Bile Duct Tumors: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Bile duct tumors (cholangiocarcinoma, CCA) arise from the bile duct epithelium and are classified by anatomical location: intrahepatic (iCCA, approximately 20%), perihilar or Klatskin tumor (approximately 50%), and distal extrahepatic (approximately 30%). Together they represent approximately 15% of hepatobiliary malignancies globally, with rising iCCA incidence worldwide.

Primary sclerosing cholangitis (PSC) carries a 10-15% lifetime CCA risk. Liver flukes (Opisthorchis viverrini, Clonorchis sinensis) are endemic risk factors in Southeast Asia. Additional risks: choledochal cysts, hepatolithiasis, biliary papillomatosis, HBV, HCV, and NAFLD. Key molecular alterations: FGFR2 fusions (approximately 15% iCCA), IDH1 mutations (approximately 15% iCCA), KRAS, ARID1A, BRCA1/2, and HER2.

Perihilar and distal CCA: painless obstructive jaundice, dark urine, pale stools, pruritis, weight loss, and right upper quadrant pain. Intrahepatic CCA: often asymptomatic until large, detected as a hepatic mass on imaging; constitutional symptoms (weight loss, fever). Cholangitis (fever, rigors, jaundice — Charcot's triad) when biliary infection complicates obstruction. CA 19-9 elevated in approximately 75%.

CT/MRI abdomen with hepatobiliary protocol plus MRCP. ERCP with biliary brushings and fluorescence in situ hybridization (FISH) for perihilar/distal CCA. Percutaneous CT-guided biopsy for iCCA. EUS-FNA for distal CCA. Comprehensive NGS panel essential: FGFR2 fusion, IDH1 mutation, KRAS, BRAF, NTRK, RET, HER2, MSI/MMR, TMB — these guide second-line targeted therapy selection. Portal vein embolization for inadequate future liver remnant before major hepatectomy.

Resectable iCCA: hepatic resection with negative margins (R0); adjuvant capecitabine. Resectable perihilar CCA: major hepatectomy including caudate lobe; Whipple for distal CCA. Liver transplantation for selected unresectable perihilar CCA (meeting strict Mayo criteria). Biliary stenting for palliation. First-line metastatic: gemcitabine plus cisplatin plus durvalumab (TOPAZ-1: OS benefit). Targeted second-line: pemigatinib or futibatinib (FGFR2+), ivosidenib (IDH1+), pembrolizumab (MSI-H), larotrectinib (NTRK), neratinib or trastuzumab (HER2+).

Resected CCA with negative margins: 5-year OS approximately 25-40%. Resection rates remain low (approximately 20-30%) due to advanced presentation. Metastatic: median OS with gemcitabine-cisplatin-durvalumab approximately 12.8 months (TOPAZ-1). FGFR2-targeted therapy: ORR approximately 25-35%, median PFS approximately 7-9 months. IDH1 inhibitor ivosidenib: median PFS 2.7 months versus 1.4 months for placebo in second line.