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Objective: Patients with a history of Helicobacter pylori -negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications. We hypothesised that a proton pump inhibitor (lansoprazole) is superior to a histamine 2 receptor antagonist (famotidine) for the prevention of recurrent ulcer bleeding in such patients., Design: In this industry-independent, double-blind, randomised trial, we recruited patients with a history of idiopathic bleeding ulcers. After ulcer healing, we randomly assigned (1:1) patients to receive oral lansoprazole 30 mg or famotidine 40 mg daily for 24 months. The primary endpoint was recurrent upper GI bleeding within 24 months, analysed in the intention-to-treat population as determined by an independent adjudication committee., Results: Between 2010 and 2018, we enrolled 228 patients (114 patients in each study group). Recurrent upper GI bleeding occurred in one patient receiving lansoprazole (duodenal ulcer) and three receiving famotidine (two gastric ulcers and one duodenal ulcer). The cumulative incidence of recurrent upper GI bleeding in 24 months was 0.88% (95% CI 0.08% to 4.37%) in the lansoprazole arm and 2.63% (95% CI 0.71% to 6.91%) in the famotidine arm (p = 0.313; crude HR 0.33, 95% CI 0.03 to 3.16, p = 0.336). None of the patients who rebled used aspirin, non-steroidal anti-inflammatory drugs or other antithrombotic drugs., Conclusion: This 2-year, double-blind randomised trial showed that among patients with a history of H. pylori -negative idiopathic ulcer bleeding, recurrent bleeding rates were comparable between users of lansoprazole and famotidine, although a small difference in efficacy cannot be excluded., Trial Registration Number: NCT01180179; Results., Competing Interests: Competing interests: GL-HL-HW has served as a speaker for Abbott, AbbVie, Bristol-Myers Squibb, Echosens, Gilead and Janssen, and an advisory committee member for Gilead and Janssen. VW-SW has served as a speaker for AbbVie, Bristol-Myers Squibb, Roche, Novartis, Abbott Diagnostics and Echosens, and an advisory committee member for AbbVie, Roche, Novartis, Gilead and Otsuka. PWYC has served as a speaker for Olympus and an advisory committee member for EndoMASTER and Aptorum. JL has served as a speaker for Boston Scientific. FKLC has served as a consultant to Eisai, Pfizer, Takeda and Otsuka, and has been paid lecture fees by Eisai, Pfizer, AstraZeneca and Takeda., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions., Objective: To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores., Design: We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores <6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding., Results: Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores <6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002)., Conclusions: Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6., Trial Registration Number: NCT01591083., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Inequalities in health are well recognized in cardiovascular disease and cancer, but in comparison, we have minimal understanding for upper gastrointestinal bleeding. Since furthering our understanding of such inequality signposts preventable disease, we investigated in detail the association between upper gastrointestinal bleeding and socioeconomic status., Design: Population-based cohort study., Setting: All English National Health Service hospitals., Population: English adult population, 1 January 2001 to 31 December 2007., Exposure Measures: Deprivation scores defined according to quintiles of neighbourhood areas ranked by the Indices of Multiple Deprivation for England 2007., Outcome Measures: Rates of all adult admissions coded with a primary diagnosis of upper gastrointestinal bleed were analysed by deprivation quintile and adjusted for age, sex, region and year using Poisson regression., Results: The annual hospitalization rate for non-variceal haemorrhage was 84.6 per 100,000 population (95% CI 83.5 to 84.1; n=237,145), and for variceal haemorrhage, it was 2.83 per 100,000 population (95% CI 2.87 to 2.99; n=8291). There was a twofold increase in the hospitalization rate ratio for non-variceal haemorrhage from the most deprived areas compared to the least deprived (2.00, 95% CI 1.98 to 2.03). The ratio for variceal haemorrhage was even more pronounced (2.49, 95% CI 2.32 to 2.67). Inequality increased over the study period (non-variceal p<0.0001, variceal p=0.0068), and adjusting for age and sex increased the disparity between deprived and affluent areas. Case fatality did not have a similar socioeconomic gradient., Conclusion: Both variceal and non-variceal haemorrhage hospitalization rates increased with deprivation, and there was a similar gradient in all areas of the country and in all age bands. The existence of such a steep gradient suggests that there are opportunities to reduce hospitalizations down to the low rates seen in the most affluent, and thus, there is the potential to prevent almost 10,000 admissions and over 1000 deaths a year.

