Abstracts
1997 Digestive Disease Week

Duodenoesophageal reflux causes esophageal adenocarcinoma without exogenous carcinogen.

M Fein, JH Peters, P Chandrasoma*, AP Ireland, MP Ritter, CG Bremner, JA Hagen, TR DeMeester. Departments of Surgery and Pathology*, University of Southern California, Los Angeles, CA.

Clinical studies have shown that reflux of duodenal and gastric juice acts synergistically in the development of Barrett's metaplasia, dysplasia, and esophageal adenocarcinoma. Our laboratory has previously shown in a rat model that Barrett's metaplasia and adenocarcinoma can be induced by surgical construction of a esophagoduodenostomy and administration of nitrosamine. Further, the addition of a gastrectomy to this model dramatically increases the prevalence of esophageal adenocarcinoma. We questioned whether carcinogen was necessary for the development of tumors in the gastrectomized model and whether esophageal acidification could compensate for the effect of gastrectomy.

Forty-two Sprague-Dawley rats (8 to 10 weeks old) underwent total gastrectomy and loop esophagojejunostomy to induce esophageal reflux of duodenal juice. One week following surgery they were randomized into two groups. One group received tap water. In the other group the drinking water was acidified with hydrochloric acid (pH 1.8). Sixteen weeks after the operation all animals were killed and the esophagus was evaluated histologically. Comparison was done with the Fisher's exact test.

Thirty seven rats survived. All had severe esophagitis. 62% (23) developed Barrett's columnar-lining of the esophagus. 43% (16) developed well differentiated adenocarcinomas at the anastomotic site. No squamous cancers occurred. Adenocarcinomas were less frequent and tumor growth was significantly retarded in the group with esophageal acidification (p<0.05).

The high incidence of esophageal adenocarcinoma in the absence of exogenous carcinogen is striking. This is the first demonstration of cancer development caused by duodenoesophageal reflux alone in a short time course. The total absence of acid enhanced tumor growth.