[13-20] Conveniently, some authors have asserted that anti-VEGF had a protective effect based on the result that VEGF is one of the causative cytokines for SOS.[24, 49] On the other hand, another report has asserted that the inhibition of VEGF receptors had an adverse effect on liver regeneration in the murine experimental model. Clinically, Aussilhou et al. demonstrated that bevacizumab impaired hypertrophy of the future remnant liver after portal

vein embolization, particularly in patients who received six cycles or more of bevacizumab treatment, and warned that major liver resection should be considered with caution in patients who have received bevacizumab.[50] Most recently, encouraging data has been published HM781-36B purchase based on hepatic volumetric analysis of bevacizumab-treated patients who underwent hepatectomy.[51] This study included 41 patients who underwent major hepatectomy (≥3 segments) with more than four cycles of neoadjuvant chemotherapy including less than 3 months of bevacizumab treatment and compared the matched 41 patients administrated the equivalent systemic chemotherapy without bevacizumab. In preoperative characteristics, patients with bevacizumab received a median of six cycles of chemotherapy that was discontinued for a median of 52 days before hepatic resection (median

cessation interval of bevacizumab, 65 days). As a result, postoperative liver regeneration was not influenced by the type of hepatic resection, the number find more of courses of chemotherapy (≥6 cycles or ≥10 cycles) or age factor Metalloexopeptidase (>65 years old), and no intergroup differences in overall morbidity or postoperative liver failure were observed. Our experimental study with rats also revealed that preoperative bevacizumab (7 days before hepatectomy) administration significantly

increased liver regeneration, and induced heat shock protein 70 mRNA, which had protective effects for organ injury, just before hepatectomy (Fig. 2). Actually, several reports are beginning to emerge on the safety and efficacy of bevacizumab in patients treated with preoperative chemotherapy and surgical treatment (Table 4).[30, 35, 37, 52-57] Most investigators have indicated that bevacizumab reduced the severity of SOS as well as decreased the incidence of SOS induced by preoperative chemotherapy, and did not increase the risk of morbidity and mortality. Ribero et al. first reported the protective effect of bevacizumab for grade 2–3 SOS in patients receiving bevacizumab preoperatively in patients receiving chemotherapy with 5-FU and L-OHP.[30] Kesmodel et al. also reported a surgical series analyzing the safety of preoperative chemotherapy including bevacizumab.