LTX in Oncology

Liver Transplantation in Oncology

Patients with end stage liver disease who have failed standard medical therapy are the usual candidates for liver transplantation. A number of acute and chronic diseases of the liver can result in end stage liver disease. Other than this, liver transplantation is also considered for various hepatic malignancies. Currently up to 10-20% of all liver transplants performed are for hepatocellular cancer (HCC). There is no controversy that hepatoblastoma is an excellent indication in pediatric patients with unresectable tumors. Similarly, liver transplantation for HCC in the adult population yields good results for patients whose tumor masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumors can be reliably selected to benefit from the procedure. Adjunctive procedures like radiofrequency ablation, chemoembolization, or cryotherapy might be indicated to limit tumor progression for patients on waiting lists. Epitheloid hemangioendothelioma is also an appropriate indication for liver transplantation. Metastatic liver disease is not an indication for liver transplantation, with the exception of cases in which the primary is a neuroendocrine tumor, for which liver transplantation can result in long-term survival and even cure in a number of patients.

Hepatocellular Carcinoma

Liver transplantation was originally conceived as an ideal therapy for advanced hepatic malignancy because it eliminates the primary liver tumor and the potential for recurrence in the liver remnant, compared with standard hepatic resection. Several attempts to implement this strategy in the 1960s, 1970s, and 1980s led to poor results, and as such transplantation for both primary and metastatic tumors was largely abandoned. In 1996, Mazzaferro and colleagues reported a novel strategy for surgical treatment of hepatocellular carcinoma—performing liver transplants in cirrhotic patients with early-stage malignancy.In their study, liver transplantation was evaluated in 48 patients with HCC, apparently meeting the preset criteria of either one tumor < 5 cm or up to three tumors < 3 cm, the now called Milan criteria. This approach has markedly changed organ allocation and established standardized indications for transplant, with excellent long-term results. More than 60 percent of liver transplant patients with advanced liver cancer are still alive after five years, compared to nearly zero survival for those patients who did not undergo transplant, In addition to the favorable five-year survival rates, the survival rates have increased steadily over the last decade, suggesting that criteria for patient selection established by other experts may assist physicians in selecting those patients most likely to respond well to the procedure.

The survival ratefollowing transplantation is both significantly better than with hepatic resection and comparable with the survival rate following liver transplantation for other indications. Milan criteria is most commonly used to determine the candidature of a patient with HCC for performing liver transplant. Detection of HCC in the cirrhotic liver provides a seemingly highly appropriate indication for LDLT. Since hepatic dysfunction in these individuals is typically modest, the transplant can be planned as a semi-elective procedure, yet more expeditiously

than is usually possible with deceased-donor transplantation. LDLT appeared to provide a distinct advantage over deceased-donor liver transplantation. Survival rates for patients undergoing LDLT versus deceased-donor liver transplantation were 86% and 71% (at 1 year) and 68% and 42% (at 5 years), respectively.

It is a common perception that the Milan criteria may be too stringent and may be excluding some patients who might benefit from the procedure from consideration for transplantation. Several other guidelines are available, more popular amongst these are the UCSF guidelines.UCSF criteria (one tumor < 6.5 cm, three or fewer nodules with the largest lesion < 4.5 cm and total diameter < 8 cm) has shown results comparable with that in the patients undergoing transplantation based on the Milan criteria.

Hilar Cholangiocarcinoma

Initial experience in patients undergoing Liver Transplantation for Cholangiocarcinoma was unsatisfactory due to early disease recurrence and poor long term survival. Treatment of patients with hilar Cholangiocarcinoma by liver transplantation has gained attention in recent years. Neoadjuvant chemo radiation in combination with liver transplantation for highly selected patients with hilar Cholangiocarcinoma has shown impressive results with 5-year survival rates of approximately 76% to 82%. This is similar to other standard indications for liver transplantation, including hepatocellular carcinoma. The Mayo Clinic has published data on the largest series of patients with hilar Cholangiocarcinoma to have undergone liver transplantation. Rigorous diagnostic criteria have been implemented to ensure the best outcome including tumor size less than 3 cm in radius, the findings of a malignant-appearing stricture confirmed by biopsy or cytology, an elevated CA 19-9 level more than 100 IU/mL, or evidence of aneuploidy in tissue samples. Unresectability is predicated based on technical considerations or the presence of intrinsic underlying liver disease. Exclusion of regional lymph node and peritoneal involvement is required by operative staging after completion of Neoadjuvant therapy.The protocol includes pretransplant external-beam irradiation followed by transcatheter irradiation and 5-fluorouracil (5-FU) followed by oral Capecitabine. An exploratory laparotomy is performed to exclude extrahilar lymph node disease, following which the patient is activated on the waiting list.

Hepatic Epitheloid Hemangioendothelioma

Epitheloid hemangioendothelioma is a disease affecting mainly younger females and resulting from a malignant transformation of vascular endothelium. An association with oral contraceptives has been suggested but not completely established. Clinical presentation may be with abdominal pain, but more frequently the lesion is an incidental finding. Since the tumor is often widespread within the parenchyma, complete resection may not be possible, even in the non-cirrhotic liver. The results after liver transplantation are quite acceptable, being comparable with those after OLT for viral-induced cirrhosis.

Hepatoblastoma

Hepatoblastoma is the most common malignant tumor of the liver in the pediatric population, affecting mostly young boys age less than 3 years and accounting for 75% of primary liver tumors in childhood. Diagnosis is usually at a late stage. The introduction of chemotherapy with cisplatin and doxorubicin has changed the treatment success of hepatoblastoma substantially, and despite a large tumor mass at presentation, a combined surgical and chemotherapeutic approach has yielded a 5-year survival rate of approximately 80%. Liver transplantation plays a role in those patients whose tumors cannot be completely resected after appropriate chemotherapy. The most complete report of liver transplantation was published by Otte et al. who reviewed the results of 147 patients from several European pediatric centers. The overall survival rate at 6 years post-transplantation was 82% in patients who had not undergone pretransplant-attempted liver resections, versus 30% at 6 years for patients who underwent liver transplantations after failed resections.

Metastatic Neuroendocrine And Colorectal Cancers

Neuroendocrine tumors are usually hormone producing (serotonin, insulin, gastrin, glucagon, etc.), but also may present as a nonfunctioning mass lesion. The clinical presentation is diverse, depending upon the hormone secreted. These tumors typically metastasize to the liver, and some patients note pain, resulting from capsule distention, as a first symptom. Even after metastasizing, these tumors often remain slow growing so that approximately one-third of the patients survive for 5 years after the development of liver metastases. Because of the somewhat indolent nature of their liver metastases, these patients are considered appropriate candidates for liver transplantation. Liver resection resulted in a 5-year survival rate of 67%, but a disease-free survival rate of only 29%. Liver transplantation resulted in a 5-year survival rate of 70% and recurrence-free survival rate of 53%.Patients with hepatic metastases from neuroendocrine tumors may have prolonged survival, especially under the ideal selection criteria: age less than 46 years, limited liver tumor burden with favorable histology, and no extra hepatic disease. Such patients often have good overall survival and quality of life.

Transplantation for metastatic liver diseasesecondary to colorectal metastasis is currently a controversial subject. In the pilot study from the Oslo Transplant Center, Hagness et al reported their experience with liver transplantation in 21 patients performed over a 4.5-year time interval. The 5-year overall survival rate was 60%, with a 1-year disease-free survival rate of 35% and no patients had long-term disease-free survival. The status of Liver Transplantation for Colorectal metastasis to the Liver at this time is investigational.