Cholangiocarcinoma at the University of Michigan

Overview
Bile Ducts
Bile Duct Cancer (cholangiocarcinoma)
Symptoms
Risk Factors
Diagnosis
Staging
Treatments
Patients Eligible
Patients Not Eligible
Evaluation, Pre-Transplant Treatment, Liver Transplant
Research
Contact Information

Overview

Cholangiocarcinoma can be an aggressive cancer of the bile ducts that may be difficult to diagnose and require complicated treatment regimens. Different treatments are available through many different disciplines in medicine. For patients to receive the best possible care and potential to be cured, all of these options should be considered for the most effective combination and order of treatments. In addition, many people are appropriately concerned about their condition and eager to have a diagnosis, begin treatment, and avoid any unnecessary delays. For these reasons, the University of Michigan has a Multidisciplinary Liver Tumor Clinic that allows a patient to see experts in different areas of treatment in one visit. All patients are then reviewed at a Multidisciplinary Liver Tumor Board. During this review, all the patient's data, laboratory tests, pathology slides, and radiology imaging are examined in detail. Experts in liver surgery, liver disease (hepatology), medical oncology, radiation oncology, pathology, radiology, liver transplant, and interventional radiology are present and discuss the best possible plan to diagnose and treat the patient's condition. In a sense, this meeting allows the patient to get a "second opinion" from multiple different experts in their specialty as well as ensure the team caring for them has exceptional communication and knowledge of all of their options. To learn more about the University of Michigan Liver Tumor Clinic visit the website at www.cancer.med.umich.edu/cancertreat/liver/the_clinic.shtml.

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Bile ducts are tubes that allow bile to flow from the liver, through the gall bladder to the small intestine. Bile is a digestive fluid produced by the liver and stored in the gall bladder that is used by the body to break down fats into fatty acids so they can be absorbed.

Cancer can occur in any portion of the bile duct system. Bile duct cancer begins when the cells in the bile duct become abnormal and grow uncontrollably. Cholangiocarcinoma is another term for adenocarcinoma that begins in the mucous glands lining the bile ducts. Cholangiocarcinoma is a rare cancer occurring in approximately 1-2 per 100,000 people each year.

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Some, but not all, patients may experience the following symptoms of bile duct cancer:

• Jaundice (a yellowing of the skin and the white areas of the eyes)
• Itching
• Weight loss
• Loss of appetite
• Fever
• Chills
• Clay-colored stools
• Dark colored urine (tea colored)
• Abdominal pain (in the upper right abdomen that may radiate to the back)
• Some tumors may be asymptomatic and identified by abnormal blood tests

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Risk factors may increase a person's chance of developing cancer, but they do not directly cause cancer. While cholangiocarcinoma is rare; the following factors may increase a person's risk of developing bile duct cancer:

• Previous disease or irritation of the bile duct, such as bile duct cysts.
• Age. Older patients are more likely to develop bile duct cancer.
• Certain chemicals, such as those found in rubber plants and automobile industries.
• Infection with liver flukes.
• Primary sclerosing cholangitis (lifetime risk of developing cholangiocarcinoma is 10-15%).
• Cirrhosis.
• Caroli's syndrome (multiple bile duct cysts within the liver)

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MRI from the U of M demonstrating a cyst of the common bile duct that developed into cholangiocarcinoma (yellow arrow)

Many tests may be used by a physician in determining whether a patient has cancer and which treatments may be most effective in treating the cancer. In determining which tests to order a physician is likely to consider the patient's age, medical condition, the type of cancer they suspect, and the severity of the patient's symptoms. In general, blood tests can help identify potential inflammation or blockages in the bile ducts. Certain imaging tests may show a mass or tumor suggesting the presence of cholangiocarcinoma or may show a blockage in the bile duct. Obtaining a biopsy and looking at the cells in pathology is the only way to definitively diagnosis cholangiocarcinoma.

Testing may include:

• Blood tests (blood chemistries, liver function tests, tumor markers (i.e. CA 19-9))
• Biopsy
• Radiological imaging:
• Ultrasound
• CT Scan
• Magnetic resonance imaging (MRI)
• PTC

• ERCP

• Laparoscopy or open surgery biopsy

There are at least 3 staging systems used for cholangiocarcinoma, but none have been shown to be the best at predicting patient survival. The most important predictor of survival is whether or not the tumor can be completely removed with surgery. This includes the presence or absence of spread to lymph nodes, metastases to the liver, growth of the tumor into surrounding organs or blood vessels (vascular invasion), or distant metastases (wide spread of cancer to other areas of the body).

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Cholangiocarcinoma can be an aggressive cancer and lead to death with a 5-year survival less than 5% if the tumor is inoperable. The only treatment option considered to cure the cancer is to remove all of the tumor with surgery.

Based on the testing described above, almost half of all patients diagnosed with cholangiocarcinoma will be found to have advanced disease and complete removal with surgery will not be possible. Even when preoperative testing suggests the tumor might be removable with surgery, almost half of patients will be identified to have metastases on exploratory surgery. For patients that have the complete tumor removed with surgery, the 5-year survival can range from 15-50%, depending on the location of the cancer within the bile duct and involvement of lymph nodes.

