title: Duodenal reflux produces hyperproliferative epithelial esophagitis--a possible precursor to esophageal adenocarcinoma in the rat.
abstract: Esophageal reflux of duodenal contents converts a rat nitrosamine esophageal cancer model from squamous cell carcinoma to adenocarcinoma. Further, there was a tendency for male rats to have a higher incidence of cancer than female rats. However, chemical castration with the gonadotropin-releasing hormone analog leuprolide did not protect male or female animals from developing cancer. We have identified an early (6-week) hyperproliferative epithelial cell reaction to duodenal reflux. We carried out experiments to assess the specificity of duodenal reflux in producing the hyperproliferative epithelial precursor lesion. Animals underwent specific surgical procedures to produce esophageal reflux of pure duodenal contents, mixed gastroduodenal, or bland intestinal contents. A hyperproliferative mucosal esophagitis developed in the group with duodenal reflux but not in the other groups. Mucosal thickness in the duodenal reflux group reached seven times that of normal mucosa at 6 weeks. These results suggest that esophageal reflux of duodenal contents plays an important role in the pathogenicity of proliferative esophagitis and the potential development of esophageal adenocarcinoma.
authors.affiliation: Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Colman K
authors.initials: CK
authors.lastname: Byrnes
authors.forename: Anil
authors.initials: A
authors.lastname: Bahadursingh
authors.forename: Nabeel
authors.initials: N
authors.lastname: Akhter
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Duncan
authors.forename: Petra H
authors.initials: PH
authors.lastname: Nass
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D004383:Duodenogastric Reflux / Q000150:complications*; D004386:Duodenum / Q000378:metabolism / Q000503:physiopathology; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology*; D004941:Esophagitis / Q000150:complications / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress; D011230:Precancerous Conditions / Q000473:pathology*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity