"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 eradication 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.

Dr. Talley has disclosed no relevant financial relationships.

Lancet. 2008;372:350-351, 392-397.

Clinical Context

H pylori plays an important role in the oncogenesis of gastric cancer, with as many as 80% of gastric cancers outside of the cardia being associated with H pylori infection. However, there is evidence that H pylori infection may have the opposite effect on the risk for esophageal cancer. A review and meta-analysis by Rokkas and colleagues, which was published in the December 2007 issue of Clinical Gastroenterology and Hepatology, demonstrated that the presence of H pylori was associated with an odds ratio of 0.64 for Barrett's esophagus vs no infection. Also, the odds ratio for esophageal cancer associated with H pylori infection vs no infection was 0.52.

Patients undergoing endoscopic resection of early gastric cancer are at significant risk for the development of gastric tumors apart from the resection site. The current study evaluates the efficacy of H pylori eradication therapy in the prevention of metachronous gastric carcinoma after endoscopic resection of early gastric cancer.

Study Highlights

• Patients eligible for study participation were between the ages of 20 and 79 years and had been diagnosed with early gastric cancer. All participants had documented H pylori infection from gastric biopsy results. Patients with a history of gastric surgery beyond endoscopic resection were excluded from study participation.
• Study participants were randomly assigned to receive H pylori eradication therapy with 1 week of lansoprazole, amoxicillin, and clarithromycin, or no eradication treatment.
• Subjects were examined with endoscopy at 6 months, 1 year, 2 years, and 3 years after randomization. The main outcome of the study was the development of metachronous gastric cancer.
• The main result of the study was adjusted to account for potential confounders, including age, sex, site of the initial cancer, and the duration between endoscopic resection and randomization.
• 544 patients underwent randomization. Baseline data were similar between the eradication and control groups. The mean duration between endoscopic resection and study randomization was 1.4 years. Three quarters of subjects were men, and the mean age was 68 years.
• H pylori was successfully eradicated in 75% of the intervention group, and H pylori infection resolved in 5% of the control group during follow-up.
• Slightly less than two thirds of participants completed 3 years of study follow-up.
• H pylori eradication significantly reduced the risk for metachronous gastric cancer (odds ratio, 0.353). The lower risk for metachronous cancer in the eradication group was evident within 1 year after randomization.
• H pylori eradication remained effective in the prevention of metachronous cancer when accounting for participants who were lost to follow-up.
• H pylori eradication was effective in preventing metachronous cancer regardless of the duration between previous resection and study randomization.
• No moderate or severe adverse events were associated with eradication treatment. Soft stools and diarrhea occurred in 12% and 7% of subjects, respectively, receiving eradication treatment.

Pearls for Practice

• A meta-analysis found that infection with H pylori was associated with reduced risks for Barrett's esophagus and esophageal adenocarcinoma.
• In the current study, eradication of H pylori significantly reduced the risk for metachronous gastric carcinoma after endoscopic resection of early gastric cancer.