Long-term proton pump inhibitor use and gastrointestinal cancer

Abstract

Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development in humans. Long-term use of proton pump inhibitors is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication. It is thus recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in patients not infected with H. pylori, but these changes are believed to be reversible and without significant cancer risk.

An experienced pathologist will have no difficulty recognizing this patient as a non-H. pylori infected chronic PPI user: the gastric corpus is completely devoid of inflammation, but parietal cells are hyperplastic and protrude into the lumen of dilated oxyntic glands. When these dilatations become more prominent (and, therefore, endoscopically visible) they are known as fundic polyps. Hematoxylin and eosin, original magnification 20×.