Influence of pancreatic and biliary reflux on the development of esophageal carcinoma

Abstract

We previously presented an experimental model of Barrett's adenocarcinoma of the esophagus by demonstrating that esophagojejunostomy combined with subcutaneous injection of 2,6-dimethylnitrosomorpholine in Sprague-Dawley rats resulted in development of adenocarcinoma in the distal esophagus. The present study was devised to investigate the influence of pancreatic and biliary duodenal-content reflux on the induction of esophageal carcinoma. Three groups of 8-week-old Sprague-Dawley rats were controls: the first was exposed to pancreatic reflux, the second to biliary reflux, and the third to both. The other three experimental groups were similar except that a 1/100 LD50 dose of 2,6-dimethylnitrosomorpholine was injected subcutaneously weekly, starting on day 15. Carcinoma of the esophagus was induced only in animals receiving the carcinogen after exposure to either pancreatic reflux (3/22, 13%) or pancreatic and biliary reflux (9/27, 33%). Half of the carcinomas were adenocarcinoma and half were squamous cell carcinoma. These findings suggest that under these experimental conditions, in which the carcinogen is used in a low dose, esophageal carcinoma is induced only when pancreatic secretions are present in the duodenal-content reflux. Biliary reflux, however, appears to exert a cocarcinogenic effect when combined with pancreatic secretions. The clinical relevance of these findings needs further evaluation. Conceivably, the elimination of pancreatic and biliary duodenal-content reflux in patients with documented Barrett's mucosa may inhibit the progression from metaplasia to adenocarcinoma.