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Descripción general de la cirugía en el tratamiento del cáncer de


páncreas exocrino y pronóstico
Autores: Carlos Fernández del Castillo, MD, Ramon E Jimenez, MD
Editores de secciones: Stanley W Ashley, MD, Kenneth K Tanabe, MD
Editores Adjuntos: Wenliang Chen, MD, PhD, Diane MF Savarese, MD

Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de revisión por pares .

Revisión de literatura vigente hasta mayo de 2019. | Este tema se actualizó por última vez el 14 de marzo de 2019.

INTRODUCCIÓN

Aproximadamente 56,770 personas desarrollan cáncer pancreático exocrino cada año en los Estados Unidos, y se
espera que casi todas mueran a causa de su enfermedad [ 1 ]. La incidencia global y por país, y las tasas de
mortalidad, están disponibles en la base de datos Globocan de la Organización Mundial de la Salud .

La mayoría de los cánceres pancreáticos exocrinos (85 por ciento) son adenocarcinomas que surgen del epitelio
ductal. La resección quirúrgica es el único tratamiento potencialmente curativo.

Aquí se revisará una descripción general del tratamiento quirúrgico de los cánceres del páncreas exocrino. Las
manifestaciones clínicas, el diagnóstico y la terapia quirúrgica y no quirúrgica se tratan por separado. (Consulte
"Manifestaciones clínicas, diagnóstico y estadificación del cáncer pancreático exocrino" y "Resección quirúrgica de
lesiones de la cabeza del páncreas" y "Resección quirúrgica de lesiones del cuerpo y la cola del páncreas" y
"Tratamiento para exocrinas potencialmente resecables cáncer de páncreas " .)

CANDIDATOS PARA LA RESECCIÓN

La resección quirúrgica es el único tratamiento potencialmente curativo. Desafortunadamente, debido a la


presentación tardía de la enfermedad, solo entre el 15 y el 20 por ciento de los pacientes son candidatos para una
pancreatectomía. El pronóstico del cáncer de páncreas es malo incluso en aquellos con enfermedad potencialmente
resecable, y a pesar del progreso en las técnicas quirúrgicas y la terapia adyuvante, la evidencia de que los
resultados mejoran con el tiempo es equívoca. (Consulte "Resultados de la pancreaticoduodenectomía 'a
continuación y " Tratamiento para el cáncer pancreático exocrino potencialmente resecable " .)

Sin embargo, en un estudio de la National Cancer Database, entre los candidatos para la resección del cáncer de
páncreas, al 38 por ciento no se le ofreció cirugía [ 2 ]. La subutilización de la cirugía para el cáncer de páncreas en
etapa temprana puede estar relacionada con factores socioeconómicos y con el pesimismo de los médicos con
respecto al pronóstico de la enfermedad.
La evaluación de imagen preoperatoria determina la candidatura para la resección. La estadificación radiográfica y el
papel de la ecografía endoscópica (USE) se discuten en detalle en otra parte. (Consulte "Manifestaciones clínicas,
diagnóstico y estadificación del cáncer pancreático exocrino", en la sección "Estudios de imágenes" y "Ecografía
endoscópica en la estadificación del cáncer pancreático exocrino" .)

La enfermedad que se limita al páncreas es más probable que se cure con resección, aunque aproximadamente el 30
por ciento de las personas que se someten a una resección completa (R0) de un cáncer de páncreas con afectación
ganglionar limitada también pueden ser sobrevivientes a largo plazo ( figura 1 ) [ 3 ]. Los tumores con participación
limitada de los principales vasos peripancreáticos, como la vena mesentérica superior, la vena porta, la arteria
mesentérica superior o la arteria hepática pueden ser técnicamente resecables. Sin embargo, el impacto de las
resecciones más agresivas (particularmente la resección arterial) en el pronóstico a largo plazo es controvertido.
(Consulte "Resección vascular" más abajo y "Resección quirúrgica de las lesiones de la cabeza del páncreas",
sección "Evaluación vascular" ).

Algunos casos se consideran resecables "en el límite", aunque la definición es variable. Algunos reservan el término
"borde resecable" para los casos donde hay un pilar tumoral focal (menos de la mitad de la circunferencia) de las
arterias viscerales o una oclusión de segmento corto de la vena mesentérica superior (SMV) o
SMV / portalconfluencia de venas. Otros sugieren que el estrechamiento venoso sin oclusión debe incluirse en la
definición de enfermedad resecable límite. El encierro (más de la mitad de la circunferencia de la vena) u oclusión de
la SMV o la confluencia de la vena porta de la SMV se consideró previamente no resecable. Sin embargo, muchos
centros han demostrado la viabilidad de la reconstrucción por SMV, y siempre que la reconstrucción venosa sea
posible, muchos consideran que ahora representa una enfermedad resecable límite. Aunque la resección de vena
agrega una medida de complejidad a la pancreaticoduodenectomía, un equipo quirúrgico experimentado en un centro
de alto volumen puede realizar una resección de manera segura cuando sea necesario. Varios grupos han emitido
directrices para definir la enfermedad resecable límite basada en estudios de imagen. Este tema se discute en detalle
en otra parte. (Ver"Manifestaciones clínicas, diagnóstico y estadificación del cáncer pancreático exocrino", en la
sección "Definiciones de enfermedad no resecable y resecable límite" y "Resección vascular" a continuación.)

Patients who have borderline resectable or locally advanced unresectable pancreatic cancer, but no metastatic
disease, are potential candidates for downstaging with neoadjuvant therapy and should be referred for medical
oncology and radiation therapy consultation. There have been reports that when surgery is performed after
neoadjuvant chemotherapy in such patients, the rates of lymph node positivity, perineural invasion, and positive
margins were lower compared with when surgery was performed without neoadjuvant chemotherapy, and that long-
term survival is possible [4,5]. (See 'Role of neoadjuvant chemotherapy' below and "Initial chemotherapy and radiation
for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer".)

Contraindications — Absolute contraindications to resection include the presence of metastases in the liver,
peritoneum, omentum, or any extra-abdominal site. Other indications of unresectability include encasement (more
than one-half of the vessel circumference) or occlusion/thrombus of the superior mesenteric artery; unreconstructable
SMV or SMV-portal vein confluence occlusion; or direct involvement of the inferior vena cava, aorta, or celiac axis, as
defined by the absence of a fat plane between the low-density tumor and these structures on computed tomography
(CT) scan or EUS. After neoadjuvant chemotherapy, radiological changes of encasement, particularly around the
arteries, do not necessarily reflect involvement by tumor [4]. (See "Clinical manifestations, diagnosis, and staging of
exocrine pancreatic cancer", section on 'Definitions of unresectable and borderline resectable disease' and "Initial
chemotherapy and radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine
pancreatic cancer" and 'Staging laparoscopy' below and "Clinical manifestations, diagnosis, and staging of exocrine
pancreatic cancer", section on 'Importance of peritoneal cytology'.)

The presence of ascites is not necessarily a contraindication to attempted resection unless peritoneal cytology is
positive. However, the management of patients with isolated positive peritoneal washings at the time of staging
laparoscopy is controversial. The presence of these cells is associated with a worse prognosis in patients with
otherwise resectable disease [6], and the American Joint Committee on Cancer (AJCC) tumor, node, metastasis
(TNM) staging system considers positive peritoneal washings to represent distant metastatic disease (table 1). In
general, most patients who have cytologically positive washings have other findings that suggest advanced disease
and unresectability such as extensive ascites and/or the presence of metastases in the liver, pelvis, or omentum.
However, if these are absent, most pancreatic surgeons would not rely solely upon the results of peritoneal washings
obtained at the time of laparoscopy to guide decision making regarding resectability. (See "Clinical manifestations,
diagnosis, and staging of exocrine pancreatic cancer", section on 'Importance of peritoneal cytology'.)

PREOPERATIVE CONSIDERATIONS

Staging laparoscopy — Currently available imaging techniques are highly accurate at predicting unresectable
disease, but they fall short in predicting resectable disease, mainly because of limited sensitivity for small-volume
metastatic disease. Radiographically occult metastases (<1 cm in diameter) on the surface of the liver or peritoneum,
which are rarely visible by computed tomography (CT), magnetic resonance imaging (MRI), or transabdominal
ultrasound, may be visualized laparoscopically. This also includes patients with a tumor of the body or tail of the
pancreas who appear to have potentially resectable disease by CT scan (one-half of whom will have occult peritoneal
metastases), large (>3 cm) primary tumors, any patient for whom high-quality imaging is in any way suggestive of
occult metastatic disease, and those with a high initial CA 19-9 level (>100 units/mL).

A selective approach to staging laparoscopy maximizes yield by limiting the procedure to those with the highest
likelihood of occult metastatic disease. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic
cancer", section on 'Staging laparoscopy' and "Surgical resection of lesions of the head of the pancreas", section on
'Staging laparoscopy' and "Surgical resection of lesions of the body and tail of the pancreas", section on 'Staging
laparoscopy'.)

Role of preoperative biliary drainage — Patients with pancreatic cancer who are jaundiced at presentation are at
risk for perioperative complications. Some surgeons advocate an endoscopically placed stent prior to surgery while
others reserve decompression for patients with a bilirubin of >20 mg/dL, with signs of cholangitis, or in those for whom
surgery will be delayed for longer than two weeks. In practice, jaundiced patients may have already undergone biliary
stenting before resectability or the time frame for resection has been determined, given that they are frequently initially
seen by a gastroenterologist. (See "Supportive care of the patient with locally advanced or metastatic exocrine
pancreatic cancer", section on 'Stents' and "Endoscopic stenting for malignant pancreaticobiliary obstruction" and
"Surgical resection of lesions of the head of the pancreas", section on 'Preoperative biliary drainage'.)

Role of neoadjuvant chemotherapy — The low rate of resectability, the poor long-term outcomes following
pancreaticoduodenectomy with adjuvant therapy, and the fact that prolonged recovery prevents the delivery of
postoperative adjuvant chemotherapy in approximately one-fourth of patients [7] have led to the investigation of
neoadjuvant therapy in patients with potentially resectable pancreatic exocrine cancer. This approach has become
standard for individuals with borderline resectable pancreatic cancer. (See "Initial chemotherapy and radiation for
nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer".)

