热碘油TACE联合乙酸消融序贯治疗中晚期肝癌的临床研究
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摘要
目的:
探讨经导管肝动脉热碘油化疗栓塞( Transcatheter hepatic arterial chemoembolization,TACE )联合经皮乙酸消融(percutaneous acetic acid interventional,PAI)治疗中晚期肝癌的临床疗效及临床应用价值。
方法:
回顾分析2006年1月至2009年1月间在我院接受TACE及热碘油TACE+ PAI治疗的资料完整的中晚期肝癌患者共60例,其中常规TACE治疗的30例患者为对照组,热碘油TACE+PAI治疗的30例患者为实验组。实验组肝癌患者经肝动脉插管行热碘油抗癌药乳剂栓塞治疗,将碘油抗癌药乳剂加热至100℃,经导管超选择栓塞,必要时加用明胶绵颗粒强化栓塞,抗癌药乳剂由超液化碘油、丝裂霉素及造影剂组成;对合并有肝动门脉瘘者(Hepatic artery and portal vein fistula,HAPS)先行瘘口栓塞,闭塞瘘口后再行肿瘤栓塞。对照组肝癌患者在室温下经导管超选择栓塞,碘油及化疗药物(种类、剂量、途径及方法均与实验组一致)不加热。术后3~4周复查CT或肝动脉造影,据碘油缺失、瘘口再通、癌灶残留及病灶进展等情况,实验组行PAI序贯治疗,对照组单纯行TACE治疗,两组均连续治疗3次为一个周期。观察比较两组有效率、AFP(a-fetoprotein)平均下降率、毒副作用、疾病进展时间及无疾病进展率、生存期。评价热碘油TACE联合PAI治疗中晚期肝癌的临床疗效。
结果:
(1)MSCT(Multi-slice spiral computed tomography)评价有效率:经过一个周期治疗后行肝脏MSCT增强扫描,实验组CR 6例,PR 14例,NC 8例,PD 2例,RR为67.67%(20/30);对照组中CR 2例,PR 10例,NC 13例,PD4例,RR为40.00%(12/30)。两组总有效率比较差异有统计学意义(P<0.05),实验组高于对照组;(2)治疗后AFP平均下降率:实验组为77.12%,对照组为44.75%,两组差异有统计学意义(P<0.05);(3)实验组与对照组中位疾病进展时间分别为12个月、9个月。3个月、6个月、1年、1.5年无疾病进展率分别为80.00%、66.67%、50.00% ,33.33%和66.67%、36.67%、20.00%、10.00%,两组差别有显著统计学意义(P<0.05)。(5)生存时间:实验组和对照组0.5年、1年、1.5年、2年累积生存率别为100.00%、90.00%、76.67%、56.67%和93.33%、80.00%、63.33%、36.67%。两组中位生存时间分别为29个月和22个月,两组生存曲线比较有统计学意义(P<0.05),实验组疗效优于对照组;(6)毒副作用:两组毒副作用相似,均未发生严重并发症,实验组行PAI治疗时50%的患者出现术中疼痛;(7)肝动-门脉瘘:对照组6例经TACE术反复封堵后仍有3例发生瘘口再通,实验组5例经热碘油TACE+PAI治疗后未出现瘘口再通。
结论:
1.热碘油TACE联合PAI综合治疗中晚期肝癌是安全、可行、并不增加毒副作用及并发症。
2.热碘油TACE联合PAI综合治疗中晚期肝癌,其有效率、AFP下降率、无疾病进展时间及生存期优于常规TACE治疗。
Objective:
To evaluate the clinical effect and application value of hot lipiodol transcatheter epatic arterial chemoembolization(TACE)combined with percutaneous acetic acid injection (PAI)in patients with advanced liver cancer.
Methods:
Retrospective analysis of 60 patients with advanced liver cancer received TACE and Hot lipiodol TACE combined with PAI in NanHua Hospital from January 2006 to January 2009.30 patients performed only in TACE were enrolled in control group.30 patients were treated with Hot lipiodol TACE+PAI as the therapy group.The patients were therapy group were treated with transhepatic arterial thermo -chemotherapy with warmed lipiodol anticancer drug emulsion (100℃).And gelatin sponge particles were used to Strengthen the embolization necessarily.The HAPS were blocked up before cure tumor. Control group were treated with ordinary transhepatic arterial chemomembolization(TACE) with the same lipiodol anticancer drug emulsion but without warming,Anticancer drug emulsion by the lipiodol, mitomycin, and contrast agent composed of;3 to 4 weeks after CT or hepatic arteriography review, according to lipiodol absence of fistula recanalization, tumor residual and disease progression, etc., the experimental group PAI-line sequential therapy,.The continuous three treatments was a periodof treatment.Then followed up the therapeutic effect rates,reduced rates of AFP,side effects, the median time to progression (TTP )and the progression free survival(PFS) rate,the rates of metastasis,survival time of the two groups.
