuck the left arm to improve theworking space of the operating surgeon. The patient is generally placed
in a reverseTrendelenburg position and rotated right side up once the pneumoperitoneum has been established.
A nasogastric tube is inserted and the stomach aspirated. The tube is kept in the stomach during the operation

278
but removed at the end of the procedure. The surgeon operates from the left side of the patient with the camera
person by his side and the assistant and scrub nurse on the other side of the operating table.

With no data to guide choices, surgeon preference should dictate room set-up. (Level III, Grade A).

Ensure that the instruments and necessary equipment like light source, telescope, CO2 insufflator, electro
cautery or other energy sources, cables and connections are adequately functioning before the start of
procedure.

STEPS

1. Creation of pneumoperitoneum and ports placement

The creation of pneumoperitoneum is the foremost step for any laparoscopic procedure. Both open and closed
methods for gaining peritoneal access are in use and are reportedly safe. A recent meta-analysis of 17
randomized controlled trials comparing a variety of open and closed access techniques found no difference in
complication rates; potentially life threatening injuries to blood vessels occurred in 0.9 per 1000 procedures and
to the bowel in 1.8 per 1000 procedures. As of now, there are no demonstrable differences in the safety of open
versus closed techniques for establishing access and creating the initial pneumoperitoneum, therefore decisions
regarding choice of technique are left to the surgeon and should be based on individual training, skill, and case
assessment. The patient is asked to empty the bladder before the procedure and stomach should be aspirated
especially when the closed technique or Verres needle is used. The various techniques are:

i) Verres needle.
ii) The open Hasson technique.
iii) Directtrocar placement without prior pneumoperitoneum.
iv) The optical view technique, in which thelaparoscope is placed within the trocar so that the layers of
the abdominal wall are visualized asthey are being traversed.

Open technique
The technique entails a small sub-umbilical incision that is taken down to the linea alba. The skin edges are
retracted with small Langenbeck retractors and the fat separated from the umbilical scar. The umbilical pillar is
lifted with a towel clip and the junction between the umbilical pillar and the linea alba is defined, this site all the
layers of linea alba and umbilical cicatrix are fused and the thinnest. An incision is made in the umbilical scar in a
vertical direction to incise only the fascia and rectus sheath. The peritoneum is entered gently with the little finger
or closed artery forceps, the little finger is used to sweep the peritoneal surface of the incision to remove any
adhesions. The trocar is introduced without its introducer and is done under vision, therefore it is said to be safer
in preventing bowel or vascular injury during the first port insertion. This is especially true for patients where
previous surgery has been done and adhesions are expected.

Closed technique or Verres Needle

The Verres needle is introduced in the peritoneal cavity directly in the infraumblical or supraumblical site. Care is
taken to lift the infraumblical abdominal wall (this makes the intestinal loops fall back in the cavity) and direct the
needle towards the pelvis. These two steps prevent the needle inadvertently entering bowel wall or major
vessel.Grasp the shaft of the Verres needle with the dominant hand like a dart and enter into the incision- at 45
degrees caudal angle (in asthenic patients) or 90 degrees vertical (in obese patients). There will be sensation of
initial resistance followed by a give at two points- traversing of fascia and peritoneum. Confirm position of needle
in peritoneal cavity and begin insufflation. The trocar is placed blindly once the abdomen has been distended.

The telescope is introduced into this first port and rest of the ports are placed under vision to ensure that no
abdominal structure is injured while penetrating. The four port technique of laparoscopic cholecystectomy as
described by Reddick is the most widely adopted technique.

A 10mm port [a] in the epigastrium at the junction ofupper 1/3rd and lower 2/3rd of the line joining xiphisternum
and umbilicus., a 5mm port [b] at the midclavicular line about 2cm below the costal margin, and a 5mm port [c] at
the anterior axillary line at the 5-8 cm below the costal margin. The epigastric port is placed just right of the
falciform ligament. A primary intra abdominal survey is done and patient moved into position.

2. Dissection of hepato-cystic triangle.

The fundus of the gall bladder is held with a ratcheted grasper and retracted by the assistant in a cranial direction
towards patients right shoulder. Adhesions are separated from the gall bladder and surrounding structures with
care to always remain close to gall bladder. The subcostal port grasper is used to grasp the gall bladder at the
infundibulum and retract it laterally and caudally to widen the peritoneal fold containing the cystic artery and duct
and to place on a stretch.Dissection commences in the safest area by division of the peritoneal fold between the
Hartmans pouch and the liver using a curved dissector or hook dissector. The dissection is blunt or using short
bursts of electrocautery. The key to safe dissection is by remaining close to the gall bladder. This space is

279
cleared till the junction between the gall bladder and cystic duct is seen and cystic artery identified. The
infundibular grasper is retracted antero-medially and the posterior aspect of Calots triangle is exposed. Again the
dissection is started from the junction of the liver and the Hartmans pouch. This is continued to separate the
cystic duct and cystic artery and to completely skeletonise these structures. Both structure should be identified
from anterior and posterior view ()

Fig. 1: Port placements

It is essential to use the Critical View of Safety (CVS) method defined by Strasberg et al and endorsed by
SAGES for identification of the cystic duct and cystic artery during laparoscopic cholecystectomy which
emphasizes three criteria-
The hepatocystic triangle is cleared of fat and fibrous tissue. The hepatocystic triangle is defined as the
triangle formed by the cystic duct, the common hepatic duct, and inferior edge of the liver. The common
bile duct and common hepatic duct do not have to be exposed.
The lower one third of the gallbladder is separated from the liver to expose the cystic plate or liver bed. .
Two and only two structures should be seen entering the gallbladder.

Fig. 2: Critical view of safety (anterior view)

rd
Both structures and lower 1/3 of cystic plate should be identified from anterior and posterior views i.e. Doublet
view.

3. Ligation and division of cystic artery and duct

Once the structures have been confirmed, the cystic duct is clipped preferably with two clips onthe proximal end
and single clip on the distal end and is divided between these clips.During clip application, traction of the
Hartmans pouch is laterally so that the cystic duct is at rightangle to the Common Hepatic Duct (CHD) and

280
Common Bile Duct (CBD) junction. This ensures thatclip is applied only on the cystic duct and does not take a
bite of the CHD or CBD. The clip is onlyapplied only after both the limbs of the clip applicator are completely
visualized. This ensures that noother structure is taken in the clip.Cystic artery is also clipped in similar way and
divided. It is desirable to divide artery before the duct, however in certain situations duct needs to be divided to
expose the artery. Care is taken not to retract the cystic duct so forcefully that the clip impinges onto common
hepatic duct. One should be aware of various anatomical aberrations of duct and artery before clipping and
dividing them. Ensure use of proper sized clips. Too large clips can slip out later and too small clips can lead to
incomplete closure of the duct leading to leakage.Commonly used clips 200 (medium) has aperture of 4 mm and
closed length of 5.39 mm, 300 (medium/large) has aperture of 6.4 mm and closed length of 8.99 mm, whereas
400 (large) has aperture of 7.5 mm and closed length of 12.26 mm.

Fig. 3: Traction on Hartmans pouch before clipping.

4. Separation of gall bladder from liver bed & Extraction of specimen

The separation of gall bladder from the liver bed is usually a combination of blunt and sharp dissection aided
significantly by the traction of gall bladder. The peritoneal folds are made taut, first medially and then laterally, the
gall bladder is separated from the fossa using a diathermy hook, spatula, scissors or Harmonic Scalpel. This
allows maximum tension on the folds and also gives upward traction on the liver so that bleeding points can be
visualized and coagulated during dissection of the gall bladder. Prior to complete detachment, the liver bed is
inspected for adequate hemostasis or bile leak. The table is positioned in the normal position.

The extraction of gall bladder can be carried out through the umbilicus or the epigastric port.
A 10 mm extractor is introduced and gall bladder is grasped at the neck. It is withdrawn in the 11 mm port and
delivered out along with the port. However if the gall bladder is too distended to come out of the port, then holding
the gall bladder with theextractor, the complete port is withdrawn out of the abdomen to bring the mouth of the
gall bladder outof the abdominal opening. The ends are held with artery forceps and bile can be aspirated, before
itsremoval, to decrease the size of the gall bladder. If the gall bladder is still too large, stones can beextracted to
allow its removal or else the fascial incision can be extended to expedite removal of gall bladder.Any such
anticipation can be dealt by placing the gall bladder in indigenously made glove bag or commercially available
Endobag.This prevents rupture of the gall bladder inside the abdomen, spill of stones or bile andconsequent
chances of contamination.

5. Final inspection and port closure

The gall bladder fossa is examined again for hemostasis, through wash with saline is given in cases of bile or
stone spill. A drain if required can be placed through the lateral most port. The instruments and ports are
withdrawn under vision to check that no bleeding occurs from trocar sites. Pneumoperitoneum is evacuated. The
fascia of the 10 mm ports is closed with polyglactin suture. Skin closure is done with sutures, clips or glue.

TIPS & COMMENTS

1. Use the Critical View of Safety (CVS) method of identification of the cystic duct and cystic artery during
laparoscopic cholecystectomy.
2. Perform an Intra-operative Time-Out during laparoscopic cholecystectomy prior to clipping, cutting or
transecting any ductal structures.
3. Understand the potential for aberrant anatomy in all cases.
4. Make liberal use of cholangiography or other methods to image the biliary tree intraoperatively.
5. Recognize when the dissection is approaching a zone of great danger and halt the dissection before entering
the zone. Finish the operation by a safe method other than cholecystectomy if conditions around the
gallbladder are too dangerous.
6. Get help from another surgeon when the dissection or conditions are difficult.

281
 The above mentioned are the 6 strategies surgeons can employ to adopt a universal culture of safety for
cholecystectomy to and minimize the risk of bile duct injury. (Adapted from The SAGES Safe
Cholecystectomy Program)

7. Stay close to the gall bladder at all times or hug the gall bladder. The dissection should always start at the
infundibulum of the gallbladder, enabling an easy location of the cystic duct.
8. Mucocoele of gall bladder should be aspirated before starting the procedure. If the gall bladder gets open
while dissection, the rent can be closed with a large clip or Endoloop.
9. Do not apply clips blindly in case of bleeding as this might lead to panic reaction. This only spells disaster.
The immediate response to bleeding should be compression.
10. Gall bladder may be used to give direct compression on the bleeding site if this is in the gallbladder bed. In
case of bleeding from the cystic artery, gauze can be used to compress the area and once the bleeding is
controlled, careful diathermy of the bleeding point can be done. Clips are rarely required.
11. In case of difficult anatomy, where the Calots triangle cannot be isolated properly, a fundus first approach
may be used to reach the junction of gall bladder and cystic duct.
12. Clips on the artery should always be double for extra safety.
13. A short cystic duct can be lengthened after dissecting and dividing the cystic artery flush with the gall bladder
and teasing out fibrous bands which kink and shorten the duct.
14. Laparoscopic cholangiography is no substitute for careful dissection. Its main indication is to exclude or
confirm presence of CBD calculi.
15. Over-confident surgeon and the easy case may spell danger.
16. Patients outcome from complications is best if detected during first surgery and correctivemeasures taken
during the same sitting.
17. Conversion to open cholecystectomy is not a failure but very judicious and wise decision of the surgeon to
prevent iatrogenic injuries to bile ducts and surrounding viscera, thus minimising the morbidity of the patient.

References

1. National Institutes of Health (NIH). Gallstones and Laparoscopic Cholecystectomy. NIH Consensus
Statement. NIH. September 14-16, 1992.
2. Keus F, de Jong JAF, Gooszen HG, van Laarhoven CJHM. Laparoscopic versus open cholecystectomy for
patients with symptomatic cholecystolithiasis. Cochrane Database of Systematic Reviews 2006:CD006231
3. Archer SB, Brown DW, Smith CD, Branum GD, Hunter JG. Bile duct injury during laparoscopic
cholecystectomy: results of a national survey. Ann Surg. 2001 Oct;234(4):549-58; discussion 558-9.
4. Giovanni Conzo, Salvatore Napolitano, Giancarlo Candela, Antonietta Palazzo, Francesco Stanzione et al. (2012).
Iatrogenic Bile Duct Injuries Following Laparoscopic Cholecystectomy: Myth or Reality? A Recent Literature
Review from 2006 to 2011, Cholestasis, Dr Valeria Tripodi (Ed.), ISBN: 978- 953-51-0043-0, InTech
5. Guidelines for the Clinical Application of Laparoscopic Biliary Tract Surgery. http://www.sages.org/
6. Strategies for Minimizing Bile Duct Injuries: Adopting a Universal Culture of Safety in Cholecystectomy. The
SAGES Safe Cholecystectomy Program. http://www.sages.org/safe-cholecystectomy-program/
7. Sherwinter DA, Adler HL,Fink SL. Laparoscopic Cholecystectomy.
http://emedicine.medscape.com/article/1582292-overview
8. Duncan CB, Riall TS. Evidence-based current surgical practice: calculous gallbladder disease. J Gastrointest
Surg. 2012 Nov;16(11):2011-25. doi: 10.1007/s11605-012-2024-1. Epub 2012 Sep 18.
9. Behari A, Kapoor VK. Asymptomatic Gallstones (AsGS) - To Treat or Not to? Indian J Surg. 2012 Feb;74(1):4-12.
doi: 10.1007/s12262-011-0376-5. Epub 2011 Dec 3.
10. Choudhary A, Bechtold ML, Puli SR, Othman MO, Roy PK. Role of prophylactic antibiotics in laparoscopic
cholecystectomy: a meta-analysis. J Gastrointest Surg 2008;12:1847-53; discussion 53.
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11. Palanivelu C. Art of Laparoscopic Surgery. 1 Ed. Jaypee Publishing; 2007
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12. Zucker KA. Surgical Laparoscopy. 2 Ed. Lippincott Williams & Wilkins; 2001
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13. Deshpande S, ed. Comprehensive Laparoscopic Surgery. 3 Ed. IAGES
14. Ahmad G, Duffy JM, Phillips K, Watson A. Laparoscopic entry techniques. CochraneDatabase Syst Rev
2008:CD006583
15. Reddick E.J. Laparoscopic Laser Cholecystectomy: Technique and Results. Dig Surg 1991;8:7983
16. Cuschieri A. How I do it- Laparoscopic Cholecystectomy. J R Coll Surg Edinb, 44, June 1999, 187-92
17. Strasberg SM, Brunt LM. Rationale and use of the critical view of safety in laparoscopic cholecystectomy. J Am
Coll Surg. 2010 Jul; 211(1):132-8. doi: 10.1016/j.jamcollsurg.2010.02.053. Epub 2010 May 26.
18. Vettoretto N, Saronni C, Harbi A, Balestra L, Taglietti L, Giovanetti M. Critical view of safety during laparoscopic
cholecystectomy. JSLS. 2011 Jul-Sep;15(3):322-5. doi: 10.4293/108680811X13071180407474.
19. Dulucq, Jean-Louis. Tips and Techniques in Laparoscopic Surgery. Springer 2005
20. Scott-Conner CEH, ed. The SAGES manual: Fundamentals of laparoscopy, thoracoscopy, and GI endoscopy. 2
ed: Birkhuser; 2005
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21. Strasberg SM A teaching program for the "culture of safety in cholecystectomy" and avoidance of bile duct
injury. J Am Coll Surg. 2013 Oct;217(4):751. doi: 10.1016/j.jamcollsurg.2013.05.001. Epub 2013 May 23.
22. Tsalis K, Antoniou N, Koukouritaki Z, Patridas D, Christoforidis E, Lazaridis C.Open-access technique and
"critical view of safety" as the safest way to perform laparoscopic cholecystectomy. Surg Laparosc Endosc
Percutan Tech. 2015 Apr;25(2):119-24.

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 Carcinoma Tongue

Ravi Kannan

Surgical anatomy
The tongue is divided by the circumvallate papillae into the anterior 2/3rds or oral tongue which is a subsite of the
oral cavity and a posterior 1/3rd or base of tongue which is a subsite of the oropharynx. This division is essential
since squamous cell carcinoma at these two sites behaves very differently and the treatment approach differs.
More than 95% of tongue cancers are squamous cell cancers to which this discussion will be limited to.

The oral cavity extends posteriorly from the lips to the junction of the hard and soft palates superiorly, the anterior
tonsillar pillars laterally, and the line of the sulcus terminalis and circumvallate papillae of the tongue inferiorly. It
is subdivided into multiple subsites: lip, oral tongue, floor of mouth, buccal mucosa, lower gingivum, retromolar
trigone, hard palate, and upper gingivum.

The oropharynx is a posterior continuation of the oral cavity and extends superiorly to the level of the soft palate
and inferiorly to the level of the hyoid bone. This is subdivided into multiple subsites: the tonsils, soft palate,
tongue base, valleculae, and posterior pharyngeal wall.

The tongue occupies portions of both the oral cavity and the oropharynx. The mobile anterior two-thirds is part of
the oral cavity and is referred to as the oral tongue. The fixed posterior one-third occupies the oropharynx and is
referred to as the tongue base. The line of demarcation of the oral tongue and the tongue base is at the sulcus
terminalis, which is a V-shaped groove just behind the circumvallate papillae. The dorsum, or upper surface, of
the tongue is velvety because it is covered by numerous filiform papillae, with interspersed larger fungiform
papillae. Just anterior to the sulcus terminalis are a row of large circumvallate papillae, which contain the taste
buds. The foramen caecum, a small blind pit at the apex of the sulcus terminalis, represents the site of origin of
the thyroid gland, and it may also be the site of ectopic thyroid tissue or a true lingual thyroid gland. The dorsum
of the tongue base is covered by lymphoid tissue, which represents the lingual tonsils.

The smooth mucosa of the ventral surface of the oral tongue transitions into the floor of the mouth mucosa
anteriorly and laterally. Anteriorly, the frenulum linguae attaches the tongue to the anterior floor of the mouth. The
muscles of the tongue consist of three sets of paired intrinsic muscles and three sets of paired extrinsic muscles.
The intrinsic muscles are the longitudinal (superior and inferior), vertical, and transverse muscles. These muscles
make up the body of the tongue and function to alter the shape of the tongue during speech and swallowing. The
extrinsic muscles include the paired genioglossus, hyoglossus, and styloglossus muscles, which serve to move
the tongue and change its shape. The hyoglossus is a flat muscle that rises from the body and greater horn of the
hyoid bone behind the mylohyoid muscle, and extends superiorly and anteriorly into the tongue, interlacing with
fibers of the other muscles. The styloglossus muscle originates from the styloid process and stylohyoid ligament,
and runs anteroinferiorly beneath the mucosa of the glossotonsillar sulcus to insert into the side of the tongue.
The genioglossus muscle originates from the mental spine on the inner surface of the mandible, immediately
above the geniohyoid muscle, and fans out as it extends posteriorly. The lower fibers insert into the body of the
hyoid bone, but the majority of fibres run superiorly and posteriorly to insert into the tongue, from the base to the
tip. The palatoglossus muscles, which insert into the posterolateral tongue do not function in tongue movement.
The midline of the tongue has a fibrous septum that attaches it to the hyoid bone posteriorly and provides an
avascular plane that separates the two sides of the tongue. The septum is present through the entire tongue but
does not reach the dorsum.

The connective tissue that separates the muscular bundles of the tongue provides a weak barrier to the spread of
tumor. This coupled with the constant mobility of the tongue results in deep invasion by malignant tumors
because significant symptoms do not occur until speech or swallowing are affected or the lingual nerve is
invaded. Tumors of the tongue are frequently advanced at diagnosis. The infiltrative nature of carcinoma of the
tongue mandates resection of large parts of the tongue to ensure clear margins. A 2 cm margin of normal
tissuearound the cancer is therefore recommended. When possible, frozen-section confirmation of clear margins
is carried out.

Infiltration of the extrinsic muscles of the tongue limits the ability to protrude the tongue out of the oral cavity, a
condition called ankyloglossia. With invasion of the root of the tongue, surgical extirpation requires total
glossectomy because all attachments of the tongue are transected with removal of the root. This will entail either
division of all the suprahyoid muscles or en-bloc resection of the hyoid bone. The upwards and forward
movement of the larynx during the third phase of deglutition will not be possible resulting in severe and
sometimes life threatening aspiration. A total laryngectomy may therefore accompant the total glossectomy or
may be necessary post operatively. When a part of the posterior tongue and its extrinsic muscles are left intact,
bulky myocutaneous flaps that overhang the larynx along with ventral suspension of the larynx may reduce
aspiration. A permanent tracheostomy may still be necessary.

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The relationship of the oral tongue to the floor of mouth is important in maintaining tongue mobility. Squamous
cell carcinoma of the oral tongue is most commonly located on the lateral surface of the middle third of the
tongue, in proximity to or involving the floor of mouth. After resection of tumors of the tongue or floor of mouth,
attempts should be made to reconstitute a sulcus between the tongue and the mandibular alveolus to prevent or
minimize tethering of the tongue, allowing optimum postoperative rehabilitation of speech and swallowing. With
resection of up to half of the tongue, primary closure, healing by secondary intention, skin grafting, or a thin
pliable flap (i.e., platysma flap, free radial forearm) will accomplish this goal and allow better tongue function
postoperatively. More extensive resection of the tongue presents more difficult problems and usually requires
reconstructive techniques to restore bulk to the tongue.

The arterial supply to the tongue is from the paired lingual arteries, which originate from the external carotid
artery at the level of the greater horn of the hyoid bone. The lingual artery passes deep to the hyoglossus muscle
and gives off one or two deep lingual branches that supply the tongue base. The sublingual artery originates near
the anterior border of the hyoglossus muscle and continues forward between the mylohyoid and genioglossus
muscles to supply these muscles, the geniohyoid muscle, and the sublingual gland. The remainder of the lingual
artery proceeds forward as a dorsal lingual artery between the genioglossus and longitudinal muscles. It reaches
the ventral surface of the tongue just deep to the mucosa, where it is accompanied by the deep lingual vein,
which can be seen through the thin mucosa of the ventral tongue. The remainder of the venous drainage
accompanies the arterial branches, ultimately joining the deep lingual vein to form the lingual vein, which empties
into the internal jugular vein. Only at the tip of the tongue is there any anastomosis across the midline between
the lingual arteries.

The hypoglossal nerve (cranial nerve XII) supplies motor innervation to the extrinsic and intrinsic muscles of the
tongue. As it travels beneath the lateral fascia of the hyoglossus muscle, it innervates the extrinsic muscles, and
as it reaches the anterior border of this muscle, it penetrates the tongue around the midportion of the oral tongue
to supply the intrinsic muscles. Sensory innervation of the oral tongue is from the lingual nerve (a branch of V3)
and that of the base tongue through the glossopharyngeal nerve (cranial nerve IX). The lingual nerve travels in
the floor of mouth above the hypoglossal nerve, between the mylohyoid and hyoglossus muscles, to innervate
the anterior two-thirds of the tongue and floor of mouth. The chorda tympani branch of the facial nerve travels
with the lingual nerve and supplies taste to the anterior two-thirds of the tongue. Sensation and taste are supplied
to the base of the tongue by the glossopharyngeal nerve. This nerve enters the oropharynx laterally through the
interspace between the superior and middle pharyngeal constrictor muscles and enters the base of the tongue
posterior to the hyoglossus muscle.

During glossectomy, preservation of at least one hypoglossal nerve is necessary to maintain some tongue
mobility and prevent severe oral dysfunction. Referred otalgia to the ipsilateral ear is a common symptom of
carcinoma of the tongue because V3 (the mandibular division of the trigeminal nerve) also provides sensory
branches to the external auditory canal, tympanic membrane, and temporomandibular joint through the
auriculotemporal nerve. The glossopharyngeal nerve also provides sensation to the middle ear via Jacobsens
nerve.
The tongue has an extensive submucosal lymphatic plexus that ultimately
drains to the deep jugular lymph-node chain. In general, the closer to the tip of
the tongue the lymphatic vessels arise, the lower the first echelon node. The
tip of the tongue drains to the submental nodes( level Ia), the lateral tongue to
the submandibular (level Ib) and jugulo-digastric nodes, (level II) and jugulo-
omohyoid(level III), and the tongue base to the jugulo-omohyoid level III and
jugulo-digastric nodes. In addition, there is communication of lymphatic
vessels across the midline of the tongue, which results in a high incidence of
bilateral metastases of tumors of the tip of the tongue and the base of the
tongue and tumors that approximate the midline of the tongue. The rich
lymphatic network results in early metastases to cervical lymph nodes, even
from small tumors (T1 or T2 upto nearly 30%). Therefore, consideration of
treatment of one or both sides of the neck, either by neck dissection or
radiation therapy, is advised in most tongue cancers.

The base of tongue is the posterior portion of the tongue, posterior to the
circumvallate papillae and sulcus terminalis. It extends posteriorly to the level
of the valleculae and is laterally continuous with the inferior pole of the tonsils.
The base of tongue contains submucosal lymphatic collections referred to as
lingual tonsils, which together with the palatine tonsils and adenoids (pharyngeal and tubal tonsils) form
Waldeyers ring, a first line of immunologic defense.

The sensory innervation of the base of tongue is through the glossopharyngeal nerve, which supplies general
and special visceral afferent fibres for taste. The base of tongue musculature is innervated by the hypoglossal
nerve. The arterial supply of the base of tongue is through the lingual arteries.

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The base of tongue has a rich submucosal lymphatic drainage system primarily to nodes at levels I, II and III.
Lymphatic drainage to both sides of the neck is common. This necessitates addressing both the ipsilateral and
contralateral neck when treating cancers of the base of tongue because of the likelihood of bilateral metastases,
even with small tumors.

The base of tongue extends posteriorly into paired concavities called the valleculae along the base of the lingual
surface of the epiglottis. The valleculae are separated in the midline by a median glossoepiglottic fold and are
bounded laterally by lateral glossoepiglottic folds, which attach the epiglottis to the base of tongue.

Points to remember:
1. The tongue is a mass of striated muscle, innervated by the hypoglossal nerve (XII) and covered with a
specialized mucosa textured with lingual papillae. Its extrinsic muscles primarily control its placement,
whereas its intrinsic muscles primarily control its shape, for manipulation of food during chewing, swallowing,
and speech. It is highly sensitive, with four cranial nerves contributing sensory fibers to it. The terminal
sulcus divides it into an anterior two thirds, receiving general sensation from the lingual nerve (V 3) and taste
fibers from the facial nerve(VII), and the posterior third receiving all
sensory innervation from the glossopharyngeal nerve ( IX).
2. Resection and reconstruction for tongue cancer needs to plan for
rehabilitation of speech, swallowing and respiration (aspiration is an
issue).

Aetiology of tongue cancer

Tobacco chewing and smoking in any form are causes of oral cancer. In
India, smoked tobacco may be in the form of cigarette, beedi, hookkah, hookli,
cheroot, cigar, chillum, chutta, dhumti, kretaka or pipe. Non smoke (or
chewing or spitting) tobacco may be in the form of ghutka, khaini, tobacco
paan, paan masala, zarda, meetha or mawa. In some tribal communities,
tobacco water is used. Tobacco is also used as snuff or applied to teeth and Fig 2: lingual cancer in a
gums as gul, gudaku dant manjan (tooth paste), creamy snuff or mishri. tobacco quid chewer. Note
leucoplakia along the floor of
Current smokers have a three-fold increased risk of oral cancer. The risk of the mouth where the quid is
oral cancer in smokers is both dose and duration dependent while smoking retained.
cessation leads to a fall in risk. http://info.cancerresearchuk.org/cancerstats/
types/oral/riskfactors/ - source1 However, a recent study showed that it takes 20 years or longer for the risk to
reduce to that of never smokers. Exposure to secondhand smoke (SHS) for 15 years or more is associated with
a 63% risk increase in never smokers exposed to SHS at home or at work while those exposed at both places
have an 84% risk increase.

Indian women who practice reverse chutta smoking, with the lighted end of the cigar inside the mouth, have
particularly high rates of oral cancer of the palatal mucosa. Smoking bidi(s) which are made of hand-rolled
tobacco wrapped in tendu leaf also increases the risk of oral cancer.

The carcinogenic potential of smokeless tobacco has been confirmed in a number of studies. The first report
linking tobacco chewing and oral cancer was made by Balram in 1895 from Neyoor in the erstwhile travancore
state. Risk varies according to the composition of smokeless tobacco used in different countries. A recent meta-
analysis showed a more than doubling in risk of oral cancer with use of smokeless tobacco in the United States
and Canada, a five-fold risk increase for India and other Asian countries and a seven-fold risk increase in Sudan.

The primary cause of the very high incidence of oral cancer in South Asia is the widespread habit of chewing
betel quid (or paan) and related areca nut use (areca nut is the seed of the fruit of the oriental palm, Areca
catechu). Chewing betel dates back at least 2000 years and finds reference in many ancient Indian texts. The
components of the betel quid vary between different populations but the main ingredients are the leaf of the betel
vine, areca nut, slaked lime (calcium hydroxide) and spices. Tobacco was introduced to India in the seventeenth
century. Areca nut chewing is carcinogenic in humans and the risk is higher when chewed with tobacco and
paan. The risk is dependent on dose and duration of tobacco use.

Alcohol is a major risk factor for oral cancer. People who both drink and smoke have a much higher risk of oral
cancer than those using only alcohol or tobacco. Heavy drinkers and smokers have 38 times the risk of
abstainers from both products. Risk of alcohol consumption also interacts with risk of smokeless tobacco, with a
combined risk of regular alcohol consumption and tobacco chewing of 24 shown in one study.

The quantity of ethanol ingested appears more important than the type (beer, wine). In Europe, rising trends in
oral cancer mortality have been related to increasing levels of alcohol consumption while a decrease in alcohol
consumption has been linked to fall in oral cancer mortality rates.

Use of mouthwashes, (even those with high alcoholic content) has not been shown to increase risks of oral
cancer.

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Diet and nutrition: A meta-analysis showed a significant risk reduction of about 50% for each additional daily
serving of fruit or vegetables. A large prospective study, published since this meta-analysis, showed a smaller
significant risk reduction for oral cavity cancer of 26% for each additional serving of vegetables, but no
association for fruit intake. Results may vary by smoking status, with a large case-control study showing risk
reductions with the highest intake of fruit and vegetables among smokers and alcohol consumers but not among
people who had never smoked or drunk alcohol.

Risk of oral cancer appears to fall with increasing body mass index (BMI). A recent case-control study in Spain
reported a significant reduction in risk of oral cancer with higher BMI at diagnosis and two years prior to
diagnosis, after adjustments for smoking, drinking, fruit and vegetable intake, although the association was not
significant among people who had never smoked. Since then, a case-control study showed a lower risk with
higher BMI two years prior to the study among never and ever smokers.

Human papillomavirus and immunosuppression: There is evidence that infection with high-risk human
papillomaviruses (HPV) increases risk of oral cancer, particularly HPV-16. The association is strongest for
cancers of the oropharynx. Studies show an increased risk of oral cancer in women with previous HPV-
associated anogenital cancer, providing more evidence of a link with HPV infection. In addition, a history of more
sexual partners or oral sex partners has been associated with an increased risk of oropharyngeal cancer, and a
younger age at sexual debut or history of oral sex with an increased risk of cancer of the tonsil and base of the
tongue, again pointing to a role of sexually-transmitted HPV. An increased risk of oral cancer has been shown in
individuals with HIV/AIDS or people who have undergone organ
transplants, supporting a role of immunosuppression. There is recent
literature evidence suggesting that HPV associated oral/ oropharyngeal
cancer may respond better to chemotherapy/ radiation therapy and may
be associated with better outcomes.

Premalignant conditions of the oral cavity

Several oral lesions and conditions precede oral carcinoma and the most
common of these are leukoplakia and erythroplakia. Other rare
precancerous conditions include lichen planus, oral submucous fibrosis,
syphilitic glossitis and sideropenic dysphagia. Leukoplakia has many
clinical variants but is much less likely to progress to malignancy than Fig 3: Leuco-erythroplakia lateral
erythroplakia. The precise prevalence of these conditions in India is border of tongue
unknown. It has recently been estimated that the annual transformation
rate of oral leukoplakia to oral squamous cell carcinoma may not exceed 1%. Erythroplakia is rare and mainly
occurs in people aged over 60. In Indian subcontinent Oral submucous fibrosis is very common. This condition is
characterized by limited opening of mouth and burning sensation on eating of spicy food. This is a progressive
lesion in which the opening of the mouth becomes progressively limited, and later on even normal eating
becomes difficult. It occurs almost exclusively in India and Indian communities
living abroad.

Oral/ oropharyngeal cancer in young individuals

The rising incidence and mortality rates in young and middle-aged adults is
incontrovertible, but there has been debate over the causes of this increase
and whether their disease is inherently more aggressive than that occurring in
older patients. A series of studies in southern England looking at risk factors
for patients under 45 years concluded that most young patients are exposed to
the traditional risk factors of tobacco smoking and alcohol while consumption
of fresh fruit and vegetables is protective. However, the relatively short
duration of exposure to these known risk factors suggests that other factors Figure 4: Second primary in
may also be involved and there was a small sub-group of patients who had the tongue following radiation
little, if any, exposure to the major risk factors. for a buccal mucosa primary.
Note the atrophic mucosa, a
Index upper aerodigestive tract cancer post radiation change
Since tobacco use results in field carcinogenesis, individuals with an index oral
or pharyngeal cancer (upper aero-digestive tract) have a 30-fold or higher risk of second oral and pharyngeal
cancer. The risk remains 20-fold higher 10 or more years after the first diagnosis. An almost seven-fold increase
in risk of oral and pharyngeal cancer has been shown after a diagnosis of squamous cell carcinoma of the
oesophagus, with risk remaining higher five or more years after the first diagnosis.

Points to remember
Tongue/ base tongue cancer risk factors
Tobacco
Alcohol
Diet and nutrition related factors

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 Human papillomavirus and immunosuppression
Oral premalignant lesions
Previous upper aerodigestive tract cancer diagnosis

Molecular biology of oral cancer:

Slaughter suggested the concept of field carcinogenesis in head and neck cancer as a result of tobacco use.
More recently, HPV associated oropharyngeal and oral cancer are on the rise in several populations and these
appear to be distinct from those caused by tobacco.

