Cholangiocarcinoma- Review, Latest Treatments Rashikh Choudhury General: -malignant epithelial tumor of the biliary tree that accounts

for about 10-15% of all hepatobiliary malignancies (most common is HCC) -surgical resection is only cure, however most patients are unresectable at diagnosis and die within 1 yr -5-10% survival in 5 years (Anderson 2004), only about 10-30% of patients resectable. Incidence: -The peak incidence is in the eighth decade of life and more common in men. -Overall, the incidence the United States is approximately 1.0/100 000 people per year Risk Factors: -Primary sclerosing cholangitis, Liver flukes infestation (Opisthorchis viverrini and Clonorchis sinensis), Choledochal cysts and Caroli's disease, Cholelithiasis and Hepatolithiasis, Chemicals (e.g., Thorotrast and Dioxin), Hepatitis C, Lynch syndrome II, Bile duct adenoma and multiple biliary papillomatosis Location:

Pathology:

-More than 90% of cholangiocarcinomas are adenocarcinomas. -Other types, which account for less than 5% each, are squamous cell carcinomas, sarcomas, small cell cancer, and lymphomas. -Divided into the following types: sclerosing, (desmoplasia most common) nodular (mass-forming), papillary (best prognosis) Presentation: -Most CCs remain clinically silent until the advanced stage. -Painless jaundice is the most common complaint of patients with cholangiocarcinoma, seen in about 70% to 90% of patients, Pruritis (66%), Abdominal pain, Weight loss (30% to 50%), Fever in about 20%. Clay colored stool -A palpable liver may be noted in patients with intrahepatic cholangiocarcinoma, A palpable gallbladder (Courvoisier's sign), Obstruction of the bile duct and biliary stasis may lead to bacterial colonization and cholangitis, Cachexia and malaise. Diagnosis: -Elevated AST, ALT, AlkPhos, GGT, CEA, Ca19-9 -Can get cytology with ERCP brush, percut biopsy not recommended -CT, MRI/MRCP Treatments: Medical: -Extremely chemo resistant -gemcitabine, or gemcitabine plus platinum found to have median survival of 9-12 months. (Lim 2010) -Surgery: -Goal of surgery is to resect lesion with negative margins Signs of unresectable disease: PSC (usually multifocal, underlying parenchymal disease) Bilateral hepatic duct involvement up to secondary

radicals, Bilateral hepatic artery involvement, Encasement of the portal vein, Atrophy of one hepatic lobe with contralateral portal vein encasement, Atrophy of one hepatic lobe with contralateral biliary radical involvement, Distant metastasis Surgical Management: -Intraoperatively, more than half of these patients are found to have either peritoneal or hepatic metastases or, more likely, locally unresectable disease. -Selective use of laparoscopy in patients with locally advanced but potentially resectable perihilar cholangiocarcinoma may avoid laparotomy in some patients with metastatic disease. -In patients who are found to have extensive metastatic disease, biliary stents should be left in place. -Lobectomy for intrahepatic (3 yr survival 20-60%)

palliation, including a Roux-en-Y hepaticojejunostomy to segment III or V., -Whipple procedure for distal cholangio (5 year survival 15-40%) Other Treatment Modalities: -Transplantation as a primary treatment modality for hilar and intrahepatic cholangiocarcinoma is a viable option -Extrahepatic nodal disease or metastases are a contraindication to transplant -1, 2, 5 year survival for traditionally unresectable disease was 72, 48, and 23% respectively. -Improved 5 year survival with transplant w/ Whipple (38%), and/or transplant with neoadjuvant chemoradiation (76%) (Mayo Clinic) -Mayo Experience-Many issues- tumor recurrence due to immunosuppression? -Controversies exist about organ allocation- Live Liver donation a potential solution?

-For type I and II lesions, the procedure is en bloc resection of the extrahepatic bile ducts and gallbladder,regional lymphadenectomy with Roux-en-Y hepaticojejunostomy. -Type II tumors may require hepatic lobectomy. Because type II and III lesions often involve the ducts of the caudate lobe, many surgeons recommend routine caudate lobectomy. -In patients with locally advanced unresectable perihilar tumors, several operative approaches are available for

References:
-Anderson CD, Diagnosis and Treatment of Cholangiocarcinoma. Theoncologist. 2004 -Ustandag, Cholangiocarcinoma: A compact review of the literature. WJG, 2008 -Nilesh, Cholangiocarcinoma presentation slides, pptfun.com/Funppt/Health_Powerpoint/Cholangiocarcinoma.pps Lim, Current and Emerging Treatments for Cholangiocarcinoma, IJH, 2010