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目的观察结肠癌术中区域化疗(regional chemotherapy,RC)中5-FU浓度及癌组织的病理学改变和Ki-67蛋白的表达。方法 RC组(n=20)行结肠癌根治术中经区域动脉灌注含5-FU(15 mg/kg)和羟基喜树碱(0.06 mg/kg)化疗液100 ml,分别于注药后2、5、10、20、30及60 min采集门静脉血、周围静脉血、腹腔液和癌旁组织,采用高效液相色谱法测定各样本中5-FU浓度;对照组(n=20)行结肠癌根治术中经区域动脉灌注生理盐水100 ml。术后观察2组结肠癌组织的病理学改变,并采用免疫组化SP法检测结肠癌组织中Ki-67蛋白的表达。结果灌注5-FU后2 min各样本中即出现峰浓度,然后逐渐降低,腹腔液中5-FU浓度最高,门静脉血次之,周围静脉血最低(P<0.01)。光镜下见RC组癌细胞轻度核固缩、肿胀,细胞浆凝固、坏死,细胞间质轻度水肿,炎性细胞浸润,有5例病例可见轻度血管炎。透射电镜下见RC组癌细胞核肿胀,核异染色质凝集,核周间隙扩大,胞质线粒体肿胀,内质网扩张,高尔基复合体扩张。RC组结肠癌组织中Ki-67蛋白表达标记指数低于对照组(P<0.05)。结论结肠癌术中RC可使腹腔液和门静脉血维持高的药物浓度,改变癌组织的病理学形态,降低Ki-67蛋白表达,对预防术中医源性转移和术后复发具有积极作用。
Objective To observe the concentration of 5-FU and the pathological changes of cancer tissue and the expression of Ki-67 in regional chemotherapy (RC) of colon cancer. Methods In the RC group (n = 20), 100 ml of 5-FU (15 mg / kg) and hydroxycamptothecin (0.06 mg / kg) , 5, 10, 20, 30 and 60 min respectively. The concentrations of 5-FU in each sample were determined by HPLC. The control group (n = 20) Radical surgery in the regional arterial infusion of saline 100 ml. The pathological changes of colon cancer tissues were observed after operation. The expression of Ki-67 protein in colon cancer tissues was detected by immunohistochemical SP method. Results The concentration of 5-FU in peritoneal fluid peaked at 2 min after perfusion of 5-FU, and then decreased gradually. The 5-FU concentration in peritoneal fluid was highest, followed by portal vein blood and the peripheral venous blood was the lowest (P <0.01). Light microscope, see the RC group of cancer cells mild nuclear pyknosis, swelling, cytoplasm coagulation, necrosis, interstitial mild edema, inflammatory cell infiltration, 5 cases of mild vasculitis can be seen. Under the transmission electron microscope, the cells in RC group showed nuclear swelling, heterochromatin condensation, enlarged perinuclear space, swelling of cytoplasmic mitochondria, dilation of endoplasmic reticulum and expansion of Golgi complex. The expression index of Ki-67 in RC group was lower than that in control group (P <0.05). Conclusion RC in colorectal cancer can maintain high drug concentrations in peritoneal fluid and portal vein blood, change the pathological morphology of cancerous tissue and decrease the expression of Ki-67 protein, which plays a positive role in preventing iatrogenic metastasis and postoperative recurrence.