In the last 2 decades we have gained tremendous insight into the molecular basis of cancer. Early in the
discovery period, it appeared that direct alteration of key genes either with loss of function that maintains normal
cellular activity (tumor suppressor genes) or gain of function that contributes to the malignant phenotype
(oncogenes) would be sufficient to explain the diverse complexity of cancer. These genetic alterations include
mutation, chromosomal rearrangement, and loss or amplification of segments of DNA. For example, point
mutation of the p53 gene occurs in approximately one half of all oral SCC, eliminating or reducing important
cellular activities affecting cell cycle control and programmed cell death (apoptosis) in response to genotoxic
stress. However, this genetic alteration alone is insufficient to account for the cancer phenotype, and the
discovery of other genes with a substantial rate of mutation if head and neck squamous cell carcinoma (HNSCC)
has not occurred. New data is emerging indicating that key portions of the DNA found in mitochondria may also
be mutated in approximately 50% of HNSCC. Loss of regions of DNA-containing genes with tumor suppressor
function is another well-established mechanism that contributes to cancer development. A prime example of this
in HNSCC is the loss of a segment of the short arm of the ninth chromosome (9p) containing the p16 gene. This
gene plays a key role in cell cycle control through the Rb pathway and loss of its function results in deregulation
of cell growth and tumorigenesis. Mutations of p16 are rare in HNSCC but homozygous deletion occurs in >50%
of cases. In another substantial group of cases, p16 transcription is blocked by hypermethylation of the promoter
region.

Promoter hypermethylation is one form of epigenetic control of gene expression. In recent years, epigenetic
events have gained attention as they have been shown to be cancer specific and frequent, while demonstration
of direct genetic alterations contributing to malignant transformation have been less forthcoming. In fact, many
regions of promoter hypermethylation have been described in HNSCC, accounting for a lack of expression of
other genes with key tumor suppressor functions. One distinct example is the deleted in colon carcinoma (DCC)
gene, frequently mutated in colon cancer, but rarely in HNSCC. Promoter hypermethylation of DCC has been
shown to be a frequent event in HNSCC. Other key genes so altered included MDM2, interferon-, and retinoic
acid receptor (RAR-). MicroRNA, short 22 base sequences that can selectively block gene transcription,
promises to provide yet another substantial mechanism for epigenetic tumor-specific alteration.

Studies of the rate and type of genetic alterations in oral premalignant lesions have helped sketch a tumor
progression pathway for oral mucosal malignancy. By examining a spectrum of histologic lesions from atypia to
dysplasia to carcinoma in situ to invasive cancer, and cataloging the molecular events present, a general pattern
of accumulated alterations correlated with progressive phenotypic change has been established. Some genetic
alterations such as loss of p16 expression, occur with high frequency in very early lesions such as atypia and
dysplasia, and do not increase greatly with further histologic progression. Other alterations only appear with
substantial frequency in invasive SCC. The spectrum of genetic alterations in oral premalignant lesions may
serve a prognostic role, providing evidence as to the risk of progression to invasion. Several studies have shown
that loss of heterozygosity (LOH) of key gene regions including 3p, 9p, and 17p portend a significantly increased
rate of progression.

A landmark article in 1995 showed that individuals with head and neck squamous cell cancer who had negative
margins at surgery but had mutations in P53 in cells at the surgical margin had a higher incidence of recurrence
after surgery. A step wise progression of molecular changes that correlates (and possibly predates) with clinical
and histological changes in the process of development of head and neck cancer has been suggested.

287
Fig 5: Step wise progression model for Head and Neck Cancer
Based on the hallmarks of cancer, several pathways in cancer are under investigation for potential clinical
manipulation. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) is used in
combination with radiation therapy with a very modest impact.

Points to remember:
Head and neck squamous cell carcinomas (HNSCCs) develop in the mucosal linings of the upper
aerodigestive tract and are the sixth leading cause of cancer worldwide. Risk factors are exposure to
carcinogens, most notably tobacco smoking and alcohol consumption, infection with high-risk types of
human papillomavirus (HPV) and genetic predisposition.
HNSCC is a heterogeneous disease. At least two genetic subclasses can be distinguished: HPV-positive
and HPV-negative tumours. Preliminary data suggest that further subclassification is likely to follow.
A key issue in HNSCC pathogenesis is that carcinomas develop within large preneoplastic fields of mucosal
epithelium made up of genetically altered cells that are clonally related to the carcinoma and often extend
into the surgical margins when tumours are excised, and can cause local recurrences and second primary
tumours.
A step wise progression of molecular changes occur in the process of formation of invasive and metastatic
cancer
Limitless replicative potential of head and neck cancer cells is caused by abrogation of the p53 and
retinoblastoma (RB) pathways that perturb cell cycle regulation, probably in the context of telomerase
reverse transcriptase (TERT) expression.
A subgroup of HNSCCs becomes independent from growth factors owing to somatic changes in the
epidermal growth factor receptor (EGFR) signalling pathway.
Some, if not all, HNSCCs escape from the growth inhibitory transforming growth factor- (TGF) pathway by
somatic mutation or chromosome loss of key genes. This pathway seems to be interconnected to the nuclear
factor-B (NF-B) pathway.
Somatic mutations and genetic changes indicate that the PI3KPTENAKT pathway is frequently activated
in HNSCC in a bid to evade apoptosis.
Metastatic dissemination of HNSCC is initially to the lymph nodes in the neck. Expression profiles predict
lymph node metastasis, but causative cancer genes have not yet been identified.
The unravelling of the biological characteristics of HNSCC will lead to novel and personalized therapies in
the near future

Incidence
Oral is the sixth most common cancer reported globally with an annual incidence of over 300,000 cases, of which
62% arise in developing countries. The age-adjusted rates of oral cancer vary from over 20 per 100,000
population in India, to 10 per 100,000 in the U.S., and less than 2 per 100,000 in the Middle East. From 1982 to
2005, tongue cancer remained amongst the top 8 cancers in most tumour registries in India, with the Chennai
registry showing a rise. The incidence remained static in Bangalore, Bhopal and Delhi.

Evaluation and staging:

A combination of history, physical examination by an experienced clinician, endoscopy and tissue sampling with
fine needle aspiration (FNA), or biopsy has been the mainstay for diagnosis and staging of HNSCC, but imaging
has now become an integral part of the work-up. Imaging allows for a more clear assessment of degree of
infiltration by the primary tumor, involvement of lymph nodes, and detection of distal metastases or second
primary tumors. This ultimately improves diagnosis and staging and allows for optimal treatment planning and
accurate posttreatment follow-up.

A thorough clinical exam is the first and possibly most important

step in the management of cancers of the tongue (head and
neck). Knowledge about the patients personal habits, co-
morbidity, nutritional status and family history is essential. Apart
from evaluating the primary and the neck, outpatient clinical exam
includes an indirect laryngoscopy and examination of the cranial
nerves.

A direct laryngoscopy and esophagoscopy are performed to rule

out the possibility of a second primary tumor and to completely
assess the extent of the primary lesion.

Assessment of the mandible is an important part of the

preoperative assessment process. Oral/ lingual cancers tend to
Fig 6: Process of involvement of the mandible
have both radial and vertical patterns of growth. When the
cancer spreads along the floor of the mouth and reaches the mucoperiosteum of the mandible further course
depends on whether the patient is dentate or edentulous and on whether the individual has received radiation or
not. The mucoperiosteum is relatively resistant to tumour infiltration.

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The teeth are attached to the alveolus by the periodontal ligaments. Following dental extraction the alveolar
socket gets filled with haematoma which then organizes and gets covered by epithelium. This offers poor
resistance to infiltration by cancer. Also in the edentulous mandible, alveolar bone gets slowly resorbed thus
reducing the height of the mandible. The cancer thus has to travel a shorter distance to reach the alveolus.

When cancer reaches the mucoperiosteum of the mandible, it tends to spread along it in preference to infiltrating
through it. When it reaches the root of the teeth, it gains access to the alveolus by destroying the periodontal
ligaments. In the process the teeth get loosened. Conversely when the teeth are loose or missing infiltration of
the alveolus is much easier. Once in the alveolus, the cancer easily spreads along the spongy bone. It can also
spread along the dental neurovascular bundle to involve the inferior alveolar canal and extend along the canal
and peri-neural space of the inferior alveolar nerve to the mandibular nerve and thence along the mandibular
nerve into the cavernous sinus, Meckels cave and gasserian ganglion.

The same pattern is observed in the radiated mandible as well. However irradiated mucoperiosteum offers less
resistance to cancer infiltration and direct infiltration of bone is an unpredictable possibility.

Radiological evaluation
Most cases of oral tongue SCC are located along its lateral border or ventral surface. The prognosis of these
tumors depends on their depth of invasion. Although superficial tumors are difficult to assess on radiologic
imaging, involvement of the extrinsic muscles of the tongue (genioglossus, hyoglossus, palatoglossus, and
styloglossus) is relatively easy to detect. Another feature of interest is whether the tumor approaches or crosses
the midline fibrofatty septum of the tongue. Posterior extension of an oral tongue tumor into the base of tongue
should be noted because this finding has the potential to change treatment. Oral tongue SCC commonly extends
into the floor of mouth.

Evaluation of the mandible for invasion by tumor is an important consideration in staging and treatment planning.
Although gross invasion is relatively easy to identify, early cortical bone loss directly adjacent to obvious tumor
should be considered indicative of bone invasion. If bone invasion is present, it is important for the radiologist to
define its extent so that the surgeon is able to determine the extent of mandibular resection. In most situations
CT is adequate for this determination, but the bone marrow may be further characterized by MR imaging if
appropriate.

Resection of the involved segment of the mandible becomes necessary if there is direct invasion of the bone. On
the other hand, if the primary tumor is in close proximity to but does not directly invade the mandible, marginal
mandibulectomy provides an adequate surgical resection while maintaining integrity of the bone. On rare
occasions, segmental mandibulectomy may become necessary in the absence of direct bone invasion. Marginal
resection of the mandible is technically not possible if the tumor is in close proximity to a substantial depth along
its lingual (inner) cortex. Clinical examination is generally unreliable in differentiating direct tumor extension
through the muscular diaphragm of the oral cavity from metastatic lymphadenopathy or an obstructed
submandibular salivary gland. This information has important implications in the staging and the surgical
approach and should be reported clearly.

N stage:
The status of the cervical lymph nodes is the most significant predictor of outcome in patients who have SCC of
the oral cavity. The risk of nodal metastases depends on the anatomic site of the primary cancer within the oral
cavity. Tumors of the oral tongue and floor of mouth have a higher propensity to metastasize to cervical lymph
nodes compared with buccal mucosa, hard palate and gingival cancers. SCCs generally metastasize to the
draining cervical lymph nodes in a predictable pattern.

Levels I-III are at highest risk for nodal metastases from oral cavity SCC. In the previously untreated neck,
metastases to levels IV or V are rare in the absence of obvious lymphadenopathy at levels I-III. Most metastatic
lymph nodes from SCC are abnormally enlarged, but the size criteria for designating cervical lymph nodes as
metastatic are not universally accepted. Normal sized lymph nodes can have focal metastasis or necrosis that is
more easily seen on CT than MR imaging. Other radiologic features of metastatic lymphadenopathy from SCC
include heterogeneous enhancement and stranding or involvement of the adjacent soft tissue if extracapsular
nodal spread is present. Extracapsular nodal spread is generally seen in larger lymph nodes but can be seen in
small lymph nodes. The radiologist also should look for and report certain other features of metastatic
lymphadenopathy that may be valuable in therapeutic decision making. The relationship of metastatic
lymphadenopathy to the great vessels of the neck, particularly the carotid artery, is an important consideration in
determining surgical resectability. If more than 270 degrees of the circumference of the carotid artery are
surrounded by tumor, it is considered encased and the tumor is generally surgically unresectable. Similarly,
extension of nodal disease into the prevertebral musculature is an adverse indicator of prognosis and should be
reported.

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Base of the tongue carcinoma
Small lesions are difficult to detect on imaging because of lymphoid tissue at the base of the tongue, which
normally enhances. The only finding on cross-sectional imaging when lesions are small may be subtle
asymmetry at the base of the tongue. Unlike superficial spread of disease, deep plane infiltration is easily
detected on imaging. The extent of superficial spread is better appreciated clinically during endoscopic
examination. On CT and MR imaging the tumors demonstrate mild to moderate enhancement. They are often
isointense to muscle on T1-weighted images but are generally slightly hyperintense relative to muscle on T2-
weighted images. The extent of the tumors is more easily appreciated on post contrast images with fat saturation.
In general, MR imaging is the preferred modality for evaluation of oropharyngeal tumors because of superior soft
tissue contrast and less amalgam artifact. Motion artifact can degrade image quality in patients who have bulky
tumors, however. PET imaging, particularly when co-registered with CT, may localize the primary tumor in
patients with unknown primaries.

The base of the tongue lymphatic drainage is mostly to level II-IV nodes. Nodal metastasis to both sides of the
neck is common because of rich lymphatics and can be seen in up to 30% of patients who have tongue base
carcinoma. Approximately 60% of patients have nodal disease at the time of diagnosis.

PET CT
The role of PET CT is evolving. The most important indication of PET CT is in evaluation responses after
chemoradiation- both at the primary and nodal sites. It is a reliable guide to decide on the need for surgery if the
patient achieves a complete response. It has also been proven to be a useful tool in post treatment surveillance
though there is no consensus on the frequency of such investigation. It allows for earlier and better identification
of second primaries.

In patients who present with metastatic disease (nodes/ distant metastases) from unknown primaries, PET CT is
a useful supplement to other modalities.

Approximately 10% to 15% of patients with primary HNSCC will have distant metastases. The most common
sites of involvement are the lungs, followed by the liver and skeletal system. The presence of distant metastases
may indicate a need for additional therapeutic measures, whereas overlooked distant metastases can lead to
inappropriately aggressive treatment [23,24]. In most patients, distant metastatic lesions will be clinically silent.
Patients with HNSCC in whom screening for distant metastases would be indicated include 4 lymph nodes
metastases, bilateral lymph node metastases, lymph node metastases larger than 6 cm, level IV lymph node
metastases, recurrent HNSCC and second primary tumors.

Points to remember:
1. A thorough clinical examination is the most important part of evaluating tongue cancers.
2. All patients with tongue/ primaries in the upper aerodigestive tract must be screened for synchronous and
metachronous second primaries.
3. Mandibular involvement usually occurs through the tooth socket.
4. Ultrasonography, CT and MRI are valuable supplements in the evaluation of head and neck primaries. They
improve the definition of local extent of the primary, pick up nodal metastases earlier and help in treatment
planning (radiation)
5. PET CT is useful in assessing response to chemoradiation. It is also useful to look for the primary when
patients present with metastases of unknown origin. In select patientsit is indicated to look for distant
metastases.

Screening
Oral cancer occurs in a region of the body that is generally accessible to physical examination by the patient, the
dentist, and the physician. Screening can be made more efficient by inspecting the high-risk sites where 90% of
all oral squamous cell cancers arise in this country: the bucco-alveolar complex and the floor of the mouth and
ventrolateral aspect of the tongue. This is because of the peculiar quid retention habit in the population. An
inspection of the oral cavity is part of a physical examination in a dentist's or physician's office. An oral
examination includes looking for leukoplakia and erythroplasia - lesions that can progress to cancer.

The term "leukoplakia" has been defined by the WHO, as a white patch that does not rub off, that cannot be
attributed to any other cause. Leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma.
Overall, less than 5% of all leucoplakia will progress to invasive cancer provided the inciting agent is withdrawn.
Erythroplasia in contrast has a more sinister outlook. It is deined as a red patch in the that cannot be attributed to
any other cause. 50% of all these lesions will harbor invasive cancer and need to be managed more
aggressively. Submucous fibrosis is a condition peculiar to the Indian subcontinent. This is attributed to the use
of a variety of pan masalas. The condition results in atrophy of the mucosa due to extensive fibrosis of the
submucosal tissues resulting in trismus.

A recent study from India demonstrated that oral cancer screening by trained health workers can lower mortality
of the disease - especially in individuals with a history of tobacco use. In this randomized, controlled trial of
almost 192,000 people, carried out over an eight-year period, there was a significant reduction in mortality in the

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intervention arm (29.9 cases per 100,000) versus the control arm (45.4 cases per 100,000), due to detection of
oral cancer at an early stage.

Points to remember:
1. Screening for oral cancer is feasible in India especially amongst tobacco users.
2. Oral cancer screening reduces mortality

Cellular Classification
Most head and neck cancers are of the squamous cell variety and may be preceded by various precancerous
lesions. Minor salivary gland tumors account for 2% of malignancies in these sites. Specimens removed from the
lesions may show the carcinomas to be noninvasive, in which case the term "carcinoma-in-situ" is applied. An
invasive carcinoma will be well differentiated, moderately well differentiated, poorly differentiated or
undifferentiated.

Tumor grading is recommended using Broder's classification (Tumor Grade (G)):

G1: well-differentiated
G2: moderately well-differentiated
G3: poorly differentiated
G4: undifferentiated

TNM classification and staging

The classification applies only to carcinomas of the vermilion surfaces of the lips and of the oral cavity, including
those of minor salivary glands. There should be histological confirmation of the disease.

The following are the procedures for assessing T, N, and M categories:

T categories Physical examination and imaging
N categories Physical examination and imaging
M categories Physical examination and imaging

Anatomical Sites and Subsites

Lip
1. External upper lip (vermilion border) (C00.0)
2. External lower lip (vermilion border) (C00.1)
3. Commissures (C00.6)

Oral Cavity
1. Buccal mucosa
(i) Mucosa of upper and lower lips (C00.3, 4)
(ii) Cheek mucosa (C06.0)
(iii) Retromolar areas (C06.2)
(iv) Bucco-alveolar sulci, upper and lower (vestibule of mouth) (C06.1)

2. Upper alveolus and gingiva (upper gum) (C03.0)

3. Lower alveolus and gingiva (lower gum) (C03.1)
4. Hard palate (C05.0)
5. Tongue
(i) Dorsal surface and lateral borders anterior to vallate papillae (anterior two-thirds) (C02.0, 1)
(ii) Inferior (ventral) surface (C02.2)
6. Floor of mouth (C04)

Regional Lymph nodes

The regional lymph nodes are the cervical nodes.
TNM Clinical Classification
T Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in Situ
T1 Tumour 2 cm or less in greatest dimension
T2 Tumour more than 2 cm but not more than 4 cm in greatest dimension
T3 Tumour more than 4 cm in greatest dimension
T4 Lip: Tumour invades adjacent structures, e.g., through cortical bone, inferior alveolar nerve,
floor of mouth, skin of face.
Oral Cavity: Tumour invades adjacent structures, e.g., through cortical bone, into deep
(extrinsic) muscle of tongue, maxillary sinus, skin. (Superficial erosion alone of bone/tooth
socket by gingival primary is not sufficient to classify a tumour as T4.)

N Regional Lymph Nodes

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 NX Regional lymph odes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in
greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest
dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest
dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm
in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest
dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest
dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Note: Midline nodes are considered ipsilateral nodes.

M Distant Metastasis
MX Distant metatasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis

Stage groupings
Stage 0
Tis, N0, M0
Stage I
T1, N0, M0
Stage II
T2, N0, M0
Stage III
T3, N0, M0
T1, N1, M0
T2, N1, M0
T3, N1, M0
Stage IVA
T4, N0, M0
T4, N1, M0
Any T, N2, M0
Stage IVB
Any T, N3, M0
Stage IVC
Any T, Any N, M1

pTNM (Pathological Classification and staging) - The pT, pN, and pM categories correspond to the T, N, and M
categories.

Principles of management
These cancers are best managed by a multimodal team approach consisting of the surgical, medical and
radiation oncologists, palliative care physician, dental surgeon, dietician, pathologist, radiologist, speech therapist
and oncologist nurse. Pretreatment dental prophylaxis is a must. Any dental extraction is best performed before
radiation therapy since extractions post radiation exposes the individual to a risk of osteoradionecrosis. Patients
in poor nutritional status will need a nasogastric tube or a gastrostomy tube placed for nutritional support. Most
of these patients are tobacco users and will need to be counseled and supported to stop tobacco use.
Continuing to use tobacco during treatment carries a poorer outcome. This would also be a good time to urge
other family members and friends to quit tobacco.

Anterior tongue
T1N0/ T2N0 anterior tongue cancers may be managed by a single modality of treatment either radiation therapy
or surgery. In principle either radiation or surgery alone would be used to treat both the neck and the primary
though this may sometimes vary. Advanced disease mandates combined modality treatment.

The choice of radiation therapy or surgery will be dictated by tumour factors (location, potential post treatment
morbidity), patient factors (co-morbidity, patient preference) and treating institution protocols. Where combined
modality (surgery and radiation therapy) treatment for resectable cancer is indicated, the issue of radiation first or
surgery first arises.

When surgery is performed prior to radiation therapy, wound healing is not an issue. The histopathology
(margins, nodal status) is available for informed decision making. Primary radiation has the advantage of

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radiating a well oxygenated cancer unhampered by post surgery fibrosis. Radiation therapy results in centripetal
contraction of the cancer thus improving the scope of surgical margins. Radiation failures (residual tumour) are
usually at the centre of the field while post surgical recurrences are usually at the margins of the resection. Post
surgical radiation must include the entire surgical margin, surgical incisions and drain sites and this necessitates
larger radiation fields with a consequent higher morbidity.

Radiation therapy results in obliterative endarteritis of the smaller arterioles in the field. This results in wound
healing problems when surgery is performed following radiation therapy. This can be reduced by rigorous quality
control of radiation technique. Using well vascularised tissue flaps from outside the radiation field for
reconstruction following resection will also reduce post operative morbidity.

In a patient with good performance status, radiation therapy for loco-regionally advanced anterior tongue cancer
(T3T4 N2N3) would be combined concurrently with chemotherapy. This chemotherapy would consist of varying
combinations of taxanes (paclitaxel or docetaxel), platinum compounds(cis-platin or carboplatin) and 5 flurouracil.
When the primary or the node is very large neoadjuvant or induction chemotherapy may be attempted to
downsize the tumour before chemoradiation.

Individuals who achieve a complete response (clinical, radiological including PET-CT) following radiation therapy/
chemoradiation may be followed up. Surgery margins for post radiation residual cancer should encompass the
original tumour volume since viable tumour cells may be left in the original tumour bed even as the cancer
shrinks.

Post radiation recurrent cancers and second primaries in the field of radiation are best dealt with by surgery. Re-
irradiation may be considered in select situations especially if the disease free interval is long.
Superficial (depth of infiltration < 4mm) and well differentiated T1N0 tongue cancers can be managed by either
surgical resection or by radiation therapy with comparable survival. The radiation therapy can be delivered by
brachytherapy.

T1N0 lesions which infiltrate more than 3mm and T2N0 cancers have a higher propensity for nodal metastases
and therefore the neck is electively addressed. This may be accomplished by either external beam radiation
therapy for the primary and neck or surgical resection of the primary along with a modified/ selective neck
dissection or a combination of brachytherapy for the primary and either external beam radiation to the neck or an
elective neck dissection.

T1T2N1N2 cancers may be managed with surgery (wide excision of the primary and a comprehensive neck
dissection) or radiation therapy for the primary and neck (external beam radiation or brachytherapy for the
primary and external beam radiation for the neck). Surgical salvage for the primary and/ or neck is reserved for
clinical/ radiological residue. Cancers located near the midine will need both sides of the neck to be addressed.
Adjuvant radiation following neck dissection is indicated when the node is large (N2a) in size (>3cm) and when
histopathology reveals multiple metastatic nodes (N2b) or nodes show extracapsular infiltration of cancer.

T3T4a N0N1N2 cancers of the anterior tongue (if resectable) may be treated by surgical resection followed by
adjuvant radiation/ chemoradiation or by primary chemoradiation with surgical salvage. Primary chemoradiation
may obviate the need for surgery if the patient achieves a complete response thus avoiding the mutilation and
functional disability produced by resection of large volumes of the tongue, floor of mouth and mandible. T4bN3
cancers are primarily treated with chemoradiation. If the cancers regresses and becomes resectable, surgical
salvage could be considered.

Criteria for unresectability include primary cancers with extensive base skull infiltration, extensive perineural
infiltration, carotid artery infiltration/ encasement by the primary or node, extensive soft tissue infiltration by the
primary or nodes and presence of extensive cutaneous lymphoedema and nodules.

Posterior tongue
Cancers of the base tongue are managed primarily with chemoradiation since surgical resections carry
unacceptable morbidity. Speech, swallowing and respiration are all affected. Post radiation residual cancers are
managed by surgical resection with bulky flaps for reconstruction to reduce aspiration during deglutition.

Palliative care
Palliation for advanced tongue cancer requires a team approach. Chemotherapy and radiation may be used
effectively for palliation of pain, fungating tumours and to relieve airway obstruction. The surgeon may be called
upon to do a tracheostomy for stridor, place feeding tubes (PEG, nasogastric tubes, gastrostomy/ jejunostomy
tubes) and ligate the external carotid artery for life threatening tumour bleed.

Core issues of palliative care like pain (often of multiple pathogenesis- neuropathic, nociceptive, inflammatory),
fungating foul smelling maggot ridden cancers, oro/ pharyngo cutaneous fistulae, problems of speech swallowing
and respiration, nutrition, psychological and social problems need to be handled with perseverance and
empathy. The role of oral morphine cannot be over stressed.

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Points to remember:
1. Management of tongue/ head and neck cancers needs team work. Treatment decisions must be made and
reviewed by the entire team
2. Treatment decisions and combinations need to be individualized.
3. Early cancers can be managed by a single treatment modality while advanced cancers need a multimodality
approach.
4. Many of these patients are chronic tobacco users with poor nutrition. Their dental hygiene is often very poor.
These must be treated before aggressive cancer directed treatment is instituted.
5. The first and subsequent interviews are an ideal time to counsel the patient, family and frends to quit tobacco
use.

Surgical procedures
The most important aspects of surgical resection of tongue cancers (both anterior and posterior) are adequate
preoperative assessment of tumor extent and reconstructive needs, and good intraoperative exposure. Adequate
tumor resection with a 12-cm margin of normal tissue and frozen-section control of margins is essential. To
optimize exposure of anterior oral cavity tumors, nasotracheal intubation is preferred.

The approaches includes transoral, transmandibular, and transpharyngeal routes.

Transoral approach
The transoral approach is used for small anterior tongue cancers that can be adequately exposed, removed with
adequate margins, and reconstructed through the mouth without additional incisions . The resection may be
combined with neck dissections as indicated

The jaws are opened using a side-

biting oral retractor. The cheeks are
retracted and the tongue is grasped
with a towel clip or a silk suture
placed through the tip of the tongue.
The margins of resection are marked
with diathermy with the tongue in a
relaxed state inside the mouth. The
tumour is resected with an
electrocautery while periodically
palpating the tumour edge between
the thumb and the index finger, taking
care not to bevel the cut toward the Fig 7: A: T1 cancer tip of the tongue; B: trans-oral resection
tumour to provide an adequate
margin. For all but very superficial tumours or carcinoma in situ, a 2 cm cuff of normal tissue is preferred. Frozen-
section margins are checked circumferentially and at the deep surface to ensure complete tumour removal.

For defects about 3 -4 cm wide primary closure is accomplished with 30 chromic or Vicryl sutures in one or two
layers for lateral tongue defects and two layers for midline tip of tongue defects. If the defect is larger, the tongue
may be folded back on itself to cover the defect. This will ultimately result in surprisingly little speech or
swallowing defect. For defects involving half the anterior tongue, a nasolabial or free radial forearm flap may be
needed better to reduce tongue tethering (that would cause reduced mobility of the tongue). Defects larger than
half the tongue will need bulkier flaps to restore loss of volume to aid speech and swallowing.

Lip splitting cheek flap transmandibular approach

Surgical access to larger anterior tongue or base tongue tumors is
limited by the size of the oral aperture. A lip-splitting check flap
incision combine with a midline or lateral mandibulotomy gives
excellent exposure to these locations. Avoiding the lip and chin split
necessitates raising a cheek flap separate from the mandibulotomy
and may give a better cosmetic result.

Since the neck is opened, this type of access is always performed in

conjunction with neck dissection. The procedure begins with the neck
incisions placed suitably for the neck dissection which is hen
completed. The neck incision is extended superiorly through the
mental skin. The design of the translabial incision can be varied,
either extending vertically through the midline of the mentum or
curving around the mentum to follow the natural mental crease. The Fig 8: Lower cheek flap with resection
incision through the mental skin is made down to the mandibular of the mandible lateral to the inferior
mental foramen on the right side.
periosteum. The translabial incision transects the inferior labial artery,
which runs deep to the mucosa.

294
 A cheek flap alone may be used if a rim or segment or hemi mandibulectomy is indicated. In that case a mucosal
incision is then made in the gingivobuccal sulcus, down to the mandible. The gingivobuccal incision is carried
posteriorly to the level of the mandibular ramus, transecting the mental nerve during flap elevation. The cheek
flap will be continuous with the previously elevated neck flap. Alternate to the midline lip split, the cheek can be
slit vertically at the level of the oral commissure.

Mandibular osteotomies may be midline, paramedian (anterior to

the mental foramen), or lateral (on the body or angle of the
mandible) or on the ascending ramus (posterior to the
mandibular foramen). All but the ramus osteotomy require
exposure through a lip-splitting incision.
The mandible is exposed at the bottom of the lip split or
commissurotomy incision. The mandibular periosteum on either
side of the proposed mandibulotomy is elevated for a few mm.
In dentulous patients, the tooth in the line of the proposed
osteotomy site is extracted (i.e., a molar for lateral osteotomies,
canine or premolar for paramedian osteotomies, and a central
incisor for midline osteotomies). Osteotomies between adjacent
teeth are not performed because of the risk of devitalizing both
Fig 9: Rim resection for cancer teeth. A step-ladder cut provides an inter-locking mechanism to
tongue-floor of mouth.
promote union and a greater surface contact area for
osteosynthesis. Prior to making the bony cuts, mandibular fixation plates are placed on the mandible, two holes
drilled on each side and screws placed to ensure better reapproximation of bone at the time of closure. The
screws and plates are removed and the mandibulotomy cuts made using an oscillating saw. Bleeding at the cut
ends can be controlled with cautery.

Fig 11: Left mandibular swing for cancer

Fig 10: A: Rim resection marked with saw; B: completed resection
located in the posterior part of anterior tongue

Fig 12: A: step cut mandibulotomy; B: right mandibular swing; C: total anterior
glossectomy specimen; D: total anterior glossectomy surgical defect; E: flap being inset
for reconstructing the defect; F: final appearance

The hemimandible on the side of the proposed resection is distracted and the mucosa of the floor of mouth
incised and underlying muscles attaching to the mandible divided ensuring clearance to the tumour. The lingual
and hypoglossal nerves should be identified and preserved if possible. The mucosal incision can be carried
superiorly along the anterior tonsillar pillar onto the soft palate. It can also be carried posteriorly through the

295
palatoglossal fold and down the lateral pharyngeal wall at its junction with the base of tongue to the level of the
hyoid bone. This provides excellent exposure of the base of tongue and vallecula.
The resection is completed. Appropriate reconstruction using suitable flaps is carried out. The mandible is
reapproximated using the previously fashioned fixation plates.

For tumors involving the entire tongue or root of tongue, total glossectomy is indicated. Through a combined
intraoral and cervical approach bilateral floor of mouth incisions are made and the tongue is pulled through the
floor of mouth and the posterior resection performed transcervically.

Reconstruction of total glossectomy defects requires large bulky flaps to prevent aspiration while preserving the
larynx. Frequently after total glossectomy, prolonged or permanent gastrostomy tube feedings are required. In
patients who have recurrent aspiration after total glossectomy, a total laryngectomy is indicated.

Lateral Pharyngotomy Approach

Small cancers of the base of tongue can be approached through a lateral pharyngotomy approach. This can be
combined with a lateral mandibulotomy for further superior exposure. Inferior exposure can be extended to the
level of the pyriform sinuses. The incision can also be extended anteriorly to allow complete oral tongue
exposure.

After a neck dissection, the hypoglossal nerve is identified and dissected anteriorly to its entrance into the fl oor
of mouth lateral to the hyoglossus muscle. The overlying posterior belly of the digastric and stylohyoid muscles
and the ansa hypoglossi are transected. The nerve is retracted superiorly out of the fi eld. The facial and lingual
arteries are ligated at their origin from the external carotid artery. The superior laryngeal nerve is identifi ed at the
level of the greater horn of the hyoid bone and mobilized along its course from the carotid sheath to its entrance
through the thyrohyoid membrane. The hyoid bone may be freed from its attachments to the middle constrictor
muscle and the greater horn or half of the hyoid bone removed.

A vertical incision is made through the middle constrictor muscle, exposing the mucosa. The mucosa is then
incised 2 cm from the cancer using an intraoral finger palpating the cancer to guide the incision. The tumour is
visualized with good headlight illumination through the pharyngotomy and the resection completed. Margins are
confirmed by frozen section. Closure of the defect depends on the extent of tissue loss. When possible, primary
closure is preferred, but for large defects flap closure is necessary.

Care is taken during the lateral pharyngotomy approach to avoid injury to the hypoglossal and superior laryngeal
nerves, as injury to these structures can result in significant swallowing problems and aspiration postoperatively.

Management of the neck

Standard radical neck dissection (indicated for node positive neck) removes nodes at levels I through V along
with non lymphatic structures : the internal jugular vein, sternocleidomastoid muscle and the spinal accessory
nerve since the lymphatic structures are closely related to these structures. A comprehensive neck dissection
that removes all the nodal stations but spares the non lymphatic structures is indicated for small volume neck
nodes.