Objective: The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed., Design and Patients: Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period., Results: Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3)., Conclusion: The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.

Background: The use of ulcerogenic drugs is the only well documented risk factor for peptic ulcer perforation, but accounts for only a quarter of the events. Smoking is a well known risk factor for uncomplicated ulcer disease, and patients with ulcer bleeding have increased death rates from smoking related disorders., Aim: To assess the role of smoking in ulcer perforation., Subjects: A total of 168 consecutive patients with gastroduodenal ulcer perforation and 4469 control subjects from a population based health survey., Methods: The association between ulcer perforation and smoking habits was analysed by logistic regression while adjusting for age and sex., Results: Current smoking increased the risk for ulcer perforation 10-fold in the age group 15-74 years (OR 9.7, 95% CI 5.9 to 15.8) and there was a highly significant dose-response relationship (p < 0.001). The results were similar in men (OR 9.3, 95% CI 4.9 to 17) and women (OR 11.6, 95% CI 5.3 to 25), and for gastric (OR 10.5, 95% CI 4.5 to 25) and duodenal (OR 8.6, 95% CI 4.9 to 15.4) ulcer perforation. No increase in risk was found in previous smokers (OR 0.8, 95% CI 0.2 to 2.2)., Conclusion: Our findings suggest that smoking is a causal factor for ulcer perforation and accounts for a major part of ulcer perforations in the population aged less than 75 years.

Background: It is presently not well understood to what extent peptic ulcer and gastric cancer represent related diseases., Aims: The objective of this study was to assess past occurrence of gastric and duodenal ulcers in patients with cancer of the gastric cardia or other parts of the stomach., Methods: The association between peptic ulcer and gastric cancer was studied among patients followed up at hospitals of the US Department of Veterans Affairs. Two populations of 1069 subjects with cancer of the cardia and 3078 subjects with cancer of other parts of the stomach were compared with a control population of 89082 subjects without gastric cancer. In multivariate logistic regressions, presence or absence of cancer served as the outcome variable, while age, sex, race, previous histories of gastric ulcer, duodenal ulcer, peptic ulcer site unspecified, gastric resection, or vagotomy served as modifier variables., Results: Old age, non-white ethnicity, and male sex proved strong and independent risk factors for non-cardiac gastric cancer. A previous history of gastric, but not duodenal ulcer was associated with a significantly raised odd ratio of 1.53 (95% confidence interval: 1.24 to 1.87). Cancer of the cardia affected predominantly whites, and was relatively more common in men than non-cardiac gastric cancer. Past gastric ulcers exerted no significant influence (1.02, 0.67 to 1.56), while duodenal ulcers and peptic ulcer site unspecified were protective (duodenal ulcer: 0.68, 0.47 to 0.95; peptic ulcer disease: 0.66, 0.47 to 1.00). Partial gastrectomy was a risk factor for non-cardiac gastric cancer (1.86, 1.32 to 2.63), but not for cancer of the cardia (1.09, 0.54 to 2.20)., Conclusion: These epidemiological patterns might stem from underlying differences in the influences of gastritis and acid secretion on the development of the two cancer types.

Background: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values., Aim: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers., Patients and Methods: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia., Results: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002)., Conclusions: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.

