Cholangiocarcinoma

Cholangiocarcinoma: It is a malignancy arising from the epithelium of the intra or extrahepatic bile ducts. Risk factors include alcoholism, smoking, diabetes mellitus, choledochal cyst, cholangitis, primary biliary cirrhosis, primary sclerosing cholangitis, anabolic steroids, cholelithiasis, cholecystitis, cholecystectomy, liver flukes, IBD, chronic pancreatitis, obesity, chronic liver disease, hemochromatosis, thorotrast (iv contrast) and Caroli disease. Any chronic inflammation in the biliary tree or biliary stasis can cause cholangiocarcinoma. Activation of NF-kB transcription factor via toll like receptor ligands like endotoxins, activation by bile acids lead to uncontrolled proliferation and neoplasia in bile ducts. Induction of nitric oxide synthase and COX 2 is seen. Post-cholecystectomy, increased levels of oxysterols is seen in bile which increases risk of carcinoma. Mutations in TP53, BAP1, SMAD4, KRAS, BRAF, EGFR are seen.

Types of cholangiocarcinoma

Intrahepatic

• Arises within the liver
• Origin from stem cells in the biliary tree
• 2nd most common primary hepatic malignancy

Extrahepatic

• Arises outside the liver
• Origin from stem cells in the biliary tree
• Can be hilar (Klatskin) or distal. Hilar are located within 2 cm of the bifurcation of the common hepatic duct; distal is further down the common bile duct.

It is asymptomatic till late stages when it presents with jaundice, abdominal pain, anorexia, weight loss. Laboratory findings include increased alkaline phosphatase, bilirubin, AST, CEA and CA 19-9. CT and MRI are used for diagnosis. The tumor mass shows calcification and forms a solid or infiltrative mass. Histology shows neoplastic glands in fibrous stroma, arranged in thyroid-like, signet ring or clear cell morphologies. Surgical resection is the preferred treatment. Erlotinib (EGFR inhibitor), gemcitabine and cisplatin are used in chemotherapy.

Biliary atresia: It is a multifactorial disease characterized by absence of part or whole of the extrahepatic biliary tree, seen in infants. It is a common cause of end-stage liver disease in children. Certain viruses like rotavirus, reoviruses and CMV have been implicated as the cause of biliary atresia. Symptoms appear in infancy and include jaundice, pale stools, hepatomegaly, irritability, failure to thrive, portal hypertension and cirrhosis. Most cases have atresia of the right and left hepatic ducts. Associated conditions like situs inversus, levocardia, VSD, renal defects, asplenia or polysplenia are seen in the less common embryonic form of biliary atresia. Laboratory findings include elevated total and direct bilirubin levels, alkaline phosphatase, GGT, AST, ALT and 5’nucleotidase. Ultrasound shows absence of gallbladder and absence of biliary dilation. Hepatobiliary scintiscan (DISIDA) shows delay or absence of secretion of radiolabelled bile into the intestine. ERCP may help, although it is difficult to do in infants. Intraoperative cholangiography delineates the biliary tree and shows the areas of obstruction. Liver biopsy shows an inflammatory infiltrate with degeneration of bile ducts, proliferation of ductal structures and fibrosis. Treatment is by Kasai procedure (portoenterostomy). Surgery should be done as early as possible as biliary atresia is a progressive disorder. Cholangitis may occur post-surgery. Some patients will need liver transplantation.