title: Rat Reflux Model of Esophageal Cancer and Its Implication in Human Disease.
abstract: OBJECTIVE
  The epidemiologic shift in esophageal cancer from squamous cell carcinoma to esophageal adenocarcinoma coincided with popularization of proton pump inhibitors and has focused attention on gastroesophageal reflux disease as a causative factor in this shift. The aim of this study is to review the literature on the rat reflux model in an effort to elucidate this phenomenon.
  
  
  METHODS
  An extensive online literature review (PubMed) was carried out to identify all seminal contributions to the study of esophageal adenocarcinoma using the rat reflux model.
  
  
  RESULTS
  The rat reflux model is a validated reproducible model for the development of Barrett's esophagus and esophageal adenocarcinoma. Esophageal reflux of an admixture of gastric acid and duodenal juice induces Barrett's esophagus followed by adenocarcinoma. A high-pH environment created by surgical gastrectomy or proton pump inhibitor therapy in combination with a high-fat diet seems to potentiate the development of Barrett's esophagus and adenocarcinoma. Early surgical intervention to prevent reflux reduces the progression toward esophageal adenocarcinoma. Anti-inflammatory, antioxidant, and nitrate-trapping agents reduce the incidence of tumorigenesis.
  
  
  CONCLUSIONS
  As in the rat so also in humans, reflux of an admixture of gastric acid and duodenal juice in a high-pH environment induces the development of Barrett's esophagus followed by esophageal adenocarcinoma. This has led to the hypothesis that to prevent Barrett's esophagus and subsequent esophageal adenocarcinoma in humans, the reflux of an admixture of acid and bile must be controlled before the development of Barrett's esophagus by methods other than acid-suppression therapy.
authors.affiliation: Keck School of Medicine of the University of Southern California, Los Angeles, CA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Greene
authors.forename: Stephanie G
authors.initials: SG
authors.lastname: Worrell
authors.forename: Tom R
authors.initials: TR
authors.lastname: DeMeester
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000517:prevention & control; D000818:Animals; D001471:Barrett Esophagus / Q000473:pathology* / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000517:prevention & control; D016629:Esophagectomy; D005764:Gastroesophageal Reflux / Q000473:pathology* / Q000628:therapy; D006801:Humans; D011230:Precancerous Conditions / Q000473:pathology* / Q000517:prevention & control; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D051381:Rats
chemical_list: D054328:Proton Pump Inhibitors