The Role of Bile Acids in the Neoplastic Progression of Barrett’s Esophagus – A Short Representative Overview

Abstract

Barrett’s esophagus (BE) is an intestinal metaplasia of the distal esophagus in which squamous cells are replaced by a columnar epithelium. It is considered as a premalignant lesion, which can lead to esophageal adenocarcinoma, a very aggressive type of cancer, and can often be found in patients with gastro-esophageal reflux disease (GERD). In spite of the widespread use of acid-suppressing therapy with proton pump inhibitors, the incidence of adenocarcinoma has been steadily rising during the last 30 years. So, it can strongly be suggested that refluxed material other than acid might contribute to the progression of cancer within Barrett’s esophagus. Along with gastric acid, bile acids enter the esophagus during an episode of reflux, and bile acids may be important in carcinogenesis. In their refluxates, patients with GERD and BE show high concentrations of the hydrophobic bile salt deoxycholic acid (DCA), which has cytotoxic effects and is able to induce DNA damage in different cell types. Other bile acids, like the hydrophilic urodeoxycholic acid (UDCA), have been therapeutically used to treat cholestatic liver diseases and to prevent colon carcinoma. This article reviews the effects of bile acids and points out new perceptions in the progression of Barrett’s-associated carcinogenesis.

Zusammenfassung

Der Barrett-Ösophagus (BE) stellt eine intestinale Metaplasie des distalen Ösophagus dar, indem Plattenepithelzellen durch Zylinderepithel ersetzt werden. Diese Veränderung ist als prämaligne Läsion zu betrachten, die zum Adenokarzinom des Ösophagus führen kann, einer sehr aggressiven malignen Neoplasie, die nicht selten bei Patienten mit vorbestehender gastroösophagealer Refluxerkrankung (GERD) gefunden wird. Trotz eines weitverbreiteten Gebrauchs an säureblockierender Therapie mit Protonenpumpeninhibitoren (PPI) hat die Inzidenz des Adenokarzinoms während der letzten 30 Jahre ständig zugenommen. Daher kann recht sicher angenommen werden, dass auch „nicht saures“ Refluxmaterial zur Krebsentstehung im Barrett-Ösophagus beitragen könnte. Neben der Magensäure benetzen auch Gallensäuren die Speiseröhre während einer Refluxepisode, was nahelegt, dass auch Gallensäuren in der Karzinogenese von Bedeutung sein könnten. In ihren Refluxaten weisen Patienten mit GERD und BE außerdem hohe Konzentrationen der Gallensalze, besonders der hydrophoben Desoxycholsäure (DCA) auf, die zytotoxische Effekte auslöst und DNA-Schäden an diversen Zelltypen induzieren kann. Andere Gallensalze der eher hydrophilen Urodesoxycholsäure (UDCA) sind bereits therapeutisch angewandt worden, um cholestatische Lebererkrankungen zu behandeln und dem Kolonkarzinom vorzubeugen. Dieser Artikel gibt einen kurzen repräsentativen Überblick zum Effekt der Gallensäuren und führt neue Betrachtungsansätze in der Barrett-assoziierten Karzinogenese aus.

Schlüsselwörter

Barrett-Ösophagus - Gallensäuren - Desoxycholsäure (DCA) - Urodesoxycholsäure (UDCA)

Key words

Barrett’s esophagus - bile acids - deoxycholic acid (DCA) - urodeoxycholic acid (UDCA)

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