What is Cholangiocarcinoma? Symptoms, Diagnosis and Treatments

Hearing the words “You have cholangiocarcinoma” can be daunting at best and terrifying at worst.

After all, anything with the words “carcinoma” in it means cancer.

The best way to combat any anxiety or fear is to learn as much as you can as quickly as you can.

This way, you have facts instead of guesses to work with.

The word “Cholangiocarcinoma” translates literally to mean “cancer of the bile vessel.”

The bile vessel in this case refers to the bile duct.

Of course, unless you can still clearly recollect your high school biology lessons, the next question now becomes, what is the bile duct?

There are actually several small ducts, or tubes, that connect the liver and gallbladder to one another and to a larger (yet still small) duct called the common bile duct.

There are five major duct systems functioning to connect the liver and gallbladder with the small intestine:

• Intrahepatic bile ducts. These ducts begin inside the liver and become the left and right hepatic ducts once they emerge from the liver.
• Left and right hepatic ducts. These ducts come out of the liver, join up, and lead into the common hepatic duct.
• Common hepatic duct. The common hepatic duct joins up with the cystic duct.
• Cystic duct. The cystic duct connects to the gallbladder.
• Common bile duct. The common bile duct is the major bile tube that connects the liver and gallbladder with the uppermost part of the small intestine (which is called the duodenum). In most people, it is between four and five inches long.

The common bile duct’s actual job is to transfer bile into the small intestine to help your body break down and digest your food.

When any or all of the bile ducts become compromised, cells may turn malignant, which leads to bile duct cancer (cholangiocarcinoma).

There are two main types of bile duct cancer as follows:

• Intrahepatic cholangiocarcinoma. As its name suggests, this type of bile duct cancer forms first inside the bile ducts that are located inside the liver itself. This type of bile duct cancer is relatively rare.
• Extrahepatic cholangiocarcinoma. With extrahepatic bile duct cancer, the cancerous cells form in the portion of the bile duct system that exists outside the liver. With this type of bile duct cancer, cancer can form in the upper (perihilar) or lower (distal) region of the common bile duct. This is a far more common type of bile duct cancer that represents most reported cases.

Identifying the precise location where the bile duct cancer exists happens during the diagnostic stage (more on that here in Section 6).

Overall, cholangiocarcinoma is a relatively rare cancer in the United States.

It is thought to affect an estimated 8,000 individuals each year.

Where it is much more common is in Southeast Asia, due to the compounding influence of a local parasite.

Cholangiocarcinoma History

Bile duct cancer was first described and named as early as the late 19th century.

In 1935, J.H. Musser was the first to describe bile duct cancer present outside the liver (extrahepatic cholangiocarcinoma).

For the next 15 years, physicians reviewing medical literature were able to identify 570+ additional cases with similar or matching symptoms.

W.A. Altemeir described and named cancer of the inside-liver (intrahepatic cholangiocarcinoma) in 1957.

From there, as new cases have arisen, further research has continued to detail and catalogue where bile duct cancer is most likely to begin and how it progresses.

Because of the interior nature of bile duct cancer, there are times the malignancy is not discovered until the patient has passed and an autopsy reveals cancer.

Today, it is estimated that approximately two percent of cancer discovered during post-mortem autopsy is bile duct cancer.

In rarer cases, bile duct tumors have been found to be benign.

However, historically speaking, even benign tumors removed from this area have tended to recur, and over time have tended to turn malignant.

As well, early symptoms of both benign and malignant bile duct tumors have tended to present similarly.

The ongoing challenge with treating cholangiocarcinoma, as autopsy findings have highlighted, is to detect the malignancy before it has spread.

Research has highlighted a possible genetic link that could predispose some individuals to develop cholangiocarcinoma later in life.

Researchers also now know that gene mutations suspected to cause cholangiocarcinoma are epigenetic (acquired during the patient’s life) versus inherited at birth.

Recently (2017), researchers have discovered a possible link between a certain kind of gut bacteria and the development of cholangiocarcinoma.

