Can Proton Pump Inhibitors Prevent Esophageal Cancer?
Proton-pump inhibitor (PPI) therapy reduces risk of esophageal cancer in patients with Barrett’s esophagus (BE), according to the April issue of Clinical Gastroenterology and Hepatology.
In BE, the squamous epithelium of the distal esophagus is replaced by metaplastic columnar epithelium, as a result of chronic exposure to stomach acid. Patients with this disorder are at increased risk for eventually developing esophageal adenocarcinoma (EAC).
Strategies to prevent the development of EAC have focused primarily on acid suppression and early detection of adenocarcinoma, but the incidence of EAC has continued to increase.
Because esophageal acid exposure can cause BE and promote its progression to EAC, patients are typically treated with acid suppressors such as PPIs or histamine-2 receptor antagonists.
However, in the absence of data from long-term prospective clinical trials, current guidelines do not provide strong recommendations for the use of acid suppressants for these patients.
Florine Kastelein et al. therefore performed a prospective study, following 540 patients with BE for an average of more than 5 years, to determine whether fewer patients taking PPIs developed high-grade dysplasia or EAC.
They associated PPI use with a 75% reduction in the risk for neoplastic progression, independent the patients’ age or sex, features of their disease, or use of other medications.
However, histamine-2 receptor antagonists use did not affect the risk for high-grade dysplasia or cancer.
Prolonged use of PPIs and good adherence were associated with an additional protective effect. The prevalence of esophagitis decreased during PPI use, but length of BE was not affected.
Cancer risk was reduced by all types of PPIs (omeprazole, esomeprazole, rabeprazole, pantoprazole, or lansoprazole), so the protective effect was probably related to the acid suppressive mechanism. However, none of the PPIs prevented cancer in all patients who took them. Kastelein et al. explain that 20% of BE patients continue to have reflux despite PPI use. Intermittent esophageal acid exposure promotes cell proliferation, which could be a reason that patients with BE remain at risk for cancer during PPI use.
Although prolonged PPI therapy is expensive, the authors conclude it is an effective strategy to prevent neoplastic progression in patients with BE that ultimately saves them from expensive endoscopy and surgery procedures. Furthermore, the drugs are effective in relieving reflux symptoms, so patients are likely to adhere to therapy.
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Kastelein F, Spaander MCW, Steyerberg EW, et al. Proton pump inhibitors reduce the risk of neoplastic progression in patients with barrett’s esophagus. Clin Gastroenterol Hepatol 2013;11:382–388.