While neoadjuvant therapy can be safely delivered to patients with localized, potentially resectable pancreatic cancer
without adversely influencing perioperative morbidity or mortality, no study has clearly demonstrated improved
resectability or survival compared with patients treated with surgery alone, and it remains unclear whether this
approach provides benefit compared with modern adjuvant (postoperative) therapy. Furthermore, whether the
neoadjuvant approach should include radiation therapy, which chemotherapy combination is optimal in the
neoadjuvant setting, and the optimal duration of neoadjuvant therapy remain unanswered questions. Randomized
trials are urgently needed.

At most institutions, neoadjuvant therapy is not yet considered a standard approach for patients with potentially
resectable pancreatic cancer outside of the context of a clinical trial. Eligible patients should be encouraged to enroll in
trials testing novel strategies. This subject is discussed in detail elsewhere. (See "Treatment for potentially resectable
exocrine pancreatic cancer", section on 'Neoadjuvant therapy'.)

TUMORS IN THE HEAD OF THE PANCREAS

Pancreaticoduodenectomy — The conventional operation for pancreatic cancer of the head or uncinate process is
pancreaticoduodenectomy. Conventional pancreaticoduodenectomy (ie, Whipple procedure) involves removal of the
pancreatic head, duodenum, first 15 cm of the jejunum, common bile duct, and gallbladder, and a partial gastrectomy
(figure 2). Modifications of the conventional pancreaticoduodenectomy procedure have been developed in an attempt
to improve outcomes or minimize the morbidity associated with the operation. These include:

● Pylorus-preserving pancreaticoduodenectomy – Pylorus-preserving pancreaticoduodenectomy preserves the


gastric antrum, pylorus, and proximal 3 to 6 cm of the duodenum, which is anastomosed to the jejunum to restore
gastrointestinal continuity (figure 3). The procedure may decrease the incidence of postoperative dumping,
marginal ulceration, and bile reflux gastritis that can occur in some patients undergoing partial gastrectomy. The
available data suggest that, for suitable cases, perioperative morbidity and mortality and long-term survival are
not adversely affected using a pylorus-preserving technique. (See "Pylorus-preserving
pancreaticoduodenectomy" and "Surgical resection of lesions of the head of the pancreas".)

● Subtotal stomach-preserving pancreaticoduodenectomy – Subtotal stomach-preserving


pancreaticoduodenectomy aims to preserve as much stomach as possible while minimizing problems related to
delayed gastric emptying that are associated with preserving the pyloric ring in the face of a loss of vagal
innervation [8,9]. (See "Surgical resection of lesions of the head of the pancreas", section on 'Pylorus-preserving
pancreaticoduodenectomy'.)

Minimally invasive (laparoscopic, robotic-assisted) pancreaticoduodenectomy is technically feasible. However, even


with the available technology, minimally invasive pancreaticoduodenectomy is a complex operation that is only suited
for selected patients. Robotic-assisted pancreaticoduodenectomy has not reduced rates of perioperative morbidity (eg,
pancreatic fistula) or mortality [10]. (See "Surgical resection of lesions of the head of the pancreas", section on 'Open
versus minimally invasive'.)

Vascular resection — Vascular resection and reconstruction at the time of pancreaticoduodenectomy is


controversial because of the added complexity of the operative procedure and the poor quality of the published data
that examine whether vascular resection represents a poor prognostic factor for survival duration (mainly due to the
lack of information as to completeness of resection). (See 'Candidates for resection' above.)

Because of these issues and the inability to consistently determine the presence or absence of tumor adherence or
invasion preoperatively, practice guidelines have suggested making decisions about vascular resection at the time of
surgery after the pancreatic neck has been divided [11]. Although this is a controversial area, our position is that
pancreaticoduodenectomy with portal vein (PV) or superior mesenteric vein (SMV) resection and reconstruction
should be considered a standard approach for pancreatic adenocarcinomas that focally involve the PV or SMV,
provided that adequate inflow and outflow veins are present, the tumor does not involve the superior mesenteric artery
or hepatic artery [12], and an R0/R1 resection can be accomplished [13]. By contrast, we do not advocate arterial
resection and reconstruction. These resections (mostly the superior mesenteric and hepatic arteries) are performed
infrequently, and few data are available to support the practice [14-16]. Morbidity and mortality increases markedly
when arterial resection and reconstruction is performed [17,18].

The available data suggest that patients with tumors involving the PV appear to be no more likely to have positive
lymph nodes or poor prognostic histologic parameters (eg, aneuploidy) than those without portal vein involvement,
suggesting that vein invasion is a function of tumor location rather than an indicator of aggressive tumor biology [19-
21]. Whether perioperative mortality rates are different is unclear:

● Single-center reports that largely reflect highly selected patients treated at high-volume institutions report similar
morbidity and perioperative mortality rates and comparable survival durations of patients who undergo venous
resection and reconstruction versus those who do not, as long as a macroscopically complete (R0 or R1)
resection has been accomplished [22-24]. A systematic review of 12 such reports concluded that portal
vein/superior mesenteric vein resection combined with pancreatectomy is a safe and feasible procedure that
increases the number of patients who undergo curative resection and therefore provides important survival
benefits to selected groups of patients [25].

● However, in contrast to these data from single-center analyses, analysis of data on 3582 patients undergoing
pancreatectomy for pancreatic cancer and derived from the American College of Surgeons National Surgical
Quality Improvement Program database suggests significantly higher rates of postoperative morbidity (39.9
versus 33.3 percent) and mortality (5.7 versus 2.9 percent) in patients who undergo pancreaticoduodenectomy
with, as compared to without, vascular resection [26]. This database includes patients treated at institutions with
different levels of expertise, and it is likely that in many, if not most, cases the vascular resection was unplanned.
These two factors could contribute to the higher perioperative morbidity and mortality rates.

