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A. Characteristics navigator

  1. Cancers of the Bile Duct Cells
    1. Includes intrahepatic, perihilar, and distal extrahepatic bile duct tumors
    2. About 65% are perihilar, 25% are distal extrahepatic, and 20% are intrahepatic
    3. ~90% are adenocarcinomas
    4. Metastatic disease is present in majority of patients at presentation
  2. Classification
    1. Type I: tumors below confluence of left and right hepatic ducts
    2. Type II: tumors reaching the confluence
    3. Type IIIa: tumors occluding common hepatic duct and right hepatic duct
    4. Type IIIb: tumors occluding common hepatic duct and left hepatic duct
    5. Type IV: multicentric (Klatskin) tumors, perihilar at confluence of both hepatic ducts (~65%)
  3. Most patients die of complications related to bile duct obstruction
  4. Epidemiology
    1. ~3% of all gastrointestinal cancers
    2. Peak age is 7th decade of life, slight male predomineance
    3. Increasing incidence of intrahepatic cholangiocarcinomas (decreasing extrahepatic)
    4. 3500 new cases per year in USA
  5. Other Biliary Tract Cancers
    1. Embryonal rhabdomyosarcoma
    2. Gallbladder cancers

B. Risk Factors navigator

  1. Cholangiocarcinoma
    1. Sclerosing cholangitis - lifetime risk 10-30%, usually presents at age <50 years
    2. Ulcerative cholitis (even without symptomatic sclerosing cholangitis)
    3. Bile duct adenoma
    4. Multiple biliary papillomatosis
    5. Choledochal cysts
    6. Various parasites (not found in North America): liver flukes (Opisthorcis, Clonorchis)
    7. Smoking
    8. Fibropolycystic liver disease - congenital diseases including Caroli's disease
    9. Cystic dilation of intrahepatic bile ducts (Caroli's disease)
    10. Cirrhosis of any causes associated with increased risk
  2. Most cases of cholangiocarcinoma occur in patients without risk factors
  3. Gall Bladder Cancer
    1. Cholecystitis
    2. Gallstones - particularly symptomatic and large stones
    3. Obesity
    4. Calcification of gall bladder ("porcelain gallbladder")
    5. Gallbladder polyps

C. Presentation navigator

  1. Obstructive, painless jaundice is most common presentation (~70%)
  2. Abdominal pain (~50%)
  3. Weight Loss (~45%)
  4. "Porcelain" gall bladder on abdominal radiography (done for other reason)
  5. Laboratory anomalies consistent with symptoms
    1. Direct hyperbilirubinemia
    2. Mild hepatic transminase elevations
    3. Elevated alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase
    4. CA 19-9 elevaged to >100U/mL in 89% of cases
    5. Carcinoembryonic antigen (CEA) also useful
    6. Combination of CA 19-9 and CEA is probably most accurate testing
    7. Overall, however, disappointing accuracy of tumor marker testing

D. Diagnosisnavigator

  1. Tissue sampling is critical for proper diagnosis
    1. Intrahepatic cholangiocarcinoma easier to diagnose
    2. Extrahepatic cholangiocarcinoma may be difficult to access
  2. Radiographic Evaluation
    1. Computerized tomographic (CT) scanning recommended
    2. Contrast enhanced, triple phase helical CT detects intrahepatic tumors >1cm
    3. Dynamic CT could improve determination of resectability
    4. CT guided needle biopsy is often used
    5. Magnetic resonance imaging (MRI) is more accurate than CT
    6. MRI likely to replace CT for initial assessment
    7. Magnetic resonance cholangiopancreatography (CP, MRCP) superior to CT scans
    8. MRCP results similar to those with invasive endoscopic retrograde CP (ERCP)
    9. MRCP better than ERCP because undrained bile ducts can be visualized
    10. Endoscopic ultrasonography can be used to visualize distal extrahepatic biliary tree
    11. Cholangiography is most important method for assessing resectability of tumor
  3. Endoscopic Retrograde Cholangiopancreatography (ERCP)
    1. Used for diagnostis (tissue sampling) and treatment (stenting to relieve obstruction)
    2. If tissue difficult to obtain, then biliary fluid can be analyzed
    3. Insulin-like growth factor 1 (IGF-1) levels in bile elevated in cholangiocarcioma [3]
    4. Biliary IGF-1 highly elevated in cholangiocarciona but not in pancreatic cancer or gallstones
    5. Serum vascular endothelial growth factor (VEGF) levels about 3X elevated in either [3] cancer compared with benign biliary abnormalities
  4. Determination of resectability is most important prognostic feature
    1. Biopsy and local radiographic evaluation
    2. Imaging of the chest, abdomment and pevlis

