March 12, 2025
Perihilar cholangiocarcinoma is a small tumor that can cause big problems for patients. According to Julie K. Heimbach, M.D., a transplant surgeon at Mayo Clinic in Rochester, Minnesota, these tumors exist in the bile ducts leading out of the liver, which are very high-stakes real estate. An artery, the portal vein and the bile duct run through this area. Even though these tumors can be relatively small, they may obstruct key structures, making it difficult to resect them completely while preserving adequate blood supply to the liver and bile outflow from the liver.
Cholangiocarcinoma is classified according to location — intrahepatic, perihilar and distal — and perihilar is the most common form. In many patients, these tumors are unresectable at the time of presentation. In the past, physicians tried isolated liver transplant to improve the chance to attain a complete resection but had negative results primarily due to high disease recurrence. They recognized that some patients who had radiation therapy seemed to have prolonged disease-free survival, although many ultimately had progressive liver damage from the radiation.
In 1993, the liver transplant team at Mayo Clinic in Minnesota partnered with colleagues in Radiation Oncology and Medical Oncology to combine radiation and liver transplant for carefully selected patients with early-stage unresectable perihilar cholangiocarcinoma using neoadjuvant chemoradiation followed by liver transplantation. Physicians at Mayo Clinic have completed more than 375 liver transplants following this protocol, which is available at all three Mayo Clinic campuses.
"We have developed quite an experience with this," says Dr. Heimbach. "It's definitely a challenging tumor to manage on many levels. We keep pushing to move the field forward."
Stringent selection drives protocol forward
The diagnostic criteria for this protocol at Mayo Clinic are identical to the diagnostic criteria required by the Organ Procurement and Transplantation Network, the national oversight system for transplantation in the United States. The criteria require the presence of a malignant-appearing stricture on cholangiography with at least one of the following:
- Endoscopic intraluminal brushings or tissue biopsy that is positive or strongly suspicious for cholangiocarcinoma.
- A CA 19-9 level greater than 100 U/mL in the absence of acute bacterial cholangitis.
- Polysomy by fluorescence in situ hybridization (FISH) or a well-defined mass on cross-sectional imaging at the site of the malignant-appearing structure.
Patients with metastatic disease, irradiation of the abdomen precluding additional radiation or a previous attempt at surgical resection are excluded.
Patients selected as candidates begin neoadjuvant chemoradiation therapy, including external beam therapy, high-dose brachytherapy and oral capecitabine. The patients then undergo operative staging as close to the time of transplant as possible to ensure the tumor has remained localized to the bile duct.
There is a sweet spot in the timing of transplantation following neoadjuvant therapy, although researchers are still learning what that exact window is. If a patient receives a transplant too early, biologically aggressive tumors might be missed, putting the patient at greater risk of recurrence following surgery. Additionally, there may be ongoing inflammation from the treatment.
If a patient waits too long for a transplant, however, the malignancy or underlying liver disease may progress and the patient can have complications from the therapy. Physicians are learning more about this ideal time frame as more patients receive this treatment protocol.
Volume empowers positive outcomes
This protocol is being adopted more widely around the world, as highlighted by a recent study reporting excellent outcomes in 17 well-experienced centers worldwide. However, it is a technically challenging procedure that requires a large team to work collaboratively toward success. It is designed specifically for perihilar cholangiocarcinoma, and experience in that area truly makes a difference in outcomes. In fact, a 2020 study published in the Annals of Surgical Oncology by a group at Henry Ford Hospital found that post-transplant outcomes were significantly better at centers that had performed more than six liver transplants for perihilar cholangiocarcinoma than at centers that had performed fewer of the same procedure.
Early detection and awareness of transplantation as a treatment option are key to success in this protocol. It can be very difficult to get a good sample of this type of tumor because of its size and location. Physicians at Mayo Clinic can support patients throughout the process and follow them until the diagnosis is clear, either by attaining a tissue diagnosis with repeat endoscopic retrograde cholangiopancreatography or by using a combination of imaging characteristics and biomarkers, FISH on cytology and clinical findings. Attaining a definitive tissue diagnosis is not required before referring a patient to physicians at Mayo Clinic. Throughout this process, it's essential to avoid a transperitoneal biopsy, which can disseminate the tumor and make the patient ineligible for transplant.
For more information
Tan EK, et al. Liver transplantation for peri-hilar cholangiocarcinoma. Journal of Gastrointestinal Surgery. 2020;24:2679.
Kitajima T, et al. Center experience affects liver transplant outcomes in patients with hilar cholangiocarcinoma. Annals of Surgical Oncology. 2020;27:5209.
Breuer E, et al. Liver transplantation as a new standard of care in patients with perihilar cholangiocarcinoma? Results from an international benchmark study. Annals of Surgery. 2022;1;276.
Refer a patient to Mayo Clinic.