In many cases, laparoscopic liver surgery may be an option, avoiding large incisions and allowing patients to recover quickly and return to their normal activity sooner.

Trans-arterial Chemoembolization (TACE)

TACE is primarily used for hepatocellular carcinoma (HCC), TACE is performed by our Interventional Radiologists, usually as an outpatient procedure to interrupt the blood supply of the tumor itself and direct chemotherapy directly into the tumor.

TheraSphere®

TheraSphere® is used for inoperable liver cancer with radioactive microspheres that are placed directly into the blood vessels going to the liver.

Radiation therapy may be used after surgical removal of the tumor to improve the chance for a cure. If all of the tumor was removed at the time of surgery (tissue margins were negative), it is unclear if radiation treatment is needed. If the margins are positive, indicating the cholangiocarcinoma was not completely removed, radiation therapy is generally recommended.

Stereotactic Boady Radiation Therapy (SBRT)

SBRT is performed by members of radiation oncology on an outpatient basis, detailed radiologic assessment allows focusing high dose liver irradiation to the site of the tumor while sparing the surrounding liver tissue. This allows larger doses of radiation to be administered to the tumor while avoiding many of the potential side effects.

Various chemotherapy regimens exist that may be combined with other therapies to allow for overall improved combined success or to decrease the stage of disease to allow for eventual resection/removal of the tumor.

In the past, cholangiocarcinoma was not considered as an indication for liver transplantation because 5-year survival for patients was only around 20%. Over the past 10 years, protocols have been developed that identify patients who have almost a 75% chance of surviving more than 5 years after a liver transplant has been performed. The University of Michigan is currently one of a handful of programs in the United States that has a United National Organ Sharing (UNOS) approved protocol that allows appropriate candidates to get a standard exception allowing improved access to deceased donor livers.

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1. Hilar cholangiocarcinoma (a tumor at the branching of the bile duct to the right and left side of the liver) that cannot be removed by surgery and is less than 3 cm wide in diameter.
2. Cholangiocarcinoma is diagnosed as a malignant appearing stricture above the level of the cystic duct (branch of the bile duct going to the gall bladder) and has at least one of the following:
1. CA 19-9 > 100 ng/ml
2. Brushing of bile duct by ERCP or PTC demonstrating cancer cells
3. A tumor seen on CT or MRI < 3 cm and suspicious for cholangiocarcinoma
3. Patients who are otherwise a candidate for liver transplantation based on hepatology, surgery, and social work evaluation

1. Spread of cancer (metastases) to the liver, lymph nodes, or any other part of the body
2. Cholangiocarcinoma in an area of the bile duct inside the liver or below the cystic duct
3. Prior attempt at removal by surgery (this increases the chance the tumor may spread if it is not completely removed)
4. Tumors that are >3cm in diameter when measured on CT or MRI
5. Previous treatment with chemotherapy or radiation therapy
6. Prior needle biopsy, either through the skin or by endoscopy, of the main tumor (this increases the risk for spread of the tumor outside of the bile duct). Lymph nodes surrounding the bile duct may be biopsied to ensure the tumor has not spread.
7. Uncontrolled infection

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Patients who cannot be treated by removal of the tumor alone but fit the criteria for transplant will undergo a series of steps to be sure the tumor has not spread, to treat the tumor before (called neo-adjuvant therapy) transplant, followed by liver transplantation. The steps include:

1. Evaluation for possible surgical resection in the University of Michigan Liver Tumor Clinic and presentation at the Multidisciplinary liver tumor board. This may require other tests including a liver MRI, chest CT, ERCP or PTC, etc.
2. Evaluation for liver transplant by a hepatologist, social worker, and surgeon
3. Biopsy (called fine needle aspiration - FNA) of the lymph nodes (not the actual tumor) by endoscopic ultrasound (EUS).
4. Begin stereotactic body radiation therapy (SBRT) for 2-3 weeks
5. Begin a chemotherapy oral medication called capecitabine and continue until transplant
6. Exploratory surgery using a small incision or laparoscopy in the operating room (OR staging) to biopsy lymph nodes to be sure the tumor has not spread
7. List for deceased donor transplant
8. Perform liver transplant when a deceased donor liver is available or if a living liver donor volunteers

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Investigational Treatment Protocols

Many investigational treatment protocols may be available for patients who are eligible for the therapies listed above, as well as patients who are not be eligible for the treatments listed above. For more information about investigational treatment therapies visit the UM Clinical Studies website.

For appointments or scheduling:

The Clinic currently sees patients on Fridays. To schedule an appointment contact:

Liver Tumor Clinic Coordinator
734-647-8916
734-615-4484 (FAX)

University of Michigan Comprehensive Cancer Center
B1-363, SPC 5912
1500 East Medical Center Drive
Ann Arbor, MI 48109-5912

Patients needing to speak with a nurse:

Liver Tumor Clinic Nurses
734-647-8902
734-647-8689 (FAX)

For information about the U-M Liver Tumor Clinic and related topics, visit the following websites:

About the Liver Tumor Clinic:
www.cancer.med.umich.edu/cancertreat/liver/the_clinic.shtml

Make an Appointment:
www.cancer.med.umich.edu/cancertreat/liver/make_an_appointment.shtml

About Liver Transplant:
www.michigantransplant.org/liver

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