Cholangiocarcinoma is a form of cancer that forms in the bile ducts that carry the digestive fluid bile. Bile ducts connect your liver to your gallbladder and to your small intestine. This condition, also known as bile duct cancer, is not a common form of cancer. This occurs mostly in older people, though it can occur at any age.
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Here, you will find information about signs and symptoms, causes and risk factors, types, diagnosis, staging and prevention about cholangiocarcinoma.
Bile duct cancer does not usually cause signs or symptoms until later in the course of the disease, but sometimes symptoms can appear sooner and lead to an early diagnosis. If the cancer is diagnosed at an early stage, treatment might work better.
Symptoms tend to depend on whether the cancer is in ducts inside the liver (intrahepatic) or in ducts outside the liver (extrahepatic), and include:
Jaundice: Normally, bile is made by the liver and released into the intestine. Jaundice occurs when the liver can't get rid of bile, which contains a greenish-yellow chemical called bilirubin.
Intensely itchy skin: Excess bilirubin in the skin can also cause itching. Most people with bile duct cancer notice itching.
Light-colored/greasy stools: Bilirubin contributes to the brown color of bowel movements, so if it doesn't reach the intestines, the color of a person's stool might be lighter.
Dark urine: When bilirubin levels in the blood get high, it can also come out in the urine and turn it dark.
Abdominal (belly) pain: Early bile duct cancers seldom cause pain, but bigger tumors may cause belly pain, especially below the ribs on the right side.
Loss of appetite/weight loss: People with bile duct cancer may not feel hungry and may lose weight without trying to do so.
Fever and chills: Some people with bile duct cancer develop fevers.
Fatigue, Nausea and vomiting
Cholangiocarcinoma occurs when cells in the bile ducts develop changes (mutations) in their DNA. DNA mutations cause changes in the instructions. One result is that cells may begin to grow out of control and eventually form a tumor, i.e., a mass of cancerous cells, though there is no clarity as to what causes the genetic mutations that lead to cancer.
A risk factor is anything that affects your chance of getting a disease like cancer. Different cancers have different risk factors. But having a risk factor, or even many risk factors, does not mean that a person will get the disease. And many people who get the disease have few or no known risk factors.
Factors that may increase the risk of cholangiocarcinoma or bile duct cancer include:
Certain diseases of the liver or bile ducts: People who have chronic (long-standing) inflammation of the bile ducts have an increased risk of developing bile duct cancer.
Inflammatory bowel disease: Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. People with these diseases have an increased risk of bile duct cancer.
Older age: Older people are more likely than younger people to get bile duct cancer.
Obesity: Being overweight or obese can increase the risk of cancers of the gallbladder and bile ducts. This could be because obesity increases the risk of gallstones and bile duct stones, as well as the risk of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease: Non-alcoholic fatty liver disease is the build-up of extra fat in the liver cells that's not caused by alcohol. Over time, this can cause swelling and scarring that can progress to cancer.
Diabetes: People with diabetes (type 1 or type 2) have a higher risk of bile duct cancer.
Alcohol: People who drink alcohol are more likely to get intrahepatic bile duct cancer. The risk is higher in those who have liver problems from drinking alcohol.
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Cholangiocarcinoma is divided into different types based on where the cancer occurs in the bile ducts:
1. Intrahepatic cholangiocarcinoma (bile duct cancers): These cancers start in the smaller bile duct branches inside the liver. Sometimes they're confused with cancers that start in the liver cells, which are called hepatocellular carcinomas, which are often treated the same way.
2. Perihilar (also called hilar) bile duct cancers: These cancers start at the hilum, where the left and right hepatic ducts have joined and are just leaving the liver. These are also called Klatskin tumors. These cancers are grouped with distal bile duct cancers as extrahepatic bile duct cancers.
3. Distal cholangiocarcinoma or Distal bile duct cancers: These cancers are found further down the bile duct, closer to the small intestine. Like perihilar cancers, these are extrahepatic bile duct cancers because they start outside of the liver.
Types of bile duct cancer by cell type:
Bile duct cancers can also be divided into types based on how the cancer cells look under the microscope.
Nearly all bile duct cancers or cholangiocarcinomas are adenocarcinomas, which are cancers that start in glandular cells. Bile duct adenocarcinomas start in the mucous gland cells that line the inside of the ducts.
Other types of bile duct cancers are much less common. These include sarcomas, lymphomas, and small cell cancers.
If symptoms and/or the results of the physical exam suggest you might have bile duct cancer, tests will be done. These could include lab tests, imaging tests, and other procedures.
Tests of liver and gallbladder function: Lab tests might be done to find out how much bilirubin is in your blood. Bilirubin is the chemical that causes jaundice. Problems in the bile ducts, gallbladder, or liver can raise the blood level of bilirubin.
Tumor markers: Tumor markers are substances made by cancer cells that can sometimes be found in the blood. People with bile duct cancer may have high blood levels of the markers called CEA and CA 19-9. High levels of these markers often mean that cancer is present.
Imaging tests: Imaging tests use x-rays, magnetic fields, or sound waves to create pictures of the inside of your body.
Imaging tests: It can be done for a number of reasons, including:
a. To look for suspicious areas that might be cancer
b. To help a doctor guide a biopsy needle into a suspicious area to take a sample for testing
c. To learn how far cancer has spread
d. To help make treatment decisions
e. To help find out if treatment is working
f. To look for signs of the cancer coming back after treatment
Ultrasound: Ultrasound uses sound waves and their echoes to create images of the inside of the body. A small instrument called a transducer gives off sound waves and picks up the echoes as they bounce off organs inside the body. The echoes are converted by a computer into an image on a screen. Abdominal ultrasound and Endoscopic or laparoscopic ultrasound are used.
Computed tomography (CT) scan: A CT scan uses x-rays to make detailed cross-sectional images of your body. It can be used to
a. Help diagnose bile duct cancer by showing tumors in the area.
b. Help stage the cancer (find out how far it has spread).
c. A type of CT known as CT angiography can be used to look at the blood vessels around the bile ducts.
d. Guide a biopsy needle into a suspected tumor. This is called a CT-guided needle biopsy.
Magnetic resonance imaging (MRI) scan: Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI scans can provide a great deal of detail and be very helpful in looking at the bile ducts and other organs. MR cholangiopancreatography (MRCP) and MR angiography (MRA) are the special types of MRI scans may also be used.
Cholangiography: A cholangiogram is an imaging test that looks at the bile ducts to see if they're blocked, narrowed, or dilated (widened). This can help show if someone might have a tumor that's blocking a duct.
Angiography: Angiography or an angiogram is an x-ray test for looking at blood vessels in and around the liver and bile ducts.
Biopsy: Imaging tests might suggest that a bile duct cancer is present, but in many cases samples of bile duct cells or tissue is removed (biopsied) and looked at with a microscope to be sure of the diagnosis. There are many ways to take biopsy samples to diagnose bile duct cancer: During cholangiography, During cholangioscopy, Needle biopsy.
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The stage of a cancer describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. The stage of a bile duct cancer is determined by the results of the physical exam, imaging and other tests, and by the results of surgery if it has been done.
A staging system is a standard way to sum up the extent of a cancer.
There are actually 3 different staging systems for bile duct cancers, depending on where they start: Intrahepatic bile duct cancers (those starting within the liver), Perihilar (hilar) bile duct cancers (those starting in the hilum, the area just outside the liver), Distal bile duct cancers (those starting farther down the bile duct system)
The staging system most often used for bile duct cancer is TNM system, which is based on 3 key pieces of information:
The extent (size) of the main tumor (T): How large has the cancer grown? Has the cancer reached nearby structures or organs?
The spread to nearby lymph nodes (N): Has the cancer spread to nearby lymph nodes?
The spread (metastasis) to distant sites (M): Has the cancer spread to distant lymph nodes or distant organs such as the bones, lungs, or peritoneum (the lining of the abdomen [belly])?
There is no way to prevent cholangiocarcinoma or bile duct cancer, but the risk can be reduced by:
Stop smoking: Smoking is linked to an increased risk of cholangiocarcinoma.
Reduce the risk of liver disease: Chronic liver disease is associated with an increased risk of cholangiocarcinoma. Some causes of liver disease can't be prevented, but others can.
Treat hepatitis infections (such as B and C) to help prevent cirrhosis.
Maintain a healthy weight.
When working with chemicals, follow the safety instructions on the container.
Following healthy diet.
Getting regular exercise.
Avoiding excessive alcohol.
The treatment of cholangiocarcinoma or bile duct cancer varies according to the location and size of the tumor, whether it has spread (metastasized), and the state of the overall health of the patient.
