Within the gastroduodenal mucosa Helicobacter pylori infection stimulates local production of a range of proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T- and B-cell responses and the development of gastric lymphoid follicles. Following bacterial eradication this mucosal inflammatory response resolves. Infiltrating neutrophils are likely to be one of the major mediators of mucosal damage. Neutrophil activation, including reactive oxygen metabolite production and the release of myeloperoxidase, will be induced directly by bacterial factors and indirectly through products of complement activation, bioactive lipids and host-derived cytokines. Interleukin-8, and related peptides of the chemokine family secreted by gastric epithelial cells, are likely to be important host mediators inducing neutrophil migration to sites of infection. Epithelial IL-8 is upregulated by TNF-alpha and IL-1 and directly by H. pylori strains expressing the CagA phenotype. The extent of mucosal injury may reflect bacterial density, the variability of different strains of H. pylori to induce chemokine expression in epithelial cells and the oxidative burst in neutrophils. Recent evidence from in vivo and in vitro studies shows that CagA+ VacA+ strains of H. pylori are associated with enhanced inflammatory responses and mucosal damage. Defining the specific bacterial mediators of mucosal inflammation will be important in elucidating the role of H. pylori in the pathogenesis of gastroduodenal disease.

In those <40 yr of age, it is concluded that both CagA-positive and CagA-negative H. pylori infections are related to risks of intestinal-type, diffuse-type, early, advanced, and distal gastric cancers.

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Complex interactions between several bacterial, host genetic and environmental factors determine whether H. pylori infected individuals develop gastric carcinoma. The importance of bone marrow stem cell engraftment during human gastric neoplasia is an area requiring urgent investigation.

Aim-To examine the vacA genotypes of Helicobacter pylori strains in Japan and to define whether any specific genotype was associated with gastric cancer. Methods-The allelic variation of vacA gene was studied using a recently introduced polymerase chain reaction based vacA genotyping system. Results-80 H pylori strains were isolated from gastric biopsies of 40 patients with gastric cancer and 40 control subjects in a Japanese population. All strains were s1/m1 subtype and 79 of 80 strains were classified as s1a subtype. Conclusions-The recently proposed vacA genotyping system is applicable to Japanese H pylori strains and most strains have the s1a genotype, associated with increased virulence. While the high frequency of s1a/m1 vacA genotype might play a role in the increased incidence of atrophic gastritis and gastric cancer in Japanese subjects, it precludes its use as a predictor of clinical outcome of H pylori infection in Japan. (J Clin Pathol 1998;51:299-301)