Cholangiocarcinoma: This is a malignancy arising from the epithelium of the intrahepatic 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. In general, any chronic inflammation in the biliary tree or biliary stasis can lead to cholangiocarcinoma.
At the molecular level, activation of the NF-kB transcription factor can occur via toll-like receptor ligands (such as endotoxins). Bile acids can also activate these pathways, leading to uncontrolled proliferation and neoplasia in the bile ducts. Induction of nitric oxide synthase and COX 2 is seen. Post-cholecystectomy, increased levels of oxysterols are seen in bile, which increases the risk of carcinoma. Mutations in TP53, BAP1, SMAD4, KRAS, BRAF, and EGFR are seen.
Cholangiocarcinoma is often asymptomatic until late stages. When symptoms occur, they include jaundice, abdominal pain, anorexia, and 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 may show calcification and can form 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: This is a multifactorial disease characterized by absence of part or all of the extrahepatic biliary tree, seen in infants. It is a common cause of end-stage liver disease in children. Certain viruses, including rotavirus, reoviruses, and CMV, have been implicated as causes 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 such as situs inversus, levocardia, VSD, renal defects, and 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 the 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 the Kasai procedure (portoenterostomy). Surgery should be done as early as possible because biliary atresia is a progressive disorder. Cholangitis may occur post-surgery. Some patients will need liver transplantation.
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