超液态碘化油联合药物洗脱微球经肝动脉化疗栓塞术治疗巴塞罗那B/C期肝细胞癌的效果分析
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摘要
目的研究超液态碘化油联合药物洗脱微球经动脉化疗栓塞术(TACE)治疗巴塞罗那(BCLC) B/C期肝细胞癌(HCC)的有效性和安全性。方法回顾性分析2016年5月-2018年9月苏州大学附属第一医院接受超液态碘化油联合药物洗脱微球栓塞治疗的51例BCLC B/C期HCC患者,比较治疗前和治疗后3 d、7 d、1个月的肝功能变化,详细记录不良反应及并发症发生情况,采用改良实体瘤疗效评价标准(mRECIST)评价术后1、3个月临床疗效。计量资料组间比较采用t检验。结果 51例患者均完成超选择栓塞,治疗病灶术后1个月疾病缓解率为70. 6%,疾病控制率为96. 1%; 3个月疾病缓解率为64. 0%,疾病控制率为88. 0%。术后3 d急性肝损伤发生率9. 8%(5/51),ALT、AST、TBil、Alb变化较术前有明显差异(t值分别为-5. 454、-3. 997、-5. 346、7. 212,P值均<0. 001),术后1周ALT、TBil、Alb变化较术前有明显差异(t值分别为-3. 177、-3. 665、3. 194,P值均<0. 05)。术后1个月1级和2级不良反应发生率为68. 6%(35/51),未出现肝衰竭、肝脓肿、胆汁瘤、消化道出血等并发症,1例患者术后61 d因肿瘤进展死于多脏器功能衰竭。结论超液态碘化油联合药物洗脱微球TACE治疗BCLC B/C期HCC是安全有效的,远期疗效及生存获益有待于进一步观察。
Objective To investigate the clinical effect and safety of transarterial chemoembolization( TACE) with ultra-liquid iodized oil combined with drug-eluting beads in the treatment of Barcelona Clinic Liver Cancer( BCLC) stage B/C hepatocellular carcinoma( HCC).Methods A retrospective analysis was performed for the clinical data of 51 patients with BCLC stage B/C HCC who underwent TACE with ultra-liquid iodized oil combined with drug-eluting beads in The First Affiliated Hospital of Soochow University from May 2016 to September 2018. Liver function was observed before treatment and at 3 days,7 days,and 1 month after treatment,and adverse events and complications were recorded in detail. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate clinical outcome at 1 and 3 months after surgery. The t-test was used for comparison of continuous data between two groups. Results Superselective TACE procedure was completed in all 51 patients. At 1 month after surgery,the target lesions had a disease remission rate of 70. 6% and a disease control rate of 96. 1%,while at 3 months after surgery,the target lesions had a disease remission rate of 64. 0% and a disease control rate of88. 0%. Of all 51 patients,5( 9. 8%) experienced acute liver injury at 3 days after surgery,and there were significant changes in alanine aminotransferase( ALT),aspartate aminotransferase,total bilirubin( TBil),and albumin( Alb)( t =-5. 454,-3. 997,-5. 346,and7. 212,all P < 0. 001). There were also significant changes in ALT,TBil,and Alb at 7 days after surgery( t =-3. 177,-3. 665,and3. 194,all P < 0. 05). Of all 51 patients,35( 68. 6%) experienced grade 1 or 2 adverse events at 1 month after surgery,and no complications of liver failure,liver abscess,bile tumor,and gastrointestinal bleeding were observed. One patient died of multiple organ failure due to tumor progression on day 61 after surgery. Conclusion TACE with ultra-liquid iodized oil combined with drug-eluting beads is safe and effective in the treatment of BCLC stage B/C HCC,and further studies are needed to observe long-term efficacy and survival benefit.