Regional pancreatectomy — Regional pancreatectomy involves resection and reconstruction of the superior
mesenteric vein-portal vein confluence and extensive en bloc regional lymph node dissection. However, the morbidity
of a regional pancreatectomy is higher than that associated with conventional pancreaticoduodenectomy, and there is
no apparent improvement in either local control or survival when a regional pancreatectomy is performed [27-29].

Extent of lymphadenectomy — Standard lymphadenectomy for pancreatoduodenectomy should strive to resect


lymph node stations 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b (figure 4) [30]. Some groups (mainly
in Japan) routinely perform extensive lymph node dissection (extended lymphadenectomy including all 8, 9, all 12, all
14, 16a2, and 16b1 lymph nodes) in conjunction with pancreaticoduodenectomy, since periampullary malignancies
frequently metastasize to lymph nodes that are beyond the confines of the conventional pancreaticoduodenectomy
[31,32]. However, the evidence to support a benefit from extended lymphadenectomy is conflicting, with some trials
suggesting benefit limited to the setting of positive nodes [33], others suggesting no survival benefit in any subgroup
[34-36], and two suggesting worse quality of life following extended lymphadenectomy [34,35].

A systematic review of standard versus extended lymphadenectomy during pancreaticoduodenectomy included 938
patients from nine studies (including four randomized trials [33-35,37]) [38]. Overall survival was no different between
the groups at one, three, or five years. Outcomes were not stratified according to nodal status. The risk for some
complications was significantly increased in the extended lymphadenectomy group (lymphatic fistula odds ratio [OR]
6.1; 95% CI 1.0-35.3; delayed gastric emptying OR 2.0, 95% CI 1.2-3.5; OR bile leak 2.6, 95% CI 1.0-6.7; OR
pancreatic leak 1.7, 95% CI 1.0-2.9). The analysis was limited by differences in the ranges of lymphadenectomy from
several studies, differences in the proportion of patients with different adjuvant therapies, and differences in the
diagnostic criteria used for complications and overall mortality. Nevertheless, extended lymphadenectomy does not
appear to convey any survival benefit and may be associated with increased perioperative morbidity and compromised
quality of life, particularly in the early postoperative period. Pancreaticoduodenectomy with standard
lymphadenectomy is the operation of choice.

Outcomes of pancreaticoduodenectomy — The prognosis for resection of adenocarcinoma of the head of the
pancreas remains poor even with pancreaticoduodenectomy with surgically negative margins. Large series show five-
year survival rates of only 10 to 25 percent and median survival between 10 and 20 months [39-45].

Although previously associated with high perioperative morbidity and mortality rates, perioperative mortality of
pancreaticoduodenectomy in modern series is less than 4 percent [39,46-51]. This relatively low perioperative
mortality rate represents a decline from over 15 percent in the 1970s.

One of the most important reasons for this improvement is the greater experience of a more limited number of
surgeons who perform the procedure on a regular basis in high-volume hepatobiliary centers [52-55]. The relationship
between surgeon and hospital volume, and postoperative mortality and survival after pancreatic cancer surgery, was
addressed in a meta-analysis of 14 studies [56]. There was a significant association between hospital volume and
postoperative mortality (OR 0.32, 95% CI 0.16-0.64) as well as overall survival (hazard ratio for death 0.79, 95% CI
0.70-0.89).

Given the increase in the proportion of patients undergoing surgery at higher-volume teaching hospitals, diminished
surgical mortality, and greater use of adjuvant chemotherapy and chemoradiotherapy in more recent years [57], it was
hoped that outcomes from resection would improve over time. However, there are conflicting reports in the literature
regarding progress in the prognosis of resected pancreatic cancer:

● In one report of 396 Medicare patients residing in 1 of 11 Surveillance, Epidemiology, and End Results (SEER)
reporting registries who underwent resection of pancreatic cancer with curative intent between 1991 and 1996,
the three-year survival rate was 34 percent, a rate that compares favorably with published reports from the earlier
literature [58]. In multivariate analysis, one of the strongest predictors for survival was the use of adjuvant
chemoradiotherapy; both median survival and three-year survival rates were significantly higher among those who
received it compared with those who did not (29 versus 12.5 months, and 45 versus 30 percent, respectively).
(See "Treatment for potentially resectable exocrine pancreatic cancer", section on 'Chemoradiotherapy'.)

Similarly, a comparison of outcomes following pancreatectomy over two different time periods (1991 to 2000 and
2001 to 2010) in a single high-volume academic institution revealed significantly lower rates of perioperative
mortality (1.6 versus 6.76 percent), a greater number of lymph nodes resected (17 versus 7), higher rates of
adjuvant therapy use (63 versus 30 percent), and significantly longer survival among patients treated during the
later time period (median 27 versus 16 months, five-year survival 27 versus 15 percent) [59].

Improvements in outcomes over time were also noted in a Korean series comparing outcomes for 746 patients
treated between 2000 and 2009 with those of 1283 patients treated between 2010 and 2016 [60]. Five-year
survival rates were 27.6 versus 22.3 percent in the two groups.

