Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

Gut, 1985, 26, 1226-1232

Gastric lesions in portal : inflammatory or congestive gastropathy? T T McCORMACK, J SIMS, I EYRE-BROOK, H KENNEDY, J GOEPEL, A G JOHNSON, AND D R TRIGER From the University Departments ofSurgery, Medicine and Pathology, Sheffield University, Royal Hallamshire Hospital, Sheffield

SUMMARY This paper reports the incidence and natural history of macroscopic gastritis in a series of 127 consecutive patients with of various aetiologies. Gastritis was observed endoscopically in 65 patients (51%) and was of two main types. Twenty eight patients had severe or persistent gastritis which caused clinically significant bleeding on 80 occasions and accounted for 25% of the bleeds from all sources. The remainder had mild gastritis. The presence of gastritis seemed to be independent of the severity of or the degree of rise of wedged hepatic venous pressure and there was no difference in age, sex, or drugs prescribed in patients with or without gastritis. The mean follow up period and the mean number of sclerotherapy treatments was significantly greater (p<0.005) in patients with gastritis. Full thickness gastric biopsies in seven surgical patients and 11 autopsy specimens showed dilated and tortuous submucosal . Endoscopic biopsies in 14 patients showed vascular ectasia in the mucosal layer which was in excess of the degree of inflammatory infiltrate. Gastritis occurred in patients with portal hypertension of all common aetiologies and the clinical and pathological that it reflects a congested and should be evidence supports the contention http://gut.bmj.com/ renamed congestive gastropathy. As injection sclerotherapy improves survival from variceal bleeding congestive gastropathy may become more common. The response to conventional ('anti-erosive') therapy is poor and measures aimed at reducing the gastric portal pressure may be the only effective means of treating this condition. on September 25, 2021 by guest. Protected copyright. Gastric mucosal lesions are common in portal mucosa were classified according to the description of hypertension. They are an important cause of blood Taor et al.3 (i) a fine pink speckling or 'scarlatina' loss, which may be slow and insidious causing type rash, (ii) a superficial reddening, particularly anaemia,1 or sudden and severe, causing massive on the surface of the rugae giving a striped and occasionally fatal haemorrhage.2 The use of appearance, (iii) a fine white reticular pattern sclerotherapy for bleeding oesophageal varices com- separating areas of raised red oedematous mucosa bined with regular endoscopic follow up has pro- resembling a 'snake skin'. vided a unique opportunity to study the progression These were included under the term 'mild gastri- of changes occurring in the gastric mucosa. We tis'. report our clinical and endoscopic experience of During the course of the study two additional gastritis in portal hypertension over a four year forms of gastric mucosal changes were noted: (i) period. discrete red spots analogous to the cherry red spots described in the oesophagus. These spots can Methods become confluent giving a local area of severe PATIENTS gastritis which may bleed, (ii) a diffuse haemorrha- Definition of gastritis gic gastritis. The endoscopic changes which occur in the gastric These were termed 'severe gastritis'. Gastritis has been arbitrarily defined as 'transient' Address for correspondence: Dr D R Triger, Department of Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF. if present at one and resolved by the next Received for publication 24 January 1985 endoscopy six to eight weeks later. If gastritis was 1226 Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

Gastropathy in portal hypertension 1227 present for more than eight weeks at two or more Table 1 Clinicalfeatures of65 patients with gastritis consecutive it was said to be 'persis- compared with 62 patients with no gastritis tent'. Gastritis occurring within two weeks of balloon tamponade was excluded as this could be Patients (no) because of contact irritation. Cause ofportal Without With Over the last four years (August 1979-August hypertension gastritis (62) gastritis(65) 1983) 127 patients with portal hypertension have Alcoholic 14 23 attended this unit. One hundred and fourteen Primary biliary cirrhosis 13 13 patients presented with bleeding and a further 13 Chronic active 9 12 had oesophageal varices with no clinical evidence of Cryptogenic cirrhosis 10 4 haemorrhage. These were discovered during routine Portal 7 5 evaluation of their portal hypertension. The pre- Others 9 8 Child's grading A 21 31 sence or absence, and the degree of gastritis was B 15 17 noted at each endoscopy. All patients were endo- C 26 17 scoped at presentation by an experienced endoscop- Age (Mean+SD) 57 5 (±12.1) 54 5 (±14.1) ist and any patient with upper Sex Male 34 35 bleeding underwent emergency endoscopy. Any Female 28 30 patients with oesophageal varices were treated by injection sclerotherapy and followed up by regular check endoscopies. hypertension of all common aetiologies and the PATHOLOGY TECHNIQUE proportion of patients who developed gastritis in Biopsies of the were studied in 41 patients each of the aetiological groups was not significantly with portal hypertension. These samples were different (X2 test). obtained (a) at endoscopy (23 patients - nine with Patients with gastritis had a significantly greater macroscopically normal mucosa and 14 with gastri- (p<0-005) number of sclerotherapy treatments per tis), (b) during surgical procedures (seven patients - patient (mean 4-0±0-3 SE) than those without four with bleeding gastritis and three with bleeding gastritis (mean 2 3±0 2 SE). The follow up period in gastric varices) and (c) at necropsy (11 patients). patients with gastritis (mean 13-8 months ± 1.5 SE)