Results:
The effect rates were 67.67%and 40.00%in the therapy group and the control group,respectively(P<0.05);The average reduced rates of AFP was 77.12%and 44.75%in the therapy group and control group,respectively(P<0.05);The median time to progression (TTP )was 12 months in the therapy group and 9 months in the control group.The progression free survival(PFS) rate of 3 months,6 months ,1 year and 1.5year was 80.00%、66.67%、50.00% and 33.33% of therapy experimental group,respectively,while was 66.67%、36.67%、20.00% and 10.00% of control group,respectively.The TTP of experimental group was significantly longer than that of control group (P< 0.05);The median survival time and 0.5-,1-,1.5-,2-year cumulative survival rate were 29 months、100.00%、90.00%、76.67%、56.67% and 22months、93.33%、80.00%、63.33%、36.67% in the therapy group and control group,respectively(P<0.05);The side effects of two groups were similar and the serious complications were not found. 50% of the control group patients will appear in pain, when they PAI therapy.;6 HAPS in the control group were blocked up repeatedly with TACE,3 of them were recanalized yet.5 HAPS in the therapy group were completely blocked,none of them was recanalized again.
Conclusions:
Hot lipiodol TACE combined with PAI could safely and effectively treat the Patients with anvanced liver cancer,and extend TTP and life span, boost PFS and not increase side effects.
探讨经导管肝动脉热碘油化疗栓塞( Transcatheter hepatic arterial chemoembolization,TACE )联合经皮乙酸消融(percutaneous acetic acid interventional,PAI)治疗中晚期肝癌的临床疗效及临床应用价值。
方法:
回顾分析2006年1月至2009年1月间在我院接受TACE及热碘油TACE+ PAI治疗的资料完整的中晚期肝癌患者共60例,其中常规TACE治疗的30例患者为对照组,热碘油TACE+PAI治疗的30例患者为实验组。实验组肝癌患者经肝动脉插管行热碘油抗癌药乳剂栓塞治疗,将碘油抗癌药乳剂加热至100℃,经导管超选择栓塞,必要时加用明胶绵颗粒强化栓塞,抗癌药乳剂由超液化碘油、丝裂霉素及造影剂组成;对合并有肝动门脉瘘者(Hepatic artery and portal vein fistula,HAPS)先行瘘口栓塞,闭塞瘘口后再行肿瘤栓塞。对照组肝癌患者在室温下经导管超选择栓塞,碘油及化疗药物(种类、剂量、途径及方法均与实验组一致)不加热。术后3~4周复查CT或肝动脉造影,据碘油缺失、瘘口再通、癌灶残留及病灶进展等情况,实验组行PAI序贯治疗,对照组单纯行TACE治疗,两组均连续治疗3次为一个周期。观察比较两组有效率、AFP(a-fetoprotein)平均下降率、毒副作用、疾病进展时间及无疾病进展率、生存期。评价热碘油TACE联合PAI治疗中晚期肝癌的临床疗效。
结果:
(1)MSCT(Multi-slice spiral computed tomography)评价有效率:经过一个周期治疗后行肝脏MSCT增强扫描,实验组CR 6例,PR 14例,NC 8例,PD 2例,RR为67.67%(20/30);对照组中CR 2例,PR 10例,NC 13例,PD4例,RR为40.00%(12/30)。两组总有效率比较差异有统计学意义(P<0.05),实验组高于对照组;(2)治疗后AFP平均下降率:实验组为77.12%,对照组为44.75%,两组差异有统计学意义(P<0.05);(3)实验组与对照组中位疾病进展时间分别为12个月、9个月。3个月、6个月、1年、1.5年无疾病进展率分别为80.00%、66.67%、50.00% ,33.33%和66.67%、36.67%、20.00%、10.00%,两组差别有显著统计学意义(P<0.05)。(5)生存时间:实验组和对照组0.5年、1年、1.5年、2年累积生存率别为100.00%、90.00%、76.67%、56.67%和93.33%、80.00%、63.33%、36.67%。两组中位生存时间分别为29个月和22个月,两组生存曲线比较有统计学意义(P<0.05),实验组疗效优于对照组;(6)毒副作用:两组毒副作用相似,均未发生严重并发症,实验组行PAI治疗时50%的患者出现术中疼痛;(7)肝动-门脉瘘:对照组6例经TACE术反复封堵后仍有3例发生瘘口再通,实验组5例经热碘油TACE+PAI治疗后未出现瘘口再通。
结论:
1.热碘油TACE联合PAI综合治疗中晚期肝癌是安全、可行、并不增加毒副作用及并发症。
2.热碘油TACE联合PAI综合治疗中晚期肝癌,其有效率、AFP下降率、无疾病进展时间及生存期优于常规TACE治疗。
Objective:
To evaluate the clinical effect and application value of hot lipiodol transcatheter epatic arterial chemoembolization(TACE)combined with percutaneous acetic acid injection (PAI)in patients with advanced liver cancer.
