Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis Laura Rubbia-Brandt, Gregory Y Lauwers, 1 Huamin Wang, 2 Pietro E Majno, 3 Kenneth Tanabe, 4 Andrew X Zhu, 5 Catherine Brezault, 6 Olivier Soubrane, 7 Eddie K Abdalla, 8 Jean-Nicolas Vauthey, 8 Gilles Mentha 3 & Benoit Terris 9 Division of Pathology, Geneva University Hospital, Geneva, Switzerland, 1 Division of Pathology, Massachusetts General Hospital, Boston, MA, 2 Department of Pathology, M. D. University of Texas Anderson Cancer Center, Houston, TX, USA, 3 Division of Visceral and Transplantation Surgery, Geneva University Hospital, Geneva, Switzerland, Divisions of 4 Surgical Oncology and 5 Oncology, Massachusetts General Hospital, Boston, MA, Divisions of 6 Gastroenterology and 7 Surgery, Ho ˆpital Cochin, Paris, France, 8 Department of Surgical Oncology, M. D. University of Texas Anderson Cancer Center, Houston, TX, USA, and 9 Division of Pathological Anatomy, Ho ˆpital Cochin, and Universite ´ Paris Descartes, Paris, France Date of submission 25 March 2009 Accepted for publication 17 August 2009 Rubbia-Brandt L, Lauwers G Y, Wang H, Majno P E, Tanabe K, Zhu A X, Brezault C, Soubrane O, Abdalla E K, Vauthey J-N, Mentha G & Terris B (2010) Histopathology 56, 430–439 Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis Aims: Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxa- liplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist’s perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage. Methods and results: The spectrum of oxaliplatin-asso- ciated liver lesions was investigated in a multi-institu- tional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moder- ate ⁄ severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal ⁄ venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX ⁄ bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an inci- dence of moderate ⁄ severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular ⁄ venular fibrosis (31.4% versus 52%, respectively) (P < 0.001). Conclusions: Pathologists should be aware of the dis- tinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multi- disciplinary management of CRLM. Address for correspondence: L Rubbia-Brandt, MD, PhD, Service de Pathologie Clinique, Ho ˆpitaux Universitaires de Gene `ve, 1 rue Michel Servet, 1211 Geneva Switzerland. e-mail: laura.rubbia-brandt@hcuge.ch Ó 2010 The Authors. Journal compilation Ó 2010 Blackwell Publishing Limited. Histopathology 2010, 56, 430–439. DOI: 10.1111/j.1365-2559.2010.03511.x