Selective neck dissection refers to dissection that spares lymph node regions usually performed for the N0 neck.
The rationale for this is the fact that lymph node
metastases in head and neck cancers is orderly
and predictable.
The first echelon nodes for both anterior and
posterior tongue are at levels I and II. It is unusual
for metastases to appear at level IV in the absence
of metastases at levels I, II or III. Metastases are
seen in level V in less than 1% of patients. A
supra-omohyoid neck dissection (levels I,II,III) or an
extended supraomohyoid dissection (including
levelIV) is, therefore, appropriate for N0 tongue
primaries.

A modified neck dissection refers to dissection that Fig 13: A: Radical neck dissection; B: Supraomohyoid neck
dissection
spares the non -lymphatic structures and is
indicated for small volume nodal metastases.

Complications of surgery on the tongue

The main complications following surgery on the oral cavity (anterior tongue) and oropharynx (base tongue)
include airway related issues, wound healing, fistulae and mandibular necrosis, haemorrhage and carotid blow
out, deglutition problems and speech related issues.

296
Major procedures on the oral cavity and oropharynx should include a tracheostomy. This reduces the risk of
aspiration and minimizes the chance of airway obstruction. Airway obstruction can occur as a result of soft tissue
edema in the oral cavity or laryngeal or pharyngeal structures postoperatively. It can also be a result of
compression of these structures due to hematoma or seroma collection. The tracheostomy is retained till oral
feeds have been commenced and swallowing un-impeded. Prior to decanulation, a direct laryngoscopy ensures
a patent rima

Because of the proximity of the carotid artery system and the internal jugular vein and its branches, there is the
risk of significant bleeding both intra and post operatively.. Repair or ligation of these vessels should be
performed when necessary, and the internal carotid artery may require stenting or grafting. Secondary
haemorrhage from a carotid blow out is a surgical emergency and results following a fistula into the neck.
Prompt proximal and distal ligation of the carotid artery may be lifesaving though a third of these patients may
suffer an immediate or delayed stroke.

Oral and pharyngeal dysfunction can result in significant postoperative problems in patients who have undergone
upper aerodigestive tract surgery. This can be the result of cranial nerve injuries such as injury to the hypoglossal
nerves, causing tongue weakness or paralysis; the glossopharyngeal nerve, causing pharyngeal hypoaesthesia;
or the vagus nerve, causing poor pharyngeal phase of swallowing and vocal cord paralysis. In addition oral and
pharyngeal tissue volume loss can significantly affect swallowing. Tethering of the tongue as a result of tight
mucosal closure or tissue loss can also reduce swallowing effi ciency. All of these factors can result in dysphagia,
dysarthria, and possibly aspiration and subsequent aspiration pneumonia. Avoidance of postoperative oral
feedings and use of a nasogastric or gastrostomy tube should be considered until the patient is able to safely
swallow and protect the airway.

Orocutaneous or pharyngocutaneous fistulae occur due to multiple factors including malnutrition, underlying
microvascular disease (following radiation therapy), mucosal closure under tension, incomplete mucosal closure,
infection the presence of a foreign body or residual tumor and hypothyroidism. Fistulae are initially managed
conservatively with wide drainage of the wound, external and/or internal packing of the wound to allow
granulation and compression dressings to prevent further accumulation. The patient should not have anything by
mouth until the fistula is healed. Persistent fistulae will require re-exploration of the wound and closure of the
fistula with vascular flaps.

Mandibular complications may occur as a result of osteotomies or poor wound healing. Osteoradionecrosis
occurs when the periosteum is stripped from the mandible leaving an avascular segment of bone especially
following radiation therapy. It can also occur following infection (as a result of salivary contamination of the
wound as a result of a complex fistula). Malocclusion or malunion or nonunion can occur when a mandibular
osteotomy site is not appropriately realigned or fixed. This can be minimized by accurate placement of
mandibular fixation plates prior to performing an osteotomy to allow accurate and rigid reapproximation. The
patient should be maintained on a soft diet for approximately 6 weeks after mandibular osteotomies. Mandibular
fracture may result if a partial rim or cortical mandibulectomy has been performed but an inadequate amount of
bone remains to support the mandibular arch.

Following lateral mandibular resections, jaw occlusion exercises must be instituted early to prevent jaw deviation
and malocclusion. Segmental mandibular resections must be reconstructed with bone. If this is not done the
ramus of the mandible will deviate inwards and protrude into the oral cavity, sometimes ulcerating into the mouth.
Partial or complete loss of a pedicled myocutaneous flap can result as a result of compression of the vascular
pedicle by drains, tight closures, inadequate size subcutaneous tunnels, haematoma and pressure dressings in
the postoperative period. Free flap loss occurs due to fault in technique in addition to these reasons.
Surveillance of the capillary refill and venous drainage of the flap is necessary to ensure early intervention to
salvage the flap.

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Gastrointestinal Polyps

Lalit Aggarwal

Introduction
The word polyp is derived from Greek & Latin words meaning many feet and is defined as a mass that
protrudes into the lumen of bowel. A polyp may be characterized by its gross appearance according to the
presence or absence of a stalk,its overall size and whether it is one of multiple masses elsewhere in the
gut.Regardless of these features, specific definition rests on the histologic characteristics.

Depending upon anatomical location, colorectal is the most common site.Other less common sites are Gastric,
esophageal,small intestine (Proximal and distal)and periampullary site.

Colorectal Poyps

Classification of GI( Colorectal)Polyps

Neoplastic Mucosal Lesions
Benign ( adenoma) Malignant ( carcinoma)
Tubular adenoma Non invasive carcinoma
Carcinoma in situ
Tubulovillous adenoma Intramucosal carcinoma
Villous adenoma Invasive Carcinoma

Non-Neoplastic Mucosal lesions

Hyperplastic polyp
Juvenile polyp
Peutz Jeghers polyp
Inflammatory polyps
Normal epithelium

Submucosal lesions
Colitis cystic profunda
Pneumatosis cystoides intestinalis
Lymphoid polyps
Lipomas
Carcinoids
Metastatic Neoplasms

Neoplastic polyps ( Adenomatous and malignant polyps)

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Neoplastic nature of adenomas is apparent by histologic examination of their glandular architecture, dysplasia ,
size of polyp.

Histology
Tubular adenomas are most common subgroup,characterized by a complex network of branching adenomatous
glands. In Villous adenomas , the adenomatous glands extend straight down from the surface to the centre of the
polyp, thereby creating long finger like projections. Tubulovillous adenomas manifest a combination of these two
histological types. Tubular adenomas are usually small and exhibit mild dysplasia, whereas villous architecture is
more often encountered in large adenomas and tends to be associated with more severe degree of
dysplasia.(Table1)

Table 1. Frequency of Adenomas : Relation of Histologic type to adenoma size and degree of dysplasia

Adenoma <1cm 1-2cm >2cm Mild dysplasia Moderate Severe

Type
Tubular 77% 20% 4% 88% 8% 4%
Tubulovillous 25% 47% 29% 58% 26% 16%
Villous 14% 26% 60% 41% 38% 21%

Dysplasia
By definition, all colorectal adenomas are dysplastic.Dysplasia can be graded subjectively on the basis of certain
cytologic and architectural features into three categories.: mild , moderate and severe.
Mild dysplasia may be found in 70% to 86% of adenomatous polyps, moderate dysplasia in 18% to 20%, severe
dysplasia in 5-10% and invasive carcinoma in 5-7%.

Size
Adenomas have classically been categorized into three size groups:
<1cm , 1-2cm , >2cm. Overall most adenomas are smaller than 1 cm
Adenoma size increases as a function of age and are more common in distal colonic segments.

Adenoma Carcinoma Hypothesis

It is generally accepted that most colon cancers originate within previously benign adenomas. Rarely, colon
cancers may develop de novo in apparently flat nonadenomatous epithelium, although as noted earlier,even
those lesions might arise from pre existing flat adenomas.Evidence in support of the adenoma carcinoma
sequence comes from epidemiologic,clinical , pathologic and molecular studies.

Diagnosis of Adenomatous Polyps

Signs and symptoms

Most patients with colonic polyps are asymptomatic. Occult or overt rectal bleeding is the most common
presenting symptom that can be attributed to colonic polyps. Other common symptoms are constipation lower
abdominal crampy pain, diarrhea,and flatulence.

Detection of adenomas
Colorectal polyps are usually silent. They are detected either in asymptomatic persons being screened for
colorectal neoplasis or incidentally during investigation for symptoms ostensibly referable to colon or evaluation
of unexplained anemia.Different modalities to diagnose polyps include :Colonoscopy ,Sigmoidoscopy , Barium
Enema, FOBT. Newer methods include Endoscope compatible optical fibre systems , Hydrocolonic
ultrasonography and Helical computed tomographic colography.

Management Of Adenomatous Polyps

Management of the patient with adeomatous polyps require an understanding of the natural history of untreated
adenomas, relationship between multiple adenomas and carcinoma and the course of patients after treatment
(Polypectomy). If a polyp is detected by barium enema , colonoscopy is usually recommended to establish the
histologic diagnosis of the polyp and search for synchronous neoplasms. If larger polyps are there, piecemeal
excision is required and for sessile growths injection of saline into polyp base can assist with complete ndoscopic
resection. After complete removal of large adenoma, it is advisable to repeat colonoscopy in 3- 6 months to
document the completeness of excision. If a polyp cannot be completely excised after two or three endoscopic
sessions, surgical therapy is recommended.

Management Of Malignant Polyp

Complete endoscopic removal of adenoma with non invasive carcinoma represents curative therapy. The
therapeutic dilemma becomes much more difficult when polyps contain invasive carcinoma. Athough majority are
treated adequately by endoscopic polypectomy, about 10% of patients will experience an adverse outcome.
Several risk factors have been predicted for such adverse outcomes with malignant polyps
(Table 2 )

300
 Favorable Unfavorable
( Low Risk) ( High Risk)
Degree of differentiation Well or Moderate Poor
Invasion of Veins or lymphatics Absent Present
Polypectomy margins Clear or >2mm margin Involved
Invasion of submucoasa of bowel Absent Present
wall

Unfavorable / high risk patients should undergo surgical resection and otherwise for most patients with malignant
polyps, polypectomy seems adequate.

Post polypectomy Management

Guidelines by American college of Gastroenterology for post polypectomy includes :
Repeat Colonosopy after 3 years for missed synchronous or metachronous adenomas, and if findings
are negative, the surveillance interval may be increased to 5years.
If the initial clearing was suboptimalor patients had multiple adenomas, follow up at 1 or 4 years may be
considered.
Presence of high grade dysplasia does not modify these recommendations.
Patients with single, small (<1cm )tubular adenomas follow up surveillance not indicated.

Non Neoplastic Polyps

Hyperplastic Polyps
The most common neoplastic polyp is the hyperplastic polyp , referred by some as metastatic polyps. They are
usually small, <5mm, usually sessile lesions. Histologic characteristics includeelongated colonic crypts and
epithelial cells assume a characteristic papillary configuration.
Management : They seldom give rise to symptoms and not likely to give rise to cancer. Because they cannot be
distinguished by gross examination , they are usually removed. However , neither proximal polyp hunting by
colonoscopy is required nor regular surveillance program is there for them.

Juvenile polyps
Juvenile polyps are mucosal tumors that consists primarily of an excess of lamina propria and dilated cystic
glands and are also called as hamartomas or retention polyps.They usually present with bleeding and prolapse
because of stalk , hence removal of these polyps are suggested. They have no malignant potential and tend not
to recur.

Peutz Jeghers Polyps

They are unique hamartomatous lesion characterized byglandular epithelium supported byan arborizing
framework of well developed smooth muscle that is contiguous with muscularis mucosae.They are always
multiple and their distinctive appearance with extraintestinal manifestations makes Peutz Jeghers syndrome
easily identifiable.

Inflammatory polyp
These poyps are found in the regenerative and healing phases of inflammation. The lesions may be large and
solitary mimicking a neoplastic mass. They are also termed as pseudopolyps. They have no intrinsic neoplastic
potential but they often appear in diseased colons that are at high risk for developing colon cancer (ulcerative
colitis, schistosomiasis): therefore must be distinguished from neoplastic lesions that do carry premalignant
potential.

Gastrointestinal Polyposis Syndromes

GI Polyposis refers to the presence of multiple polypoid lesions throughout the GItract. These lesions may be
characterized by their distribution in the gut or tendency to be inherited within a family , but they are best
understood in the context of histopathology.

Classification of GI Polyposis includes

Inherited Adenomatous Polyposis Syndromes
Familial Hamatomatous Polyposis Syndromes
Nonfamilial GI Polyposis Syndromes

Inherited Adenomatous Polyposis Syndromes

It includes several entities that are characterized by the development of large numbers of adenomatous polyps in
the colon. This include FAP syndromes and clinical variants ( Table 3)

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SYNDROME POLYPS EXTRAINTESTINAL GENETIC LESION
ABNORMALITIES
Classic FAP Colonic adenomas,Duodenal, Mandibular Osteomas Mutation of APC gene
Gastric fundic gland hyperplasia , Dental abnormalities: ( usually results in
Jejunal and ileal adenomas, Ileal impacted teeth , truncated gene product)
lymphoid polyps supernumerary teeth
Gardners variant Same as FAP Osteomas of mandible, Same as FAP ( CHRPE-
skull,long bones mutations distal to exon9)
CHRPE
Desmoid tumors
Epidermoid cysts
Thyroid adrenal ,
hepatobiliary tumors
Attenuated FAP Colonoic adenomas Mandibular Osteomas ( rare) APC mutations of 5 region
( fews to tens; proximal colon)
Duodenal, periampullary
adenomas
Gastric fundic gland hyperplasia
Turcots variant Colonic adenomas Medulloblastoma Same as FAp
( fewer than classic FAP) CHRPE DNA mismatch repair
Glioblastoma multiforme enzyme mutation

Management of FAP
Surgical Management : Surgery is the only reasonable option for FAP.The options include Total
proctocolectomy ith conventional ileostomy or ileal pouch anal anastomosis. & Subtotal colectomy with ileorectal
anastomosis.
Medical Management : Different drugs in trial are ascorbic acid (4gm/day),alpha tocoferol (vitamin
E,400mg/day),and supplemental fibre (22.5g/day). A modest effect was seen after 2 years of therapy.
Sulindac ( NSAIDs) has shown to decrease the number and size of colorectal adenomas in FAP patients.

Familial Hamatomatous Polyposis Syndromes

There are five discerete familial syndromes that are characterized by hamartomatous polyps of the GI tract.These
includes Peutz Jeghers syndrome , juvenile polyposis ,neurofibromatosis,Cowdens syndrome and basal cell
nevus syndrome.

Nonfamilial GI Polyposis syndromes

It includes Cronkhite Canada syndrome, inflammatory polyposis, Lymphoid polyposis, Pneumocystosis
cystoides intestinalis

Gastric Polyps

Usually incidental finding on UGI Endoscopy (6%) .Rarely cause symptoms. Nevertheless the diagnosis and
management of gastric polyps are important, as polyps have malignant potential.
Hyperplastic polyps, Fundic gastric polyps and adenomas are common types.

Hyperplastic Polyps
Incidence is common where H Pylori is common. Usually asymptomatic. Bleeding and intermittent obstruction are
the other symptoms.On UGI looks like smooth,stalked size 5mm, multiple and are in antrum, body, fundus ,
cardia.Malignancy develops in hyperplastic polyps through a dysplasia/carcinoma sequence. Between 1-20% of
hyperplastic polyps have been reported to harbour foci of dysplasia. Risk of malignancy is when polyp size is
>1cm and pedunculated.Management includes complete resection when > 5mmand also normal appearing antral
mucosa to be sampled. In patients with carcinoma or dysplasia beyond the confines of polyp, a subtotal
gastrectomy or EMR be prefromed.

Fundal gastric Polyps

Usually Asymptomatc and are common with use of PPIs.Rarely can sometimes cause obstruction.Female
>male.Endoscopy features includes small, hyperaemic sessile smooth polyps. They rarely progress to
cancer.Management includes only biopsy but if >1cm, ulcerated , antral polyps then they should be resected.

Gastric Adenomas
Most common gastric neoplastic polyp. It constitutes around 6-10% of gastric polyps. Clinical manifestation
usually asymptomatic, bleeding and obstruction. Endoscopy features includes flat <2cm solitary in fundus and
antrum. 8% 60% are associated with synchronous carcinomas. Presence of invasive carcinoma in adenomas
usually correlates with increasing size, villous contour and degree of dysplasia.
Management involves endoscopic resection of polyp.

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Esophageal Polyp

Esophagus is uncommon site for polyps. Occasional cases have been reported. Classification of esophageal
polyps includes :
Glycogen acanthosis
Inflammatory polyp
Cysts
Gastric Heterotopia
Leiomyoma
Squammous papilloma

Small intestinal polyps

Classification of small intestinal polyps divided into Proximal and Distal Small intestinal polyps.
Proximal (Mostly Hyperplastic)
Brunners Gland hyperplasia
Lymphoid hyperplasia
Nodular duodenitis
Heterotopia ( Gastric, pancreas)
Adenoma
Hamartoma
Distal ( Mostly Neoplastic)
Carcinoid tumour
Lymphoid hyperplasia
Lymphoma
Lipoma
GIST
Adenocarcinoma

References

1. Ahnen DJ et al. The approach to the patient with colonic polyps http://www.uptodate.com/home. Accessed March
2014.
th
2. Feldman M etal. Selsinger GIandLiver Disease:9 ed. Philadelphia Pa:Saunders Elsevier;2010.
3. ElumunzerBJ. Endosopic resection of sessile colonic polyps. Gastroenterology.2013:144:30
4. Sharma P etal. Advanced imaging in colonoscopy and its impact on quality.Gasrointestinal
endoscopy.2014;79:28
th
5. Goldman L etal . Goldmans Cecil Medicine.24 ed. Philadelphia: Saunders Elseveir ,2012
6. Golden AK. Decision Support System.Mayo clinic, Rochester, Minn.March10,2014

Local and regional anaesthesia

Overview
Local anesthetics provide a reversible regional loss of sensation. Local anesthetics reduce pain, thereby
facilitating surgical procedures. Delivery techniques broaden the clinical applicability of local anesthetics. These
techniques include topical anesthesia, infiltrative anesthesia, ring blocks, and peripheral nerve blocks (see the
Technique section below for links to detailed, illustrated articles demonstrating these techniques).

Local anesthetics are safer than general or systemic anesthetics; therefore, they are used whenever possible. In
addition, they are relatively easy to administer and readily available. Local anesthetics have been undergoing
development for centuries, and, as this article illustrates, research continues to provide surgeons with
pharmacologic variety and to provide patients with anesthetic agents that have superior safety and efficacy
profiles.

Background
Although the medical world cannot cure every disease, the control of pain to ensure patient comfort should be a
goal. In 1860, cocaine, the oldest anesthetic, was extracted from the leaves of the Erythroxylon coca bush. In
1884, Sigmund Freud and Karl Koller were the first to use it as an anesthetic agent during ophthalmologic
procedures.

Procaine, a synthetic alternative to cocaine, was not developed until 1904. Procaine is an ester of para-
aminobenzoic acid (PABA). As procaine is metabolized, PABA, a known allergen, is released as a metabolic
product. The potential for severe allergic reactions limits the use of procaine and other ester-type anesthetic

303
agents. Tetracaine, another ester-type anesthetic, was introduced in 1930. Tetracaine is more potent than
procaine, and it causes similar allergic reactions.

In 1943, an alternative class of anesthetics was discovered when Lofgren developed lidocaine. This agent is an
amide derivative of diethylaminoacetic acid, not PABA; therefore, it has the benefit of a low allergic potential.
Since then, multiple amide-type anesthetics have been introduced into clinical use. Slight chemical alterations to
the compounds have imparted beneficial characteristics, including increased duration and potency, to each.
These compounds offer the surgeon more choices, and anesthetics can be appropriately matched to different
procedures.

Major types of regional anesthesia include:

Peripheral nerve blocks.
Epidural and spinal anaesthesia

Pathophysiology
Reviewing the physiology of nerve conduction is important before any discussion of local anesthetics. Nerves
transmit sensation as a result of the propagation of electrical impulses; this propagation is accomplished by
alternating the ion gradient across the nerve cell wall, or axolemma.

In the normal resting state, the nerve has a negative membrane potential of -70 mV. This resting potential is
+ +
determined by the concentration gradients of 2 major ions, Na and K , and the relative membrane permeability
to these ions (also known as leak currents). The concentration gradients are maintained by the sodium/potassium
ATP pump (in an energy-dependent process) that transports sodium ions out of the cell and potassium ions into
the cell. This active transport creates a concentration gradient that favors the extracellular diffusion of potassium
ions. In addition, because the nerve membrane is permeable to potassium ions and impermeable to sodium ions,
95% of the ionic leak in excitable cells is caused by K+ ions in the form of an outward flux, accounting for the
negative resting potential. The recently identified 2-pore domain potassium (K2P) channels are believed to be
responsible for leak K+ currents.

When a nerve is stimulated, depolarization of the nerve occurs, and impulse propagation progresses. Initially,
sodium ions gradually enter the cell through the nerve cell membrane. The entry of sodium ions causes the
transmembrane electric potential to increase from the resting potential. Once the potential reaches a threshold
level of approximately -55 mV, a rapid influx of sodium ions ensues. Sodium channels in the membrane become
activated, and sodium ion permeability increases; the nerve membrane is depolarized to a level of +35 mV or
more.

Once membrane depolarization is complete, the membrane becomes impermeable to sodium ions again, and the
conductance of potassium ions into the cell increases. The process restores the excess of intracellular potassium
and extracellular sodium and reinstates the negative resting membrane potential. Alterations in the nerve cell
membrane potential are termed the action potential. Leak currents are present through all the phases of the
action potential, including setting of the resting membrane potential and repolarization.

Mechanism of action
+ +
Local anesthetics inhibit depolarization of the nerve membrane by interfering with both Na and K currents. The
action potential is not propagated because the threshold level is never attained.

Although the exact mechanism by which local anesthetics retard the influx of sodium ions into the cell is
unknown, 2 theories have been proposed. The membrane expansion theory postulates that the local anesthetic
is absorbed into the cell membrane, expanding the membrane and leading to narrowing of the sodium channels.
This hypothesis has largely given way to the specific receptor theory. This theory proposes that the local
anesthetic diffuses across the cell membrane and binds to a specific receptor at the opening of the voltage-gated
sodium channel. The local anesthetic affinity to the voltage-gated Na+ channel increases markedly with the
excitation rate of the neuron. This binding leads to alterations in the structure or function of the channel and
+
inhibits sodium ion movement. Blockade of leak K currents by local anesthetics is now also believed to
contribute to conduction block by reducing the ability of the channels to set the membrane potential.

On the basis of their diameter, nerve fibers are categorized into 3 types. Type A fibers are the largest and are
responsible for conducting pressure and motor sensations. Type B fibers are myelinated and moderate in size.
Type C fibers, which transmit pain and temperature sensations, are small and unmyelinated. As a result,
anesthetics block type C fibers more easily than they do type A fibers. Therefore, patients who have blocked pain
sensation still feel pressure and have mobility because of the unblocked type A fibers.

All local anesthetics have a similar chemical structure, which consists of 3 components: an aromatic portion, an
intermediate chain, and an amine group (see molecular diagram below). The aromatic portion, usually composed
of a benzene ring, is lipophilic, whereas the amine portion of the anesthetic is responsible for its hydrophilic
properties. The degree of lipid solubility of each anesthetic is an important property because its lipid solubility

304
enables its diffusion through the highly lipophilic nerve membrane. The extent of an anesthetic's lipophilicity is
directly related to its potency.

Local anesthetics are weak bases that require the addition of hydrochloride salt to be water soluble and therefore
injectable. Salt equilibrates between an ionized form and a nonionized form in aqueous solution. Equilibration is
crucial because, although the ionized form is injectable, the nonionized base has the lipophilic properties
responsible for its diffusion into the nerve cell membrane. The duration of action of an anesthetic or the period
during which it remains effective is determined by its protein-binding activity, because the anesthetic receptors
along the nerve cell membrane are proteins.

The intermediate chain, which connects the aromatic and amine portions, is composed of either an ester or an
amide linkage (see molecular diagram above). This intermediate chain can be used in classifying local
anesthetics.

Indications
Anesthesia is indicated to reduce pain before surgical procedures.

Contraindications
Patient allergies may preclude the use of a particular anesthetic agent (see Complications section below).

Anesthesia
Local anesthetics are classified into 2 groups: the ester group and the amide group. The classification is based
on the chemical structure of the intermediate chain. This structural difference affects the pathway by which local
anesthetics are metabolized and the allergic potential.

Ester anesthetics are listed in the Table below. They are metabolized by hydrolysis, which depends on the
plasma enzyme pseudocholinesterase. Some patients have a rare genetic defect in the structure of this enzyme
and may be unable to metabolize ester-type anesthetics; this inability increases the possibility of their having
toxic reactions and elevated levels of anesthetics in the blood. In addition, 1 of the metabolic products generated
by hydrolysis is PABA, which inhibits the action of sulfonamides and is a known allergen. In patients with a known
allergy to an ester anesthetic, the use of all other ester-type anesthetic agents should be avoided.

Amide-type local anesthetics (see Table below) are metabolized by microsomal enzymes located in the liver. The
specific microsomal enzyme responsible for the elimination of lidocaine is cytochrome P-450 3A4. Therefore,
amide-type anesthetics should be used with care in patients with severe liver disease and patients taking
medications that interfere with the metabolism of the anesthetic, and the patients should be carefully monitored
for signs of toxicity.

Cytochrome P-4503A4 is present in the small bowel and the liver. Commonly used medications known to inhibit
cytochrome P-4503A4 are listed below (adapted from Klein and Kassarjdian). [1] Specific potent inhibitors of
cytochrome P-4503A4 that have been associated with clinically relevant interactions include itraconazole,
ketoconazole (azole antifungals), erythromycin, clarithromycin, cyclosporin (macrolides), amprenavir, indinavir,
nelfinavir, ritonavir (HIV protease inhibitors), diltiazem, mibefradil (calcium channel blockers), and nefazodone.
Grapefruit juice is also a potent inhibitor of P-4503A4 but appears to affect only the enteric enzyme, which does
not play a role in the metabolism of local anesthetics.

If the enzyme is inhibited because of the concurrent use of medications, it is unavailable to metabolize the
anesthetic and potentially toxic levels of the anesthetic can occur. In addition, beta-blockers may decrease blood
flow to the liver; therefore, they may also decrease the metabolism of amide-type anesthetics and may cause
serum levels of the anesthetic to increase.

Various types of regional blocks described include Digital, Deep Peroneal, Dorsal Penile, Inferior Alveolar,
Infraorbital, Oral, Median, Mental, tibial, radial, sephanous, Peroneal, supraorbital, sural, etc.

Complications

Local effects
Local effects are usually a result of the injection technique. These effects include pain, ecchymosis, hematoma
formation, infection, and nerve laceration. Pain is always felt when a local anesthetic is injected; however,
associated discomfort can be minimized by using good technique. Several factors, including needle puncture of
the skin, tissue irritation resulting from the anesthetic, and distention of tissues caused by infiltration, are
responsible for the discomfort associated with the use of local anesthetics.

Pediatric patients and patients who are extremely anxious may benefit from pretreatment of the injection area
[3]
with a topical anesthetic. Pretreatment eliminates the initial pain that occurs when the needle perforates the
skin. Small-diameter needles also decrease the pain associated with injection. Fortunately, for most dermatologic
procedures, a 30-gauge needle can be used to infiltrate tissue.

305
Table. Common Local Anesthetics*
Duration Without Duration With Maximum Dose Maximum Dose With
Anesthetic Epinephrine, Epinephrine, Without Epinephrine, Epinephrine,
min min mg/kg mg/kg
Esters
Cocaine 45 - 2.8 -
Procaine 15-30 30-90 7.1 8.5
Chloroprocaine 30-60 - 11.4 14.2
Tetracaine 120-240 240-480 1.4 -
Amides
Lidocaine 30-120 60-400 4.5 7
Mepivacaine 30-120 30-120 4.5 7
Bupivacaine 120-240 240-480 2.5 3.2
Etidocaine 200 240-360 4.2 5.7
Prilocaine 30-120 60-400 5.7 8.5
*Adapted from Dinehart.

Tissue irritation caused by local anesthetics is related to the acidity of the infiltrated solution; therefore, increasing
the pH of the mixture can decrease associated discomfort. The addition of epinephrine to an anesthetic solution
decreases the pH of the solution, making it more acidic (pH 3.5-4.5) and leading to a more painful injection. The
solution can be neutralized by the addition of sodium bicarbonate 8.4% to minimize discomfort. For example,
sodium bicarbonate 8.4% can be added to lidocaine with epinephrine in a 1:10 ratio to achieve a solution pH
similar to that of tissue fluid (pH 7.3-7.4).

Discomfort associated with distension of the tissues during the injection of local anesthetics is caused by the rate
of injection and the volume of fluid injected. To limit the pain, the anesthetic should be slowly administered to
allow the stretch receptors time to accommodate the new volume of fluid. [4] In addition, the volume of solution
injected should be the smallest volume needed to achieve a loss of sensation at the surgical site.
Studies have shown that patients receiving subcutaneous or intradermal injection of local anesthetics that were
warmed to body temperature, as opposed to room temperature, experienced less pain during injection. If
possible, warming of local anesthetics should be done prior to administration. [5]

The formation of ecchymosis or a local hematoma is a result of the perforation of cutaneous blood vessels.
These complications are encountered more commonly in areas of high vascularity, including the mucous
membranes, head, and genitalia. Ecchymosis and hematoma are even more pronounced when the patient has a
bleeding diathesis or when the patient has been taking aspirin or other anticoagulants. If ecchymosis occurs, the
patient should simply be reassured. If hematoma formation occurs, the patient should be evaluated. The
hematoma may require drainage with an 18-gauge needle, followed by the application of a pressure dressing.
Infection is an additional local complication of anesthetic use that usually occurs when proper sterile technique is
not used. Cleansing the skin surface with alcohol is adequate in otherwise clean or noninfected areas. If signs of
infection are noted, treatment includes appropriate culture studies and antimicrobial therapy. If abscess formation
occurs, drainage may also be required.

Nerve laceration, although rare, may occur during the infiltration of a local anesthetic. This complication more
commonly occurs during the placement of regional blocks than the placement of other blocks. Clinical indications
of nerve laceration include paresthesias, shooting or sharp stinging sensations, and excessive pain during needle
insertion. Paresthesias of the infraorbital nerve are characterized by sharp or shooting sensations involving the
upper lip, nasal ala, and upper teeth.

If the needle is suspected to have entered or lacerated a nerve, it should be withdrawn slowly and deliberately by
1-2 mm, until the paresthesias are no longer present. The needle should never be advanced further, moved
laterally, or inserted into the foramen, because these maneuvers further increase the risk of nerve laceration.
Although dysesthesias may remain for an extended duration, in most patients, the nerve regenerates and
sensation normalizes over time.

Tendon injury is an inherent aspect of transthecal digital anesthesia since the needle is pushed through the
tendon. This may cause persistent discomfort lasting 1-2 days post surgery. Tendon sheath infection and late
occurrence of trigger finger have also been reported.

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Cutaneous adverse effects that have been reported with the most commonly used topical anesthetic EMLA
include itching, burning, pain, pallor, erythema, edema, and purpura. Irritant dermatitis, allergic contact dermatitis,
and contact urticaria have also been reported, but these are very unusual. [6]
Amethocaine may induce an urticarial reaction at the site of application, and the risk of such a reaction seems to
be significantly higher when amethocaine is used over the antecubital fossa and in younger children.

Systemic effects
[7]
Systemic effects usually occur when blood concentrations of local anesthetic increase to toxic levels. Effects
are most often encountered after the unintentional intravenous injection or administration of an excessive dose of
an anesthetic. Adding a vasoconstrictor (eg, epinephrine) can reduce the systemic absorption of an anesthetic.
When using topical anesthetics, strict adherence to the maximal dose or area recommended is advised;
additionally, great caution must be exercised when using topical anesthetics on mucosal surfaces because of the
much greater absorption.

Importantly, remember that (1) the metabolism of ester anesthetics is decreased in patients with deficient
pseudocholinesterase activity and (2) the metabolism of amide anesthetics in patients who are taking
medications that inhibit the cytochrome P-450 system is decreased. In addition, the potency of an anesthetic is
directly correlated with the potential for toxicity. Allergic reactions, although systemic, are not related to serum
levels of the anesthetic, but rather, they are considered idiosyncratic and can occur at any dose.

Maximal safe doses of lidocaine for local anesthesia have been determined. For adults, a maximum of 4.5 mg of
lidocaine per kilogram of body weight can be administered, whereas as much as 7 mg/kg can be used if the
lidocaine solution has 1:100,000 epinephrine added as a vasoconstrictor. For children, lower maximal doses are
recommended; only 1.5-2.5 mg/kg of plain lidocaine and 3-4 mg/kg of lidocaine with epinephrine should be used.
Systemic toxicity resulting from excessive blood levels of anesthetics is clinically manifested as adverse reactions
in the CNS and cardiovascular system. The CNS is affected in a predictable and dose-dependent fashion. As
serum levels of lidocaine increase, effects on the CNS become more severe.

Any physician who uses local anesthetics must be aware of the signs and symptoms of systemic toxicity. At
serum lidocaine levels in the range of 1-5 mcg/mL, patients may complain of tinnitus, lightheadedness, circumoral
numbness, diplopia, or a metallic taste in the mouth. In addition, they may complain of nausea and/or vomiting, or
they may become more talkative. As serum levels increase to 5-8 mcg/mL, nystagmus, slurred speech, localized
muscle twitching, or fine tremors may be noticed. Patients also have been noted to have hallucinations at these
levels. If blood lidocaine levels reach 8-12 mcg/mL, focal seizure activity occurs; this can progress to generalized
tonic-clonic seizures. Respiratory depression occurs at extremely high blood levels (20-25 mcg/mL) and can
progress to coma.