D. Pathologynavigator

  1. Majority of primary tumors are carcinomas
  2. Majority are adenocarcinomas
  3. Papillary and mucinous carcinomas are next most common
  4. Rare cystadenocarcinoma
  5. Very Rare: squamous cell carcinoma, small-cell carcinoma, mesenchymal tumors
  6. In HIV+ persons, Kaposi sarcomas and bile tract lymphomas reported
  7. In most cases clusters of cells are found with desmoplasmtic (fibrous) reaction
  8. Histologic grade from well differentiated to undifferentiated

E. TNM Stagingnavigator

  1. Tumor (T)
    1. Tis - carcinoma in situ
    2. T1 - invasion of subepithelial connective tissue
    3. T2 - invasion of perifibromuscular connective tissue
    4. T3 - invasion of adjacent organs
  2. Lymph Nodes (N)
    1. N(o) - no regional LN
    2. N1 - metastasis to hepatoduodenal ligament LN
    3. N2 - metastasis to peripancreatic, periduodenal, periportal, celiac and/or superior mesenteric artery LN
  3. Stage 0: carcinoma in situ
  4. Stage I: T1 N0 M0
  5. Stage II: T2 N0 M0
  6. Stage III: T1 or T2, N1 or N2, M0
  7. Stage IV-A: T3, any N, M0
  8. Stage IV-B: M1 (distant metastasis)

F. Treatmentnavigator

  1. Resectability of tumor is associated with improved 5 year survival
    1. Specific surgical protocols for each of the types of cancer
    2. Preoperative biliary drainage of no overall benefit
    3. Attempt to remove ducts, put in biliary stents
    4. Palliative surgery also appears to improve survival (with bile duct stent placement)
    5. Patients with negative resection margins have up to 47% survival at 5 years
  2. Contraindications to surgical exploration
    1. Poor performance status
    2. Major cardiopulmonary disease
    3. Pre-existing cirrhosis
    4. Involvement of the main hepatic artery or portal vein (most centers)
    5. Extension of cholangiocarcinoma to involve segmental bile ducts in both liver lobes
  3. Total cholecystectomy and common bile duct resection
  4. Laparoscopic cholecystectomy effective for Stage O and Stage I gallbladder cancers
  5. Adjuvant radiotherapy remains experimental
  6. Chemotherapy of little value - no role outside of trial setting
  7. Palliation
    1. Appropriate for ~80% of cholangiocarcinomas
    2. Reduces symptoms, improves sepsis
    3. Survival ~3 months without and ~6 months with biliary drainage
    4. Bacterial cholangitis and/or liver failure usually contribute to death
    5. Surgical or endoscopic palliative biliary drainage
    6. Palliiative external radiotherapy is likely beneficial
    7. No proven benefit to palliative chemotherapy

G. Prognosisnavigator

  1. 1 year survival ~50%
  2. 3 year survival <10%
  3. 5 year survival <5%

References navigator

  1. Kahn SA, Thomas HC, Davidson BR, Taylor-Robinson SD. 2005. Lancet. 366(9493):1303 abstract
  2. de Groen PC, Gores GJ, LaRusso NF, et al. 1999. NEJM. 341(18):1368 abstract
  3. Alvaro D, Macarri G, Mancino MG, et al. 2007. Ann Intern Med. 147(7):451 abstract