Methods:
Retrospective analysis of 60 patients with advanced liver cancer received TACE and Hot lipiodol TACE combined with PAI in NanHua Hospital from January 2006 to January 2009.30 patients performed only in TACE were enrolled in control group.30 patients were treated with Hot lipiodol TACE+PAI as the therapy group.The patients were therapy group were treated with transhepatic arterial thermo -chemotherapy with warmed lipiodol anticancer drug emulsion (100℃).And gelatin sponge particles were used to Strengthen the embolization necessarily.The HAPS were blocked up before cure tumor. Control group were treated with ordinary transhepatic arterial chemomembolization(TACE) with the same lipiodol anticancer drug emulsion but without warming,Anticancer drug emulsion by the lipiodol, mitomycin, and contrast agent composed of;3 to 4 weeks after CT or hepatic arteriography review, according to lipiodol absence of fistula recanalization, tumor residual and disease progression, etc., the experimental group PAI-line sequential therapy,.The continuous three treatments was a periodof treatment.Then followed up the therapeutic effect rates,reduced rates of AFP,side effects, the median time to progression (TTP )and the progression free survival(PFS) rate,the rates of metastasis,survival time of the two groups.
Results:
The effect rates were 67.67%and 40.00%in the therapy group and the control group,respectively(P<0.05);The average reduced rates of AFP was 77.12%and 44.75%in the therapy group and control group,respectively(P<0.05);The median time to progression (TTP )was 12 months in the therapy group and 9 months in the control group.The progression free survival(PFS) rate of 3 months,6 months ,1 year and 1.5year was 80.00%、66.67%、50.00% and 33.33% of therapy experimental group,respectively,while was 66.67%、36.67%、20.00% and 10.00% of control group,respectively.The TTP of experimental group was significantly longer than that of control group (P< 0.05);The median survival time and 0.5-,1-,1.5-,2-year cumulative survival rate were 29 months、100.00%、90.00%、76.67%、56.67% and 22months、93.33%、80.00%、63.33%、36.67% in the therapy group and control group,respectively(P<0.05);The side effects of two groups were similar and the serious complications were not found. 50% of the control group patients will appear in pain, when they PAI therapy.;6 HAPS in the control group were blocked up repeatedly with TACE,3 of them were recanalized yet.5 HAPS in the therapy group were completely blocked,none of them was recanalized again.
Conclusions:
Hot lipiodol TACE combined with PAI could safely and effectively treat the Patients with anvanced liver cancer,and extend TTP and life span, boost PFS and not increase side effects.
引文
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[1]郭晓华,何建荣,金红来,等.TACE联合经皮无水乙醇注射在原发性肝癌治疗中的价值[J].医学影像学杂志,2009,5(19):555-557.
[2] Koda M,Murawak Y,Mitsuda A,et a1.Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection along for patients with small hepatoceHular hepatocel1ular carcinoma:a randomized control study[J].Cancer,2001,92(6):l516-1524.PMID: 11745230
[3]朱芳来,凌安生.经动脉灌注化疗栓塞联合经皮无水乙醇注射治疗原发性肝癌临床研究[J].介入放射学杂志,2008,17(4):286-289.
[4] Ohnishi K,Ohyama N,Ito S,et a1.Small hepatocellular carcinoma:treatment with US guided intratumoral injection of aceticacid[J].Radiology,1994,193(3):747-752.PMID: 7972818
[5]周胜利,张旭,王宗盛,等.CT引导下经皮乙酸注射联合肝动脉化疗栓塞治疗原发性肝癌[J].介入放射学杂,2007,6(16):414-416.