If signs of CNS toxicity are noted, steps must be taken to reduce hypoxia and acidosis, because these states
increase the toxicity of local anesthetics. The patient's airway should be maintained, and supplemental oxygen
provided. If blood levels of carbon dioxide increase, protein binding of lidocaine decreases and results in higher
levels of free lidocaine in the blood. Increased respiration and respiratory alkalosis increase the seizure threshold
and decrease the uptake of the local anesthetic into the CNS. If convulsions occur, the patient's airway should be
maintained, and supplemental oxygen administered. If seizure activity is sustained, 5-10 mg of diazepam should
be administered slowly (1-2 mg/min) until the seizures cease.

Compared with the CNS, the cardiovascular system is less susceptible to the effects of local anesthetics. Most
adverse effects of the cardiovascular system that occur with the administration of local anesthetics are a result of
the addition of epinephrine rather than direct effects of the anesthetic. However, high blood levels of local
anesthetics directly reduce cardiac contractility. In addition to the direct vasodilatory effects of most local
anesthetics, the decrease in cardiac function can cause hypotension. Atrioventricular blocks, bradycardia, and
ventricular arrhythmias also are reported; these are more common in patients with known conduction
disturbances and requiring antiarrhythmic medications.

The treatment of conduction disturbances should be appropriately tailored to the type of reaction. The treatment
of hypotension requires the physician to initiate advanced cardiac life support protocols, that is, he or she should
ensure that the patient has a patent airway, provide supplemental oxygen, and elevate the patient's legs. If
necessary, intravenous fluid should be administered, and the use of vasopressor agents such as ephedrine
should be considered. Ephedrine can be intravenously administered in 5-mL incremental doses to a total of 15-30
mg, until a blood pressure response is noted.

Lidocaine and the FDA-approved topical anesthetics EMLA and LMX are pregnancy category B medications.

Allergic reactions
Allergic reactions to local anesthetics are extremely rare, especially with amide local anesthetics, and account for
less than 1% of the reactions caused by local anesthetics. Reactions can be type 1 (ie, anaphylactic) or type 4
(ie, delayed-type hypersensitivity) reactions. These reactions are not dose related, but, rather, they are

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idiosyncratic. Skin prick and intradermal test results are negative in the vast majority of patients, but some
authors recommend testing with the most commonly used amide local anesthetic (lidocaine).
Type 1 reactions are usually caused by ester-type anesthetics. The ester group of local anesthetics have a much
greater allergenic potential than that of the amide group. Pseudocholinesterases, which produce the highly
allergenic metabolic product PABA, break down ester-type anesthetics. Cross-reactivity exists among ester
anesthetics; therefore, the use of all anesthetics in this structural group should be avoided in a patient with an
established sensitivity to one ester-type anesthetic.

No cross-reactivity appears to exist between ester and amide anesthetics; however, cross-reactivity in
anaphylactic reactions has not been investigated thoroughly. In addition, reactions to preservatives, specifically
methylparaben and sodium metabisulfate (found in multiple-dose vials of amide anesthetics), may cause adverse
reactions in a patient who is allergic to an ester-type anesthetic. Preservative-free single-dose vials of lidocaine
are available for use if an amide anesthetic is to be used in a patient with a true hypersensitivity reaction to ester-
type anesthetics.

Clinical signs of type I reactions include pruritus, urticaria, facial swelling, wheezing, dyspnea, cyanosis, laryngeal
edema, nausea, vomiting, and abdominal cramping. Epinephrine with a concentration of 1:1000 should be
subcutaneously administered at a dose of 0.3-0.5 mL. This dose can be repeated every 20-30 minutes to a
maximum of 3 doses. If anaphylaxis ensues, a 5-mL dose of epinephrine 1:10,000 should be administered
intravenously.

Type IV (ie, delayed-type hypersensitivity) reactions account for 80% of allergic reactions to local anesthetics.
They are more common with the use of topical anesthetics and may occur with anesthetics of the amide and
ester subtypes. Clinical manifestations are similar to those of allergic contact dermatitis and include erythema,
plaques, and pruritus. Patients with a history of type IV reactions are not at an increased risk of type I reactions
due to amide-type anesthetics. Contact dermatitis caused by topical anesthetics should be treated with topical
steroid preparations.

Alternative agents for use as anesthetics in patients with a known allergy to both ester- and amide-type local
anesthetics include isotonic sodium chloride solution and injectable antihistamines. An intradermal injection of
0.9% sodium chloride solution can provide temporary anesthesia suitable for shave or punch biopsy. Physical
pressure on the nerve endings resulting from the volume injected is postulated to be responsible for the
anesthetic effect. Nonbacteriostatic sodium chloride solution should be used if the patient has an allergy to the
methylparaben preservative in the local anesthetic. A bacteriostatic solution, which contains benzyl alcohol, has
known anesthetic properties and can be used for limited procedures such as punch biopsy.

Injectable antihistamines, such as diphenhydramine, have been administered to patients who are allergic to local
anesthetics. The mechanism of anesthetic action is unknown. Injectable diphenhydramine is effective, but it has a
short duration of activity, it is sedating, and its injection is painful. In addition, tissue necrosis is reported after the
local injection of 5% diphenhydramine. If used for injection, diphenhydramine should be diluted to 1% by mixing 1
vial of 50-mg diphenhydramine with 4 mL of a bacteriostatic sodium chloride solution.

Reactions to local anesthetic additives

Epinephrine
With the exception of cocaine, local anesthetics directly cause relaxation of the vascular smooth muscle, which
leads to vasodilation. This effect increases bleeding at the surgical site. Vasoconstrictors, such as epinephrine,
are often added to anesthetic solutions to counteract this effect. The vasoconstrictor effect of epinephrine is
maximal at 7-15 minutes, and this effect is clinically evident as blanching of the skin. This blanching also is useful
in determining the area that is anesthetized.

Vasoconstriction not only decreases bleeding but also slows the rate of systemic absorption of the anesthetic,
which allows the body more time to metabolize the anesthetic and prolongs anesthesia. Therefore, larger
volumes of anesthetic can be injected when epinephrine is added to a solution. A premixed solution of lidocaine
with epinephrine in a concentration of 1:100,000 (1 mg/100 mL) is available. Concentrations greater than this are
associated with a higher rate of adverse effects, including an increased risk of tissue necrosis as a result of
prolonged ischemia.

Systemic effects of epinephrine can occur with a dose as little as 2 mL of an anesthetic solution containing
epinephrine in a concentration of 1:100,000. The most common clinical manifestation is transient tachycardia. At
higher doses and with an inadvertent intravascular injection, palpitations, diaphoresis, angina, tremors,
nervousness, and hypertension can occur. The maximum dose of epinephrine is 1 mg or 100 mL of a 1:100,000
solution. In patients with a history of heart disease, especially unstable angina and arrhythmias, the maximum
dose should be decreased to 0.2 mg or 20 mL of a 1:100,000 solution (recommendation of the NY Heart
Association).

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Epinephrine is contraindicated in patients with pheochromocytoma, hyperthyroidism, severe hypertension, or
severe peripheral vascular occlusive disease. Relative contraindications include pregnancy and psychological
instability; epinephrine can induce an acute psychotic episode in predisposed patients.
The FDA designates epinephrine as a pregnancy category B medication (ie, usually safe but benefits must
outweigh the risks). No known adverse effects on the fetus are reported; however, during the first trimester,
vasoconstriction may cause fetoplacental ischemia and affect organogenesis. In the last trimester, epinephrine
can induce premature labor if placental ischemia occurs. If possible, surgery should be performed without
epinephrine, or it should be postponed until after delivery.

Epinephrine must be used with caution in patients taking propranolol because life-threatening reactions have
been reported; these include hypertension, myocardial infarction, and stroke. Epinephrine stimulates alpha-
receptors to cause vasoconstriction and increase vascular resistance. Beta-receptors balance this effect by
causing vasodilation (beta2-receptors) and an increased heart rate (beta1-receptors). Like other nonselective
beta-blockers, propranolol antagonizes both beta1-receptors and beta2-receptors. Therefore, in the presence of
propranolol, the effects of epinephrine on alpha-receptors are unbalanced, and the result is pure alpha
stimulation, which leads to severe hypertension and reflex bradycardia.

Although propranolol is the only nonselective beta-blocker reported to have this effect, probably all nonselective
beta-blockers have the potential to cause severe hypertension and reflex bradycardia in the presence of
epinephrine. A significant risk does not appear to be associated with the use of epinephrine and cardioselective
beta-blockers. Although the use of epinephrine in patients who are taking nonselective beta-blockers is not
contraindicated, it should be avoided if possible. Apparently, the effect may be dose related, and caution should
be exercised because individual variability is reported.

In addition to nonselective beta-blockers, monoamine oxidase inhibitors, tricyclic antidepressants,

butyrophenones, and phenothiazines can cause hypotension or hypertension in patients who are taking
epinephrine.

Pain resulting from the infiltration of a local anesthetic can be reduced by using a solution with a pH close to
physiologic range (ie, pH 7.3-7.4). The pH of plain lidocaine is 6.3-6.4. When epinephrine is added to lidocaine,
the pH decreases to 3.5-4.5. The pH of the solution must be acidic to prevent the degradation of epinephrine.
Sodium bicarbonate

To reduce the pain of an injection of lidocaine and epinephrine, 1 mL of sodium bicarbonate 8.4% is added to 10
mL of the anesthetic solution to neutralize the solution. Buffered solutions should be discarded after 1 week
because the effectiveness of epinephrine decreases by almost 25% during this time.
Hyaluronidase

Hyaluronidase is a bovine-derived enzyme that hydrolyzes hyaluronic acid in the connective tissue and facilitates
the diffusion of the anesthetic. Although it can increase the spread of anesthesia, hyaluronidase also decreases
the duration of action of the anesthetics because it increases absorption. As expected, this increased absorption
leads to the potential for a greater incidence of toxic reactions that correspond to elevated blood levels. To
decrease distortion of the surgical site, the addition of hyaluronidase is useful for nerve blocks and procedures
around the orbit.

Hyaluronidase is marketed in ampules. One ampule is equivalent to 150 United States Pharmacopeia (USP)
units per milliliter. The usual dilution is 150 U in 30 mL of anesthetic. A patient can have an allergy to
hyaluronidase. Hyaluronidase is a foreign protein, and its use is contraindicated in patients with a known allergy
to bee stings. In addition, hyaluronidase contains the preservative thimerosal, which is a known allergen. To
evaluate the potential for an allergic reaction before infiltration, a test dose should be injected intradermally. If
urticaria is observed at the site of the test injection, the use of hyaluronidase is contraindicated.

Future of Regional Anesthesia

Tumescent anesthesia
In 1987, Jeffery Klein, a dermatologist, first created the technique of tumescent anesthesia in liposuction
[1]
procedures. Tumescent anesthesia is based on the use of dilute solutions of lidocaine (0.05-0.1%) in large
volumes to provide superior anesthesia. Epinephrine (1:1,000,000) is added for hemostasis, and the solution is
buffered with sodium bicarbonate to decrease injection discomfort. Concentrations as high as 55 mg/kg have
been used safely with the tumescent technique.

The use of such high total doses of anesthetic without systemic toxicity is understood. The absorption kinetics of
lidocaine change when high-volume, low-concentration solutions are used. Decreased concentrations of
lidocaine also result in slower plasma absorption with decreased peak plasma levels. The development of this
anesthetic delivery system has revolutionized the surgical technique of liposuction.

Electrical nerve stimulators and localization of peripheral nerves

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The use of nerve stimulation became commonplace in clinical practice only in the mid- to late 1990s. Research
on the needle-nerve relationship and the effect of stimulus duration ensued. More recently, the principles of
electrical nerve stimulation were applied to surface mapping of peripheral nerves using percutaneous electrode
guidance (PEG) for confirmation and epidural catheter placement (16-18) and peripheral catheter placement.
This chapter discusses the electrophysiology of nerve stimulation, electrical nerve stimulators, various modes of
localization of peripheral nerves, and integration of the technology into the realm of modern regional anesthesia.

Monitoring and documentation

The incidence of complications from general anesthesia has diminished substantially in recent decades, largely
due to advances in respiratory monitoring. The use of objective monitors such as pulse oximetry and
capnography allows anesthesiologists to quickly identify changing physiologic parameters and intervene rapidly
and appropriately.
In contrast, the practice of regional anesthesia has traditionally suffered from a lack of similar objective monitors
that aid the practitioner in preventing injury. Practitioners of peripheral nerve blocks were made to rely on
subjective end points to gauge the potential risk to the patient. This is changing, however, with the introduction
and adoption of standardized methods by which to safely perform peripheral nerve blocks with the minimal
possible risk to the patient. For example, instead of relying on feeling "clicks," "pops," and "scratches" to identify
needle tip position, the anesthesiologist can now directly observe it using ultrasonography. It follows that
advancements such as this may help in reducing the three most feared complications of peripheral nerve
blockade: nerve injury, local anesthetic toxicity, and inadvertent damage to adjacent structures ("needle
misadventure").

Bier Block
Intravenous regional anesthesia (IVRA) was first described in 1908 by the German surgeon A.G. Bier, hence the
procedure name Bier block. Originally, anesthesia was obtained by the intravenous injection of procaine in a
previously exsanguinated vascular space, isolated from the rest of the circulation by two Esmarch bandages
used as tourniquets. After initial enthusiasm, the technique fell into obscurity for >50 years. In 1963, Holmes
reintroduced the Bier block with the novel use of lidocaine, describing a series of 30 patients in The Lancet.
Today, intravenous regional anesthesia of the upper limb remains popular because it is reliable, cost effective,
safe, and simple to administer. It is a widely accepted technique well suited for brief minor surgeries such as wrist
or hand ganglionectomy, carpal tunnel release, Dupuytren contractures, reduction of fractures, and others. Since
the duration of anesthesia depends on the length of time the tourniquet is inflated, there is no need to use long-
acting or more toxic agents. Its application for longer surgical procedures is precluded by the discomfort caused
by the tourniquet, typi- cally beginning within 30 to 45 minutes. Other disadvantages include incomplete muscle
relaxation (where important) and lack of postoperative pain relief. With the implementation of a safety protocol
and with meticulous attention to detail, concerns about local anesthetic (LA) toxicity should merely be a
theoretical issue.

The only relevant anatomy is the location and distribution of peripheral veins in the extremity to be blocked. By
preference, a vein as distal as possible is chosen. The antecubital fossa is an alternative only when more distal
peripheral access is lacking.

The entire extremity below the level of the tourniquet is anesthetized. Numerous radiographic, radioisotope, and
neurophysiologic studies looked into the site of action of IVRA. However, the exact mechanism still remains the
subject of debate and controversy. The likely mechanism is that the local anesthetic, via the vascular bed,
reaches both peripheral nerves and nerve trunks (vasae nervorum), and nerve endings (valveless venules).
Diffusion of local anesthetic into the surrounding tissues also plays a role. Ischemia and compression of the
peripheral nerves at the level of the inflated cuff is probably another contributory component of the mechanism of
IVRA. Again, anesthesia achieved by intravenous regional anesthesia is limited only by the inevitable pain due to
tourniquet application; and, therefore, it is used typically for procedures lasting 30 to 45 minutes.

Blood component therapy

R.N. Makroo

Blood is the main oxygen carrier in the body yet it cannot be used as a tonic. The use of blood should be
judicious. The benefits attached to blood transfusion should be weighed against the risks involved with
transfusion of blood Since blood can not be sterilized, so there is possibility of transmitting any agent present in
red cells or plasma which has not been detected by routine screening tests for transfusion-transmissible
infections ,including HIV, hepatitis B & C ,other hepatitis viruses, syphilis , malaria etc.

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Unlike earlier times, whole blood is now considered as raw material rather than transfusion medium. The only
one indication for whole blood transfusion is exchange transfusion. The use of whole blood is obsolete and is
now completely replaced by various blood components like:

Packed Red Cell.

Leuko reduced red blood cells
Leuko reduced platelet concentrate
Fresh Frozen Plasma
Cryo precipitate
Cryo poor plasma
Granulocyte concentrate
Apheresis blood components

PACKED CELLS
Indications
Severe chronic anaemia to reduce chances of overload.
Hypoplastic anaemia
Hemolytic anaemia especially in aplastic crisis

Advantages
Less blood group antibodies so O Negative blood (group-non- specific) can be given to patients with other
groups.
Less Plasma proteins with packed cells so there are minimum anaphylactic reactions.

TRANSFUSION TRIGGER
It has now been reduced to 7.5gm/dl as opposed to 10gm/dl being used earlier from surgical and leukemia
patients however, transfusion requirement of each patient should be based on clinical status rather than
Hb value on HCT.

LEUCOREDUCED RED BLOOD CELLS

A red cell suspension containing <5 x 108 white cells per pack, prepared by collecting blood in a special top &
bottom blood collection bags ( Opti Bags ) and using opti press.

Advantages: -
Prevents febrile non-haemolytic transfusion reactions to a great extent.

Indications:
Severe chronic anaemia to reduce chances of overload.
Hypoplastic anaemia
Hemolytic anaemia especially in aplastic crisis
Storage :4 - 6 c
Expiry : 42 days Day of collection zero day.

Administration of Packed / Leucoreduced red blood cells

Check the identity of patient properly before transfusion

Must be ABO & Rh D compatible with patients.

Alternative blood group can be given at times if group specific blood is not available eg
For AB the alternative blood in order of preference should be A, B & O
For A group ---------- O group
For B group ----------- O group
No alternative blood for O group
Transfuse within 4 hrs.
Transfuse blood within hr of issue from Blood Bank.
Complete the transfusion within 4 hrs.
Blood once issued will not be recieved back.
Infection risks same as for whole blood.

PLATELET CONCENTRATE
Derived from single blood donation
Volume : 65 80 ml. Should not have any visible RBC contamination (red cells ( 1.2 x 10 9 red cells)
Storage : 5 days Day of collection zero day at 22 c + 2
Indication :
Thrombycytopenia of any cause except ITP unless life saving.
Platelet functional defects of any cause
Dosage : 1 unit of platelet concentrate / 10 kg body weight eg for 60kg man 6 units of random donor platelets
concentrate.

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Administration :
1. No special transfusion sets required
2. No cross-matching required, however if contaminated with red cells cross match is indicated.
3. Use group specific platelets, however group non-specific platelets can be used if group specific platelets
not available.
4. Platelet dont carry Rh antigen however in young ladies of child bearing age, dont give Rh Positive
platelets incase there is any RBC contamination.

Complications
Allergic & febrile transfusion reaction are not uncommon,especially in patients recieving multiple
Transfusions. Infection risks are same as for whole blood.

FRESH FROZEN PLASMA

Description
Volume 180 220 ml
Contains stable cougulation factors albumin & immunoglobulin
Factor VIII ( 20% of normal )
Fibrinogen 150-230

Dosage : 12-15ml/ kg body wt.

Indications
Replacement of multiple coagulation factor deficiencies eg.
Liver disease
Massive blood loss
Over dose of antigoagulants eg (Warfarion & Dicumerol)
DIC
TTP

Storage
Stored at -20c below & before use should be thawed at 37c & once thawed should be storaged at 4 - 6c &
used within 6 8 hrs.

Complications
Allergic & febrile transfusion reaction
Transmission of infections same as for whole blood.

CRYOPRECIPITATE

Description
Prepared from FFP by thawing it under controlled conditions at 4c. It contains approximately 80-100 iu of factor
VIII & 150-300mg of fibrinogen per pack.

Storage : At 30c & below for 1 year.

Indications
As an alternative factor VIII concentrate in the treatment of: -
Vonwillibrand disease
Hemophilia A
Factor XIII deficiency
Fibrinogen deficiency eg Dic
Infection risks are same as for whole blood.

Dosage
Depends upon severity of the factor deficiency normally 4-6 packs to be repeated 12 hourly.

Administration
To be given immediately within 6 hrs after thawing
Use standard blood administration set
No compatibility testing required

CRYO POOR PLASMA

Plasma which is deficient in factor VIII& fibrinogen but contains all other plasma constituents

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Indication :
For volume replacement
As replacement fluid in exchange transfusion
As a source of plasma proteins.
Infection risks are same as for whole blood.

FRESH BLOOD
There is no indication of fresh blood today when the blood components are available, as the fresh whole blood is
not going to meet the requirements of the patients

APHERESIS BLOOD COMPONENTS.

Apheresis blood components is gaining importance because;
a) 1.Provide adequate adult dose from single donor.
b) 2.Reduce donor exposure to the patient,thus improves blood safety.
c) 3.Reduce bacterial contamination,especially in platelets.
d) 4.Lower chances of refractoriness to blood components.
e) 5.One donor can donate platelets twice a week provided platelets counts
f) are adequate.

IRRADIATED BLOOD COMPONENTS

Indications
Severe immuno-suppresed patients to prevent graft versus host disease (GVHD)
Bone marrow transplant patients
Peripheral blood progenitor cell transplant patients
Pre-mature new borns
Patients with haematologic malignencies
Intrauterine transfusion
Before sending the request for irradiated blood components consultant incharge of the patient should discuss
with the consultant of transfusion medicine department.

Getting the right Blood to the right patient at right time

1. Assess the Patients clinical need for blood & when it is required.
2. Inform the patient and/or relative about the proposed transfusion.
3. Record the indications for transfusion in the patients notes.
4. Select the blood product & quality required. Use a blood ordering schedule as a guide to transfusion
requirement for common surgical procedures.
5. Complete the blood request from accurately and legibly. Write the reason for transfusion so the blood
bank can select the most suitable product for compatibility testing.
6. If blood is needed urgently, contact the blood bank by telephone immediately.
7. Obtain & correctly label a blood sample for compatibility testing.
8. Send the blood request form & blood sample to the blood bank.
9. Laboratory performs blood grouping to reconfirm the blood group &selects the unit of Blood for cross
matching. Cross-matching label is a fixed on the unit of blood & reactionform made
10. Blood is issued to the ward on reciept of issue slip after properly checking the identity.
11. Store blood products in correct storage conditions if not immediately required for transfusion.
12. Check the identity on :
Patients
Blood Products
Patients documentation.
13. Administer the blood products.
14. Record in the patients notes:
Type & volume of each product transfused
Unique donation number of each unit transfusion.
Blood group of each unit transfused
Time at which the transfusion of each unit commenced
Signature of the person adminstering the blood
15. Monitore the patientbefore,during and on completion of transfusion.
16. Record the completion of transfusion.
17. Identify and respond immediately to any adverse effect of transfusion &record in the patients file.

RESPONSIBILITIES OF CLINICIAN IN CASE THE PATIENT NEEDS TRANSFUSION

1. Inform and explain to the patient or relatives about the proposed transfusion of blood/blood products(
BENIFITS & RISKS) and record the same in the patients file.
2. Ensure proper identity of the patient &Correctly complete a blood request form.
3. Collect the blood sample from the right patient in the right sample tube & correctly label the Sample tube.

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4. Order blood in advance, whenever possible.
5. Provide the blood bank with clean information on :
The Products and number of units required
The reason for transfusion
The urgency of the patients requirement for the patient
When and where the blood is required.
6. Ensure the correct storage of blood and blood products in the clinical area before transfusion.
7. Formally check the identity of the patients, the product and the documentation at the patients bedside before
transfusion.
8. Correctly record transfusion in the patients notes:
Reason for transfusion
Products & volume transfusion
Time of transfusion
Monitoring of the patient before, during and after transfusion
Any adverse events.

COLLECTING BLOOD/BLOOD COMPONENTS PRIOR TO TRANSFUSION FROM BLOOD BANK

A common cause of transfusion reactions is the transfusion of an incorrect unit of blood that was intended for a
different patient. This is often due to mistakes when collecting blood from the blood bank.It is important to follow
these instructions.
1. Bring written documentation to identify the patient.
2. Check that the following details on the compatibility label attached to the blood pack exactly match the
details on the patients documentation :
Patients family name and given name
Patients hospital reference number ( I.P.NO)
Patients ward, operating room or clinic
Patients ABO and Rh D group.

Storing blood products prior to transfusion

Once issued by the blood bank, the transfusion of whole blood, frozen plasma should be commenced
within 30 minutes .
If the transfusion cannot be started within this period, they must be stored in an approved blood refrigerator at a
temperature of 2 to 6 C. The temperature inside every refrigerator used for blood storage in wards and operating
rooms should be monitored and recorded daily to ensure that the temperature remains between 2 to 6 C
If the ward or operating room does not have a refrigerator that is appropriate for storing blood the blood should
not be released from the blood bank until immediately before transfusion.

Whole Blood and Red Cells

Should be issued from the blood bank in a cold box or insulated carrier (brought from the ward / theater )which
will keep the temperature between 2 6 c if the ambient (room) temperature is greater than 25C or there is a
possibility that the blood will bot be transfused immediately.

Should be stored in the ward or operating theatre refrigerator at 2 6 C until required for transfusion.
The upper limit of 6C is essential to minimize the growth of any bacterial contamination in the unit of blood.
The lower limit of 2 C is essential to prevent haemolysis, which can cause fatal bleeding problems or renal failure.

Whole blood and red cells should be infused within 30minutes of removal from refrigeration.

Platelet concentrates
Should be issued from the blood bank in a cold box or insulated carrier ( brought from the ward /theater ) that will
keep the temperature at about 20 24C. Platelet concentrates that are held at lower temperatures lose their
blood clotting capability; they should never be placed in a refrigerator.Platelet concentrates should be
transfused as soon as possible.

Fresh frozen plasma and cryoprecipitate

FFP should be thawed in the blood bank in accordance with approved procedures and issued in a blood transport
box ( brought from the ward / theatre ) in which the temperature is maintained between 2 6 C
Fresh frozen plasma should be infused within 30minutes of thawing
If not required for immediate use, it should be stored in a refrigerator at a temperature 2-6C and transfused within
24hrs.
As with whole blood or red cells, bacteria can prolifeate in plasma that is held at ambient (room ) temperature.

Administering blood products

Staff involved in the administration of blood / blood components should ensure the final identity check of the
patient, the blood pack, the compatibility label and the documenatiaon.

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For each unit of blood supplied, the blood bank should provide documentation stating:
Patients family name and given name
Patients ABO and Rh-D group
Unique donation number of the blood pack
Blood group of the blood pack

Compatibility label
A compatibility label should be attached firmly to each unit of blood, showing the flowing information.
THIS BLOOD IS COMPATIBLE WITH Blood Pack NO._____________
Patients Name :
Patients hospital reference number ( I.P.NO ) Patients ward
Patients ABO and Rh-D group
Expiry date of blood /blood component
Date of compatibility test
Blood group of blood pack /cmponent

Checking the blood pack

The blood pack should always be inspected for signs of deterioration on arrival in the ward / operating room.
However the staff taking the blood /blood component from blood bank should check for any leakage
before signing the issue register..
Discoloration or signs of any leakage may be the only warning that the blood has been contaminated by
bacteria and could cause a severe or fatal reaction when transfused

The final identiy check should be undertaken at the patients bedside immediately before commencing the
administration of the blood product. It should be under taken by two persons at least one of whom should be
registered nurse or doctor .

THE FINAL PATIENT IDENTITY CHECK

- Ask the patient to identify himself / herself by family name, given name date of birth and any other
appropriate information
If the patient is unconscious ask a relative or a second member of staff to state the patients identity Check
the patients identity and gender.
Patients identity wristband or label
Patients medical notes
- Check the following details on the compatibility label attached to the blood pack exactly matching the details
on the patients documentation and identity wristband
Patients family name and given name
Patients hospital reference number
Patients ward or operating room
Patients blood group
- Check that there are no discrepancies between the ABO & Rh-D group on
Blood pack
Compatibility label
- Check there is no discrepancies between the unique donation number on
Blood pack
Compatibility label
- Check the expiry date on the blood pack has not been passed.

The final check at the patients bedside is the last opportunity to detect an identification error and prevent
a potentially incompatible transfusion which may be fatal

TIME LIMITS FOR INFUSION

Start Infusion Complete Infusion
Whole blood or red cells Within 30 minutes Within 4 hrs ( or less in high)
Of removing pack ambient temperatures
From refrigerator
Platelet concentrates Immediately Within 20 mintues
Fresh Frozen plasma As soon as possible Within 20 minutes
And cryoprecipitate

Disposable equipment for blood adminsitration

Cannulas for infusing blood products ;
Must be sterile and must never be reused
Use flexible plastic cannulas if possible as they are safer and preserve the veins

Whole blood, red cells, plasma and cryoprecipitate

Use a new sterile blood administration set containing an integral 170-200 micron filter

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Change the set at least 12 hourly during blood component infusion
In a very warm climate change the set more frequently and usually after every four units of blood ,if given within a
12 hours period.

Platelet concentrates
Use a fresh blood administration set or platelet transfusion set primed with saline

Paediatric patients
Use a special paediatric set for paediatric patients
These allow the blood or other infusion fluid to flow into a gradutated container build into the infusion set.This
permits the volume given and the rate of infusion to be controlled simply and accurately.

Warming blood
There is no evidence that warming blood is beneficial to the patient when infusion is slow
At infusion rates greater than100ml/minute cold blood may be contributing factor in cardiac arrest. However
keeping the patient warm is probably more important than warming the infused blood.
Warmed blood is commonly required in ;
Large volume rapid transfusion
Adults : greater that 50ml /kg/hour
Children : greater that 15ml/kg/hour
- Exchange transfusion in infants
- Patients with clinically significant cold agglutinins
Blood should only be warmed in a blood warmer. Blood should never be warmed in a bowl /oven as this can
result in haemolysis of red cells which can prove fatal.

Recording the transfusion

Before administering blood products, It is important to write reason for transfusion in the patients case-notes. It
the patient later has a problem that could be related to the transfusion, the records should show who ordered the
products and why.This information is also important in conducting the an audit of transfusion services.

The following information should be recorded in the patients notes

Whether the patient and or relatives have been informed about the proposed transfusion treatment
The reason for transfusion
Signature of the prescribing clinician
Pre-trasnsfusion check on
Patients identity
Blood pack
Compatibility label

Signature of the person performing the pretransfusion identity check

- The transfusion
Type and volume of each product transfused
Unique donation number of each unit transfused
Blood group of each transfused
Time at which the transfusion of each unit commenced
Signature of the person administering the blood component
Monitoring of the patient before, during and after the transfusion.

- Any transfusion reactions

Severe reaction mostly occur within first 15 minutes of start of transfusion.So all patients should
Be monitored carefully during this peroid & this should be followed for every subsequent unit of
Blood to be transfused. In case of any suspected transfusion reaction following instruction to be
followed.
1.Stop Transfusion
2.Keep the I.V. line open with normal saline.
3.Inform the attending Physician and blood bank.
4. Recheck all labels forms and identify of Patient to determine that the patient received the
correct unit of blood/ component sent from blood bank.
5.Send following sample to Transfusion Medicine Deptt. ( Blood Bank):-
- An immediate post transfusion clotted and EDTA blood sample of the patient.
- Implicated blood bag/ component along with transfusion set.
- The first specimen of the patients urine following reaction.

Record the clinical details and action taken in the patient file.

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 Energy sources in Surgery

Rajdeep Singh

It is impossible to imagine doing surgery nowadays without some type of energy source being used. From the
electrosurgical unit used in practically all surgeries, to vessel sealing systems and lasers used for advanced and
endoscopic surgeries, there is a wide variety of energy sources, which the surgeon uses without realising how
easy his life has been made by use of technology.

Since electrosurgery is the commonest form of energy used in surgery, more emphasis will be laid on its
principles. The following energy sources will be discussed:
Electrosurgery
Argon plasma coagulator
Vessel sealing systems - Ligasure Enseal
Ultrasonic vessel sealing systems Harmonic scalpel
Lasers

ELECTROSURGERY

Electrosurgery is commonly wrongly referred to as cautery, electrocautery or diathermy. Cautery refers to the
direct application of a heated object to a bleeding area to achieve haemostasis, akin to the use of a heated knife
blade in older movies. Through the ages, similar techniques have been used, such as application of a heated
1
metal plate after guillotine amputation of the breast or inguinal hernia. When an electric source is used to heat a
metal piece, which is then directly applied on to a bleeding point, it is known as electrocautery.
Electrosurgery on the other hand is different as it does not cause heating of the metal tip, but causes generation
of heat from within the cells itself.
Diathermy is the production of deep heat, in which the aim is not to destroy cells but to produce relaxation of
muscles and promote tissue repair. Different types of diathermy are used by physiotherapists.

History
The introduction of electrosurgery to surgery is credited to two Americans: William T Bovie and Harvey Cushing
the Father of Neurosurgery. Bovie, a biophysicist, had originally designed and made a prototype of the
electrosurgical generator which he had displayed in a conference. Residents of Cushing brought it to his notice.
Neurosurgery at that time was plagued with high operative mortality due to bleeding. In fact, this device was first
used in 1926 on a patient who had previously been declared inoperable on account of the vascular nature of a
tumour. The tumour was successfully removed with the prototype unit. American books often refer to bovie as a
verb e.g. they might say bovie the bleeding point. It refers to the same thing.

There have been numerous changes over the years, but the basic principle remains the same. The base unit
generates a high frequency alternating current, which is sometimes referred to as a radiofrequency current.
Electrical supply in India is 220V alternating current at 50Hz frequency. Inadvertent contact with a live electrical
wire produces a shock. This shock is due to the stimulation of neuromuscular tissue, which causes pain and
contraction of muscles. This shock is not desirable during surgery, so the frequency is increased to the level
beyond which neuromuscular stimulation occurs this corresponds to 100 kHz in most animals.2To be on the
safe side, most machines commercially available nowadays work beyond 300kHz.