● In contrast to these data, a lack of progress in long-term survival over time was noted in a large series of 1147
pancreatic resections performed over three decades at the Memorial Sloan Kettering Cancer Center [61].
Although patients treated between 2000 and 2009 experienced lower rates of operative mortality and had greater
one-year survival, long-term survival rates were nearly identical for patients treated in the 1980s, 1990s, and
2000s (median 23.2, 25.6, and 24.5 months, respectively). The corresponding five-year survival rates were 17,
20, and 8 percent. These data underscore the need for earlier detection and more effective adjuvant therapies.

TUMORS IN THE BODY OR TAIL

Because ductal adenocarcinomas involving the body or tail of the pancreas usually do not cause obstruction of the
intrapancreatic portion of the common bile duct, early diagnosis is rare; the majority have locally advanced or
metastatic disease at the time of presentation. In the rare patient who appears to have potentially resectable disease
by computed tomography (CT) scan, laparoscopic exploration should precede attempted resection, since a significant
proportion will have occult peritoneal metastases. (See "Clinical manifestations, diagnosis, and staging of exocrine
pancreatic cancer", section on 'Staging laparoscopy'.)

Surgical resection of cancers located in the body or tail of the pancreas consists of a distal subtotal pancreatectomy,
usually combined with splenectomy. Many of these procedures can be performed laparoscopically, which has not
affected the ability to achieve a complete resection. Thus far, oncologic outcomes have not been inferior. Clinical
factors that may influence the choice between an open or laparoscopic approach are reviewed separately. (See
"Surgical resection of lesions of the body and tail of the pancreas", section on 'Open surgical versus laparoscopic
distal pancreatectomy'.)

Outcomes of distal pancreas resection — The scant data available regarding the outcome of surgical resection for
tumors of the body and tail of the pancreas suggest a poor prognosis compared with those with cancers involving the
head of the pancreas [62,63], although this is not a universal finding [64]. In one study, for example, only 13 of 105
patients (12 percent) with cancer of the body or tail of the pancreas had resectable tumors, and median survival was
only 13 months after surgery, with only five patients remaining alive at two years [62].

TUMORS INVOLVING THE ENTIRE GLAND

Total pancreatectomy is sometimes required in order to achieve a microscopically negative resection margin [65-67].
However, the metabolic consequences of total pancreatectomy, which include permanent exocrine insufficiency and
brittle diabetes, have a detrimental impact on quality of life and long-term survival [68-71]. Contemporary data on total
pancreatectomy are lacking, and single-institution series are limited by small numbers [67,72,73].

Total pancreatectomy was first advocated to remove more tissue potentially involved with the malignancy and to avoid
a pancreaticojejunal anastomosis, the source of considerable morbidity and mortality. However, single-institution
studies suggested higher operative morbidity and mortality compared with pancreaticoduodenectomy [68,71,74]. Over
time, perioperative (30-day) mortality has progressively declined; however, as with pancreaticoduodenectomy,
morbidity remains high [73]. A review of the American College of Surgeons-National Surgical Quality Improvement
Program (ACS-NSQIP) database (2005 to 2009) found a mortality rate of 5.4 percent among 166 patients who
underwent total pancreatectomy [51]. Perioperative mortality for pancreaticoduodenectomy (n = 4317) and distal
pancreatectomy (n = 2364) were 2.9 and 1.7 percent, respectively. The incidence of complications was similar
between the procedures at 31.9, 34.7, and 27.8 percent for total pancreatectomy, pancreaticoduodenectomy, and
distal pancreatectomy, respectively.

Long-term oncologic outcomes are not necessarily better following total as compared with partial pancreatectomy
[73,75]. This was illustrated in a retrospective cohort study of 4021 patients who had a pancreatectomy with curative
intent for adenocarcinoma and were reported to the National Cancer Institute Surveillance, Epidemiology, and End
Results (NCI SEER) database between 1998 and 2004 [75]. The following findings were noted:

● Among the 376 patients who had a total pancreatectomy, perioperative mortality rates at one month (8.6 versus
6.3 percent) and three months (13.8 versus 10.8 percent) were not significantly higher than in patients who
underwent partial pancreatectomy. There were no significant differences when the analysis was conducted
separately according to primary tumor site (head, body/tail, unspecified location).

● Kaplan-Meier survival estimates for all three tumor locations demonstrated similar long-term survival after total as
compared with partial pancreatectomy (at three years, 20 versus 15 percent for head, 22 versus 24 percent for
body/tail, and 20 versus 25 percent for unspecified location, respectively).

These data support the use of total pancreatectomy where oncologically appropriate (ie, under conditions where it
would yield a tumor-free resection margin while a conventional Whipple procedure would not). This typically occurs
when a tumor of the pancreatic head extends into the body or tail of the pancreas. Total pancreatectomy also plays a
role in the treatment of some main-duct intraductal papillary mucinous neoplasms (IPMNs), which may involve the
entire length of the pancreatic duct, either continuously or in a multifocal fashion. When both types of pancreatic
resection would provide a tumor-free margin, total pancreatectomy provides no additional benefit. (See "Intraductal
papillary mucinous neoplasm of the pancreas (IPMN): Evaluation and management".)

