0016-5107/90/3606-0575$02.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1990 by the American Society for Gastrointestinal Endoscopy

Endoscopic and histologic appearance of the gastric mucosa in patients with portal hypertension S. P. Misra, MO, OM, M. Owivedi, MO, OM V. Misra, MO, S. K. Agarwal, MBBS R. Gupta, MO, S. C. Gupta, MO, FRC Path, MRCP V. P. Mital, MO Allahabad, India

To assess reliability of the endoscopic and histologic appearance of the gastric mucosa for diagnosing portal hypertension, 50 patients with portal hypertension and 1323 controls were studied. Endoscopic evidence of mild gastritis was seen more frequently in patients with portal hypertension than in the control group (42% vs. 13.1%, p < 0.001). The mosaic sign was also seen more frequently in patients with portal hypertension compared with controls (14% vs. 0.9%, P < 0.001). However, the mosaic sign was found to be nonspecific, and the sensitivity for diagnosis of portal hypertension was only 14%. Biopsy specimens from the stomach of all patients with portal hypertension and 100 controls with a normal endoscopic appearance revealed mucosal vascular congestion in 72% of patients with portal hypertension compared with 59% of controls (NS). There was no correlation between endoscopic and histologic evidence of congestive gastropathy. Similarly, there was no correlation between the severity of mucosal vascular congestion and the degree of inflammatory changes observed in the biopsy specimens; both in the control (r = 0.1) and in patients with portal hypertension (r = 0.14). It is concluded that endoscopic and histologic features of the gastric mucosa in patients with portal hypertension are of low sensitivity and nonspecific and cannot be used to diagnose portal hypertension. (Gastrointest Endosc 1990;36:575-579)

During the last few years, the endoscopic and histologic appearance of the gastric mucosa of patients with portal hypertension has been the focus of attention of several investigators.l~9 These features have been labeled by different workers as mild or severe gastritis, hemorrhagic gastritis, erosive gastritis, acute gastric lesions, bleeding gastritis and congestive gastropathy.1-7,9 The importance of these lesions lies in the fact that they have been noted to be responsible for 10 to 70% of bleeding episodes in patients with portal hypertension.l~7 Papazian et al. 8 observed during endoscopy erythematous areas, outlined by a subtle yellowish network, which they labeled the mosaic pattern and found

to be more sensitive and specific than esophageal varices for diagnosing portal hypertension. However, in an earlier study,lO this sign was noted to be of high specificity but very low sensitivity. The overall predictive value was only 74%. Similarly, the histologic signs of capillary dilation and ectasia seen in biopsy specimens of gastric mucosa, though noted to be of high predictive value by some,5,7,8 have been found to be nonspecific9 and of no use lO by others. The present study was, therefore, undertaken to determine the sensitivity and specificity of the endoscopic and histologic appearance of the gastric mucosa in patients with portal hypertension. PATIENTS AND METHODS

Received April 25, 1990. For revision June 27, 1990. Accepted July 30,1990. From the Department of Gastroenterology and Pathology, M.L.N. Medical College, Allahabad, India. Reprint requests: S. P. Misra, MD, Department of Gastroenterology, M.L.N. Medical College, Allahabad-211001, India. VOLUME 36, NO.6, 1990

Patients

A total of 1373 patients were studied. They were divided into two groups. Group 1. There were 1323 patients in this group who 575

