Resection Versus Transplantation for Liver Metastases From Neuroendocrine Tumors J. Coppa, A. Pulvirenti, M. Schiavo, R. Romito, P. Collini, M. Di Bartolomeo, A. Fabbri, E. Regalia, and V. Mazzaferro L IVER metastases from neuroendocrine tumors (NET) is the main cause of death for patient with neuroen- docrine tumors originating from the intestine and pancreas. In about 90% of patients, the distribution of liver metasta- ses is multifocal and bilateral so that curative liver resection is feasible in no more than 20% of the referred cases. 1–3 Large liver metastases often cause hormone-related symp- toms (carcinoid syndrome) with severe consequences on patient quality of life. 4 Both surgical and medical treat- ments have been proposed for patients with liver metastases from NET (systemic and intraarterial chemotherapy, soma- tostatin analogues, interferon therapy) with cumulative patient survival not exceeding 25 to 35% at five years. 1,5 Resective surgery with curative intent has been associated with an improved 5 year survival in nearly 50% of cases, but the number of eligible patients is low. 2 Total hepatectomy and liver transplantation (OLT) has been advocated for patients with bilateral unresectable symptomatic liver me- tastases from NET although a clear consensus on stage of disease, pathological subtypes, and patient conditions ame- nable of transplant candidacy are still lacking. 6,7 In this report, we describe our experience with 29 pa- tients affected by liver metastases from NET who were treated with either hepatic resections or liver transplanta- tion. Pre-transplantation selection criteria currently applied in our centre are also proposed. PATIENTS AND METHODS During the 12 year period from January 1987 to December 1999, 331 patients with a confirmed histological diagnosis of hepatic metastases from NET were seen at the National Cancer Institute of Milan, Italy, with 55 of those cases (16.6%) referred for possible surgical treatment. After a complete work-up, the disease was judged unresectable in 26 patients (48% of the series) whether at pre-operative stage (n = 9) or at laparotomy (n = 17). The remaining 29 patients (52% of the referred surgical group) under- went liver surgery with curative intent. Out of 29 cases there were 20 hepatic resection (36%) and 9 liver transplant (16%). The main characteristics of the patients gathered in each group are summarized in Table 1. Chemotherapy was given either before or after surgery in a total of 19 patients, according to different treatment protocols based on combinations of 5-fluorouracil, dacarbazine, doxorubicin, and cisplatin (Table 1). In 6 cases, specific somatostatin analogs (mainly octreotide) were also added at various stages of follow-up. All patients were followed in our outpatient clinic during follow- up. Selection Criteria for OLT Patients with non-resectable disease were considered suitable candidates for OLT if they complied with the following criteria: a) confirmed carcinoid histology (excluding non carcinoid primary tumors), b) primary tumor drained by the portal system (excluding tumors with systemic venous drainage), c) 50% hepatic replace- From the Department of Surgery, Liver Transplantation Unit, Department of Pathology, and Department of Medical Oncology, National Cancer Institute, Milan, Italy. Supported by the Italian Association for Cancer Research (AIRC). Address reprint requests to Dr Vincenzo Mazzaferro, Chirurgia Generale 1, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan—Italy. Table 1. Main Characteristics of the 29 Patients With Metastatic Hepatic NET Treated With Liver Resection (n  20) or liver transplantation (n  9). Liver Resection (20 cases) Orthotopic Liver Transplantation (9 cases) Age (median, range) 1 (29 – 66) 33 (14 –53) M/F 9/11 4/5 CAR/NCAR 18/2 9/0 Venous drainage of primary tumor Portal (pancreas-ileum) 12 (60%) 9 (100%) Systemic (lung-rectum) 8 (40%) — Presence of carcinoid syndrome 4 (20%) 3 (33%) Percentage of liver involvement 50% 19 (95%) 7 (78%) 50% 1 (5%) 2 (22%) Treatment schedule with chemotherapy 4 (20%) 9 (9/9) Treatment plan including chemotherapy 10 — Chemo 3 surg 3 chemo 3 — Surgery 3 chemo 5 — Chemo 3 surg 2 9 Treatment plan excluding chemotherapy Surgery alone 10 — CAR, carcinoid; MCAR, noncarcinoid apudomas: one gastrinoma and one pancreatic neuroendocrine carcinoma © 2001 by Elsevier Science Inc. 0041-1345/01/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(00)02586-0 Transplantation Proceedings, 33, 1537–1539 (2001) 1537