术中腹腔氟尿嘧啶缓释剂不同留置方式对胃肠道恶性肿瘤患者疗效和安全性的影响

目的探讨术中腹腔氟尿嘧啶（5-FU）缓释剂不同留置方式对胃肠道恶性肿瘤患者腹腔药物浓度、术后并发症发生率及炎症和免疫指标的影响。方法将45例拟行开腹胃癌或结直肠癌根治性手术患者，按随机数字表法随机分为游离播撒组（15例）、固定留置组（15例）和对照组（14例）（1例不符合入组标准而剔除）。关腹前游离播撒组根据肿瘤部位将5-FU缓释剂600mg均匀播散于肿瘤切除创面至系膜根部淋巴结清扫创面；固定留置组除均匀播撒相同剂量的5-FU缓释剂外，在化疗粒子表面喷洒生物蛋白胶并加盖胶原蛋白海绵固定；对照组仅在创面喷洒生物蛋白胶并加盖胶原蛋白海绵覆盖。术前及术后第1、4、7、10天检测3组患者的血常规、肝肾功能、血清c反应蛋白（CRP）、白细胞介素6（IL-6）、T细胞亚群。术后第1、2．4、7天留取血液及腹腔引流液标本，检测5-FU血药浓度和组织液浓度。记录各组术后并发症。结果游离播撒组和固定留置组5-FU血药浓度均未达到高效液相色谱检测值下限。术后第4天，固定留置组患者血清CRP水平低于对照组[（60±29）mg／L比（1104-61）mg／L，P〈0．05]；术后各时间点3组血清IL-6水平差异无统计学意义（P≥0．05）；术后第1天，游离播撒组患者CD；和CD4细胞低于对照组[分别为（47±11）％比（60±13）％和（23±6）％比（34±13）％，P〈0．05]。3组患者术后并发症发生率差异无统计学意义（P〉0．05）。结论不同留置方式的5-FU缓释剂对患者术后腹腔引流液5-FU药物浓度无明显影响，腹腔内可维持高浓度5-FU超过7d；缓释化疗药物并未增加胃肠道癌术后并发症发生率；固定留置方式对机体炎症和免疫功能影响更小，具有较好的安全性。

Safety and effects of different type of intra-peritoneal implantation of sustained-releasing 5-fluorouracil in patients with gastrointestinal cancer

Objective To observe the change in the 5fluorouracil （5FU） concentration of abdominal cavi ty, rate of postoperative complications and immunomodulations of the patients with gastric or colorectal cancer after intraabdominal implantation of sustainedreleasing 5FU. Methods Fortyfive selected patients who underwent open radical gastroenterological surgery were randomly divided into 3 groups （dissociated implantation group, fixed implantation group, or reference group） at the ratio of 1： 1：1 according to the random number table. Routine blood test, biochemistry, systemic levels of C reactive protein （CRP） and interleukin 6 （ IL6）, percentage of CD3＋ , CD4＋ , and CDs lymphocytes were evaluated preoperatively and on postoperative dl, d4, d7 and dl0. 5FU concen tration of blood or abdominal cavity drainage samples was evaluated on postoperative dl, d2, d4 and d7. Occurrence of postoperative complications was evaluated. Results The blood 5FU concentration was below 100 ng/ml and un detectable by high performance liquid chromatography assay in both experimental groups. No differences between the 3 groups were noticed in serum levels of IL6 on postoperative days. CRP serum levels of patients in fixed implanta tion group were lower than those of reference group on postoperative d4 [ （60±29）mg/L vs （110± 61 ）mg/L, P 〈 0.05 ]. Compared with those of reference group on postoperative dl, percentage of CD3＋ and CD4＋ lymphocytes was significantly depressed in the dissociated implantation group[ （47 ± 11）% vs （60 ± 13）% and （23 ± 6）% vs （34 ± 13 ） %, respectively, P 〈 0.05 ]. Conclusions Different methods of intraabdominal implantation of sus tainedreleasing 5FU during radical surgery of gastrointestinal cancer has little effect on 5FU concentrations of ab dominal cavity. Maintenance of high level of 5FU in the abdominal cavity can be obtained more than 7 days. Im plantation of sustainedreleasing 5FU did not increase the rate of postoperative complications, and had negligible in fluence on routing blood test and liver and kidney functions. In consideration of the change of immunomodulation and inflammation parameters, fixed implantation of sustainedreleasing 5FU was preferred method of intraperitoneal chemotherapy.