It is necessary that electric current passes through the tissue to produce heating simple keeping the electrode
away from the tissue and activating the machine produces no heat. In other words, the electrical circuit has to be
completed. As the current passes through the tissues, it causes the intracellular ions to separate out according to
the polarity of the applied current. Therefore, all positive ions (e.g. H + ions) move towards the negative electrode
and negative ions (most proteins) move towards the positive elctrode. However, in the next fraction of a second,
the polarity of the applied current is reversed (remember, it is a high frequency alternating current); the
intracellular ions now move to the opposite direction. Hence, the ions are oscillating in sync with the frequency of
the applied current. It is this vibration of intracellular ions which produces heat; this heat production can be so fast
3
as to cause vapourization of intracellular water.

There are two primary modalities of use of an electrosurgical unit: Cutting mode and Coagulation mode. All other
modalities are modifications or variations of these two modes.

Cutting mode

The passage of a continuous alternating current produces rapid heating within the cells so rapid that the water
is converted into steam and the cells simply explode. This produces a cutting effect some haemostasis does
occur. To get the best cutting effect, the tip of the electrode should not be in contact with the tissue when it is
activated. This produces small sparks, which localize the effect and result in a cutting effect. It the electrode tip is
in firm contact, it actually produces coagulation.

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There has been a controversy as to whether cutting electrosurgery is safe for incising skin. Numerous studies
have shown that it is safe and produces no long term effects such as wound infection or worse scar. Some
surgeons however have had bad experience with the use of a cautery. The reason may be faulty technique if it
is used as a knife (more pressure cuts better) then it does not work. To get a good cutting effect, keep the tip
slightly away from the tissue to be cut.

Coagulation mode

To achieve coagulation, our aim is to decrease the temperature produced, so that the proteins coagulate and
produce haemostasis. In electrosurgery, this in achieved by producing an intermittent current the alternating
current is stopped for fractions of a second. This allows the tissues to cool down, producing a coagulum which
stops bleeding.

For optimum coagulation, the tissue should be in firm contact with the electrode. This is the most common mode
employed, where a bleeder is held with forceps and an activated electrode applied to it.

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Spray mode

This is a variant of coagulation mode, where the voltage is increased so much that it overcomes the resistance of
air. Long sparks fly from the tip to cause surface coagulation most commonly used for achieving surface
haemostasis from liver surface. Though attractive this is an inherently dangerous mode, especially during
laparoscopy, since the current can jump normal insulation and burn surrounding tissue.

Blend mode

Sometimes we prefer a mixture of cutting and coagulation modes, e.g. while cutting subcutaneous fat. To achieve
this combination, the machine alters the on period during coagulation phase. During full coagulation, the curent
flows for 6% of the time. In blend mode, the current flows for 25%, 40% or 50% of the time, depending upon the
settings.

Bipolar electrosurgery

It should be emphasized that an electrical current cannot flow unless there are two poles. The term monopolar
and bipolar refer to what the surgeon is holding in his hand. There is a single electrode which is used in
monopolar electrosurgery, and two electrodes in case of bipolar.

Using a bipolar has many advantages. Foremost is that current has to pass through a small amount of tissue,
hence the applied voltages are much lower. Secondly, there are lesser chances of stray currents causing
vascular thrombosis or cardiac arrhythmias. However, bipolar cannot achieve cutting effect, since the tissue has
4
to be firmly held for the current to flow. Therefore, monopolar is more versatile as compared to bipolar.

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Radiofrequency generator

It is the same unit and works with the same principle as the conventional electrosurgical unit. The only difference
is that the operating frequency is increased even higher to megahertz range. The advantage is that the effects
become more precise; the disadvantage is that high frequencies are difficult to isolate and insulate. RF
generators are commonly used for varicose veins, liver and renal tumours.

Complications

1. Burns: may occur due to inadvertent touching of activated electrode to skin, or viscera. Electrical burns are
considered deep burns, hence suturing of bowel or excision of burnt part is recommended. Relatively more
common are burns at the site of return electrode improper application can cause current concentration and
a burn. This is accentuated if fluid collects between the return electrode and the skin fluid concentrates the
current and causes burns. The ideal site for abdominal surgeries is over the thigh, bandaged into position.
2. Smoke inhalation: the smoke produced during electrosurgery is considered toxic and carcinogenic. Live
viruses have been recovered from the smoke. Current recommendations include the use of a smoke
scavenging system whenever electrosurgery is used.
3. Arrhythmias: If monopolar current passes through the heart, it can induce arrythmias. It is therefore prudent
to ensure that the path of current does not cross the heart.
4. Skin necrosis: Never use monopolar when there is an end artery concentration of current is preferably to
fluid containing structures. When used on an extremity, the current will concentrate on the vessels and cause
thrombosis, resulting in distal gangrene. Circumcision is one such example, where monopolar electrosurgery
should be avoided.
5. Direct coupling: refers to the inadvertent passage of current through an unintended path. E.g. while holding
bowel with left hand in laparoscopic surgery, the right handed dissector accidentally touches the bowel
holder during activation.5
6. Insulation failure: more applicable to laparoscopic surgery, where insulation failure can cause burns to
viscera outside the visual field5
7. Capacitative coupling: The reason why surgeons get shocks despite wearing gloves. Alternating current is
not limited by insulation, as it can jump across it by a dielectric effect. In laparoscopic surgery, it can cause
electrical charge to build in a metallic port. If this charge is not safely grounded, it can discharge onto a
5
nearby viscera, causing a burn outside the visual field of the surgeon.
8. Bowel explosion: stray incidents have been reported. It was more common when mannitol was used for
colonic preparation. Still, to be on the safe side, a distended colon should be opened with a knife to allow the
inflammable gases to dissipate, before using the electrode.

How to minimize risks

Inspect insulation
Use lowest possible power setting
Use a low voltage waveform (cut)
Use brief intermittent activation
Do not activate in open circuit
Do not activate in close proximity or direct contact with another instrument
Use bipolar electrosurgery when appropriate
Select an all metal cannula system as the safest choice.

ARGON PLASMA COAGULATOR

Similar to monopolar electrosurgery in its basic function. The electrode is replaced by argon gas, which gets
ionized and carries the current to the area being coagulated. It causes excellent superficial coagulation,
especially raw surfaces of liver after partial hepatectomy. The advantage of argon plasma over spray cautery is
that argon reaches into crevices also, producing uniform haemostasis. Another advantage is that it can be carried
through fine tubes during colonoscopy, and is used for coagulation of angiodysplasias. Conventional cautery in
such cases can cause full thickness burns.

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LIGASURE , ENSEAL
Similar to bipolar in principle. The companies have added an added layer of feedback sensing, so that as the
tissue dries out, it apllies a higher voltage so that proper coagulation does not stop. When a complete seal has
formed, the current flow stops automatically. In addition, a component of pressure has also been added, so that
these electrodes need to be locked before optimal activation. These machines are said to seat arteries up to
7mm in diameter. It should be noted that veins are not as effectively sealed, since they have less collagen in their
walls.

HARMONIC SCALPEL

The precursor of many similar units, the harmonic scalpel is unique in its operation in not requiring the passage of
current through the tissue. Hence it is the safest in this regard. It works on the principle of friction the passage
of current through a piezoelectric crystal causes it to vibrate at a fixed frequency (55.5kHz for the Harmonic
Scalpel). This vibration is amplified through the instrument which drives the active end of the probe. Any tissue
held between its jaws is subjected to a sawing motion, which divides the tissue. Using a lower setting (2,3)
decreases the amplitude, producing more coagulating effect and less cutting. The harmonic scalpel claims to seal
vessels up to 5mm in diameter. Similar to Ligasure, veins are not so effectively coagulated.

LASERS

An acronym for Light Amplification by the Stimulated Emission of Radiation, Lasers have now a wide variety of
applications. Their names are derived from the lasing medium used e.g. CO2, KTP, Holmium, etc. Use of
different lasing mediums produces highly collimated light of different frequencies. Different frequencies are
absorbed by different tissues, hence their limitation.

Carbon dioxide laser

Limited to use on surface lesions. It produces a very fine cutting effect, so often used for excision of skin lesions
such as warts, skin cancers, moles, keloids, etc. Since it cannot be used through endoscopes, its use in general
surgery is quite limited.

Holmium laser
Extensively used in urology for enucleation of prostate and breaking of calculi. Also used for intracorporeal
lithotripsy of CBD calculi, either laparoscopically or endoscopically.

KTP laser
A Potassium-Titanyl-Phosphate laser causes near bloodless evaporation of prostate. This is a slow process, but
the advantage is that longer operating times are possible.

Excimer laser
Used for LASIK eye surgery and angioplasty.

Conclusion
Correct choice of an energy source makes a lot of difference in surgery. It is said that a good surgeon does not
need advanced energy sources- this is probably not true in the present era of laparoscopic, endoscopic and
endourologic surgery. Not only the correct choice, but understanding the limitations of various technologies is
also essential. The operating surgeon would certainly not want excessive bleeding at the same time there are
anecdotal reports of important structures being destroyed because tissue dissection was not done. Energy
sources help the surgeon, but they cannot replace poor surgical technique.

References

1. Fornaciari A, Giuffra V. Surgery in the early middle ages: Evidence of cauterisation from Pisa. Surgery
2012;151:351-2
2. Taheri A, Mansoori P, Sandoval LF, Feldman SR, Pearce D, Williford PM. Electrosurgery: part I. Basics and
principles. J Am Acad Dermatol. 2014;70:591
3. Massarweh NN, Cosgriff N, Slakey DP. Electrosurgery: history, principles, and current and future uses. J Am Coll
Surg. 2006;202:520-30
4. Vilos GA, Rajakumar C. Electrosurgical generators and monopolar and bipolar electrosurgery. J Minim Invasive
Gynecol. 2013;20:279-87
5. Brill AI, Feste JR, Hamilton TL, Tsarouhas AP, Berglund SR, Petelin JB, Perantinides PG. Patient safety during
laparoscopic monopolar electrosurgery--principles and guidelines. Consortium on Electrosurgical Safety During
Laparoscopy. JSLS. 1998;2:221-5

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 Functional Imaging of Cancer

INTRODUCTION
Imaging technologies used to assess patients with cancer may be grossly subdivided into structural and
functional imaging categories. Structural imaging entails the assessment of morphologic features of normal
tissues and organs of the body and of malignant lesions within these structures. Computed tomography (CT),
magnetic resonance imaging (MRI), and ultrasonography (US) are the prototypical imaging technologies that are
currently used to perform oncological structural imaging. These can be used to assess the morphologic features
of lesions and of changes in these features over time through use of serial imaging. However, structural imaging
alone may not provide the clinician or researcher with all of the information that is necessary to fully characterize
or monitor lesions in those with cancer or at risk for cancer.

As such, functional imaging has come into existence and is comprised of a multitude of noninvasive, quantitative
imaging techniques that are currently in use to study tumor physiology, to probe tumor molecular processes, and
to study tumor molecules and metabolites in vitro and in vivo. Functional imaging can be implemented through
use of CT, MRI, and US, as well as through positron emission tomography (PET), single-photon emission
computed tomography (SPECT), and optical imaging (OI). Such functional imaging techniques can be used in
conjunction with structural imaging techniques, often in a synergistic fashion, to detect, diagnose, characterize, or
monitor tumors before and after therapeutic intervention. These can also be used to study tumor gene
expression, to track cells and therapeutic drugs, to optimize individualized treatment planning for patients with
tumors, and to foster new oncologic drug development.

RATIONALE FOR FUNCTIONAL IMAGING OF CANCER

Cross-sectional structural imaging by CT, MRI, and US is currently used in standard clinical practice on a daily
basis to qualitatively or semiquantitatively detect, characterize, stage, assess posttherapeutic response, and
determine recurrence of malignant tumors based on structural features such as tumor shape, size, margins,
location, spatial extent, attenuation (on CT), signal intensity (on MRI), echogenicity (on US), or gross degree of
enhancement after intravenous administration of contrast agents. Despite its many contributions to the
management of patients with cancer, structural imaging alone suffers from many shortcomings in such settings.
The first is that gross macroscopic changes in tissues or organs due to cancer generally lag in time following
alterations at the molecular, subcellular, or cellular levels. This has significant implications with regard to early
detection of cancer for screening purposes, as well as for monitoring response to therapeutic intervention. The
second is that macroscopic abnormalities are often nonspecific and often seen in nonneoplastic conditions. For
example, enlarged lymph nodes in the setting of known malignancy may either be due to metastatic disease or
benign hyperplasia. The third is that data regarding physiology, biological processes, and molecular
characteristics of tumors are not obtained. As such, structural imaging at a single time point may not provide
adequate information regarding patient prognosis, probability of tumor response to therapeutic intervention, and
new drug development. This shortcoming is exemplified by the Response Evaluation Criteria in Solid Tumors
(RECIST) criteria to assess for tumor response to therapy based on unidimensional lesional size measurements.
These criteria completely disregard functional imaging information about tumors that may be relevant to accurate
definition of early tumor response.

Fortunately, quantitative functional imaging techniques may be used with structural imaging techniques to
maximize the amount and value of data acquired for tumor detection, characterization, staging, prognosis
assessment, treatment planning, and early treatment monitoring, as well as for monitoring of cell trafficking (ie,
how different types of cells distribute to various organ or tissue locations in the body) and new drug development.

These techniques involve specialized applications of CT, MRI, and US, as well as SPECT, PET, and OI.PET and
SPECT are 2 types of emission computed tomography that are used to study the distribution of radiolabeled
tracers within the body. PET radiotracers emit positrons that, after encountering electrons, lead to emission of 2
gamma rays directed at 180 degrees from each other. Sites of tracer accumulation in the body are thus
determined by detection of these paired gamma rays, which is termed coincidence detection. SPECT involves
the use of radioisotopes that emit single gamma rays in arbitrary directions, thus requiring the presence of a
metallic collimator to determine sites of tracer accumulation in the body. While the collimators provide
directionality, they screen out most of the emitted photons. As a result of these features, SPECT generally has
lower sensitivity than PET and is not as readily quantifiable as PET. Furthermore, in contrast to positron-emitting
radionuclides, single photon-emitting radionuclides cannot be labeled to most biologically important compounds.
This also limits its use both for clinical and research purposes.

OI uses visible light to create images following administration of an agent that can be detected through
fluorescence or luminescence. However, as biologic tissues are opaque to light at most wavelengths, only small
animals that are relatively transparent to light, as well as structures superficially located in the human body within
the lumina of hollow organs or along the external bodily surface, are generally amenable to OI.

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FUNCTIONAL IMAGING TECHNIQUES TO STUDY TUMOR PHYSIOLOGY

Perfusion Imaging
Perfusion imaging may be used to improve detection and characterization of tumors, to monitor tumor response
to therapeutic intervention, to improve delineation of residual or recurrent tumor, and to assess patient prognosis
before and after treatment. As such, MRI, CT, US, PET, SPECT, and OI have all been used to study the
vascularity of malignancies. However, use of perfusion imaging techniques requires development of standardized
measurement approaches in the context of prospectively specified, biologically valid endpoints.

MRI has been commonly applied to study tumor perfusion through the dynamic contrast-enhanced MRI (DCE-
MRI) technique, performed by acquiring images before, during, and after intravenous administration of a
paramagnetic contrast agent (most often a gadolinium [Gd] chelate). This has been used to study various
cancers where measurement of tumor microvascularity has been shown to correlate with tumor grade,
microvessel density, tendency for metastasis and recurrence, levels of vascular endothelial growth factor (VEGF)
expression, and survival outcomes. For example, George et al reported that rectal tumors with higher
permeability at presentation as measured on DCE-MRI appeared to respond better to chemoradiotherapy than
those with lower permeability. Perfusion MRI also has utility in the diagnosis and characterization of tumors. For
instance, perfusion-weighted MRI has been used to differentiate pyogenic brain abscesses from cystic or necrotic
brain tumors, which can be challenging when structural MRI features alone are used for this purpose.
9
Furthermore, effects of antiangiogenic and antivascular therapy can also be assessed with this technique. As
such, DCE-MRI has been used in clinical trials as an indicator of biological activity to assess the effectiveness of
such therapies.

Currently, CT is the most frequently used imaging tool for clinical assessment of the structural features of cancer.
However, perfusion techniques can also readily be incorporated into existing CT protocols by acquiring images at
multiple time points before and after intravenous administration of iodinated contrast agents. Tumor angiogenesis
correlates with tumor perfusion and vascular permeability, which can be assessed by determination of peak
contrast enhancement and measurement of time-to-peak enhancement on dynamic contrast-enhanced CT (DCE-
CT). Measurements of tissue perfusion in tumors such as lung cancer have also been shown to correlate with
markers of angiogenesis, such as VEGF expression. Ng et al demonstrated that in non-small-cell lung carcinoma
(NSCLC), quantitative whole-tumor assessment of vascular permeability and blood volume with CT is
reproducible and may be useful to monitor effects of antivascular or antiangiogenic agents. Perfusion CT analysis
can also be applied to characterize lesions, and a primary example of this application is the assessment of the
solitary pulmonary nodule. For example, Swensen et al reported that absence of significant enhancement
(defined as 15 Hounsfield units) on CT at 1 to 4 minutes after contrast administration is strongly predictive of a
benign histology.

US has been used to assess the velocity of flowing blood within vessels by measurement of the frequency
(Doppler) shift of sound waves reflected from blood cells and can be applied to quantitatively study tumor
vascularity. In addition, quantitative estimation of tumor perfusion may be performed following the intravenous
administration of sonographic contrast agents composed of encapsulated microbubbles that reflect sound waves.
For example, Su et al used three-dimensional power Doppler US to monitor response of primary peritoneal
papillary serous carcinoma to treatment and to differentiate residual tumor from post-treatment fibrosis.

Perfusion imaging with SPECT and PET is performed with nontargeted tracers that have very high first-pass
extraction, mostly for assessment of large organs such as the heart and brain where detailed spatial resolution is
of limited value. With increasing availability of PET/CT and SPECT/CT instrumentation, perfusion and related
imaging techniques can be carried out successfully in most clinical settings. However, the value of this approach
in cancer diagnosis and management is presently unclear.

Diffusion Imaging
The random translational diffusion of water molecules can be quantitatively measured with diffusion-weighted
MRI (DWI). DWI provides indirect information about tissue structure, water content, and intra/extracellular space
and can be used to estimate tumor cellularity and detect early changes following therapeutic intervention. When
cellular and subcellular compartmental membranes break down with necrosis or apoptosis, water molecules
become less restricted to motion by diffusion. However, when cellular swelling or an increase in tumor cellularity
are encountered, water molecules become more restricted to motion by diffusion due to reduction in the
extracellular space, where most of the translational movement of water molecules occurs.

DWI was first used clinically to detect cellular changes due to acute cerebral infarction, but has also been applied
to characterize tumors and monitor changes in tumors after therapeutic intervention, most often in the brain. For
example, Hamstra et al performed DWI in patients with malignant glioma before and 3 weeks following the start
of treatment with radiotherapy (often with chemotherapy, as well) and showed that changes in tumor diffusion at
3 weeks provided an early biomarker for tumor response, time to progression, and overall survival that correlated
with structural imaging changes at 10 weeks. DWI can also differentiate residual or recurrent brain tumor from
treatment-induced damage to brain parenchyma following radiation therapy. Furthermore, it has been used to

323
differentiate pyogenic brain abscesses from cystic or necrotic brain tumors and to differentiate lymphomas from
gliomas, as the former have more limited water diffusion due to a higher nuclear-cytoplasmic ratio.
Through diffusion tensor MRI (DTI), anisotropic diffusion of water molecules in tissues such as the cerebral white
matter (due to organization of myelinated axons in bundles) can be quantitatively measured, providing exquisite
detail of tissue microstructure. This is particularly useful for pretreatment planning for brain tumors through
differentiation of peritumoral edema from infiltrative tumor, pretreatment assessment of white-matter tract
involvement by tumor, and intraoperative visualization and localization of major white-matter tracts to decrease
the chance of injury to normal tissues.
DWI and DTI have been more difficult to use outside of the brain, in part due to increased motion artifacts. For
example, investigators have shown that DWI may provide information regarding extent of breast cancer, as well
as early response to therapeutic intervention. However, these applications are still under active investigation.

Functional Lymph Node Imaging

Lymph node imaging is of great importance for the staging of malignant tumors. However, assessment of lymph
nodes based on structural imaging features alone is limited in sensitivity and specificity for microscopic metastatic
disease. Hence, functional imaging techniques are currently under development to overcome these limitations.

Functional lymph node imaging has largely been performed with radiolabeled particles to identify nodes that most
99m
likely represent probable sites of metastasis. The best known is Tc sulfur colloid, which is used for
conventional sentinel node imaging In the early stages of metastasis when the flow of lymph through an affected
lymph node has not yet been altered, conventional sentinel node imaging can correctly identify this lymph node.
However, as the number of cells in an affected lymph node increases due to tumor growth, the flow of lymph
through the node may be diverted to the next draining lymph node due to increased resistance, leading to lack of
depiction of the originally involved sentinel lymph node. At this stage, blood supply to the involved lymph node is
primarily provided by capsular arterial vessels to sustain the viability of cancer cells. Therefore, systemically
administered compounds such as 18F-2-fluoro-2-deoxy-D-glucose (FDG) will be directly delivered to these cancer
cells and permit visualization of these sites of nodal involvement in the whole body. Thus, in such settings,
conventional sentinel lymph node imaging is complementary with whole-body FDG-PET nodal imaging. However,
these observations are based on preliminary results from a limited number of patients and thus will require further
validation for clinical utility in the future.

A new agent to evaluate lymphatic drainage using MRI is ferumoxtran-10, a particular ultrasmall
superparamagnetic iron oxide-based biodegradable nanoparticle composed of an iron oxide core and a dextran
coating, which is an example of a nontargeted contrast agent that leaks into the interstitium and reaches the
reticuloendothelial cells of lymph nodes via the lymphatic system, allowing for detection of micrometastases
within normal-sized lymph nodes. Normal lymph nodes become dark in signal intensity after ferumoxtran-10
administration due to shortening of T2 and T2* relaxation times of water protons, whereas metastatic deposits
within lymph nodes remain bright. This agent has been used to evaluate lymph nodes in the setting of a wide
variety of malignancies. For example, Deserno et al showed that ferumoxtran-10-enhanced MRI significantly
improved nodal staging in those with bladder carcinoma by depicting metastases even in normal-sized lymph
nodes, with accuracy, sensitivity, specificity, and positive and negative predictive values of 95%, 96%, 95%, 89%,
and 98%, respectively. Also, Harisinghani et al reported that MRI with lymphotropic superparamagnetic
nanoparticles correctly identified all patients with nodal metastases due to prostate carcinoma and that nodal
analysis had a significantly higher sensitivity (90.5%) compared with conventional MRI (35.4%). Will et al
performed a meta-analysis of prospective studies that compared MRI, with and without ferumoxtran-10, with
histological diagnosis after surgery and biopsy and showed that ferumoxtran-10-enhanced MRI is sensitive and
specific in detection of nodal metastases for a variety of tumors and offers higher diagnostic precision than
unenhanced MRI for detection of lymph node metastases. As such, ferumoxtran-10-enhanced MRI, like PET, has
the potential to become a useful clinical functional imaging tool to evaluate lymph nodes of the whole body in the
setting of cancer.

Conventional sentinel lymph node imaging will continue to be a very important technique to identify potential sites
of regional nodal metastasis for malignancies such as breast cancer and melanoma. This technique, however,
does not allow for direct detection of involved lymph nodes, but directs surgical exploration to nodal sites that are
potentially most vulnerable to cancer spread. In contrast, FDG-PET or ferumoxtran-10-enhanced MR-based
lymph node imaging allows for visualization of sites of nodal abnormality throughout the body. Whereas FDG-
PET directly targets cancer cells in involved lymph nodes, ferumoxtran-10-enhanced MRI indirectly reveals
cancer sites in lymph nodes. Therefore, the specificity of the latter may prove suboptimal in lymph nodes that are
involved by nonneoplastic processes. As such, multicenter clinical trials are currently either in development or in
progress as part of the ongoing safety and diagnostic performance assessment of the latter approach in relation
to different types and locations of cancer.

FUNCTIONAL IMAGING TECHNIQUES TO PROBE TUMOR MOLECULAR PROCESSES

Metabolic Imaging
Metabolic imaging relies on differential utilization of various substrates through different biochemical pathways in
cancer cells compared with normal tissue. In general, any small molecule that contains a radioisotope can be
identified by various detection methods as it passes through biochemical pathways. Positron-emitting compounds

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dominate this category of tracer molecules, largely due to the feasibility of utilizing positron-emitting isotopes
11 18
such as C and F to replace nonradioactive carbon and hydrogen atoms, respectively, in any organic molecule.
These positron-emitting analogues of metabolically relevant molecules can then be detected with PET in
picomolar to nanomolar concentrations in vivo. The superb sensitivity of this approach allows for administration of
these positron-emitting compounds in nonpharmacologic concentrations and imaging of metabolic pathways
without perturbation of cellular, subcellular, or molecular processes. A wide variety of metabolic tracers have
been developed to target the transport and metabolism of glucose and amino acids.

Glucose Metabolism
FDG, a glucose analogue first tested in humans in 1976, is by far the most widely used metabolic tracer in the
world. Pioneering work since its conception has helped to solidify FDG-PET as a powerful diagnostic imaging
2
modality in oncology and has sparked a growing interest in molecular imaging. FDG-PET can be used to assess
any malignancy that has accelerated glucose metabolism.

FDG is transported into cells via glucose transporters such as GLUT-1 and subsequently phosphorylated by
hexokinase. The metabolic product 2-fluorodeoxyglucose-6-phosphate is effectively trapped intracellularly, as it
cannot undergo further metabolism through the glycolytic pathway. Persistent glucose uptake in many cancer
cells in a low serum insulin state makes FDG an ideal tracer for cancer imaging. In fact, the Centers for Medicare
and Medicaid Services (CMS) has approved reimbursements for diagnosis, staging, and restaging of lung
cancer, esophageal cancer, colorectal cancer, melanoma, lymphoma, head and neck cancer, and breast cancer.
Characterization of the solitary pulmonary nodule, restaging of noniodine-avid thyroid cancer, and evaluation of
metastases in cervical cancer before therapy are also reimbursable by Medicare. Recently, the CMS has
approved reimbursement for virtually all cancers if conducted in centers participating in certain patient registries
such as the National Oncologic PET Registry (NOPR).

FDG-PET provides complementary information to structural imaging techniques for diagnosis and staging of
cancer. For example, meta-analysis by Gould et al reported a sensitivity of 97% and a specificity of 78% for the
evaluation of solitary pulmonary nodules. In addition, meta-analysis by Toloza et al indicates that FDG-PET has
an 84% sensitivity and an 89% specificity for mediastinal staging of NSCLC, whereas CT alone has a sensitivity
and specificity of 57% and 82%, respectively. The difference in sensitivities between metabolic imaging with
FDG-PET and anatomic imaging using CT-size criteria highlights a typical advantage of metabolic imaging when
compared with structural imaging. With its high sensitivity for metabolically active lesions, FDG-PET has also
been shown to detect unexpected extrathoracic metastases in 10% to 20% of patients and leads to changes in
therapeutic management in about 20% of patients with lung cancer. In general, FDG-PET adds value to the
staging workup of patients with relatively aggressive and metabolically active cancers such as lymphoma,
melanoma, and breast, lung, head and neck, cervical, esophageal, or colorectal cancer by increasing the
sensitivity for nodal and distant metastatic disease and by increasing the specificity for malignancy relative to the
diagnostic performance of structural imaging alone. However, FDG-PET in general has lower sensitivity for
slower growing, less metabolically active tumors such as prostate cancer, thyroid cancer, neuroendocrine tumors,
and bronchioloalveolar cell lung carcinoma. FDG-PET is also particularly useful for restaging of malignancy
because structural changes caused by surgery or radiation therapy may render anatomic imaging techniques
inconclusive at most anatomic sites. Cancer restaging with FDG-PET has a general sensitivity of 80% to 95%, a
43
specificity of 75% to 90%, and an accuracy of 80% to 90% for the detection of persistent or recurrent disease.
With the introduction of a recent generation of PET and PET/CT scanners, as well as well-established diagnostic
criteria for interpretation of FDG-PET scans, the value of FDG-PET in evaluation of patients with cancer has been
enhanced even more. Please note that a detailed review of the specific clinical indications for PET is beyond the
scope of this article.

FDG-PET also provides complementary information to structural imaging techniques for cancer treatment
planning. For example, FDG-PET in conjunction with CT or MRI is increasingly being used to define tumor
volumes for radiation treatment planning. FDG-PET improves target-volume coverage at both the primary tumor
level and regional lymph node level and tends to enlarge the radiation field when hypermetabolic normal-sized
regional lymph nodes are identified. In fact, incorporation of both FDG-PET and CT images in target-volume
selection has been shown to change treatment planning in over 50% of patients with Stage I to III NSCLC
compared with treatment planning using CT alone. FDG-PET can also lead to a reduction in radiation volume for
primary tumors, with sparing of nonmalignant tissues. This is particularly true in the setting of lung tumors due to
the ability to separate collapsed, fibrotic, or necrotic tissues from tumor, which may otherwise be indistinguishable
using structural imaging alone. Ciernik et al reported that in patients with head and neck cancer who were
undergoing radiation treatment planning with CT, gross target volume (GTV) changed in 32% with addition of
PET data, and the mean change in planning target volume (PTV) was 20%. Moreover, the interobserver
variability in target-volume definition also improved when PET data were included.

Degrees of FDG uptake in malignant lesions at baseline and during follow up after therapy may also be used to
provide prognostic value. For example, in surveying 155 patients with NSCLC, Ahuja et al found that patients with
standardized uptake values (SUVs) of less than 10 in the primary lesion had a median survival of 24.6 months,
whereas those with SUVs of more than 10 had a median survival of 11.4 months. Although evidence suggests
that FDG uptake from a single FDG-PET scan has prognostic value, threshold SUVs vary considerably in

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reported studies, limiting its clinical applicability. However, serial imaging, especially before and after treatment, is
useful as a prognostic indicator in patients with cancer and as a means of monitoring therapeutic response.
Ceresoli et al noted that after 2 cycles of chemotherapy for mesothelioma, patients who had a metabolic
response on FDG-PET had a median time-to-tumor progression of 14 months compared with 7 months for those
without metabolic response. Serial FDG-PET treatment monitoring has also been used in clinical trials for new
therapeutics. Stroobants et al performed FDG-PET 8 days after the start of therapy to assess the efficacy of
imatinib (Gleevac) treatment for gastrointestinal stromal tumors (GIST) and found that 92% of patients with
negative FDG-PET scans had 1-year progression-free survival (PFS), whereas only 12% of patients with positive
post-treatment FDG-PET scans had 1-year PFS. Currently, treatment monitoring with FDG-PET to assess for
tumor response appears to be the most promising functional imaging alternative to structurally based RECIST
criteria using CT or MRI alone.

Despite its strengths, FDG-PET has some limitations. FDG-PET is of limited use for slowly growing tumors with
minimal glucose metabolism such as bronchioloalveolar cell lung carcinoma, prostate cancer, thyroid cancer, and
carcinoid tumor. Due to its limited spatial resolution, PET in general underestimates accurate radiotracer
concentration in small lesions, and thus may not always be sensitive enough as a single modality to detect and
monitor certain malignancies, although PET/CT may overcome some of these deficiencies. Another limitation of
FDG-PET relates to the physiologic biodistribution of FDG in the kidneys and collecting systems, as well as in the
bowel, which may obscure uptake in lesions located in adjacent tissues. However, PET/CT with oral contrast can
diminish this deficiency by providing coregistered structural and metabolic images, allowing for more accurate
localization of sites of FDG uptake. Lastly, FDG uptake may be seen in sites of infection or inflammation,
potentially leading to a false-positive diagnosis of sites of malignancy. However, specificity can be improved
through dual-time-point imaging, where PET images are obtained at 2 separate time points on the same day of
examination. Malignancies often demonstrate an increase in FDG uptake over time, whereas infectious or
inflammatory lesions tend to demonstrate no change or a decrease in FDG uptake over time. Specificity can also
be improved on through certain CT morphologic features of lesions that may strongly indicate benignity.

Amino Acid Metabolism

Analogues of methionine, tyrosine, and L-dihydroxyphenylalanine (L-DOPA) have potential for widespread
clinical application and sometimes have better diagnostic performance characteristics in certain PET applications
when compared with those utilizing FDG. 11C-L-methionine is chemically identical to nonradioactive L-
methionine. Consequently, it is metabolized and trapped in the cell by incorporation into proteins or even RNA
molecules. Advantages of imaging brain tumors with11 C-methionine are well documented, as there is low
background uptake of 11C-methionine in the brain. A recent study by Jacobs et al showed a sensitivity of 91% for
detecting gliomas, as well as larger detected tumor volumes compared with those detected with Gd-enhanced
11
MRI, which may have an impact on radiation treatment planning. However, the major shortcoming of C-
11 18
methionine is the 20-minute half-life of the C isotope, although F-fluorinated amino acid analogues have been
developed to overcome this limitation since 18F has a 109-minute half-life.
18 18
Tyrosine analogues such as L-3 F-fluoro--methyl tyrosine (FMT) and O-(2 F-fluoroethyl) L-tyrosine (FET)
may be of clinical value in imaging certain tumors. For example, FMT-PET had a sensitivity of 73% and a
specificity of 85% in a series of 75 patients with musculoskeletal tumors (whereas the specificity of FDG-PET was
lower at 66%).
18 18
F-6-fluorodihydroxyphenylalanine ( F-FDOPA), an analogue of L-DOPA, accumulates in dopaminergic
neurons in the basal ganglia and can be used to study patients with melanoma, carcinoid tumor, medullary
thyroid cancer, and brain tumors. A recent study with FDOPA-PET in 19 patients with abdominal carcinoid tumors
showed 93% sensitivity and 89% accuracy. FDOPA-PET has also been shown to be more accurate than FDG-
PET for evaluation of low-grade and recurrent brain tumors and for differentiation of low-grade tumors from
necrosis.

