CHOLANGIOCARCINOMA; UPDATES IN DIAGNOSIS AND TREATMENT

Abstract

Cholangiocarcinoma is an epithelial cell malignancy arising from varying locations within the biliary tree. The most contemporary classification based on anatomical location includes; intrahepatic, perihilar, and distal cholangiocarcinoma. Average incidence is one case per 100,000 persons per year.The frequency of intrahepatic cholangiocarcinoma has increased over time and is most commonly noted in women older than 60 years. Most cholangiocarcinomas arise de novo, and no risk factors are identified. Recently, cirrhosis and viral hepatitis C and B have been recognised as risk factors for cholangiocarcinoma, especially intrahepatic disease. The contribution of hepatitis C and hepatitis B in tumour development differs in western countries, where hepatitis C is more prevalent, versus Asian countries, where hepatitis B is endemic. There is a well established association between primary sclerosing cholangitis, marked by chronic inflammation with liver injury and likely proliferation of the progenitor cells, and cholangiocarcinoma, especially perihilar disease. The lifetime incidence of cholangiocarcinoma in this patient population ranges between 5% and 10%. Only a small number of bile duct cancers are found before they have spread too far to be removed by surgery. If the cancer is diagnosed at an early stage, treatment might be more effective.Cholangiocarcinoma is suspected based on signs of biliary obstruction, abnormal liver function tests, elevated tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen), and ultrasonography showing a bile stricture or a mass, especially in intrahepatic cholangiocarcinoma. Magnetic resonance imaging (MRI) or computed tomography (CT) is performed for the diagnosis and staging of cholangiocarcinomas. However, differentiation of an intraductal cholangiocarcinoma from a hypovascular metastasis is limited at imaging. Brush cytology during endoscopic or transhepatic procedures is the most common technique for tissue sampling in patients with presumed malignant biliary stricturesAlthough brush cytology combined with biopsy allows for the correct identification of 40% to 70% of perihilar and distal ECCs,Cholangioscopy-guided biopsies using mini-forceps also have been used to increase diagnostic yield. There are limited treatment options that are effective for cholangiocarcinoma. Treatment options will be determined by the performance status of the patient, theextent of the spread and resectability of the tumor, and the presence or absence of cirrhosis and portal hypertension.Cure for cholangiocarcinoma requires a complete surgical resection with histologically negative margins. In general, surgical resection with curative intent is associated with 5-year survival rates of 22% to 36% for ICC and up to 30% to 40% for perihilar lesions. Five year survival rates of 20% to 54% have been reported for distal cholangiocarcinomas managed by pancreatoduodenectomy. Using of neoadjuvant therapy before surgical resection of cholangiocarcinomas is sparse. In one small series, neoadjuvant chemoradiation increased surgical resectability in patients with ECCs. Neoadjuvant photodynamic therapy (PDT) of the biliary tree was used in another small study to treat tumors with free margin of 2cm to improve R0 resection rate. The preoperative biliary drainage in management of patients with cholangiocarcinoma is controversial. It mayimprove hepatic function and nutritional status, reduces the risk of cholangitis, facilitates hilar dissection, and reduces the risk of postoperative liver failure. Preoperative, ipsilateral PVE can potentially reduce the risk of liver dysfunction and failure after extended lobar resections by inducing compensatory hypertrophy of the (non-embolized) FLR. In patients being considered for lobar or extended lobar resections, direct cholangiography or portal vein embolization (PVE) may be required. In studies that combined preoperative biliary drainage with PVE before surgical resection of perihilar cholangiocarcinomas, nearly all patients experienced near-complete relief of their jaundice.