Further operative samples were also taken during was also significantly greater (p<0.005) than in the http://gut.bmj.com/ refashioning of an ileostomy and at resection of an non-gastritis group (mean 6*7 months ± 1-2 SE). oesophagojejunal anastomosis. Two patients with Mild gastritis was noted in 37 of the 65 patients. also had endoscopic biopsies taken. This was not of any clinical significance and in only Endoscopic biopsies and surgical specimens were two patients did this progress to severe gastritis. On fixed by immersion in formal saline. Post mortem the other hand severe gastritis led to clinical specimens were fixed by gently filling the unopened bleeding in almost all instances (see below). Gastri- stomach and oesophagus with formal saline and tis both mild and severe was noted on initial immersing the whole specimen in formal saline. presentation in about one third of patients, and on September 25, 2021 by guest. Protected copyright. Paraffin sections were prepared and stained by developed during follow up in the remainder. The haematoxylin and eosin (H and E) or Miller's elastic age, sex, and Child's grading(s) was similar in stain counterstained by van Gieson's stain for patients with mild transient gastritis and in those collagen (EVG). with severe or persistent gastritis (Table 2), but both the mean follow up period and the number of Results sclerotherapy treatments were significantly greater (p<0-0025 and p<0-005 respectively) in the pa- ENDOSCOPIC FINDINGS tients with severe or persistent gastritis. The mean Sixty five patients (51%) had macroscopic gastritis number of treatments per patient month, however, at some stage during follow up. The changes were was similar in both groups. most commonly seen in the fundus and body of the stomach. There was no significant difference in age BLEEDING or sex in patients with gastritis compared with the Clinically significant bleeding from gastritis occur- rest (Table 1). Although there was a trend for red on 80 occasions in 29 patients, and blood gastritis to be more frequent in patients with less transfusion (2-15 units) was required for 60 bleeds. severe liver disease (as assessed by Child's grading)5 Bleeds from gastritis accounted for 25% of the total this did not reach statistical significance number of bleeds from all sources (Table 3). (0-05

1228 McCormack, Simms, Eyre-Brook, Kennedy, Goepel, Johnson, and Triger Table 2 Clinicalfeatures of65patients with gastritis who had not bled before the study. There was no significant difference in the mean pressure in the 12 Persistent or Mild ± severe gastritis gastritis with gastritis (mean WHVP 17-3 mmHg 1P6 SE) (28) (37) compared with those who had no gastritis (mean WHVP 16*0 mmHg ± 1-6 SE). Age mean±SE 52-0±2.5 (NS)* 56-9±2-8 range (31-79) (21-84) GASTRITIS Sex male 15 20 RELATION OF MEDICATION TO female 13 17 Seventy patients were receiving diuretics, 11 pa- Follow-up (months) tients penicillamine, six patients corticosteroids and mean±SE 17-8±2-3 (p<0.0025)* 8-9+1-5 13 patients were being treated for diabetes. Patients range 1 day-4 years 1 day-2-2 years receiving these drugs were equally distributed be- Child's grade tween the gastritis and non-gastritis groups. A 14 17 B 8 9 C (NS)t 11 EFFECT OF SCLEROTHERAPY ON GASTRITIS 6 In six patients gastritis appeared for the first time Sclerotherapy treatment per patient after successful sclerotherapy while in another five mean+SE 5-3±0-5 (p<0.005)* 2-8+0-3 patients the obliteration of oesophageal varices treatment per patient appeared to coincide with the disapppearance of month mean± 0-39±0-07 (NS)* 0-51±0-09 gastritis. Students t test for unpaired numbers. t x test. PATHOLOGICAL CHANGES The most consistent finding was dilatation of the submucosal veins which were tortuous and irregular presenting bleeds, but after initial sclerotherapy, it in diameter. Elastic staining emphasised the irregu- accounted for over one third of rebleeding episodes. larity of the vein wall and showed foci of intimal Fifty one bleeds from gastritis occurred in the thickening (Fig. 1). These features were visible in presence of thrombosed or obliterated oesophageal veins sampled from all areas of the stomach but varices. In the presence of patent oesophageal were particularly prominent in the proximal part of varices, bleeding from gastritis was diagnosed only if the gastric body and cardia. The mucosal vessels

