SHORT REPORT Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases Celien P H Vreuls, 1 Maartje A Van Den Broek, 2,3 Alison Winstanley, 4 Ger H Koek, 5 Eddie Wisse, 6 Cornelis H Dejong, 2 Steven W M Olde Damink, 2,7 Fred T Bosman 8 & Ann Driessen 1 1 Department of Pathology, Maastricht University Medical Centre, Maastricht, the Netherlands, 2 Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands, 3 NUTRIM, School for Nutrition, Toxocology and Metabolism, Maastricht University, Maastricht, the Netherlands, 4 Department of Cellular Pathology, University College London, London, UK, 5 Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands, 6 Electron Microscopy Unit, Maastricht University Medical Centre, Maastricht, the Netherlands, 7 Department of HPB Surgery and Liver Transplantation, Royal Free Hospital, University College London, London, UK, and 8 Erasmus University Medical Center, Rotterdam, the Netherlands Date of submission 14 September 2011 Accepted for publication 14 November 2011 Vreuls C P H, Van Den Broek M A, Winstanley A, Koek G H, Wisse E, Dejong C H, Olde Damink S W M, Bosman F T & Driessen A (2012) Histopathology Hepatic sinusoidal obstruction syndrome (SOS) reduces the effect of oxaliplatin in colorectal liver metastases Aims: Oxaliplatin is an important chemotherapeutic agent used to reduce hepatic colorectal metastases, resulting in tumour reduction and permitting surgical resection. This treatment has significant side effects, as oxaliplatin can induce sinusoidal obstruction syndrome (SOS) in the non-tumour-bearing liver, resulting in increased morbidity. We hypothesized that SOS might impede hepatic perfusion, thereby interfering with the tumour environment and attenuate the response to the chemotherapy. Methods and results: From the prospective database of the Maastricht University Medical Centre we collected 50 patients with hepatic colorectal carcinoma metas- tases. All patients received neo-adjuvant oxaliplatin followed by partial hepatectomy. Metastases and non- tumour-bearing liver were studied histopathologically. Thirty-two of 50 (64%) patients showed SOS lesions, classified as mild (26%) and moderate–severe (38%). The response to treatment, as expressed in the tumour regression grade (TRG), was grade 1 (10%); grade 2 (14%); grade 3 (28%); grade 4 (32%) and grade 5 (16%). Statistical analysis showed that a higher grade of SOS was associated with a higher grade of TRG (P = 0.016). Conclusion: Developing SOS is associated with a lower tumour response to neo-adjuvant oxaliplatin treat- ment. Hepatic hypoperfusion due to sinusoidal obstruc- tion syndrome might induce hepatic hypoxia, diminishing the response to chemotherapy. Keywords: hypoxia, liver, oxaliplatin, sinusoidal obstruction syndrome, tumour regression grade Abbreviations: HIF, hypoxia-induced family; NRH, nodular regenerative hyperplasia; RECIST, response criteria in solid tumours; SEC, sinusoidal endothelial cells; SOS, sinusoidal obstruction syndrome; TRG, tumour regression grade Address for correspondence: C Vreuls, Department of Pathology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, the Netherlands. e-mail:celien.vreuls@mumc.com Ó 2012 Blackwell Publishing Limited. Histopathology 2012 DOI: 10.1111/j.1365-2559.2012.04208.x