Ilyas Sumera I, Khan Shahid A, Hallemeier Christopher L, Kelley Robin K, Gores Gregory J
Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Department of Hepatology, St Mary's Hospital, Imperial College London, Praed Street, London W2 1NY, UK.
Nat Rev Clin Oncol. 2018 Feb;15(2):95-111. doi: 10.1038/nrclinonc.2017.157. Epub 2017 Oct 10.
Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.
胆管癌根据解剖位置分为肝内型（iCCA）、肝门周围型（pCCA）或远端型（dCCA）。每种亚型都有独特的流行病学、生物学特性、预后及临床管理策略。在过去几十年中，胆管癌尤其是iCCA的发病率在全球范围内呈上升趋势。手术切除仍然是所有这三种疾病亚型潜在治愈性治疗的主要手段，而新辅助放化疗后的肝移植仅限于早期pCCA患者的一个亚组。对于晚期或不可切除疾病的患者，局部和全身化疗是主要的治疗选择。外照射放疗的改进促进了胆管癌的治疗。此外，全面的全外显子组和转录组测序的进展已经明确了每种胆管癌亚型的基因图谱。因此，已经确定了有前景的精准医学分子靶点，并正在临床试验中进行评估，包括探索免疫治疗的试验。生物标志物驱动的试验，即根据胆管癌的解剖亚型和基因异常对患者进行分层，对于靶向治疗的发展至关重要。结合靶向治疗针对胆管癌丰富的肿瘤基质也可能是有用的。在此，我们综述胆管癌在流行病学、发病机制和管理方面的不断发展。
