However, these benefits are taken against the risks of chemotherapy induced parenchymal damage including steatosis, steatohepatitis, and sinusoidal obstruction (SOS). Steatosis (fatty liver disease) is most recognized in alcoholic hepatitis and nonalcoholic fatty liver disease (NAFLD). This pathology is represented macroscopically as a yellow liver, and histologically Inhibitors,research,lifescience,medical by retained lipid in micro and macrovesicles, altering the normal architecture of hepatocytes and their associated function (62). Steatohepatitis represents progression of steatosis, presumably from oxidative stress

which causes lipid peroxidation and the development of necrotizing inflammation and unregulated hepatocellular apoptosis (63-65). Sinusoidal obstruction syndrome (SOS) represents the endpoint of progression of chemotherapy toxicity. Microscopically this condition is represented by edema of central zone hepatocytes and fibrosis and

congestion of the sinusoids (66-68). 5-Fluorouracil (5-FU) alone has been reported to induce steatosis Inhibitors,research,lifescience,medical in 40-47% of patients (69-71). Addition of the platinum based agents like oxaliplatin or the topoisomerase inhibitor irinotecan has also shown to have hepatic toxicity with oxaliplatin being independently Inhibitors,research,lifescience,medical associated with steatohepatitis and irinotecan with SOS (65). The addition of the anti-VEGF antibody bevacizumab Inhibitors,research,lifescience,medical has increasing adoption as a chemotherapeutic and it is found to have a protective effect against oxaliplatin induced SOS (72). Taking into account neoadjuvant chemotherapy toxicities, multiple groups have examined perioperative outcomes as they relate to steatosis, steatohepatitis, and SOS (Table 2). Patients with steatosis after chemotherapy and Inhibitors,research,lifescience,medical eventual hepatectomy are predisposed to increased post-operative complications, but without increased Sirtuin pathway mortality

(75-77). For patients with steatohepatitis, there is a more significant effect on post operative liver function and patient survival following resection (65). Fewer studies have directly examined SOS as a perioperative risk factor, but as described earlier, the venous congestion in this condition predisposes to risk of transfusion, and likely the detrimental effects of transfusions are Chlormezanone consequently involved (78). Table 2 Demonstration of hepatic parenchymal injury after chemotherapy for metastatic colorectal cancer. While many groups have examined these histopathologies as they relate to perioperative outcomes, there is little consensus on the time interval between neoadjuvant therapy and hepatectomy and duration of chemotherapy. Welsh et al. showed that patients with a history of neoadjuvant chemotherapy had increased post-operative complications, with a duration of greater than five weeks protecting against complications (79). Karoui et al.