Holzinger F, Z'graggen K, Büchler M W
Department of Visceral and Transplantation Surgery, Inselspital, University of Berne, Switzerland.
Ann Oncol. 1999;10 Suppl 4:122-6.
Carcinomas of the biliary tract are rare cancers developing from the epithelial or blast-like cells lining the bile ducts. A variety of known predisposing factors and recent experimental models of biliary carcinogenesis (e.g., infection with the liver fluke Opisthorchis viverrini, models of chemically induced carcinogenesis and experimental models of pancreaticobiliary maljunction) have elucidated different stages of this complex system of biliary tumorigenesis. Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxification mechanisms, activation of oncogenes, functional loss of tumor-suppressor genes and dysregulation of cell proliferation and cell apoptotic mechanisms have been identified as important contributors in the development of cholangiocarcinomas. In this review, the known mechanisms involved in the carcinogenesis of biliary epithelium are addressed. We will divide the topic into four stages: 1) Predisposition and risk factors of biliary cancer. 2) Genotoxic events and alterations leading to specific DNA damage and mutation patterns. 3) Dysregulation of DNA repair mechanisms and apoptosis, permitting survival of mutated cells and 4) Morphological evolution from premalignant biliary lesions to cholangiocarcinoma. Finally, established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addressed.
胆管癌是一种罕见的癌症，由胆管内衬的上皮细胞或原始样细胞发展而来。多种已知的诱发因素以及最近的胆管癌发生实验模型（例如，感染肝吸虫华支睾吸虫、化学诱导致癌模型和胰胆管连接异常实验模型）已经阐明了这个复杂的胆管肿瘤发生系统的不同阶段。慢性炎症过程、活性氧自由基的产生、细胞解毒机制的改变、癌基因的激活、肿瘤抑制基因的功能丧失以及细胞增殖和细胞凋亡机制的失调已被确定为胆管癌发生发展的重要因素。在这篇综述中，我们将探讨胆管上皮癌变的已知机制。我们将这个主题分为四个阶段：1）胆管癌的易感性和危险因素。2）导致特定DNA损伤和突变模式的基因毒性事件和改变。3）DNA修复机制和细胞凋亡的失调，使突变细胞得以存活，以及4）从癌前胆管病变到胆管癌的形态学演变。最后，我们将探讨针对胆管癌发生过程中特定致病事件的既定和假设性未来治疗策略。
