Effects of medical treatment on gastric mucosal abnormalities in gastroduodenal ulcer disease.

The development of carcinoma in cases of gastric ulcer disease during long-term H(2)-blocker treatment is slowly increasing, and ulcers that require such treatment exhibit the characteristics of intractable conditions, including linear ulcers, simultaneous gastric and duodenal ulcers, immature intestinal metaplasia of the gastric epithelium, and atrophic gastritis accompanied with multiple ulcer cicatrices. The incomplete form of intestinal metaplasia resembling Filipe's type III lesions and showing structural atypia developed in the background gastric mucosa in such cases, and the characteristics of this metaplasia included structural atypia, a residuum of gastric-type mucous cells, rapid proliferative activity, and in some areas abnormal expression of P53 protein. In addition, in rat studies it was demonstrated that prolonged administration of H(2)-blockers while gastric ulcers were present accelerated cell proliferation in the background gastric mucosa in the long term. Accordingly, it was considered possible that the development of the incomplete form of intestinal metaplasia, which was strongly suggested to have some relation to the sites where intestinal-type gastric carcinoma appeared, was accelerated by mucosal injury due to chronic ulcers and by persistent elevation in intragastric pH. The results of the present study of gastric carcinoma as a complication of peptic ulcer disease indicated the possibility that Helicobacter pylori was a major contributory factor to the development of the incomplete form of intestinal metaplasia from damage to the background mucosa, but it was unclear whether H. pylori made any direct contribution to carcinogenesis.