Even with more than a century of knowledge, research, diagnosis, and treatment of bile duct cancer, much more remains to be learned about how to detect this type of cancer sufficiently early to improve prognosis.

Risk Factors

A number of risk factors for cholangiocarcinoma have been identified.

Some known risk factors are relatively easy to minimize, while others may exist from birth.

However, having risk factors does not mean an individual will definitively develop cholangiocarcinoma.

Similarly, not having risk factors for cholangiocarcinoma does not exempt an individual from the risk of developing bile duct cancer.

Known risk factors for developing cholangiocarcinoma include these:

• Smoking

People who smoke have a higher incidence of cholangiocarcinoma than non-smokers.

• Age

The average age of cholangiocarcinoma diagnosis is when a person is in their 60’s or 70’s.

• Inherited family history

In some individuals who have a close family member diagnosed with cholangiocarcinoma, their risk is greater.

• Inflammatory bowel disease

Individuals previously diagnosed with a form of IBD (Crohn’s disease, ulcerative colitis) are more at risk to develop cholangiocarcinoma.

• Overweight/obesity

If an individual is overweight or obese, the risk of developing cholangiocarcinoma is higher.

• Overuse of alcohol

Because of alcohol’s detrimental effect on the liver, individuals who use alcohol to excess are at higher risk to develop bile duct cancer.

• Diabetes

An individual previously diagnosed with diabetes has a slightly elevated risk of developing bile duct cancer in the future.

• Thorotrast exposure

Thorotrast, or thorium dioxide, was a common contrast dye used with X-ray imaging up until the 1950s.

It was discontinued due to a heightened risk to the patient of developing bile duct cancer and other types of cancer.

• Exposure to other toxins

Exposure to asbestos, radon, radioactive materials, PCBs (polychlorinated biphenyls), dioxin, or nitrosamines can also lead to bile duct cancer.

• Pre-existing liver or bile duct diseases

A higher risk exists for individuals previously diagnosed with cirrhosis of the liver, primary sclerosing cholangitis (inflammation of the bile ducts), bile duct stones, common bile duct (choledochal) cysts, hepatitis B or C, polycystic liver disease, pancreatic gastric reflux or inherited Caroli syndrome.

• Exposure to HIV

Individuals living with HIV/AIDS are at greater risk for developing bile duct cancer.

• Diet

Individuals who eat raw or undercooked fish may contract a parasite called a fluke.

This fluke can infect the liver and lead to cholangiocarcinoma.

• Inflammation of body systems

Researchers are starting to learn more about the link between inflammation in certain body systems, and especially those associated with the liver, gallbladder, pancreas, upper small intestine, and bile ducts, and the development of bile duct cancer.

• Known gene mutations

Epigenetic (acquired) gene mutations in genes TP53, KRAS, HER2, and MET may be linked with the onset of bile duct cancer.

Screening

At this time, there is no known routine screening procedure that has been developed specifically to test for cholangiocarcinoma risk.

There are a number of reasons for this.

The first and foremost reason is that the relative rarity of cholangiocarcinoma in the United States and Europe.

Only in Southeast Asia, where consumption of raw or undercooked fish is high, are there many more reported cases of bile duct cancer annually due to exposure to the flukes parasites.

Interestingly, in 2015, a test study was launched to develop a cholangiocarcinoma screening and care program for individuals in Southeast Asia because of their much higher risk of developing this type of cancer.

In 2016, it was reported that advance screening via ultrasound combined with a complete blood count (CBC) test, stool samples tested for parasites, testing for hepatitis exposure, and tests for a liver function could detect cholangiocarcinoma earlier and improve patient outcomes.

In the United States and Europe, researchers are working to develop accurate early screening methods for patients previously diagnosed with a related condition called primary sclerosing cholangitis (PSC).

Because the link between previous or existing primary sclerosing cholangitis and later onset of bile duct cancer is so strong, it is thought the development of a specific screening protocol could make for much early diagnosis and treatment in these individuals.

Another patient group that is routinely screened for cholangiocarcinoma is individuals undergoing liver transplants.

Patients who have PSC are screened for cholangiocarcinoma prior to being approved for a liver transplant.

However, other than with these special population groups in the United States, Europe, and Southeast Asia, no additional screening protocols are currently being tested.

This is due to the fact that often, bile duct cancer produces no symptoms at all until it reaches the later stages.

Symptoms

While the medical community now has a detailed list of known cholangiocarcinoma symptoms, the issue of detecting bile duct cancer sufficiently early on in its development still remains.

This is because the cancer is located in such an internal place in the body that by the time symptoms begin to manifest, cancer has already spread to adjacent body systems.

These are the known symptoms of bile duct cancer:

• Jaundice. Often, jaundice, a yellowing of the skin and eyes, is the only symptom that arises early enough to potentially serve as an early warning system. Jaundice is caused when the bile duct system gets blocked by tumors and the bile begins to build up in the body. Jaundice is also a symptom of hepatitis and gallstones, but when it presents, the patient should always be screened for bile duct cancer as well.
• Pain in the abdominal area. Individuals often report pain below the ribs on the right side of the body. This symptom tends to manifest when the cancer is already at a later stage.
• Changes to urine and feces. When urine darkens in color and stools lighten in color, this can be caused by a build-up of bile in the system. Stool color can also be lightened due to excess fat content (because the bile cannot reach the fatty foods to break them down and help the body digest them, so they pass through the feces out of the body).
• Skin itching. The buildup of bile in the body can cause itching on the surface of the skin.
• Fever. Fever can be a by-product of the body’s attempts to fight off cancer.
• Weight loss. A lack of hunger and subsequent weight loss can be a sign of bile duct cancer.
• Nausea or vomiting. Later stage cancer patients may experience nausea or vomiting if a secondary infection develops due to blocked bile ducts. However, this symptom is not commonly reported.

Because so many of these symptoms are shared with other serious diseases and conditions, it can be relatively easy to mistake cholangiocarcinoma for hepatitis, gallstones, or even a virus or bacterial infection.

For this reason, detailed diagnostic and testing is needed.

Diagnosis and Stages

Diagnosing bile duct cancer typically begins only once the patient has begun expressing worrisome symptoms, such as jaundice, changes to urine/feces, or abdominal pain and bloating.

As with any illness, the first step the physician will take is to do a thorough physical exam and to collect a comprehensive individual and family medical history.

The patient will be asked to list all symptoms and the duration of each to their best recollection.

The physical exam will focus on the area where symptoms are manifesting.

The physician will examine the eyes and skin for signs of jaundice and then palpate the abdomen for lumps, bumps, tenderness, bloating, or discomfort.

The physician will then evaluate the results of the medical history, all reported symptoms, and the physical exam to determine whether to proceed to the testing stage of the diagnostic process.

If the data suggests the possibility of bile duct cancer, there are a number of tests and procedures that can help to clarify the cause of the symptoms.

Blood testing

Blood testing is normally the first step in the testing phase.

The physician can order a number of blood tests, including these:

• Complete blood count (CBC) and blood chemistry. This comprehensive blood test will look at all levels in the blood and also measure the amount of bilirubin (bile), which can indicate a problem in the liver, gallbladder, or bile duct function.
• Liver function blood tests. Testing can also be done to evaluate overall liver function. Common tests include albumin, liver enzymes, and proteins that all test liver function and can indicate whether the potential issue may be in the liver, the gall bladder or the bile ducts.
• Tumor marker tests. The blood can also be tested for the presence of proteins called tumor markers. If the protein levels are high, this can indicate cancer, but further testing will be required to determine what kind of cancer it is. (As well, sometimes bile duct cancer can still be present even if no markers are found, which often makes this test a better fit to measure the results of bile duct cancer treatment instead of to diagnose it.)

Imaging tests

Depending on what the results of the blood tests may indicate, the next step in the diagnostic process is often to order imaging tests.

Imaging tests can be helpful in any number of ways, including to identify warning signs of malignant cells or a tumor as well as a potential blockage in the bile duct system.

Imaging is also often prescribed as a part of another testing where it is necessary to inject certain areas with contrast dye.

The imaging helps the physician accurately inject the dye.

The most commonly used imaging tests include these:

• Abdominal ultrasound. This test is essentially the same as the test pregnant women have done to evaluate the health of their developing baby. The ultrasound device is moved over the abdomen to look for suspicious areas, especially in areas such as the lower right side where patients may be reporting pain or other symptoms.
• Needle-guided ultrasound. In the case where the physician needs to inject contrast dye in a certain area or take a tissue biopsy from a certain area, the ultrasound test can help ensure proper placement.
• Endoscopic or laparoscopic ultrasound. Here, the ultrasound machine travels inside the body via a very thin tube to look at the suspicious area. This is often prescribed prior to surgery to help the surgeon plan for the most effective results.
• Computed tomography (CT) scan. A CT scan is a very useful test that uses X-ray technology to make detailed pictures of certain areas of the body. Often, CT scan tests are prescribed using injectable or orally administered contrast dye.
• Needle-guided CT scan. This test uses CT technology to help the surgeon biopsy an area of suspicious tissue.
• Magnetic resonance imaging (MRI) scan. An MRI scan test offers a different way to see the soft tissue areas of the body, whether used with or without contrast dye. The MRI test can be used to figure out if a tumor is benign or malignant and to get detailed visuals of the bile ducts and surrounding blood vessels.
• Angiography. This test combines X-ray, CT, or MRI scan technology with contrast dye to look at the blood flow to and from and surrounding a tumor. This test is often used to help plan surgery for bile duct cancer.
• Cholangiography. There are several different ways this test can be performed. The goal of the test is to thoroughly examine the bile duct system looking for blockages or narrowing and to take biopsies of tissue for further testing.
• Cholangioscopy. This test is usually done with a cholangiography to get a detailed image of the bile duct system using a tiny guided camera.
• Laparoscopy. This minimally invasive test uses a very small camera and instruments to examine the abdominal area, including major organs and systems. This test can also be ordered as a tool for planning the most effective surgery.

Biopsy tests

Finally, biopsies are an important part of the diagnostic process for any patient suspected to have bile duct cancer.

Tissues that may be taken for the purposes of biopsy can include liver tissue, gallbladder tissue, bile duct tissue, bile duct cells, bile duct lining, tumor tissues, and cells.

Depending on the amount of tissue needed, a biopsy can be done via fine-needle aspiration (for less tissue) or core needle aspiration (for more tissue).

Together, blood tests, imaging tests, and biopsy tests can deliver sufficient high-quality information about the blood, cells, and tissues to determine what is causing an individual’s symptoms and recommend a course of treatment.

Staging

Once the diagnostic process is complete and bile duct cancer is confirmed, it must be staged.

The staging process can get very detailed to describe whether there are one or multiple tumors, what type of cholangiocarcinoma it is, and exactly where it exists in the body.

Staging uses a three-step process called TNM. T is for tumor, N is for lymph node and M is for metastasizing.

Together, the TNM staging process describes where the cancer is located, how far it has spread, and which organs/systems it is affecting.

Treatments and Drugs

When it comes to treating cholangiocarcinoma, surgeons often use a simpler staging method called Resectable/Unresectable.

The term “resect” essentially means “remove.”

A resectable cholangiocarcinoma is one that surgeons believe they can remove entirely during the course of surgery.

An unresectable cholangiocarcinoma is one that surgeons believe cannot be fully removed due to where it is or how far it has spread or both.

Surgery

Surgery is the number one treatment choice for bile duct cancer today.

If the cancer is considered to be resectable, the post-treatment prognosis looks much more positive and there will be a lower need for drug therapy.

However, surgery has the potential to impact other body systems depending on where the cancer is, so it is critical to review all options and decide on the best course of action.

