3. Introduction
• Bile duct cancers arising from epithelium of intra-hepatic, perihilar, or
distal(extra-hepatic) biliary tree, exclusive of gallbladder or ampulla of
vater.
• Intra-hepatic: originates either from small ductules(peripheral) or
large intra-hepatic ducts proximal to the bifurcation of right and left
hepatic ducts
• Extra-hepatic:Perihilar (including bifurcation) and distal.
6. Epidemiology
• Rare tumors accounting for 3% of all GI tumor
• Males>Females, 60’s and 70’s age group
• Uncommon before 40’s except in primary sclerosing cholangitis.
• Incidence – 0.85/100,000 US
96/100,000 (Thailand) due to prevalence of liver fluke
infestations.
8. Primary sclerosing cholangitis(PSC)
• PSC an inflammatory disease of biliary tract that leads to fibrosis and
structuring of intra-hepatic and /or extra-hepatic ducts.
• 1.5% per year –annual risks
• Prevalence 8-40%
• Increased risk if associated with IBD
• Cancer develops 2 to 3 decades earlier with PSC
• Life time risk of cancer with PSC is 10-15%
• Factors predictive for cancer in PSC are
->Sudden jaundice
->Weight loss
->Marked dilation proximal to stricture
->Presence of hypovascular mass with contrast
9. Fibrocystic liver disease
• Caroli’s disease, congenital hepatic fibrosis, choledochal cysts carries
15% risk of cancer.
• Average age at diagnosis is 34 years
• Untreated cysts has 28% development of cancer
• Related to stasis , chronic inflammation due to reflux of bile.
10. Parasitic infections
• Liver flukes: Opisthorchis viverni & Clinorchis sinensis are strongly
associated with cholangiocarcinoma.
• Trematodes :Fasciola hepatica are rare cause.
11. Hepatolithiasis
• Also known as recurrent pyogenic cholangitis
• Strongly associated with cholangiocarcinoma.
• Bile stasis leading to chronic infection and inflammation with
malignant transformation.
12. Viral infections
• HCV,HBV, cirrhosis are associated with IHCC.
• HIV is a independent risk factor for cancer.
13. Chemical agents
• Thorotrast (thorium dioxide)
Alfa emmiter
Accumulates in reticuloendothelial cells in liver and spleen and
increased risk of cancer by 300 times.
• Others include
Asbestos
Vinyl chloride
Nitrosamines
OCP
15. Pathology
• IHCC
• Gross :Appears as scirrhous primary hepatic lesions with a non
capsulated infiltrative pattern of growth that produces defined tumor
margin.
• Histology : Poorly differentiated adenocarcinoma.
16. Hilar and Extra-hepatic cholangiocarcinonoma
• 3 macroscopic types:
Sclerosing(70%)
• Most common
• Usually hilar in location
• Early invasion to bile duct
• Circumferential ductal thickening with
periductal fibrosis and inflammation
Nodular(20%)
• Tumor extending irregularly into duct lumen
Papillary(10%)-
• Distal location, rare tumor
• Projecting into duct lumen early as pedunculated lesion.
• High resectability and favourable outcome.
22. Tumor markers
Serum markers
• CA 19.9: >100 U/mL ,
Sensitivity and specificity 90%
• CEA : >5.2ng/mL
Sensitivity 70%
Specificity 80%
• IL-6: alone or in conjugation with CA 19.9
Correlates with tumor burden
• MUC5AC:Abnormal expression of mucin 5AC
70% associated with carcinoma
And associated with poor prognosis
23. Bile markers
• CEA :
sensitivity and specificity 80%
• CA 19.9:
sensitivity and specificity 60-70%
• IGF-1 :
sensitivity and specificity 100%
24. Imaging
• Ultrasonography: Confirms duct dilatation,
site of obstruction and excludes gallstones.
• IHCC: Hypoechoic mass lesion
Satellite lesions with capsular retraction.
• Hilar and EHCC:
• Intrahepatic and extra-hepatic biliary dilation
• Obstructing lesion is suggested by dilatation >6mm
• Proximal lesions: cause intra-hepatic dilatations
• Distal lesions : both intra and extra-hepatic dilatations
25. CT scan
• Used for intrahepatic tumors, level of biliary obstruction,
and presence of liver atrophy
• Hypodense lesions with irregular infiltrative margins
• Proximal intrahepatic biliary dilatation, portal and
hepatic venous involvement.
