A Japanese study of patients with early gastric cancer shows that eradicating the bacteria Helicobacter pylori after surgery greatly reduces the risk of gastric cancer developing again. This adds to data from previous studies showing a causal relation between H. pylori infection and gastric cancer, and supports eradicating H. pylori to prevent gastric cancer, say the researchers of the study published in the August 2 issue of the Lancet.
“Preventing gastric cancer by eradicating H. pylori in high-risk regions should be a priority,” writes Nicholas Talley, MD, PhD, from the Mayo Clinic Jacksonville, in Florida, in an accompanying editorial. Worldwide, gastric cancer kills more people than colorectal cancer, and there is better evidence that H. pylori can prevent mortality than there is that colonoscopy screening can, he notes.
However, the case is not cut and dried. Screening for and treatment of infected people to prevent gastric cancer is not generally accepted, Dr. Talley comments. This is despite the fact that H. pylori has been classified as a carcinogen for stomach cancer by the World Health Organization (WHO), and that an Asian-Pacific consensus conference in 2007 concluded that population-based screening and antibiotic treatment of H. pylori in high-risk populations is now recommended (J Gastroenterol Hepatol. 2008;23:351-365).
According to Dr. Talley, this needs to change. “Population screening and treatment should be pursued by governments in populations at very high risk and by the WHO,” he writes. “Compelling evidence now exists to show that H. pylori eradication reduces the risk of subsequent gastric adenocarcinoma.”
Results From Latest Study Are Clear
The latest study from Japan adds to the accumulated evidence. Conducted by Kazutoshi Fukase, MD, from the Yamagata Prefectural Central Hospital, and colleagues, for the Japan Gast Study Group, the trial involved 544 patients with early gastric cancer. Patients underwent endoscopic resection and then underwent endoscopy at 6, 12, 24, and 36 months.
Half the patients were randomized to receive treatment to eradicate H. pylori infection with lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg, all given twice daily for a week. In this eradication group, 19 patients (7%) reported diarrhea and 32 patients (12%) reported soft stool.
The other half of the patients acted as a control group. They did not receive placebo, because it would not have made much difference, Dr. Fukase and colleagues comment. Endoscopists can guess from the look of the gastric mucosa whether or not a patient has had H. pylori eradication therapy, they explain. In addition, the trial was designed to be open label to attract participants, because “Japanese individuals feel strong anxiety when they do not know whether they are being given active drugs or not, and thus often refuse to join placebo-controlled trials,” they comment. For ethical reasons, after the final analysis, patients in the control group were given eradication therapy, as were patients in the eradication group who still had H. pylori infection.
After 3 years, cancer had developed at another site in the stomach (metachronous gastric cancer) in 9 of 272 patients in the eradiation group and in 24 of 272 patients in the control group (odds ratio, 0.353; 95% confidence interval [CI], 0.161–0.775; P = .009).
These patients were at very high risk for recurrent gastric cancer, Dr. Talley points out, and yet the risk for subsequent cancer decreased from 4 in 100 every year to 1.4 in 1000 every year in the eradication group.
Dr. Talley states that this is an important study and that the results are clear: gastric cancer rates are substantially reduced, although not abolished, after H. pylori eradication in a high-risk population.
Some Previous Studies Were Less Clear-Cut
However, the researchers point out that previous studies have had less clear-cut results. A large double-blind randomized study in China showed that gastric cancer still occurred after successful eradication of H. pylori, and that eradication did not lead to a significant decrease in the incidence of gastric cancer (JAMA. 2004;291:187-194). Another study, a meta-analysis of 4 randomized intervention studies with gastric cancer incidence as a secondary outcome, showed a nonstatistically significant overall odds ratio of 0.67 (95% CI, 0.42–1.07) (Aliment Pharmacol Ther. 2007;25:133-141).
The benefits and risks of H. pylori eradication still need to be tested in large randomized trials in Asia, but these studies would be expensive and time-consuming, noted Dr Talley. Hence, he urges action now for populations who are at high risk for gastric cancer.
The study was supported by the Hiroshima Cancer Seminar Foundation. The researchers have disclosed no relevant financial relationships.
Lancet. 2008;372:350-351, 392-397.
Reviewed by Ramaz Mitaishvili, MD
