History
Signs and symptoms of cholangiocarcinoma include the following:
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Jaundice
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Clay-colored stools
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Bilirubinuria (dark urine)
Jaundice is the most common manifestation of bile duct cancer and, in general, is best detected in direct sunlight. The obstruction and subsequent cholestasis tend to occur early if the tumor is located in the common bile duct or common hepatic duct. Jaundice often occurs later in perihilar or intrahepatic tumors and is often a marker of advanced disease. The excess of conjugated bilirubin is associated with bilirubinuria and acholic stools.
Pruritus usually is preceded by jaundice, but itching may be the initial symptom of cholangiocarcinoma. Pruritus may be related to circulating bile acids.
Weight loss is a variable finding. It may be present in one third of patients at the time of diagnosis.
Abdominal pain is relatively common in advanced disease. It often is described as a dull ache in the right upper quadrant.
Physical
If the cholangiocarcinoma is located distal to the cystic duct takeoff, the patient may have a palpable gallbladder, which is commonly known as Courvoisier sign.
An abdominal mass or palpable lymphadenopathy is uncommon, but hepatomegaly may be noted in as many as 25% of patients.
Causes
The etiology of most bile duct cancers remains undetermined. Autoimmune conditions, especially primary sclerosing cholangitis, appear to increase the risk for cholangiocarcinoma. [14] Currently, gallstones are not believed to increase the risk. Chronic viral hepatitis and cirrhosis also do not appear to be risk factors.
Infections
In Southeast Asia, chronic infections with liver flukes (Clonorchis sinensis and Opisthorchis viverrini) have been causally related to cholangiocarcinoma.
Other parasites, such as Ascaris lumbricoides, have been implicated in the pathogenesis of cholangiocarcinoma.
Observations have raised the possibility that bacterial infections with Helicobacter species may play an etiologic role in biliary cancer. [15]
Inflammatory bowel disease
A strong relationship exists between cholangiocarcinoma and primary sclerosing cholangitis. Cholangiocarcinoma generally develops in patients with long-standing ulcerative colitis and primary sclerosing cholangitis. [16] The lifetime risk of developing this cancer in the setting of primary sclerosing cholangitis is 10-20%. At increased risk are patients with ulcerative colitis without symptomatic primary sclerosing cholangitis and a small subset of patients with Crohn disease.
Chemical exposures
Certain chemical exposures have been implicated in the development of bile duct cancers, primarily in workers in the aircraft, rubber, and wood-finishing industries.
Cholangiocarcinoma has developed decades after administration of the radiologic contrast medium thorium dioxide (ie, Thorotrast). This product, which results in lifelong alpha particle irradiation by thorium decay products, was in use from the 1930s until the 1950s. [17]
Miscellaneous conditions
Congenital diseases of the biliary tree, including choledochal cysts and Caroli disease, have been associated with cholangiocarcinoma.
Other conditions rarely associated with cholangiocarcinoma include bile duct adenomas, biliary papillomatosis, and alpha1-antitrypsin deficiency. Obesity may also be a risk factor. [18]
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Bismuth classification for perihilar cholangiocarcinoma. Shaded areas represent tumor location.
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Tight stricture of a common hepatic duct in a patient presenting with jaundice. Cytologic studies confirmed cholangiocarcinoma.
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Three-dimensional treatment planning uses CT scan slices to reconstruct the patient as a volume. Shown here is the display for planning external-beam radiotherapy to the cholangiocarcinoma (green structure). A biliary catheter (red tube) runs through the tumor volume and was used to deliver brachytherapy, which was given in addition to external-beam radiotherapy. Such technology has assisted greatly in the delivery of high doses to the tumor, while sparing vital normal structures, such as the kidney and spinal cord.