Cell Proliferation Imaging

Cell proliferation imaging assesses the uptake and metabolism of nucleosides used in nucleic acid synthesis. The
most widely used nucleoside analogue for cell proliferation imaging to date is 3-deoxy-3-18F-fluorothymidine
(FLT), which enters cells through carrier-mediated diffusion. The tracer is trapped when a thymidine kinase (TK)
such as TK1 phosphorylates FLT to fluorothymidine-phosphate, which cannot be metabolized further. Shields et
al was the first to propose the use of FLT-PET to measure cellular TK activity and thereby infer the rate of cellular
proliferation. Overall, FLT-PET has lower sensitivity compared with FDG-PET and amino acid analogue PET for
the detection of cancer. However, FLT-PET provides images for rates of proliferation, whereas most other tracers
do not. The specificity of FLT for assessment of cellular-proliferative activity makes it an ideal tracer for
monitoring tumor treatment response, especially when antiproliferative cytostatic agents are employed. For
example, Yang et al tested radiation treatment monitoring with FLT-PET in mouse tumor models and found
decreased FLT uptake 24 hours after radiation treatment with no detectable change in FDG uptake. This
suggests that FLT-PET can shorten the timeframe to detect a therapeutic response and may become an effective
tool for monitoring treatment.

Oxygenation Imaging
Tumor hypoxia triggers tumor angiogenesis, may be a factor in the activation of extracellular matrix-degrading
proteases, and is associated with tumor progression, likelihood of metastatic tumor spread, and poor clinical

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outcome. However, there may be marked variability of intratumoral, as well as intertumoral, oxygen tension
values, and hypoxic tumor cells are generally more radioresistant and possibly more chemoresistant than
normoxic tumor cells. Thus, ability to identify hypoxic tumor tissue noninvasively may be valuable to identify those
patients who may benefit from intensity-modulated radiation therapy (IMRT) or other new treatment strategies
such as photodynamic therapy.
18
Nitroimidazole-based compounds such as F-fluoromisonidazole (FMISO) are currently the most widely used
agents to image hypoxia with PET. Fluoromisonidazole is a lipophilic compound that binds to intracellular
proteins in live cells with active mitochondria when oxygen concentration is below 20 mmHg. In a recent study of
58 patients with head and neck cancer, pretherapy FMISO-PET had independent prognostic value. In addition,
FMISO-PET can be used to monitor chemoradiation therapy in patients with advanced head and neck cancer
where early resolution of FMISO uptake during treatment is associated with excellent locoregional control.
64 64
Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) ( Cu-ATSM) is another tracer that is used to image hypoxia.
In hypoxic cells, the redox state of the copper atom changes, and 64Cu becomes trapped in mitochondria after
dissociation of the Cu-ATSM complex. However, recent animal testing using various tumor models shows that
64
Cu-ATSM is a valid PET hypoxia marker in some, but not all, tumor types, implying that it may not be useful as
a general hypoxia imaging agent.
18
F-EF5, a 2-nitroimidazole analogue, is another potential positron-emitting hypoxia tracer. Hypoxic regions
18
delineated by F-EF5-PET have been shown to influence patient survival and lack of response to radiation
18
treatment, and preliminary tests of F-EF5 in patients with head and neck and brain tumors show promising
results.

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) has been used as a noninvasive method to
preoperatively map functional cerebral cortex and to identify eloquent areas of the cerebral cortex in relation to
brain cancers, potentially reducing the time of surgery and minimizing intraoperative cortical stimulation methods,
which are sometimes used during the surgical resection of brain tumors. In addition, BOLD fMRI, as well as other
functional MRI techniques such as Overhauser-enhanced MRI and electron paramagnetic resonance imaging
(EPRI), may be useful to study oxygenation in human tumors and to monitor changes in tumors related to
therapy.

Molecular Imaging with Targeted Imaging Agents

Somatostatin Receptors
Somatostatin receptors (SSTRs) are overexpressed in many neuroendocrine tumors, including small-cell lung
cancer, carcinoid tumor, insulinoma, VIPoma, gastrinoma, and medullary thyroid cancer. Whole-body SSTR
imaging is performed with radiolabeled derivatives of octreotide, which have a preference for subtype 2 SSTRs
(ie, SSTR2). The most commonly used agent is 111 In-pentetreotide for SPECT imaging, although SSTR-targeted
68 68
tracers have also been developed for PET, including Ga-D-Phe1-Tyr3-octrotide ( Ga-DOTATOC) and Gluc-
Lys(18 F-fluoropropionyl-TOCA). Meisetschlager et al used Gluc-Lys (18F-fluoropropionyl-TOCA)-PET to study 25
111 18
patients with SSTR-positive tumors. Compared with In-pentetreotide SPECT, Gluc-Lys ( F-fluoropropionyl-
TOCA)-PET revealed more than twice the number of lesions and resulted in near-perfect interobserver
18
agreement. Gluc-Lys( F-fluoropropionyl-TOCA) also demonstrated better biodistribution, biokinetics, and
diagnostic performance in comparison with 68 Ga-DOTATOC in the assessment of neuroendocrine tumors.

Estrogen Receptors
Currently, in vitro examination of biopsy specimens with immunohistochemistry is required to assess levels of
estrogen receptor (ER) expression, although not all tumor sites are accessible by biopsy. ER targeting tracers,
therefore, may be used to noninvasively assess the ER status of tumors in vivo through use of 18F fluorinated
estrogen analogues, and 16-18F-fluoroestradiol-17 (FES) is commonly used for this purpose due to its
favorable biodistribution. FES-PET may show a faster treatment response than FDG-PET at 7 to 10 days after
treatment initiation when monitoring breast cancer therapy using tamoxifen. FES-PET may also assist in the
selection of the appropriate therapy for breast cancer patients. Use of FES-PET may increase overall response
rate following therapy with tamoxifen from 23% to 34%, and for patients with HER2/neu-negative breast cancer,
treatment response may improve from 29% to 46% if selection is made using FES-PET.

Angiogenesis Imaging
Angiogenesis, the formation of new blood vessels, is now the target of many new therapeutic agents. Perfusion
imaging as described above can indirectly provide information about tumor angiogenesis, although some tumors
may have dense but mostly quiescent endothelium that is resistant to antiangiogenic therapy. Accurate
assessment of angiogenesis thus requires approaches that can directly quantify activated endothelial cells, such
as through detection of V3 integrins that are present on activated endothelial cells undergoing angiogenesis.

Peptides containing the amino acid sequence arginine-glycine-aspartate (RGD) have a general affinity toward
integrins. It has been shown that fine-tuning of the stereochemistry adjoining the RGD peptide allows for selective
binding to specific integrins. This led to the development of RGD-based pentapeptide integrin antagonists, such
18
as EMD 121974 (Cilengitide), which can be used to inhibit tumor angiogenesis. F-labeled RGD compounds

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have also been synthesized to allow for rapid visualization of V3 expression in the whole body using PET. For
18
example, F-galacto-RGD PET was used by Beer et al in 19 patients with various solid tumors. Tumoral uptake
18
of F-galacto-RGD correlated with V3 expression, as well as microvessel density as observed at histology.
Thus, 18F-galacto-RGD PET has potential use for individualized treatment planning and antiangiogenic therapy
monitoring, although a drawback is that it binds to V3 integrins present on the membranes of tumor cells, as
well as membranes of tumor-associated endothelial cells. As such, imaging agents based on targeting of cell
receptors, such as vascular endothelial cell growth factor receptor, that are overexpressed on endothelial cells
during angiogenesis are currently under development. Nevertheless, ability to quantify total tumor V3 integrin
levels is important, given that V3 expression by tumor cells is linked to increased metastatic potential.

Apoptosis Imaging
Apoptosis, or programmed cell death, is a characteristic feature of normal human cells that is essential for normal
tissue homeostasis and tissue differentiation. However, tumor growth is often associated with insufficient
apoptosis. In vivo imaging of apoptosis offers another noninvasive approach to monitor therapeutic response
independent of changes in glucose metabolism or cell proliferation. Annexin V binds to phosphatidylserine (PS)
99m
that has moved to the outer surface of cell membranes during apoptosis and can be labeled with either Tc,
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I, or F to image apoptosis in vivo using SPECT or PET, respectively. OI of apoptosis in preclinical animal
models or in vitro is also possible using Annexin V labeled with Cy5.5, a near-infrared fluorescent dye. The
source of light emission for fluorescent imaging is either from fluorescent organic compounds called fluorophores
or semiconductor-based nanoparticles called quantum dots.

Superparamagnetic iron-based contrast agents, as well as other paramagnetic contrast agents in conjunction
with targeted carrier nanoparticles, are also under development in animal models to specifically target particular
molecules or biologic processes for detection, predominantly using MRI. For example, Schmieder et al
noninvasively characterized melanoma in its earliest phase of growth in mice using V3-targeted paramagnetic
nanoparticles to detect V3 integrin expression in tumor neovasculature using MRI, and Schellenberger et al
have used nanoparticles conjugated to Annexin V to target apoptosis for noninvasive monitoring using MRI or OI.
However, limitations of such approaches using MRI for detection include low signal-to-noise ratio with low
sensitivity, lack of standardization of imaging and analytic methodologies, and inconsistent availability of these
new technologies at sites around the country.

Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) is a noninvasive diagnostic tool that allows one to quantitatively assess
the amount, type, and location of various small molecular compounds within a tissue or organ of interest at the
same time that MRI is performed. It does so by taking advantage of the quantum-mechanical properties of the
nuclei of certain atomic isotopes, which permit them to be manipulated through the application of magnetic fields
and radiofrequency pulses. The data are typically displayed as a grid of spectra of chemical compound
abundances obtained at either single or multiple locations in a tissue or organ of interest. These spectra are
1
collected from spinning nuclei (spins), most often H given the abundance of water in tissue, although they can
be collected from other nuclei such as 13C or 31P with more difficulty due to lower tissue concentrations. Proton
1
H MRS enables accurate quantitative assessment of the spatial distribution of tissue metabolites such as
creatinine, choline, amino acids, nucleotides, lactate, and lipids. Unfortunately, there is no one cancer signature
on MRS, but there are MRS findings that are seen more often in cancer. For example, increased concentrations
of cell membrane metabolites such as phosphocholine may be seen due to increased membrane synthesis, a
higher concentration of lactate may be seen due to increased metabolism through the glycolytic pathway, and
lower concentrations of normal tissue metabolites (such as N-acetyl aspartate in cerebral tissue or citrate in
prostatic tissue) may be encountered.
1
H MRS is most often applied clinically to evaluate brain tumors due to the relative lack of motion artifact in this
location relative to other body sites. As such, many single-center studies of 1H MRS in the setting of brain cancer
have been reported. In patients with gliomas, 1H MRS and perfusion-MRI analysis provide complementary
information to assess tumor grade and to detect residual or recurrent tumor. 1H MRS enables better
discrimination between normal and abnormal tissue than regional cerebral blood-flow maps, whereas regional
cerebral blood-flow maps may better reflect the heterogeneity of tumor regions because of their higher resolution.
In addition, 1H MRS may be useful to predict patient prognosis. Oh et al reported that patients with glioblastoma
multiforme had significantly shorter median survival when a large volume of metabolic abnormality was seen at 1
H MRS. Many investigators have also demonstrated significant spatial discordance between morphologic lesions
1
and metabolic lesions using H MRS in brain tumors, which has significant implications with regard to treatment
planning for surgery and/or radiotherapy. Moreover, 1H MRS can be used to distinguish pyogenic brain
abscesses from cystic or necrotic brain tumors, gliomas from solitary brain metastases, and residual or recurrent
brain tumor from post-therapy radiation necrosis.
1
H MRS has occasionally been applied to study tumors in other body locations. Swindle et al reported that 1H
MRS has a high sensitivity (97%) and specificity (88%) for prostate carcinoma. Furthermore, 1H MRS can lead to
more accurate assessment of the presence, location, and extent of prostate cancer; may reveal overall tumor
1
clinicopathologic status and aggressiveness; and can be used to assess therapeutic response. H MRS has also
been used to study tumors of the breast, pancreas, cervix, and thyroid gland.

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31
P MRS also has potential utility to noninvasively assess tumors. It has shown some promise to differentiate
prostate carcinoma from benign prostatic hypertrophy. Others have shown that it can differentiate benign from
malignant head and neck neoplasms and can predict treatment response and monitor therapeutic effects for
31
head and neck cancer. Arias-Mendoza et al reported that P MRS pretreatment measurement of
phosphoethanolamine and phosphocholine content within non-Hodgkin lymphoma predicts long-term response to
treatment and time-to-treatment failure, particularly when combined with the international prognostic index.
13
Research efforts directed toward use of hyperpolarized C MRI/MRS agents for metabolic and molecular
imaging are currently underway, although many technical challenges still exist. 13C MRI/MRS has the potential to
provide information about any molecule that contains hyperpolarized 13 C and to distinguish between different
13
molecules that contain C atoms. This suggests the potential utility of this approach to study carbon-based
compounds in vivo for oncologic applications such as tumor perfusion and metabolism assessment, as well as
new drug pharmacokinetic and pharmacodynamic assessment.

Although MRS has been around for several decades and can sensitively detect and characterize metabolites
within tumors and nonneoplastic tissue, it is still considered to be a prebiomarker by most investigators as it is not
yet fully established as reproducible across multiple institutions. Difficulties in performing multicenter trials with
MRS include differences in hardware and software among different sites due to lack of standardization, as well as
effects of patient motion.

OTHER APPLICATIONS OF FUNCTIONAL IMAGING TO STUDY TUMORS

Gene Expression and Cell Tracking

Gene expression imaging has been used to study tumor biology and molecular changes in tumors before and
after treatment in vitro and in animal models. It is typically performed through detection of an expressed reporter
protein, such as a transporter, enzyme, or receptor that is controlled by the regulatory element of a reporter gene
of interest. Some examples of reporter proteins include green fluorescent protein (GFP) analogues, luciferase
mutants, and herpes simplex virus thymidine kinase (HSV-tk). Depending on the choice of reporter protein and
reporter probe, gene expression may be imaged with OI, SPECT, or PET. In general, this technology is difficult to
adapt to routine clinical use because it requires the introduction of marker genes and, therefore, is most relevant
to in vitro or animal models.

Several investigators have focused on use of OI to study gene expression. For example, Cao et al used GFP
linked to hypoxia-inducible factor (HIF-1) promoter in a tumor cell line that expressed red fluorescent protein
(RFP) constitutively and was able to differentiate between normoxic tumor cells and hypoxic tumor cells in a
growing tumor environment. At present, use of OI to study gene expression in tumors is limited to use in small
animals and for superficial human structures such as the breast due to limited light penetration through tissue.

Other investigators have focused on PET to study gene expression in tumors. A prototypical reporter protein for
use with PET is HSV-tk, which can be imaged following administration of a positron-emitting nucleoside analogue
reporter probe that can be phosphorylated and trapped intracellularly by HSV-tk.

Cell tracking is important to study the behavior of tumor cells in vitro and in animal models and can potentially be
used to track cellular therapies for cancer, to track stem cells, and to assess the effectiveness of gene therapy
against cancer cells. Cell tracking is possible when cells of interest are engineered to constitutively express a
reporter protein that is detectable by either OI or PET. For example, Jenkins et al developed bioluminescent
prostate cancer and breast cancer models to observe treatment response to chemotherapy using OI. In addition,
investigators have introduced luciferase and GFP into genetically transformed cells during gene therapy to
monitor efficiency of transfection using OI or PET. Recently, some investigators have successfully performed in
vivo cell tracking using MRI in animal models through use of superparamagnetic iron oxide nanoparticles or
paramagnetic contrast agents that are introduced into cells, although efforts to translate this approach into
humans are currently under active investigation.

Molecular Imaging-based Personalized Treatment Planning

Molecular phenotypes of tumors may affect their susceptibility to chemotherapeutic agents, which may be
extremely important to know about for individualized treatment planning. For example, epidermal growth factor
receptor (EGFR) mutations are found in about 10% of NSCLC, and patients with these mutations have a
statistically significant better outcome following EGFR tyrosine kinase inhibitor therapy with gefitinib (Iressa;
AstraZeneca, London, UK). In the remaining 90% of patients without these mutations, unnecessary exposure to
this drug may be avoided, leading to monetary savings and fewer adverse events from drug toxicity, as well as
earlier use of alternative, more effective therapies.

As seen by this example, the personalized medicine paradigm is becoming a reality in treatment planning for
many patients with malignancies, particularly as therapeutics are increasingly targeted toward specific cellular
receptors. As such, molecular imaging will increasingly become a part of individualized treatment planning and
pharmacogenomics. Molecular imaging will increasingly supplement in vitro molecular diagnostic testing of tissue

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or bodily fluid specimens, as it can be used for quantitative, noninvasive serial evaluation, as well as whole-body
assessment of multiple lesions, including those that are in difficult to reach locations. Moreover, molecular
imaging using radiolabeled preparations of intended drugs may be used to determine appropriate
pharmacological doses on an individualized basis.

An example of this concept is the pretreatment evaluation of pharmacokinetics of radiolabeled antibodies or

peptides to be used for therapeutic purposes using PET. In order to predict treatment success using radiolabeled
antibodies or peptides against a tumor, it is important to demonstrate appropriate targeting to the diseased tissue.
124 131 86 90
Positron-emitting isotopes such as I (as a surrogate for I) and Y (as a surrogate for Y) can be utilized for
optimal visualization of these agents to targeted sites and may significantly improve the ability to select optimal
patient candidates for subsequent treatment with antibodies or peptides radiolabeled with therapeutic beta-
emitting radionuclides. Through this approach, one may identify patients who are good candidates for antibody or
peptide treatment by comparing images acquired with nonspecific radiotracers such as FDG that reveal overall
disease activity with PET images generated with positron-emitting radiolabeled antibodies or peptides for
diagnostic purposes. Since radiolabeled antibodies result in a favorable response if they target the entirety of the
tumor burden, disparity between uptake within tumor on the FDG-PET images and diagnostic PET images using
radiolabeled antibodies or peptides may indicate a poor outcome following treatment with beta-emitting agents.

New Drug Development

Functional imaging techniques have the potential to accelerate cancer drug development during the preclinical
and clinical phases of testing. This is especially relevant given the difficulties in both designing targeted cancer
therapies and monitoring their efficacy. Tumors may be spatially and temporally heterogeneous in terms of gene
expression, metabolism, oxygenation status, angiogenesis, cell proliferation, apoptosis, signal transduction, and
other phenotypic features, but functional imaging can help investigators to better understand these features.

As such, functional imaging can aid in molecular target-based drug screening, definition of in vivo target
specificity, rapid characterization of in vivo pharmacokinetic and pharmacodynamic properties of candidate drugs,
development of animal models of human tumors, and visualization of in vivo effects of therapeutic molecules on
target biological processes. These approaches are particularly useful as they could reduce the length of time for
developing effective drugs (which usually can take more than a decade) and reduce the costs of drug
development (often in the range of hundreds of millions of dollars) during preclinical evaluation and clinical trial
assessment. For example, any new therapeutics for GIST may use the post-therapy FDG-PET scan as the
surrogate endpoint of the trial since the 8-day post-therapy FDG-PET scan has been shown to predict outcome
for imatinib treatment. Recently, FLT-PET has been used to monitor the preclinical testing of histone deacetylase
inhibitors (HDACI), an expanding class of growth-inhibiting compounds targeting DNA and RNA. In animal
models of colon carcinoma, Leyton et al reported that decreasing FLT uptake in tumor correlates with escalating
doses of LAQ824, a new HDACI, and that the quantity of FLT uptake correlates with decreased expression of
thymidine kinase 1 (TK1).

Transformation of therapeutic compounds themselves into imaging agents and testing for the presence of the
compound at intended target sites is another way functional imaging can be used to facilitate drug development.
18
F, 11C, and 13N PET can offer this possibility given its high sensitivity. Similarly, 19F and 31P MRS can be used
for the detection, identification, and quantification of fluorine-containing or phosphorous-containing therapeutic
agents, and their metabolites in biofluids may play a role in the therapeutic monitoring of fluorinated or
phosphorylated chemotherapeutic drugs such as fluorouracil and cyclophosphamide, respectively, in specific
groups of patients and may provide further understanding into drug metabolic pathways. However, the main
challenge to widespread application of these MRS techniques is a more limited sensitivity in the micromolar-
millimolar concentration range.

CONCLUSION
A wide variety of functional imaging techniques are currently under active investigation that have great potential
to noninvasively provide never before available quantitative information regarding physiologic and biological
properties of tumors at the molecular, subcellular, cellular, tissue, organ, and systemic levels unavailable from
routine structural imaging techniques alone. Such functional imaging techniques will enhance the efficiency and
effectiveness of oncologic research, will help to characterize biomarkers of disease and new endpoints for
assessment of tumor response, and will positively impact those with cancer due to improvements in early
detection, characterization, staging, and monitoring of therapeutic response of tumors, as well as improvements
in individualized treatment planning, prognosis assessment, and cell tracking. Thus, we believe that quantitative
functional imaging, in conjunction with quantitative structural imaging, will be the future of personalized
radiology, personalized oncology, personalized medicine, and of oncologic research in the 21st century and
beyond.

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 Application of Telemedicine in Surgery

S. K. Mishra

Introduction
1
Telemedicine has been practiced for over 30 years . Recent technological advances, however, have expanded
the scope of medical interaction that may be achieved. Whereas consultative services, examination of still
documents (photos, x-rays, slides, or ECGs), and interactive voice sessions previously defined the state of the
art, the telemedical event may now involve "live" manipulations of patients and/or tissues "at a distance". In fact,
there are now many levels of health care-related interaction that may take place in the telecommunications
medium: physician-to-physician consultation, physician-to student (physician, nurse, other care giver) teaching,
physician-to-patient examination and consultation, and physician-to-patient treatment2-9.

Telemedicine in surgery, or telesurgery, has been defined as: Surgery, procedure or technique performed on an
inanimate trainer, animate model, or patient in which the surgeon is not at the immediate site of the model or
patient being operated on. Visualization and manipulation of the tissues and equipment is performed using
10
electronic devices . Telesurgery is an umbrella term covering educational and professional assessment
techniques, surgical discussion among remote participants, and surgery using telemanipulation (the expansion of
a persons movements to a remote location) and telepresence (telemanipulation with added sensory information
11
to make the operator feel that they are physically present at the remote site) . Besides telesurgery the other
applications of telemedicine in surgery is in the same line as in any other medical disciplines such as
teleconsultation, telefollow up, distance education, and teleconference.

Application of Telemedicine in Surgery:

Various applications of telemedicine technology in surgical practice can be grouped into following categories.
1. Tele healthcare for surgical patients
Teleconsultation
Pre referral screening
Tele follow up
Remote treatment planning
2. Distant surgical education
Teleconferencing of surgical conferences, CMEs and Workshops
Web casting
Surgical education portals
Interactive virtual class room
3. Telesurgery
Telepresence Surgery
Telerobotics
Telementoring / Teleproctoring

A) Tele healthcare for surgical patients

Evaluation of patient(s) or patient data and consultation regarding patient management from a distant site using a
telecommunications interface. The tele-health care, by definition, does not have the ability to physically interact
with the patient, except through the telecommunications interface. It may be categorized as follows:
Tele-consultation
Pre referral screening
Tele follow up
Remote treatment planning

Appropriate Use: Initial urgent evaluation of patients, triage decisions, and pre-transfer arrangements for
patients in an urgent/emergency situation
Intra-operative consultations
Supervision and consultation for primary care encounters in sites where an equivalently qualified
physician/surgeon is not available
Routine consultations and second opinions based on history, physical findings, and available test data
Public health, preventive medicine, and patient education

B) Distant surgical education

Tele-education is an effective tool of disseminating the knowledge and developing the skill of surgical trainees in
a virtual class room environment from the distant site. It may be categorized as follows:
4
Teleconferencing of surgical conferences, CMEs and Workshops - Tele-conferencing is the
discussion and interaction between surgeons during surgical conferences, about surgical cases in a
virtual class room environment and live surgery demonstration workshop transmitted through

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 videoconference. One of the widely used technology it has now changed the concept of physical
presence in any of the above events. Different kinds of teleconferencing modalities are now in use such
as Interactive two way, one way broadcast, web cast etc. Once the cost of broadband
telecommunication comes down and internet technology is advanced more and more people would like
to stay afoot at their place of work and participate in events remotely.

Figure 1: Surgical Video Conference in Progress

Web casting- According to National Association of Broadcaster's publications/training manuals that

says webcasting is sending audio and/or video live over the Internet or on digital networks, as well as
listening or watching on-demand files.7
Surgical education portals - Surgical Education Portal is a gateway to several websites providing
reliable information about education and training in surgical field.

C) Telesurgery (remote surgery)

Surgery, procedure or intervention performed on an inanimate trainer, animate model, or patient, in which the
surgeon or operator is not at the immediate site of the model or patient being operated upon. Direct real-time
visualization and manipulation of the tissues and equipment is performed using tele-electronic devices. It may be
categorized as follows:
Telepresence surgery. Uses a computerized interface to transmit the surgeons actions at a surgical
workstation to the operative site at the remote surgical unit, with haptic (forced feedback) input to
transmit to the surgeon the tactile environment of the operative field.
Telerobotics. Remote control with a robotic arm, usually in conjunction with a laparoscope, without
haptic feedback.
Telementoring. An experienced surgeon acts as a preceptor for a remote inexperienced surgeon by
observing the surgeon via interactive video. Teleproctoring is an extension of telementoring, referring to
documentation of performance for privileging purposes.

2.Tele-consultation

Figure 2: Tele-Consultation in Progress

Tele-consultation and tele-follow-up for surgical patients is the commonest application of telemedicine in surgery

332
currently practised in India. From March 2003 to August 2015, doctors at SGPGIMS, Lucknow provided 1409 real
time tele-consultations. In Uttaranchal Telemedicine Project from September 2005-September 2006, patients of
Base Hospital, Almora received tele-consultation (n=12) through store and forward technology.

3. Tele-Follow up

Figure 3: Patients Followup in Progress

The patients who undergo thyroid and parathyroid surgery at Endocrine Surgery department at SGPGIMS from
the Indian state of Orissa are then subsequently followed up through telemedicine. During these tele-visits at the
remote telemedicine center, post operative symptoms and signs are assessed, investigations are reviewed and
medications are advised. Further, follow up dates and subsequent investigations to be done are suggested. The
sessions involve exchange of documents containing the investigations and necessary prescriptions for drugs. A
total of 1570 patients received tele-follow up services from December 2003 to September 2015.

4. Pre-referral screening
The centers at Orissa and Uttaranchal states refer difficult and complicated cases to SGPGIMS, a tertiary care
center for Endocrine surgery. Before referral a preliminary case presentation is done from the remote centers and
a decision on the appropriate investigations required is made. Once the investigations are reviewed the patients
are given appointment for surgery and hence their hospital stay at SGPGIMS is reduced. Pre-referral screening
was started in 2005 and patients from MKCG Medical College Berhampur, and SCB Medical College, Cuttack
avail this service.

5. Tele-conferencing

Figure 4: Surgical Telepresence Suite used for telesurgical workshop

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 SGPGIMS has organized various tele-surgical conferences and workshops in the years between 1999 and 2014
(table - 1). Image quality of operative area of interest were good enough for remote participating surgeons to
identify pertinent anatomic structures, understand the steps of surgery, and take part in active two way
discussion. In April 2004 one of the Surgeons delivered his lecture to a conference organized at AIMS, Kochi and
similarly in January 2006 keynote lecture to Rawalpindi, at the Pakistan Surgical Society meet was delivered from
SGPGIMS in real time. In March 2005 SGPGIMS directly telecasted live surgical procedure from its operation
theater to an international conference INTELEMED 2005 organised by ISRO at Bangalore to demonstrate the use
of this upcoming use of telemedicine. A total of 21 live surgical transmissions transmitted between year 1999 to
year 2014.

Yr Course Conducted Duration Hrs Centers Connected

st th th
1999 1 Endocrine Tele-surgery Workshop 25 -29 Oct 40 Hospitals in Kochi & Lucknow, European
(2 Days) Institute of Telesurgery, Strasbourg, France
2000 Tele-Endocrine Pathology Workshop February (2days) 12 PGIMER, Chandigarh,
2000 Tele-endocrine Imaging workshop September (2days) 12 PGIMER, Chandigarh,
nd th nd
2002 2 Endocrine Telesurgery Conference 18 to 22 Mar 36.5 SCB Medical College Cuttack, Orissa
(5 Days)
rd th th
2002 3 International Workshop on Minimally 13 -17 Oct 40 SCB Medical College, Cuttack and hospitals
Invasive Endocrine Surgery (5 Days) in Apollo, Chennai and Bangalore
rd th th
2003 3 Endocrine Telesurgery Conference 13 -17 Oct 40 SCB Medical College, Cuttack and hospitals
(5 Days) in Apollo, Chennai and Bangalore
st th th
2005 1 SGPGI Breast Course 5 -6 Mar (2 Days) 16 SCB Medical College, Cuttack AIMS, Kochi

th th
2005 4 Endocrine Telesurgery Conference 6-10 Nov (5 Days) 36 SCB Medical College, Cuttack and AIMS,
Kochi, Ranguel University, Toulouse, France
th
2005 Diabetic Foot Care Workshop 14 Nov (1 Day) 7.5 SCB Medical College, Cuttack, AIMS, Kochi,
Base Hospital Almora and Srinagar
th
2006 XIV Surgical Gastroenterology Week (SGE 24-26 Mar 18 AIMS Kochi
Week) (3 Days)
nd th th
2006 2 Diabetics Footcare Workshop 24 -25 Nov 7.5 SCB Medical College Cuttack, Orissa
(2 Days)
th th
2006 2nd SGPGI Breast Course 25 -26 Nov 16 SCB Medical College Cuttack, Orissa &
(2 Days) Orange, California, USA
th nd th
2007 8 Postgraduate Course in Endocrine 22 -25 Nov 20 SCBMC Cuttack, MCKG Medical College
th
Surgery & 8 Annual Conference of Indian (2 Days) Berhampur, AIMS, Kochi, & CMC Vellore
Association of Endocrine Surgeons (IAES)

th th
2008 XIVth Surgical Gastroenterology (SGE) 28 -30 Mar 18 AIMS, Kochi
Week (3 Days)

2008 Diabetic foot Care 22 & 23 Nov 8 SCBMC, Cuttack , Orissa

(2 Days)
th
2009 9 Postgraduate Course in Endocrine 13- 15 Nov 28 Shimla through VPN, Bhutan through IP,
Surgery (3 Days) Cuttack Through ISRO IP, Boston, USA,
Through ISDN
2009 4th National Workshop on Diabetic Foot 05-06 Dec 18 Kabul, Bhutan through IP,Shimla Through
Care (2 Days) VPN,Cuttack Through ISRO IP
th
2011 10 PGES of Endocrine Surgery 3-6 Nov 3 IGMC Shimla, SCBMC Cuttack, Holyfamily
(4 Days) Hospital Pakistan, CMC Vellore, Worcester
MA, USA
st rd
2013 Tele conference of XVII surgical 1 -3 Mar 11 Live feed transmitted to Lecture Theatre
gastroenterology week: post graduate course (3 Days)
is proctology
th th th
2013 11 PGES Workshop 7 -10 Nov 40 CMC Vellore, SCBMC Cuttack
(4 Days)

2014 Breast Course-2014 and ABSI Skills Course 8 Feb-9 Feb 12 Tata Memorial Hospital Mumbai
(2 Days)

12-13
6. Tele-mentoring Case Study
In March 2004 the first telementoring trial was carried out in India between SGPGIMS, Lucknow and AIMS,
Kochi. In this case study we successfully used tele-mentoring to remove a parathyroid tumor in a patient with
residual hyperparathyroidism after two previous unsuccessful attempts in tumor excision. A 21-yr-old patient
crippled with advanced hyperparathyroidism was taken up for third-time exploration at AIMS, Kochi, with
guidance from the SGPGIMS using telemedicine technology. These two centers are located 2,500 km apart, and

334
telementoring from the more experienced endocrine surgeons at SGPGIMS resulted in successful tumor
localization and removal at AIMS. For this session both the institutions were provided with a dedicated 512 Kbps
VSAT link and two-way video-audio connectivity. Even though two previous explorations were unsuccessful, with
the help of telemedicine technology the same surgeon was successful in locating and removing the tumor. The
video and audio quality was of good enough quality for the expert at SGPGIMS to guide the team at AIMS
satisfactorily. The patient benefited since he did not have to travel to a far-off specialized center for surgery. This
case report testifies the usefulness of telemedicine in the field of surgery, especially in developing countries,
which have few medical experts in certain specialized areas. The network diagram is shown in Fig. 5.

Figure 5: Network Architecture for Surgical Tele-Mentoring

6. Telemedicine as a tool to develop surgical subspecialty Case study with Endocrine Surgery,
SGPGIMS Experience14-15
Newer sub-specialties in medicine are coming up in recent years. Due to the financial and logistic constraints
such advancement is not taking place in developing world in contrast to the industrialized nations. Access to few
such specialized disciplines existing in developing countries could be possible by telemedicine technology. In this
direction we have taken Endocrine Surgery as a prototype to audit the outcome of telemedicine based outreach
activity to develop this subspecialty in a developing country like India.

For this experiment the network partners involved are SCB Medical College Cuttack, MKCG Medical College
Berhampur and VSS Medical college, Burla (all in the Indian state of Orissa located 1500 km from SGPGIMS),
AIMS, Kochi (in the Indian state of Kerala located 2500 km from SGPGIMS), Base Hospitals at Almora and
Srinagar both district hospitals (in Uttaranchal state and 500 km away). Apart from the Indian locations the
network has been recently expanded to link with Ranguel University, Toulouse, France (from April 2005) and Holy
Family Hospital, Rawalpindi, Pakistan (from March 2006).Different modules are used at aiming at patient care
and skill development of remote care physicians. At SGPGIMS, the Endocrine Surgery Department used the
following modules i.e. Tele-consultation, Tele-education, Tele-CMEs (table-1), Tele-surgical conference, Surgical
treatment planning, Tele-pathology, Tele-radiology, Tele-follow up for the subspecialty growth. (Fig -6)

Fig 6 Different modules used for the Surgical Sub-specialty Growth

335
Endocrine surgery is a unique developing sub-specialty compared to other surgical branches. Teaching, training
and skill acquisition are essential in capacity building and this along with patient care can be done satisfactorily
with telemedicine technology. However this method is to be validated by more centers for wide spread
acceptance.

