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Liver Transplantation for Neuroendocrine Tumors in Europe—Results and Trends in Patient Selection: A 213-Case European Liver Transplant Registry Study

Le Treut, Yves Patrice MD*; Grégoire, Emilie MD*; Klempnauer, Jürgen MD; Belghiti, Jacques MD; Jouve, Elisabeth MSc*; Lerut, Jan MD, PhD, FACS§; Castaing, Denis MD; Soubrane, Olivier MD; Boillot, Olivier MD, PhD**; Mantion, Georges MD, PhD††; Homayounfar, Kia MD‡‡; Bustamante, Manuel MD§§; Azoulay, Daniel MD, PhD‖‖; Wolf, Philippe MD, PhD¶¶; Krawczyk, Marek MD***; Pascher, Andreas MD, PhD, MBA, FEBS†††; Suc, Bertrand MD‡‡‡; Chiche, Laurence MD, PhD§§§; de Urbina, Jorge Ortiz MD, FACS‖‖‖; Mejzlik, Vladimir MD¶¶¶; Pascual, Manuel MD****; Lodge, J. Peter A. MD, FRCS††††; Gruttadauria, Salvatore MD, PhD, FACS‡‡‡‡; Paye, François MD, PhD§§§§; Pruvot, François-René MD, PhD‖‖‖‖; Thorban, Stefan MD, FACS¶¶¶¶; Foss, Aksel MD, PhD*****; Adam, René MD, PhDFor ELITA

doi: 10.1097/SLA.0b013e31828ee17c

Objective: The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period.

Background: LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases.

Methods: This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1–149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures.

Results: Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT.

Conclusions: LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

This retrospective multicentric study describes a cohort of 213 patients who underwent liver transplantation for neuroendocrine tumors in 35 centers from 11 European countries between 1982 and 2009. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to transplantation, poor tumor differentiation, and hepatomegaly. Long-term outcome significantly improved over time, in relation with changing patient selection criteria by surgical teams.

*Hôpital La Conception, Marseille, France

Medizinische Hochschule, Hannover, Germany

Hôpital Beaujon, Clichy, France

§Cliniques Universitaires St Luc, Brussels, Belgium

Hôpital Paul Brousse, Villejuif, France

Hôpital Cochin, Paris, France

**Hôpital Edouard Herriot, Lyon, France

††Hôpital Jean Minjoz, Besançon, France

‡‡Georg August Universität, Göttingen, Germany

§§Complexo Hospitalario Universitario, Santiago de Compostela, Spain

‖‖Hôpital Henri Mondor, Créteil, France

¶¶Hôpital de Hautepierre, Strasbourg, France

***Medical University, Warsaw, Poland

†††Charité Campus Virchow-Klinikum, Berlin, Germany

‡‡‡Hôpital Rangueil, Toulouse, France

§§§Hôpital Côte de Nacre, Caen, France

‖‖‖Hospital de Cruces, Bilbao, Spain

¶¶¶Center of transplantation, Brno, Czech Republik

****CH Universitaire Vaudois, Lausanne, Switzerland

††††St James University Hospital, Leeds, United Kingdom

‡‡‡‡ISMETT, Palermo, Italy

§§§§Hôpital St Antoine, Paris, France

‖‖‖‖Hôpital Claude Huriez, Lille, France

¶¶¶¶Technische Universität, München, Germany

*****Rikshospitalet, Oslo, Norway.

Reprints: Pr. Yves Patrice Le Treut, MD, Aix-Marseille Université, Service de chirurgie générale et transplantation hépatique, Hôpital de La Conception, 147 Bd Baille, 13005 Marseille, France. E-mail:

Part of this work was presented at the International Liver Congress, Barcelona, April 19–22, 2012, and at the 10th World Congress of the International Hepato-Pancreato-Biliary Association, Paris, July 1–5, 2012.

Disclosure: The authors declare no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins.