Diagnostic value of cell free tumor DNA in bile and its relation to biliary bile acids for Biliary Tract Carcinoma.

Biliary tract carcinoma includes gallbladder carcinoma, intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma and distal cholangiocarcinoma. (1) The 5 year survival rate is <10% in patients with advanced or metastatic BTCs (2). Most patients are ineligible for surgical resection at the time of diagnosis of BTC (3). Since the current treatments are minimally effective, a multi-omic approach combining genomic, transcriptomic, and metabolomic landscapes would be beneficial and could lead to earlier diagnosis and improved treatment. In addition, the etiological role of biliary bile acids in biliary tract carcinomas still remains equivocal. This trial aims to analyze the utility of biliary cell free DNA for the diagnosis of BTCs, and correlation of biliary cell free DNA and relative proportions of  biliary bile acids in biliary tract carcinoma. All eligible patients who have biliary tract carcinomas (BTC), benign biliary diseases with high risk for BTC and symptomatic gallstone disease during the study period will be included in the study. Bile samples collected at the time of surgery or at the time of interventional procedures like PTBD, ENBD, ERCP, will be analyzed for cell free tumor DNA (cft DNA) and biliary bile acids. The collected bile samples will be stored at -20 degrees Celsius. The cell free tumor DNA (cft DNA) in bile is analyzed using NGS through a somatic panel of 16 genes. Biliary bile acids (Total bile acids, Cholic acid, Chenodeoxycholic acid, Deoxycholic acid, Lithocholic acid and Ursodeoxycholic acid) are analyzed using LCMS.