Cholangiocarcinoma—controversies and challenges

Abstract

Cholangiocarcinomas are a diverse group of tumors that are presumed to originate from the biliary tract epithelium either within the liver or the biliary tract. These cancers are often difficult to diagnose, their pathogenesis is poorly understood, and their dismal prognosis has resulted in a nihilistic approach to their management. The two major clinical phenotypes are intrahepatic, mass-forming tumors and large ductal tumors. Among the ductal cancers, lesions at the liver hilum are most prevalent. The risk factors, clinical presentation, natural history and management of these two types of cholangiocarcinoma are distinct. Efforts to improve outcomes for patients with these diseases are affected by several challenges to effective management. For example, designations based on anatomical characteristics have been inconsistently applied, which has confounded analysis of epidemiological trends and assessment of risk factors. The evaluation of therapeutic options, particularly systemic therapies, has been limited by a lack of appreciation of the different phenotypes. Controversies exist regarding the appropriate workup and choice of management approach. However, new and emerging tools for improved diagnosis, expanded indications for surgical approaches, an emerging role for locoregional and intrabiliary therapies and improved systemic therapies provide optimism and hope for improved outcomes in the future.

Inflammatory Bowel Disease and Risk of Cholangiocarcinoma: Evidence from a Meta-analysis of Population-based Studies

“…Cholangiocarcinoma (CC), a malignant tumor arising from the epithelial cells (cholangiocytes) lining the biliary tree, is characterized by a diagnostically and therapeutically challenging cancer (Patel, 2011). It is the second most common primary hepatic malignancy after hepatocellular cancer, contributing to approximately 10-25% of all hepatobiliary malignancies (Blechacz et al, 2008;Sripa et al, 2008;Gatto et al, 2010).…”

“…Differing exposure to risk factors is considered to account for the variation of geographic incidences (Shaib et al, 2004;Sripa et al, 2008;Songserm et al, 2012). Anatomically, CC can be categorized as intrahepatic CC (ICC) and extrahepatic CC (ECC) on the basis of its location (Patel., 2011). Klatskin tumor, i.e Hilar CC, is typically classified as extrahepatic (Tyson et al, 2011).…”

High Expression of HIF-1α, BNIP3 and PI3KC3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival and Metastasis

“…Cholangiocarcinoma (CCA), a bile duct cancer, arises from biliary epithelium within either the intrahepatic or the extrahepatic biliary tract (Patel, 2006). Recent epidemiological studies show that the incidence and mortality rates of CCA are increasing worldwide (Patel, 2006).…”

“…Recent epidemiological studies show that the incidence and mortality rates of CCA are increasing worldwide (Patel, 2006). Surgical intervention is the only promising curative treatment in the early stage of disease; unfortunately, the prognosis of advanced CCA is extremely poor and chemotherapy is the only feasible treatment for this stage of disease (Thongprasert et al, 2005).…”

Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development

“…They are relatively rare cancers (about 3 % of malignant tumors) in western countries (USA and Europe), but remain difficult to diagnose and treat, respond very poorly to chemotherapy and radio-therapy and have a high mortality rate: over 50 % in untreated patients within a few months of diagnosis (Patel 2011).…”