Rabeprazole Impedes the Development of Reflux-Induced Esophageal Cancer in a Surgical Rat Model

Abstract

The role of proton pump inhibitors in Barrett's metaplasia and esophageal adenocarcinoma has been an area of controversy. We evaluated the effectiveness of the proton pump inhibitor rabeprazole as a chemoprevention agent in a surgical rat reflux model of esophageal cancer. The rat reflux model was created by performing a jejuno-esophagostomy on Sprague-Dawley rats. The surgery promoted the reflux of gastro-duodenal contents into the esophagus. Rabeprazole sodium (Eisai, Tokyo, Japan) was dissolved in 0.9% physiological saline to a desired concentration of 1.5% (W/V). Beginning 4 weeks post-surgery, all animals were administered either 0.2 ml per 100 g body weight injections of rabeprazole or equivalent injections of saline 3 days per week into the subcutaneous tissue of the back. Forty animals were killed 40 weeks after surgery and their esophagi were examined. Of these, 23 were included in the control group, while the remaining 17 were subjected to rabeprazole. While 74% (17/23) of the controls developed esophageal cancer, animals administered rabeprazole had an incidence of cancer of 29% (5/17) (p < 0.05, Fisher's exact test). Barrett's metaplasia was found on 100% (23/23) of the rats in the placebo group, but there was a protective effect in the rabeprazole group with 65% (11/17) of the rats displaying signs of Barrett's metaplasia (p < 0.05, Fisher's exact test). All of the rats developed proliferative hyperplasia. Rabeprazole protected against the development of esophageal cancer in a clinically relevant surgical reflux model. Rabeprazole warrants further investigation for potential clinical use as a chemoprevention agent.