Gastric Juice Protects Against the Development of Esophageal Adenocarcinoma in the Rat

Ireland, Adrian P.; Peters, Jeffrey H.; Smyrk, Thomas C.; DeMeester, Tom R.; Clark, Geoffrey W.B.; Mirvish, Sidney S.; Adrian, Thomas E.

doi:10.1097/00000658-199609000-00012

Cited by 116 publications

(88 citation statements)

References 27 publications

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“…However, gastric acid is not the only substance that refluxes from the stomach into the esophagus. Animal studies have suggested that exposure to bile acid, a major component of duodenal juice that originates in duodenum and may reflux into the esophagus through duodenogastro-esophageal reflux (DGER), increases the risk of EA (24)(25)(26). In a rat model, duodenal juice refluxed into esophagus although DGER induced histologic changes, from squamous-cell epithelium into columnar-cell epithelium, in the lining of the distal esophagus (25).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, another animal study showed that the Table 3. ORs for OTC acid neutralizing drugs in relation to esophageal, gastric cardia, and distal gastric adenocarcinomas, by history of physiciandiagnosed UGI disorders prevalence of EA increased as the amount of acid gastric juice that was permitted to reflux with duodenal juice into the esophagus decreased (26), suggesting that acid suppression therapy may be detrimental by encouraging esophageal metaplasia and tumorigenesis in participants with DGER reflux. In humans, it has been shown that the degree of esophageal damage increases with increasing amount of DGER, with the highest DGER levels found in patients with Barrett's esophagus (27).…”

Section: Discussionmentioning

confidence: 99%

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Antacid Drug Use and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

Duan

Sullivan‐Halley

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objectives: Concern has been expressed that antacid drugs increase the risk of esophageal and gastric adenocarcinomas.Methods: This population-based case-control study recruited patients with incident esophageal adenocarcinoma (n = 220), gastric cardiac adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) diagnosed between 1992 and 1997, and 1,356 control participants in Los Angeles County. Unconditional polychotomous multivariable logistic regression analyses were done to evaluate the association between antacid drug use and these cancers. Results: Among participants who took nonprescription acid neutralizing agents for >3 years, the odds ratio for esophageal adenocarcinoma was 6.32 compared with never users (95% confidence interval, 3.14-12.69; P trend < 0.01). Analyses stratified by history of physician diagnosed upper gastrointestinal (UGI) disorders revealed a greater increase in esophageal adenocarcinoma risk associated with nonprescription antacid use among persons with no UGI disorder than among those with an UGI disorder (homogeneity of trends P = 0.07). Regular use of nonprescription acid neutralizing agents was not associated with risk of adenocarcinomas of the gastric cardia or distal stomach. Regular use of prescription acid suppressive drugs was not associated with risk for any of these cancers. Conclusion: We found risk of esophageal adenocarcinoma was greater among long-term nonprescription acid neutralizing drugs in participants without physician-diagnosed UGI conditions than among those with these conditions; this may represent self medication for undiagnosed precursor conditions or it may be that nonprescription acid neutralizing drugs, taken without limitation on amount used when symptoms are most intense, may permit alkaline bile reflux into the lower esophagus, thereby increasing esophageal adenocarcinoma risk. (Cancer Epidemiol Biomarkers Prev 2009;18(2):526 -33)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antacid Drug Use and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

Duan

Sullivan‐Halley

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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%

“…They afford resolution of symptoms using lifelong PPIs. Antacids and H 2 receptors antagonists no longer have a major role in the treatment of Barrett's oesophagus (Ireland et al, 1996).…”

Section: Role Of Medication In the Control Of Dgermentioning

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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“…Stopniowe i harmonijne narastanie zmian w zastosowanych modelach umożliwia obserwację kolejnych etapów kancerogenezy w jej naturalnym przebiegu, prowadzącym do konwersji BE w EAC bez użycia substancji chemicznych, które mogłyby przyspieszyć ten proces. Ponadto w większości przeprowadzonych dotychczas badań, w których sprawdzano wpływ kancerogenów na rozwój nowotworu, uzyskane zmiany potwierdzone w badaniu histopatologicznym miały charakter raków płaskonabłonkowych [22,[27][28][29]. W obecnym modelu w znamiennej większości doszło do rozwoju gruczolakoraka, który jest najczęstszym histologicznym typem nowotworu transformującym z BE.…”