[6]李世平,马善符,周殿伦.术后肝血管灌注化疗预防肝癌复发[J].腹部外科,2000,13(1):20-21.
[7]陈晚平,易继林,李兴睿.原发性肝癌术中化疗泵埋置途径选择的研究[J].消化外科,2004,3(5):313-315.
[8] Yamakado K,Nakatsuka A,Ohmor S,et a1.Radiofrequency ablation combined with chemoembolization inhepatocellu1ar carcinoma:treatment response based on tumor size and morphology[J].J Vasc Interv Radiol,2002,13(2):1225-l232.PMID: 12471186
[9]靳殿功,孔棣,王桐,等.射频消融联合经导管肝动脉栓塞化疗序贯性治疗原发性肝癌[J].中国中西医结合外科杂志,2009,2(15):141-143.
[10]朱志刚,曹建民,许健.氩氦刀联合肝动脉介入治疗原发性肝癌的免疫效应研究[J].介入放射学杂志,2009,9(18):661-663.
[11]王帆,周石.肝动脉化疗栓塞联合氩氦刀治疗原发性肝癌疗效评价[J].介入放射学杂志,2005,6(14):637-639.
[12]魏云涛,郭大伟,侯学忠,等.微波固化治疗对肝癌患者免疫功能的影响[J].现代肿瘤医学,2009,7(17):1300-1302.
[13]周培华,邓和军,许国辉,等. TACE联合PMCT治疗中晚期肝癌的临床观察[J].肿瘤预防与治疗,2009,3(22):294-296.
[14] Chia-Hsien,Cheng J,Chuang VP.Cheng SH,et a1.Unresectable hepatocellular carcinoma treated with radiotherapy and chemoembolization[J].Int J Cancer,2001,96(4):243-252.PMID: 11474499
[15]陈建江,丁阳.调强适形放射治疗联合肝动脉化疗栓塞治疗原发性肝癌疗效观察[J].中国现代医药杂志,2008,12(10):67-69.
[16]程树群,周信达,汤钊猷,等.碘化油与高功能聚焦超声破坏肝组织的协同升温效应研究[J].中国超声医学杂志,l997,13(4):1-4.
[17]黄耀,张卫星,魏杨辉,等.高强度聚焦超声联合肝动脉化疗栓塞治疗门静脉癌栓的临床研究[J].浙江临床医学,2009,10(11):1028-1030.
[18]金成兵,朱辉,王智彪,等.HIFU联合TACE治疗不能手术切除中晚期肝癌的临床分析[J].中国超声医学杂志,2008,8(24):741-744.
[19] Bown SG.Photothermpy in tumors[J].World J Surg,1983,7(6):700-709.PMID: 6419477
[20] Pacella CM ,Bizzarri G ,Cecconi P,et a1.Hepatoeellular carcinoma long term results of combined treatment with laser thermalablatio and transcatheter arterial chemoembolization[J].Radiology,2001,219(3):669-679.PMID: 11376253
[21]郝强,田建明,曹雪涛,等.经肝动脉插管注射重组腺病毒治疗大鼠转移性肝癌的实验研究[J].中华放射学杂志,2000,34(10):666-669.
[22] Noboru H,Mitsuo S,Shinji O,et a1.IL-12 gene therapy is all effective therapeutic strategy for hepatocellular carcinoma inimmuno suppressedmice[J].J Immunology,2004,173(11):6635-6644.PMID: 15557154
[23]陈世唏,陈骏,徐卫东,等.动脉灌注p53基因治疗晚期肝癌的初步临床应用[J].介入放射学杂志,2007.2,16:127-129.
[24]熊壮,王建华.溶瘤病毒在肝癌介入治疗中的应用[J].介入放射学杂志,2007, 16(3):206-208.
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[26]侯立泳.TACE联合免疫治疗对肝癌患者免疫学指标的影响[J].山东医药,2007,13(47):38-38.
[27]黄素贞,李海妍,陈丽萍.国产胸腺五肽联合化疗药物经肝动脉化疗栓塞治疗原发型肿癌的临床观察[J].中国疗养医学,2007,7(16):417-418.
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[1]郭晓华,何建荣,金红来,等.TACE联合经皮无水乙醇注射在原发性肝癌治疗中的价值[J].医学影像学杂志,2009,5(19):555-557.
[2] Koda M,Murawak Y,Mitsuda A,et a1.Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection along for patients with small hepatoceHular hepatocel1ular carcinoma:a randomized control study[J].Cancer,2001,92(6):l516-1524.PMID: 11745230
[3]朱芳来,凌安生.经动脉灌注化疗栓塞联合经皮无水乙醇注射治疗原发性肝癌临床研究[J].介入放射学杂志,2008,17(4):286-289.
