Eradication of Helicobacter pylori in patients with early-stage gastric cancer reduced the risk of subsequent gastric carcinoma significantly, compared with controls, in a Japanese study of more than 500 patients.
H. pylori is a known gastric carcinogen, according to the World Health Organization, and its casual effect on the development of gastric cancer has been proved in animal studies, wrote the department of gastroenterology at Yamagata (Japan) Prefectural Central Hospital.
“This excellent study importantly assessed the preventive effect of H. pylori eradication in patients with very advanced disease [i.e., those who progressed to early gastric cancer] on the risk for a second cancer. It clearly showed a 65% reduction in the development of the second cancer, based on intention-to-treat analysis.”
“It has been difficult to establish the benefit of H. pylori eradication on gastric cancer development in randomized, prospective studies, due to need for very large numbers of patients to establish a significant benefit.”
“A previous study did not show an overall decrease in gastric cancer incidence, the primary end point, but did show a marked decrease in cancer in patients who did not have preneoplasia (e.g., intestinal metaplasia) at study entry (i.e., subgroup analysis or secondary end point). This study thus suggested that only patients who did not have advanced disease would benefit,” according to the Silberberg professor of medicine and chief of the division of digestive and liver diseases at Columbia University College of Physicians and Surgeons.
“On the other hand, studies in mice have strongly suggested that eradication of gastric Helicobacter could halt and even reverse much of the atrophy and metaplasia, and prevent progression of advanced lesions such as dysplasia.” In the current multicenter, open-label, randomized, controlled study, 544 patients with early gastric cancer either planned to have endoscopic treatment. Half (272 patients) were given a drug regimen to eradicate the H. pylori bacterium, and half served as controls.
The treatment group received a combination of lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week. All patients had follow-up clinic visits at 6 months, 1 year, 2 years, and 3 years after randomization, to see if new cancer had developed and to confirm their H. pylori status.
Three-quarters of patients in both groups were men, and all patients were aged 62-73 years. A modified intention-to-treat analysis included 255 patients in the treatment group and 250 in the control group, after 17 treatment patients and 22 controls were lost to follow up.
“During 3 years of follow-up after endoscopic treatment of primary gastric cancer, metachronous gastric cancer developed in 33 participants — 9 in the eradication group and 24 in the control group.” There were no differences between the patients who developed cancer in each group in terms of sex, age, location of the cancer, histologic type, or depth of the invasion of the diameter of the metachronous cancers.
“The risk of subsequent cancer was reduced from about 4,000/100,000 individuals per year to 1,400/100,000 individual per year.”
In a comment accompanying the article, of the department of internal medicine at the Mayo Clinic in Jacksonville, Fla., wrote, “In high-risk population, gastric cancer rates are substantially reduced, but not abolished, by H. pylori eradication.”
He added that the potential risks associated with H. pylori eradication — including a possible increased risk of gastroesophageal reflux disease, barrett’s esophagus, and esophageal adenocarcinoma, as well as a potential for asthma and atopy — are small.
“One potential criticism of the study is that it was open-label, but the findings are believable nonetheless.” “The investigators used a standard PPI triple (LAC) regimen, and it is important to note that only 75% of patients were successfully eradicated. This points to the need for, and potential benefit of, a more effective H. pylori eradication regimen.”
“Early studies suggested that prevention of gastric cancer H. pylori eradication would be cost effective if only 30% of cancers could be prevented. The current study suggests that a much larger percentage of cancer cases could be eliminated in high-risk population.”
“There are some concerns about extrapolating the results from this study in patients with early gastric cancer to a broader population of H. pylori-infected patients that have never had cancer, however, from what the histopathogical progression that occurs in patients with chronic gastritis, this extrapolation is likely to be reasonably accurate.”