Background: Helicobacter pylori infection of the gastric mucosa is vital in the pathogenesis of duodenal ulcer disease. H pylori will only colonise gastric epithelium and its association with duodenal disease is therefore not easily explained., Aims: To determine if gastric metaplasia in the duodenum increases the risk of duodenal ulcer disease in children infected with H pylori., Patients: All children undergoing upper endoscopy over a 20 month period in a children's hospital in Ireland., Methods: Two biopsy specimens were obtained from the antral mucosa and two from the first part of the duodenum. One antral biopsy specimen was used in a rapid urease test (Clo Test). Biopsy sections were stained with haematoxylin and eosin and also with cresyl violet for identification of H pylori. Periodic acid Schiff (PAS) stain was performed to identify areas of gastric metaplasia., Results: Gastric and duodenal biopsy specimens were obtained from 148 patients (M:F 1:2:1). Twenty five children (17%) had H pylori positive gastritis. Thirty four children (23%) had gastric metaplasia in the duodenum. Nine per cent of children under the age of 8 years had gastric metaplasia compared with 38% in those 12 years of age or over (p < 0.005). Seven children had duodenal ulcer disease. Gastric metaplasia was present in six of seven (86%) children with duodenal ulcer disease compared with 28 of 141 (20%) without ulceration (p < 0.001). While both H pylori and gastric metaplasia were each significant risk factors for duodenal ulcer disease, the combined presence of both factors was associated with a pronounced increase in duodenal ulcer disease. Duodenal ulcer disease occurred in over 50% of children with both H pylori infection and gastric metaplasia. In contrast duodenal disease did not occur in children (0 of 100) when both were absent., Conclusion: The presence of gastric metaplasia in the duodenum is the major risk factor for duodenal ulcer disease in patients colonised by H pylori.

This study examines the relationship between Helicobacter pylori infection and peptic ulcer disease and gastric cancer--in particular, the presence or absence of bacteria, the grading of gastritis, and the degree of inflammation in the antral and oxyntic mucosae. The grading of gastritis and the detection of H pylori were determined by histology using the Sydney system. Of the 1006 patients examined, 34.5% had duodenal ulcer disease, 3.5% gastric ulcer disease, and 2% with coexistent ulceration. Most patients (50.2%) were classified as having non-ulcer dyspepsia. Altogether 2.4% of patients had gastric cancer and two further patients had carcinoma in the gastric stump. Of the ulcer disease patients, 87.2% had histological evidence of H pylori infection. After patients who had taken antibiotics or bismuth compounds in the preceding four weeks were excluded, 98.9% of the duodenal ulcer disease, 100% of the gastric ulcer disease, and 100% of the coexistent ulcer disease patients had evidence of H pylori infection. In patients with gastric cancer who had not taken antimicrobial agents in the four weeks before endoscopy, 83.3% had evidence of H pylori infection. Thus, there was a high rate of duodenal ulcer disease and a low rate of gastric ulcer disease in southern China, an area of low gastric cancer mortality. There was a specific topographical relationship between H pylori, the histological response, and gastroduodenal disease. Our data suggest that the status of a nation as either 'developed' or 'developing' can not be used to predict the upper gastrointestinal disease profile of its population.

A patient undergoing repeated endoscopic injection therapy for important bleeding from a duodenal ulcer developed intestinal perforation followed by extrahepatic obstructive jaundice resulting from benign biliary stricture. It is proposed that these complications were a consequence of the use of ethanolamine oleate as part of the injection regimen and caution against the use of this material is needed, particularly as current clinical trials suggest that sclerosants offer no advantage over injection therapy with dilute adrenaline alone.

Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03 microgram/l-1) against Helicobacter pylori (H pylori). This study aimed at determining the eradication rate using clarithromycin 500 mg thrice daily and omeprazole 40 mg daily for two weeks. Patients were given an endoscopy and H pylori status assessed by antral culture (microaerobic conditions, for up to 10 days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains), and 13C-urea breath test (13C-UBT, European standard protocol, positive result = excess delta 13CO2 excretion > 5 per mil). Compliance was assessed by returned tablet counts. H pylori clearance at the end of treatment and eradication four weeks after finishing treatment were assessed by the 13C-UBT. Seventy three patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM) excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral histology (n = 72) or positive antral culture (n = 35) were studied. Before treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and five isolates were resistant to metronidazole. In 70/73 (96%) the 13C-UBT was negative immediately after finishing treatment. Four weeks later the 13C-UBT was negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil, eradication rate = 78%). Forty eight (66%) patients experienced a metallic taste while taking the tablets. Although four (5%) patients, however, could not complete the course of treatment, in only one of these four was H pylori not eradicated. These results show that duel therapy with clarithromycin and omeprazole is well tolerated. With an eradication rate of 78% it is an effective treatment for metronidazole resistant H pylori and may be an alternative to standard triple therapy.

