Alterations in Colonic Mucosal Vessels in Patients With Cirrhosis and Noncirrhotic Portal Hypertension

LAURA W. LAMPS, MD, CHRISTINE M. HUNT, MD, ANNETTE GREEN, MPH, GEORGE F. GRAY, JR, MD, AND KAY WASHINGTON, MD, PHD
Changes in intestinal mncosal microvasculature as a cause of lower gastrointestinal hemorrhage in patients with portal hypertension have been well documented clinically, but the analogous histomorphological changes have not been well characterized. The goal of this study was to evaluate qualitative and quantitative changes in colonic mucosal vessels in patients with cirrhosis or clinically evident portal hypertension and to correlate these changes with endoscopic and clinical findings. Colon biopsy or resection specimen slides from 46 patients with biopsy-proven cirrhosis (44 patients) or noncirrhotic portal hypertension (two patients) were reviewed. Immunoperoxidase stain for CD34 antigen was used to facilitate visualization of mucosal vessels, and vessel diameter was measured with a micrometer. Patients with inflammatory bowel disease were excluded. Twentyfour normal colon biopsy specimens served as controls. Mucosal vessels were divided into superficial, intermediate, and deep layers. As a group, the cirrhotic patients had a significantly higher mean diameter of vessels in all three layers. Qualitatively, increased numbers of small vessels and prominent branching were noted, especially in the superficial and intermediate layers. Tortuous, thick-walled vessels, suggesting arterialization of venules, were present in some cases. Eleven patients had endoscopic findings suggestive of vascular abnormalities, including erythematous mucosal patches, red macules, and telangiectasias. Eighteen had esophageal varices, and five had portal gastropathy. Nineteen patients had gastrointestinal (GI) bleeding, localized to the lower GI tract in 11. These qualitative and quantitative findings suggest that colonic mucosal vascular lesions are common in portal hypertension and may represent a potential source of clinically significant lower GI hemorrhage in these patients. HUM PAxnoL 28:527-535. Copyright 1998 by W.B. Saunders Company Key words: portal colopathy, portal hypertension, cirrhosis, colon, vascular ectasias. Abbreviations: GI, gastrointestinal; H&E, hematoxylin-eosin.

A l t h o u g h h e m o r r h o i d s a n d r e c t a l varices a r e rep o r t e d to b e t h e m o s t c o m m o n causes o f l o w e r gastrointestinal (GI) b l e e d i n g in p a t i e n t s with p o r t a l h y p e r t e n sion, ~,2 t h e r e has r e c e n t l y b e e n i n c r e a s e d i n t e r e s t in c h a n g e s o f t h e i n t e s t i n a l m u c o s a l m i c r o v a s c u l a t u r e as a cause o f b o t h a c u t e a n d c h r o n i c l o w e r GI t r a c t h e m o r r h a g e in this p o p u l a t i o n Y T h e m o r p h o l o g i c a l f e a t u r e s o f p o r t a l g a s t r o p a t h y a r e well defined7-1; however, a n a l o g o u s c h a n g e s o f t h e m u c o s a l vessels w i t h i n t h e small b o w e l a n d c o l o n have n o t b e e n extensively studied or characterized. E n d o s c o p i c a l l y , c o l o n i c m u c o s a l c h a n g e s in patients with p o r t a l h y p e r t e n s i o n have i n c l u d e d t e l a n g i e c tasias o r a n g i o d y s p l a s i a - l i k e l e s i o n s , e r y t h e m a t o u s p a t c h e s , a n d varices; 2,4,n t h e s e lesions have b e e n rep o r t e d t h r o u g h o u t t h e e n t i r e c o l o n . 6 T h e clinical signific a n c e o f t h e s e v a s c u l a r lesions, t h e i r r e l a t i o n s h i p to t h e severity o f t h e u n d e r l y i n g liver disease, t h e risk o f b l e e d i n g a s s o c i a t e d with t h e m , a n d t h e i r a s s o c i a t i o n with p o r t a l g a s t r o p a t h y a r e n o t well e s t a b l i s h e d . I n this study, we e v a l u a t e d t h e qualitative a n d q u a n t i t a t i v e c h a n g e s in c o l o n i c m u c o s a l vessels in 46 p a t i e n t s with c i r r h o s i s o r clinically e v i d e n t p o r t a l h y p e r t e n s i o n a n d c o r r e l a t e d t h e m with e n d o s c o p i c a n d clinical findings. From the Department of Pathology, Varlderbilt University Medical Center, Nashville, TN; the Department of Medicine, Duke University Medical Center, Durham, NC; and Independent Consultant in Biostatistics, Durham, NC. Accepted for publication September 3, 1997. Address correspondence and reprint requests to Kay Washington, MD, PhD, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232. Copyright 1998 by W.B. Saunders Company

