Biliary tract cancers are rare, with an estimated 12,000 newly diagnosed cases per year, not including intrahepatic cholangiocarcinoma.1 Biliary tract cancers are divided into intrahepatic, extrahepatic cholangiocarcinoma, and gallbladder cancer. Extrahepatic cholangiocarcinoma can then be divided into perihilar cholangiocarcinoma (Klatskin tumor) and distal common bile duct cancer.2 Gallbladder cancer is the most common type of biliary tract cancers, followed by perihilar and then distal common bile duct cholangiocarcinoma. Although intrahepatic cholangiocarcinoma represents only approximately 10 percent of biliary tumors, in recent years, incidence of intrahepatic cholangiocarcinoma has increased.
The cholangiocarcinoma also can be classified by the growth pattern of the tumor: mass-forming, periductal infiltrating, and intraductal. The mass-forming type is most commonly observed for intrahepatic cholangiocarcinoma and is associated with a high rate of lymph node metastasis.2 The periductal infiltrating type is commonly seen in perihilar cholangiocarcinoma. Intraductal growth type can be seen in any part of the biliary tree and is the rarest of the three. For intrahepatic cholangiocarcinoma, mixed type of mass-forming and periductal infiltrating is associated with significantly worse prognosis with no reported five-year survival and median overall survival of 8.3 months.3
Intrahepatic cholangiocarcinoma
Extrahepatic cholangiocarcinoma typically presents with obstructive jaundice. On the other hand, intrahepatic cholangiocarcinoma rarely exhibits symptoms and is incidentally detected by cross-sectional imaging. Consequently, intrahepatic cholangiocarcinoma often is diagnosed in late stage. Furthermore, diagnosis of intrahepatic cholangiocarcinoma is a diagnosis of exclusion, with broad differential diagnoses of metastatic cancer, hepatocellular carcinoma, cholangiocarcinoma, or benign liver mass. Meticulous and systemic diagnostic work-ups should be employed to establish the diagnosis of intrahepatic cholangiocarcinoma. High-quality, enhanced cross-sectional imaging is a must and sometimes needs both computed tomography (CT) and magnetic resonance imaging (MRI) to characterize the mass and narrow the list of differential diagnoses. Detailed medical history, including colon cancer risk and screening, alcohol consumption, viral hepatitis risk, travel history, and exposure to hepatotoxin, should be taken. Lab tests should include viral hepatitis panel, autoimmune hepatitis serology, iron studies, copper studies, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and alpha fetoprotein. CA19-9 could be diagnostic in cases of primary sclerosing cholangitis; however, in other cases, sensitivity is relatively low, particularly in the presence of biliary obstruction or cholangitis.4
High-quality cross-sectional imaging is the cornerstone of the diagnosis and treatment of this difficult disease. Particularly for hilar cholangiocarcinoma, liver protocoled CT or preferably enhanced MRI should be obtained before any instrumentation to the biliary tree. Once the biliary tree is decompressed, it is difficult to accurately assess the extent of the tumor in biliary tree, which creates significant difficulty in assessing whether the tumor can be resected and developing a surgical plan.
Biliary tract cancers are biologically aggressive with poor prognosis. Even for resected distal cholangiocarcinoma, which has better prognosis among cholangiocarcinoma, five-year survival has been reported as 36–42 percent.5,6 Five-year survival rates among patients with perihilar and intrahepatic cholangiocarcinoma are reported as 20–43 percent and 20–35 percent, respectively.6,7
Surgical resection is the mainstay of the curative-intent treatment; however, resection typically involves either large liver resection or pancreaticoduodenectomy with nodal dissection. Node dissection is an integral part of the surgical treatment because nodal metastasis is one of the strongest prognostic factors. Dissection of the node should include the lymph nodes along the hepatic artery to the celiac axis and lymph nodes along the common bile duct to retropancreatic area. Another important prognostic factor is margin negative resection. For the hilar cholangiocarcinoma, many experts recommend routine addition of caudate lobe resection to necessary liver resection to decrease the risk of margin positive resection because bile ducts of the caudate lobe originate from the hilar portion of the bile duct. Most cases of perihilar cholangiocarcinoma require resection of a significant amount of the liver—either lobectomy or trisectionectomy. Because of the magnitude of the operation, associated morbidities and mortalities are significant.
NCDB data analysis
The National Cancer Database (NCDB) from 2012 to 2014 captured 72.5 percent of the cancer cases in U.S.8 For the following analysis, NCDB data from 2010 to 2013 for patients 18 to 79 years old diagnosed with their first or only malignant or in situ primary were analyzed for intrahepatic, perihilar, and distal cholangiocarcinoma. The three types of cholangiocarcinoma were defined by primary site, histology/behavior, and a site-specific factor that distinguishes the subsite of the primary site C24.0.
The primary site for intrahepatic cholangiocarcinoma was C22.1, whereas distal and perihilar were C24.0. For all three cholangiocarcinoma types, the histology/behavior codes were 8160/3 and 8180/3. Only distal and perihilar cholangiocarcinoma used the site-specific factor to define cholangiocarcinoma type.
Distal cholangiocarcinoma’s site-specific factor values consisted of distal bile duct, common bile duct, common duct not otherwise specified, and subsite of extrahepatic bile ducts not stated or subsite stated as middle extrahepatic bile duct and treated with pancreaticoduodenectomy.
Perihilar cholangiocarcinoma site-specific factor values consisted of perihilar bile duct(s), proximal extrahepatic bile duct(s), hepatic duct(s), Klatskin tumor, and subsite of extrahepatic bile ducts not stated or subsite stated as middle extrahepatic bile duct and treated with combined hepatic and hilar resection.
Three-year survival analysis was performed using the Kaplan-Meier method and 95 percent confidence limits. The Commission on Cancer (CoC) program category—academic versus community (consisting of community and comprehensive community) cancer programs—was examined by the type of cholangiocarcinoma and the American Joint Committee on Cancer, 7th Edition pathologic stage group. This analysis was completed using Statistical Analysis System (9.4, Cary, NC) along with the significance threshold of p <0.05.
Of the three types of cholangiocarcinoma, 63.6 percent were intrahepatic, 18.7 percent were distal, and 17.7 percent were perihilar, with the majority of cholangiocarcinomas diagnosed and/or treated at academic cancer programs (see Table 1).
Table 1. Cancer type for diagnosis years 2010–2013