underwent upper gastrointestinal endoscopy for dyspeptic symptoms. Endoscopic diagnosis in these patients was normal (N=960); esophagitis (N=25), gastritis (N=42), gastric (N=3) or duodenal ulcer (N=l71), duodenitis (N=70), carcinoma of the stomach (N=32), gastric (N=6) or duodenal polyp (N=l), prepyloric ulcer (N=l1) or stomal ulcer after gastrojejunostomy (N=2). Patients where the stomach could not be entered due to malignant or benign strictures or those taking antibiotics, antacids, antiulcer drugs, non-steroidal anti-inflammatory agents, or alcohol were not included. None of these patients had clinical or endoscopic evidence of portal hypertension. Group 2. This group consisted of 50 patients with portal hypertension of various etiologies. None of these patients had variceal sclerotherapy. The etiology of portal hypertension is shown in Table 1. The majority (72%) of these patients had cirrhosis (post-hepatitic 34, alcoholic 2). Two patients had non-cirrhotic portal fibrosis (NCPF) and 12 had extra-hepatic portal vein obstruction (ERO). All patients had evidence of esophageal varices at endoscopy and had bled at least once before. The severity of liver disease was classified according to the Child-Pugh classification. l l Esophageal varices were graded after Conn. 12 The diagnosis of cirrhosis, ERO or NCPF was made as previously described. 13 All patients were endoscoped by one of us (S .P. M. or M. D.) and the visual endoscopic findings suggestive of congestive gastropathy were carefully evaluated. 6 •lo Two biopsies were taken from the antrum within 4 cm of the pylorus and two from the body of the stomach high on the greater curvature from 100 patients with a normal endoscopic appearance and all 50 patients with portal hypertension. Multiple sections were cut from each biopsy specimen and were stained with hematoxylin and eosin for evaluation of mucosal vascular changes and with modified Giemsa stain 14 for the presence of Helicobacter pylori. Slides were evaluated by one of the pathologists (V. M.), who was not aware of the clinical diagnosis of the patients. Mucosal vascular congestion was considered present if observed in any two biopsy specimens. H. pylori was evaluated only in the antral biopsy specimens. Congestive gastropathy was classified as described by McCormack et a1.6 Mild gastritis was recognized by any of the following endoscopic appearances: (1) a fine pink speckling or "scarlatina" type appearance; (2) a superficial reddening, particularly on the surface of the rugae giving a striped appearance; or (3) a fine white reticular pattern separating areas of raised red edematous mucosa resembling a snakeskin. This was labeled as the mosaic pattern after Papazian et a1. 8

The type of gastritis was classified after Whitehead et a1. 15 as superficial active or chronic, atrophic active or chronic; and full thickness when inflammation was deep in the mucosa without noticeable glandular atrophy. The severity of the inflammatory inflltrate was graded as absent or mild, moderate, or severe, depending on the increasing number of inflammatory cells in the lamina propria and distortion of the crypts. The severity of histologic congestive gastropathy was graded as absent (0); mild (+): one to three dilated ectatic capillaries in the deeper parts of lamina propria; moderate (++): more than three dilated ectatic capillaries limited to the deeper areas of the lamina propria; or severe (+++): prominent dilated ectatic capillaries even in the superficial lamina propria. Congestive changes were analyzed in relation to the severity of gastritis. The sensitivity, specificity, positive and negative predictive value, and the overall diagnostic accuracy was calculated as described by Goldman. 16 Statistics

Statistical analysis was performed using the chi-square test with or without Yate's correction as appropriate. RESULTS Endoscopic appearance

Group 1. One-hundred seventy-four (13.1%) patients in this group showed evidence of gastritis which was mild in all cases. None of the patients bled from these mucosal lesions. Twelve (0.9%) of these showed the mosaic sign. The diagnosis of patients with gastritis is shown in Table 2. Group 2. Twenty-one (42%) patients in this group had gastritis which was mild in all (Table 2). The difference from the control group was highly significant (p < 0.001). It was present in 15 of 36 (41%) cirrhotic, and 6 of 12 (50%) patients with EHO. The difference between the two groups with portal hypertension was not significant. Neither of the two patients with NePF had gastritis. Seven (14%) patients showed the mosaic sign. The difference from the control group was highly significant (p < 0.(01). It was present in 6 of 36 (16.6%) cirrhotics and 1 of 12 (8%) patients with EHO. The difference between the two groups with portal hypertension was not significant. However, considering the total number of patients with the mosaic sign, six (85.7%) were cirrhotics and only one (14.3%) was a

Table 1. Etiology of portal hypertension and the Child's grade of patients with portal hypertension (group 2)

Child's B

Child's C

4 0

10 0

20 2

2

0 0

0 0

Child's A Cirrhosis Post-hepatitic Alcoholic NCPF" EHO a

576

12

Total

36 2

12

NCPF, Non-cirrhotic portal fibrosis; EHO, Extra-hepatic portal vein obstruction.

GASTROINTESTINAL ENDOSCOPY

Table 2. Endoscopic diagnosis of patients (N 174) showing gastritis in the control group (group 1)

=

Scarlantina appearance

Superficial reddening

Mosaic sign

64 16 28

18

4

7

0 0 0 3

Duodenal ulcer Duodenitis Gastritis Carcinoma stomach Gastric ulcer Stomal ulcer Esophagitis

4 0 5

9 8

6 0 2

patient with EHO. Five of the six cirrhotic patients had Child's C liver disease. Sensitivity, specificity, positive and negative predictive value, and the overall diagnostic accuracy of the mosaic sign for diagnosing portal hypertension was 14%,99%,37%,97%, and 96%, respectively. There was no correlation between the grade of varices and endoscopic features of congestive gastropathy. Histology

