Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma

By Sumera I. Ilyas, G. Gores. Gastroenterology, 2013

1,224 citations recorded by the source corpus.

Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic (iCCA), perihilar (pCCA), or distal CCA (dCCA). 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 y 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 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 are usually treated surgically, whereas liver transplantation following neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology, pathogenesis, of CCA, along with advances in classification, diagnosis and treatment.

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Citations in the corpus

Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways (2015, background): “compartment that promote recruitment of myofibroblasts.(26) Together, these data suggest that the interaction of cholangiocytes with multiple cell types—including lymphocytes, HSCs, and portal fibroblasts—contributes to chronic inflammation and fibrosis in cholestatic liver disease.”
Chronic Inflammation and Cytokines in the Tumor Microenvironment (2014, background): “Researchers have since identified several substances that can be produced by CCAassociated fibroblasts, including periostin, hepatocyte growth factor (HGF), tenascin-C, and CXCL-12 [243, 244].”
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer (2016, background): “HCC and CCA have poor prognoses, with a 5-year survival rate of less than 12% for HCC (6) and 10% for CCA (7) due to a combination of late diagnosis and the lack of efficient therapies for advanced stages.”