Diagnosis

Cholangiocarcinoma

Etiology

Cause [7wz][wqo]

• The etiology of most bile duct cancers remains undetermined

• Adenocarcinoma (95%)

• Squamous cell tumor (5%)

Pathophysiology [7wz]

1. Long-standing inflammation

2. Hyperplasia, cellular proliferation

3. Ultimately malignant transformation: mutations K-RAS, B-RAF, TP53, SMAD4

Risk factors [7wz][wqo]

• Chronic liver infection --> Cirrhosis:

  • Parasite: liver fluke

  • Viral hepatitis

• Autoimmune/inflammatory conditions --> Cirrhosis:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD)

  • Primary sclerosing cholangitis

  • Ulcerative colitis

  • Crohns disease

  • Chronic cholecystitis

  • Toxins (alcohol)

  • Chemical exposure (asbestos)

  • Choledochal stones

• Anatomical conditions:

  • Choledochal cysts

  • Caroli disease

  • Bile duct adenoma

  • Biliary papillomatosis

• Genetic: Alpha 1-antitrypsin deficiency, Lynch syndrome, multiple biliary papillomatosis, cystic fibrosis, hemochromatosis

• Lifestyle: Type 2 diabetes, obesity, alcohol, cigarette smoking

Complications [wqo]

• Liver failure

• Cholangitis

• Cirrhosis

• Metastasis

Epidemiology

Incidence per 100.000 [tis][8pd][pqb]

Approach

• Diagnosing cholangiocarcinoma can be difficult: [wqo]

  • Biopsy techniques lack diagnostic sensitivity

  • Surgical intervention may be indicated even without a confirmatory biopsy

• Blood test: CA 19-9, complete blood count, comprehensive metabolic profile, liver function tests, coagulation studies

• Ultrasound abdomen

• CT abdomen

• MRI abdomen

• PET-CT

• MRCP

• ERCP-guided biopsy

• EUS-guided biopsy

• PTC for decompression of dilated bile ducts

Treatment

1. Surgical resection --> 10% with early-stage disease --> curative resection [wqo]

   • Intrahepatic Cholangiocarcinoma

     • Hepatic resection with microscopically negative margins (R0)

     • Liver transplantation with variable 5-year survival (53-80%) [zte][pm2]

   • Perihilar Cholangiocarcinoma: Bismuth Corlette Classification

     • Resection of the extrahepatic bile duct and adjacent liver (or hemihepatectomy)

     • Liver transplantation

   • Distal Cholangiocarcinoma:

     • Pancreaticoduodenectomy

2. Palliative treatment:

   • Stenting (ERCP or PTC) --> treat biliary obstruction --> relieve pruritus

   • Photodynamic therapy --> restoring biliary drainage

   • Localized radiofrequency ablation:

     • An electrode is placed in the center of the tumor --> microwave energy

   • Localized radiation therapy --> reduce tumors --> resectable [wqo]

     • Transarterial radioembolization (TARE): Yttrium 90 via the hepatic artery directly into the tumor, followed by vessel embolization. This results in a high dose of radiation in the immediate vicinity of the tumor

   • Localized chemotherapy: [wqo]

     • Transarterial chemoembolization (TACE): Chemotherapeutic agents (Doxorubicin and platinum agents) directly instilled into the hepatic artery, followed by embolization of the artery

     • Hepatic artery infusion: chemotherapy is instilled directly into the hepatic artery proper via a subcutaneously placed pump

   • Targeted Therapy: fibroblast growth factor receptor 2-inhibitors

Differential diagnoses

Benign bile duct tumor, Bile duct stricture, Biliary obstruction, Cholangitis, Cholecystitis, Choledochal cysts, Choledocholithiasis, Cholelithiasis, Gallbladder cancer, Hepatocellular carcinoma, Pancreatic cancer, Primary biliary cirrhosis, Primary sclerosing cholangitis