• Lobar atrophy caused by biliary and venous obstruction
in long standing cases
• Involvement of lymph nodes
• Staging of disease.
• Intrahepatic duct dilatations with non union of hepatic ducts,
contracted gallbladder suggests Klatskin tumor.
• In contrast, dilated gallbladder without intrahepatic and
extra-hepatic duct dilatations suggests cystic duct tumors
26. Magnetic Resonance
Cholangiopancreatography(MRCP)
• Non invasive technique for evaluation of extra
and intra hepatic biliary ducts and pancreatic duct
without contrast.
• Advantages over CT :
1. Evaluation of liver parenchyma and intra hepatic lesions
eg: atrophy of liver parenchyma
↓
indicates biliary or portal venous obstruction by the tumor
↓
indicates partial hepatectomy
2. Creates 3D view of biliary tree
( above and below the stricture) and vascular structures.
27. • Advantage over ERCP:
Superior in evaluation of anatomical extent of the tumor.
• Disadvantage:
Non therapeutic.
28. Cholangiography
• Performed by ERCP or PTC approach.
• Identifies site and extent of obstruction
• Indications
Preoperative cholangiography for biliary obstruction
Preoperative biliary drainage
Distal obstructions
Tissue diagnosis.
29. Endoscopic ultrasound
• For distal duct tumors.
• Visualize local extend of tumor and regional lymph node status.
• Guided biopsy from tumor and lymph node is performed.
30. Pre-operative tissue diagnosis
• Done in following conditions
• Strictures of indeterminate origin(previour bile duct surgery,CBD
stones,PSC)
• Prior to chemo or radiotheraphy
31. Pre-operative biliary drainage(PBD)
• Done using endoscopic or percutaneous approach.
• To bring total bilirubin upto 2.5 to 3 mg%
• Cholestasis, liver dysfunction, biliary cirrhosis develop rapidly with
obstruction.
• Extent of liver dysfunction is main factor for increased post-operative
morbidity and mortality.
32. Surgery
• Distal carcinomas:
• Pancreatico-duodenectomy
• 5 year survival rate upto 50% in node negative patients with an R0
resection
33. Peri-hilar cholangiocarcinoma
• Type I and type II tumors:
• En-block resection of CBD+ cholecystectomy+ 5 to 10 mm bile duct
margins + resection of regional nodes + Roux-en-y hepatojejunostomy
• Type III: above + hepatic lobectomy
• Type II and III tumors often involve ducts of caudate lobes so caudal
lobectomy is recommended.
• Type IV: Multiple segmental resection to attain negative margin with
resection and reconstruction of portal vein and hepatic artery
34. Intrahepatic
• Hepatic resection is TOC
• Resection done to obtain clear margin with adequate biliary and
vascular drainage.
• 60-80% Hepatic resection is done.
• 5 year survival rate after curative resection 30 to 40%
35. Criteria for unresectability of IHCC
• Multiple intrahepatic tumors
• Metastatic disease.
• Obstruction to inflow or outflow.
Unresectable IHCC medial survival < 12 months.
36. • Neoaduvant :Limited or no role
• Adjuvant :
• Most common used is 5 FU
Others include irinotecan,
Mitomycin-C
Gemcitabine
Cisplatin
Erlotinib in combination with gemcitabine or
Erlotinib with Bevacizumab combination for unresectable biliary cancer
37. NCCN guidelines
• For resectable tumors
• EHCC: for resected margin negative, lymph nodes –observation or
fluoropyridine based chemotherapy
• For positive margins,LN,Ca in situ,invasive – fluoropyridine based
chemotherapy
38. IHCC
• For negative margins – observations
• For positive margins- fluoropyridine or gemcitabine chemotherapy
• For unresectable IHCC and EHCC
• Fluoropyridine or gemcitabine chemotherapy is recommended.
39. Radiotherapy
• Conventional dose of 40-50.4 Gy is recommended after R0 resection.
• R1 and R2 , and unresectable cases 54-60 Gy recommended IMRT.
40. Palliative for jaundice.
• Either by operative biliary-enteric bypass or
endoscopic/percutaneous stenting
• Surgical bypass- performed during an unsuccessful attempt at
resection.