A prospective study of dyspepsia was carried out in a primary referral hospital between 1974-1987 including 1540 patients of whom 1433 were seen as outpatients. The study protocol was agreed in advance and a structured questionnaire was used to elicit relevant clinical information: up to three diagnoses were permitted for each patient. The commonest principal diagnoses were duodenal ulcer (26%), functional dyspepsia (22%), and irritable bowel syndrome (IBS) (15%); alcohol related dyspepsia (4%) was as common as gastric carcinoma or symptomatic gall stones. Multiple diagnoses were common (31% given two diagnoses, and 6% given three) so that in all 2111 diagnoses were given to 1540 patients; the functional disorders (IBS and functional dyspepsia) considered together accounted for 39% of all diagnoses made. Whereas organic conditions were diagnosed by clinicians with confidence (63-98% considered 'certain'), even when given as the principal or first diagnosis IBS was considered 'certain' in only 61% and functional dyspepsia 48%. The demographic symptom data, together with information on tobacco and alcohol use, and work lost are described in detail.

Perforated gastroduodenal ulcer was studied in 1483 patients in the Bergen area during the years 1935-90 to discover time trends in age and sex, disease characteristics, treatment, and outcome. The male:female ratio fell from 10:1 to 1.5:1, median age increased from 41 to 62 years. Most perforations were found in the duodenum in 1935-64, and in the pyloric and praepyloric area in 1965-90. There was a 10% occurrence of gastric ulcers throughout the study period. Ulcer site was related to age (more gastric and less duodenal perforations with increasing age) and sex (more pyloric and less duodenal ulcers among women). There were twice as many perforations in the evening compared with the early morning. The diurnal variation was more pronounced for duodenal and pyloric than for gastric and praepyloric perforations. Circadian and seasonal variation of ulcer perforation did not change during the 56 years studied. Treatment delay increased from median five hours to median nine hours. Infective complications and mortality fell with the introduction of antibiotics around 1950. General complications has increased in recent years because of the increase of elderly patients. Among patients who died, the proportion with associated disease rose from 27 to 85% during the study period.

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p < 0.0001). Endoscopies were performed depending on physicians' decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p < 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p < 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.

A controlled, randomised study was performed to evaluate the efficacy of treatment with heater probe in the prevention of rebleeding from peptic ulcer with a non-bleeding visible vessel. One hundred and one patients were randomised into two groups: patients to be treated by heater probe (n = 51) and controls without active treatment (n = 50). In the heater probe group rebleeding occurred in five patients (10%) v 13 (26%) in the control group (p = 0.03), with a comparative risk of 0.38 in favour of the heater probe group. The difference in proportions of successful treatment for each group was 16.2% in favour of the heater probe (95% CI = 2 to 31%). Haemorrhage directly related to heater probe treatment occurred in four patients. In three of them bleeding was easily controlled by further heater probe pulses. There were no other complications and no death in the heater probe group. One patient in the control group died of pulmonary embolism. No significant differences in the length of stay in hospital, blood transfusions, surgical rates, or death were found; the design of the study, however, precluded an adequate assessment of these variables, because the heater probe was an optional rescue treatment when high surgical risk patients rebled. These results suggest that the heater probe is an effective and safe procedure in the prevention of recurrent haemorrhage in peptic ulcer with a non-bleeding visible vessel.

Post-bulbar ulceration is uncommon, but a pilot study in Hyderabad showed a high incidence. We therefore carried out a prospective endoscopic study of the distribution of peptic ulceration and its relation to symptoms and demography. Of the 360 consecutive patients referred for endoscopy, 113 (92 men, 21 women) had peptic ulceration. Median age 35 years, median duration one year. Five patients (4%) had gastric ulcer, 77 (68%) had duodenal ulcer, and 31 (28%) had coexisting gastric and duodenal ulcer. The duodenal ulcer was found in the pyloric canal in 14% of patients, in the bulb in 80%, and the post-bulbar region in 56% of patients. Sixty seven per cent of duodenal ulcers were located at more than one site. The incidence of post-bulbar v bulbar ulcer was 1:1.5. Deformed bulb was seen in 50% of duodenal ulcer patients, but haemorrhage and stenosis were uncommon. Except for nocturnal pain, there were no differences in symptoms between the groups. Forty two per cent of patients smoked, 15% chewed tobacco, and 18% drank alcohol; almost all were men. Sixty four per cent drank tea. The staple diet (85%) was rice, and 70% used tamarind and spices daily. Duodenal ulcer was three times more common than gastric ulcer with a high incidence of post-bulbar and coexisting ulcer. It affected a younger and predominantly male population, and was not associated with a higher rate of complication.

