Effect of gastroduodenal juice and dietary fat on the development of barrett's esophagus and esophageal neoplasia: An experimental rat model

Clark, Geoffrey W.B.; Smyrk, Thomas C.; Mirvish, Sidney S.; Anselmino, Marco; Yamashita, Yoshihisa; Hinder, Ronald A.; DeMeester, Tom R.; Birt, Diane F.

doi:10.1007/bf02303531

Cited by 108 publications

(81 citation statements)

References 19 publications

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“…Whereas obesity is associated with gastroesophageal reflux disease in multiple studies (37)(38)(39)(40)(41)(42), the association between dietary fat and gastroesophageal reflux disease is controversial. In rat models, dietary fat in conjunction with exposure of the distal esophagus to gastroduodenal juice promotes development of Barrett esophagus and esophageal adenocarcinoma (43,44). Experimental studies in humans have generally failed to find an association between dietary fat and acid reflux.…”

Section: Discussionmentioning

confidence: 99%

Low-Fat, High Fruit and Vegetable Diets and Weight Loss Do Not Affect Biomarkers of Cellular Proliferation in Barrett Esophagus

Kristal

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Risk factors for esophageal adenocarcinoma include obesity, high fat intake, and low consumption of fruits and vegetables. This trial tested whether an intervention to reduce these risk factors in patients with Barrett esophagus, a preneoplastic condition for esophageal adenocarcinoma, could reduce biomarkers of cellular proliferation and, by inference, the risk of neoplastic progression. Eighty-seven men and women with Barrett esophagus were randomized to an intensive dietary intervention or control group. At baseline, 18 and 36 months after intervention, biopsies were obtained at 2-cm intervals throughout the length of the Barrett segment. Ki67/DNA content flow cytometry was used to assess (a) % Ki67-positive proliferating diploid G 1 cells, (b) % total Ki67-positive proliferating cells, (c) presence of aneuploidy, and (d) presence of >6% of cells in the 4N (G 2 / tetraploid) fraction of the cell cycle. We also assessed reepithelialization and length of the Barrett segment, reflux symptoms, and medication use. The intervention effects for energy, fat, fruits and vegetables, and weight were, respectively, À314 kcal, À12.2% energy, 1.8 servings/d, and À4.0 kg at 18 months (all P < 0.005) and were smaller but remained significant at 36 months. There were no significant effects of the intervention on any biomarker of cellular proliferation. The intervention effects F SE for mean %G 1 Ki67+ cells were 0.98 F 1.58 at 18 months and 1.79 F 1.31 at 36 months; the relative risks (95% confidence interval) for developing >6% of cells in 4N were 0.5 (0.1-2.6) at 18 months and 0.75 (0.2-3.1) at 36 months. A single control participant developed aneuploidy. There were no significant effects on re-epithelialization, segment length, or reflux medication use. We conclude that substantial dietary change has no short-term effects on biomarkers of cellular proliferation in Barrett esophagus or on clinical observations of the Barrrett segment.

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Section: Discussionmentioning

confidence: 99%

Low-Fat, High Fruit and Vegetable Diets and Weight Loss Do Not Affect Biomarkers of Cellular Proliferation in Barrett Esophagus

Kristal

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…1 2 Experimental studies in the rat have shown that chronic duodenal contents reflux into the oesophagus induces severe oesophagitis and also plays a role as a cocarcinogenic factor by increasing the number of oesophageal carcinomas when a carcinogen is given simultaneously. [3][4][5] Moreover, chronic refluxed duodenal contents per se caused squamous cell carcinoma, adenosquamous carcinoma, and adenocarcinoma. [6][7][8] Although the precise mechanism by which duodenal reflux causes oesophageal injury and predisposes to neoplasia is uncertain, there is considerable evidence that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis.…”

mentioning

confidence: 99%

Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's metaplasia induced by duodenal contents reflux

Jang

Min²,

Bae³

et al. 2004

Gut

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Background and aim: It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. A large body of genetic and biochemical evidence indicate that the biosynthetic pathway of prostaglandin E 2 (PGE 2 ) may play an important role in human and rodent tumours. Therefore, we examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux. Methods: Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1, and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Results: Normal control oesophageal tissues showed COX-1 expression in subepithelial stromal cells, including endothelial cells and muscular cells, and did not reveal expression of COX-2 or mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was similar to that of normal lesions, and COX-2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2 expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP 2 , EP 3 , and EP 4 were higher in the experimental groups than in controls. Conclusions: We suggest that the biosynthetic pathway of PGE 2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.

