超微化白芨粉栓塞剂治疗原发性肝癌（PHC）的临床研究
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摘要
目的:评估超微化白芨粉栓塞剂治疗原发性肝癌(primary hepitia cancer, PHC)的临床价值,为临床应用超微化白芨粉栓塞剂提供可靠的依据。方法:66例原发性肝癌患者随机分成两组,实验组:36例,超微化白芨粉、羟基喜树碱、超液态碘化油(又称乙碘油)混悬液栓塞肿瘤供血动脉; 对照组:30例,乙碘油、羟基喜树碱栓塞肿瘤供血动脉。所有患者均在DSA下行肝动脉栓塞灌注化疗术(TACE)。观察两组术后肿瘤缩小率、近期疗效、毒副反应和生存状况(术后3、6、12、24个月生存率)。结果:实验组栓塞治疗后, 3、6、12个月肿瘤缩小率分别为36.1±2.3%,55 .5±4.5% ,72.2±3.4%,高于对照组; 实验组术后3、6、12、24个月生存率分别为97.2 %、91.6%、80.5%、44.4%,平均生存期为18.8±4.1月; 对照组患者术后3、6、12、24个月生存率分别为93.3%、86.8%、66.6%、23.3%,平均生存期为15±5.3月,两组比较(P值<0.05)有显著差异。两组毒副反应无显著差异。结论:超微化白芨粉栓塞剂治疗原发性肝癌,介入治疗栓塞后肿瘤转移、复发率低,可明显提高介入治疗的疗效和肝癌患者的远期生存率。
Objective: To observe the clinical effects of supermicro-bletilla striata powder mixture on the embolization of primary hepatocellular carcinoma. Method: 66cases with PHC were randomly divided into two groups: Test group and control group.Test group included 36 cases treated with mixture of supermicro-bletilla striata powder plus hydroxyl camptothecinum and iodine oil, control group included 30 cases with hydroxyl camptothecinum and iodine oil .all the patients were operated with TACE under DSA. To observe the decreased ratio of tumour, recent effects, toxication and side effects and survival condition(postoperative survival rate in 3,6,12 and 24month, respectively). Results: Decreased rat of tumor in test group were 36.1±2.3%,55.5±4.5% and 72.2±3.4% after 3, 6,and12 month respectively, distinguished with that in control group. Postoperative survival rate of test group were 97.2 % 、91.6%、80.5% and 44.4% in 3,6,12,and 24 month respectively,remarkably different from that of control group. The side effects and toxications of two groups were no difference. Conclusion: Supermicro –bletilla striata powder mixture as embolism reagent used in TACE could reduced the reccurence and transfusion of tumor, remarkeably increase the survival rate.
Objective: To observe the clinical effects of supermicro-bletilla striata powder mixture on the embolization of primary hepatocellular carcinoma. Method: 66cases with PHC were randomly divided into two groups: Test group and control group.Test group included 36 cases treated with mixture of supermicro-bletilla striata powder plus hydroxyl camptothecinum and iodine oil, control group included 30 cases with hydroxyl camptothecinum and iodine oil .all the patients were operated with TACE under DSA. To observe the decreased ratio of tumour, recent effects, toxication and side effects and survival condition(postoperative survival rate in 3,6,12 and 24month, respectively). Results: Decreased rat of tumor in test group were 36.1±2.3%,55.5±4.5% and 72.2±3.4% after 3, 6,and12 month respectively, distinguished with that in control group. Postoperative survival rate of test group were 97.2 % 、91.6%、80.5% and 44.4% in 3,6,12,and 24 month respectively,remarkably different from that of control group. The side effects and toxications of two groups were no difference. Conclusion: Supermicro –bletilla striata powder mixture as embolism reagent used in TACE could reduced the reccurence and transfusion of tumor, remarkeably increase the survival rate.
引文
[1] 陈庆华. 肝动脉栓塞微球的动物药动学和药效学研究[J]. 中国药师 1998,1(1):3～5.