Most patients with chronic duodenal ulcer disease have Helicobacter pylori infection and eradicating it considerably reduces the relapse rate. The prevalence of H pylori in 80 patients (mean age = 52 years, range 17-85) presenting with acute perforated duodenal ulcer was examined and compared with age and sex matched hospital control patients. H pylori state was assessed by serum anti-H pylori IgG (Helico-G kit, Porton) using a titre of 18 or less as negative with a specificity of 89% and sensitivity of 88%. Only 47% of the perforated duodenal ulcer patients were positive for H pylori and this was similar to the value of 50% in the controls. In 51 of the perforated duodenal ulcer patients 14C-urea breath tests were also performed 4-10 weeks after surgery and this confirmed that only 49% were positive for H pylori. None of these patients had received perioperative drugs that might have eradicated the infection. The H pylori positive and H pylori negative perforated duodenal ulcer patients were similar with respect to age (53, 51), smoking (84%, 83%), and consumption of more than 15 units of alcohol per week (42%, 38%). Duodenal ulcer disease had been diagnosed before acute perforation in only 24% of those with H pylori and also 24% of those without the infection. Regular non-steroidal anti-inflammatory drug (NSAID) use was common in both those with (44%) and without (45%) H pylori. In conclusion, the lack of association of acute perforated duodenal ulcer and H pylori infection suggests that perforated duodenal ulcer has a different pathogenesis from chronic duodenal ulcer disease, and that the first should not be regarded simply as a complication of the second.

Pain site and radiation and the effect of various foods were studied prospectively in a consecutive series of patients with chronic upper abdominal pain. Patients followed for less than one year were excluded unless peptic ulcer or abdominal malignancy had been diagnosed or laparotomy had been carried out. A total of 632 patients were eligible for the first study and 431 for the second. Gastric ulcer pain was more likely to be left hypochondrial (17%) compared with pain from duodenal ulcer (4%) or from all other conditions (5%). It was less likely to be epigastric (54%) compared with duodenal ulcer pain (75%). Oesophageal pain was more likely to be both retrosternal and epigastric (25%) compared with non-oesophageal pain (2%). Radiation to the back was more common in peptic ulcer (31%) and biliary pain (35%) compared with functional pain (20%). Pain precipitation by fatty foods was commoner in biliary disease (40%) than in duodenal ulcer (11%), peptic ulcer (9%), or non-ulcer dyspepsia (19%). Orange, alcohol, and coffee precipitated pain more frequently in duodenal ulcer (41%, 50%, and 43% respectively) than in biliary disease (17%, 0%, and 14% respectively). Chilli precipitated pain in one quarter to one half of subjects regardless of diagnosis. Approximately one tenth of all subjects avoided chilli, curry, coffee, and tea because of medical or other advice.

Surgical management of massive upper gastrointestinal bleeding after failed medical treatment may be hazardous because of diffuse bleeding from several sites, further complicated in some patients by intercurrent disease, age, or previous surgery. Experience with combined somatostatin and octreotide therapy in five such patients is described. All were treated initially with either intravenous somatostatin (250 micrograms/hour) or octreotide (Sandostatin) (50 micrograms/hour) for periods ranging from three to five days, after which they were given subcutaneous octreotide (50 or 100 micrograms three times daily). Bleeding was controlled by this regimen in all cases. The patients were all discharged from hospital on either ranitidine (n = 4) or omeprazole (n = 1). Repeat endoscopy at the end of the treatment period with somatostatin and octreotide (n = 1) or four weeks after discharge (n = 3) showed complete healing of the bleeding sites. Somatostatin and octreotide may be of value in controlling severe upper gastrointestinal bleeding in patients in whom surgery is hazardous because of bleeding from several peptic lesions further complicated in some by intercurrent disease or age.

We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).

