顺铂和铜绿假单胞菌注射液联合腹腔循环热灌注治疗兔胃癌伴幽门梗阻

Cis- diammin- odichloroplatinum and pseudomonas aeruginosa- mannose sensitive haemaggluti- nation combined with continuous cycle hyperthermie intraperitoneal perfusion chemotherapy in the treatment of gastric cancer with pyloric obstruction in rabbit model

目的建立兔VX-2胃癌伴幽门梗阻模型，探讨顺铂（DDP）和铜绿假单胞菌注射液（PA-MSHA）联合腹腔循环热灌注对胃癌伴幽门梗阻兔模型的治疗效果及安全性。 方法通过注射VX-2肿瘤细胞悬液建立兔胃癌伴幽门梗阻模型，将42只兔模型随机分为对照组和治疗组。所有兔模型治疗前行血常规、肝肾功能、电解质检测，对照组兔21只，给予直接胃癌切除手术；治疗组兔21只，给予术前DDP和PA-MSHA联合腹腔循环热灌注后再行手术。记录联合腹腔循环热灌注化疗治疗后兔模型生存情况，所有兔死亡当天予以剖腹及开胸，观察胃窦部原发癌灶大小和幽门梗阻程度等，分别于治疗前开腹探查时、死亡当天取原发病灶及转移病灶标本，行苏木素-伊红（HE）染色，在光学显微镜下观察。兔死亡后取胃原位癌灶及转移癌灶。免疫组织化学检测血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）表达水平。结果实验组和对照组胃癌根治性切除率分别为85.5%（18/21）和66.7%（14/21），实验组显著高于对照组，差异有统计学意义（P=0.025）。实验组与对照组在术中出血量、手术时间及术后发生吻合口瘘或十二指肠瘘、大出血、应激性溃疡出血和肠梗阻差异无统计学意义（P=0.253）。而治疗组在术后发生腹腔感染、肺部感染及胃瘫较对照组明显降低（P=0.019）。对照组死亡标本解剖见典型胃癌转移瘤特征，与对照组比较，实验组腹腔转移程度较轻，出现肝转移较少，转移结节较小。对照组实验性腹膜转移癌指数（ePCI）评分为（18.00±1.55）分，实验组ePCI评分为（12.00±1.79）分，两组间差异有统计学意义（P=0.013）。对照组腹腔内粘连评分为（3.67±0.52）分，实验组腹腔内粘连评分为（1.17±0.75）分，两组间腹腔内粘连评分比较差异有统计学意义（P=0.016）。对照组VEGF相对表达量为77.33±6.77，实验组VEGF相对表达量为200.17±4.26，对照组PCNA相对表达量为83.33±3.49，实验组PCNA相对表达量为184.83±3.76，两组比较差异均有统计学意义（P=0.006、0.011）。结论术前DDP和PA-MSHA联合腹腔循环热灌注化疗支持治疗对控制胃癌进展和缓解幽门梗阻具有较好效果，且安全性较高。

ObjectiveTo establish rabbit models of VX-2 carcinoma with pyloric obstruction and explore the curative effects and safety of Cis-diammin-odichloroplatinum （DDP） and pseudomonas aeruginosa-mannose sensitive haemagglutination （PA-MSHA） combined with continuous cycle hyperthermie intraperitoneal perfusion chemotherapy （CCHIPC） on gastric cancer with pyloric obstruction in a rabbit model.MethodsVX-2 tumor cell suspension was injected to establish the rabbit model of gastric cancer with obstruction. Forty-two rabbits were randomly divided into the control group and the treatment group. All rabbit models treatment blood routine, liver and kidney function, electrolytes detection forward, the control group rabbits were 21, give direct resection of gastric cancer; treatment group rabbits were 21, given preoperative combined with enteral and parenteral nutrition after reoperation. Records of chemotherapy combined with enteral and parenteral nutrition in the treatment of rabbit model of survival, all the rabbits died the day be abdominal and thoracic, determine the primary tumor size in the gastric antrum, pyloric obstruction degree, respectively in treatment before laparotomy, died that day to take primary lesions and metastasis lesions were, he staining, under optical microscope observed. After the death of rabbits, gastric cancer was taken in situ and metastatic tumor. The expression levels of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （PCNA） were detected by immunohistochemistry.ResultsExperimental group and control group of gastric cancer radical resection rate was 85. 5% （18/21） and 66. 7% （14/21）, the experimental group was significantly higher than the control group, the difference was statistically significant （P=0.025）. In the experimental group and control group, the amount of bleeding, operation time, and postoperative anastomotic leakage or duodenal fistula, bleeding, stress ulcer bleeding and intestinal obstruction were not statistically significant （P=0.253）. In the treatment group, the incidence of postoperative abdominal infection, pulmonary infection and gastric paralysis was significantly lower than that of the control group （P=0.019）. Compared with the control group, the degree of metastasis of abdominal cavity in the experimental group was less than that in the control group, and there was less liver metastasis and less metastatic nodules. Control group experimental peritoneal carcinomatosis index （ePCI） score was 18.00±1.55, the experimental group ePCI score was 12.00±1.79, the difference between the two groups was statistically significant （P=0.013）. The abdominal adhesion score of control group was 3.67±0.52, the abdominal adhesion score of the experimental group was 1.17±0.75, and there was a significant difference between the two groups （P=0.016）. The gray value of VEGF expression in the control group was 77.33±6.77, the gray value of the experimental group VEGF was 200.17±4.26, the gray value of the control group PCNA was 83.33±3.49, the gray value of the experimental group PCNA was 184.83±3.76. The difference between the two groups was statistically significant （P=0.006, 0.011）.ConclusionPreoperative adjuvant DDP and PA-MSHA combined with enteral and parenteral nutrition support treatment to control the progression of gastric carcinoma and relieve pyloric obstruction has a better effect and higher safety.