From Pages to Practice

By Karen Sokal-Gutierrez, MD, MPH, FAAP

Published March 21, 2018


A 62-year-old Korean American man visits his family physician after treatment for early gastric cancer. The physician reviews the gastroenterologist’s report describing successful endoscopic resection of a small tumor localized to the stomach. The patient says, “The doctor said that the surgery went well, but there’s a risk that the stomach cancer might return. Can I do anything to reduce the risk?”

Gastric cancer is one of the most common cancers worldwide, with the highest prevalence in East Asia, Eastern Europe, and South America. Studies have identified some behavioral and environmental risk factors for gastric cancer. These include dietary practices, such as frequent consumption of high-salt foods (e.g., salt-preserved fish, meat. and vegetables) and nitrates (e.g., cured meats), and low intake of raw vegetables and fruits, especially citrus. Other risk factors are obesity, smoking, and occupational exposures (e.g., mining, metal processing, and rubber manufacturing). However, among the risk factors for gastric cancer, Helicobacter pylori infection has been identified as a primary cause as it leads to gastritis that can progress to gastric atrophy, metaplasia, dysplasia, and gastric carcinoma.

Epidemiologic studies have shown a high prevalence of gastric cancer in regions with high prevalence of H. pylori infection, and cross-sectional studies have found high rates of H. pylori infection in patients with gastric cancer. In prospective studies, patients with H. pylori infection had a greater risk of developing gastric cancer and gastric lymphoma. Clinical trials have demonstrated that eradication of H. pylori can significantly reduce the incidence of primary gastric cancer. However, the question that remains is whether patients with early gastric cancer who undergo tumor resection benefit from H. pylori eradication therapy to prevent the development of subsequent (metachronous) gastric cancers which arise at a rate of approximately 3% per year.

This week in NEJM, researchers from the National Cancer Center in South Korea report the results of a double-blind, randomized-controlled trial of eradication treatment for H. pylori in 396 patients (age range, 18-75 years) who had undergone endoscopic resection of early gastric cancer or high-grade adenoma. Patients had a tumor localized to the stomach without lymph node or distant metastasis on computed tomography, and no previous history of gastric cancer or H. pylori treatment. They were randomized to receive either H. pylori eradication therapy (amoxicillin, clarithromycin and the proton-pump inhibitor rabeprazole twice daily for 7 days) or placebo plus rabeprazole.

During a median follow-up of 5.9 years, subsequent gastric cancer was identified in 27 of 202 patients (13.4%) in the placebo group, but only about one-half the rate (14 of 194; 7.2%) in patients in the treatment group (hazard ratio, 0.50; 95% CI, 0.26 to 0.94; P=0.03). Furthermore, subsequent gastric cancer, was identified in 32 of 228 patients (14.0%) with persistent H. pylori infection, but only one-third the rate (9 of 167; 5.4%) in patients with successfully-eradicated H. pylori infection (HR, 0.32; 95% CI, 0.15-0.66; P=0.002). Histologic analysis of precancerous gastric mucosal atrophy at baseline and 3-year follow-up showed atrophy-grade improvement in only 15.0% of patients in the placebo group compared to 48.4% of patients in the H. pylori treatment group — a three-fold difference in the rate of improvement (P<0.001). No serious adverse events were reported in either group. The authors concluded that even in patients with gastric cancer with severe histologic changes, H. pylori eradication significantly improved gastric mucosal atrophy and reduced the development of subsequent gastric cancer.

Returning to the patient recovering from gastric cancer surgery, the physician should reassure him that the results of the surgery look good. In addition, the physician can explain that most people with gastric cancer carry H. pylori infection in their stomachs, and that a recent study found that one week of medicine to eliminate H. pylori can significantly reduce the risk of reoccurrence of gastric cancer. After contacting the gastroenterologist to discuss treating the patient with a 7-day course of amoxicillin, clarithromycin and rabeprazole, the physician should review other risk factors with the patient and counsel him to limit consumption of high-salt foods and nitrates, eat plenty of raw vegetables and fruits, maintain a healthy weight, and quit smoking.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.