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The Place of Liver Transplantation in the Treatment of Hepatic Epitheloid Hemangioendothelioma: Report of the European Liver Transplant Registry

Lerut, Jan P. MD, PhD*; Orlando, Giuseppe MD*; Adam, Rene MD, PhD; Schiavo, Marcello MD; Klempnauer, Jurgen MD§; Mirza, Darius MD; Boleslawski, Emmanuel MD; Burroughs, Andrew MD, PhD**; Sellés, Carlos Fernandez MD††; Jaeck, Daniel MD††; Pfitzmann, Robert MD§§; Salizzoni, Mauro MD¶¶; Söderdahl, Gunner MD∥∥; Steininger, Rudi MD***; Wettergren, Andre MD†††; Mazzaferro, Vincenzo MD†††; Le Treut, Yves Patrice MD‡‡‡; Karam, Vincent PhDEuropean Liver Transplant Registry

doi: 10.1097/SLA.0b013e31815c2a70
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Background: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up.

Material and Methods: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7–369) from moment of diagnosis and a median of 78.5 (range, 1–245) from the moment of LT.

Results: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6–98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion.

Conclusions: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

This is the first large study with long-term follow-up to focus on the value of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma, a rare vascular hepatic disorder. The results suggest a more aggressive attitude toward hepatic epitheloid hemangioendothelioma seems to be warranted after a thorough staging of the disease. This attitude remains valid even in the presence of close (lymph nodes) or distant extrahepatic disease localization.

From the *Abdominal Transplant Unit, University Hospitals St. Luc, Brussels, Belgium; †Centre Hépatobiliaire Paul Brousse, Paris, France; ‡Istituto Nazionale Tumori, Milano, Italy; §Medizinsche Hochschule Hannover, Hannover, Germany; ¶Queen Elizabeth Hospital, Birmingham, UK; ∥Hôpital Pitié Salpétrière, Paris, France; **Royal Free Hospital, London, UK; ††Hospital Juan Canalejo, La Coruna, Spain; ‡‡Hôpital Hautepierre, Strasbourg, France; §§Charité Campus Virchow Klinikum, Berlin, Germany; ¶¶Azienda Ospedaliera S. Giovanni Battista, Torino, Italy; ∥∥Karolinska University Hospital, Huddinge, Stockholm, Sweden; ***Transplantationszentrum Universität, Wien, Austria; †††Rigshospitalet, Copenhagen, Denmark; and ‡‡‡Hôpital de la Conception, Marseille, France.

The ELTR is supported in part by a grant from Astellas, Novartis and Roche and logistic support of the Paul Brousse Hospital-Assistance Publique, Hôpitaux de Paris (FR). The ELTR is a service of ELITA.

The order of the authors is determined following the guidelines for publication approved by the boards of European Liver and Intestinal Transplant Association (ELITA) and European Liver Transplant Registry (ELTR) and according to the number of transplantations recorded in the ELTR.

Reprints: Jan P. Lerut, MD, PhD, FACS, Department of Abdominal Surgery and Transplantation, Abdominal Transplant Unit, STARZL Room, Cliniques Universitaires St. Luc, Avenue Hippocrates 10, 1200 Brussels, Belgium. E-mail: lerut@chir.ucl.ac.be.

© 2007 Lippincott Williams & Wilkins, Inc.