[2] 陈庆华. 肝动脉栓塞微球的动物药效学研究[J]. 中国新药杂志,1996; 5(6): 462～465.
[3] 葛勤,刘同华,黄林清等. 中药白芨作为血管栓塞剂及药物载体的研究概况[J]. 中国药房,2003,14(5):305～307.
[4] 张润青.中药白芨粉肾动脉栓塞治疗肾肿瘤的临床[J].中华泌尿外科杂志,1988,(3):155～159.
[5] 林丽珠,周岱翰.羟基喜树碱对耐药性晚期恶性肿瘤的治疗 中国肿瘤临床(羟喜树碱临床应用专辑)1997,24(10):39—41
[6] Zhu X,Kumar R,Mandal M,el a1.Cell cycle-dependent nlodulation of telomerase actives in tumor cells[J].Proc-Natl Acad Sci USA,1996,93(12):6091～6098.
[7] Terashima M,Takiyanm I,Uesugi N,et a1.Telomerase assay as a possible predictor of the lesponse to anticancer chenlotherapy[J].Anticancer Res,2000,20(1 ):293～297.
[8] 叶小卫,周岱翰,王芳军,等.羟基喜树碱在肝动脉化疗栓塞术治疗原发性肝癌中的应用[J].新中医,1999,31 (6):3～6.
[9] 刘子江.肺癌的介入治疗[J].实用肿瘤杂志,1996,11:197～202.
[10] 林钧华,宋明志,于尔辛,等. 华蟾素与羟基喜树碱肝动脉灌注栓塞治疗原发性肝癌的疗效观察[J].上海中医药杂志,1997,(11):18～22.
[11] 冯敢生,郑传胜,张彦舫.中药白芨胶栓塞治疗肝癌的应用研究[J].中国肿瘤, 1997,6(4):1O～16.
[12] 冯敢生 ,郑传胜,周汝明等. 中药白芨栓塞肝动脉治疗肝癌的对比性研究[J].临床医学影像,1996,7(4):209～212.
[13] 李宝杰,中药白芨明胶海绵栓塞治疗中晚期原发性肝癌疗效的对比观察[J].哈尔滨医科大学学报,1993,(6):488～491.
[14] 郑传胜, 冯敢生, 张彦舫.中药白芨作为血管栓塞剂的实验研究.中华放射学杂志,1998,32(3):188～195.
[15] Feng G Kramann B.Zheng C Zhou R.Comparative study on the long—term effect of permanent embolization of hepatic artery with Bletilla striata in patien with primary liver cancer[J].Tong ji Med Un 1996; 16:1111～ 1116.
[16] 于志坚,孟宪镛,徐克成,等.羟基喜树碱、斑蝥素联合顺氯氨铂经肝动脉栓塞治疗原发性肝癌48例[J].中国中西医结合杂志,1993,13(6):32～37.
[17] 苏同义 朱严冰 倪海英 动脉灌注羟喜树碱等药物治疗44例恶性肿瘤 北京军区医药 2001,13(1):31～ 32.
[18] 董生,肝动脉注入羟基喜树碱明胶微球对大鼠移植性肝癌的疗效研究[J].中华放射学杂志,1996,30(l):45～50.
[19] 郑传胜,冯敢生,周汝明,等.中药白芨的新用途—— 栓塞肝动脉治疗肝癌[J].中华肿瘤杂志,1996,18:305 ～307.
[20] 中华人民共和国卫生部药典委员会编. 中华人民共和国药典.第二部[M].北京:人民卫生出版杜,1990.109～111.
[21] 冉江喜,王正颜 翟仁友,等.一种新型栓塞剂:A~iostat肝动脉栓塞的动物实验及初步临床应用[J].中华放射学杂志.1993,27:4O5～407.
[22] 王田力,谢敬霞,李选,等.外磁场控制磁性明胶微球肝动脉栓塞的实验研究 [J].中华放射学杂志,1994,28:46～49.
[23] 李小明,胡国栋,陈孝平,等.无水乙醇碘油乳栓塞治疗原发性肝癌的病理研究[J].中华放射学杂志,1994,28: 749～752.