it-was seen to be coming from an area of gastritis and showed focal areas of abnormality. These consisted http://gut.bmj.com/ no other source of haemorrhage was identifiable. of ectasia of and veins (Fig. 2) which at times formed a leash of mucosal vessels. In some WEDGED HEPATIC VENOUS PRESSURE cases this could be seen to overlie areas of abnormal Wedged hepatic venous pressure (WHVP) was submucosal veins. Although chronic gastritis as measured in 18 patients with oesophageal varices characterised by mononuclear infiltrate did occa- sionally occur, the vascular changes were usually in excess of that expected with the degree and activity of gastritis. We have termed these changes 'conges- on September 25, 2021 by guest. Protected copyright. Table 3 Sites ofpresenting bleeds in 114patients and 202 tive gastropathy'. subsequent bleeds in 48patients who rebled In the jejunal and ileal surgical samples and duodenal biopsies there was also marked vascular Site ofbleeding Presenting bleed Subsequent bleed ectasia in the mucosa, (Fig. 3) with no evidence of an inflammatory infiltrate. Oesophageal varices 88 64 Gastritis 9 71 Upper GI tract ENDOSCOPIC SPECIMENS (unknown site) - 13 Biopsies were not done in endoscopically severe Post injection slough - 16 for fear of inducing major haemorrhage. Gastric varices 6 11 gastritis Peptic ulcer 4 3 Classic histological features of chronic inflammatory Duodenitis - 3 gastritis were seen in four of 14 patients, while the Oesophagogastric junction - 14 other 10 had vascular ectasia with little or no Mallory Weiss 1 1 infiltrate. Six of the nine biopsies from Rectal varices 3 2 inflammatory Oesophagojejunal macroscopically normal mucosa were histologically anastomosis 1 4 normal, the remainder showing vascular ectasia. It Intra-abdominal 1 - should be remembered, however, that endoscopic Ileostomy 1 - biopsies are of necessity small and superficial and 114 202 therefore liable to sampling error. Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

Gastropathy in portal hypertension 1229 http://gut.bmj.com/

Fig. 1 Dilated submucosal veins (arrows to walls) with intimal thickening (arrow heads). (Post mortem stomach, elastic van Gieson, x8 original magnification).

SURGICAL SPECIMENS aetiologies and occurred in patients with both patent These were taken from patients with severe gastritis and obliterated varices. or bleeding gastric varices and all showed mucosal It should be emphasised that, with the exception on September 25, 2021 by guest. Protected copyright. and submucosal vascular abnormalities. of the cherry red spots, the gastritis described here is macroscopically identical to that seen in patients AUTOPSY SPECIMENS without portal hypertension, but the histological Marked submucosal vascular ectasia was seen in all appearance is quite different from that described by cases, but mucosal vascularity could not be assessed because of mucosal post mortem autolysis. The correlation between the macroscopic appear- Table 4 Summary ofmacroscopic and histological ances and histological findings are summarised in findings in gastric specimens Table 4. Type of No Macroscopic Microscopic Discussion specimen appearance appearance Endoscopic 9 Normal 6 normal In this series, gastritis has been observed at some biopsy 3 mucosal ectasia time in 51% of with varices Endoscopic 14 Mild gastritis 4 inflammatory patients oesophageal biopsy 10 mucosal ectasia and it has been responsible for 25% of the total 4 severe gastritis All mucosal and number of bleeds. Other workers have noted that Surgical 7 3 bleeding gastric submucosal bleeding in portal hypertension can be caused by varices ectasia in 30-40% of cases.678 Autopsy 11 All submucosal gastritis Gastric mucosal ectasia changes were seen in portal hypertension of all Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

1230 McCormiack, Simms, Eyre-Brook, Kennedy, Goepel, Johnson, and Triger

Fig. 2 Gastric antral biopsy showing prominent dilated vessels (arrows) near the surface. (PAS x 160 original magnification). http://gut.bmj.com/ on September 25, 2021 by guest. Protected copyright.

