Bile duct cancer, also known as cholangiocarcinoma, forms in the thin tubes that carry bile from your liver to your gallbladder and small intestine. Though relatively rare, cholangiocarcinoma is often diagnosed in later stages, making it more difficult to treat, and cases in the U.S. are increasing.

In a review article published in Nature Reviews Clinical Oncology in 2023, lead author Sumera I. Ilyas, M.B.B.S., and co-authors share advances in diagnosing, staging and treating bile duct cancer. Dr. Ilyas is a Mayo Clinic physician-scientist and a transplant hepatologist whose research focuses on the immunobiology of liver cancer. Here is a summary of their review:

The immune microenvironment of bile duct tumors promotes their growth.

Dr. Ilyas says bile duct cancers have distinct tumor immune microenvironments (TIMEs). Researchers have begun to understand the complexity of these TIMEs and their relationship with the three different types of cholangiocarcinoma — intrahepatic, hilar and distal. The TIMEs of bile duct cancer have fewer cytotoxic cells — immune cells that help kill mutated and cancerous cells— and more cells that suppress the immune system. TIMEs may affect how the disease progresses and whether it can be treated with immunotherapy.

The genetic profile of different segments of bile duct tumors can also vary, known as heterogeneity. This makes it more challenging to target characteristics of the tumor for treatment.

Researchers are trying to understand how TIMEs help bile duct cancer grow and progress, evade the immune system and resist chemotherapy. Altering the TIME could make treatments more effective,  including immune checkpoint inhibitors and other immunotherapy treatments.

Blood and bile samples may help diagnose bile duct cancer earlier.

Diagnosing bile duct cancer early, when it's easier to treat, is a challenge. This is partly because cancer experts don't yet have the right tests and biomarkers to detect cholangiocarcinoma. "Efforts to identify better biomarkers to help diagnose the disease at an early stage and help gauge response to treatment are important," explains Dr. Ilyas. "Currently, there is a great deal of ongoing research focused on the use of tumor DNA in diagnosing and monitoring cholangiocarcinoma in patients receiving treatment."

Dr. Ilyas says research has identified potential biomarkers for cholangiocarcinoma. Researchers are now studying how biomarkers obtained through blood and bile samples from patients can help improve cholangiocarcinoma diagnosis. They are also looking for ways to detect and monitor tumors using liquid biopsies, which use DNA that breaks away from the tumor to circulate in bodily fluids like blood or bile. "Although we anticipate that liquid biopsy may enhance early detection of cholangiocarcinoma, larger scale studies are needed to confirm its effectiveness," she says.

Bile duct cancer treatments are improving.

"Systemic treatment options for cholangiocarcinoma were once quite limited and not very effective," says Dr. Ilyas. Systemic therapies are drugs used to treat cancer, such as chemotherapy, targeted therapy and immunotherapy.

Targeted therapies are drugs targeting mutations that control how cancer cells grow, divide and spread. With a better understanding of the different genetic profiles of bile duct cancer subtypes, cancer experts are developing new treatments tailored to specific types of cholangiocarcinoma. The Food and Drug Administration has approved several new drugs that target specific genetic mutations associated with bile duct tumor growth. "The emergence of targeted therapies has broadened treatment options and, in doing so, given much more hope to our patients," says Dr. Ilyas.

Immunotherapy uses the body's immune system to attack cancer. While immunotherapy has not yet proven effective for treating cholangiocarcinoma, Dr. Ilyas says ongoing research to identify biomarkers and to understand why bile duct cancer doesn't respond to immunotherapy may improve outcomes.

Researchers are also studying liver transplants as a treatment option for cholangiocarcinoma in select patients with certain tumor types. However, Dr. Ilyas says this form of treatment needs further research.

Learn more

Learn about cholangiocarcinoma and find a clinical trial at Mayo Clinic.

Join the Cancer Support Group on Mayo Clinic Connect, an online community for patients and caregivers.

This article first published on the Mayo Clinic Comprehensive Cancer Center blog.

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DEAR MAYO CLINIC: My mother has been experiencing unusual and persistent fatigue, abdominal pain, and jaundice. After undergoing a CT scan, her doctor diagnosed her with cholangiocarcinoma. What is this type of cancer? And what treatment options are available?