There are 2 general types of surgery for bile duct cancer: potentially curative surgery (resectable and unresectable) and palliative surgery.
1. Potentially curative surgery for bile duct cancer: Resectable (potentially curative surgery) means imaging tests or the results of earlier surgeries show there's a good chance that the surgeon can remove all of the cancer along with a rim (margin) of healthy tissue around it.
2. Palliative surgery for bile duct cancer: Palliative surgery is done to relieve symptoms or treat (or even prevent) complications, such as blockage of the bile ducts. This type of surgery is done when the cancer is too widespread to be removed completely. Palliative surgery is not expected to cure the cancer, but it can sometimes help a person feel better and sometimes can even help them live longer.
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Radiation therapy uses high-energy rays or particles to destroy cancer cells. Radiation isn't often used to treat bile duct cancer, still, it might be used in these ways:
a. After surgery to remove the cancer: This is called adjuvant therapy. It's used to kill any tiny deposits of cancer cells that are left after surgery but are too small to see.
b. Before surgery for cancers that might be able to be taken out: This is done to try to shrink the cancer and make it easier to take it out. This is called neoadjuvant therapy.
c. As part of the main therapy for some advanced cancers: Radiation therapy can also be used as a main therapy for some patients whose cancer has not spread widely throughout the body, but can't be removed with surgery.
d. As palliative therapy: Radiation therapy is often used to ease symptoms when a cancer is too advanced to be cured. It can help relieve pain or other symptoms by shrinking tumors that block bile ducts or blood vessels, or press on nerves.
The 2 main types of radiation therapy are external beam radiation therapy (EBRT) and brachytherapy. EBRT is the most common form of radiation for bile duct cancer.
External beam radiation therapy (EBRT): In this type of radiation therapy, a machine sends x-rays to a specific part of the patient's body to kill cancer cells. Three-dimensional conformal radiation therapy (3D-CRT), Intensity-modulated radiation therapy (IMRT), Stereotactic body radiotherapy (SBRT) and Chemoradiation are some of the ways EBRT might be given.
Brachytherapy (internal radiation therapy): This type of treatment uses small pellets of radioactive material that are put next to or right into the tumor. The radiation travels a very short distance, so it affects the cancer without causing much harm to nearby healthy body tissues. For bile duct cancer, brachytherapy is sometimes done with a thin radioactive wire that's put into the bile duct for a short time. This may be called intrabiliary brachytherapy. Brachytherapy can be used alone, or it may be used along with EBRT. At this time it's mostly used as a palliative treatment.
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Chemotherapy (chemo) is treatment with cancer-killing drugs that are usually given into a vein (IV) or taken by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment useful for some cancers that have spread to organs beyond the bile duct. Because the drugs reach all the areas of the body, this is known as a systemic treatment.
a. After surgery to remove the cancer: Chemo may be given after surgery (often along with radiation therapy) to try to lower the risk that the cancer will come back. This is called adjuvant chemo.
b. Before surgery: It may be given before surgery for cancers that might be able to be completely removed. Chemo might shrink the tumor enough to improve the odds that surgery will be successful. This is called neoadjuvant treatment.
c. As part of the liver transplant process: Chemo may be used to keep bile duct cancer under control while waiting for a liver transplant.
d. As part of the main treatment for some advanced cancers: Chemo can be used (sometimes with radiation therapy) for more advanced cancers that cannot be removed or have spread to other parts of the body. Chemo does not cure these cancers, but it might help people live longer.
e. As palliative therapy: Chemo can help shrink tumors or slow their growth for a time. This can help relieve symptoms from the cancer, for instance, by shrinking tumors that are pressing on nerves and causing pain.
The drugs used most often to treat bile duct cancer include: 5-fluorouracil (5-FU), Gemcitabine (Gemzar®), Cisplatin (Platinol®), Capecitabine (Xeloda®), Oxaliplatin (Eloxatin®)
In some cases, 2 or more of these drugs may be combined to try to make them more effective. For example, combining gemcitabine and cisplatin may help people live longer than getting just gemcitabine alone.
Targeted therapy is used to treat a lot of different kinds of cancer. Targeted therapy drugs work differently from standard chemotherapy (chemo) drugs. They sometimes work when standard chemo drugs don't. They can be used either along with chemo or by themselves.
Immunotherapy is the use of medicines to help a person's immune system better recognize and destroy cancer cells.
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