The histamine concentration was determined by enzymatic isotopic method in biopsy specimens of oxyntic mucosa from 37 children. Nineteen of the 37 had Helicobacter pylori associated gastritis (9 with duodenal ulcer). The histamine concentration in the H pylori negative group was mean (SD) 54.1 (23.1) micrograms/g fresh weight, and that in the H pylori positive group was 26.3 (14.2) micrograms/g (p less than 0.01). There was also a significant difference between H pylori positive patients with duodenal ulcer (19.8 (6.3) micrograms/g) and those without ulcer (31.4 (17.9) micrograms/g) (p less than 0.05). These results suggest that H pylori positive patients, especially those with duodenal ulcer, have reduced 'stored' histamine, perhaps because of increased histamine liberation.

Duodenocaval fistula is usually caused by abdominal trauma. We report a patient in whom it was associated with peptic ulcer.

Emergency endoscopy on 332 patients with acute upper gastrointestinal bleeding showed that 178 had peptic ulcers; 28 of these were actively bleeding (spurting) and 108 showed stigmata of recent haemorrhage (vessels or spots in the ulcer base) suggesting a risk of rebleeding. These 136 patients were randomly allocated to Argon laser photocoagulation or to no additional therapy (controls) at the time of initial endoscopy. All patients received conventional management, and the controlling clinicians did not know whether or not the laser had been used in any individual patients. The laser system proved both simple and safe in use. Initial haemostasis was achieved by the laser in 10 of 15 'spurting vessels', but four of 13 'control' spurting vessels also stopped bleeding spontaneously. Overall, there were no statistically significant differences between the laser treated and control groups in terms of rebleeding, the need for surgical intervention, or death. These results require amplification in larger trials, and comparison with other studies using different protocols and other haemostatic methods.

An endoscopic Doppler device has been used to predict which patients with bleeding peptic ulcers will require surgery to stop their bleeding. The results show that if a Doppler signal can be elicited from an ulcer then the likelihood of rebleeding sufficient to require surgery or lead to death is increased very significantly.

The Gastroenterology Unit of the Royal Newcastle Hospital treats all acute bleeders in the hospital and has followed a policy of conservative blood transfusion and early surgery directed to gastric ulcer upon rebleeding. A prospective study of 201 consecutive episodes is presented and compared with recent series treated more conventionally. Our patients were transfused less, and operated upon less often with a lower mortality rate in those with chronic peptic ulcers. The data suggest that a reversion to the less aggressive treatment policies of several decades ago, combined with early limited surgery directed to endoscopically proven gastric ulcer is worthy of trial.

Sixty-seven patients with rheumatic disease, treated with non-steroidal anti-inflammatory drugs (NSAIDs), entered a controlled trial with a diagnosis of duodenal (n = 51), gastric (n = 14), or gastric and duodenal (n = 2) ulcers. The main objectives of the study were a comparison of ranitidine and sucralfate in ulcer treatment, and to observe the influence of continued NSAID administration during peptic ulcer therapy. Ulcers healed within nine weeks in 52 patients. The mean healing time was similar in 27 patients given ranitidine 150 mg bd (4.9 weeks) and 25 patients given sucralfate 1 g qid (4.6 weeks). In patients with unhealed ulcers after nine weeks of treatment, healing was obtained in seven after further therapy for 3-9 weeks. Of the 30 patients who continued NSAIDs during treatment with either ranitidine or sucralfate, 23 ulcers healed (mean healing time: 5.0 weeks). Of 32 patients in whom NSAIDs were stopped, ulcer healing was documented in 29 (mean healing time: 4.6 weeks). The difference in healing rates was not statistically significant (p greater than 0.10). The outcome of ulcer treatment did not differ in patients with rheumatoid arthritis and patients suffering from osteoarthritis. During a 12 month follow up 14 symptomatic ulcer recurrences were recorded.

This paper describes the clinical presentation of 360 patients suffering from "dyspepsia" at the time of their initial visit to two hospitals in Yorkshire. Disease categories studied were cholecystitis, duodenal ulcer, gastric ulcer, gastric cancer, and "functional" dyspepsia, with at least 50 patients in each category. The findings of this series are contrasted with "textbook" descriptions of these conditions. Some contrasts are quite surprising-for example, most of the 360 patients claimed that their pain was not aggravated by food. It is suggested that one reason for diagnostic error in this area of medicine is that clinicians have a faulty mental "database" of information with regard to the presentation of the various diseases concerned.