[24] 贾雨辰,王振堂,田建明,等.肝癌介入放射学治疗(综述)[J].临床医学影像杂志,1993 4:96—98.
[25] 冯敢生,郑传胜,周汝明.等.白芨与明胶海绵栓塞治疗肝癌疗效的对比研究[J].中华放射学杂志,1996,30:135～137.
[26] Feng G Kramann B.Zheng C Zhou R.Comparative study onthe long—term effect of permanent embolization of hepaticartery with Bletilla striata in patien with primary Ever cancer[J].China,Radio 1996; 18:116～119.
[27] Zheng C,Feng G,Zhou R.New use of Bletilla striata as embolizing agent in the intervention treatment of hepatic carcinoma[J].Zhonghua Zhongliu Zazhi 1996; 18:305～307.
[28] Zheng CS,Feng GS,ZhangYF.Bletilla colloid as a vascularembolization agent:experimental studies[J].China,Radio 1998; 32:188～191.
[29] Zheng C,Feng G,Liang H.Bletilla striata as a vascularembolizing agent in interventional treatment of primary hepatic carcinoma[J].China Medicine(Eng1) 1998; 11:1060～1063
[30] Li W Y,Du DM ,Feng GS,Chen HT.Preparation of Bletilla striata microspheres and experim ental study on embolization of hepatic artery in pigs[J].Acta Univ M Tongji 1999; 28:62～65.
[31] LiⅥ ,Feng GS,Zheng CS,Zhen Y.Pharmacokinetics of 5-Fu Bletilla microspheres following renal arterial embolization in Rabbits[J].Acta Univ Med Tongji 2001; 30:501～502
[32] Feng GS,Li X,Zheng C Zhou CK,Liu X,W u HP.Mechanism of inhibition of tumor angenesis by Bletilla colloid:an ex—perimental study[J].China Med,2003; 83:412～416.
[33] ZhangZ,LiuQ.He J,Yang J,YangG,W uM.The effectof preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma[J].Cancer 2000; 89:610～612.
[34] Sangro B,Herraiz M ,M artinez-Gonzalez M A,Bilbao I,HeITero I,Beloqui O,Betes M,de-la-Pena A,Cienfuegos JR,Quiroga I Prieto [J]. Prognosis of hepatoce Uular carcinomain relationto treatment:A multivariate analysis of 178 patien from a single European institution[J].Surgery 1998; 124:575～583.
[35] Chia-Hsien Cheng J,Chuang VP,Cheng sH,Lin YM,Cheng TI,Yang PS,Jian JJ,You DL,Horng CF,Huang AT.Unresectable hepatocellular carcinoma treated w ith radio-therapy and/or chemoembolization[J].Int,Cancer 2000,96:243～252.
[36] Fan J,Ten GJ,He SC,Guo JH,Yang DP,W ang GY.Arterialchemoembolization for hepatocellular carcinoma[J].World,Gastroenterol 1998,4:33～37.
[37] Suilleabhain CB,Poon RT.Yong JL,Ooi GC.Tso WK,FanST.Factors predictive of 5-year survival aftetransarterialchemoembolization for inoperable hepato celular carcinoma[J].Br,Surg 2003,90:325～331.
[38] Poyanli A,Rozanes I,Acunas B,Sencer S.P liative treatment of hepato cellular carcinom a by chemoembolization[J].Acta Radiol 2OO0,142:6O2～607
[39] Acunas B,Rozanes I.HepatoceUular carcinoma:treatm ent with ranscatheter a~erial chemoembolization[J].Eur l Radiol ,1999,32:86～89.
[40] RoseDM ,ChapmanWC,BrockenbroughAT,W rightJK,RoseAT,Meranze S,Mazer M,Blair T,Blanke CD,Debelak JP,Pinson CW .Transcatheter arterial chemoembo lization as primary treatment for hepatocelular carcinoma[J].Am ,Surg 1999,17:405～410.
