Ulcers and Gastritis

Gastric Cancer: Identification of High-Risk Individuals

Gastric cancer is still the second commonest cause of cancer-related death in the world. Helicobacter pylori is now thought to be responsible for more than 95 % of gastric cancers. However, the prevalence of gastric cancer varies with age, within and between populations and regions, and between the sexes. The natural history of the disease and the risk factors for developing gastric cancer are still poorly defined.

In a prospective endoscopic cohort study by Watabe et al., patients were stratified into different risk groups according to their baseline H. pylori infection status, as well as serum pepsinogen levels [1]. They were divided into four groups: group A, with normal pepsinogens and negative H. pylori serology (normal); group B, with normal pepsinogens but positive for H. pylori antibodies; group C, with low pepsinogens and positive for H. pylori; and group D, with low pepsinogens and negative serology for H. pylori. A total of 6983 patients were followed up for a mean of 4.7 years with annual upper endoscopy examinations for health screening. Forty-three patients developed cancer during the follow-up period, with an annual incidence rate of cancer development of 130 per 100 000/year (95 % CI, 100 - 180). The annual incidence rates differed between the groups; they were similar in the normal uninfected group and the group of patients infected with H. pylori but with normal pepsinogens (40 and 60, respectively), in comparison with 350 and 600 in the atrophic groups with and without H. pylori antibodies, respectively. Two of the seven patients in the normal uninfected group who developed cancer had lesions located in the cardia. The adjusted hazards ratios for gastric cancer development in groups B, C, and D were 1.1 (95 % CI, 0.4 - 3.4), 6.0 (2.4 - 14.5), and 8.2 (3.2 - 21.5), respectively. In addition, age over 60 and male sex were associated with a significantly higher risk of developing gastric cancer.

The results of this large-scale endoscopic cohort study confirm and extend the observation that H. pylori-induced gastric atrophy is the most important risk factor for the development of gastric cancer, with age and sex being additional important factors. Apparently paradoxically, those with an atrophic pepsinogen pattern and negative serology for H. pylori had the highest risk for gastric cancer. This group of patients were also the oldest and had the lowest level of pepsinogen I, indicating that they had atrophy severe enough to lead to the natural disappearance of H. pylori, consistent with atrophy or changes in the gastric milieu being critical elements.

The study has a number of implications. Firstly, it is possible to stratify individual cancer risk using simple serology tests in such a way that limiting surveillance studies to those who are at increased risk will increase the cost-effectiveness of screening. Secondly, the risk of gastric cancer correlates with gastric atrophy; H. pylori eradication therapy should therefore be administered early and targeted to prevent the progression to atrophy. Once advanced atrophy develops, H. pylori eradication alone cannot be expected to eliminate the cancer risk. In this high-risk group, surveillance endoscopy is potentially useful for identifying early cancer and thus reducing cancer deaths.

In keeping with these results, Ohkusa et al. showed that there was improvement in the serum pepsinogen I/II ratio 12 - 15 months after H. pylori eradication, with the levels becoming similar to those in patients without H. pylori infection [2]. These results are consistent with those of earlier studies showing an improvement in gastric acid secretion after H. pylori eradication. Both the improvement in pepsinogen levels and acid secretion correlate with reduced inflammation. A new study has also added another dimension, showing that the expression level of H⁺/K⁺-ATPase in the gastric mucosa increased 250-fold after H. pylori eradication. This increase was accompanied by an attenuation of mucosal interleukin-1 beta levels [3]. This increase in H⁺/K⁺-ATPase expression was also observed in patients with severe atrophic gastritis. However, there was no change in the total numbers of parietal cells. Together, these data suggest that the improvement in gastric function is related to improvements in the function of existing cellular components, but does not exclude the regeneration of new cellular elements (i. e., actual reversal of atrophy). These results provide additional data in favor of early eradication of H. pylori in order to prevent the development of gastric cancer; the recovery of gastric acid production appears to play an instrumental role in this respect.

References

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