Bile Duct Cancer (Cholangiocarcinoma)

Jaundice, abdominal pain, and bloating are symptoms and signs of bile duct cancers.

Bile duct cancer arises from the cells that line the bile ducts, the drainage system for bile that is produced by the liver. Bile ducts collect this bile, draining it into the gallbladder and finally into the small intestine where it aids in the digestion process. Bile duct cancer is also called cholangiocarcinoma.

Bile duct cancer is an uncommon form of cancer, with approximately 8,000 new cases diagnosed in the United States each year. There are three general locations where this type of cancer may arise within the bile drainage system:

• Within the liver (intrahepatic) affecting the bile ducts located within the liver
• Just outside of the liver (extrahepatic or perihilar) located at the notch of the liver where the bile ducts exit
• Far outside of the liver (distal extrahepatic) near where the bile ducts enter the intestine (called the ampulla of Vater)

Bile duct cancers are most commonly found just outside of the liver in the perihilar area and least commonly found within the liver.

What are the statistics for bile duct cancer? 

There are approximately 8,000 new cases of bile duct cancer diagnosed each year in the United States. The average age at diagnosis for people with intrahepatic (located within the liver) bile duct cancer is 70. For extrahepatic (outside the liver) bile duct cancer, the average age at diagnosis is 72.

Depending upon where the bile duct blockage occurs, this can lead to inflammation of the liver (hepatitis) and/or pancreas (pancreatitis).

The incidence of bile duct cancer increases with age. It is slow-growing cancer that invades local structures and for that reason, the diagnosis is often made late in the disease process when the bile ducts become blocked. This blockade prevents bile drainage from the liver into the gallbladder and intestine. Depending upon where the blockage occurs, this can lead to inflammation of the liver (hepatitis) and/or pancreas (pancreatitis).

It is not understood why most people with bile duct cancer develop the disease. However, chronic inflammation of the bile ducts may be a risk factor for this cancer. Diseases that can cause this type of chronic inflammation include primary sclerosing cholangitis (especially when associated with ulcerative colitis), chronic liver disease, including hepatitis B, hepatitis C, chronic alcoholic hepatitis, and cirrhosis.

Certain parasitic infections found in the Far East that cause liver infections are also associated with an increased risk.

Gallstones are not a risk factor for developing bile duct cancer, but stones within the liver do pose an increased risk. Liver stones are not often seen in the North American population but are more common in Asian countries.

There are rare congenital diseases that increase the risk of bile duct cancer, including Lynch II syndrome (hereditary nonpolyposis colorectal cancer associated with biliary tree and other cancers) and Caroli's syndrome (portal hypertension, hepatic fibrosis, and biliary tree cysts).

Native Americans are six times more likely to develop bile duct cancer. Asian Americans may also be at higher risk. Bile duct cancer is also more prevalent in Israel and Japan, but it is a very rare disease in North America.

The initial symptoms of bile duct cancer are jaundice, itching, abdominal pain, bloating, and weight loss.

The initial symptoms of bile duct cancer occur because of the inability of bile to drain normally from the liver where it is produced. This causes liver inflammation (hepatitis). Cholangiocarcinoma symptoms include yellow coloring of the skin and eyes (jaundice), itching, abdominal pain, bloating, and weight loss. Low-grade fever may be present, and there can be darkening in the color of urine and stool.

Unfortunately, bile duct tumors may not cause any symptoms until they have grown in size and cancer has spread (metastasized) from beyond its original location. Abdominal pain is often a late symptom and is usually located in the right upper quadrant of the belly and may be associated with a tender, enlarged liver.

History and physical examination are key clues for the diagnosis of bile duct cancer. Painless jaundice (yellow/orange coloring of the skin and eyes) may be the only initial clue. The history often includes reviewing alcohol use, drug use, or recent illnesses that may be associated with hepatitis, or inflammation of the liver. Other cholangiocarcinoma symptoms may include weight loss, loss of appetite, weakness, loss of energy, and easy bruising or bleeding (factors that clot the blood are manufactured in the liver and loss of liver function may decrease the clotting factors in the bloodstream).

The physical examination may be useful in detecting tenderness in the abdomen, especially in the right upper quadrant beneath the ribs (where the liver is located). A quarter of patients with bile duct cancer will have an enlarged liver that can be palpated or felt on exam. During general exam, the patient is often jaundiced, having yellow-tinged skin. This may be seen most easily in the white portion (sclera) of the eyes or under the tongue.

Blood tests are often ordered to assess liver function. Liver enzymes (AST, ALT, GGT, alkaline phosphatase), bilirubin levels, complete blood count, electrolytes, BUN and creatinine, and INR/PTT (international normalized ratio/partial thromboplastin time), and PT (prothrombin time).

There is no blood test that can specifically diagnose bile duct cancer. The diagnosis is confirmed by tissue sample obtained by biopsy by a surgeon, gastroenterologist, or interventional radiologist and a pathologist using a microscope to exam the cells obtained by that biopsy sample.

Imaging may be used to evaluate the structure of the liver, gallbladder, bile ducts, and other surrounding organs. Tests like ultrasound, CT scan, and MRI may be performed to look for a tumor and its location.