MATERIALS AND METHODS

Patients with histologically proven cirrhosis or noncirrhotic portal hypertension were identified by searching the surgical pathology files of Duke University Medical Center and Vanderbilt University Medical Center. A subset of 46 of these patients (44 patients with cirrhosis, two with noncirrhotic portal hypertension) had colon biopsies (59 specimens) or resections (six specimens: two, right colon; one, transverse colon; two, entire colon; one, sigmoid colon) available for review. Medical records for each patient were reviewed to confirm that the patient was cirrhotic at the time the colon biopsy or resection specimen was obtained, for signs and symptoms of portal hypertension, and for estimated duration of cirrhosis. The following were considered indicative of portal hypertension: splenomegaly, esophageal varices, portal gastropathy, and evidence of hypersplenism such as thrombocytopenia. Other information recorded included the cause of cirrhosis, indication for colonoscopy or resection, and findings at endoscopy or surgery. The presence of rectal varices or hemorrhoids was noted, as well as descriptions of the colonic mucosa suggestive of vascular lesions such as red macules or telangiectatic lesions. Patients with inflammatory bowel disease or prior abdominal surgery were excluded from the study. Resection specimens from patients with adenocarcinoma of the colon were also excluded. A group of 24 control colon biopsy specimens was chosen randomly from recent cases with no diagnostic abnormality. Medical records were reviewed to determine that none of these 16 patients had known liver disease or inflammatory bowel disease, and that none had undergone previous abdominal surgery. All colon biopsies or resection specimens were fixed in buffered formalin and processed routinely. At least two hematoxylin and eosin (H8cE)-stained levels were available for review for each biopsy. An immunoperoxidase stain for CD34 (HPCA-1, Becton Dickinson, San Jose, CA; 1:10 dilu-

0046-8177/98/2805-001658.00/0

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HUMAN PATHOLOGY

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tion) was performed to facilitate visualization of mucosal vessels in all cases with available blocks. Vessel diameter was measured on the CD34-stained slides at 400 magnification with a calibrated ocular micrometer. For one case, no block was available, and vessels were measured on the H&E-stained slide. The area of greatest vascular dilatation was chosen, and all identifiable vessels were measured in 5 to 10 high-power fields. The mean vessel diameter was calculated for superficial, intermediate, and deep mucosal vessels. The Wilcoxon test for unpaired data, a nonparametric test based on a ranking system and reputed to have a high degree of efficiency, was used to determine whether there were a significant difference in mean vessel dilatation between cases and controls.
RESULTS Normal Mucosa

The vessels in normal colonic mucosa from control cases were classified into three layers: superficial, intermediate, and deep vessels (Fig 1). Superficial vessels were defined as the chainlike layer of small capillaries, lying just beneath the surface epithelial cells. This layer was inconspicuous on H&E-stained sections of normal colon and was better visualized on CD34-stained sections. Intermediate vessels were defined as the vessels in the midportion of the lamina propria. In normal mucosa, these vessels rarely had identifiable branches and were often vertically oriented. Deep vessels were defined as the layer of vessels immediately adjacent to the muscularis mucosae; these were usually seen in cross section in well-oriented specimens. No site-specific differences in vascular diameter were shown in the control biopsy specimens, which consisted of 14 specimens from the left colon or rectum, five from the cecum or right colon, and five r a n d o m biopsy specimens.
Cirrhosis

t h o u g h there was overlap between the groups as illustrated by the frequency histograms for each layer of vessels (Figs 2-4). For the superficial layer of vessels, the mean vessel diameter in 17 of 65 biopsy specimens or resections fell outside the range of the control cases. For the intermediate layer o f vessels, the mean vessel diameter in 31 cases fell outside the range of control cases. For the deep layer of vessels, the mean vessel diameter in 33 cases fell outside of the range of the control cases (Fig 5). Subtle degrees of vascular dilatation (defined as vascular luminal diameter greater than the u p p e r range of the control cases) were difficult to recognize on H&E-stained slides and were more readily appreciated on the CD34-stained sections. Many of the biopsies contained dilated vessels in more than one layer. Fourteen patients had dilated vessels in two layers only; seven had dilated vessels in all three layers. A total of 34 of 46 patients (73.9%) with cirrhosis or noncirrhotic portal hypertension had dilated vessels in at least

TABLE | , Mean Diameter of Colonic Mucosal Vessels in Patients With Cirrhosis or Noncirrhotic Portal Hypertension and Controls
Cirrhosis/Portal Hypertension (N = 65 specimens, 46 patients) Superficial vessels Mean diameter (tam) Range Standard deviation P Intermediate vessels Mean diameter (lam) Range Standard deviation P Deep vessels Mean diameter (pro) Range Standard deviation P Controls (N = 24 specimens, 16 patients)

7.84 4.03-22.68 3.15 <<.001 12.86 6.92-31.68 4.64 <<.001 15.50 3.78-26.41 6.93 <<.001

5.27 3.354.50 1.11

9.07 5.38-13.83 2.22 9.03 6.04-13.61 2.52

Vessels in colon biopsy specimens and resection specimens from cirrhotic patients had significantly higher mean diameters in all three vessel layers than mucosal vessels in the control group (Table 1), al528

COLONIC MUCOSAL VESSELSIN CIRRHOSIS (Lamps et al) 16

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one layer. Twelve cirrhotic patients had no dilated vessels in any of the three layers. Qualitative changes in mucosal vessels were noted in addition to quantitative changes in vascular diameter.

Thin-walled superficial vessels were diffusely dilated and tortuous and often congested in biopsy specimens from some cirrhotic patients. Thickened vascular walls were not seen in this superficial layer. In other patients, the

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associated inflammation, was p r o m i n e n t in specimens from five patients (Fig 9). An increased density of small vessels in the lamina propria was focally present in an additional 26 specimens from 17 patients. In all but one of these specimens, dilation of mucosal vessels was present in other areas. Colonic crypts in p r o m i n e n t areas of increased vascular density were lost or distorted, but diffuse mucosal architectural changes of chronic colitis were not seen in any case (Fig 10). O t h e r mucosal changes included slight mucosal edema (three cases), reactive changes in crypt epithelium (three cases), focal infiltration of the lamina propria by neutrophils (three cases), and focal mucosal architectural distortion (13 cases) consisting of d r o p o u t

Range, Vessel Diameter in microns

increase in vascular diameter in the superficial layer was focal and more readily visible on the CD-34-stained section than on H&E stain (Fig 6). In general, vascular dilatation involving this layer was more difficult to identify than in other layers. Similarly, in some cirrhotic patients, the intermediate vessels were more tortuous (Fig 7), and the branches were more readily seen than in normal mucosa. In resection specimens and some biopsy specimens with abundant submucosa, dilated submucosal vessels that narrowed as they traversed the muscularis mucosae were seen; in most cases, these vessels had thin walls, but in others a thickened muscular layer was present (Fig 8). A granulation tissue-like proliferation of densely packed small vessels, without

FIGURE 5. Dilated vessels in the intermediate and deep layers of the colonic mucosa. (Hematoxylin and eosin, original magnification x400). 530

FIGURE 6. CD 34 staining highlights a dilated, branched vessel in the superficial layer. (Indirect immunoperoxidase staining for CD34, original magnification 400.)

