Pathogenesis, diagnosis, and management of cholangiocarcinoma

Gastroenterology. 2013 Dec;145(6):1215-29. doi: 10.1053/j.gastro.2013.10.013. Epub 2013 Oct 15.


Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic CCA (iCCA), perihilar CCA (pCCA), or distal CCA. These subtypes differ not only in their anatomic location, but in epidemiology, origin, etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has been increasing over the past 3 decades, and only a low percentage of patients survive until 5 years after diagnosis. Geographic variations in the incidence of CCA are related to variations in risk factors. Changes in oncogene and inflammatory signaling pathways, as well as genetic and epigenetic alterations and chromosome aberrations, have been shown to contribute to the development of CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer-associated fibroblasts, which promotes their progression. We have gained a better understanding of the imaging characteristics of iCCAs and have developed advanced cytologic techniques to detect pCCAs. Patients with iCCAs usually are treated surgically, whereas liver transplantation after neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology and pathogenesis of CCA, along with advances in classification, diagnosis, and treatment.

Keywords: CA19-9; CAF; CCA; CT; CXCR4; Cancer-Associated Fibroblasts; Distal Cholangiocarcinoma; ECM; EGFP; EGFR; EMT; ERBB2; ERC; ERK; FGFR; FISH; HBV; HCC; HCV; HGF; IDH; IL 6; Intrahepatic Cholangiocarcinoma; KRAS; Kirsten rat sarcoma viral oncogene homolog; MAPK; MCL1; MET; MMP; MRI; Molecular Pathogenesis; OR; PDGF; PI; PI3K; PSC; STAT; TP53; cancer-associated fibroblast; carbohydrate antigen 19-9; chemokine (C-X-C motif) receptor 4; cholangiocarcinoma; computed tomography; dCCA; distal cholangiocarcinoma; endoscopic retrograde cholangiography; enhanced green fluorescent protein; epidermal growth factor–receptor; epithelial–mesenchymal transition; extracellular matrix; extracellular signal regulated kinase; fibroblast growth factor receptor; fluorescence in situ hybridization; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; hepatocyte growth factor; iCCA; interleukin 6; intrahepatic cholangiocarcinoma; isocitrate dehydrogenase; magnetic resonance imaging; matrix metalloproteinase; met proto-oncogene; miR; microRNA; mitogen-activated protein kinase; myeloid cell leukemia sequence 1; odds ratio; pCCA; perihilar cholangiocarcinoma; phosphatidyl inositol; phosphatidylinositol-4,5-bisphosphate 3-kinase; platelet-derived growth factor; primary sclerosing cholangitis; signal transducer and activator of transcription; tumor protein 53; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2; α-SMA; α-smooth muscle actin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / etiology*
  • Bile Duct Neoplasms / therapy
  • Bile Ducts, Intrahepatic*
  • Chemoradiotherapy
  • Cholangiocarcinoma / diagnosis*
  • Cholangiocarcinoma / etiology*
  • Cholangiocarcinoma / therapy
  • Combined Modality Therapy
  • Disease Management*
  • Disease Models, Animal
  • Humans
  • Incidence
  • Liver Transplantation
  • Mesothelin
  • Proto-Oncogene Mas
  • Risk Factors
  • Survival Rate