Liver transplant for PSC-associated cholangiocarcinoma

Mayo Clinic is one of the few centers in the United States that performs liver transplantation for cholangiocarcinoma in the setting of primary sclerosing cholangitis (PSC). Mayo Clinic is a pioneer of this treatment, which provides aggressive radiation and chemotherapy before transplant.

"The approach isn't commonly done and requires multiple specialized teams. We have the experience to successfully manage patients through this complex protocol with good outcomes," says Julie K. Heimbach, M.D., chair of Transplantation Surgery at Mayo Clinic in Rochester, Minnesota. "Our five-year survival rate is 70 to 75 percent, which approaches what we can achieve with other indications for liver transplant."

PSC is the top risk factor for the development of perihilar cholangiocarcinoma (pCCA), which is the subtype of bile duct cancer associated with PSC. The 30-year risk of developing pCCA in the setting of PSC is about 20 percent. Without transplant, the five-year survival rate is less than 5 percent.

Successful management of these patients is highly challenging — starting with establishing a diagnosis of cancer in patients who have PSC. To be eligible for transplant, these patients must have the cancer diagnosis before the disease spreads beyond the liver. But early diagnosis is difficult because pCCA cells tend initially to grow longitudinally along the bile ducts, mimicking on MRI the appearance of the strictures that characterize PSC.

"Our intensive surveillance of patients with PSC means we tend to find cancer earlier," says Sumera H. Rizvi, M.B.B.S., a liver transplant specialist at Mayo Clinic in Rochester, Minnesota.

That surveillance involves testing for tumor markers such as CA19-9 and annual imaging studies. If the results are concerning — such as a new stricture — then endoscopic retrograde cholangiopancreatography, with cytologic analysis of biliary brushings and fluorescence in situ hybridization (FISH), is performed.

"For us, FISH analysis has proved very valuable, particularly in cases where diagnosis is difficult," Dr. Rizvi says. "We are one of the few centers in the country that offers FISH analysis of biliary brushings."

Careful evaluation with multiple tests is required because cells in PSC are inflamed and can mimic cholangiocarcinoma cells on cytology, and tumor markers might be high due to jaundice.

"We have to look at a variety of criteria. But our biggest strength is our multidisciplinary approach," Dr. Rizvi says. "We have specialists in radiology, hepatology, cytopathology and transplant surgery all working together to make a diagnosis of cholangiocarcinoma. We have to be confident about the diagnosis because the undertakings associated with this liver transplant protocol are significant."

The protocol involves three weeks of radiation treatment with concurrent continuous infusion of 5-fluorouacil chemotherapy. Patients then receive brachytherapy, followed by oral capecitabine for two out of every three weeks while they await liver transplantation.

"The optimal window, to allow for patient recovery between brachytherapy and transplantation, is somewhere around eight weeks," Dr. Heimbach says. "Ideally, the patient has a living donor. Many of our patients in this protocol have had living-donor transplantation. If not, the wait for a donated liver is difficult to predict."

The transplant procedure poses additional challenges. "This type of radiation therapy really alters the surgical field," Dr. Heimbach says. "We've been able to adapt our techniques to manage that — figuring out how to hook up radiated blood vessels without having them clot off or stricture down."

As a fully integrated, tertiary center, Mayo Clinic is able to coordinate scheduling of radiation and chemotherapy and to perform highly specialized adjuvant and surgical treatment. An experienced hospital team cares for patients as needed while they await transplant, and after surgery.

"The protocol requires more than one team to achieve the desired results," Dr. Heimbach says. "Every step requires experienced specialists who can coordinate their work. This is the epitome of what we can do well at Mayo Clinic."