COLONIC MUCOSAL VESSELSIN CIRRHOSIS(Lamps et al)

FIGURE 7. Markedly tortuous vessel in intermediate layer of mucosa. (Hematoxylin and eosin, original magnification x400,)

of occasional crypts and minor degrees of distortion in crypt orientation (Fig 10). Branching crypts were not present. The mononuclear inflammatory cell infiltrate in the lamina propria was in general sparse, although it was slightly increased in five specimens from patients with dilated vessels. No increase in chronic inflammatory cells was seen in any of the biopsy specimens without dilated vessels from patients with cirrhosis or noncirrhotic portal hypertension. On endoscopic exami-

FIGURE 9. Granulation tissue-like proliferation of densely packed small vessels without associated inflammation, (Hematoxylin and eosin, original magnification 200),

FIGURE 8. Dilated deep vessel which traverses the muscularis mucosae. (Hematoxylin and eosin, original magnification 400.)

FIGURE 10. Architectural changes including crypt dropout and mild distortion can mimic quiescent inflammatory bowel disease, (Hematoxylin and eosin, original magnification x l00.)

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nation, four patients, all with dilated mucosal vessels, had mucosal friability or other changes suggestive of colitis. Biopsy specimens in two of these cases showed focal crypt distortion; the mncosa in the other two biopsy specimens was edematous, and in one biopsy specimen, rare small collections of neutrophils were present in the lamina propria. Cirrhotic patients with dilated colonic mucosal vessels were more likely to have portal gastropathy, hemorrhoids, and lower gastrointestinal hemorrhage than those with vessels of normal diameter (Table 2), although these associations were not statistically significant when compared using Fisher's exact test. They were less likely to have had episodes of upper GI hemorrhage, although the prevalence of esophageal varices was roughly the same as in the cirrhotic patients who did not have dilated colonic mucosal vessels. The specific location of the dilated vessels (superficial, intermediate, or deep layer) was not significantly associated with gastrointestinal hemorrhage. Dilated intermediate vessels were more likely to occur in the left colon, but for many cases random biopsy specimens were taken, or the precise biopsy site was not specified, making correlation of vascular changes with site difficult. Endoscopic findings suggestive of vascular lesions in cirrhotic patients with dilated vessels on histologic examination included patchy erythema, punctate red macules, telangiectasia, and, in one patient, visualization of a bleeding vessel in the cecum (Table 3). Biopsy specimens of mucosa that appeared normal to the endoscopist rarely showed mucosal vascular changes. Biopsy specimens of mucosal erythema suggestive of colitis or lesions characterized as "vascular" on endoscopy showed vascular abnormalities in more than half the cases (Table 3). Erythema or endoscopic findings suggestive of vascular changes were seen in 3 of 12 cirrhotic patients without dilated vessels on histologic examination. One of these patients had findings suggestive of cecal angiodysplasia; no biopsy of the cecum was obtained, and the sigmoid, which underwent biopsy and was histologically unremarkable, was free of macroscopic lesions suggestive of vascular abnormalities. Another patient who underwent endoscopy to rule out
TABLE 2.

inflammatory bowel disease had rectal erythema, thought to be secondary to preparation for endoscopy; the biopsy specimen in this case was also normal. A third patient with cecal erythema had focal acute colitis on biopsy, without dilated vessels. In all six cases with resection specimens, the indication for surgery was active lower GI bleeding. Dilated deep vessels were identified in all six specimens; in addition, two had dilated intermediate vessels, and three had dilated superficial vessels. Biopsy specimens from 12 patients with portal hypertension contained vessels of normal diameter in all three layers. There was no difference in the prevalence of esophageal or gastric varices in this group compared with the cirrhotic group with dilated vessels. Cirrhotic patients without dilated mucosal vessels were more likely to have had previous episodes of upper GI hemorrhage but were less likely to have had lower GI hemorrhage or hemorrhoids. No cases of portal gastropathy were identified in the cirrhotic patients without dilated colonic vessels who had undergone upper GI endoscopy.
Clinical Features

The mean age of the patients with cirrhosis or noncirrhotic portal hypertension was 53.2 years (range, 18 to 82 years), compared with a mean age of 57.1 years (range, 36 to 75) for the control group. In the cirrhosis group, 17 of the patients were women and 29 were men, compared with 10 women and six m e n in the control group. No relationship between cause of cirrhosis and changes in colonic mucosal vessels was noted (Table 4). Indications for colonoscopy in the cirrhotic group included screening for colon polyps/carcinoma (eight patients), exclusion of inflammatory bowel disease in three patients with primary sclerosing cholangitis, evaluation of diarrhea (seven patients), and evaluation of gastrointestinal bleeding or anemia (14 patients). The indication for surgery in all six resection cases was lower GI bleeding. Twenty-six cirrhotic patients had upper gastrointestinal endoscopy, which revealed esophageal varices in eighteen, gastric varices in three, and portal gastropathy in five. Nineteen patients had prior epi-

Endoscopic and Clinical Features of Patients With Cirrhosis or Noncirrhotic Portal Hypertension
Dilated Vessels, Any Layer Dilated Superficial Vessels 18/46 (39.1%) 54.9 7/1;[* (63.6%) 1/11" (9.1%) 2/11" (18.2%) 1 (5.6%) 4 (22.2%) 5 (27.8%) 7 (38.8%) 2 (11.1%) 6 (33.3%) 3 (25.0%) Dilated Intermediate Vessels 17/46 (40.0%) 56.8 6/8* (75.0%) 1/8" (12.5%) 3/8* (37.5%) 2 (11.1%) 4 (22.2%) 5 (27.8%) 3 (13.6%) 3 (13.6%) 11 (50.0%) 5 (22.7%) Dilated Deep Vessels 25/46 (54,3%) 51.1 10/12" (83,0%) 2/12" (16,7%) 4/12" (33.3%) 3 (11.5%) 8 (30.8%) 8 (30.8%) 10 (38.5%) 2 (7.7%) 12 (46.2%) 9 (34.6) No Dilated Vessels 12/46 (26.1%) 57.3 5/8* (62.5%) 1/8" (12.5%) 0/8* (0.0%) 4 (33.3%) 1 (8.3%) 1 (8.3%) 2 (16.7%) 2 (16.7%) 5 (41.7%) 3 (25%)

No. of patients Mean age (yr) Esophageal varices Gastric varices Portal gastropathy UGI hemorrhage LGI hemorrhage Hemorrhoids Site: Right colon Transverse Left colon Unknown

34/46 (73.9%) 49.8 13/17" (76.5%) 2/17" (11.8%) 5/17" (29.4%) 4/34 (11.8%) 10/34 (29.4%) 10/34 (29.4%) 12/48 4/48 19/48 13/48 (25%) (8.3%) (39.6%) (27.1%)

*Denominator represents number of patients who underwent upper gastrointestinal endoscopy.

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TABLE 3.
Findings

Colonoscopic Findings in Patients With Cirrhosis or Noncirrhotic Portal Hypertension

Dilated Vessels, Any Layer 6/19" (31.6%) 4/19" 2/19" 2/19" 2/19" 1/19" (21.0%) (10.5%) (10.5%) (10.5%) (5.3%) Superficial Vessels Dilated 5/10" (50.0%) 3/10" 1/10" 1/10" 2/10" (30%) (10%) (10%) (20%) 0 Intermediate Vessels Dilated 3/10" (30%) 3/10" 1/10" 2/10" 1/10" (30%) (10%) (10%) (10%) 0 Deep Vessels Dilated 6/16" (37.5%) 4/16" (25%) 1/16" (6.3%) 0 1/16" (6.3%) 1/16" (6.3%) No Dilated Vessels 3/6* (50.0%) 0 0 0 2/6* (33.3%) 1/6" (16.7%)

Endoscopic Vascular lesions "Colitis" Prominent fold or ileocecal valve Ulcer Diverticular Normal

*Denominator represents number of patients ,adth available endoscopic reports.

sodes of GI bleeding, localized to the lower GI tract in 11. Eleven patients had hemorrhoids, specified as internal in eight and external in one. Indications for colonoscopy in the control group of 16 patients were evaluation of diarrhea (13 patients), abdominal pain (two patients), and screening/surveillance for colon polyps (one patient).
DISCUSSION

Mterations in colonic mucosal vasculature, as visualized on endoscopic examination in patients with cirrhosis or noncirrhotic portal hypertension, have been recognized in the clinical literature for some time and given various names, including "portal colopathy, ''6 "portal hypertensive colopathy, ''5 and "portal hypertensive intestinal vasculopathy. ''3 Descriptions of the endoscopic appearance of the lesions noted in these studies include cherry red spots (similar to those described in portal gastropathy), spider telangiectasias, and angiodysplasia-like lesions. 2,4-6,11Mucosal erythema, friability, and granularity suggestive of colitis have also been described in these patients. 11-13 In some of these studies, few of the patients u n d e r w e n t biopsy of the lesions because of the risk of bleeding. 11However, in the cases with biopsies, descriptions of the microscopic findings include dilatation and tortuosity of mucosal vessels, as well as increased numbers of small vessels with thickened walls in the lamina propria. 3,5 Our results show that mucosal vascular dilatation and ectasia, present in 72% of our cases, are c o m m o n in the colon in portal hypertension. In addition to the quantitative changes in vascular diameter, qualitative changes, such as thickening of the vessel walls, inTABLE 4.
Cause Autoimmune hepatitis Alcohol Hepatitis B Hepatitis C PBC PSC Secondary biliary cirrhosis Noncirrhotic PHT NASH Cryptogenic Total 3 8 3 9 5 3 2 2 2 12

creased density of small vessels, and tortuousity, are also present in many of the cases. Large dilated vessels, some with thickened walls, were seen traversing the muscularis mucosae into the lamina propria from the submucosa; these vessels most likely represent ectatic venules. Endoscopic findings in these patients were similar to those reported in other studies of portal colopathy 4-6,11 and included patchy erythema, punctate red macules, and telangiectasias. No particular cause for the cirrhosis of portal hypertension was associated with the presence of portal colopathy, as reported by other investigators. 2,4,6,11O f the patients with cirrhosis who u n d e r w e n t u p p e r GI endoscopy, only those with colonic mucosal vascular changes had portal gastropathy. Gastrointestinal bleeding localized to the lower GI tract was more c o m m o n in patients with portal colopathy; u p p e r gastrointestinal tract h e m o r r h a g e was more c o m m o n in those without dilated colonic mucosal vessels. Esophageal varices were not particularly associated with portal colopathy, and they were present in most patients with portal hypertension. Recognition of these vascular changes on biopsy of the colonic mucosa can be difficult. At one end of the spectrum, there is considerable overlap with normal vascular architecture, and it is difficult if not impossible to recognize simple vascular dilatation on routine histological preparations. Furthermore, vascular dilatation without structural changes (such as tortuosity and vessel wall thickening) in the microanatomy of the blood vessels is not specific and can be seen in inflammatory disorders or even as an artifact of biopsy. In an effort to clarify terminology, some investigators have proposed that the term ectasia be reserved for this combination of dilatation and structural changes in

Causes of Cirrhosis/Portal Hypertension

Dilated Intermediate Vessels 1 1 1 2 2 2 1 1 1 5 Dilated Deep Vessels 2 4 2 4 3 0 2 0 2 7 No Dilated Vessels 0 3 0 4 1 0 0 0 0 4

Dilated Superficial Vessels 1 3 0 1 2 2 1 0 1 5

Abbreviation: NASH, nonalcoholic steatohepatitis.