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“…AMJ the metaplasia-dysplasia-carcinoma sequence (Gillen et al, 1988a;Attwood et al, 1992;Miwa et al, 1995;Nishijima et al, 2004;Kivilaakso et al, 1980;Fujimura, 1991;Clark et al, 1994;DeMeester et al, 1987;DeMeester and Ireland, 1997;Di Marco et al, 1990;Fein et al, 2000a;2000b;Fujikawa et al, 1994;Gerlach et al, 1997;Harmon et al, 1978;Hofmann et al, 1969;Hofmann and Mysels, 1992;Hossain et al, 1988;Isozaki et al, 1995;Kauer and Stein, 2002;Kauer, 2005;Kivilaakso et al, 1981;Segalin et al, 1994;Lillemoe et al, 1983;Miwa et al, 1992b;Smallwood and Hoffman, 1976;Theisen et al, 2003;Ireland et al, 1996). Manifold et al (2000a) studied the role of omeprazole in gastric carcinogenesis induced by duodeno-gastric reflux.…”

Section: Science Publicationsmentioning

confidence: 99%

Review Article; Duodeno-Gastro-Esophageal Reflux Combined and Isolated

Nasr¹

2013

American Medical Journal

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Barrett's esophagus is the chief risk factor for esophageal adenocarcinoma. Reflux of gastric acid has long been related to the development of esophagitis and Barrett's esophagus, but the role of duodenal contents is controversial. We review the literature on the role of duodenal contents in the development of esophagitis, Barrett's esophagus and adenocarcinoma in addition to the role of acid suppressant therapy in the development or prevention of these changes. A computer-based search of the literature using the terms "Bilirubin, Barrett, Bile Reflux, duodeno-gastric reflux and oesophagus/esophagus" was performed. The role of bile and other constituents of duodenal refluxate were examined. Techniques for identifying nonacid reflux were also reviewed, as were the role of pH, medication and surgery in modulating disease severity. Complicated Barrett's esophagus is associated with increased exposure to gastric and duodenal refluxate. Biological effect of bile acids depends on the conjugation status, the pH of the milieu and the pKa of bile acids. While Proton Pump Inhibitors reduce the levels of DGER, they also produce changes in gastric and lower esophageal pH that activate different bile acids at different pH levels resulting in unexpected injury. Conjugated bile acids are harmful in acidic environment while unconjugated bile acids are harmful at neutral pH environment. An overlap of toxicity among conjugated and unconjugated bile acids occurs between strongly acidic and neutral pH levels. Normalisation of gastric and duodenal refluxate should ideally be the goal of treatment.

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Effect of gastroduodenal juice and dietary fat on the development of barrett's esophagus and esophageal neoplasia: An experimental rat model

Cited by 108 publications

References 19 publications

Low-Fat, High Fruit and Vegetable Diets and Weight Loss Do Not Affect Biomarkers of Cellular Proliferation in Barrett Esophagus

Low-Fat, High Fruit and Vegetable Diets and Weight Loss Do Not Affect Biomarkers of Cellular Proliferation in Barrett Esophagus

Expression of cyclooxygenase 2, microsomal prostaglandin E synthase 1, and EP receptors is increased in rat oesophageal squamous cell dysplasia and Barrett's metaplasia induced by duodenal contents reflux

Review Article; Duodeno-Gastro-Esophageal Reflux Combined and Isolated

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