结肠癌术中区域化疗5-FU浓度测定及其病理学意义  

Detection of 5-FU Concentration and Pathological Effects in Intraoperative Regional Chemotherapy for Colon Cancer

作　　者：杜江[1] 赵圆宇[2] 夏术森[1] 魏寿江[1] 寇红艳[1] 侯华芳[1] 王崇树[1] 

机构地区：[1]川北医学院附属医院普外一科,四川南充637000 [2]川北医学院组织胚胎学教研室,四川南充637000

出　　处：《中国普外基础与临床杂志》2011年第5期523-527,共5页Chinese Journal of Bases and Clinics In General Surgery

基　　金：四川省教育厅科研基金(项目编号:2006C013)~~

摘　　要：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 detect 5-FU concentration and investigate the changes of pathology,and Ki-67 protein expression after intraoperative regional chemotherapy（RC） for colon cancer.Methods All the patients were randomized into two groups： RC group（n=20）,received intra-operational RC with 100 ml physiological saline contained 5-FU（15 mg/kg） and camptothecine（0.06 mg/kg）;control group（n=20）,saline alone.The samples from portal vein blood,peripheral blood,peritoneal fluid,and peri-cancerous tissues in RC group were taken to detect the 5-FU concentration by high performance liquid chromatography（HPLC）,respectively at 2,5,10,20,30,and 60 minutes after treatment.The pathological changes were observed and Ki-67 protein expressions were examined by immunohistochemical staining for all the cancer tissues postoperatively in two groups.Results Peak concentration of 5-FU appeared at 2 min after treatment,and decreased gradually.5-FU concentration in peritoneal fluid was the highest,and the lowest in the peripheral blood（P0.01）.In RC group,light karyopyknosis,nuclear swelling,and coagulative necrosis of cancer cells,and light intercellular substance hydropsia,inflammatory cells invasion were observed under light microscopic examination;light vasculitis presented also in five cases.Nuclear swelling,heterochromatin agglutination,perinuclear gap expansion,mitochondrial swelling,endoplasmic reticulum expansion,and Golgi complex expansion were observed with transmission electron microscope.Ki-67 protein expression of colon cance tissues in RC group was lower than that in control group（P0.05）.Conclusions Intraoperative RC for colon cancer may sustain a high concentration of chemotherapy drugs in peritoneal fluid and portal vein blood,and alter histopathological morphology of cancer cells,and suppress Ki-67 protein expression.So,intraoperative RC may play an important role in preventing intraoperative spreading and postoperative recurrence of colon cancer.

关 键 词：结肠癌 术中区域化疗 5-氟尿嘧啶 病理学 KI-67蛋白 

分 类 号：R735.35[医药卫生—肿瘤]