ANSWER: Cholangiocarcinoma is a rare cancer that develops from the bile ducts, which are slender tubes that carry the digestive fluid bile and connect the liver to the gallbladder and small intestine.

The tumor can occur anywhere along the biliary “tree” and is divided into three subtypes based on where it starts. The intrahepatic subtype starts in the bile duct inside the liver and typically appears as a mass in the liver, which may affect the organ’s function. The second subtype, called perihilar cholangiocarcinoma, occurs just outside of the liver, where the bile ducts come together and exit the liver. Patients diagnosed with this form of cholangiocarcinoma typically present with jaundice. Distal cholangiocarcinoma is the third subtype. It occurs in the portion of the bile duct that is outside of the liver and nearest to the intestine. This subtype also typically presents with jaundice.

An initial CT scan can be suggestive of cholangiocarcinoma, but additional testing, including a biopsy or brushings, is required to establish the diagnosis and the stage. For all three subtypes, a health care professional typically also will order a CT scan of the chest to look for any signs of metastasis, or spread, to the lungs.

If there is blockage of the bile ducts and jaundice, symptoms most commonly occurring with the perihilar or distal subtypes, then a health care professional may perform an endoscopic evaluation with an endoscopic retrograde cholangiopancreatography. This allows for collection of a sample of the area of concern and placement of an internal stent to open the bile ducts so the liver can drain appropriately. Biliary drainage helps relieve signs and symptoms of biliary blockage, which can include jaundice, poor appetite and itching.

For intrahepatic tumors that present as a liver mass, it is common to have an ultrasound-guided biopsy performed by a radiologist to establish the diagnosis and obtain tissue for further testing, such as sequencing studies.

There are several options for treating these rare tumors, but determining the optimal approach for your mother will depend on the stage, location and subtype of her tumor. For example, most patients with localized disease, meaning the cancer has not spread to any other organs, are candidates for surgery to remove the tumors.

If your mother is diagnosed with intrahepatic or perihilar cholangiocarcinoma, removing part of the liver may be required. However, standard surgical approaches to remove the tumor may not be possible for some patients diagnosed with perihilar cholangiocarcinoma. In certain situations, a liver transplant may be an option instead.

Finally, the most common surgery to treat distal cholangiocarcinoma is called the Whipple procedure, which is a complex operation that involves removing a portion of the pancreas.

Surgery is the only curative treatment option for these tumors, but for those patients who are not candidates for surgery, other treatment options should be considered. These include chemotherapy, targeted therapy, immunotherapy, radiation and radioembolization. These treatments often are given in combination, and the combination and order of the treatments is dependent on the specific tumor subtype and extent of the disease.

As part of the testing for patients diagnosed with cholangiocarcinoma, it is now common to perform an analysis for mutations, called next-generation sequencing. These tests can identify certain mutations in tumors for which we have targeted therapy options, and these mutations occur more frequently in intrahepatic cholangiocarcinoma.

Finally, for patients who have not responded to standard treatments or have tumors that have progressed on standard treatments, we recommend considering enrollment in clinical trials evaluating new treatment strategies.

Ultimately, if your mother has been diagnosed with cholangiocarcinoma, it is important that she be seen at a cancer center with experience treating these tumor types because the treatment options, and determining which patients are candidates, is complex. — Dr. Rory Smoot, Surgery, Mayo Clinic, Rochester, Minnesota

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Related Article

• Consumer Health: Treating liver cancer published 10/27/22

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The gallbladder is a small, pear-shaped organ that sits just beneath the liver, on the right side of the abdomen. Slender tubes that carry bile fluid also are also located in that area. Because of the relatively hidden nature of the gallbladder and bile ducts, cancers can grow without being detected. Late detection can mean a poor prognosis.

Dr. Kabir Mody, past co-chair of the Hepatobiliary Disease Group at Mayo Clinic Cancer Center, says February is the awareness month set aside to educate people about these rare cancers.

In this Mayo Clinic Q&A podcast, Dr. Mody talks about symptoms, detection, surgical interventions and treatments for gallbladder and bile ducts cancers.

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Watch: Dr. Mody discusses gallbladder and bile duct cancers.

Read the full transcript.

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For the safety of its patients, staff and visitors, Mayo Clinic has strict masking policies in place. Anyone shown without a mask was either recorded prior to COVID-19 or recorded in a nonpatient care area where social distancing and other safety protocols were followed.