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blood vessels. 3 Ectatic vessels, as defined in this way, can be readily recognized as abnormal on routine H&E histological preparations. The pathogenesis of these lesions remains unclear. H u m a n and animal studies have shown that chronic portal hypertension is associated with increased blood flow t h r o u g h o u t the entire gastrointestinal tract and with decreased vascular resistanc@ 4 although other investigators report that mucosal blood flow is diminished 15,16 or that the mucosa is relatively ischemic. 17,1s This increased vascular pressure may lead to an increase in capillary filtration and subsequent dilated vessels and mucosal e d e m a ? 4 This chronic increase in vascular pressure also may explain the thickening of small venular walls (arterialization) noted in many of these cases. The vascular dilatation in portal colopathy bears some resemblance to the changes seen in angiodysplasia of the colon, and both entities can cause lower GI bleeding, sometimes massive. 19 Naveau et al 2 have shown that although the lesions of portal colopathy are similar to angiodysplasia, the angiodysplastic lesions contained fewer dilated capillaries, and these were smaller in diameter. Angiodysplastic lesions were also less widely distributed than the lesions of portal colopathy. 2 Angiodysplasia is considered by many to be a degenerative process attributable to repeated partial intermittent obstruction of submucosal veins from muscular contraction of the colon. 21 In portal colopathy, the increased venous pressure is probably sustained rather than intermittent and may be of greater intensity, thus leading to more p r o n o u n c e d and widespread lesions. We found that alterations of colonic mucosal vessels were seen in patients with similar changes in gastric mucosal vessels (portal gastropathy), although this finding was not statistically significant in our study. However, this association has also been reported by other investigators, with 42% to 50% of patients with portal colopathy also having portal gastropathy on u p p e r GI endoscopy.4'6'11 Whereas in most reports patients with portal colopathy also had esophageal varices, 5 in our study, an equal n u m b e r of patients with esophageal varices did not have identified vascular changes in the colon on biopsy. Other investigators r e p o r t no correlation between severity of esophageal varices and portal colopathy. 2,11 Although some studies r e p o r t that patients with portal colopathy are more likely to have bled from esophageal varices, our study did not support this finding. 5 It has been reported that alterations in colonic mucosal vessels can cause clinically significant GI bleeding in a subset of patients with portal h y p e r t e n s i o n y ,5,6 although determining the likelihood of bleeding from this lesion is problematic. We know from previous studies that the presence of portal gastropathy can lead to heine-positive stools without overt bleeding episodes, 22 making it difficult to determine whether the source is the u p p e r or lower GI tract. In addition, anorectal varices and hemorrhoids are very c o m m o n causes of lower GI tract bleeding in cirrhotic patients, 12 and these lesions are also very c o m m o n in patients with

the mucosal vascular changes of portal colopathy. 4,5 In our study, dilatation of colonic mucosal vessels was associated with lower GI hemorrhage, and other investigators 2,3,5,6have f o u n d a similar association. However, in the most striking example of portal colopathy in our study, the patient did not have a history or present with lower GI hemorrhage, and the lesion was f o u n d when the patient u n d e r w e n t colonoscopy for evaluation of diarrhea. Therefore, although the changes of portal colopathy may potentially cause GI bleeding in a subset of patients, determining the likelihood of clinically significant bleeding for an individual patient with the lesion remains problematic. Some endoscopic studies report changes suggestive of colitis, such as mucosal granularity and friability in patients with portal hypertension. 6,11,12 Histological examination often shows e d e m a and a nonspecific increase in chronic inflammatory cells in the lamina propria. Minor distortion of mucosal architecture also has been reported. In our study, focal collections of neutrophils were seen in a few cases, and some biopsy specimens showed slight mucosal distortion. The major significance of this finding is that these changes should probably not be interpreted as subtle evidence of ulcerative colitis, in the absence of more substantial evidence. ~,6 Kozarek et al 6 have suggested that the increase in inflammatory cells may be due to increased penetration of gut luminal antigens into the lamina propria. The architectural distortion suggests an elem e n t of chronic mucosal ischemia, and studies of mucosal perfusion in portal gastropathy suggest that, despite the increased blood flow, the gastric mucosa is relatively u n d e r p e r f u s e d and ischemicJ 7,1s A similar mechanism in the colonic mucosa may be responsible for the minor architectural changes. In summary, we believe that recognition of the changes of portal colopathy is important, because this lesion may cause clinically significant lower GI tract bleeding in a subset of patients. We propose the following strategy and terminology for evaluating colon biopsy specimens from patients with portal hypertension. First of all, we cannot overemphasize the importance of correlation with clinical history. To make meaningful clinicopathological correlations in these patients, it is critical that the pathologist be told the indication for colonoscopy and that the patient has cirrhosis or portal hypertension. Although the endoscopic findings are nonspecific, these should also be communicated, and the site of biopsy should be specified. The pathologist should c o m m e n t on the presence or absence of vascular changes in the mucosa, reserving the term ectasia for vascular dilatation with structural abnormalities. 3 The presence of a granulation tissuelike proliferation of small thick-walled vessels and tortuous ectatic vessels is relatively specific for mucosal changes caused by portal hypertension, a and the term portal colopathy should be applied only to these welldeveloped changes. It also should be recognized that a nonspecific increase in chronic inflammatory cells in the lamina propria and m i n o r degrees of mucosal architectural distortion often accompany these changes

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COLONIC MUCOSAL VESSELSIN CIRRHOSIS(Lamps et al)

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