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

Hiroaki Sugita; Shinichi Nakanuma; Seiichi Munesue; Tatsuya Ishikawa; Tomokazu Tokoro; Ryohei Takei; Mitsuyoshi Okazaki; Kaichiro Kato; Satoshi Takada; Isamu Makino; Noriyuki Ozaki; Yasuhiko Yamamoto; Shintaro Yagi

doi:10.1111/jgh.16508

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

J Gastroenterol Hepatol. 2024 Feb 13. doi: 10.1111/jgh.16508. Online ahead of print.

Affiliations

¹ Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University, 13-1 Takara-Machi, Kanazawa, 920-8641, Japan.
² Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
³ Department of Functional Anatomy, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.

PMID: 38348885
DOI: 10.1111/jgh.16508

Abstract

Background and aim: 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.

Material and methods: 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 48 h 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.

Results: 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).

Conclusion: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS.

Keywords: Cilostazol; Hepatectomy; Liver sinusoidal endothelial cells; Prognosis; Sinusoidal obstruction syndrome.