PROGNOSIS AND PROGNOSTIC FACTORS

As noted above, even in the setting of completely resected, node-negative pancreatic cancer, the majority of patients
die of their disease. The most important prognostic factor for completely resected patients is nodal status. Five-year
survival after pancreaticoduodenectomy is only approximately 10 percent for node-positive disease (even if only one
node is positive [76]), while it is approximately 30 percent for node-negative disease [3].

Tumor stage is the most important prognostic factor. The influence of tumor stage on survival according to the newest
eighth edition tumor, node, metastasis (TNM) staging classification (table 1) can be illustrated by a series of 8960
patients undergoing treatment for potentially resectable pancreatic adenocarcinoma and reported to the Surveillance,
Epidemiology, and End Results (SEER) database between 2004 and 2013 (figure 5) [77].

Although five-year overall survival rates remain poor overall, survival estimates for individual patients are dynamic,
and they may change over time, based upon the time already survived (a concept referred to as "conditional survival").
This was illustrated in a retrospective analysis of 1822 patients undergoing curative-intent surgery for pancreatic
cancer at Johns Hopkins between 1970 and 2008 [78]. The two-year conditional survival at three years (ie, the
probability of surviving to postoperative year 5 given that the patient had already survived three years) was 66 percent,
versus a five-year actuarial survival calculated from the time of surgery of 18 percent. Patients with high lymph node
ratios (the number of metastatic divided by the total number of resected nodes) or positive margins saw the greatest
increases in two-year conditional survival as more time elapsed since treatment.

Only limited prognostic information exists for 5- to 15-year survivors. In an analysis of data from the Surveillance,
Epidemiology, and End Results database of the National Cancer Institute, prognosis continued to improve with
accrued survival beyond five years (table 2) [79]. However, deaths due to pancreatic cancer occurred as late as 20
years after diagnosis. The hazard of overall and pancreatic cancer-related death was highest at year 3 after diagnosis,
declined until year 13, and then remained less than 3 percent per year. Between years 9 and 13, there was still an
approximately 10 percent per year risk of pancreatic cancer-specific death. The hazard of death due to other causes
did not exceed that of pancreatic cancer-related death until 8.75 years post-diagnosis.

In addition to stage, other factors that influence prognosis after resection are the status of the surgical margins
(involved or uninvolved), possibly the width of the surgical margin, tumor differentiation and the presence or absence
of lymphatic invasion within the tumor, both preoperative and postoperative serum CA 19-9 levels, and cigarette
smoking [23,39-42,80-88]. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer".)

However, long-term survival is possible, even in the presence of positive nodes or involved margins. As an example, in
the Charité Onkologie (CONKO)-001 trial examining the benefit of adjuvant gemcitabine, 15 percent of patients
survived five years or more [89]. Among the 53 long-term survivors, 29 (54 percent) had node-positive disease, while
7 (13 percent) had undergone R1 (microscopically positive margins) resection. (See "Treatment for potentially
resectable exocrine pancreatic cancer", section on 'CONKO-001 trial'.)

The number of positive nodes is of prognostic significance. The eighth edition TNM staging system (2017 (table 1))
subdivides node-positive disease according to the number of positive nodes to provide better prognostic stratification
(figure 1) [3]. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer", section on 'Staging
system and the staging workup'.)

Finally, as has been seen in colon and gastric cancer, the total number of nodes examined also impacts prognosis
[90,91]. At least some data support the view that pathologic examination of at least 15 nodes in the pancreatectomy
specimen is necessary to accurately stage a node-negative adenocarcinoma [91].

A postresection nomogram has been developed [92] and validated [90] to predict the probability that a patient will die
of pancreatic cancer within three years of surgery. In addition to the T and N status (according to the seventh edition
[2010] criteria), this nomogram incorporates clinical (age, sex, presence of back pain or weight loss, tumor location),
pathologic (histologic differentiation, tumor size, margin status, number of positive nodes), and surgical (type of
resection) variables. Other nomograms are available that incorporate adjuvant treatment [93], but few have integrated
the eighth edition (2017) American Joint Committee on Cancer (AJCC) staging criteria [94]. (See "Clinical
manifestations, diagnosis, and staging of exocrine pancreatic cancer", section on 'Staging system and the staging
workup'.)

SOCIETY GUIDELINE LINKS


Links to society and government-sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Pancreatic cancer".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient
education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five
key questions a patient might have about a given condition. These articles are best for patients who want a general
overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics
to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info"
and the keyword(s) of interest.)

● Basics topics (see "Patient education: Pancreatic cancer (The Basics)")

● Beyond the Basics topics (see "Patient education: Pancreatic cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Surgical resection is the only potentially curative treatment for pancreatic adenocarcinoma. Unfortunately, because of
the late presentation of the disease, only 15 to 20 percent of patients are candidates for pancreatectomy. (See
'Introduction' above.)

● Absolute contraindications to resection include (see 'Contraindications' above and 'Vascular resection' above and
"Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer", section on 'Definitions of
unresectable and borderline resectable disease'):

• Metastases in the liver, peritoneum, omentum, or any extra-abdominal site.

• Encasement (more than one-half of the vessel circumference) or occlusion/thrombus of the superior
mesenteric artery; unreconstructable superior mesenteric vein (SMV) or SMV-portal vein confluence
occlusion; or direct involvement of the inferior vena cava, aorta, celiac axis, or hepatic artery, as defined by
the absence of a fat plane between the low-density tumor and these structures on computed tomography
(CT) scan or endoscopic ultrasound (EUS). After neoadjuvant chemotherapy, radiological changes of
encasement, particularly around the arteries, do not necessarily reflect involvement by tumor.