Fig. 3 Duodenal biopsi showing marked vascular ectasia (arrows) particularly in the villi. Acute inflammatory changes are absent. (H & E x20 original magnification). Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

Gastropathy in portal hypertetnsion 1231 Whitehead and colleagues9 where chronic inflam- ments in these patients. Our experience suggests matory cells predominate and there is a strong that while gastropathy may develop after sclerother- association with gastric ulcer. Our observations are apy in some individuals the converse is true in similar to that of Brown and colleagues'( who found others. In theory obstruction of blood flow at the no evidence of an increased incidence of classical gastro-oesophageal junction may increase conges- chronic gastritis in a series of cirrhotics, despite the tion by blood vessels flowing from the stomach. This presence of gastric ulcers and erosions in nearly 20% effect is likely to be very variable as recent studies of their patients. Furthermore, they comment that using Doppler ultrasound'6 have shown that blood gastric erosions tended to occur in histologically flow in oesophageal varices may sometimes be normal mucosa. Their study, however, did not towards the stomach and therefore thrombosis of include assessment of the mucosal and submucosal these varices would reduce and certainly not induce vascular channels. congestion in the gastric mucosa. In the majority of Gastritis in portal hypertension might be caused by patients, therefore, the relationship between sclero- several factors. Alcohol can be excluded because we therapy and gastropathy is not straightforward and have observed the changes in non-alcoholic cirrhosis the presence of the gastric lesion is probably as frequently as in alcoholic cirrhosis. The observa- independent of the patency of oesophageal varices. tion of severe gastritis in two patients who had undergone truncal vagotomies makes it unlikely that gastric acid plays a major role. THERAPEUTIC IMPLICATIONS The most important element causing gastritis may Congestive gastropathy was mild and transient in be the raised portal pressure itself. Obstruction of more than half of the patients. Complications did the venous drainage from the stomach can induce not occur and progression was uncommon during changes in the gastric mucosa. Palmer, in 195711 the short period of follow up. In contrast, patients induced portal hypertension in dogs by portal vein with severe or persistent gastropathy are prone to ligation and found that both the mucosal and clinically significant haemorrhage. submucosal veins in the stomach wall became Twenty five of our patients with severe changes dilated. Both he and Sandblom'2 observed similar received H2 receptor antagonists, five received changes in gastric biopsies from patients with portal sucralfate and all were prescribed antacids at some hypertension. Alternatively gastritis might be be- stage. None of these agents had any significant

cause of gastric mucosal ischaemia secondary to effect upon either the gastritis or the bleeding. This http://gut.bmj.com/ arteriovenous shunting which can be demonstrated tends to support the hypothesis that it is congestion in the stomachs of both animals13 and humans14 with rather than erosion which is the major factor portal hypertension. damaging the gastric mucosa. The rational approach The histological changes are entirely consistent to treatment is therefore a reduction of the portal with an increase in venous pressure producing a venous pressure which should thus reduce the congested gastric mucosa. The occurrence and congestion in the gastic mucosa.2. severity of this congestive gastropathy may depend, Portosystemic shunting effectively reduces portal however, not only on the total level of portal pressure and bleeding from gastritis is rare after this on September 25, 2021 by guest. Protected copyright. pressure but also on local blood flow characteristics procedure.2 17-19 An alternative surgical approach is which may or may not transmit this increased to reduce the gastric blood flow alone by devascular- pressure to the gastric mucosal and submucosal ising the upper two thirds of the stomach and veins. Differences in local blood flow patterns may combining it with an oesophageal transection. We explain why some patients develop gastropathy and have used this procedure in eight patients, specific- others do not. Successful sclerotherapy of ally for controlling severe haemorrhagic gastritis and oesophageal varices may induce local changes in it has been successful in five. As with portosystemic blood flow patterns and if this results in an increased decompression this procedure is not without con- venous pressure in areas proximal to the site of siderable risk in patients with advanced liver thrombosis, congestive gastropathy might be pre- disease. dicted. Methods aimed at reducing portal The mean number of sclerotherapy treatments in or flow by pharmacological means would clearly be patients with gastropathy was significantly greater preferable to surgery. Although Lebrec and col- than in those without it. Sclerotherapy appears to leagues20 reported that propranolol reduced variceal increase long term survival15 and the greater inci- haemorrhage, close inspection of their paper reveals dence of the gastric lesion in the longer survivors that the drug also reduced the incidence of gastritis. may be related either to the progression of disease On an anecdotal basis we have observed significant or to the greater number of sclerotherapy treat- improvement in several patients with severe persis- Gut: first published as 10.1136/gut.26.11.1226 on 1 November 1985. Downloaded from

