Cilostazol improves the prognosis after hepatectomy in rats with sinusoidal obstruction syndrome.

Abstract

Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model. Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS+CZ (MCT+CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48h after MCT administration. Postoperative survival rates were evaluated (n=9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury. The cumulative 10-day postoperative survival rate was significantly higher in the SOS+CZ group than in the SOS group (88.9% vs 33.3%, P=0.001). Total SOS scores were significantly lower in the SOS+CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS+CZ group than in the SOS group on POD 1 (86.1±8.2% vs 63.8±9.3%, P=0.003). Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.