Endoscopic retrograde cholangiopancreatography (ERCP) is a specialized test used to examine the bile duct as it enters the duodenum. ERCP is performed by a gastroenterologist using a fiberoptic camera at the end of a flexible viewing tube. The tube is passed through the mouth and threaded through the stomach into the first part of the small intestine where the common bile duct enters. This test is commonly performed to examine the lining of the esophagus and stomach, but is also very effective in detecting conditions that affect the bile ducts, including bile duct cancer, gallstones stuck in the bile duct, and abnormal narrowing of the bile duct. Dye can be injected through the tube into the bile duct opening to outline the bile ducts and detect obstruction. Biopsies or cell washings can be obtained to look for cancer cells. If a blockage is found, during the same procedure the gastroenterologist may be able to place a stent to keep the duct open and allow bile to drain.

Sometimes, an interventional radiologist may obtain a tissue biopsy by threading a needle through the skin into the liver.

Once the diagnosis of bile duct cancer is made, it is important to stage the cancer to help direct potential treatment. The three parts of TNM staging include the following:

• T is for the primary tumor and how much it has grown locally and invaded other structures. For a bile duct tumor, this includes the liver, gallbladder, pancreas, stomach, and intestine.
• N is for the lymph nodes that are involved. The more nodes involved and the farther the distance from the bile duct, the more severe the cancer.
• M is for metastasis. Has the tumor spread to other parts of the body?

Cancer can be staged from 0 to 4, where 0 is a precancerous condition, 1 is local tumor with no spread to lymph nodes or other parts of the body, and 4 is significant local growth and lymph node involvement and spread to other parts of the body.

While staging is important, as well as detecting tumor spread beyond the liver and bile duct, often the critical staging questions can only be answered at surgery. During an operation, the surgeon can decide whether or not the whole tumor can be resected or removed. Survival rates are markedly improved if complete resection is possible.

Treatment for bile duct cancer depends upon where the cancer is located and whether it is possible for it to be completely removed by surgery. Unfortunately, those afflicted with this cancer tend to be older and may be unable to tolerate and recover from a significant operation. The decision regarding surgery needs to be individualized for the specific patient and their situation.

Other treatment options tend to be palliative, not curative, and are meant to preserve quality of life. Chemotherapy and radiation therapy may be options that are suggested to treat bile duct cancer.

Photodynamic therapy is another alternative to help shrink the tumor and control symptoms.

Radioembolization is an option if the tumor cannot be removed by surgery. With radioembolization, small amounts of radioactive material are injected into the arteries that supply the tumor in hopes of shrinking the tumor size by impeding its blood supply.

ERCP is a procedure done under imaging guidance that may be used to place a stent in the bile duct, keeping it open to allow bile drainage from the liver and gallbladder into the intestine. This is often very helpful in controlling symptoms but does not treat the tumor itself.

Targeted drug treatments are used in tumors that contain certain specific genetic abnormalities. By blocking these abnormalities, targeted drug treatments aim to destroy cancer cells. DNA sequencing (genomic) tests are often used to identify targets for therapy.

Immunotherapy takes advantage of the body's disease-fighting immune system to attempt to destroy cancer cells. Immunotherapy is often used in advanced cancers and may be an option if other treatments have failed.

Pain control may be an additional treatment issue because the enlarging tumor can cause significant pain in the abdomen and back. Regional anesthetic blocks may be useful in controlling pain.

As with all cancers, the treatment is individualized for the patient. Discussion between the patient, health care professional, and family are important to help understand treatment options, including cure versus palliative care or symptom control and quality of life. The patient's wishes are key.

Obstruction of the bile duct can lead to infection of the bile drainage system or cholangitis. Blockage of the bile ducts also can cause inflammation of the liver (hepatitis) or pancreas (pancreatitis). The liver inflammation can also lead to cirrhosis, or liver cell destruction and scarring. This is especially true in patients with primary sclerosing cholangitis. Both cirrhosis and sclerosing cholangitis are listed as potential risk factors for bile duct cancer.

Other complications may be a consequence of the procedures used to diagnose and treat the cancer. These include complications of surgery, chemotherapy, and radiation therapy.

How well a patient does after the diagnosis of bile duct cancer depends upon many factors, including where the tumor is located, if and how much it has spread, and the patient's underlying general health. The tumor cell type and the presence of certain genetic markers can influence the prognosis as well. Prognosis is worse for those patients whose tumor has invaded adjacent tissues, has lymph node involvement, or has spread to distant places in the body.

If untreated, bile duct cancer survival is 50% at one year, 20% at two years, and 10% at three years with virtually no survival at five years.

Being able to completely remove the tumor increases survival but this mostly depends upon the location of the tumor and whether it has invaded other tissues.

Since the cause of bile duct cancer is uncertain, specific methods of prevention do not exist. However, preventing liver inflammation and cirrhosis may decrease the risk of developing this cancer. This includes moderating the use of alcohol, being vaccinated for the hepatitis B virus, and abstaining from risky behaviors that might cause infection with hepatitis C.

As with all diseases that tend to develop at an older age, living a healthy lifestyle may extend lifespan, as well. This includes not smoking, eating a balanced diet, keeping physically active, and maintaining a healthy weight.