Liver transplantation for metastases of neuroendocrine tumors is still a subject of ... an individual basis with particular emphasis on the tumor biology.
Review
Liver transplantation for neuroendocrine tumors: review of the literature and future perspectives
Liver transplantation for metastases of neuroendocrine tumors is still a subject of controversial discussion. Over the years, more and more data have been collected to demonstrate that transplantation is feasible and contributes to long-term overall survival. Most data are of retrospective nature and, thus, it is difficult to draw definitive conclusions. Over the years, indications, surgical technique and perioperative care have improved. The most recent data have been collected prospectively and show a very favorable outcome in selected patients. Liver transplantation should be considered in patients with neuroendocrine liver metastases, but the decision needs to be made on an individual basis with particular emphasis on the tumor biology. In the future, we may need to work more with living organ donation and perhaps, especially in Europe, think about challenging the scoring system model of end-stage liver disease for this indication.
Christine Wurst1, Karin Jandt1, Silke Schuele1, Falk Rauchfuß1 & Utz Settmacher*,1 1 University of Jena, Department of General Visceral & Vessel Surgery, Erlangerallee 101, 07740 Jena, Germany *Author for correspondence: utz.settmacher@ med.uni-jena.de
Keywords: liver transplantation • neuroendocrine • metastasis
Neuroendocrine tumors (NETs) are a rare and heterogeneous entity. The incidence is 2% of all malignancies with rising tendency [1] . The major part of these tumors originates from the pancreas or the small bowel. At the time of diagnosis there are metastases in 50–75% of patients [2] . If NETs develop metastases, the liver is the most frequently affected organ. The treatment strategy for NET metastases of the liver is complex and includes biological and targeted therapy, systemic chemotherapy, local ablative procedures, radionuclide therapy and partial liver resection or hepatectomy and transplantation. Liver transplantations (LTs) have been performed for over 20 years in patients with nonresectable liver metastases from NETs. Individual case reports and small case series have been published by the respective centers. LT is an accepted treatment option worldwide because contrary to other solid tumors that metastasize into the liver, NETs progress slowly, they are often well differentiated and the long-term outcomes are good. The heterogeneity of the
10.2217/IJE.14.8 © 2014 Future Medicine Ltd
individual tumors and the absence of a prospective comparison of LT versus other treatment options still make it difficult to assess the impact of LT for this indication. Current results & consequences In the 1990s, the first reports about LT as a treatment option for NET metastases were published. Bechstein et al. had compiled the data of 30 patients from the literature [3] . The long-term results of the observed survival up to 36 months post-transplant were reported. Approximately half of the 1-year mortality was due to transplant-associated complications and the other half was due to NET recurrence [3] . The 1-year survival was 52% in 1994. Over time and also depending on the individual centers, there was no uniform decision-making for LT for NET metastases. Tumor characteristics on one hand and the possibilities, as well as the limitations of organ allocation on the other hand play an important role. Hepatomegaly, nonresectability by partial liver resection, oncological
Int. J. Endo. Oncol. (2014) 1(2), 195–201
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Review Wurst, Jandt, Schuele, Rauchfuß & Settmacher resection with R0 intention or simply tumor debulking, particularly in symptomatic patients were the primary indications for LT. The results after LT changed with improved surgical technique and perioperative care, as well as with the introduction of criteria for patient selection (Box 1) . The 5-year survival is in some cases better than that of patients who have been transplanted for hepatocellular carcinoma (HCC) in cirrhosis with a low tumor burden (within the Milan criteria), but slightly inferior than in patients with benign underlying disease. Many transplanted patients develop recurrent metastases and die in the long term from tumor metastases after transplantation. It is still not clear which patients benefit from LT in the long run. For this reason, many centers have introduced early different selection criteria for LT listing. The use of different selection criteria, however, makes it difficult to evaluate and to compare the results after transplantation. With their experience from their first patients, the group of Mazzaferro recommended to transplant only patients below the age of 50 years with or without symptoms of hormone production of the lesions, and with the primary tumor drained by the portal system and resected prior to transplantation. The disease should have been stable for 6 months prior to transplantation [4] . These criteria have been further refined and currently are as follows [5] : Inclusion criteria: • Confirmed histology of carcinoid tumor (low-grade NETs) with or without syndrome; • Primary tumor drained by the portal system (pancreas and intermediate gut: from distal stomach to sigmoid colon) removed with a curative resection (pretransplant removal of all extrahepatic tumor deposits) through surgical procedures different and separate from transplantation; • Metastatic diffusion to liver parenchyma
