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Bile duct cancer, also known as cholangiocarcinoma, is a type of cancer that occurs in the bile ducts—a network of convergent tubes that carry bile, a digestive fluid, from the liver to the small intestine. This relatively rare cancer can develop in the small ducts within the liver (intrahepatic) or in the larger ones that run from the liver to the small intestine (extrahepatic).

While still rare, the number of new cholangiocarcinoma cases has been increasing in recent years, although the exact reasons for this increase are not well understood. Some of the factors that may contribute to this trend include an aging population and an increase in underlying medical conditions such as primary sclerosing cholangitis and hepatitis B or C. Improved diagnostic methods and imaging technologies may also contribute to the increased number of patients diagnosed with bile duct cancer.

Dr. Juan Rocca, a leading hepatobiliary and liver transplant surgeon, offers answers to many of your questions about a disease that is as complex as it is hard to treat. Dr. Rocca is Surgical Director for the Liver Cancer Program, an attending surgeon in the Division of Liver Transplantation and Hepatobiliary Surgery and associate professor of surgery at ÈÕ±¾avÉ«ÇéƬ.

Please discuss any risk factors that may predispose patients to bile duct cancer (cholangiocarcinoma).

Risk factors for the disease include age, sex, ethnicity and underlying medical conditions, such as primary sclerosing cholangitis and hepatitis B or C. It is more common in individuals over 60, and it affects men more frequently than women. Despite its relatively low frequency, bile duct cancer can be aggressive and has a poor prognosis, with a 5-year survival rate of only 10 to 40 percent for those with advanced disease.

The increasing frequency of cholangiocarcinoma highlights the importance of early diagnosis and effective treatment strategies, as well as the need for continued research into the causes and risk factors of the disease.

Describe the different subtypes of cholangiocarcinoma.

There are several subtypes of cholangiocarcinoma, based on the location and origin of the cancer cells. Each one has unique characteristics, and the appropriate treatment and prognosis may vary depending on the subtype.

Intrahepatic cholangiocarcinoma

This subtype of cholangiocarcinoma originates within the liver and affects the small bile ducts within that organ. It is less common than other subtypes of cholangiocarcinoma. Overall, the prognosis for intrahepatic cholangiocarcinoma is less favorable than for other subtypes.

Extrahepatic cholangiocarcinoma

This subtype of cholangiocarcinoma affects the larger bile ducts that run from the liver to the small intestine.

Hilar cholangiocarcinoma

This subtype occurs at the hilum, where the bile ducts enter the liver. Also called Klatskin tumors, named after the anatomist who first described them, these tumors are the most common type of extrahepatic cholangiocarcinoma.

Distal cholangiocarcinoma

This subtype occurs at the end of the common bile duct, near the point where it enters the small intestine.

What are the main symptoms of bile duct cancer?

Symptoms can include jaundice (yellowing of the skin and eyes), abdominal pain, weight loss and itching. These can vary depending on the location of the tumor. The disease is frequently silent when found within the liver in the smaller ducts, as other unaffected ducts can still drain bile into the intestine.

Are screenings available to patients at risk for cholangiocarcinoma?

There are currently no routine screening tests for cholangiocarcinoma. However, people with known risk factors, such as those with primary sclerosing cholangitis or liver cirrhosis, may benefit from regular monitoring with imaging tests to detect any bile duct abnormalities or early-stage cancer.

Screening tests for cholangiocarcinoma are not routinely recommended for the general population, as the disease is relatively rare and the tests are not always accurate. In addition, the potential risks and benefits of screening tests must be carefully considered, as false-positive results can lead to unnecessary anxiety, testing and intervention.

People at increased risk for cholangiocarcinoma should discuss the potential benefits and limitations of screening with their healthcare provider.

That having been said, early detection and prompt treatment are critical for improving outcomes in patients with cholangiocarcinoma.

How is bile duct cancer diagnosed?

