Rabeprazole impedes the development of reflux-induced esophageal cancer in a surgical rat model.
BACKGROUND
The role of proton pump inhibitors in Barrett's metaplasia and esophageal adenocarcinoma has been an area of controversy.


OBJECTIVE
We evaluated the effectiveness of the proton pump inhibitor rabeprazole as a chemoprevention agent in a surgical rat reflux model of esophageal cancer.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, Maryland 21224, USA.
Tomoharu
T
Miyashita
Furhawn A
FA
Shah
Guy P
GP
Marti
Jiaai
J
Wang
Pramod
P
Bonde
Michael K
MK
Gibson
Tetsuo
T
Ohta
Elizabeth A
EA
Montgomery
Mark
M
Duncan
John W
JW
Harmon
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D005764:Gastroesophageal Reflux / Q000150:complications*; D008297:Male; D064750:Rabeprazole; D051381:Rats; D017207:Rats, Sprague-Dawley
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064750:Rabeprazole