● Some cases are considered "borderline" resectable, although the definition is variable. Some reserve the term
"borderline resectable" for cases where there is focal (less than one-half of the circumference) tumor abutment of
the visceral arteries or short-segment occlusion of the SMV or SMV/portal vein confluence. Others suggest that
venous narrowing without occlusion be included in the definition. Several groups have issued guidelines to define
resectability based on imaging. (See 'Candidates for resection' above and "Clinical manifestations, diagnosis, and
staging of exocrine pancreatic cancer", section on 'Definitions of unresectable and borderline resectable
disease'.).
● Patients who have borderline resectable or locally advanced unresectable pancreatic cancer, but no metastatic
disease, are potential candidates for downstaging with neoadjuvant therapy and should be referred for medical
oncology and radiation therapy consultation. (See 'Candidates for resection' above and "Initial chemotherapy and
radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic
cancer".)

At most institutions, neoadjuvant therapy is not yet considered a standard approach for patients with potentially
resectable pancreatic cancer outside of the context of a clinical trial. Eligible patients should be encouraged to
enroll in trials testing novel strategies. (See 'Role of neoadjuvant chemotherapy' above.)

Tumors in the head/uncinate process — For potentially resectable pancreatic cancers within the head or uncinate
process, the standard operation is pancreaticoduodenectomy. (See 'Pancreaticoduodenectomy' above.)

● Cancers of the pancreatic head and uncinate process can be treated by either a conventional or a pylorus-
preserving Whipple operation. No compelling evidence is available to suggest that either of these procedures is
superior to the other, and the preferences of the surgeon and patient should prevail. Although some studies
suggest modestly higher rates of delayed gastric emptying with a pylorus-preserving approach, the impact on
gastrointestinal function remains an open question. (See 'Pancreaticoduodenectomy' above.)

● There is no added benefit to be gained by regional pancreatectomy or extended lymphadenectomy, and we


recommend that these procedures not be performed (Grade 1B). (See 'Regional pancreatectomy' above and
'Extent of lymphadenectomy' above.)

● Total pancreatectomy should be limited to only those cases for which resection of the entire gland is needed to
achieve negative margins. (See 'Tumors involving the entire gland' above.)

● Although this is a controversial area, vein resection and reconstruction is a standard approach for pancreatic
adenocarcinomas focally involving the portal vein or SMV, providing that adequate inflow and outflow veins are
present, the tumor does not involve the superior mesenteric artery (SMA) or hepatic artery, and a macroscopically
complete (R0/R1) resection can be accomplished. (See 'Vascular resection' above.)

● For patients presenting with obstructive jaundice, uncertainty as to the benefit of preoperative drainage has led to
differing approaches. We suggest biliary decompression for selected patients in whom surgery will be delayed for
longer than two weeks (Grade 2C), and we recommend it in the presence of cholangitis (Grade 1B). (See 'Role
of preoperative biliary drainage' above and "Surgical resection of lesions of the head of the pancreas", section on
'Preoperative biliary drainage'.)

Tumors of the tail/body — Surgical resection of cancers located in the body or tail of the pancreas consists of a
distal pancreatectomy, usually combined with splenectomy. We suggest laparoscopic exploration prior to attempted
resection, since a significant proportion will have occult peritoneal metastases (Grade 2B). (See 'Tumors in the body
or tail' above and "Surgical resection of lesions of the body and tail of the pancreas", section on 'Staging laparoscopy'.)

Tumors involving the entire gland — Total pancreatectomy is sometimes needed to achieve a microscopically
negative resection margin. However, the metabolic consequences of total pancreatectomy, which include permanent
exocrine insufficiency and diabetes, have a detrimental impact on quality of life and long-term survival. (See 'Tumors
involving the entire gland' above.)
ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Michael Steer, MD, who contributed to an earlier version of
this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 2482 Version 38.0


GRAPHICS

Survival according to T category and the number of positive nodes for patients undergoing resection
of exocrine pancreatic cancer, stratified according to the revised AJCC 8th edition TNM staging
criteria

(A) Overall survival by T stage of 525 patients who underwent resection for node-negative pancreatic cancer, stratified by proposed AJCC 8th
edition criteria (training set only).
(B) Overall survival by number of positive nodes for all patients who underwent a R0 resection (training set, n = 1551), stratified by proposed
AJCC 8th edition criteria.

T: tumor; AJCC: American Joint Committee on Cancer; TNM: tumor, node, metastasis; R0: no residual tumor.

From: Allen PJ, Kuk D, Castillo CF, et al. Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and
N Staging in Patients with Pancreatic Adenocarcinoma. Ann Surg 2017; 265:185. DOI: 10.1097/SLA.0000000000001763. Copyright © 2017 American
Surgical Association and European Surgical Association. Reproduced with permission from Lippincott Williams & Wilkins. Unauthorized reproduction of
this material is prohibited.

Graphic 111137 Version 1.0


Exocrine pancreatic cancer TNM staging AJCC UICC 8th edition

Primary tumor (T)


T category T criteria

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ.


This includes high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous
neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and
mucinous cystic neoplasm with high-grade dysplasia.

