Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Abstract

Cholangiocarcinoma (CCA) constitutes a diverse group of malignancies emerging in the biliary tree. CCAs are divided into three subtypes depending on their anatomical site of origin: intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) CCA 1,2 (Fig. 1). Of note, considered as an independent entity, mixed HCC-CCA tumours are a rare type of liver malignancy sharing features of both iCCA and HCC and presenting an aggressive disease course and poor prognosis 3,4. iCCAs arise above the second-order bile ducts, whereas the point of anatomical distinction between pCCA and dCCA is the insertion of the cystic duct. pCCA and dCCA can also be collectively referred to as 'extrahepatic' (eCCA) 5. In the USA, pCCA is the single largest group, accounting for approximately 50-60% of all CCAs, followed by dCCA (20-30%) and iCCA (10-20%) 1,6,7. CCA is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), comprising approximately 15% of all primary liver tumours and 3% of gastrointestinal cancers 1,6,7. CCAs are usually asymptomatic in early stages and, therefore, often diagnosed when the disease is already in advanced stages, which highly compromises therapeutic options, resulting in a dismal prognosis 1,8. CCA is a rare cancer, but its incidence (0.3-6 per 100,000 inhabitants per year) 1 and mortality (1-6 per 100,000 inhabitants per year, globally 9 , not taking into account specific regions with incidence >6 per 100,000 habitants such as South Korea, China and Thailand) have been increasing in the past few decades worldwide, representing a global health problem. Despite advances in

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

“…Large bile duct iCCA arises in large intrahepatic bile ducts and contains mucinproducing columnar tumor cells. 17 …”

“… 12 , 13 The first type is called small-duct type iCCA showing an almost exclusively mass-forming growth pattern, 14 , 15 whereas the second type is a mucinous iCCA, called large-duct type and appears as massforming, periductal infiltrating or intraductal growing. 16 , 17 In fact, according to the World Health Organization (WHO) classification, CCAs include a pure mucin-secreting and a mixed form. 18 The large-duct type iCCAs arise from the mucin secreting epithelium lining large ducts formed by mature cells; whereas, the small-duct type originates from non mucin-secreting cells lining small bile ducts or canals of Hering formed by immature cholangiocytes.…”

Translating Biomarkers of Cholangiocarcinoma for Theranosis: A Systematic Review

“…Cholangiocarcinomas (CCA) are a group of cancers of the biliary system which are usually diagnosed late, often with a dismal prognosis [ 1 , 2 , 3 , 4 ]. The most commonly used classification of CCA is anatomical and describes peripheral or intra-hepatic (iCCA), hilar or perihilar (pCCA), and distal (dCCA); the latter two being subtypes of extra-hepatic CCA (eCCA) [ 2 ].…”

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma

“…The small-duct-type cancer usually has a history of chronic liver disease (five-year overall survival is longer ~60%, most of which are genetic changes of IDH1, BAP1 and FGFR2) and large-duct iCCA and pCCA have many clinicopathological characteristics and are accompanied by premalignant biliary intraepithelial neoplasia (BiIIN) in adjacent ducts (five-year overall survival is shorter, accounting for about 20%, most of which are genetic changes of SMAD4 and KRAS7) [ 4 ]. The incidence of CCA has been increasing worldwide, especially in Asia [ 5 ]. Analyzing the annual mortality rate of CCA, the average mortality rate for the period 2010–2014 was 0.3–2.88 (per 1 × 10 5 inhabitants) [ 6 ].…”