Conclusion
The experience at SGPGIMS has shown that Telemedicine technology has different applications in surgical
practice and can be used for education, knowledge sharing, health care and appropriate surgical skill
development. Some of the modules have been developed keeping the local country need in mind. More and more
academic medical centers should get involved in such exercises to validate this area of application of
telemedicine in surgery. Currently it is not feasible to practice tele-robotic surgery in view of high cost of the
surgical robotic equipment. However, the technology holds a great promise in many areas of surgery as
highlighted in this document.

References

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3. Eide T J, Nordrum I. Current status of telepathology. APMIS 1994; 102(12): 881-90.
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195(1): 73-81,.
7. Sweet HA, Holaday BA, Leffell 0, et. al. Telemedicine: delivering medical expertise across the state and around
the world. Connecticut Medicine 1995 October; 59(10): 593-602.
8. Nakamura K, Takano T, Akao C. Assessment of the value of videophones in community model networks for
developing a comprehensive home health care system employing multimedia. Paper presented at the Second
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Telemedicine Journal 1995; 1(2): 174.
9. Darkins A, Gough 0, Opett L, et. al. Inner city telemedicine--management of patients with minor injuries by low
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New Delhi: JAYPEE Brothers Medical Group Publisher Pvt. Ltd., 263-277.
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surgery. Telehealth in the Developing World. London: Royal Society of Medicine Press Ltd, 109-120.
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Springers, Sajeesh Kumar Jacques Marescaux (Eds.), 153-159.
15. Pradeep PV, Anjali Mishra, Lily Kapoor, Rajesh Basnet, Gaurav Agarwal, Amit Agarwal, AK Verma, S K Mishra.
Surgical sub-specialty growth in Developing country: Impact of Telemedicine technology; A Case study with
Endocrine Surgery. Proceedings of 8th International Conference on e-Health Networking, Applications and
Services, Healthcom 2006, ISBN: 1-4244-9704-5 2006 IEEE, P78-83, New Delhi, India, 17-19 August 2006

Investigations for peripheral vascular disease

Anjali Prakash

Evaluation of the Peripheral Arterial System

Peripheral arterial disease is usually secondary to stenotic or occlusive atherosclerosis. The majority of
symptomatic patients have intermittent claudication and only a minority (<2% and typically those with diabetes
mellitus or renal failure) progress to critical limb ischaemia, heralded by the onset of rest pain and/or loss.
Imaging is largely reserved for patients with disabling symptoms in whom revascularisation is planned. In these
patients, accurate depiction of the vascular anatomy is critical for clinical decision making as the distribution and
severity of disease are key factors determining whether revascularisation should be by endovascular techniques
or open surgery. Non-invasive vascular imaging has recently undergone significant refinement and has replaced
conventional digital subtraction angiography for many clinical indications.

Radiological Evaluation
Radiological evaluation of Peripheral arterial disease is aimed at providing the following information.
Presence or absence of significant obstruction to flow.
Site and anatomical extent of obstruction.

336
 Condition of collateral flow and distal vasculature for planning treatment.
Results of therapy and disease progression.

Imaging Modalities
Ultrasound and Doppler Scanning
The arteries of the upper and lower extremities are easily accessible to sonographic imaging with high resolution
transducers. Duplex Doppler (the term duplex refers to the combination of B mode and colour Doppler
ultrasound) is typically the initial imaging modality of choice. It is widely available and requires no exposure to
either ionising radiation or potentially toxic intravascular contrast agent. It is highly portable and in the emergency
setting permits a rapid targeted examination.. It can also provide detailed haemodynamic information;
Power Doppler depicts very slow flow, improves visualisation of vascular borders and contours and in cases of
stenosis it improves delineation of residual lumen

Flow Patterns on Spectral Doppler

The normal spectral Doppler pattern of arterial flow in the extremities is a high resistance wave form. It consists
of a narrow sharply defined tracing indicating that all blood cells are moving at an equivalent speed at any time in
the cardiac cycle. The configuration of this wave form is typically triphasic indicating strong forward component of
blood flow during systole, followed by a short reversal of flow during diastole. A return to forward flow of lower
amplitude normally follows and lasts for a variable length of diastole. The diastolic portion of blood flow is
extremely variable disappearing with vasoconstriction due to cold or increasing with warmth or exercise. The
diastolic flow is absent in vessels that have lost compliance as in atherosclerosis and diabetes.

Once an abnormal flow pattern is detected by color Doppler, pulsed Doppler spectral sampling is done to better
characterise the lesion.

Focal peripheral arterial stenosis is categorised as mild, moderate or severe.

1. With mild stenosis (1-19% luminal diameter reduction) the spectral Doppler tracing reveals mild spectral
broadening but waveform maintains its triphasic appearance. PSV is upto 30 per cent greater than the
velocity of the normal proximal segment
2. With moderate stenosis (20% to 49% diameter reduction), the waveform remains triphasic but has increased
spectral broadening. Doppler tracing demonstrates an increase in PSV that is upto 100 per cent greater than
the proximally sampled segment with a velocity ratio 1.5:2.
3. A severe stenosis represents a 50 per cent or greater luminal diameter reduction. This lesion is considered
haemodynamically significant as it results in decreased blood pressure and blood flow across the stenosis.
There is marked spectral broadening and the waveform at the level of stenosis is monophasic with a PSV
that is more thandouble the velocity measured in the proximal segment, i.e. a velocity ratio > 2. In addition
because of the pressure drop across the stenosis, the waveform loses its normal diastolic reverse flow
component1. This is a significant feature of critical stenosis, and defines a pressure reducing lesion PSV
ratios of > 4 correspond to a greater than 80 per cent stenosis and ratios >7 correspond to > 90 per cent
stenosis respectively.An occlusion is characterized by absence of flow within an arterial segment.

Ratios of PSV are superior to absolute PSV measurement for classification of peripheral arterial stenosis. In the
absence of collaterals high resistance waveform is identified proximal to the occlusion/high grade stenosis. Distal
to a significant stenosis/occlusion the waveform shows a typical low resistance pattern due to opening up of
collaterals and loss of normal arteriolar tone. There is also a characteristic tardus parvus waveform in the distal
vessel.

The iliac arteries and the vessels of thecalf however are difficult to evaluate in any patients. Evaluation of the
superficial femoral in the adductor canal may also be difficult. In the upper limb the origins of
brachiocephalic/subclavian arteries are difficult to evaluate. Besides Doppler is a very operator dependent and
time consuming procedure and extensive vessel calcification may prevent insonation of stenosis. Further, when
an artery is occluded assessment of distal circulation and collaterals is rarely possible.

CT Angiography (CTA)
CTA is a noninvasive means of evaluating blood vessels requiring only an IV injection of contrast. The images
can be evaluated in 2D as well as 3DThe advent of multi detector row CT has had substantial impact on CT
angiography offering shorter acquisition times, lower doses of contrast medium, increased volumetric coverage
and/ or improved Z axis resolution. The introduction of 64 and recently 128 slice CT scanners has further reduced
examination times, while increasing volumetric coverage and improving resolution to the tune of 0.24 mm voxel
size. The main post processing techniques used are; volume rendering, multiplanar and maximum intensity
projections (MIPs). Dual energy CTA is a promising new approach for bone and calcium removal

Advantages of CTA over DSA include 3 D- volumetric data analysis and display, smaller volumes of contrast
material, minimal invasiveness and thus a lower complication rate, better visualization of distal arteries and
shorter examination times. The peripheral venous rather than central aortic administration of contrast material as
is done in DSA allows better opacification of collateral circulation and thus of arteries distal to an occlusion site.

337
CTA unlike sonography is relatively investigator independent and can also assess aspects external to the vessel
lumen, not assessed by DSA, including mural thrombus, atheroma, inflammation and periarterial tissues.

In the evaluation of peripheral vascular occlusive disease CTA can be used for characterisation of inflow and run
off vessels, as an aid to therapeutic planning and the post operative evaluation after angioplasty or bypass
procedures. CTA can be invaluable for planning stent deployment and evaluation of post procedure
complications in iliac arteries. Results of recent studies suggest that the use of MD-CTA instead of DSA as the
initial diagnostic imaging test for Peripheral arterial occlusive disease provides sufficient information for
therapeutic decision making and reduces imaging costs (Sensitivity and specificity of CTA using the latest 64
slice scanners has ranged from 91% to 100% and 81% to 100% respectively including distal pedal arteries. CTA
can at times display eccentric stenoses and arterial segments distal to occlusions more accurately than
angiography. Not only is the technique accurate for gradation of stenosis but also for evaluating exact lesion
length and number of stenoses which are important determinants in choosing the optimal therapeutic option.
Vessel wall calcification decreases the clinical utility of CTA in patients with peripheral arterial disease.

MR Angiography(MRA)
MRA provides a minimally invasive approach for direct anatomic imaging of the peripheral vasculature. Two basic
techniques are used for non contrast MRA Time of flight (TOF) and Phase Contrast angiography (PCA). Three
dimensional contrast MRA (CE-MRA) has substantially changed imaging strategies in patients with peripheral
vascular disease. With CE-MRA signal of flowing blood is no longer flow dependent. Flow induced artifacts seen
with non contrast MRA techniques are therefore largely eliminated. Metallic stents or clips however may produce
artifacts significantly degrading image quality. The advantages of MR angiography include absence of ionising
radiation, ability to depict larger vascular territories in 3D imaging volumes and absence of iodinated contrast
media. Since risk factors like diabetes,cardiacdisease and age over 84 years are independently predictive for
presence of vessel wall calcification, such patients may be considered for MRA as the initial diagnostic
modality.3- Dimensional CE-MRA in recent years has become a well accepted imaging method for evaluation of
Peipheral arterial vascular disease.

Use of dedicated peripheral vascular coils result in better signal to noise ratio and contrast to noise ratio as
compared to body coils. The accurate grading of stensosis in the small calf and foot vessels requires high
resolution imaging with an in plane resolution below 1mm 3.

Nephrogenic systemic fibrosis has been reported in patients with impaired renal function, who have been
administered the MR contrast gadolinium, the incidence being highest with gadodiamide.. It is preferable to use
macrocyclic gadolinium chelates like gadoterodol or gadoterate meglumine which are more stable than linear
chelates.

Conventional Angiography/DSA
DSA is the gold standard for arterial imaging. DSA uses image subtraction so that bones do not obscure vascular
details. Contrast resolution is improved through use of image enhancement software, lower volumes of contrast
medium can be used, and image acquisition is rapid. Angiography provides better anatomic detail and higher
resolution than any other modality. Haemodynamic information regarding pressure gradients across stenoses
can be obtained simultaneously. Most importantly percutaneous interventions like angioplasty, stenting,
thrombolysis, thrombo-aspiration are possible at the same time.

DSA has certain limitations. It is an invasive procedure requiring intra-arterial catheters with resultant
complications. The use of iodinated contrast media is associated with contrast reactions and nephrotoxicity
especially in patients with renal compromise. Increasingly angiography is becoming a secondary imaging
modality to resolve conflicting results of non invasive tests, or to confirm an abnormality prior to intervention.
Surgical bypass can be performed on the basis of high quality US, MRA or CTA

Lower Limb Arteriography9

The procedure includes:
Abdominal aortography; bilateral lower extremity (run off) study; bilateral oblique pelvic arteriography; selective
arteriography sometimes in multiple projections or after intravascular vasodilator injection to evaluate
equivocal findings.
Measurement of pressure gradients in the aorta and iliac arteries to determine the significance of moderate or
suspicious stenoses.

Atherosclerosis
Typically diffuse, bilateral and often strikingly symmetric. Patients with claudication usually have single level
disease, while patients with rest pain or more severe ischaemia have multilevel disease. Clinically relevant
disease includes stenosis, thrombotic occlusion and ulcerated or exophytic plaques. Plaques may be
characterised as focal or long, calcified or non-calcified, concentric or eccentric and smooth or ulcerated.

338
Arteritis
The most prevalent form of large vessel arteritis of the lower limbs Buergers disease or thromboangitis
obliterans. It typically affects young males and has a strong correlation with smoking. Lower extremities are
involved in 90 per cent cases and upper extremities in 50 per cent cases.. CTA or MRA may not show any
characteristic findings that distinguish it from atherosclerosis other than distribution of disease. The conventional
angiographic findings are often striking. There is relative sparing of CFA, SFA and popliteal arteries with
extensive involvement of medium and small arteries. Typically the disease is segmental and occlusions
intervene with normal segments. Characteristic corkscrew collaterals are seen. Cessation of smoking is crucial
and amputation is fairly common as reconstructive surgery or endovascular therapies are usually not possible
due to lack of distal runoff vessels.

Upper Extremities:- The brachiocephalic and left subclavian arteries are typically catheterised from the aortic
arch. Significant atherosclerotic disease is less common in the arm. With proximal subclavian stenosis flow in the
ipsilateral vertebral artery may be reversed resulting in subclavian steal syndrome. In uncomplicated Raynauds
disease the arteries may be constricted but remain morphologically normal.

Aneurysms
An aneurysm is defined as focal or diffuse dilatation of an artery by more than 50 per cent of its normal diameter.
Aneurysms are most often degenerative and they may be fusiform or saccular. Common sites for degenerative
aneurysms in the extremities include iliac, popliteal and common femoral arteries in the lower limb and
brachiocephalic and subclavian arteries in the upper limb. The entire popliteal artery may be aneurysmal, but
focal aneurysms most often involve the vessel above the joint line.

Standard grey scale imaging can demonstrate the presence of either a focal bulge or more diffuse increase in
arterial size. This diagnostic task is well performed by standard grey scale images that it now serves as a gold
standard for the diagnosis of peripheral arterial aneurysms. It can visualize progressive deposition of mural
thrombus not appreciated by arteriography. The sensitivity and specificity of ultrasound compared to surgery are
close to 100 per cent. Doppler techniques are useful in confirming the continued patency of a channel within the
thrombosing aneurysm either at presentation or following surgery.

CT Angiography demonstrates the exact size and extent of aneurysm, the presence of thrombus, presence of a
patent lumen, and relationship of the aneurysm to adjacent bony structures.. Multiplanar reconstructions are
particularly useful in planning surgical intervention providing information about the degree of extension of the
aneurysm in sagittal and coronal planes and its relationship with adjacent structures. CE-MRA is an excellent
technique for the diagnosis of aneurysms Aneurysms can be missed by catheter angiography if they are non-
calcified and thrombosed or lined by mural thrombus. Catheter angiography is usually reserved for preoperative
planning when percutaneous therapy is being considered or rarely when the diagnosis cannot be made by cross
sectional imaging.

Pseudoaneurysms
In a pseudoaneurysm/false aneurysm one or more layers of the arterial wall are disrupted. Blood may be
contained by the outer adventitia and surrounding connective tissue. The collection of blood remains in
communication with the patent artery by means of a channel of variable size and length. The principal etiology is
penetrating trauma and includes knife wound, bullet wound and medical intervention. Pseudoaneurysms of the
CFA commonly develop following catheterization. Colour doppler is almost 100 per cent accurate in the
diagnosis of pseudoaneurysms. The grey scale image shows an echolucent or mixed echogenic collection in
close proximity to the artery. The colour flow image has a quite dramatic appearance: that of a swirl of colour
sometimes referred to as the colour Yin Yang sign. This sign is not specific to pseudoaneurysms because
saccular aneurysms share similar flow patterns. Colour flow mapping helps to locate the communicating channel
which may be difficult to localise on grey scale imaging. The spectral waveform from the communicating channel
shows a very typical pattern diagnostic of pseudoaneurysms and is called the to and fro sign .During systole the
pseudoaneurysm distends and stores energy. Blood flows quickly into the collection. During diastole the effective
pressure within the collection is greater than the systemic arterial pressure thereby pushing blood out from the
collection. Blood flow outwards is slower and has lower amplitude.

CTA, MRA (esp. CE-MRA) and catheter angiography can also accurately diagnose pseudoaneurysms but are
rarely required for diagnosis. Whenever, definitive pseudoaneurysm therapy is delayed frequent follow-up
ultrasound examinations are recommended.

Surgical repair of post-catheterization femoral pseudoaneurysms is contemplated only when ultrasoundguided

compression repair fails and the aneurysm continues to expand. In these cases Doppler may be used to mark the
actual physical location of the communication obviating the need for preoperative angiography. Compression
repair has also been successfully achieved in axillary and brachial arteries.

Arteriovenous Malformations
Arteriovenous malformations comprise an anomalous communication directly between an artery and a vein
without an intervening capillary network. Clinically they present as pulsatile warm and sometimes painful

339
masses). Colour Doppler shows a wide variety of flow patterns such as colour aliasing, colour persistence and
colour bruit, spectral Doppler studies always show a high velocity low resistance and frequently turbulent flow.
CT and MRI are superior to ultrasound for demarcation of the boundaries of the lesion and for determining the
relationship with adjacent structures. Three dimensional CE MRA can detect arteriovenous malformations or
fistulas of the upper or lower extremities. It is helpful to obtain a multiphase exam in order to demonstrate early
filling of the draining veins. It is useful to use a dedicated coil for evaluation of the AVM since high resolution
images are desired. Angiography demonstrates markedly dilated inflow arteries, numerous feeding arterioles,
pools of contrast within the AVM and early filling of draining veins.

Arteriovenous Fistulae (AVF)

It is always acquired from accidental or iatrogenic trauma. These can be quickly detected using Colour doppler.
They may present with local symptoms, distal ischaemia (from steal phenomenon) or a high output cardiac
failure.

In large traumatic A-V fistulae, the diagnosis is easily made on Doppler by noting distention of a recipient vein
with turbulent and in some cases pulsatile venous flow (arterialization of venous flow). The feeding artery has a
monophasic turbulent continuous flow. The arterial Doppler signals distal to the lesion are likely to be normal. In
some cases direct visualization of the communication is possible; however, this may not be always possible due
to associated turbulence. An indirect sign of the fistula is dilatation of the vein and a poor Valsalvas response.

These findings may be absent in smaller A-V fistulae. In these cases colour flow imaging can locate the physical
communication between the artery and the vein guiding placement of the Doppler gate exactly over the fistulous
communication. Loss of high velocity signals in the recipient vein with Valsalva maneuver (i.e. positive Valsalva
response) suggests that the communication is a small one and can be safely followed up without the need for an
intervention. CTA or MRA can also be used to evaluate AVF. Good arteriography is important in demonstrating
the anatomy of abnormal communication and requires a fast injection with adequate volume of contrast with early
rapid serial filming to clearly define the anatomy and site of the fistula. The dilated feeding artery fills early and so
does the dilated vein.

Acute Limb Ischemia

Prompt recognition of acute limb ischemia is vital to proper patient management. Only a narrow window of
opportunity may exist in which to salvage the threatened limb. When acute limb ischemia is present, immediate
diagnosis and intervention is necessary to restore blood flow.

A major diagnostic goal is the distinction between embolic and thrombotic occlusion. Embolic occlusions tend to
result in profound ischemia owing to the absence of developed collaterals. Thrombosis of a pre existing stenosis
is tolerated well because the collateral circulation is already established. The patient presents with a cold limb
that is painful, pale or cyanotic and numb. Peripheral pulses are absent or diminished.

Imaging
Patients with critically ischemic limbs should proceed directly to surgery while those with less threatened limbs
and extensive underlying vascular disease or complex vascular surgical history benefit from preoperative imaging
Catheter angiography is the procedure of choice in most patients with acute limb ischemia, since patients require
Immediate intervention/surgery and when acute ischemia is suspected clinically patients usually proceed directly
to catheter angiography

Angiography
An acute embolus produces a discrete filling defect with reconstitution of the distal vessels. However it may also
appear as a sharp cutoff point that mimics a thrombotic occlusion. Angiographic signs of acute arterial embolism
include a meniscus or filling defect, mild or absent disease in other vessels, lack of contralateral disease, poorly
developed collaterals and emboli at other sites. In > 50 per cent cases emboli lodge in the brachial artery in the
upper limb and the femoral or popliteal artery in the lower limb frequently at major bifurcations. Total occlusion
can hide an unusual cause for thrombosis such as popliteal artery aneurysm. In patients with microembolization
syndromes, proximal atherosclerotic disease or aneurysms are often found.

In thrombotic occlusions on the other hand evidence of diffuse atherosclerotic disease in the ipsilateral and
contralateral limb is common. Usually collaterals are well developed and thrombosis produces midvessel
occlusion rather than at vessel bifurcations.

CDFI, CTA and MRA can all depict arterial occlusion especially in the larger vessels, emboli in small vessels may
be missed.

Trauma
The upper and lower extremity arteries are subject to injury from penetrating trauma, blunt trauma, fracture
dislocations medical procedures chronic vibrational injury or use of crutches.

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The increased acquisition speed of MDCT lends itself well to the emergency setting. Peripheral CTA can be
performed within 10-15 min of room time. Due to good availability and fast scanning MD CTA may replace
catheter angiography in the trauma setting. The main limitations for the use of MRA in trauma patients are logistic
in nature. Patients in a critical condition, such as victims of multiple trauma are difficult to monitor properly in the
MR scanner. These patients often have MR incompatible life supporting devices; hence the utility of MRA in
trauma patients is limited.

Catheter arteriography is the most accurate technique for detecting traumatic injuries to the extremity arteries.
Guidewires and catheters must be positioned away from the area of injury so that catheterization related
vasospasm is not mistaken for vessel damage. The spectrum of angiographic abnormalities produced by trauma
include intimal tears, intraluminal thrombus, vasospasm, intramural hematoma, dissection, transection with or
without thrombosis, vessel deviation, A-V fistula formation, pseudoaneurysm formation and compartment
syndrome which causes slow flow in proximal arteries.

Sonographic evaluation of traumatic arterial injury is controversial. At this time Colour doppler can be used safely
to observe and to follow up lesions such as intimal flaps, pseudoaneurysm and AV fistulae. Doppler evaluation
may be useful in patients with venous injury which may be undetected by angiography and a source of
considerable morbidity.

Thoracic Outlet Syndrome (TOS)

The various forms of TOS are a distinct set of clinical disorders of the upper extremity caused by extrinsic
compression of major nerves and blood vessels exiting or entering the thorax. In >95 per cent cases, symptoms
are caused by compression of the brachial plexus and related nerves; arterial compression is responsible for only
1 per cent of cases. There are three locations in which thoracic outlet syndrome can occur the scalene triangle,
costoclavicular space and subpectoral space.

Imaging
Imaging is directed at evaluating both the lumen of subclavian artery and surrounding structures. The arterial
lumen is imaged in order to confirm the compression and diagnose complications such as distal embolisation.
Imaging should begin with a simple chest x ray which may reveal a cervical rib or other bony anomalies.

Colour Doppler may demonstrate extrinsic compression of the subclavian artery especially in abduction. Post
stenotic dilatation may also be demonstrated. Cross sectional imaging of the upper thorax with CT /CTA or
MR/MRA is useful for evaluating both the artery and the surrounding structures. Bony abnormalities are well
shown by CT while MR studies are particularly useful in characterizing fibro-muscular abnormalities. A complete
angiographic examination from the arch to the hand is mandatory. Besides neutral position angiography may be
performed in the position which provokes patients symptoms, in which extrinsic compression of subclavian artery
is demonstrated. However evocative maneuvers can induce arterial compression in half of normal patients. Other
possible angiographic findings include aneurysm formation, distal embolization and complete thrombosis. The
findings can be bilateral even when symptoms are not

Evaluation of Bypass Grafts

Colour flow imaging and duplex ultrasound are now the recommended noninvasive examinations for the post
operative monitoring of bypass graft patency. They are used to detect focal stenoses before they progress and
lead to graft occlusion.

The current approach to bypass graft imaging relies on colour flow image to identify sites of increased velocity
seen as aliasing with appropriate PRF setting and spectral Doppler traces are then obtained from this site. PSV
ratios are calculated compared to the normal segment, 2 to 4 cm proximal. Values above 2 are considered to
represent lesions causing 50 per cent diameter narrowing or more. However in complex grafts, anastomotic sites
may have high velocities with no stenosis. This is due to the anatomy of the anastomosis where a larger graft is
attached to a smaller vessel or an area of vessel dilatation is constructed at the point where the graft joins the
native vessel. In the distal anastomoses of aortobifemoral grafts for example stenosis should not be considered
until the ratio exceeds 3 or 4.

MD-CTA and CE-MRA are at least as accurate as colour Doppler sonography for screening, but due to the longer
procedure time and higher costs they are usually reserved for more complex cases. They, however, provide more
thorough evaluation of the inflow and outflow vessels, often obviating the need for catheter angiography before
surgery.

EVALUATION OF THE PERIPHERAL VEINS

Deep Venous Thrombosis

Acute DVT is a common problem with an overall lifetime risk of about 2 to 5%. A number of conditions are known
to predispose to DVT. These include prolonged immobilization to hypercoagulability syndromes, trauma, and
malignancy.

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Sonography and Colour Doppler Flow
Snography has revolutionized the diagnosis of deep venous thrombosis (DVT). The test is extremity accurate,
easy to perform, relatively inexpensive and completely safe. It has essentially replaced contrast venography in
diagnosing symptomatic patients. With optimal grey scale settings, the normal vein lumen is echo free with the
exception of valve cusps Grey scale images also document intraluminal thrombus and compressibility. Normally
with application of moderate pressure, patent veins collapse and anterior and posterior walls appose. The
pressure required is generally less than that required to deform the adjacent artery.. Inability to completely
obliterate the vein lumen with compression is the cardinal sonographic criterion for diagnosis of venous
thrombosis. As the echogenicity of the thrombus is variable direct visualization of echoes within the venous
lumen is less reliable. However direct compressibility is difficult to evaluate in the pelvis, adductor canal and calf
veins.

Colour Doppler facilitates vessel identification and confirmation of patency of venous segments unable to be
compressed directly. When using Doppler sonography DVT can be excluded when there is complete colour flow
saturation of the entire deep venous system. Lack of colour fill in despite augmentation on the other hand
suggests DVT.

There are several flow characteristics that are present in patent venous system which may be absent or altered
with significant venous obstruction. These characteristics include spontaneous flow, cardiac and respiratory
phasicity, the valsalva response and augmentation. Spontaneous flow should be present at rest but may not be
present in veins of the calf and foot. The demonstration of a flow void or defect by colour Doppler, or absence of
flow in a venous segment by colour or pulsed Doppler are findings highly suggestive of thrombus. Respiratory
phasicity results from the normal flow velocity changes that occur in response to variation in intrathoracic
pressure. The presence of cardiac and respiratory phasicity in a vein suggests patency of the venous system
between the thorax and site of insonation. When DVT is present, the venous segment distal to the thrombosis
shows absence of respiratory phasicity. However respiratory phasicity may not be depressed in patients who are
shallow breathers, who have spinal cord injuries and when the thrombosis is partial. Respiratory phasicity may
be made more prominent by asking the patient to take a deep breath which results in cessation of flow.
Evaluation of phasicity should be performed at both groins to facilitate comparison.

Augmentation entails mechanically propelling venous blood from distal portion of an extremity to the point of
insonation by squeezing the calf. This results in a rush of blood which is detected by Doppler upstream, and is
said to indicate absence of significant obstruction between the site of augmentation and insonation.

Isolated calf vein thrombi are difficult to detect by CDFI and anticoagulation controversial, so routine imaging of
calf veins is not performed at many centers. Some studies demonstrate that a repeat above knee
ultrasonography performed at day 5 to 7 after the first negative above knee study is all that is required to rule out
significant DVT. While evaluating for lower limb DVT proximal portion of great saphenous should also be
evaluated as thrombosis within this can extend into the deep system.

The sensitivity and specificity of sonography and Doppler in the diagnosis of DVT is 95 per cent and 98 per cent
respectively in symptomatic patients. The sensitively and specificity are closer to 80% for calf DVT and
asymptomatic patients due to higher incidence of isolated calf DVT and presence of smaller non occlusive
segmental thrombi. Causes of misdiagnosis include - underlying chronic venous disease, isolated calf/iliac vein
disease, venous duplication, small focal thrombi and technical errors.

Chronic DVT
About 48% of veins remain abnormal even after 6 months of the acute episode. There may be partial
recannalisation,residual clot or organized thrombus.

The distinction between acute and chronic residua of venous thrombi is of great clinical importance as chronic
thrombi are epithelialized and unlikely to embolise. However, sonographic distinction between acute and chronic
DVT may be difficult to make and venography is the technique of choice. In chronic thrombosis the vein shows
thickened walls, reduced caliber and may show patchy Since CDFI is a simple, accurate, non invasive diagnostic
test for upper and lower extremity DVT, other cross sectional modalities are rarely indicated for diagnosing DVT.

CT Venography
Venography may be performed after helical computed tomographic pulmonary angiography for pulmonary
embolism. In this setting evaluation can be made for both pulmonary embolism and lower extremity DVT without
the need for additional contrast medium. Venous imaging may be performed afer a delay of 2 to 3 min. Arterial
enhancement is however always present which can make identification of weakly opacified small veins difficult,
Infusion of diluted contrast via a foot veins is feasible with multidetector technology but has found little clinical
application in daily practise.

However CTV may prove to be useful in assessing the proximal extent of thrombus into the iliac veins or IVC in
patients where these are difficult to evaluate by Doppler. Findings in acute DVT include filling defects encircled

342
by a rim of contrast, venous dilatation and perivenous congestion. In chronic DVT, web like or thread like filling
defects that are, peripherally located or calcified may be seen.

MR and MR Venography
This plays a limited role compared with ultrasound and contrast venography due to limited availability and high
cost of examination. MR direct thrombus imaging (MR-DTI) is a technique which, allowing direct visualization of
pulmonary emboli and simultaneous imaging of the legs without the need for intravenous contrast. flowing blood
to maximize thrombus conspicuity.

CE-MRA may be performed by an indirect technique (i.e. following MR angiography) or by a direct technique
using diluted gadolinium injection from pedal veins/antecubital vein.

Venography
The procedure is uncomfortable for the patient and has a small but definite risk of significant complications. For
these reasons venography is infrequently performed.

The most reliable venographic findings is an intraluminal filling defect outlined by contrast. When the defect is
smooth and fills a normal sized or enlarged vein, the thrombus is likely to be acute, i.e. less than 7 days. When
the filling defect is contracted irregular and the vein is smaller than normal the thrombus is chronic.

Chronic Venous Disease

Imaging is central to the management of patients with chronic lower extremity venous disease. The most
important determinants are patency of the deep system, valvular incompetence in superficial, deep and
perforating veins, the extent of reflux and exact site of incompetent veins.

Sonography
Colour Doppler sonography is the standard tool for studying patients with venous insufficiency and varicose veins
when invasive therapy is being considered. It can also identify venous reflux in the superficial and deep systems.
If the deep venous system is normal, varicose veins is considered to be a primary problem. Sonography can also
identify residual deep vein occlusion or partial recanalization. Reflux is defined as the retrograde flow of blood in
veins of the lower extremity caused by absent or incompetent valves. Assessment of incompetence is performed
by applying distal compression and observing the direction of flow. In the normal situation flow will not reverse
following release of compression. If flow reversal for 0.5 sec to 2 sec is observed then incompetence is very likely
while reversal of more than 2 sec is diagnostic. This must be performed with the patient standing and weight
supported on the contralateral limb. Refluxing and non refluxing segments may be seen in the same vein.
Assessment of reflux should be made in the superficial,especially saphenofemoral and saphenopopliteal junction
and deep venous system separately. The more proximal veins may also be assessed following a Valsalva
maneuver. In the normal condition there should be complete retardation of flow without flow reversal, should
reversal be observed this is again evidence of venous incompetence. US with CDFI is >95% sensitive and
specific for detection of reflux.

Perforating Veins
Incompetent perforating veins can also be identified by duplex sonography. One looks for veins coursing between
the deep and superficial veins and then during manual compression and release one looks for bidirectional flow.
Compression can be applied proximal or distal to the duplex interrogation site. In one study all perforators >4 mm
were incompetent, irrespective of whether flow reversal was seen or not38 and those less than 3 mm were
competent. Sonography can also be used to mark out the incompetent perforators however it may miss some
incompetent perforators detected by venography, being about 80% sensitive but very specific. Doppler can also
be used to evaluate patients postoperatively. In patients with varicose veins and reflux, superficial femoral
venous reflux could be abolished by greater saphenous stripping. If the deep venous reflux persists after surgery
the prognosis for cure of symptoms may be guarded. Ultrasound has also been used for guidance of
radiofrequency or thermal ablation of saphenous vein for treatment of varicosities.

Venography
Ascending or descending venography is needed only when the results of duplex sonography are inconclusive,
the study is technically inadequate or the anatomy is complex. The appearance of chronic DVT can vary from
recanalised veins with narrow, irregular, web filled lumens with distorted valves and incompetent perforators to
non- opacification of deep veins with preferential filling of superficial veins and collateral channels. Descending
venography, though considered the gold standard is not without limitations. False positive results may occur due
to seepage of high density radiographic contrast through a competent valve, also presence of a competent valve
upstream does not allow evaluation of the valves located downstream.

In patients with primary varicose veins, descending venography, ascending venography or varicography may
show filling of varicosities that communicate with valve less, dilated perforating veins.

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CE-3D- MR Venography has also been performed in patients with recurrent varicosities after surgery and has the
potential to affect clinical decisions in patients with recurrent varicose veins by helping to delineate complex
venous anatomy.