To evaluate the oesophageal motor activity preceding episodes of reflux, 10 pathological and 10 non-pathological refluxers and 26 normal subjects were investigated. The pressure events in spontaneous short periods of pressure activity (less than or equal to 60 sec) and in long activity periods were registered. The last contraction before reflux was more frequently found non-propagating than the last contraction of pressure periods not followed by reflux (p less than 0.01). The interval from the last contraction to reflux was shortest, if the contraction terminated in, or confined to the upper part of the oesophagus (p less than 0.001). Increased proportion of reflux episodes were preceded by an upper segmentary contraction (p less than 0.05) and a short activity period (p less than 0.02) in patients with pathological reflux in comparison with non-pathological refluxers. Spontaneously occurring sphincter relaxations might be triggered by preceding non-propagated contractile activity. The relative number of reflux episodes preceded by non-propagated pressure activity seems to be increased in patients with frequent episodes of acid reflux, compared with patients with infrequent episodes, or with normal subjects.

In order to evaluate the effect of somatostatin in the treatment of massive upper gastrointestinal bleeding a randomised double blind trial of 95 patients has been undertaken during a 28 months period. Patients with oesophageal varices have been excluded as well as patients with diabetes. All patients were endoscoped within eight hours of admission to the hospital, whereupon the source of bleeding and types of stigmata were assessed. Forty six patients, chosen at random, were given a 72 hour infusion of somatostatin, while the remaining 49 patients received infusion of placebo. The two groups were well matched for sex, age, and source of bleeding. On the day after admission, an additional endoscopy was performed at which eight patients in the somatostatin group and 16 in the placebo group were found to have a persistent bleeding. A total of five patients in the somatostatin group and 14 in the placebo group underwent surgery (Fisher's exact test, 2-tail, p = 0.04). Rebleeding occurred in six patients in the somatostatin group, of whom five experienced rebleeding after completion of the somatostatin treatment. In the placebo group, rebleeding occurred in five patients, of whom four rebled on the day after admission. The need for blood transfusions and the mortality rate did not differ significantly between the two groups. No toxic side effects were found as a result of the infusion of somatostatin. In this study, somatostatin reduced the number of patients needing surgery with massive upper gastrointestinal bleeding.

Ultrastructural and immunohistochemical studies of the small intestine are described in a Japanese patient with alpha heavy chain disease who had a history of colonic ulcers. Endoscopic examinations revealed multiple gastric erosion, duodenal ulcer, and a thickened, cobblestone-like pattern composed of small nodules in the duodenum and jejunum, which was similar in appearance to Crohn's disease. An electron microscopic study showed that the numerous, infiltrated cells in the jejunal lamina propria were matured plasma cells with atypical structure of the organelles. These plasma cells had alpha heavy chain protein devoid of light chain. Although secretory component was demonstrated normally in the epithelial cells by immunofluorescent methods, no association of this component with alpha heavy chain protein could be observed in any of the plasma and epithelial cells of this case. These facts suggest the absence of secretory alpha chain or secretory IgA, and a deficiency of the mucosal secretory immune system in this patient.

A consecutive series of 12 patients with stenosis secondary to duodenal ulceration were treated by proximal gastric vagotomy (PGV) and duodenoplasty or PGV and dilatation of the stenosis. Three months after operation the rate and pattern of gastric emptying of a solid meal was measured in each patient and compared with 18 patients with uncomplicated duodenal ulcer treated by PGV alone. Two patients developed gastric stasis in the early postoperative period which resolved with medical treatment. All patients were asymptomatic and were eating normally three months after operation. There was no significant difference in the rate of gastric emptying postoperatively between the patients who had stenosis and those who had uncomplicated duodenal ulcers. These results indicate that despite early postoperative difficulties in some patients pyloric dilatation or duodenoplasty with PGV are both effective treatments for stenosis due to duodenal ulceration.

Clinical data and histology from the oesophagus, gastric antrum, and duodenum were collected from 36 patients undergoing surgery for duodenal ulcer. Gastritis was present in 94% of the patients (25% of atrophic type), oesophagitis in 72% and duodenitis in 39%. Abnormal biopsies were present from all three sites in 33% of the patients. Only one patient showed three normal biopsies. The low incidence of duodenitis does not support the theory that duodenitis is part of the same spectrum as duodenal ulcer. Heartburn was related to the presence of gastritis (100%) and oesophagitis (76%) but not to duodenitis (52%). No relationship was found between the length of history, severity of pain, and histological abnormalities.

