Thursday, May 19, 2022

Part II

Last week we introduced the subject of Helicobacter pylori, a bacterium in the stomach that has been found to be associated with gastritis and duodenal ulcers. Infection with H. pylori is very widespread throughout the developing world and Far East and less prevalent in the U.S. and the West.

H. pylori prevalence has been declining in countries of the West, and gastric cancer incidence has been declining in parallel. In the U.S., the prevalence of H. pylori is less than 20% at the age of 20 years and increases to 40-50% by 50 years. In Japan and Korea, it is also less than 20% at 20 years but increases to 80% at 50 years, and in Korea to 90%.

An association between H. pylori infection and gastric cancer has been shown in numerous studies. One of the classic studies was published in the New England Journal of Medicine in 2001. The study, conducted in Japan, enrolled 1,526 patients with gastric or duodenal ulcers, or dyspepsia. All underwent gastroduodenoscopy at baseline; 1,246 (81.7%) were H. pylori-positive. All the patients were followed for a mean of 7.8 years; repeat endoscopy was performed between one and three years after baseline. During follow-up, 36 gastric cancers developed, all of them among the 1,246 H. pylori-positive patients and none among the 280 uninfected patients.

The general thinking is that the bacterium causes inflammation and that this leads to the carcinogenic process. The gastritis and ulcers are also part of the causal pathway. Thus, gastric cancer associated with H. pylori generally occurs in the distal part of the stomach or antrum, the part of the stomach adjacent to the duodenum/small intestine, where the large majority of gastric cancers occur.

Recent years have seen a decline in the prevalence of H. pylori in the U.S., brought about by more aggressive monitoring and antibiotic eradication. While this has led, in part, to the dramatic decline in distal gastric cancer observed in the U.S., it may not have been an uncompensated gain.

Martin Blaser has been an outstanding authority on the gastric microbiome for decades. He previously served as chair of medicine at New York University and is presently the director of the Center for Advanced Biotechnology and Medicine at Rutgers. He contributed a great deal to our understanding of specifically how H. pylori leads to gastric cancer, what co-factors play a role, etc. More importantly, Blaser suggested, and demonstrated, that H. pylori played a useful role in human physiology, protecting the cardia (the proximal portion of the stomach, the part closer to the esophagus) and lower esophagus from the effects of the acid generated in the distal stomach. Thus, as H. pylori prevalence has declined, these protections have likewise been reduced and there has been a concomitant rise in gastroesophageal reflux disease (GERD) and Barrett’s esophagus.

At least one good study has shown that the risk of esophageal adenocarcinoma is 45% higher in individuals who are H. pylori-negative. Both adenocarcinoma of the distal esophagus and cancer in the cardia portion of the stomach have been rising dramatically over the past several decades, and perhaps the decline in H. pylori prevalence and decline in distal gastric cancer incidence have been counterbalanced by these two malignancies.

There’s no free lunch!

We are not finished yet. There is another malignancy that occurs in the stomach, a form of non-Hodgkin lymphoma, called a MALT lymphoma (mucosa-associated lymphoid tissue). While MALT lymphomas may occur elsewhere in the body, when they occur in the stomach, they are almost always associated with the presence of inflammation in the presence of H. pylori. A biopsy and cultures for H. pylori can establish the diagnosis. If that is done, then treatment for this malignancy can be achieved by simply treating the H. pylori infection with antibiotics. The large majority of cases will respond successfully to this treatment approach. A small number of cases may require chemotherapy or radiation therapy. But in effect, this is a malignancy that can be treated and cured solely with the use of antibiotics!

Most experts, Blaser included, believe that H. pylori has been present as a part of the human microbiome for millennia. This suggests strongly that it has a powerful beneficial effect on our health and lives. The widespread profligate use of antibiotics in our society may have contributed to its decline in our population as compared to Africa or other parts of the world. And there may be benefits from this in some ways, e.g., the decline of distal gastric cancer. Nonetheless this change in our gut microflora may not have let us off scot-free.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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