A new liver may be just the cure for some with cancer of liver, bile ducts

Liver transplantation is an attractive modality for hepatocellular carcinoma (HCC), and also for some cholangiocarcinomas, with careful patient selection.

Liver transplantation for cancer (HCC and cholangiocarcinoma) is controversial topic that has been evolving over the last decade, a Professor of Surgery at the University of Pittsburgh School of Medicine and Co-director of the Liver Cancer Center at the Thomas E. Starzl Transplantation Institute, in Pittsburgh said.

Liver transplant for HCC

The rationale supporting liver transplantation for HCC is strong. Approximately 70% to 90% of tumors arise in the setting of cirrhosis, and the cirrhotic liver has poor hepatic reserve to tolerate a major resection. Additionally, HCC rumors are often multifocal and are underestimated by current computed tomography and magnetic resonance imaging. Recurrence rates exceed 50% even five years after resection.

Transplant is an appealing modality as it removes the cancer and the precancerous conditions, i.e., cirrhosis that leads to HCC so why not transplant all patients. For one reason, there is a critical shortage of organ donors. The number of patients on the UNOS (United Network for Organ Sharing) wait list for liver transplantation is now over 16,500.

Liver transplantation can cure HCC in the appropriate setting. Data from UNOS and the Organ Procurement and Transplantation Network between 2000 and 2002 showed survival from deceased donor transplantation to be 88% at one year, 80% at three years and 75%  at five years. However, not all patients with HCC benefit. Survival correlates with tumor stage, which means that liver transplantation works best for early-stage HCC.

Current transplantation policy maintains that the appropriate candidates are:

• Patients with cirrhosis and any Child-Pugh score (A, B or C)

• Patients with stage II HCC who have one tumor that is 5 cm or less in diameter or three tumors that are all less than 3 cm; or

• Patients who do not have gross vascular invasion or metastases.

But are we too restrictive? What about pushing the limit transplanting patients with tumors 6 to 7 cm in size without macro-vascular invasion? Should we deny a potentially curative operation to a patient based on a centimeter? This is controversial, and some centers have pushed for expanding the size criteria.

Liver transplantation for cholangiocarcinoma

Cholangiocarcinoma (adenocarcinoma of the bile ducts) can be hard to diagnose and even harder to treat. It preferentially grows along the length of the common bile duct, often involving the periductal lymphatics, and commonly metastasizes to the lymph nodes.

For hilar cholangiocarcinoma (tumor above the cystic duct), surgical resection is the treatment of choice in the absence of associated primary sclerosing cholangitis (PCS). However, approximately 10% of patients with cholangiocarcinoma have undying PSC, and the results of resection in this setting are dismal. Furthermore, cholangiocarcinoma in the setting of PSC is frequently multicentric, and is often associated with underlying liver disease with eventual cirrhosis and portal hypertension.

This scenario led transplant centers to consider liver transplantation for hilar cholangiocarcinoma; however, the results were disappointing, with three-year survival rates less than 3%. The situation improved with the inclusion of neoadjuvant chemoradiation, which was based on the concept that the growth of hilar cholangiocarcinoma is locoregional.

Neoadjuvant chemoradiation for cholang-iocarcinoma was introduced by the transplant team at the University of Nebraska in the late 1993 by the multidisciplinary team at Mayo Clinic protocol, which begins treatment with external beam radiation therapy, followed by protracted venous infusion of fluorouracil (5-FU) and brachytherapy (Iridium), and then abdominal exploration for staging with endoscopic ultrasound and finally capecitabine for two or three weeks until the final option of liver transplantation. The five-year survival rates for patients undergoing liver transplantation at Mayo Clinic after completing the neoadjuvant cholangiocarcinoma treatment protocol are excellent, at approximately 70%.

According to an associate professor of surgery at the Mayo Clinic College of Medicine and Chief of Liver Transplantation with the Mayo Clinic Transplant Center in Rochester, Minn., of 90 patients who underwent transplantation  according to the Mayo Clinic protocol between 1993 and 2007, five-year survival was 71% and disease-free survival was 65%. For 15 patients, disease recurred after the transplant, with a mean time to recurrence of 25 months. Current eligibility for the Mayo Clinic protocol based on the presence of an unresectable tumor above the cystic duct or a resectable cholangiocarcinoma arising in the PSC; radial dimension of the tumor should be 3 cm or less, intra- or extrahepatic metastases should not be present and there should be no history of prior radiation therapy or transperitioneal biopsy.

Combined chemoradiation therapy and liver transplantation achieves excellent results for highly selected patients with early-stage hilar cholangiocarcinoma; five-year patient survival after transplantation with this protocol 71%, and exceeds the results reported with resection for hilar cholangiocarcinoma. These results approach the survival after transplantation for chronic liver disease and HCC. Operative staging is essential, as positive findings preclude transplant in about 20% of patients.