Although controversial, clinicians generally consider patients who present with gastric ulcer to have an increased risk of gastric cancer, while the risk for patients with duodenal ulcer is reduced in comparison with that of the general population. Infection with Helicobacter pylori and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are the major causes for peptic ulcers, but their roles in relation to the risk of gastric cancer in patients with peptic ulcer may be different.

This article reviewed existing literature to assess our understanding of the risk of gastric cancer in patients with gastric and duodenal ulcers more than 25 years after the discovery of H. pylori and also examined whether gastric ulcers induced by NSAID carry a lower risk of gastric cancer as compared to those induced by H. pylori infection or other causes.

Helicobacter pylori (HP) infection may cause extradigestive manifestations directly or indirectly, by potential mechanisms. HP infection triggers a marked local inflammatory response and a chronic systemic immune response. Some of the mediators that are thought to be possibly involved in the pathogenesis of extradigestive diseases caused by HP infection include IL-1, TNF-alpha, interferon (IFN)-gamma, leukotriene C4 and platelet-activating factor. Previous epidemiological and serological case control studies have revealed that HP infection might have a role in the development of chronic bronchitis, bronchiectasis, lung cancer and tuberculosis. However HP infection does not appear to have a role in the development of bronchial asthma. Considering the importance and prevalence of respiratory system diseases, it may be time to conduct well-designed sets of studies to clarify whether there is an association with HP infection and respiratory system diseases, and to answer questions that have been posed regarding the patterns of histology, genotypes of HP, and the effects of eradication therapy. The aim of this review was to analyze the possible association between HP and respiratory disease and provide a critical review of the relevant literature.

We performed a detailed analysis of the epidemiology of gastric carcinoma, based upon a review of the literature in English. The analysis reveals many puzzling features. There has been a steady fall in the incidence of gastric carcinoma in most societies studied, but a more recent steady rise in the incidence of adenocarcinoma of the cardia and lower esophagus, largely confined to White males. Although the evidence for a major role for Helicobacter pylori (H. pylori) in the etiology of gastric corpus cancer is compelling; in Western society, it probably accounts for fewer than half the cases. The relative roles of dietary constituents such as salt and nitrites and the phenotyping of H. pylori in causation and the beneficial effects of a high fruit and vegetable diet and an affluent lifestyle, for all of which there is some evidence, are yet to be quantified.

Duodenogastric reflux predisposes to gastric cancer. This study investigates whether ulceration induced by duodenogastric reflux is associated with the development of neoplasms in the stomach.

In a rat experiment, duodenal fluid was directed into the corpus (jejunal reflux) or through the pylorus into the antrum (pyloric reflux). Sham-operated animals served as controls. The animals were sacrificed after 24, 36, or 52 weeks.

Ulcerations and neoplasms occurred more frequently in the corpus than in the antrum. In the corpus, ulceration was observed significantly more often in animals with jejunal reflux (62, 55, and 53% at 24, 36, and 52 weeks, respectively) than in animals with pyloric reflux (15, 21, and 30%). The incidence of neoplasm in the corpus increased significantly with time from 38% at 24 weeks to 89% at 52 weeks in animals with jejunal reflux and from 12 to 33% in animals with pyloric reflux. Ulceration and neoplasms shared location in the corpus adjacent to the gastrojejunostomy and by 24 weeks, all but one neoplasm in the jejunal reflux and one in pyloric reflux groups occurred adjacent to ulceration. In the antrum, 37% of the animals had a prepyloric ulceration after 24 weeks of pyloric reflux and only one of these animals had a neoplasm. By 52 weeks 20% of animals with pyloric reflux had a neoplasm that appeared in the prepyloric area.

Ulceration and neoplasm occurred at the same sites in the stomach, and ulcerations preceded the development of neoplasms in the antrum and very likely in the corpus. The results suggest that ulceration plays an important role in the genesis of neoplasms in the stomach and that the vulnerability to duodenogastric reflux is more pronounced in the corpus than in the antrum mucosa.

To clarify the usefulness of endoscopic ultrasonography (EUS) and endoscopy in the endoscopic mucosal resection (EMR) of early gastric cancer. Patients/Methods-EMR was performed in 61 patients with early gastric cancer over the past five years. The accuracy of the assessment of the depth of cancerous invasion was studied in 49 patients who had EUS before EMR. Forty eight patients were treated with endoscopy alone; in these patients, EUS and endoscopic findings correlated with the clinical course.

Forty six patients showed no changes in the submucosal layer or deeper structures on EUS. Pathologically these included 37 patients with mucosal cancer and nine with submucosal cancer showing very slight submucosal infiltration. Three patients showed diffuse low echo changes in the submucosal layer on EUS; pathologically, these included two with submucosal cancer and one with mucosal cancer with a peptic ulcer scar within the tumour focus. Of 48 patients receiving endoscopic treatment alone, 45 showed no tumour recurrence or evidence of metastases on EUS and endoscopy. Three cases of recurrence were observed. Two of these patients had a surgical gastrectomy, and one was re-treated endoscopically. In the former cases, the surgical results correlated well with assessment by EUS and endoscopy. In addition, the latter patient who was re-treated endoscopically after evaluation with EUS and endoscopy has so far had no recurrence.