Group 1. Of the 200 pairs of tissues obtained (two each from body and antrum), the biopsy was too superficial for good histologic examination in 10 (4 from the body and 6 from the antrum). Biopsies from at least one site were available in each patient. Congestion. Mucosal capillary dilation and ectasia were noted in 59 of 100 biopsy specimens in this group. It was mild (+) in 29, moderate (++) in 18, and severe (+++) in 12 specimens (Fig. 1). Congestion was seen at only one site in 17 specimens (8 in body and 9 in antral biopsies) where adequate biopsies were obtained from both sites. Gastritis. Normal gastric mucosa was seen in 37 of 96 (38.5%) of the biopsies from the body and in 27 of 94 (29%) of antral biopsies. Evidence of inflammation was seen in the other 59 (61.5%) of the biopsies obtained from the body and 67 (71%) of the antral biopsies. There was no correlation between the severity of congestion and the severity of inflammatory changes seen in the biopsy specimens (r = +0.1, t = 0.98; Table 3). Helicobacter pylori. Histologic examination revealed the presence of H. pylori in 63 of 94 (67%) antral biopsy specimens. Thirty-seven (62.7%) of 59 patients having evidence of mucosal vascular congestion showed the presence of H. pylori. There was a strong positive correlation between the severity of H. pylori colonization and the severity of inflammation seen in the biopsy specimens (r = +0.71, t = 9.8). Group 2. Of the 100 pairs of tissue obtained (2 from each site), the biopsy material was insufficient in 7 (3 from the body and 4 from the antrum). However, in none of the patients were both biopsies insufficient. Congestion. Evidence of capillary dilation and ecVOLUME 36, NO.6, 1990

Figure 1. Dilation of mucosal capillaries (arrows) in a patient with irritable bowel syndrome (H&E, original magnification

Xl00). Figure 2. Capillary dilation (arrows) in gastric mucosa of a patient with portal hypertension. To the right infiltration by mononuclear cells is also seen throughout the mucosa (full thickness gastritis active) (H&E, original magnification xl 00).

tasia were noted in 36 (72%) of 50 patients. The difference from the control group (group 1) was not significant. It was mild (+) in 19, moderate (++) in 12, and severe (+++) in 5 patients (Fig. 2). In nine patients in whom both biopsies were adequate, congestion was seen at only one site, four in the body and five in the antrum. Fifteen of these 36 (42%) patients showed the presence of gastritis at endoscopy, the other 21 (58%) had a normal endoscopic appearance. Four patients who showed gastritis had no evidence of congestion at histology. All seven patients with the mosaic sign showed evidence of congestion at histology. It was mild in three and moderate in four patients. Gastritis. Normal mucosa was seen in 16 of 47 (34%) of the biopsies from the body and 14 of 46 (30.4%) from the antrum. In the other 31 of 47 (66%) biopsies from the body and 32 of 46 (69.6%) biopsies from the antrum, there was evidence of inflammation. The difference from the control group was, however, not significant. There was no correlation (r = 0.14, t = 1.0) between the severity of mucosal vascular conges577

Table 3. Association of inflammation with the severity of mucosal vascular congestion in the two groups Inflammation Congestion Controls (N = 100) 0 (N = 41)

+

Normal (%)

Severe (%) Mild (%)

Moderate (%)

15 (36.6)

12 (29.3)

12 (29.3)

2 (4.8)

10 (34.5)

6 (20.7)

12 (41.4)

1 (3.4)

2 (11.1)

5 (27.8)

10 (55.6)

1 (5.5)

5 (41.7)

3 (25)

3 (25)

1 (8.3)

6 (43)

3 (21.4)

4 (28.6)

1 (7)

12 (63.1)

5 (26.3)

0(0)

(N = 29)

++ (N = 18)

+++ (N = 12) Portal hypertension (N = 50) 0 (N = 14)

+

2 (10.5)

(N = 19)

++

3 (25)

3 (25)

6 (50)

0(0)

1 (20)

2 (40)

1 (20)

1 (20)

(N = 12)

+++ (N = 5)

tion and the severity of inflammation seen in the biopsy specimens (Table 3). Helicobacter pylori. Helicobacter pylori were seen in a total of 26 of 46 (56.5%) biopsies obtained from the antrum. The difference from the control group was not significant. Eighteen of 36 (50%) patients having mucosal vascular congestion showed the presence of H. pylori. Although less than that seen in the control group, the difference was not statistically significant. There was a strong positive correlation (r = 0.69, t = 6.4) between the severity of H. pylori colonization and the severity of inflammation. DISCUSSION