There are two main types of surgery that are prescribed:

• Curative. With curative surgery, the potential exists that cancer can be completely removed during surgery to effect a full remission of bile duct cancer.
• Palliative. With palliative surgery, the goal is to make the individual more comfortable by reducing or treating symptoms and slowing the progress of bile duct cancer. However, with this type of surgery, a cure is not possible.

In some cases, a surgeon may discover only once the surgery has begun that the cancer is not resectable.

In these cases, it may be possible to perform palliative surgery instead, provided the patient has given prior consent.

Drug Treatment

Chemotherapy and radiation drugs are the number one medication-based treatment choice for bile duct cancer.

Often chemotherapy and radiation are prescribed as a follow-up treatment after surgery is performed.

This can be the case even if the surgery was for resectable cancer.

• Radiation. Radiation therapy is a type of drug treatment that uses high-energy particles or beams to destroy cancer cells and shrink tumors. There are two main types of radiation: external beam radiation therapy (EBRT), or external X-ray radiation, and brachytherapy, or internal pellet-based radiation. This type of drug treatment is considered very targeted to minimize damage to surrounding healthy tissues and organs.
• Chemotherapy. Chemotherapy can be prescribed on its own or in conjunction with radiation therapy to treat cholangiocarcinoma. Chemotherapy can be administered orally or via injection. Chemotherapy is considered a systemic treatment since it is administered through the bloodstream and will affect all tissues and organs.

There are times when radiation and/or chemotherapy may be prescribed prior to surgery, after surgery, or instead of surgery, depending on the stage of the bile duct cancer, the patient’s prognosis, and the patient’s wishes.

In cases where it is prescribed prior to surgery, the drugs are typically used to try to shrink the tumors to make surgery more successful.

Palliative Care

Finally, in cases where the patient does not wish to undergo invasive treatment or the prognosis is poor overall, the option for what is called palliative (comfort) care also exists.

The goal of palliative care is purely to provide comfort to the patient by reducing symptoms as cancer progresses.

An example would be to insert a stent to open up a previously blocked bile duct so the bile can pass through again.

Often palliative care includes the use of pain-relieving treatments and medications.

Some common options include these:

• Alcohol Injection. By injecting alcohol into relevant nerves to deaden pain sensations coming from the cancerous areas.
• Photo-Dynamic Therapy (PDT). Photodynamic therapy involves the use of a light-sensitive drug that helps surgeons target and destroy tumors endoscopically.
• Cryosurgery/Radiofrequency Ablation. Targeted tumor destruction can be achieved using extreme cold or heat to kill the cells.
• Radiation. Very targeted radiation can kill cancerous cells that are impacting surrounding systems.
• Pain-Relieving Drugs. Various medications exist that can ease pain and discomfort.

Coping and Support

Coping with a diagnosis of cholangiocarcinoma is not an easy challenge for patients or loved ones.

Because this cancer is so difficult to detect in the early stages, often families are grappling with a more severe diagnosis and less rosy prognosis.

However, support and coping resources do exist.

The American Cancer Society offers free referrals to local support resources across the country.

The Cholangiocarcinoma Foundation also offers information and resources for support and education.

The National Cancer Institute maintains an ongoing list of clinical trials that may be relevant for cholangiocarcinoma patients who wish to participate in evolving treatment methods.

Many bile duct cancer patients also find it helpful to avail themselves of alternative or complementary therapies including biofeedback/neurofeedback for pain management, meditation and deep breathing for stress management, appropriate exercise to combat treatment deep fatigue, dietary and nutritional counseling to improve energy and cope with digestion-related drug side effects and mental/emotional support via cancer groups or one-to-one counseling or support.

For patients opting for palliative care, hospice can be a welcome source of support for both the individual and their carers and family members.

One of the main benefits of hospice is it can offer respite care for carers as well as the ability for the patient to remain in place at home while receiving palliative care.

Patients with resectable bile duct cancer that experience a full remission may still struggle with the lingering concern of a recurrence.

Here, the National Coalition for Cancer Survivorship can offer information, support, and the chance to participate in advocacy efforts on behalf of others.