Conclusion
Advances in non-invasive imaging modalities like Doppler sonography, CT angiography and MR angiography
have greatly reduced the role of invasive arteriography/ venography. Although therapeutic strategy may be
planned on the non-invasive imaging techniques, angiography is often required for pre-interventional planning
especially when the noninvasive modalities are inconclusive or technically inadequate.

References

1. Pellerito JS. Current Approach to peripheral arterialsonography. Radiol Clin North Am 2001;39(3):553-67.
2. Chow LC, Rubin GD. CT angiography of the arterial system.Radiol Clin of North Am 2002;40(4):729-50.
3. Hiatt MD, Fleischmann D, Hellinger JC, et al. Angiographic Imaging of the Lower Extremity with Multidetector
CT.Radiol Clin N Am 2008;43,1119-27.
4. Valji K (Eds). Pelvic and lower extremity arteries In: Vascular and Interventional Radiology, WB Saunders 2006;96-
135.
5. Kaufman JA. Lower Extremity arteries. In Vascular and interventional radiology: The Requisites, Elsevier.
Kaufman JA and Lee MJ (Eds) 2004:407-44.
6. PolakJE, Karmel ML, Mannick JA, et al. Determination of extent of lower extremity peripheral arterial disease with
color assisted duplex sonography: Comparison with angiography,AJR 1990;155:1085-89.
7. Alexander JQ, Leos SM, Katz SG: Is duplex ultrasonography an effective single modality for the preoperative
evaluation of peripheral vascular disease? Am Surg 2002;68(12):1107-10.
8. Quwendijk R, Kock MCJM, Dijk LCV, et al. Vessel wallcalcifications at multidetector row CT angiography in
patients with peripheral arterial disease: Effect on clinical utility andclinical predictors, Radiology 241(2)603-608
2006.
9. Nael K, Krishnam M, Nael A, et al. Peripheral contrast enhanced MR angiography at 3.0T, improved spatial
resolution and low dose contrast : Initial clinical experience. Eur Radiol2008;18,2893-900.
10. Valji K (Eds). Upper extremity arteries. In Vascular and Interventional Radiology, WB Saunders 2006;136-53.
11. Kaufman JA. Upper extremity arteries. In Vascular and interventional radiology : The Requisites. Kaufman JA and
Lee MJ (Eds) 2004;142-62. Elsevier.
12. Polak. Color flow and duplex sonography in lower extremity ischaemia Clinical Applications of Doppler
Ultrasound, 2nded. Raven Press 1994;337-54.
13. Rumack CM, Wilson SR, Charboneaus JW (Eds): The Peripheral Arteries in Diagnostic Ultrasound (2nd ed)
1998;921-42.
14. Lavanier GL, Sacks D, Robinson ML. Acute limb ischemia. Em Med Clin of N Amer 1992;10(1):103-19.
15. Valji K (Eds). Pathogenesis of vascular diseases. In Vascular and Interventional Radiology, WB Saunders
1999;38-58.
16. Kaufman JA. Lower- extremity veins. In Vascular and interventional radiology: The Requisites. Mosby 2004;445-
68.
17. Gaitini D. Multimodality Imaging of the Peripheral Venous System. Int.J. Biomed Imaging 2007.
18. Garg K, Mao J. Deep venous thrombosis; spectrum of findings and pitfalls in interpretation on CT venography.
AJR 2001;177:319-23.
19. Reimer P, Landwehr P. Non-invasive vascular imaging of peripheral vessels. Eur Radiol 1998;8:858-72.
20. Phillips GWL, Chang LS. The value of ultrasound in the assessment of incompetent perforating veins. Australas
Radiol 996;40:15.
21. OwenAR, Roditi GH. Peripheral arterial disease;the evolving role of non-invasive imaging.Postgrad Med J;87:189-
198
22. Dixit R.Imaging of Peipheral vascular disease.In Diagnostic Radiology-Chest and Cardiovascular Radiology (3rd
ed)Jaypee Brothers.2010:459-482

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 Management with Endovenous Laser Therapy

Dr. Gulshan Jit Singh

Overview
Chronic venous disorders (CVDs) of the lower extremity are common problems caused by venous hypertension,
which is commonly the result of reflux in one or more of the saphenous veins and their primary tributaries.
Treatment options in patients with saphenous vein incompetence include elimination of these refluxing pathways
using minimally invasive therapy i.e.,endovenous techniques. These include Endovenous Laser Ablation (EVLA),
Radiofrequency Ablation (RFA)and Foam Sclerotherapy . In this article we will be discussing EVLA and RFA .
Both procedures are associated with high success and low complication rates. The procedures are generally
performed on an ambulatory basis with local anesthetic and typically require no sedation. The patients are fully
ambulatory following treatment, and the recovery time is short.

Mechanism of action
The mechanism of vein wall injury after ELA is controversial. It has been postulated to be mediated both by direct
effect and indirectly via laser-induced steam generated by the heating of small amounts of blood within the
vein.(1) This causes thermal damage to the endothelium and sub-endothelial layer resulting in focal coagulative
necrosis and shrinkage leading to thrombotic occlusion in the vein (2) Histological studies at 3 and 6 months
following EVLA indicate failure of endothelial regeneration and progressive damage to the muscle layers of the
vein wall resulting in the further shrinkage. (3)

Diode lasers are most commonly used for ELA. Laser generators exist with multiple different wavelengths,
including lower wavelengths that are considered hemoglobin specific and include 810 nm, 940 nm, 980 nm,
and 1064 nm. Higher wavelengths are considered water specific and include 1320 nm and 1470 nm. Although it
is still not definitively established in the literature, some authors suggest that the higher wavelength lasers
produce similar efficacy at lower power settings with less postprocedure symptoms.(4)

It can be performed with multiple different laser fiber designs (ie, bare-tip fibers, jacket-tip fibers , radial fibers)
and diameters available from a variety of vendors. Each of the fiber designs has been demonstrated to be
effective in closing the saphenous vein. At this point, there are no conclusive data demonstrating a superiority of
a given fiber, wavelength and energy deposition combination, efficacy, significant adverse effects, or
complications .

Target Veins
ELA has been successfully and safely used to ablate the great and small saphenous veins .ELA has been used
to treat long straight competent tributary veins outside the superficial fascia, particularly in patients who are
obese and who either sclerotherapy or microphlebectomy would be difficult, time consuming, or prone to side
effects.(5)

Indications
Assessment of patient suitability for EVLA requires ultrasound confirmation of the sites of venous incompetence,
along with historyand physical examination. Indications for endovenous treatment are listed below.

Symptoms affecting quality of life are as follows:

Aching Throbbing
Heaviness Fatigue
Restlessness Night Cramps
Pruritus Spontaneous hemorrhage

Skin changes associated with chronic venous hypertension are as follows:

Eczema, and pigmentation
Lipodermatosclerosis
Atrophie blanche
Healed or active ulceration
Edema
Superficial phlebitis (SVT) in varicose veins

Cosmetic (restorative) concerns are indications for treatment.

Anatomical indications are as follows:
Significant reflux documented on DUS examination (reflux >0.5 seconds)
Straight vein segment
Intrafascial or epifascial vein segment meeting other anatomical criteria that can be pushed away from the skin
with tumescent anesthetic

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 Reflux responsible for venous hypertension leading to the clinical abnormalities Ambulatory patient without
contraindication

Contraindications
Patients who are pregnant or breastfeeding (concerns related to anesthetic use and heated blood effluent that
may pass through the placenta to the fetus)
Obstructed deep venous system inadequate to support venous return after ELA
Liver dysfunction or allergy making it impossible to use a local anesthetic (cold saline may be useful as an
alternative)
Allergy to both amide and ester local anesthetics (cold saline may be an alternative)
Severe uncorrectable coagulopathy (ELA is safe with warfarin use if the international normalized ratio is
between 2 and 3.) (6)
Severe hypercoagulability syndromes (where risk of treatment outweighs potential benefits despite prophylactic
anticoagulants)
Inability to adequately ambulate after the procedure
Sciatic vein reflux
Thrombus or synechiae in the vein or tortuous vein making passage of an endovenous device impossible
(unless multiple access points are chosen)

The use of ELA to close incompetent perforating veins has been described, and studies show a benefit in ulcer
healing and recurrence.(7,8)
Tumescent anesthetic, Large volumes of dilute anesthetic solutions are infiltrated into the perivenous space of
the veins to be treated.
Rationale of its use include as a local anesthetic,
Its ability to empty the vein to maximize the contact of the thermal device and the vein wall for efficient
thermal transfer to the vein wall.
It provides a protective heat sink around the treated vein to minimize heating of adjacent structures.

Dilute tumescent anesthetic solution of lidocaine with or without epinephrine in normal saline, often buffered with
sodium bicarbonate (a concentration of 0.1% lidocaine is typically used with an average volume of about 510
mL/cm of treated vein). This should be delivered with ultrasound guidance into the perivenous space (saphenous
sheath) of the vein to be treated. It can be injected either manually or with an infusion pump, such that upon
completion of the process the vein is surrounded along its entire treated length with the anesthetic fluid, as
demonstrated in the image below.

Transverse ultrasound image of tumescent anesthetic fluid surrounding centrally located great saphenous vein
and laser fiber/sheath.

Equipment
Basic equipment and supplies for ELA are listed below.
Procedure table that can tilt to Trendelenburg and reverse Trendelenburg
DUS with at least a 7.5 MHz transducer
Sterile gowns, gloves, masks, drapes, gauze
Ultrasound gel, sterile ultrasound probe and cord cover
Antiseptic preparation fluid
Local anesthetic
No. 11 scalpel blade, 18-gauge needle
18-gauge needle for percutaneous entry
21- to 25-gauge needle for administration of tumescent anesthesia
Syringes
Normal saline

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 Compression stockings.

Endovenous laser wavelengths commercially available include:

810 nm (AngioDynamics Queensbury, NY)
940 nm (Dornier MedTech Americas, Inc, Kennesaw, Ga)
980 nm (Biolitec, Inc, East Longmeadow, Mass)
1064 nm (Sharplan, Inc., NJ)
1320 nm (CoolTouch, Roseville, Calif)
1470 nm (Biolitec, Angiodynamics)

Limited data are available that compare the different configurations, but anecdotally it is thought that
higher, water-specific wavelengths produce less postprocedure pain with equivalent outcomes.

Positioning
Access to the target vein should be performed with the patient in the supine position. The use of a reverse
Trendelenburg position (feet down) in order to increase pressure in the target vein and increase the likelihood of
a successful puncture is advisable, especially with small-diameter veins. Once the sheath and laser fiber are
inserted as described below, the patient is positioned flat and then in the Trendelenburg position after positioning
the laser fiber at the desired starting location. The Trendelenburg position helps to empty the vein and improve
energy transfer from the fiber to the vein wall. This is particularly important at the upper end of the greater
saphenous vein (GSV), where the vein diameter is larger and the vein is less susceptible to spasm

Technique

1. Perform preprocedural DUS for mapping of the venous segments to be treated. Mark the course of the
vein(s) to be treated and important anatomical landmarks associated with the ablation on the skin,
including the proposed venous access site(s) and deep vein junctions. The access site is ideally at the
inferior end of the incompetent segment or segments of the treated vein. In most cases, the entire
incompetent segment(s) can be treated with 1 puncture. If microphlebectomy will be performed along
with ELA, the veins to be removed should be marked at this time as well.
2. Prepare the operative tray and equipment. Aside from the thermal ablation device and a venous access
kit, only basic supplies such as gauze, a sterilizing solution, sterile barriers, and the tumescent solution,
with delivery syringes and needle and an ultrasound probe cover, are needed.
3. Patient is supine with the leg to be treated flexed and externally rotated at the hip, and the knee slightly
flexed.
4. Carry out sterile preparation and draping of the leg to be treated. Preprocedural antibiotics are not
necessary in almost all circumstances as the procedure is performed sterilely and is considered clean.
5. Visualize the access site with DUS. Placing the patient in a reverse Trendelenburg prior to the venous
puncture keeps the vein more distended and may facilitate venous access.
6. Access site should be just above or below knee ( mid calf for SSV).Anesthetize the access site. Nick the
skin just large enough to facilitate entry of the sheath through the skin.
7. Insert the 18 G needle into the great saphenous vein (GSV) under sonographic guidance.
8. Place a 0.035-in guidewire into the vein.
9. Confirm intravenous placement with ultrasonography.
10. Pass 5 Fr. sheath over the wire and position to the starting point for ablation i.e., 1 cm. distal to the
junction.
11. Remove the wire. Check for venous return by aspirating the syringe attached to the sheath and flush.
Recognize that the sheath tip may be against the vein wall and may not aspirate freely. Also realize that
when flushing, microbubbles of air introduced into the vein may produce an acoustic shadow that may
limit the ability to see venous detail and device positions.
12. Introduce the laser fiber into the sheath so that the fiber reaches the sheath tip. Then fix the laser fiber
and carefully pull back the sheath to expose about 2 cms. of fiber. Then withdraw the entire sheath-laser
fiber to the ablation starting spot.
13. Fine tune the location of the tip of the laser fiber to just below the superficial epigastric vein, anterior
accessory GSV (AAGSV), or other large normal junctional vein for the GSV, and just below the thigh
extension junction with the short saphenous vein (SSV) for SSV ablations. Some operators choose to
position the laser fiber 1-3 cm below the saphenofemoral junction (SFJ) without consideration of the
position of the junctional branches. No data support superiority of any of the above procedures in terms
of ablation success, junctional recurrences, or common femoral vein thrombosis post procedure.

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Longitudinal (sagittal) duplex ultrasound image of the saphenofemoral junction during the positioning of the tip of
a laser fiber during an endovenous laser ablation. The laser tip is in the greater saphenous vein (GSV) just
beyond the superficial epigastric vein (SEV) origin and is marked by the arrow. FV=femoral vein.
14. Connect the laser fiber to its generator and confirm that the tip is in the correct general location by
viewing the visible light aiming beam that can be delivered into the laser fiber tip and visualized through
the skin. This is an additional way to ensure that the tip of the laser is being visualized accurately and
that the laser connections were made appropriately. If the light is not seen in the expected location,
troubleshoot the position of the laser or the connection to the laser to understand why.
15. Administer tumescent anesthesia with ultrasound guidance after the patient has been placed into the
Trendelenburg position to help drain the vein.
16. Place appropriate laser safety goggles on everyone in the procedure room and use other appropriate
laser safety measures. Connect the laser fiber to the laser and verify proper laser settings. Setting
recommendations vary, but aim to deliver at least 7080 J/cm length of vein treated: at 14 W this is
achieved with a pullback rate of 2 mm/s.
17. Set the laser to continuous mode and select the power to be used. Re-verify placement of the laser tip
with ultrasound.
18. Activate the laser and withdraw the fiber and sheath at the speed that is dependent on the amount of
energy you wish to deliver at the power setting selected with the laser in continuous mode. Many
operators deliver 70-100 J/cm at 12 W in continuous mode at 810 nm throughout the length of the
abnormal vein For the GSV and AAGSV, use more energy for the first 10-12 cm (140 J/cm) and less as
the laser tip progresses lower down the leg (100 J/cm to the knee and 70 J/cm below the knee). This is
done to ensure closure of the proximal vein segment just below the deep vein junction, where failure
occurs most, and to decrease the risk of nerve injuries lower in the leg.
For the SSV, the use about 110 J/cm for the first 3-4 cm, then 100 J/cm for the next 3-4 cm, and then
70 J/cm for the remaining vein.
19. Stop laser energy delivery at the distal aspect of the vein and place the laser in standby mode.
20. Remove the fiber/sheath from the vein. Be sure the entire fiber is removed to exclude the possibility of a
fracture of the device intravascularly.

Record the watts, laser on-time, total joules delivered, and length of the segment treated. Calculate the
withdrawal rate and joules delivered per cm to ensure you have reached the targets for success

Pearls
Technique considerations
High rates of vein occlusion and ultimate DUS disappearance was noted in a series where the thermal dose in
each segment of the GSV was tailored to the diameter in that segment. The ranges of energies used to achieve
durable ablation included 50 J/cm for veins 4.5 mm and 120 J/cm for veins >10 mm in diameter. No increase in
complications was seen with any of the higher energy strategies.(9)
In a study comparing Closure Fast (CF) and ELA, equivalent treatment times and anatomical success at 6
months were seen with slightly less immediate postprocedure bruising and postprocedure discomfort noted with
CF.(10)
Excellent anatomic success of 90-100% occlusion rates has been shown for lasers with wavelengths between
810 and 1470 nm.(11) Recently, the 1470-nm radial laser fiber has been shown to have the lowest amount of
postprocedure bruising, pain, parasthesia, induration, and superficial phlebitis due to the water-specific
wavelength that is thought to directly act on the vessel wall.(12) Moreover, this study showed equivalent anatomic
success of 99.6% closure at 1 year following use of the 1470-nm radial fiber.

Complications

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Adverse events and complications
Adverse events following ELA occur, but almost all are minor.
Ecchymosis over the treated segment frequently occurs and normally lasts for 7-14 days.
About one week after ELA, the treated vein may develop a feeling of tightness similar to that after a
strained muscle. This transient discomfort, likely related to inflammation in the treated vein segment, is
self-limited and may be ameliorated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs),
ambulation, stretching, and graduated compression stockings.
Superficial phlebitis is another uncommon side effect of ELA, being reported after about 5% of
treatments as mentioned previously. There are no published reports of superficial phlebitis after ELA
progressing to deep vein thrombosis and it has been managed in most series with NSAIDs, graduated
compression stockings, and ambulation.
Neurologic injuries The overall rate of these complications has been shown to be higher in low-volume
centers than high-volume centers. The nerves at highest risk include the saphenous nerve, adjacent to
the GSV below the mid-calf perforating vein, and the sural nerve adjacent to the SSV in the mid and
lower calf. Both of these nerves have only sensory components. The most common manifestation of a
nerve injury is a paresthesia or dysesthesia, most of which is transient. The nerve injuries can occur with
the trauma associated with catheter introduction, during the delivery of tumescent anesthesia, or by
thermal injury related to heating of the perivenous tissues.
In general, paresthesias caused by ELA are usually temporary with the rate of permanent
paresthesias typically reported for GSV and SSV as 010%.
Skin burns following ELA have been reported. Skin burns are fortunately relatively rare and seem to be
avoidable with adequate tumescent anesthesia.
DVT following ELA is unusual. DVT can occur as an extension of thrombus from the treated truncal vein
across the junctional connection into the femoral or popliteal veins. The reported rates of junctional
thrombosis following GSV ELA varies widely. This variability may relate to the time of the follow-up
examination and the methods used. Most published series using early DUS (around 72 hours or less
after ELA) document a proximal extension for the GSV around 1%.
Endothermal heat-induced thrombosis (EHIT) defines the extent of superficial thrombosis and its
extension into the deep venous system as proposed by Kabnick.(13)
EHIT 1 represents thrombus up to the SFJ. EHIT 1 is treated conservatively.
EHIT 2 represents thrombus extending into the femoral vein occupying less than 50% of luminal
diameter. If identified, EHIT 2 is usually treated with anticoagulation (full or prophylactic intensity are
both used), although some advocate early re-examination and conservative care for more minor forms.
EHIT 3 represents thrombus occupying greater than 50% of femoral vein luminal diameter.
EHIT 4 represents occlusive thrombus in the femoral vein.
EHIT 3 and 4, which are much less common, probably merit full anticoagulation.
Those performing the DUS at a later interval identify a lower rate of EHIT. Possibly, the rates are
different for different operators with different protocols or the proximal extension of thrombus may be
self-limited and may resolve by 1 month without a clinical event.The incidence of junctional extension of
thrombus after SSV ablation has also been described to be low (0-6%).
Neovascularity at the SFJ after ELA, as a form of recurrence of varicose veins, seems to be rare at 1-
to 3-year follow-up.. Neovascularization may be less common following endovenous procedures
because the junctional tributary flow, which was usually ligated at their confluence with the SFJ, is
generally not affected with GSV ELA.
Case reports of laser fiber fracture or retained venous access sheaths have been made.
.
Postoperative Care and Instructions
The most common recommendation is for class II compression stockings (3040 mm Hg) applied immediately
after the procedure and worn for 12 weeks. The clinical value of this practice is not substantiated by data.
Anecdotally, patients feel better with the use of compression, especially during the second week when the pulled-
muscle feeling occurs.

Patients are encouraged to ambulate for at least 3060 minutes after leaving the procedure room and at least 1
2 hours daily for 12 weeks.

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Hot baths, running, jumping, heavy lifting, and straining are discouraged by many physicians for 12 week.
NSAIDs may be taken on an as-needed basis for discomfort.

Some physicians recommend a follow-up Duplex 4872 hours after the procedure to rule out junctional thrombus
extension into deep vein. Extension of thrombus beyond the deep junction extending into the femoral vein for
GSV or popliteal vein for SSV ablation is at most 1%. Moreover, treatment of such nonocclusive extensions is
controversial and increasingly conservative care is recommended.

Patients are generally seen at 1 month after the procedure to assess the results by clinical examination and DUS

Repeat Duplex Ultrasound at about 9-12 months after the procedure ultimately determines the anatomical
success of the ablation.

Results of Treatment
General comments
ELA is safely and effectively performed using local anesthesia in an office setting requiring about 4590 minutes
of room time to be performed. Procedure times are dependent on the number of concurrent treated veins, length
of segment(s) treated, and whether ancillary procedures, such as ambulatory phlebectomy, are carried out.
Patient satisfaction has been reported to be very high.

GSV Occlusion
Observational studies report GSV closure rates of 94 100 % (assessed by duplex ultrasound ) with relief of
symptoms and improvement in the appearance of superficial varicosities. For most studies the follow up was less
than a year (14,15) whilst that for the study reporting 100% success was only 2 weeks (16) In a later report Min et
al (17) described the outcome in almost 500 patiets followed for upto 3 years. GSV occlusion rates were 98% at
one month and 93% at 2 years (n=121). Delivery of 70-80 J/cm results in optimum GSV/SSV occlusion rates.

Small Saphenous Vein Occlusion

A potential risk to use of EVLA at this site is effect of heat on the common peroneal nerve and its branches that
are in close proximity to te SPJ and proximal SSV. The tumescent anaesthesia should eliminate the potential for
significant nerve injury.The risk of sural nerve injury can be further minimized by canulating the SSV at or above
the mid-point of the calf , the point at which the nerve normally joins the vein. There are reports of SSV ablation in
a total of 78 limbs which describe the success rates of 95% and 97 %(15,16) Although the follow up was
relatively short in these studies (Median of 3 months), the results are encouraging.

The total cost (cost of the procedure plus societal cost) of endovenous procedures is likely equal to or better than
that of surgery. This is debatable in a hospital setting, but is almost certainly true if the ELA can be performed in a
nonspecialized office setting. These techniques are being rapidly adopted and are now being performed more
often than traditional HL/S in the United States.

Anatomical success rates

The anatomical outcomes following endovenous treatment include
Occlusion of the treated segment,
Early failure (complete or segmental).
Late recanalization (complete or segmental).

Anatomic success following ELA should result in the treated vein having no lumen and either shrink to a fibrous
cord < 2.5 mm in diameter or become sonographically absent 612 months after treatment. Anatomical success
with ELA of the GSV has been reported between 93100%. The follow-up for these evaluations varies from 3
months to 4 years.

Fewer data are published following SSV ablation with ELA but the results are qualitatively similar to that found
with GSV ablations.

Patients with a high body mass index have been shown to have a higher rate of failure with laser.(18) The
rationale for this observation is unclear, although it is known that obese patients have higher central venous
pressures and a higher frequency of chronic venous disease. ELA success has been demonstrated in a
retrospective data review to be independent of vein diameter in many studies. However, a prospective
confirmation of this conclusion has not been performed.

Evaluation of Clinical Outcomes

Clinical outcomes from varicose vein ablation can be quantified by numerous reporting systems
Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) classification.
Revised Venous Clinical Severity Score (VCSS)
Aberdeen Varicose Vein Questionnaire (AVVQ)

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 Chronic Venous Insufficiency Questionnaire (CIVIQ) 2.
Venous Insufficiency Epidemiological and Economic Study (VEINES).
Varicose Veins (VV) Symptoms Questionnaire (VVsymQ). The VVsymQ may be the best patient-
reported metric because it has been approved by the FDA for use in device and drug trials. Summary

Since its introduction, ELA has replaced ligation and stripping procedures of the GSV and SSV to eliminate
reflux. The procedure has been validated to result in reliable elimination of saphenous vein reflux, is safe, well
tolerated, and durable. In addition, it has been shown to produce less periprocedural pain, shortening the
recovery to allow for earlier return to work.

Radiofrequency Ablation Therapy for Varicose Veins

Technology
The original radiofrequency endovenous ablation system worked by thermal destruction of venous tissues using
electrical energy passing through tissue in the form of high-frequency alternating current. This current was
converted into heat, which causes irreversible localized tissue damage. Radiofrequency energy is delivered
through a special catheter with deployable electrodes at the tip; the electrodes touch the vein walls and deliver
energy directly into the tissues without coagulating blood. The newest system, called ClosureFast, delivers
infrared energy to vein walls by directly heating a catheter tip with radiofrequency energy.

Energy delivery
In the original radiofrequency catheter system, the catheter was pulled through the vein while feedback is
controlled with a thermocouple to a temperature of 85C to avoid thermal injury to the surrounding tissues or
carbonization of the vein wall. With the new system, the catheter is held in place while energy heats the catheter
to a specified temperature of 120C. As the vein is denatured by heat, it contracts around the catheter.

With the previous-generation radiofrequency system, as shrinkage and compaction of tissue occurred,
impedance was decreased which decreased heat generation; however, this is no longer the case. Only the
temperature of the catheter metal core is monitored as it delivers heat to the vessel wall in 20-second increments.
Previously, the radiofrequency generator could be programmed to rapidly shutdown when impedance rose, thus
assuring minimal heating of blood but efficient heating of the vein wall. In the present system, catheter core
temperature is monitored and adjusts energy to keep the core at 120 C. Heat delivered to the vein wall causes
the vessel to shrink in the treated area, and the catheter is gradually withdrawn along the course of the vein until
the entire vessel has been treated. This is performed in 7-cm segments.

Catheters
Many different radiofrequency ablation catheters are available for medical applications, but the Closure catheter,
manufactured by VNUS Medical Technologies, is the only commercially available radiofrequency ablation system
designed for venous ablation.

Radiofrequency ablation console (VNUS Medical Technologies) showing time, temperature, and power (in
watts).
Closure radiofrequency ablation catheters in 2 sizes (VNUS Medical Technologies).

Histologic Findings
Immediately after treatment, biopsy specimens show a significant reduction in the size of the vein lumen, with
denudation of endothelium, thrombus formation, thickened vessel walls, loss of collagen birefringence, and
inflammatory changes. The zone of thermal damage is limited to 2 mm beyond the point of contact with the
electrodes.

In more than 90% of patients, biopsy specimens demonstrate complete occlusion of the vein lumen 6 weeks after
treatment. The lumen is completely ablated in most areas, with some portions of the vessel demonstrating a
small residual lumen containing organized fibrous thrombi. Birefringence is present, and new collagen growth is
evident.
Technique

Radiofrequency ablation catheters cannot be easily passed along a tortuous superficial vein; therefore, the
procedure is principally of use in the treatment of truncal varicose veins, such as the great saphenous vein.
Radiofrequency ablation is also used with small saphenous vein incompetence.

Preprocedure
Duplex ultrasonography is used to confirm and map all areas of reflux and to trace the path of the refluxing great
saphenous trunk from the saphenofemoral junction down the leg to the lower thigh or upper part of the calf. The
vein, the saphenofemoral junction, and the anticipated entry point are marked in same way on the skin. An

351
appropriate entry point is selected just above or just below the knee, at a point permitting cannulation of the
vessel with a 16-gauge needle introducer.

Procedure
The leg is prepared and draped, and a superficial local anesthetic agent is used to anesthetize the site of
cannulation. Needle puncture of the vessel is guided by duplex ultrasonography. The Seldinger technique is used
to place a guidewire into the vessel, and an introducer sheath is passed over the guidewire, which is removed.
The ClosureFast catheter is passed through the sheath, and the tip is advanced to 2 cm below the
saphenofemoral junction under duplex ultrasonographic visualization.

With ultrasonographic guidance, a local anesthetic agent is injected into the tissues surrounding the great
saphenous vein above and within its fascial sheath. The anesthetic is injected along the entire course of the vein
from the catheter insertion point to the saphenofemoral junction. In most patients, 200-400 mL of lidocaine 0.1%
is sufficient to both anesthetize and compress the vessel. Note the importance of delivering the anesthetic agent
in the correct intrafascial location, with a volume sufficient to compress the vein and dissect it away from other
structures, such as nerves, along its entire length.

Duplex ultrasonography is used to position the catheter tip 2 cm below the level of the terminal valve of the
saphenofemoral junction. The catheter must not extend into the femoral vein because injury to the femoral vein
may cause deep vein thrombosis.

In the previous radiofrequency ablation system, when the console is switched on and the test mode is activated,
the baseline impedance should be 250-300 ohms and the baseline temperature should be 32-37C. When
radiofrequency energy is applied, the thermocouple temperature should rise to 80-85C within 10-15 seconds. In
the new system, when the radiofrequency is activated, the catheter core temperature should rapidly rise to 120C
and should be sustained for 15 seconds of the 20-second pulse cycle. If the temperature does not rise quickly, a
malpositioned catheter tip should be strongly suspected.

In the previous system, after the temperature reaches 85C and remains constant for 15 seconds, the catheter tip
is slowly withdrawn at a rate of approximately 1 cm per minute (1 mm every 6 seconds). In the new system, two
20-second cycles are performed in the proximal section, after which the catheter is withdrawn 7 cm as per
catheter markings. The next 20-second cycle is repeated once, and, if 120C is maintained, the catheter is then
withdrawn another 7 cm until the entire vein is treated.

When proper tumescent anesthesia is applied, the patient should never experience a sudden heat sensation. If
this happens, more anesthesia is injected.

Postprocedure
Posttreatment duplex ultrasonography confirms the contraction of the vessel and the absence of flow along the
entire length of the treated vessel. In the previous system, if persistent flow is observed, the procedure may be
repeated immediately, provided the catheter can still be easily passed along the vessel to the desired site of
treatment. In the new system of ClosureFast, the procedure is not repeated because the targeted vessel typically
shows no flow.
Follow-up Care

Compression is of vital importance after any venous procedure. Compression is effective in reducing
postoperative bruising and tenderness, and it can also reduce the risk of venous thromboembolism in both the
treated leg and the untreated leg.

A class II (30- to 40-mm Hg gradient) compression stocking is applied to the treated leg, and, if the patient is
willing, it is also applied to the untreated leg. Bed rest and lifting of heavy objects are forbidden, and normal
activity is encouraged.

The patient is reevaluated 3-7 days after the operation, at which time duplex ultrasonography should demonstrate
a closed greater saphenous vein and no evidence of thrombus in the femoral, popliteal, or deep veins of the calf.
At 6 weeks, an examination should reveal clinical resolution of truncal varices, and an ultrasonographic
evaluation should demonstrate a completely closed vessel and no remaining reflux. If any residual open
segments are noted, sclerotherapy is performed under ultrasonographic guidance.

Complications
Reported complications of the procedure are rare.
Local paresthesias can occur from perivenous nerve injury but are usually temporary.
Thermal injury to the skin was reported in clinical trials when the volume of local anesthetic was not
sufficient to provide a buffer between the skin and a particularly superficial vessel, especially below the
knee.

352
 Progression of thrombus from local superficial phlebitis has occasionally been observed when
compression was not used. The greatest current area of concern is deep vein thrombosis, with one
2004 study documenting deep vein thrombus requiring anticoagulation in 16% of 73 limbs treated with a
radiofrequency ablation procedure.(28,29,30)

Outcomes
Published results show a high early success rate with a very low subsequent recurrence rate up to 10 years after
treatment. Early and mid range results are comparable to those obtained with other endovenous ablation
techniques. In one of the series, there has been a 90% success rate, with rare patients requiring a repeat
procedure in 6-12 months. Overall efficacy and lower morbidity have resulted in endovenous ablation techniques
replacing surgical stripping.

Patient satisfaction is high and downtime is minimal, with 95% of patients reporting they would recommend the
procedure to a friend.

A study by Bush et al indicated that perforating veins are the most frequent cause of recurrent varicose veins
after radiofrequency or laser ablation. Of 2380 patients involved in the study, 164 had a recurrence of varicose
veins, with the median period to recurrence being 3 years. Among the patients who experienced recurrence, 159
had undergone great saphenous vein ablation as their initial treatment, including 52 who had concurrently
undergone small saphenous vein or anterior accessory great saphenous vein ablation. Along with perforating
veins (64% of patients), the most common factors behind varicose vein recurrence were as follows.(31)
Recanalized great saphenous vein (29% of patients)
New anterior accessory great saphenous vein reflux (24% of patients)
New small saphenous vein reflux (15% of patients)

Features

It was also found that a higher rate of recanalization occurred with radiofrequency ablation than with the laser
procedure.

Intuitive user interface includes colors, symbols, large fonts and clear instructional messages

Large color screen

Continuous real-time temperature and power feedback
Tones communicate procedure status and prompt user

Newer Modality using Laser with Foam

L.A.FO.S. ( Laser Assisted Foam Sclerotherapy )
Dr. A Frullini MD, Florence, Italy presentation at UIP-2015, 27-29 August,2015,Seoul, Korea
This is a new approach to the incompetent saphenous veins. Holmium laser having 2100-nm wave length is used
and energy delivered between 2.5 5 watts. This causes thermal shrinkage due to Type III collagen fibres of the
vein in tunica media without affecting the tunica intima.Intima integrity is prerequisite for good sclerosis with foam.
Vein diameter is reduced so less volume of the foam is required. As soon as he fibre is retrieved, foamis
immediately injected through the same sheath. Larger vein diameters upto 2 cms. Vein can be treated with this.

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