Generally, the process of diagnosing extrahepatic cholangiocarcinoma involves a combination of clinical evaluation, blood tests, imaging tests like a CT scan or MRI, typically performed by a multidisciplinary team of specialists. In addition to imaging tests and biopsy, this subtype also requires a specialized endoscopic procedure that allows the gastroenterologist to examine the inside of the bile ducts and obtain a biopsy using an endoscopic approach.

Intrahepatic cholangiocarcinoma is diagnosed with the same imaging tests. However, the biopsy may be performed by different access points, either endoscopically or through the skin, depending on the location within the liver.

Discuss the range of types of available treatments for bile duct cancer.

The choice of treatment will depend on several factors, including the stage and location of the cancer, the overall health of the patient and the patient's preferences and goals for treatment. A multidisciplinary team will work together to develop a personalized treatment plan for each individual patient with cholangiocarcinoma.

Surgery

Surgical removal of the cancer is the most effective treatment option for cholangiocarcinoma. The type of surgery will depend on the location of the cancer and the overall health of the patient.

Chemotherapy

Chemotherapy involves the use of drugs to kill cancer cells and slow the growth of the tumor. It is often used in combination with other treatments. 

Targeted therapy and immunotherapy

Targeted therapy and immunotherapy use drugs to target specific proteins or genetic mutations that drive the growth and spread of cancer cells.

Immunotherapy for specific, cancer-promoting genetic alterations represents a breakthrough in the management of cholangiocarcinoma that is significantly prolonging survival.

Among the most promising immunotherapies for cholangiocarcinoma are checkpoint inhibitors. These drugs work by blocking certain proteins that prevent the body's immune system from recognizing and attacking cancer cells. Some commonly used checkpoint inhibitors for the treatment of cholangiocarcinoma are pembrolizumab, nivolumab and atezolizumab.

These drugs have shown promise when used in combination with chemotherapy, radiation or surgery. Immunotherapy has been rapidly changing the treatment landscape for patients with cholangiocarcinoma.

Radiation therapy

Radiation therapy uses high-energy beams to kill cancer cells and shrink the tumor. It is often used in combination with other treatments.

Endoscopic therapies

Endoscopic therapies, such as biliary stenting or photodynamic therapy, may be used to relieve symptoms and improve quality of life in individuals with advanced or inoperable cholangiocarcinoma.

Why is bile duct cancer so hard to treat?

Cholangiocarcinoma or bile duct cancer is a challenging form of cancer to treat due to the location of the cancer in difficult-to-reach areas of the bile ducts, making it challenging to surgically remove the cancer. As well, there are limited treatment options, and the cancer tends to recur. However, early detection and prompt treatment, along with new medical treatment protocols that complement surgery, can improve outcomes in people with cholangiocarcinoma.

Is a liver transplant ever appropriate for patients with bile duct cancer?

In some cases, a liver transplant can be considered as a treatment option for cholangiocarcinoma.

There is a well-established liver transplant protocol for select cases of hilar cholangiocarcinoma that includes treatment with chemotherapy and radiation prior to the transplant. A liver transplant under this protocol can result in long-term survival for some patients with perihilar cholangiocarcinoma who are eligible for the procedure and have a suitable organ donor.

Other liver transplant protocols are being examined for intrahepatic cholangiocarcinoma after a combination of chemotherapy, immunotherapy and radiation. Many patients have achieved long-term survival under these investigational protocols.  

However, liver transplantation is not appropriate for all patients with cholangiocarcinoma. Factors such as the size, location and stage of the tumor, as well as the patient's overall health and medical history, will be considered in determining the suitability of liver transplantation.

We recommend that patients discuss the potential benefits and risks of a liver transplant with our team as well as other treatment options, in order to determine the best course of action for their specific case.

Do clinical trials play an important role for some patients?

Clinical trials are an important component of the treatment of cholangiocarcinoma and provide patients with access to innovative treatments. Our multidisciplinary team can provide specific information on a case-by-case basis to see whether a patient is eligible to participate in clinical trials for cholangiocarcinoma.

Learn more about Liver Transplantation, Hepatobiliary and Pancreatic surgery team at ÈÕ±¾avÉ«ÇéƬ.