Effect of gastroduodenal juice and dietary fat on the development of Barrett's esophagus and esophageal neoplasia: an experimental rat model.
BACKGROUND
Reflux of duodenal content into the lower esophagus of rats enhances the formation of nitrosamine-induced esophageal cancer and results in the induction of adenocarcinoma. We investigated the extent of the mucosal injury that was produced when the lower esophagus of rats was exposed to the reflux of gastroduodenal juice in the presence or absence of a carcinogen and tested the hypothesis that induction of esophageal cancer in this model would be influenced by the intake of dietary fat.


METHODS
Esophagoduodenostomy with gastric preservation was performed in 165 Sprague-Dawley rats in order to expose the lower esophagus to the reflux of gastroduodenal juice. Postoperatively selected groups of rats were treated with the carcinogen methyl-n-amylnitrosamine (MNAN). Subsequently, rats were fed diets of differing fat and calorie content for 20 weeks until they were put to death.


RESULTS
Refluxed gastroduodenal juice, in the absence of MNAN, induced esophageal inflammatory changes (diffuse papillomatosis and hyperkeratosis) in 38 of 39 rats (97%), specialized columnar metaplasia (Barrett's esophagus) in four of 39 (10%), dysplasia in three of 39 (8%), and squamous cell carcinoma in one of 39 (3%). Diet did not influence the incidence of neoplasia in the absence of MNAN treatment. In rats treated with MNAN, refluxed gastroduodenal juice induced inflammation in 110 of 111 rats (99%), columnar metaplasia in 14 of 111 (13%), and cancer in 63 of 111 (57%). Fifty-eight percent of esophageal tumors were squamous cell carcinoma and 42% were adenocarcinoma. The highest incidence of tumors was observed in rats fed the semipurified high-fat diet (24 of 29; 83%) compared with rats fed the semipurified control diet (13 of 29; 45%), semipurified, calorie-restricted diet (15 of 27; 55%), and chow diet (11 of 26; 42%), p < 0.05.


CONCLUSIONS
Reflux of gastroduodenal content into the lower esophagus of rats can induce both Barrett's metaplasia and neoplasia. Addition of a carcinogen increases the tumor yield and results in a proportion of the lesions being adenocarcinoma. This carcinogenic process is promoted by a diet with a high fat content.
Clark
G W
GW
Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033-4612.
Smyrk
T C
TC
Mirvish
S S
SS
Anselmino
M
M
Yamashita
Y
Y
Hinder
R A
RA
DeMeester
T R
TR
Birt
D F
DF
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001471:Barrett Esophagus / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects*; D004383:Duodenogastric Reflux / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004947:Esophagus / Q000473:pathology; D005750:Gastric Juice; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats