Effect of bevacizumab on sinusoidal injury in patients receiving oxaliplatin-based chemotherapy and liver damage after massive hepatectomy in rats.

Abstract

276 Background: The aim of this study was to clarify impact of bevacizumab (Bev) on both hepatic sinusoidal injury after oxaliplatin (L-OHP)-based chemotherapy for metastatic colorectal cancer, and on liver regeneration after massive hepatectomy (Hx). Methods: <Study 1: Clinical> Fourteen patients who underwent Hx after receiving L-OHP-based chemotherapy for liver metastases from colorectal cancer were divided into two groups (Bev group (n=8) and No-Bev group (n=7)). Histology of non-cancerous liver tissue, blood chemistry such as hyaluronic acid (HA), spleen size, and postoperative complications were compared between the two groups. <Study 2: Experimental> Male Wister rats that underwent 90%-Hx were divided into two groups (Control group (n=7) and Bev group (n=7), in which Bev was injected intraperitoneally (5mg/kg) 7days before Hx). The following parameters were compared; blood chemistry, liver weight to body weight (Lw/Bw) ratio, and cytokines in liver tissues by RT-PCR, and survival rate. Results: <Study 1> Incidence of sinusoidal dilatation in Bev group was lower than that in No-Bev group (25% vs. 67%). Serum HA before Hx in Bev group (28 ng/ml).was lower than that in No-Bev group (155ng/ml). Spleen size in Bev group (174 ml) tended to be smaller than that in No-Bev group (252 ml). No significant postoperative complication was observed in Bev group, while 4 out of 7 patients had complications in No-Bev group. <Study 2> Liver damage such as ALT in Bev group (1471 IU/L) was smaller than that in Control group (2287 IU/L). Regeneration rate (Lw/Bw ratio) in Bev group was greater than that in Control group (0.80 vs. 0.67). Expression levels of IL-1β, MMP2 and MMP9 in Bev group tended to be lower than those in Control group. Survival rate at 72 hours after Hx in Bev group (83%) tended to be better than that in Control group (50%). Conclusions: Bev could reduce sinusoidal injury in patients with L-OHP-based chemotherapy, furthermore, Bev reduced liver injury and promoted liver regeneration after massive hepatectomy in rats. Those data strongly suggest Bev has beneficial effects for patients receiving L-OHP-based chemotherapy who undergo massive Hx.