The combined use of EUS and endoscopy is effective in diagnosing the depth of cancerous invasion in patients undergoing EMR as well as in clarifying changes both within and between anatomic levels during follow up.

To study the epithelial kinetics of the post-surgical stomach with reference to dietary salt intake and H pylori.

Endoscopic biopsies of the antrum/anastomosis and corpus were taken for histology and MIB-1 immunostaining. The labelling index (LI%) was determined in the three zones of the gastric glands (zone 1 = surface + gastric pit; zone 2 = isthmus; zone 3 = gland base) in patients with vagotomy and pyloroplasty (n = 12), gastroenterostomy + vagotomy (n = 4), partial gastrectomy (n = 3), and Billroth I operation (n = 3). Dietary salt was determined by urinary sodium/creatinine ratio. Twelve patients were H pylori positive (10 vagotomy and pyloroplasty; 2 partial gastrectomy) and had a repeat biopsy three months after antihelicobacter treatment (10 were H pylori negative after treatment).

There was no correlation between salt intake and antrum/anastomosis (r = -0.34; p = 0.2) or corpus (r = -0.16; p = 0.2) labelling indices. Gastric mucosal proliferation is increased in the antrum/ anastomosis compared to the corpus in H pylori positive (p = 0.014) but not H pylori negative subjects (p = 0.084). This may reflect the different types of post-surgical stomach in each group. Gastric mucosal proliferation is reduced in antrum/anastomosis (p = 0.002) and corpus (p = 0.016) following H pylori eradication.

Dietary salt does not influence gastric mucosal proliferation in the post-surgical stomach but H pylori may have a role in gastric stump carcinogenesis.

Helicobacter pylori infection, now considered to be a cause of gastric cancer, is also strongly associated with gastric and duodenal ulcer disease. The discovery of these relations has brought the long-controversial connection between peptic ulcers and gastric cancer into focus.

We estimated the risk of stomach cancer in a large cohort of hospitalized patients with gastric or duodenal ulcers, as recorded in the Swedish Inpatient Register between 1965 and 1983. Altogether, 57,936 patients were followed through 1989, for an average of 9.1 years. The standardized incidence ratio--the ratio of the observed number of cancers to the number expected on the basis of the incidence in the Swedish population at large--was used as a measure of relative risk.

After peaking in the first 3 years of follow-up, the standardized incidence ratio for gastric cancer among 29,287 patients with gastric ulcers leveled off at 1.8 (95 percent confidence interval, 1.6 to 2.0) and remained significantly increased throughout follow-up, which was as long as 24 years for some patients. Prepyloric ulcer, diagnosed in 8646 patients, was not associated with a significant excess risk (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.8 to 1.6). In the cohort of patients with duodenal ulcers (24,456 patients), the incidence of gastric cancer was significantly lower than expected. After the second year of follow-up, the standardized incidence ratio was only 0.6 (95 percent confidence interval, 0.4 to 0.7) and remained stable thereafter.

Gastric ulcer disease and gastric cancer have etiologic factors in common. A likely cause of both is atrophic gastritis induced by H. pylori. By contrast, there appear to be factors associated with duodenal ulcer disease that protect against gastric cancer.

Helicobacter pylori is now recognized as the major acquired factor in the pathogenesis of duodenal ulcer disease (DU). There is also an association between H. pylori infection and the subsequent development of gastric cancer. The mechanisms by which such infection predisposes the host to these diseases are incompletely understood, but disorders induced by the bacterium in gastric function play a pivotal role. In most patients, H. pylori infection stimulates acid secretion, leading to a predisposition to DU development. However, in some patients, the infection is associated with a significant decrease in acid secretion, a predisposition to gastric cancer. These divergent effects of H. pylori on gastric acid secretion explain the early conflicting reports on changes in acid secretion associated with the infection. The reason why H. pylori infection produces divergent effects on gastric acid secretion is unclear, but may be related to differences in bacterial strains or genetic, dietary or other environmental factors.