Two hundred and thirty five consecutive patients with a life threatening complication of peptic ulceration, who either died or required emergency surgery, have been studied over a 36 month period. Seventy eight of these high risk patients died; 25 at home, 19 in hospital without surgery and 34 postoperatively. Ninety eight patients had bleeding ulcers, 132 perforated ulcers and five had both bleeding and perforated ulcers. One hundred and forty one of these 235 patients (60%) were taking a non-steroidal anti-inflammatory drugs (NSAID) and the individual agents have been listed. The overall incidence of NSAID use in a hospital control group was 9.9%. The first sign of an ulcer was a life threatening complication in 58.2% of patients taking a NSAID. Nearly 80% of all ulcer related deaths occurred in patients using an anti-inflammatory agent. Patients using these drugs were older, with more pre-existing medical conditions and had larger ulcers than those not taking NSAIDs. The mortality associated with a peptic ulcer complication in patients taking a NSAID was more than twice that in patients with no such drug history. There appears to be a relationship between the development of a life threatening complication of peptic ulceration and NSAID ingestion. Much of the associated mortality and morbidity may be potentially avoidable.

Chronic (atrophic) gastritis (AG) is common in active duodenal (DU) and gastric ulcer (GU) disease. In this case control study in consecutive prospective outpatients (571 cases and 1074 controls) who had undergone diagnostic upper gastrointestinal endoscopy and routine biopsies from both antral and body mucosa, we calculated the risk of coexisting active DU and/or GU in different gastritis of the antrum or body and according to grade (superficial gastritis, mild, moderate or severe atrophic gastritis). The risk of coexisting active gastroduodenal ulcer (ulcer in duodenum and/or stomach), as well as the risk of DU or GU, was dependent upon the presence and grade of gastritis in antrum and body mucosa. The risk of coexisting ulcer, as expressed as an age adjusted relative risk (RR) and calculated as odds ratio of gastritis in cases and controls, was significantly increased in the presence of superficial antral and body gastritis (RR = 8.5 (7.0-20.0) in men; RR = 5.8 (3.3-10.2) in women), as compared with the risk of ulcer in subjects with histologically normal mucosa (RR = 1). The risk of ulcer, and the risk of GU in particular, increased further with increasing severity of antral gastritis. In such patients with moderate or severe atrophic antral gastritis the RR of coexisting ulcer even exceeded 20 in men and 10 in women (RR = 25.6 (9.0-72.7) in men; RR = 11.7 (5.9-23.0) in women). On the other hand, the RR of ulcer, and the RR of DU in particular, was below 1 in the presence of atrophic gastritis in the gastric body, irrespective of the grade of gastritis in the antrum. We conclude that the type and grade of gastritis strongly predicts the risk of coexisting peptic ulcer, and that the risk of coexisting DU or GU increases with an increase in grade of AG of the antrum but decreases with an increase in grade of AG of the gastric body.

The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.

Seventy two patients admitted to a medical department with dyspepsia but without a previous diagnosis of peptic ulcer disease or chronic pancreatitis were studied consecutively. A pancreatic function test (Lundh meal test) and an upper endoscopy was made in all patients. There was no difference in age, sex ratio, occurrence of upper abdominal pain or chronic alcoholism between the groups of patients with reduced pancreatic function (20) and the group with normal function (52). Seven duodenal ulcers were found, two in patients with normal pancreatic function (2/52 = 3.8%; 95% conf lim: 0.5-13.2) and five in patients with reduced pancreatic function (5/20 = 25%; 95% conf lim: 8.7-49.1). This difference was statistically significant (p less than 0.01). Duodenitis occurred with equal frequency in the two groups.

One hundred and twenty six consecutive patients presenting with upper alimentary bleeding were endoscoped. Seventeen gastric and 11 duodenal lesions with visible blood vessels were identified and cauterised with the electrohydrothermoprobe. One gastric and four duodenal vessels rebled, necessitating surgery. For the gastric vessels this represents about one tenth of the expected rebleeding rate, and is a significant reduction. The technique appears to have no effect on the rebleeding rate in duodenal vessels.