The mutagenic potential of duodeno-gastroesophageal reflux

Theisen, Jörg; Peters, Jeffrey H.; Hughes, Michael; Laird, Peter W.; Bremner, Cedric G.; Lord, Reginald V.; DeMeester, Steve R.; Öberg, Stefan; Hagen, Jeffrey A.; DeMeester, Tom R.

doi:10.1016/s0016-5085(00)82050-8

Cited by 14 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent publications emphasized the mutagenic potential of duodenogastric reflux, both for the gastric and for the esophageal mucosa, associating it even to the occurrence of Barrett's esophagus and adenocarcinoma that appears on this epithelium 2,5,13 . Ovrebo et al 21 studied the histological alterations in the gastric mucosa of rats 24, 36 and 52 weeks after gastrojejunal anastomosis, concluding that the ulcers and carcinomas appear more frequently in the body than in the antrum, with ulcers preceding the onset of carcinomas…”

Section: Discussionmentioning

confidence: 99%

“…Several investigations were carried out to clarify whether patients undergoing surgery with techniques that promote duodenogastric reflux, such as partial gastrectomies in case of benign disorders, would be at higher risk than the non-gastrectomized population for development of cancer of the remaining gastric stump 3,4,5 . Since the start of the 80s decade, by means of wellconducted research, it has been definitively established that patients submitted to techniques that promote duodenogastric reflux, such as Billroth II reconstruction, are more susceptible to neoplasia after a postoperative period longer than 20 years 6,7,8,9 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gastric proliferative lesions induced by duodenogastric reflux in rats

et al. 2006

View full text Add to dashboard Cite

Purpose: To analyze mucosal proliferation and its characteristics, through specific models of duodenogastric reflux, in the stomach of Wistar rats. Methods: Seventy-five healthy and adult male rats were divided into three groups: group Icontrol (n = 25 animals), submitted to gastrotomy of the posterior wall of the glandular stomach; group II -DGR (n = 25 animals), submitted to duodenogastric reflux through latero-lateral gastrojejunal anastomosis in the posterior wall of the glandular stomach and group III -DGR-P (n = 25 animals), submitted to duodenogastric reflux through the pylorus following the same procedure of group II, sectioning and closing the afferent loop. The animals were observed during 36 weeks and subsequently the mucosal lesions were analyzed, with macroscopic and microscopic examination of the prepyloric, the gastrojejunostomy and the squamous area of the stomach. Results: Group I did not present any kind of lesion. Macroscopic lesions of the prepyloric area in groups II and III were 0% and 20%, respectively. Macroscopic lesions of the gastrojejunal stoma in groups II and III were 36% and 88%, respectively, and 12% and 28%, respectively, in the squamous area. Microscopically, adenomatous hyperplasia (AH), squamous hyperplasia (SH) and adenocarcinoma (AC) were diagnosed. The occurrence of AH at the prepyloric area in groups II and III was 0% and 40%, respectively, and in the gastrojejunal stoma, 40% and 72%, respectively. The occurrence of SH in the squamous area in groups II and III was 12% and 20%, respectively, without statistical differences between the groups. AC was found only in three animals of groups III (12%). Conclusions: The duodenogastric reflux in this experimental model caused high frequency of proliferative lesions of the gastrojejunal stoma and in the prepyloric area, while adenocarcinoma was a rare occurrence. Key words: Duodenogastric Reflux. Hyperplasia. Adenocarcinoma. Rats. RESUMOObjetivo: Avaliar as lesões proliferativas que se desenvolvem na mucosa gástrica de ratos Wistar após modelo específico de refluxo duodeno-gástrico. Métodos: Foram utilizados 75 ratos adultos machos divididos em três grupos experimentais: o grupo I (controle) submetido a gastrotomia na parede posterior do estômago glandular (25 animais); o grupo II (RDG), foi submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular (25 animais) e o grupo III (RDG-P) submetido a gastrojejunoanastomose látero-lateral na parede posterior do estômago glandular, com secção e fechamento da alça (25 animais). Os animais foram observados durante 36 semanas, após o que foram realizados estudos macroscópicos e microscópicos da anastomose gastrojejunal, da região pré-pilórica e região escamosa do estômago. Resultados: Os animais do Grupo I não apresentaram nenhum tipo de lesão. No grupo II observou-se 40% de lesões do tipo hiperplasia adenomatosa na anastomose e 12% de hiperplasia escamosa. No grupo III obteve-se 40% de hiperplasia adenomatosa na mucosa pré-pilórica, 72 % de hiperplas...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gastric proliferative lesions induced by duodenogastric reflux in rats

et al. 2006

View full text Add to dashboard Cite

show abstract

“…A duodeno-esophageal anastomosis has been frequently used to study combined duodeno/GastroEsophageal Reflux (DER/GER), similar to but more intense than the regular DGER. Theisen et al (2005) used this model to demonstrate the mutagenic effect of combined reflux through standard big blue mutagenic assay technique. They demonstrated specific mutations similar to those found in p53 mutations of human esophageal adenocarcinoma.…”

Section: What We Have Learned From Animal Reflux Modelsmentioning

confidence: 99%

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

Nasr¹

2013

American Medical Journal

View full text Add to dashboard Cite

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.

show abstract

“…The role of bile reflux has been established from surgical models in rats, where esophagojejunostomy and esophagogastroduodenostomy results in a mixed bile and gastric refluxate that leads to intestinal metaplasia, with many similarities to human BE, including early induction of Cdx1 and Cdx2 expression and the development of a columnar-lined epithelium containing intestinal mucin-secreting goblet cells, [21][22][23][24][25] and esophageal adenocarcinoma. 26,27 Bile acids, particularly unconjugated bile acids such as deoxycholate that induce DNA damage, are one component of gastroduodenal reflux that has been strongly linked to the development of BE, as well as to other cancers a leucine-rich orphan G protein-coupled receptor, was shown to specifically label stem cells in the small intestinal and colon crypts, the so-called crypt based columnar (CBC) cells.…”

Section: Proton Pump Inhibitor Therapy and Hypergastrinemia In Bementioning

confidence: 99%

Barrett esophagus

et al. 2012

View full text Add to dashboard Cite

T he incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE. In addition, validated animal models could help stratify BE patients given the limited predictive power of current standard endoscopic measures and clinical assessment. Here, we review the findings from recently developed mouse models of BE and EAC and their impact on clinical decision making, surveillance programs and therapeutic options. The data, taken together, suggest potential origins of BE from the gastric cardia, a role of bile acid and hypergatrinemia for carcinogenesis, a growing importance for columnar-like epithelium and a critical role for Notch signaling.

show abstract

The mutagenic potential of duodeno-gastroesophageal reflux

Cited by 14 publications

References 0 publications

Gastric proliferative lesions induced by duodenogastric reflux in rats

Gastric proliferative lesions induced by duodenogastric reflux in rats

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

Barrett esophagus

Contact Info

Product

Resources

About