T1 Tumor ≤2 cm in greatest dimension

T1a Tumor ≤0.5 cm in greatest dimension

T1b Tumor >0.5 and <1 cm in greatest dimension

T1c Tumor 1 to 2 cm in greatest dimension

T2 Tumor >2 and ≤4 cm in greatest dimension

T3 Tumor >4 cm in greatest dimension

T4 Tumor involves the celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of
size

Regional lymph nodes (N)


N category N criteria

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in one to three regional lymph nodes

N2 Metastasis in four or more regional lymph nodes

Distant metastasis (M)


M category M criteria

M0 No distant metastasis

M1 Distant metastasis

Prognostic stage groups


When T is... And N is... And M is... Then the stage group is...

Tis N0 M0 0

T1 N0 M0 IA

T1 N1 M0 IIB

T1 N2 M0 III

T2 N0 M0 IB

T2 N1 M0 IIB

T2 N2 M0 III

T3 N0 M0 IIA

T3 N1 M0 IIB

T3 N2 M0 III

T4 Any N M0 III

Any T Any N M1 IV

TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging
Manual, Eighth Edition (2017) published by Springer International Publishing.

Graphic 111135 Version 5.0


Conventional pancreaticoduodenectomy (Whipple procedure; Polya)

Polya refers to the style with which the gastrojejunostomy is constructed.

Graphic 82519 Version 3.0


Pylorus-preserving pancreaticoduodenectomy

Graphic 60689 Version 2.0


Lymph node stations pancreatic cancer

The lymph node drainage of the pancreas is depicted in the figure. The labels correspond to the
lymph node stations as classified by the Japanese Pancreas Society.

Adapted from: Japan Pancreas Society. Classification of pancreatic carcinoma, 2nd English Edition.
Tokyo: Kanehara & Co. Ltd, 2003.

Graphic 96774 Version 2.0


Predicted overall survival for patients with resected pancreatic cancer
according to the eighth edition (2017) American Joint Committee on
Cancer (AJCC) prognostic stage groups

The eighth edition AJCC Staging System predicts overall survival for patients with resected
pancreas cancer and indicates the corresponding number of patients at risk.

Reprinted by permission from: Springer: Annals of Surgical Oncology. Kamarajah SK, Burns WR, Frankel
TL, et al. Validation of the American Joint Commission on Cancer (AJCC) 8th Edition Staging System for
Patients with Pancreatic Adenocarcinoma: A Surveillance, Epidemiology and End Results (SEER) Analysis.
Ann Surg Oncol 2017; 24:2023. Copyright © 2017. https://link.springer.com/journal/10434.

Graphic 113536 Version 3.0


Cancer-specific conditional survival probabilities in pancreatic cancer

Already Cancer-specific conditional survival probabilities (%)


accrued
Total survival time (years)
survival time
(years) 6 9 12 15 18 21

T1 to T2; N0

3 77.3 67.7 63.5 58.5 57.3 57.3

6 87.6 82.2 76.1 74.1 74.1

9 93.8 86.9 84.6 84.6

12 92.6 90.1 90.1

15 97.3 97.3

18 100.0

T3 to T4; N0

3 63.4 53.9 47.6 47.0 45.5 42.6

6 85.1 75.1 74.1 71.8 67.3

9 88.3 87.1 84.3 79.1

12 98.7 95.5 89.6

15 96.8 90.7

18 93.7

T1 to T4; N1

3 51.2 40.0 35.3 30.9 30.9 22.1

6 78.2 69.0 60.5 60.5 43.2

9 88.2 77.3 77.3 55.2

12 87.6 87.6 62.6

15 100.0 71.5

18 71.5

Data from: Swords DS, Mulvihill SJ, Firpo MA, Scaife CL. Causes of death and conditional survival estimates of medium- and long-term survivors of
pancreatic adenocarcinoma. JAMA Oncol 2018; 4:1129.

Graphic 118829 Version 1.0


Contributor Disclosures
Carlos Fernandez-del Castillo, MD Nothing to disclose Ramon E Jimenez, MD Nothing to disclose Stanley W Ashley,
MD Nothing to disclose Kenneth K Tanabe, MD Grant/Research/Clinical Trial Support: Enanta Pharmaceuticals [Liver fibrosis
(EDP2305, EDP2191, EDP6556, EDP7750, EDP5513, EDP2294, EDP6591, EDP6856, EDP7315, EDP3533, EDP4297)]; Zafgen
Pharmaceuticals [Hepatocellular carcinoma (ZGN-1345, ZGN-1136)]. Consultant/Advisory Boards: Best Doctors [GI cancers,
melanoma (Medical care)]; Cancer Expert Now [GI cancers, melanoma (Medical care)]; Advanced Medical [GI cancers, melanoma
(Medical care)]; Leidos [Melanoma, GI cancers (Grant application review for the Congressionally Directed Medical Research
Program)]. Patent Holder: EGF SNP to determine risk for HCC [Cirrhosis, hepatocellular carcinoma]; Use of EGFR inhibitors to
prevent HCC [Cirrhosis, hepatocellular carcinoma]. Equity Ownership/Stock Options: Helix12 [Breast cancer (Company owns IP on
selective estrogen receptor modulators for breast cancer)]. Wenliang Chen, MD, PhD No hay nada que divulgar Diane MF
Savarese, MD Nada que divulgar

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