The results of this study show that although significantly more common, endoscopic features of congestive gastropathy are not specific for portal hypertension and are seen in a variety of other conditions, and above all, are not a sensitive indicator of portal hypertension. The sensitivity of the mosaic sign was only 14%. These observations are similar to those reported earlier. 6,10 However, Papazian et a1.8 noted the mosaic sign to be very sensitive and specific for portal hypertension. The difference between these observations may be due to a different patient population. In the study of Papazian et a1.8 90% of the patients were alcoholic, only 32% presented with bleeding, and only 7% had bleeding from esophageal varices whereas 25% bled from mucosal lesions or ulcers. In the present study, on the other hand, the majority (94%) of patients were nonalcoholic, all had bled in the past, and in only one patient, who had previously bled from esophageal varices, was the bleeding attributable to the mucosa (on follow-up after 578

variceal obliteration). All patients had esophageal varices. Neither ofthe two patients with NCPF in this study demonstrated gastritis. This may be due to the small number of patients with NCPF. The incidence of the mosaic sign was higher in patients with cirrhosis (16.6%) than in those with EHO (8%), although the difference was not significant. Similar results were obtained earlier. 1o However, of the 7 patients with the mosaic sign, 6 (85.7%) were cirrhotics. This suggests that mechanisms other than portal hypertension alone are responsible for the mosaic sign. This view is reinforced by the findings noted at histology. Although biopsy specimens from all seven patients with the mosaic sign showed evidence of congestion, it was only of mild or moderate severity. None of the patients showing severe congestion at histologic examination of the gastric mucosa showed the mosaic sign. The higher incidence of the mosaic sign in patients with cirrhosis may be due to formation of arteriovenous shunts in the stomach wall, which has been observed in experimental animals l7 as well as humans. 18 Earlier reports have noted the incidence of gastritis and the mosaic sign to be more common in patients who had undergone sclerotherapy.6,lo However, all the patients in this study were studied before sclerotherapy. The incidence of gastritis was 42% and the incidence of the mosaic sign was 14%. This is higher than reported earlier, where the incidence of the mosaic sign in a pre-sclerotherapy group was only 2.6%.10 This might be due to the higher number of cirrhotics in the present study (72%) compared with 47% reported earlier. 1O It has been suggested that after variceal obliteration congestion in the stomach may increase.6 If this is so, the incidence of gastritis and the GASTROINTESTINAL ENDOSCOPY

mosaic sign may increase after obliteration of varices. In support of this is our observation in one patient with Child's C cirrhosis who bled from congested mucosa after variceal obliteration. Full-thickness biopsies have been used to study vascular congestion in the gastric mucosa, and have the added advantage of allowing submucosal congestion to be studied. However, for practical purposes, mucosal vascular changes seen in endoscopic pinch biopsies must be defined because of the ease with which they can be obtained. Several reports have used endoscopic biopsies for this purpose with conflicting results. 5 ,7-1O In the present study histologic examination of biopsy material obtained in patients with portal hypertension showed evidence of congestion in 72% of cases. This was similar to those noted by McCormack et al.,6 who noted mucosal ectasia in 71 % of patients with endoscopic features of mild gastropathy. However, in the present study, not all patients with mild gastropathy showed congestion at histology. In another study only 47% of patients with portal hypertension demonstrated mucosal vascular changes, 9 whereas other workers have noted these changes in 100% ofpatients. 7 ,8 We found no correlation between histologic gastritis and endoscopic features of mild gastropathy. Only 42% of patients showing vascular congestion in biopsy specimens had endoscopic features of mild gastropathy. Similar results were obtained by Hosking et aU In the present study it was also observed that mucosal vascular changes were nonspecific. These changes (noted in 72% of patients with portal hypertension) were also seen in 59% of the controls, and though the incidence was higher in patients with portal hypertension, the difference between the two groups was not significant. Corbishley et al. 9 have also noted capillary dilation to be nonspecific. Indeed, they noted these changes to be more common in patients with noncirrhotic liver disease (85%) and patients with normal endoscopic appearance (84%) compared with that seen in patients with portal hypertension (47%). More recently, Foster et aU 9 noted mucosal capillary dilation to be more common in biopsy specimens of patients with portal hypertension using factor VIII related antigen as a specific marker for endothelial cells. However, by conventional staining methods this difference was not apparent. Sixty-six percent of specimens from the body and 69.6% ofthose from the antrum of patients with portal hypertension showed evidence of inflammation compared with 61.5 and 71%, respectively, seen in the control group. The difference between the two groups was not significant. Similarly, there was no correlation between the severity of congestion and inflammation in either group. Other investigators have also reported similar findings. 7 ,9,l0 In a study of 19 patients with portal hypertension, VOLUME 36, NO.6, 1990

Foster et al. 19 noted the presence of H. pylori in only 17%, and suggested that the gastric mucosa of these patients may be unfavorable for colonization by H. pylori. However, we found colonization of the antral mucosa by H. pylori in 56.5% of patients with portal hypertension, although this was not significantly different than in the control group (67%). The reason for the difference between these two studies is not clear. It may be due to a different patient population. Further studies are needed to clarify this issue.

