PPIs May Reduce Esophageal Cancer Risk in Barrett's Esophagus

November 26, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Nov 26 - Patients with Barrett's esophagus who used proton pump inhibitors (PPIs) had a lower risk of esophageal adenocarcinoma, in a systematic review and meta-analysis of seven observational studies.

"I think, given the observational nature of these studies, we would still consider this evidence as preliminary," Dr. Siddharth Singh from the Mayo Clinic, Rochester, Minnesota told Reuters Health by email. "Hence, for now, I would recommend that a patient with Barrett's esophagus (BE) be prescribed proton pump inhibitor therapy for an indication of gastroesophageal reflux disease (GERD) or erosive esophagitis."

"In patients with particularly high risk of progression to esophageal adenocarcinoma (EAC) based on demographic, clinical, and BE-related factors, then I would discuss this evidence, weighing the risks and benefits to make an informed, individualized decision," Dr. Singh said.

Although BE confers a 30- to 125-fold increased risk of EAC, only a small proportion of patients with BE go on to develop EAC. PPI therapy can prevent or delay progression of dysplasia to BE, but there are concerns surrounding the long-term acid suppression resulting from PPI treatment, and it remains unclear whether PPI treatment prevents progression of BE to EAC.

As reported November 12 online in Gut, Dr. Singh and colleagues undertook their systematic review and meta-analysis to evaluate the association between acid-suppressive medications and the risk of EAC or high-grade dysplasia in patients with BE.

The seven studies included 2813 patients, including 317 who progressed to EAC or high-grade dysplasia. Most patients (84.4%) received PPIs; some received histamine receptor antagonists (H2RAs).

The use of a PPI at the time of diagnosis of BE was associated with a 74% reduction in the risk of EAC and/or high-grade dysplasia, although divergent results in two case-control studies resulted in considerable heterogeneity in the overall analysis.

The protective association between PPIs and the risk of EAC and/or high-grade dysplasia persisted after adjustment for the concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin/statins.

The protective effect emerged only after long-term exposure to PPIs (>2-3 years), however.

The estimated numbers needed to treat with PPIs to prevent one case of EAC or high-grade dysplasia were 147 for all patients with BE, 220 for patients with nondysplastic BE, and 82 for patients with BE and low-grade dysplasia.

Neither of the two studies that reported the risk of advanced neoplasia in patients treated with H2RAs showed a protective association, the researchers say, so no meta-analysis was performed.

"The rate and risk of progression to EAC from BE with different grades of dysplasia is poorly understood," Dr. Singh said. "Hence it is difficult to infer how long PPI therapy needs to be continued."

"It is likely that these patients will have persistent increase in EAC risk, and theoretically, lifelong PPI therapy would afford protection against EAC," Dr. Singh said. "However, this needs to be considered in the context of competing risk of mortality due to cardiovascular diseases in these patients - EAC is not the leading cause of death in these patients."

Dr. Pieter Jan de Jonge from Erasmus MC, Rotterdam, The Netherlands, who has studied the effect of PPIs in patients with BE, told Reuters Health, "PPI therapy in patients with BE is effective in controlling reflux symptoms and esophagitis, and current evidence seems in favor of a concurrent antineoplastic effect, although robust evidence is lacking."

"Regular once daily dosing of a PPI is indicated for patients with BE," Dr. de Jonge said. "However, high-dose maintenance therapy should only be prescribed when symptoms of esophagitis are insufficient controlled by once daily dosing, but not primarily to prevent neoplastic progression, as evidence for this indication is lacking, and the risk of side effects and complications of long term high dose PPI use might increase."

Dr. de Jonge added, "Large randomized controlled trials are needed, which in particular are not affected by confounding by indication. The Aspirin Esomeprazole Chemoprevention Trial (Aspect), will provide a more definitive assessment of the effects of acid suppressing medications and aspirin as chemoprevention agents in BE." That trial will be completed in 2019: http://www.clinicaltrials.gov/show/NCT00357682.

SOURCE: http://bit.ly/18EPHHg

Gut 2013.

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