C P H Vreuls1, A Driessen2, S W M Olde Damink3, G H Koek4, H Duimel5, M A J van den Broek6, C H C Dejong6, F Braet5, E Wisse7. 1. Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Pathology, Amphia Hospital, Breda, The Netherlands. Electronic address: celienvreuls@hotmail.com. 2. Department of Pathology, Antwerp University Hospital, Edegem, Belgium; University of Antwerp, Antwerp, Belgium. 3. Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, and GROW: School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of HPB Surgery, Royal Free Hospital, London, United Kingdom. 4. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM, School for Nutrition, Toxocology and Metabolism, Maastricht, The Netherlands. 5. Maastricht Multimodal Molecular Imaging Institute, Division of Nanoscopy, University of Maastricht, The Netherlands. 6. Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, and GROW: School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. 7. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM, School for Nutrition, Toxocology and Metabolism, Maastricht, The Netherlands; Maastricht Multimodal Molecular Imaging Institute, Division of Nanoscopy, University of Maastricht, The Netherlands; School of Medical Sciences (Discipline of Anatomy and Histology) - The Bosch Institute and Australian Centre for Microscopy & Microanalysis, The University of Sydney, Australia.
Abstract
AIMS: Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). METHODS AND RESULTS: Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. CONCLUSION: Sinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings.
AIMS: Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of humanSOS, using both light microscopy (LM) and electron microscopy (EM). METHODS AND RESULTS: Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. CONCLUSION: Sinusoidal endothelial cell detachment was present in humanSOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings.