Jürgens S, Meyer F, Spechler S J, Souza R
Dept. of Surgery, Otto-von-Guericke-Universität Magdeburg.
Z Gastroenterol. 2012 Sep;50(9):1028-34. doi: 10.1055/s-0032-1312922. Epub 2012 Sep 10.
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.
巴雷特食管(BE)是食管远端的一种肠化生,其中鳞状细胞被柱状上皮取代。它被认为是一种癌前病变,可导致食管腺癌,这是一种侵袭性很强的癌症,常见于胃食管反流病(GERD)患者。尽管质子泵抑制剂等抑酸疗法被广泛应用,但在过去30年里,腺癌的发病率仍在稳步上升。因此,强烈提示除酸以外的反流物质可能促使巴雷特食管内的癌症进展。胆汁酸与胃酸一起在反流发作时进入食管,胆汁酸可能在致癌过程中起重要作用。在GERD和BE患者的反流物中,疏水性胆盐脱氧胆酸(DCA)浓度很高,DCA具有细胞毒性作用,能够在不同细胞类型中诱导DNA损伤。其他胆汁酸,如亲水性的熊去氧胆酸(UDCA),已被用于治疗胆汁淤积性肝病和预防结肠癌。本文综述了胆汁酸的作用,并指出了巴雷特相关致癌过程中的新观点。