The impact of bevacizumab on liver regeneration following hepatectomy in rats.

Abstract

228 Background: In our clinical data, we had the interesting findings that the pathologic sinusoidal obstruction syndrome and serum hyaluronic acid after neoadjuvant oxaliplatin-associated chemotherapy for liver metastatic colorectal cancer with bevacitumab (Bev) was ameliorated compared to those without Bev. The purpose of this study was to investigate the influence of bevacizumab administration on regenerating liver in rat 70% and 90% hepatectomy (Hx) model as a surrogate model of human massive hepatectomy for liver metastatic colorectal cancer. Methods: Male Wister rats weighing 180-230g were divided into the following four groups: 70%Hx, 70%Hx + Bev, 90%Hx and 90%Hx+Bev group. The rats were pretreated with intraperitoneal administration of bevacizumab (5mg/kg) 7 days before hepatectomy. The remnant liver and blood samples were taken one day after hepatectomy, and the following parameters were evaluated: blood analysis (AST, ALT, LDH, T- Bil, and hyaluronic acid), liver weight to body weight (Lw/Bw) ratio, and postoperative survival rate for three days. Results: In the 70%Hx model, there was no significant difference between the 70%Hx group and 70%Hx + Bev group in blood analysis one day after hepatectomy; AST (1928 vs. 923 IU/L), ALT (1282 vs. 670 IU/L), T-Bil (0.17 vs. 0.19 mg/dl), LDH (3822 vs. 2967 U/L) and hyaluronic acid (995.7 vs. 1026.6 ng/ml) and in Lw/Bw ratio (1.78 vs. 1.84). In 90%Hx model, AST and ALT of blood analysis in 90%Hx+Bev group significantly decreased compared to those in 90%Hx group; AST (3428 vs. 4995 IU/L, P<0.05), ALT (1471 vs. 2287 IU/L, P<0.05), T-Bil (1.94 vs. 2.57 mg/dl), LDH (3229 vs. 5351 U/L) and hyaluronic acid (3865.7 vs. 7862.2 ng/ml). The Lw/Bw ratio in 90%Hx+Bev group significantly increased compared to that in 90%Hx group (0.80 vs. 0.67, P<0.05). The postoperative survival rate in 90%Hx+Bev group showed tendency to improve compared to that in 90%Hx group (75% vs. 50%, P=0.19). Conclusions: The administration of bevacizumab seven days before hepatectomy did not significantly affect the liver functions and liver regeneration rate. These findings suggest that hepatectomy might be safe and feasible after the use of bevacizumab. No significant financial relationships to disclose.