A critical evaluation has been made of the available evidence in man of the effects of prolonged low acid states on the structure and function of the stomach. Various human models have been examined. 1. Ageing does not affect acid output from the normal male stomach, and there may be an increase in women. With progressive atrophy of the corpus mucosa, which is more frequent and rapid in patients with gastric ulcer, there is an associated loss of secretory function. Chronic gastritis and atrophy are the most important age-related changes, which in many cultures are hypothesized to develop via a prior Helicobacter pylori-related gastritis. However, H. pylori colonization of the mucosa decreases with increasing grades of gastric atrophy probably because intestinal metaplasia provides a hostile environment. Atrophy and intestinal metaplasia are associated with precancerous lesions and gastric cancer. Apparent hyperplasia of the gastric argyrophil endocrine cells is a common and spontaneous phenomenon in patients with atrophic gastritis, which in part may be related to the preferential loss of nonendocrine cells. 2. Pernicious anemia is associated with a complete lack of acid production, marked hypergastrinemia, and endocrine cell hyperplasia in the majority of patients. ECL-cell carcinoids and gastric cancer occur with a prevalence of 3-7%, and endoscopic surveillance in routine clinical practice is not warranted. 3. Gastric ECL-cell carcinoids are rare events that have been described in association with two diseases in man, pernicious anemia and Zollinger-Ellison syndrome as part of multiple endocrine neoplasia syndrome type I, and usually relate to marked hypergastrinemia and the presence of chronic atrophic gastritis with gastric antibodies or a genetic defect rather than the presence or absence of acid. Regression or disappearance of ECL-cell carcinoids, either spontaneously or after removal of the gastrin drive, has been recorded. Lymph node, and rarely hepatic, metastases are documented but death in these cases has been anecdotal. 4. Therapy with H2 antagonists may result in up to a twofold rise in serum gastrin levels but in man no endocrine cell hyperplasia has been recorded. However, the data for H2 antagonists on these aspects are very limited. There is no drug-related risk of gastric or esophageal cancer, although the incidence of the latter may be raised. Long-term treatment with omeprazole is associated with a two- to fourfold increase in gastrin levels over baseline values in one third of patients and apparent endocrine cell hyperplasia in 7% of cases overall.(ABSTRACT TRUNCATED AT 400 WORDS)

Gastric adenocarcinoma is among the most common malignancies worldwide. Its etiopathogenesis is complex and, as yet, incompletely understood; however, diet, infection with Helicobacter pylori, and genetic factors are involved. It may be classified into two main types, intestinal and diffuse. The intestinal type has decreased in incidence, whereas the diffuse tumors as well as those confined to the cardia are increasing. Numerous conditions, such as gastritis, gastric atrophy, and intestinal metaplasia (IM), are associated with intestinal type gastric cancer in retrospective studies, but only epithelial dysplasia has a positive predictive value for malignancy. These precursor conditions and lesions are analyzed for their clinicopathological significance in this review, which concludes with a brief summary of curable (early) forms of gastric cancer.

Atrophic gastritis is a well-known risk condition for gastric carcinoma (GCA). Less is known about the risk of GCA in subjects with nonatrophic ('superficial') gastritis. To investigate this, we estimated the risk of GCA in patients with nonatrophic gastritis as compared with that in subjects with normal, nongastritic mucosa. Two hundred and forty-three consecutive GCA patients and 1408 non-GCA outpatients (controls), for whom histologic data (endoscopic biopsy) of gastric mucosa was available, were included in the study. To estimate the relative risk (RR) of GCA, the odds ratio of gastritis was calculated in patients and controls by adjusting for age and sex. The RR (95% confidence interval) of GCA in patients with nonatrophic antral gastritis and with nonatrophic pangastritis was 1.8 (1.2-2.7) and 2.5 (1.4-4.3), respectively. Correspondingly, the risks of GCA were 9.1 (5.4-15.5) in patients with atrophic antral gastritis or pangastritis (atrophy of any degree) and 4.4 (1.9-10) in those with severe atrophic corpus gastritis (severe corpus limited atrophy of 'A type'). In nonatrophic gastritis the risk of diffuse-type GCA was emphasized, whereas the risk of intestinal-type GCA was emphasized in patients with atrophic gastritis. These results indicate that an increased risk of GCA is not confined to subjects with atrophic gastritis but is also slightly but significantly increased in patients with chronic nonatrophic gastritis.

The activity of the DNA repair enzyme O6-alkyltransferase has been studied in a series of stomachs with abnormal gastric mucosa and the activities found compared with those in normal stomachs. Enzyme activities found in stomachs with the macroscopic abnormalities of gastric ulcer, duodenal ulcer or gastric cancer were not significantly different from normal. In those stomachs where there was histological evidence of chronic atrophic gastritis or intestinal metaplasia however enzyme activities (mean 398 fmole/mg) were significantly higher than normal (mean activity 228 fmole/mg activity P < 0.001). We speculate that the conditions which stimulate these histological changes also give rise to induction of O6-alkyltransferase.

Fasting gastric juice pH and concentrations of vitamin C in gastric aspirate and plasma were measured in 73 patients undergoing endoscopy. Vitamin C concentrations were significantly lower in those with hypochlorhydria (pH greater than 4; n = 23) compared with those with pH less than or equal to 4 (p less than 0.005) and there was a significant correlation between gastric juice and plasma concentrations (p = 0.002). Patients with normal endoscopic findings had significantly higher intragastric concentrations of vitamin C than those with gastric cancer (p less than 0.001), pernicious anaemia (p less than 0.005), gastric ulcer (p less than 0.01), duodenal ulcer (p less than 0.05), or after gastric surgery (p less than 0.01). There was a strong trend (0.05 less than p less than 0.1) towards lower intragastric concentrations of vitamin C in patients with chronic atrophic gastritis. In vitro, vitamin C concentrations remained stable in acidic but fell significantly over 24 hours in alkaline gastric aspirate. Gastric secretory studies in five volunteers showed that vitamin C concentrations increased significantly after intramuscular pentagastrin. These findings suggest that the low fasting levels of vitamin C in hypochlorhydric gastric juice may be caused by chemical instability and that vitamin C may be secreted by the human stomach.