[2] 陈庆华. 肝动脉栓塞微球的动物药效学研究[J]. 中国新药杂志,1996; 5(6): 462～465.
[3] 葛勤,刘同华,黄林清等. 中药白芨作为血管栓塞剂及药物载体的研究概况[J]. 中国药房,2003,14(5):305～307.
[4] 张润青.中药白芨粉肾动脉栓塞治疗肾肿瘤的临床[J].中华泌尿外科杂志,1988,(3):155～159.
[5] 林丽珠,周岱翰.羟基喜树碱对耐药性晚期恶性肿瘤的治疗 中国肿瘤临床(羟喜树碱临床应用专辑)1997,24(10):39—41
[6] Zhu X,Kumar R,Mandal M,el a1.Cell cycle-dependent nlodulation of telomerase actives in tumor cells[J].Proc-Natl Acad Sci USA,1996,93(12):6091～6098.
[7] Terashima M,Takiyanm I,Uesugi N,et a1.Telomerase assay as a possible predictor of the lesponse to anticancer chenlotherapy[J].Anticancer Res,2000,20(1 ):293～297.
[8] 叶小卫,周岱翰,王芳军,等.羟基喜树碱在肝动脉化疗栓塞术治疗原发性肝癌中的应用[J].新中医,1999,31 (6):3～6.
[9] 刘子江.肺癌的介入治疗[J].实用肿瘤杂志,1996,11:197～202.
[10] 林钧华,宋明志,于尔辛,等. 华蟾素与羟基喜树碱肝动脉灌注栓塞治疗原发性肝癌的疗效观察[J].上海中医药杂志,1997,(11):18～22.
[11] 冯敢生,郑传胜,张彦舫.中药白芨胶栓塞治疗肝癌的应用研究[J].中国肿瘤, 1997,6(4):1O～16.
[12] 冯敢生 ,郑传胜,周汝明等. 中药白芨栓塞肝动脉治疗肝癌的对比性研究[J].临床医学影像,1996,7(4):209～212.
[13] 李宝杰,中药白芨明胶海绵栓塞治疗中晚期原发性肝癌疗效的对比观察[J].哈尔滨医科大学学报,1993,(6):488～491.
[14] 郑传胜, 冯敢生, 张彦舫.中药白芨作为血管栓塞剂的实验研究.中华放射学杂志,1998,32(3):188～195.
[15] Feng G Kramann B.Zheng C Zhou R.Comparative study on the long—term effect of permanent embolization of hepatic artery with Bletilla striata in patien with primary liver cancer[J].Tong ji Med Un 1996; 16:1111～ 1116.
[16] 于志坚,孟宪镛,徐克成,等.羟基喜树碱、斑蝥素联合顺氯氨铂经肝动脉栓塞治疗原发性肝癌48例[J].中国中西医结合杂志,1993,13(6):32～37.
[17] 苏同义 朱严冰 倪海英 动脉灌注羟喜树碱等药物治疗44例恶性肿瘤 北京军区医药 2001,13(1):31～ 32.
[18] 董生,肝动脉注入羟基喜树碱明胶微球对大鼠移植性肝癌的疗效研究[J].中华放射学杂志,1996,30(l):45～50.
[19] 郑传胜,冯敢生,周汝明,等.中药白芨的新用途—— 栓塞肝动脉治疗肝癌[J].中华肿瘤杂志,1996,18:305 ～307.
[20] 中华人民共和国卫生部药典委员会编. 中华人民共和国药典.第二部[M].北京:人民卫生出版杜,1990.109～111.
[21] 冉江喜,王正颜 翟仁友,等.一种新型栓塞剂:A~iostat肝动脉栓塞的动物实验及初步临床应用[J].中华放射学杂志.1993,27:4O5～407.
[22] 王田力,谢敬霞,李选,等.外磁场控制磁性明胶微球肝动脉栓塞的实验研究 [J].中华放射学杂志,1994,28:46～49.
[23] 李小明,胡国栋,陈孝平,等.无水乙醇碘油乳栓塞治疗原发性肝癌的病理研究[J].中华放射学杂志,1994,28: 749～752.
[24] 贾雨辰,王振堂,田建明,等.肝癌介入放射学治疗(综述)[J].临床医学影像杂志,1993 4:96—98.
[25] 冯敢生,郑传胜,周汝明.等.白芨与明胶海绵栓塞治疗肝癌疗效的对比研究[J].中华放射学杂志,1996,30:135～137.
[26] Feng G Kramann B.Zheng C Zhou R.Comparative study onthe long—term effect of permanent embolization of hepaticartery with Bletilla striata in patien with primary Ever cancer[J].China,Radio 1996; 18:116～119.
[27] Zheng C,Feng G,Zhou R.New use of Bletilla striata as embolizing agent in the intervention treatment of hepatic carcinoma[J].Zhonghua Zhongliu Zazhi 1996; 18:305～307.
[28] Zheng CS,Feng GS,ZhangYF.Bletilla colloid as a vascularembolization agent:experimental studies[J].China,Radio 1998; 32:188～191.
[29] Zheng C,Feng G,Liang H.Bletilla striata as a vascularembolizing agent in interventional treatment of primary hepatic carcinoma[J].China Medicine(Eng1) 1998; 11:1060～1063
[30] Li W Y,Du DM ,Feng GS,Chen HT.Preparation of Bletilla striata microspheres and experim ental study on embolization of hepatic artery in pigs[J].Acta Univ M Tongji 1999; 28:62～65.
[31] LiⅥ ,Feng GS,Zheng CS,Zhen Y.Pharmacokinetics of 5-Fu Bletilla microspheres following renal arterial embolization in Rabbits[J].Acta Univ Med Tongji 2001; 30:501～502
[32] Feng GS,Li X,Zheng C Zhou CK,Liu X,W u HP.Mechanism of inhibition of tumor angenesis by Bletilla colloid:an ex—perimental study[J].China Med,2003; 83:412～416.
[33] ZhangZ,LiuQ.He J,Yang J,YangG,W uM.The effectof preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma[J].Cancer 2000; 89:610～612.
[34] Sangro B,Herraiz M ,M artinez-Gonzalez M A,Bilbao I,HeITero I,Beloqui O,Betes M,de-la-Pena A,Cienfuegos JR,Quiroga I Prieto [J]. Prognosis of hepatoce Uular carcinomain relationto treatment:A multivariate analysis of 178 patien from a single European institution[J].Surgery 1998; 124:575～583.
[35] Chia-Hsien Cheng J,Chuang VP,Cheng sH,Lin YM,Cheng TI,Yang PS,Jian JJ,You DL,Horng CF,Huang AT.Unresectable hepatocellular carcinoma treated w ith radio-therapy and/or chemoembolization[J].Int,Cancer 2000,96:243～252.
[36] Fan J,Ten GJ,He SC,Guo JH,Yang DP,W ang GY.Arterialchemoembolization for hepatocellular carcinoma[J].World,Gastroenterol 1998,4:33～37.
[37] Suilleabhain CB,Poon RT.Yong JL,Ooi GC.Tso WK,FanST.Factors predictive of 5-year survival aftetransarterialchemoembolization for inoperable hepato celular carcinoma[J].Br,Surg 2003,90:325～331.
[38] Poyanli A,Rozanes I,Acunas B,Sencer S.P liative treatment of hepato cellular carcinom a by chemoembolization[J].Acta Radiol 2OO0,142:6O2～607
[39] Acunas B,Rozanes I.HepatoceUular carcinoma:treatm ent with ranscatheter a~erial chemoembolization[J].Eur l Radiol ,1999,32:86～89.
[40] RoseDM ,ChapmanWC,BrockenbroughAT,W rightJK,RoseAT,Meranze S,Mazer M,Blair T,Blanke CD,Debelak JP,Pinson CW .Transcatheter arterial chemoembo lization as primary treatment for hepatocelular carcinoma[J].Am ,Surg 1999,17:405～410.