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On the Mayo Clinic Radio program, Dr. S. Vincent Rajkumar, a Mayo Clinic hematologist and researcher, discusses herd immunity, antibodies and how the body works to fight off disease. Dr. Bret Petersen, a Mayo Clinic gastroenterologist, will discuss treatment for bile duct cancer. And Dr. Randall DeMartino, a Mayo Clinic vascular surgeon, will explain peripheral artery disease, a common circulatory problem.

Information in this post was accurate at the time of its posting. Due to the fluid nature of the COVID-19 pandemic, scientific understanding along with guidelines and recommendations may have changed since the original publication date. 

Check the Centers for Disease Control and Prevention website for additional updates on COVID-19. For more information and all your COVID-19 coverage, go to the Mayo Clinic News Network and mayoclinic.org.

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On this Mayo Clinic Radio podcast, Dr. Brent Bauer, director of research for the Mayo Clinic Integrative Medicine Program, will share how integrative medicine is used in cancer care. Also on the program, Dr. Bret Petersen, a Mayo Clinic gastroenterologist, will discuss treatment for bile duct cancer. And Dr. Randall DeMartino, a Mayo Clinic vascular surgeon, will explain peripheral artery disease, a common circulatory problem.

Here's your Mayo Clinic Radio podcast.

The post Complementary medicine during cancer care: Mayo Clinic Radio appeared first on Mayo Clinic News Network.

Complementary medicine, also known as integrative medicine, uses wellness practices to help people cope with cancer, persistent pain, chronic fatigue, fibromyalgia and other medical conditions. Integrative therapies, such as stress management, meditation, massage therapy and acupuncture, are intended to complement — not replace — conventional Western medicine. Combining integrative therapies with conventional medicine aims to help patients better manage their symptoms and improve their quality of life by reducing fatigue, pain and anxiety.

On the next Mayo Clinic Radio program, Dr. Brent Bauer, director of research for the Mayo Clinic Integrative Medicine Program, will share how integrative medicine is used in cancer care. Also on the program, Dr. Bret Petersen, a Mayo Clinic gastroenterologist, will discuss treatment for bile duct cancer. And Dr. Randall DeMartino, a Mayo Clinic vascular surgeon, will explain peripheral artery disease, a common circulatory problem.

To hear the program, find an affiliate in your area.

Use the hashtag #MayoClinicRadio, and tweet your questions.

Mayo Clinic Radio is on iHeartRadio.

Access archived shows or subscribe to the podcast.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Complementary medicine during cancer care appeared first on Mayo Clinic News Network.

On the next Mayo Clinic Radio program, Dr. Brent Bauer, director of research for the Mayo Clinic Integrative Medicine Program, will share how integrative medicine is used in cancer care. Also on the program, Dr. Bret Petersen, a Mayo Clinic gastroenterologist, will discuss treatment for bile duct cancer. And Dr. Randall DeMartino, a Mayo Clinic vascular surgeon, will explain peripheral artery disease, a common circulatory problem.

To hear the program, find an affiliate in your area.

Miss the show? Here's your Mayo Clinic Radio podcast.

Use the hashtag #MayoClinicRadio, and tweet your questions.

Mayo Clinic Radio is on iHeartRadio.

Access archived shows or subscribe to the podcast.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Mayo Clinic Radio: Complementary medicine during cancer care / bile duct cancer / peripheral artery disease appeared first on Mayo Clinic News Network.

The search for treatment targets for patients with bile duct cancer, also known as cholangiocarcinoma, has taken a 360 degree turn, offering new hope for patients. That’s according to Mitesh Borad, M.D., deputy director for Center for Individualized Medicine Biomarker Discovery Program at Mayo Clinic’s Arizona campus, Dr. Borad and his colleagues are using new genomic technologies and innovative approaches to data analysis to uncover genetic mutations driving the disease with the goal of developing new targeted therapies.

Genomics opens door to new treatment options    

The bile duct is a network of tubes that connects the liver, gallbladder and small intestine. Each year, 6,000 patients in the U.S. are diagnosed with bile duct cancer. For years, there were limited treatment options for this rare cancer, with fewer than 10% of patients surviving for five or more years.

