ReviewDiagnosis and management of intrahepatic cholangiocarcinoma: A comprehensive update for the radiologist
Introduction
Cholangiocarcinoma is the most common neoplasm of the biliary tree. It is further classified based on its location as intrahepatic or extrahepatic. Extrahepatic cholangiocarcinoma is subdivided as perihilar (Klatskin's tumour) and distal extrahepatic cholangiocarcinoma. The anatomical site of origin distinguishing intrahepatic cholangiocarcinoma (IHCC) from extrahepatic cholangiocarcinoma is the second-order (segmental) bile duct, with extrahepatic cholangiocarcinoma originating from the first-order bile duct (right and left hepatic ducts) to the common bile duct (CBD).1, 2 The exact distinction between perihilar and distal cholangiocarcinoma is not well-defined, with some using the junction of the cystic duct and the CBD as the landmark (although this can be variable) and others using the point where the CBD passes under the first part of the duodenum.3, 4 IHCC is the least common of the three, accounting for approximately 8–10% of cholangiocarcinoma.3, 5, 6 The incidence of IHCC is significantly different worldwide with a much higher incidence in Asia than in Europe and America (0.95 per 100,000 in USA as compared to 96 per 100,000 in Thailand).7 However, its incidence is increasing across the world, attributable to a true increase rather than to improved diagnosis. This has lead to an increasing focus on IHCC in recent times.8 Mortality, however, has shown a progressive decrease in USA between 1996 to 2010 as per a recent study of 8805 patients from the Surveillance, Epidemiology and End Results (SEER) database.9
The imaging features of IHCC have been well described. However, in addition to diagnosis, radiology also plays an important role in patient prognostication and management, which will be an important focus of this article. In this review, we will discuss the aetiopathogenesis of IHCC, explain the revised 2009 TNM classification, which introduced a separate staging for IHCC for the first time, discuss in detail the role of imaging in the diagnosis, prognostication, and follow-up of IHCC, and provide an update on the management of IHCC with emphasis on the role of the radiologist.
Section snippets
Aetiopathogenesis
The most common age group affected by IHCC is between 55–75 years, with a slight male preponderance in both incidence and mortality.10, 11, 12, 13 Risk factors include various disorders, which cause chronic biliary inflammation, including primary sclerosing cholangitis, parasitic infestation (endemic in Southeast Asia), hepatolithiasis, hepatitis B and C, and cirrhosis, as also congenital abnormalities of the biliary tract such as choledochal cyst and fibrocystic liver disease.10, 12, 14
The
Revised TNM classification
Until the sixth edition (2002) of the American Joint Committee on Cancer (AJCC)/ International Union Against Cancer (UICC) TNM staging system, no distinction was made between the classification of hepatocellular carcinoma (HCC) and IHCC. However, a study of 598 patients obtained from the SEER database concluded that tumour size was not an important prognostic factor, whereas the presence of vascular invasion and multiple nodules predicted worse prognosis in IHCC. In light of these findings, the
Imaging features
Imaging can be discussed with regards to three aspects: imaging features of primary IHCC, role of imaging in patient prognostication, and imaging of recurrent/metastatic disease.
Initial evaluation of “carcinoma of unknown primary”
When a patient presents with an isolated hepatic lesion that is proven to be adenocarcinoma on biopsy, extensive work-up is needed to differentiate between a cancer of unknown primary (metastatic disease) and IHCC. This includes CT of the chest, abdomen, and pelvis along with correlation with tumour markers including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and alpha-foetoprotein (AFP). Classic radiological findings help in the diagnosis, besides ruling out other
Future directions
Molecular targeted therapy (MTT) has changed the face of treatment in various cancers such as gastrointestinal stromal tumours and renal cell cancers. Various promising trials using MTT including VEGF (vascular endothelial growth factor) inhibitors (bevacizumab, sunitinib, sorafenib), and EGFR (epidermal growth factor receptor) inhibitors (erlotinib, cetuximab) alone or in combination with conventional chemotherapy are currently ongoing and need to be validated on a larger scale.7 Orthotopic
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