[4] Ohnishi K,Ohyama N,Ito S,et a1.Small hepatocellular carcinoma:treatment with US guided intratumoral injection of aceticacid[J].Radiology,1994,193(3):747-752.PMID: 7972818
[5]周胜利,张旭,王宗盛,等.CT引导下经皮乙酸注射联合肝动脉化疗栓塞治疗原发性肝癌[J].介入放射学杂,2007,6(16):414-416.
[6]李世平,马善符,周殿伦.术后肝血管灌注化疗预防肝癌复发[J].腹部外科,2000,13(1):20-21.
[7]陈晚平,易继林,李兴睿.原发性肝癌术中化疗泵埋置途径选择的研究[J].消化外科,2004,3(5):313-315.
[8] Yamakado K,Nakatsuka A,Ohmor S,et a1.Radiofrequency ablation combined with chemoembolization inhepatocellu1ar carcinoma:treatment response based on tumor size and morphology[J].J Vasc Interv Radiol,2002,13(2):1225-l232.PMID: 12471186
[9]靳殿功,孔棣,王桐,等.射频消融联合经导管肝动脉栓塞化疗序贯性治疗原发性肝癌[J].中国中西医结合外科杂志,2009,2(15):141-143.
[10]朱志刚,曹建民,许健.氩氦刀联合肝动脉介入治疗原发性肝癌的免疫效应研究[J].介入放射学杂志,2009,9(18):661-663.
[11]王帆,周石.肝动脉化疗栓塞联合氩氦刀治疗原发性肝癌疗效评价[J].介入放射学杂志,2005,6(14):637-639.
[12]魏云涛,郭大伟,侯学忠,等.微波固化治疗对肝癌患者免疫功能的影响[J].现代肿瘤医学,2009,7(17):1300-1302.
[13]周培华,邓和军,许国辉,等. TACE联合PMCT治疗中晚期肝癌的临床观察[J].肿瘤预防与治疗,2009,3(22):294-296.
[14] Chia-Hsien,Cheng J,Chuang VP.Cheng SH,et a1.Unresectable hepatocellular carcinoma treated with radiotherapy and chemoembolization[J].Int J Cancer,2001,96(4):243-252.PMID: 11474499
[15]陈建江,丁阳.调强适形放射治疗联合肝动脉化疗栓塞治疗原发性肝癌疗效观察[J].中国现代医药杂志,2008,12(10):67-69.
[16]程树群,周信达,汤钊猷,等.碘化油与高功能聚焦超声破坏肝组织的协同升温效应研究[J].中国超声医学杂志,l997,13(4):1-4.
[17]黄耀,张卫星,魏杨辉,等.高强度聚焦超声联合肝动脉化疗栓塞治疗门静脉癌栓的临床研究[J].浙江临床医学,2009,10(11):1028-1030.
[18]金成兵,朱辉,王智彪,等.HIFU联合TACE治疗不能手术切除中晚期肝癌的临床分析[J].中国超声医学杂志,2008,8(24):741-744.
[19] Bown SG.Photothermpy in tumors[J].World J Surg,1983,7(6):700-709.PMID: 6419477
[20] Pacella CM ,Bizzarri G ,Cecconi P,et a1.Hepatoeellular carcinoma long term results of combined treatment with laser thermalablatio and transcatheter arterial chemoembolization[J].Radiology,2001,219(3):669-679.PMID: 11376253
[21]郝强,田建明,曹雪涛,等.经肝动脉插管注射重组腺病毒治疗大鼠转移性肝癌的实验研究[J].中华放射学杂志,2000,34(10):666-669.
[22] Noboru H,Mitsuo S,Shinji O,et a1.IL-12 gene therapy is all effective therapeutic strategy for hepatocellular carcinoma inimmuno suppressedmice[J].J Immunology,2004,173(11):6635-6644.PMID: 15557154
[23]陈世唏,陈骏,徐卫东,等.动脉灌注p53基因治疗晚期肝癌的初步临床应用[J].介入放射学杂志,2007.2,16:127-129.
[24]熊壮,王建华.溶瘤病毒在肝癌介入治疗中的应用[J].介入放射学杂志,2007, 16(3):206-208.
[25]肖恩华,胡国栋.肝癌介入性化学生物疗法[J].放射学实践,1999,14(2):119-121.
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