2. Denote cancers arising in the intrahepatic or
extrahepatic biliary tree, exclusive of the ampulla
of Vater and gallbladder.
Incidence of cholangiocarcinoma in the United
States is 1 or 2 cases per 100,000 population
Majority of patients are 65 years and older
3. Risk Factors
Primary sclerosing cholangitis
Liver flukes infestation (Opisthorchis viverrini
and Clonorchis sinensis)
Choledochal cysts
Caroli's disease
Hepatolithiasis
Chemicals (e.g., Thorotrast and Dioxin)
Hepatitis C
Lynch syndrome II
Bile duct adenoma
6. Sclerosing (most frequent)
An intense desmoplastic reaction, and is seen as
diffuse thickening of the ducts without a defined
mass.
Hilar and extrahepatic cholangiocarcinomas are
more likely to be sclerosing.
This form is the most difficult to treat.
7. Nodular (mass-forming)
Tends to result in a mass lesion, and usually arises
within the liver.
Intrahepatic forms are more likely to be nodular
and mass-forming
8. Papillary (rare)
It represents a low-grade adenocarcinoma that is
represented by a polypoid mass filling the lumen
of the bile duct, with minimal invasion and no
desmoplastic reaction.
It is associated with a favorable outcome.
10. Classified into three groups according to their
anatomic location:
(1) intrahepatic or peripheral (10%),
(2) perihilar (65%), and
(3) distal (25%).
Tumors involving the hepatic duct bifurcation are
known as Klatskin tumors.
11. Bismuth classification of perihilar
cholangiocarcinomas
Type i-involvement of common hepatic duct.
Type ii-bifurcation involved without involvement of
secondary intrahepatic duct.
Type iiia-extends into the right secondary intrahepatic
duct.
Type iiib-extends into the left secondary intrahepatic
duct.
Type iv- secondary intrahepatic ducts involved on both
sides.
12.
13. AJCC Staging of Intrahepatic
Cholangiocarcinoma
T1 Solitary tumor without vascular invasion
T2 Solitary tumor with vascular invasion or multiple tumors none
more than 5 cm
T3 Multiple tumors more than 5 cm or tumor involving a major
branch of the portal or hepatic veins
T4 Tumor(s) with direct invasion of adjacent organs other than
the gallbladder or with perforation of visceral peritoneum
N1 Nodal metastases to the hepatoduodenal ligament
M1 Any distant metastases
14. Stage I T1 N0 M0
Stage II T2 N0 M0
Stage IIIA T3 N0 M0
Stage IIIB T4 N0 M0
Stage IIIC AnyT N1 M0
Stage IV AnyT Any N M1
15. AJCC Staging for Extrahepatic
Cholangiocarcinoma
T1 Tumor confined to the bile duct
T2 Tumor invades beyond the wall of the bile duct
T3 Tumor invades the liver, gallbladder, pancreas, and/or
unilateral branches of the portal vein (right or left) or
hepatic artery (right or left)
T4 Tumor invades any of the following: main portal vein or its
branches bilaterally, common hepatic artery, or other
adjacent structures, such as the colon, stomach,
duodenum, or abdominal wall
N1 Regional lymph node metastasis
M1 Distant metastasis
16. Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T3 N0 M0
Stage IIB T1-3 N1 M0
Stage III T4 Any N M0
Stage IV AnyT Any N M1
17. Frequency of Mutations in Cholangiocarcinoma
Oncogenes
K- ras 10%-54%
BRAF 22%
EGFR 5%-20%
PIK3CA 9%
ERBB2 5%
Supressor genes
P16Ink4A 55%-88%
TP53 33%-37%
SMAD4 13%-55%
STK11 6%
19. Laboratory Tests
Liver function tests show elevated
Bilirubin levels
alkaline phosphatase, and
Y-glutamyltransferase.