1232 McCormack, Simms, Eyre-Brook, Kennedy, Goepel, Johnson, and Triger tent gastritis treated with propranolol and we are 7 Thomas E, Rosenthal WS, Rymer W, Katz D. Upper currently evaluating its effectiveness by means of a gastrointestinal haemorrhage in patients with alcoholic controlled trial. liver disease and oesophageal varices. Am J Gastro- In conclusion, the macroscopic gastritis noted in enterol 1979; 72: 623-9. 8 Khodadoost J, Glass GBJ. Erosive gastritis and acute patients with portal hypertension differs from that gastroduodenal ulcerations as source of upper gastro- seen in the absence of liver disease in that (a) the intestinal bleeding in liver cirrhosis. Digestion 1972; 7: histological appearance is quite distinct (b) it is 129-38. unrelated to the aetiology of the portal hypertension 9 Whitehead R, Truelove SC, Gear MWL. The histo- (c) it does not respond to conventional anti- logical diagnosis of chronic gastritis in fibreoptic inflammatory drug therapy and (d) the histological gastroscope biopsy specimens. J Clin Pathol 1972; 25: changes are found elsewhere in the gastrointestinal 1-11. tract. In the light of the clinical, haemodynamic and 10 Brown RC, Hardy GJ, Temperley JM, Miloszewski histological observations the term 'congestive KJA, Gowland G, Losowsky MS. Gastritis and cir- rhosis - no association. J Clin Pathol 1981; 34: 744-8. gastropathy' appears to be more appropriate. 11 Palmer ED. Erosive gastritis in cirrhosis. Am J Dig Dis 1957; 2: 31-6. We wish to thank those involved with the care of 12 Sandblom P. The source of bleeding in portal hyper- these patients. Sister Salisbury and the staff of the tension. Bull Soc Int Chin 1975; 3: 165-7. endoscopy unit, Sisters Ellis and Barry, and the staff 13 Manabe T, Suzuki T, Honjo I. Changes of gastric in the operating theatres. blood flow in experimentally induced cirrhosis of the liver. Surg Gynecol Obstet 1978; 147: 753-7. 14 Hashizume M, Tanaka K, Inokuchi K. Morphology of gastric microcirculation in cirrhosis. Hepatology 1983; References 6: 1008-12. 15 MacDougall BRD, Westaby D, Theodossi A, Dawson 1 Wenger J, Huffman RT, Landy MS. Persistent blood JL, Williams R. Increased long-term survival in loss from the stomach of patients with cirrhosis and variceal haemorrhage using injection sclerotherapy. oesophageal varices. South Med J 1970; 63: 560-6. Results of a controlled trial. Lancet 1982; 1: 124-7. 2 Sarfeh IJ, Juler GL, Stemmer EA, Mason GR. Results 16 McCormack T, Smallwood RH, Walton L, Martin T, of surgical management of haemorrhagic gastritis in Robinson P, Johnson AG. Doppler ultrasound probe patients with gastroesophageal varices. Surg Gynecol for assessment of blood-flow in oesophageal varices. Obstet 1982; 155: 167-70. Lancet 1983; 2: 677-8. 3 Taor RE, Fox B, Ware J, Johnson AG. Gastritis - 17 Jackson FC, Perrin EB, Felix WR, Smith AG. A http://gut.bmj.com/ gastroscopic and microscopic. Endoscopy 1975; 7: clinical investigation of the portacaval shunt: V. sur- 209-15. vival analysis of the therapeutic operation. Ann Surg 4 Japanese Research Society for Portal Hypertension. 1971; 174: 672-701. The general rules for recording endoscopic findings on 18 Resnick RH, Iber FL, Ishihara AM, Chalmers TC, oesophageal varices. Jap J Surg 1980; 10: 84-7. Zimmerman H. A controlled study of the therapeutic 5 Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni portacaval shunt. 1974; 67: 843-57. MC, Williams R. Transection of the oesophagus for 19 Rueff B, Prandi D, Degos F et al. A controlled study of bleeding oesophageal varices. Br J Surg 1973; 60: therapeutic portacaval shunt in cirrhosis. Lancet 1976; on September 25, 2021 by guest. Protected copyright. 646-9. 1: 655-9. 6 Dagradi AE, Mehler R, Tan DT, Stempien SJ. Sources 20 Lebrec D, Poynard T, Hillon P, Benhamou JP. of upper gastrointestinal bleeding in patients with liver Propranolol for prevention of recurrent gastrointestinal cirrhosis and large esophagogastric varices. Am J bleeding in patients with cirrhosis. N Engl J Med 1981; Gastroenterol 1970; 54: 458-63. 305: 1371-4.