REFERENCES 1. Dagradi AE, Mehler R, Tan DTD, et al. Sources of upper gastrointestinal bleeding in patients with liver cirrhosis and large esophagogastric varices. Am J GastroenteroI1970;54:45863. 2. Khodadoost J, Glass GBJ. Erosive gastritis and acute gastroduodenal ulcerations as source of upper gastrointestinal bleeding in liver cirrhosis. Digestion 1972;1:129-38. 3. Teres J, Bordas JM, Brue C, Diaz F, Bruguera M, Rodes J. Upper gastrointestinal bleeding in cirrhosis. Clinical and endoscopic correlations. Gut 1976;17:37-40. 4. Poynard T, Chaput JC, Mary JY, et al. Upper digestive tract haemorrhage in cirrhotic patients. Contribution of multidimensional analysis to the cause of hemorrhage. Dig Dis Sci 1981;26:232-6. 5. Sarfeh IJ, Juler GL, Stemmer EA, Mason GR. Results of surgical management of haemorrhagic gastritis in patients with gastroesophageal varices. Surg Gynecol Obstet 1982;155:16770. 6. McCormack TT, Sims J, Eyre-Brook I, et al. Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy? Gut 1985;26:1226-32. 7. Hosking SW, Kennedy HJ, Seddon I, Triger DR. The role of propranolol in congestive gastropathy of portal hypertension. Hepatology 1987;7:437-41. 8. Papazian A, Braillon A, Dupas JL, Sevenet F, Capron JP. Portal hypertensive gastric mucosa: an endoscopic study. Gut 1986;27:1199-1203. 9. Corbishley CM, Saverymuttu SH, Maxwell JD. Use of endoscopic biopsy for diagnosing congestive gastropathy. J Clin PathoI1988;41:1187-90. 10. Sarin SK, Misra SP, Singal A, Thorat V, Broor SL. Evaluation of the incidence and significance of the "Mosaic Pattern" in patients with cirrhosis, noncirrhotic portal fibrosis, and extrahepatic obstruction. Am J GastroenteroI1988;83:1235-9. 11. Pugh RNH, Murray-Lyon JM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646-9. 12. Conn HO. Ammonia tolerance in the diagnosis of esophageal varices. A comparison of endoscopic, radiologic and biochemical techniques. J Lab Clin Med 1967;70:442-9. 13. Sarin SK, Sachdev G, Nanda R. Follow-up of patients after variceal eradication. A comparison of patients with cirrhosis, non-cirrhotic portal fibrosis, and extrahepatic obstruction. Ann Surg 1986;204:78-82. 14. Gray SF, Wyatt JI, Rathbone BJ. Simplified techniques for Clin Pathol identifying Campylobacter pyloridis. J 1986;39:1279-80. 15. Whitehead R, Truelove SC, Gear MWL. The histological diagnosis of chronic gastritis in fibreoptic gastroscope biopsy specimens. J Clin PathoI1972;25:1-11. 16. Goldman L. Harrisson's Principle's of Internal Medicine. 11th ed. New York: McGraw Hill, 1987:5-11. 17. Manabe T, Suzuki T, Honjo I. Changes of gastric blood flow in experimental induced cirrhosis ofthe liver. Surg Gynecol Obstet 1978;147:753-7. 18. Hashizume M, Tanaka K, Inokuchi K. Morphology of gastric microcirculation in cirrhosis. Hepatology 1983;6:1008-12. 19. Foster PN, Wyatt JI, Bullimore DW, Losowsky MS. Gastric mucosa in patients with portal hypertension: prevalence of capillary dilatation and Campylobacter pylori. J Clin Pathol 1989;42:919-21.

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Endoscopic and histologic appearance of the gastric mucosa in patients with portal hypertension.

To assess reliability of the endoscopic and histologic appearance of the gastric mucosa for diagnosing portal hypertension, 50 patients with portal hy...
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