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First in Region Liver Transplant for Perihilar Cholangiocarcinoma at Penn Medicine

CT scan of patient with perihilar cholangiocarcinoma.

The following article was originally published in the Penn GI News in April 2018.

A clinical team affiliated with the Divisions of Gastroenterology and Liver Transplantation at Penn Medicine has performed the first liver transplant in the region in a patient with perihilar cholangiocarcinoma (pCCA).

The Penn transplantation team included hepatologists Maarouf Hoteit, MD and Rajender Reddy, MD; endoscopist Gregory Ginsberg, MD; transplant surgeons Kim Olthoff, MD and Abraham Shaked, MD, PhD; oncologist Nevena Damjanov, MD; and dadiation oncologist Edgar Ben-Josef, MD.

The second most common primary hepatic malignancy, cholangiocarcinomas (CCAs) are epithelial tumors arising from the the biliary tree. The CCAs are classified as intrahepatic (iCCA), perihilar (pCCA), or distal CCA (dCCA). Half of all CCAs are perihilar, making pCCAs the most common subtype.

Curative therapy for early stage pCCA involves resection with regional lymphadenectomy. Cancer recurrence is common after resection, however, and many patients with pCCA will have unresectable disease at presentation owing to the involvement of bilateral hilar structures, or underlying parenchymal liver disease.

Liver Transplantation as a Curative for Perihilar Cholangiocarcinoma

The treatments for patients with unresectable disease include chemotherapy or chemotherapy combined with radiation therapy, with limited effectiveness and no chance at cure.

As long as the tumor is confined to the biliary tree in the absence of intrahapatic or extrahepatic metastases, liver transplantation may circumvent many of the issues that prevent resection, such as poor liver function or involvement of bilateral hilar structures. While the concept is attractive, the early experience of transplantation for pCCA was associated with poor outcomes, due mostly to local cancer recurrence.

“The key issues with transplantation for cholangiocarcinoma are patient selection and the application of neoadjuvant therapy,” says Dr. Maarouf Hoteit, a member of the Penn team that performed the region’s first liver transplant in a patient with perihilar cholangiocarcinoma. "For example, potential candidates must have no evidence of tumor outside of the liver on imaging studies and on biopsy of the regional lymph nodes.”

Prior to subsequent neoadjuvant chemoradiation therapy, in addition, the patient must have a liver transplant evaluation and be deemed a good candidate. An essential component of the protocol, chemoradiation therapy makes the surgical field a particularly challenging one for transplant procedures, and is often associated with significant bile duct and liver injury with subsequent risk of infection and deterioration in liver function. Since the tumor usually obstructs the bile ducts in pCCA, ensuring proper biliary drainage is essential for this step of treatment.

After completion of neoadjuvant chemoradiation and before transplant, an operative staging procedure with dissection of the regional lymph nodes is required to establish with certainty the preoperative absence of intrahepatic or extrahepatic metastases.

For patients who meet these rigorous selection criteria, undergo the intensive treatment protocol, and are then are transplanted, the benefits are substantial. In a 2012 report, 65% of patients who completed the protocol were alive at five years.

"This is a remarkable outcome for unresectable cholangiocarcinoma, which, with other treatments, has a much worse outcome," Dr. Hoteit says.

Requisites for Liver Transplantation in Perihilar Cholangiocarcinoma

In addition to meeting the protocol criteria, Dr. Hoteit says, candidates for transplantation must have access to medical centers with the capacity to successfully apply the protocol. A center must have key prerequisites integrated in a collaborative multidisciplinary team approach including extensive expertise and excellence in hepatology, transplant surgery, interventional endoscopy, medical and radiation oncology, interventional radiology, diagnostic radiology and pathology.

Although Penn Medicine has long had both the skilled faculty and resources to meet these requisites, the transplant team chose to refer local patients with pCCA to the academic medical center that created the protocol—until a patient arrived whose circumstances wouldn’t accommodate travel.

The patient was a 55-year-old woman who had been followed at Penn for several years for Primary Sclerosing Cholangitis – a chronic cholestatic liver disease. In April 2017, she had an ERCP to evaluate worsening jaundice and was diagnosed with unresectable perihilar cholangiocarcinoma. She was an otherwise excellent transplant candidate, and had no evidence of tumor outside the liver.

“Our first concern was getting her through the neoadjuvant treatment regimen,” Dr Hoteit says. “And here we had several things to consider. It’s a very intensive regimen, and the patient was quite ill at the outset.”

After enduring the adverse effects of therapy (including mucositis, cholangitis and new onset ascites) and a three month wait on the liver transplant waiting list, however, the patient had a successful combined staging surgery and transplantation at the Penn Transplant Institute.

“Today, she’s doing very well,” Dr Hoteit says. “She’ll need to be followed up closely over the next several months, but we have every reason to be optimistic. The explanted liver suggested a very low risk for recurrence, and the area around the liver had no evidence of disease. These are very good signs.”

The liver transplant protocol now available at Penn offers an opportunity for curative treatment in some patients with unresectable pCCA in our region for the first time.

Image courtesy of Dr. Ian Bickle, Radiopaedia.org, rID: 49009

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The Penn Physician Blog is a resource for health care professionals featuring Penn Medicine physicians and their research, innovations, programs and events. 

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