“In the past, rare cancers like bile duct cancer did not receive the attention or resources to help identify new treatments. As a result, the biology and genetics of this cancer were poorly understood. At the same time, there was a great unmet patient need for more precise therapies with fewer side effects,” explains Dr. Borad.

But over the last decade, Dr. Borad’s team has refined a framework now used around the country to open the door for new treatment options.

Using genetic testing on tissue samples from thousands of patients, the team searched for genetic mutations that may be driving the disease. They uncovered more than 25 genetic mutations that hold the potential to be treated with available targeted therapies or immunotherapies, which harness the power of the patient’s own immune system to fight their cancer.

The Mayo team has also shown that newly developed targeted therapies, known as fibroblast growth factor receptor (FGFR) inhibitors, can shrink bile duct tumors in patients who have mutations in certain FGFR genes. 

“Our initial research in this area is now being validated in larger scale clinical trials, and we hope results will lead to approval for this new treatment approach,” says Dr. Borad.

Liquid biopsies – a simple blood test to detect, treat cancer sooner

Dr. Borad and his colleagues are also developing blood tests, known as liquid biopsies, to detect traces of DNA shed into the bloodstream from cholangiocarcinoma tumors.

As he explains, cholangiocarcinoma can be difficult to diagnose, depending upon where it is located. Frequently, the disease is not diagnosed until it has advanced and spread to other areas of the body.

“Because of the location of cholangiocarcinoma, it can be difficult to obtain a high quality tissue sample with a traditional biopsy. Liquid biopsies offer a faster, non-invasive and lower cost approach to detecting the early signs of cancer or cancer recurrence. They can also identify specific genetic mutations in a patient’s tumor that may be targeted with therapies.”

In one of the largest patient studies to date, the Mayo team used liquid biopsies to analyze tumors from 124 patients with cholangiocarcinoma.

“We identified several genes, 55% of which may have implications for treatment options. This could help patients avoid harmful side effects from an ineffective treatment,” says Dr. Borad.

The team’s next step is to compare the validity of these liquid biopsies against results from traditional tissue biopsies.

For Dr. Borad, this research has been rewarding. As a hematology and oncology fellow at Tulane University, he saw the need for developing new treatments for patients who did not respond to standard therapy or whose cancer returned after treatment.

Committed to finding answers, he spent three years as a Genomics Medicine Scholar at Translational Genomics Research Institute (TGen), joining Mayo Clinic in 2008.

“The new options for patients with bile duct cancer are a perfect example of how precision medicine can make a real difference. In fact, bile duct cancer is one of the gastrointestinal diseases most amenable to a precision medicine approach, offering individualized care based on a patient’s specific needs.”  

The latest advances in cancer care

Hear from Dr. Borad and other researchers and innovators in oncology at Individualizing Medicine 2019 Conference: Precision Cancer Care through Immunotherapy and Genomics on Sept. 20-21, in Scottsdale, Arizona.

Key conference themes include:

• CAR-T therapy
• Clonality
• Pharmacogenomics
• Lineage Plasticity
• National Cancer Institute

Stay informed

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Cancer caregivers: Remember to take care of yourself
Just as your loved one with cancer needs care, so do you. From enjoying your favorite music or walking in the woods, to asking for help when you need it, here are some easy ways you can reconnect and take care of yourself, too.

Cancer treatment myths
Misconceptions about cancer treatment might make you feel confused or unsure when choosing a treatment. Knowing the truth can help you feel more comfortable. Learn more from Dr. Timothy Moynihan, a Mayo Clinic medical oncologist.

The post Living With Cancer: What is cholangiocarcinoma? appeared first on Mayo Clinic News Network.

Cancer caregivers, remember to take care of yourself 
It's so essential for the person living with cancer to take the time to heal his or her body and recover. However, if you're the caregiver, it’s also important to take care of yourself. Here are a few ideas to help you reconnect and start your self-care plan.

Photodynamic therapy: An effective treatment for lung cancer? 
Learn about photodynamic therapy, which may play a limited role in lung cancer treatment — generally complementing, rather than replacing, other forms of treatment.

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Hilar cholangiocarcinoma is a type of bile duct cancer that occurs in the bile ducts that lead out of the liver (hepatic ducts) and join with the gallbladder. Learn more about its diagnosis and treatment.

The post Living With Cancer: Caregivers Need Care, Too appeared first on Mayo Clinic News Network.