Serum aminotransferase levels may be normal
or mildly elevated
20. Tumor markers
Serum carcinoembryonic antigen (CEA)
CA 19-9
CA 242,
CA 72-4,
CA 50,
CA 125,
RCAS1, and
serum MUC5AC
22. Endoscopic ultrasound may be useful for distal
common bile duct cancers for defining a mass or
abnormal thickening, which can direct biopsies
Positron emission tomography (PET) scans
23. Biopsy and Cytology
Bile can be collected for cytology
brushings of the bile duct
Endoscopic ultrasound-directed fine-needle
aspiration
24. Treatment for bile duct cancer include:
· Surgery
· Radiation therapy
· Chemotherapy
· Palliative therapy
25. Surgery for Cholangiocarcinoma
contraindications include
(1) major comorbidities precluding safe surgery,
including cirrhosis,
(2) metastatic disease,
(3) invasion of the main portal vein or hepatic artery
proximal to their bifurcations,
(4) bilateral invasion of portal vein and/or hepatic
artery branches,
(5) bilateral hepatic duct involvement (up to
secondary radicles bilaterally), and
(6) unilateral duct and/or vessel involvement with
contralateral liver lobe atrophy.
26. Preoperative Stenting of the Bile Duct
major advantage is the rapid palliation of
symptoms
disadvantage is the subsequent bacterial
colonization of bile that leads to cholangitis
27. Intrahepatic Cholangiocarcinoma
Resectable intrahepatic cholangiocarcinomas are
treated using standard liver resections
Usually this requires a lobectomy
If both lobes of the liver are involved with
metastases, curative resection is unlikely
28. Perihilar cholangiocarcinomas
Exploratory laparoscopy to rule out the presence of
disseminated disease
Proceed with laparotomy through either an upper
midline or a right subcostal incision
Enlarged regional lymph nodes are biopsied
The presence of metastasis in lymph nodes beyond
the regional ones (N1) is a contraindication to radical
resection.
Transect the CBD at proximal to where it assumes a
retroduodenal location
The resection is completed by transecting the biliary
duct(s) proximal to the tumor
29. The bile duct and surrounding lymph node–bearing
soft tissues should be cleared en bloc from the portal
vein and the hepatic artery.
Reconstruction following resection of Klatskin's
tumors consists of bilateral hepaticojejunostomies
Hepatic lobectomy, caudate lobectomy
Pancreaticoduodenectomy may be required
30.
31.
32. Distal Cholangiocarcinoma
Requires a pancreaticoduodenectomy with
resection of the extrahepatic bile duct to the level
of the confluens for complete clearance of
disease.
A pancreaticoduodenectomy has a reasonable
chance of providing a margin-negative resection
for tumors of the distal bile duct.
If resection is not possible owing to vascular
encasement, cholecystectomy, Roux-en-Y
hepaticojejunostomy proximal to the tumor, and a
gastrojejunostomy to prevent gastric outlet
obstruction should be performed.
34. Follow-up after Resection
No clear guidelines exist
A physical examination with routine laboratory
tests every 3 to 4 months for the first 3 years after
surgery
and then at longer interval of 6 months till year 5
is reasonable.
The pattern of failure after curative resection
includes peritoneal spread, hepatic metastases,
local extrahepatic recurrence, and distant
metastases (most commonly lung).
35. Adjuvant Therapy
Adjuvant chemotherapy, radiotherapy, or
chemoradiotherapy is offered commonly
Postoperative adjuvant radiotherapy for biliary
tract cancer can be administered either by
external-beam radiotherapy (EBRT),
brachytherapy, intraoperative radiotherapy
(IORT), or a combination of radiotherapy
modalities.
36. Palliation
The major goal of palliation is relief of symptoms
of biliary obstruction.
Endoscopic or percutaneous biliary stenting
Metal stents tend to provide more durable
palliation than plastic (polyethylene) stents
The palliative options for patients with
unresectable perihilar cholangiocarcinoma include
(1) Tumor debulking with Roux-en-Y
hepaticojejunostomy and intraoperative
placement of Silastic transhepatic catheters
(2) Roux-en-Y hepaticojejunostomy using the
segment 3 or 4 duct
37. External-beam radiation and transcatheter
brachytherapy may contribute to pain relief and
biliary decompression
Palliative chemotherapy regimens include agents
such as 5-FU/leucovorin alone or with
gemcitabine, gemcitabine plus cisplatin, and
gemcitabine alone.
Photodynamic therapy (PDT), in which
endoscopic application of light activates a
photosensitizer, leading to local cell death, has
been associated with promising results.
38. Transplantation for Cholangiocarcinoma
Transplantation as a primary treatment modality
for hilar and intrahepatic cholangiocarcinoma is a
viable option.
Extrahepatic nodal disease or metastases are a
contraindication to transplant.