Tables
T - Primary tumor |
|||
TX |
Primary tumor cannot be assessed |
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T0 |
No evidence of primary tumor |
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Tis |
Carcinoma in situ (intraductal tumor) |
||
T1 |
Solitary tumor without vascular invasion, ≤5 cm or > 5 cm |
||
T1a |
Solitary tumor ≤5 cm without vascular invasion |
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T1b |
Solitary tumor > 5 cm without vascular invasion |
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T2 |
Solitary tumor with intrahepatic vascular invasion, or multiple tumors with or without vascular invasion |
||
T3 |
Tumor perforating the visceral peritoneum |
||
T4 |
Tumor involving local extrahepatic structures by direct invasion |
||
N – Regional lymph nodes |
|||
NX |
Regional lymph nodes cannot be assessed |
||
N0 |
No regional lymph node metastasis |
||
N1 |
Regional lymph node metastasis present |
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M – Distant metastasis |
|||
M0 |
No distant metastasis |
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M1 |
Distant metastasis present |
||
T - Primary tumor |
|||
TX |
Primary tumor cannot be assessed |
||
T0 |
No evidence of primary tumor |
||
Tis |
Carcinoma in situ – high-grade dysplasia |
||
T1 |
Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue |
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T2 |
Tumor invades beyond the wall of the bile duct to surrounding adipose tissue, or tumor invades adjacent hepatic parenchyma |
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T2a |
Tumor invades beyond the wall of the bile duct to surrounding adipose tissue |
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T2b |
Tumor invades adjacent hepatic parenchyma |
||
T3 |
Tumor invades unilateral branches of the portal vein or hepatic artery |
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T4 |
Tumor invades main portal vein or its branches bilaterally, or the common hepatic artery; or unilateral second-order biliary radicals bilaterally with contralateral portal vein or hepatic artery involvement |
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N – Regional lymph nodes |
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NX |
Regional lymph nodes cannot be assessed |
||
N0 |
No regional lymph node metastasis |
||
N1 |
One to three positive lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes |
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N2 |
Four or more positive lymph nodes from the sites described for N1 |
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M – Distant metastasis |
|||
M0 |
No distant metastasis |
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M1 |
Distant metastasis |
||
T - Primary tumor |
|
TX |
Primary tumor cannot be assessed |
T0 |
No evidence of primary tumor |
Tis |
Carcinoma in situ – high-grade dysplasia |
T1 |
Tumor invades the bile duct wall with a depth less than 5 m |
T2 |
Tumor invades the bile duct wall with a depth of 5–12 m |
T3 |
Tumor invades the bile duct wall with a depth greater than 12 mm |
T4 |
Tumor involves the celiac axis, superior mesenteric artery, and/or common hepatic artery |
N – Regional lymph nodes |
|
NX |
Regional lymph nodes cannot be assessed |
N0 |
No regional lymph node metastasis |
N1 |
Metastasis in 1-3 regional lymph nodes |
N2 |
Metastasis in ≥4 regional lymph nodes |
M – Distant metastasis |
|
M0 |
No distant metastasis |
M1 |
Distant metastasis |
Intrahepatic bile duct tumor |
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Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
IA |
T1a |
N0 |
M0 |
IB |
T1b |
N0 |
M0 |
II |
T2 |
N0 |
M0 |
IIIA |
T3 |
N0 |
M0 |
IIIB |
T4 |
N0 |
M0 |
|
Any T |
N1 |
M0 |
IV |
Any T |
Any N |
M1 |
Perihilar bile duct tumor |
|||
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
I |
T1 |
N0 |
M0 |
II |
T2a-b |
N0 |
M0 |
IIIA |
T3 |
N0 |
M0 |
IIIB |
T4 |
N0 |
M0 |
IIIC |
Any T |
N1 |
M0 |
IVA |
T4 |
N2 |
M0 |
IVB |
Any T |
Any N |
M1 |
Distal bile duct tumor |
|||
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
I |
T1 |
N0 |
M0 |
IIA |
T1 |
N1 |
M0 |
|
T2 |
N0 |
M0 |
IIB |
T2 |
N1 |
M0 |
|
T3 |
N0 |
M0 |
|
T3 |
N1 |
M0 |
IIIA |
T1-3 |
N2 |
M0 |
IIIB |
T4 |
N0-2 |
M0 |
IV |
Any T |
Any N |
M1 |
