Chemotherapy hepatotoxicity : histologic injury and impact on motbility after hepatectomy for colorectal cancer liver metastases

Abstract

Introduction: Advances on neoadjuvant chemotherapy (NCT) have allowed surgical treatment in otherwise unresectable patients with colorectal liver metastases (CRLM). It is well known that NCT induces liver lesions such as sinusoidal obstruction syndrome (SOS) and steatohepatitis (SH). However, whether it affects postoperative morbidity remains controversial. The aim of this study was both to evaluate the impact of NCT on liver parenchyma and postoperative morbidity and to identify preoperative predictive markers for liver injury. Patients and Methods: Among 140 patients undergoing liver resection for CRLM between 2010 and 2013, 70 underwent systemic NCT. Liver function tests, pathology, postoperative morbidity and mortality were compared between the two groups. Results: Univariate analysis revealed NCT as a cause of sinusoidal dilation (p=0.09), peliosis (p=0.028), NRH (p=0.049) and moderate to severe SOS (p=0.004) and bevacizumab as a protective agent against moderate to severe SOS (p=0.045). Diabetic patients were identified as having a lower incidence of sinusoidal dilation (p=0.034). Multivariate analysis confirmed sinusoidal dilation as an independent cause for morbidity (p=0.02) and liver-specific complications (p=0.016). Preoperative level of GGT was identified as predictive factor for moderate to severe SOS and peliosis (p<0.001 and p=0.004, respectively). Conclusion: The administration of NCT induces SOS lesions, but can be partially prevented by bevacizumab. Sinusoidal dilation is an individual cause of postoperative morbidity. Preoperative GGT level can be used to predict the presence of SOS