Studies on experimental animals involving surgical procedures and/or nitrosamine treatment related to the etiology of esophageal adenocarcinoma

Cancer Lett. 1997 Aug 19;117(2):161-74. doi: 10.1016/s0304-3835(97)00228-0.


After a brief review of the epidemiology and etiology of lower esophageal adenocarcinoma (EAC), this paper describes long-term experiments on animals (mostly rats) demonstrating that reflux of duodenal contents into the stomach can induce gastric and pancreatic cancer, that gastric reflux into the esophagus can induce Barrett's esophagus; that esophagoduodenostomy to facilitate duodenal reflux into the esophagus, together with administration of carcinogenic nitrosamines, induces squamous cancer and EAC in the lower esophagus; that both pancreatic juice and bile are involved in this induction of EAC; that a high-fat diet increases EAC induction; and that esophagoduodenostomy with gastrectomy and nitrosamine treatment or esophagojejunostomy without a carcinogen can produce up to an 88% incidence of EAC. Short-term animal experiments are reviewed in which bile salts and trypsin have damaged the esophagus and duodenal reflux has produced lipid peroxidation in the lower esophagus. Finally, I review arguments mostly derived from the animal experiments that reflux of unacidified duodenal juice via the stomach into the lower esophagus may help cause Barrett's esophagus and EAC, that excessive use of acid blockers might contribute to EAC induction, and that EAC induction may be reduced by surgery to repair the lower esophageal sphincter or perhaps by taking non-steroidal anti-inflammatory drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenocarcinoma / chemically induced*
  • Animals
  • Bile Acids and Salts / physiology
  • Bile Reflux / complications
  • Cimetidine / adverse effects
  • Duodenogastric Reflux / complications
  • Esophageal Neoplasms / chemically induced*
  • Esophageal Neoplasms / epidemiology
  • Esophagus / surgery
  • Hydrogen-Ion Concentration
  • Nitrosamines*
  • Pancreatic Juice / physiology
  • Ranitidine / adverse effects
  • Rats
  • Stomach / surgery


  • Bile Acids and Salts
  • Nitrosamines
  • Cimetidine
  • Ranitidine