Section: Fig 5 Comparison Of Macroscopic Lesions Of the Oesophagealunclassified

Natural development of Barrett’s oesophagus and adenocarcinoma in experimental models of gastroesophageal reflux disease

Pabianczyk¹,

Majka²,

Drozdowicz³

et al. 2011

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StreszczenieWstęp: Do rozwoju choroby refluksowej (gastroesophageal reflux disease -GERD) dochodzi w momencie zaburzenia rów-nowagi pomiędzy czynnikami drażniącymi reflu ksatu a czynnikami ochraniającymi błonę śluzową przełyku. Przewlekły stan zapalny przełyku może doprowadzać do poważ-nych powikłań w postaci metaplazji Barretta i w konsekwencji rozwoju raka przełyku. W ostatnich latach stwierdza się coraz częstsze występowanie refluksu jelitowo-żołądkowego powikłanego rozwojem gruczolakoraka przełyku, zwłaszcza w krajach o wysokim rozwoju cywilizacyjnym. Cel: Podjęcie próby stworzenia przewlekłych modeli refluksu przełykowego, które naśladują tę patologię u człowieka, w celu badania mechanizmu powstawania uszkodzeń przełykowych, ich porównanie oraz ocena przydatności do prowadzenia badań nad wieloetapowym procesem nowotworzenia bez za stosowania egzogennych kancerogenów. Stworzenie modelu przewlekłego zapalenia przełyku mogłoby się przyczynić do opracowania skutecznych metod zapobiegania i leczenia tych zmian. Materiał i metody: W badaniach wykorzystano grupę 90 szczurów rasy Wistar płci mieszanej. Eksperyment przeprowadzono w trzech zasadniczych grupach badawczych, w któ-rych wykonano: A -połączenia przełykowo-dwunastnicze bok przełyku do boku dwunastnicy, B -połączenie przełykowo--dwunastnicze koniec przełyku do boku dwunastnicy i Cpołączenie przełykowo-dwunastnicze koniec przełyku do boku dwunastnicy wraz z całkowitą resekcją żołądka. Dwa pierwsze typy operacji (grupy A, B) charakteryzował refluks treści mieszanej dwunastniczo-żołądkowej, a w trzecim typie zabiegu (grupa C) uzyskano refluks treści wyłącznie alkalicznej do przełyku. Wyniki: We wszystkich trzech grupach zoperowanych zwierząt po 1-3 mies. od zabiegu obserwowano zmiany morfologiczne AbstractIntroduction: Development of gastroesophageal reflux disease (GERD) takes place when the balance between irritant and protecting mucous membrane mechanisms is impaired. The chronic inflammation of the oesophagus results in serious complications including Barrett's metaplasia progression into esophageal adenocarcinoma. In the last few years the incidence of chronic gastroesophageal reflux disease has been increasing, especially in highly developed countries, and this chronic disease may result in the development of oesophageal adenocarcinoma, which is also observed with increased frequency. Aim: Creation and comparison of chronic gastroesophageal reflux disease models, as well as estimation of their suitability for the investigation of the process of natural carcinogenesis in the oesophagus. Material and methods: Ninety Wistar rats were used for the study on development of chronic oesophageal inflammation. Three major groups, A -side to side anastomosis, B -side to end anastomosis and C -side to end anastomosis with total gastrectomy, were selected. In each group a different operation technique was performed to induce chronic oesophageal reflux. Groups A and B were characterized by mixed gastroduodenal reflux while group C included animals with only alkaline r...

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Gastric Juice Protects Against the Development of Esophageal Adenocarcinoma in the Rat

Cited by 116 publications

References 27 publications

Antacid Drug Use and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

Antacid Drug Use and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County

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

Natural development of Barrett’s oesophagus and adenocarcinoma in experimental models of gastroesophageal reflux disease

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