Liver failure after extended hepatectomy represents a major challenge in the surgery of hepatic colorectal metastasis. A previous study has indicated that inhibition of phosphodiesterase type 3 (PDE 3) stimulates liver regeneration. However, little is known whether PDE 3 inhibitors, such as cilostazol, also stimulate the growth of remnant metastases. Therefore, we herein studied the effect of cilostazol on engraftment, vascularization and growth of colorectal liver metastasis after major hepatectomy. WAG-rats underwent either major hepatectomy or sham operation. Metastases were induced by subcapsular implantation of 5 × 10(5) CC531-colorectal cancer cells. Animals were daily treated with cilostazol (5 mg/kg body weight) or glucose solution. Tumor growth was measured by high-resolution ultrasound at days 7 and 14. Tumor vascularization and tumor cell proliferation were determined by immunohistochemistry and western blotting. High-resolution ultrasound analysis in hepatectomized and non-hepatectomized animals showed that cilostazol does not stimulate tumor growth. Accordingly, the number of PCNA-positive tumor cells did not differ between cilostazol-treated animals and sham-treated controls. Interestingly, cilostazol reduced tumor vascularization in both hepatectomized and non-hepatectomized animals. This was indicated by a significantly lower number of platelet-endothelial cell adhesion molecule (PECAM-1)-positive cells in tumors of cilostazol-treated animals compared to sham-treated controls. The PDE 3 inhibitor cilostazol does not stimulate the growth of colorectal metastases during liver regeneration after major hepatectomy.

译文

扩大肝切除术后的肝衰竭是肝结直肠转移手术中的主要挑战。先前的研究表明,抑制3型磷酸二酯酶 (PDE 3) 可刺激肝再生。然而,尚不清楚PDE 3抑制剂 (例如西洛他唑) 是否也刺激残余转移的生长。因此,我们在此研究了西洛他唑对大肝切除术后结直肠肝转移的植入,血管形成和生长的影响。WAG-大鼠接受了主要的肝切除术或假手术。通过5 × 10(5) CC531-colorectal癌细胞的包膜下植入诱导转移。每天用西洛他唑 (5 mg/kg体重) 或葡萄糖溶液处理动物。在第7天和第14天通过高分辨率超声测量肿瘤生长。通过免疫组织化学和western印迹法确定肿瘤血管形成和肿瘤细胞增殖。肝切除和非肝切除动物的高分辨率超声分析表明,西洛他唑不会刺激肿瘤生长。因此,在西洛他唑处理的动物和假治疗的对照组之间,PCNA阳性肿瘤细胞的数量没有差异。有趣的是,西洛他唑减少了肝切除和非肝切除动物的肿瘤血管形成。与假治疗的对照组相比,在西洛他唑治疗的动物的肿瘤中血小板-内皮细胞粘附分子 (PECAM-1) 阳性细胞的数量明显减少,表明了这一点。PDE 3抑制剂西洛他唑不会刺激大肝切除术后肝再生过程中结直肠转移瘤的生长。

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