Objective To investigate the clinical effect and safety of transarterial chemoembolization( TACE) with ultra-liquid iodized oil combined with drug-eluting beads in the treatment of Barcelona Clinic Liver Cancer( BCLC) stage B/C hepatocellular carcinoma( HCC).Methods A retrospective analysis was performed for the clinical data of 51 patients with BCLC stage B/C HCC who underwent TACE with ultra-liquid iodized oil combined with drug-eluting beads in The First Affiliated Hospital of Soochow University from May 2016 to September 2018. Liver function was observed before treatment and at 3 days,7 days,and 1 month after treatment,and adverse events and complications were recorded in detail. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate clinical outcome at 1 and 3 months after surgery. The t-test was used for comparison of continuous data between two groups. Results Superselective TACE procedure was completed in all 51 patients. At 1 month after surgery,the target lesions had a disease remission rate of 70. 6% and a disease control rate of 96. 1%,while at 3 months after surgery,the target lesions had a disease remission rate of 64. 0% and a disease control rate of88. 0%. Of all 51 patients,5( 9. 8%) experienced acute liver injury at 3 days after surgery,and there were significant changes in alanine aminotransferase( ALT),aspartate aminotransferase,total bilirubin( TBil),and albumin( Alb)( t =-5. 454,-3. 997,-5. 346,and7. 212,all P < 0. 001). There were also significant changes in ALT,TBil,and Alb at 7 days after surgery( t =-3. 177,-3. 665,and3. 194,all P < 0. 05). Of all 51 patients,35( 68. 6%) experienced grade 1 or 2 adverse events at 1 month after surgery,and no complications of liver failure,liver abscess,bile tumor,and gastrointestinal bleeding were observed. One patient died of multiple organ failure due to tumor progression on day 61 after surgery. Conclusion TACE with ultra-liquid iodized oil combined with drug-eluting beads is safe and effective in the treatment of BCLC stage B/C HCC,and further studies are needed to observe long-term efficacy and survival benefit.
引文
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[15]YOU JX,WANG JB,AI ST,et al.TACE by using microspheres and lipiodol for the treatment of hepatocellular carcinoma:Analysis of short-term efficacy[J].J Intervent Radiol,2017,26(6):531-534.(in Chinese)游建雄,王精兵,艾松涛,等.微球联合碘油栓塞治疗肝癌的近期疗效分析[J].介入放射学杂志,2017,26(6):531-534.
[16]NAKAO N,UCHIDA H,KAMINO K,et al.Determination of the optimum dose level of lipiodol in transcatheter arterial embolization of primary hepatocellular carcinoma based on retrospective multivariate analysis[J].Cardiovasc Intervent Radiol,1994,17(2):76-80.
[17]XIAO CJ,ZHENG LY.Clinical effect of transarterial chemoembolization in treatment of liver injury:An analysis of 100 cases[J].Chin J Radiol,1997,31(11):777-779.(in Chinese)肖承江,郑丽吟.肝动脉栓塞化疗对肝损害的观察(附100例分析)[J].中华放射学杂志,1997,31(11):777-779.
[18]DUFOUR DR,LOTT JA,NOLTE FS,et al.Diagnosis and monitoring of hepatic injury.I.Performance characteristics of laboratory tests[J].Clin Chem,2000,46(12):2027-2049.
[19]KAN XF,ZHENG CS,XIONG B,et al.Simple conventional hepatic artery chemoembolization for the treatment of Barcelona stage C liver cancer:A clinic analysis[J].J Intervent Radiol,2018,27(12):1182-1185.(in Chinese)阚雪锋,郑传胜,熊斌,等.单纯经典肝动脉化疗栓塞术治疗巴塞罗那C期肝癌的临床分析[J].介入放射学杂志,2018,27(12):1182-1185.
[20]WANG FS,FAN JG,ZHANG Z,et al.The global burden of liver disease:The major impact of China[J].Hepatology,2014,60(6):2099-2108.
[21]ZHANG MY,NIU JQ.Prevalence of primary liver cancer in Eastern countries and related influencing factors[J].J Clin Hepatol,2018,34(7):1399-1402.(in Chinese)张明媛,牛俊奇.东方国家原发性肝癌发病趋势及影响因素[J].临床肝胆病杂志,2018,34(7):1399-1402.
[22]CAO K,BAO ZM,ZHOU XY,et al.Effects and mechanisms of hepatitis B virus X protein on invasion and migration of hepatocellular carcinoma cells[J].Chin J Dig Surg,2017,16(2):177-182.(in Chinese)曹宽,鲍仲明,周新宇,等.乙型肝炎病毒X蛋白对肝癌细胞侵袭与迁移能力的作用及机制[J].中华消化外科杂志,2017,16(2):177-182.
[2]LEWIS AL,GONZALEZ MV,LEPPARD SW,et al.Doxorubicin eluting beads-1:Effects of drug loading on bead characteristics and drug distribution[J].J Mater Sci Mater Med,2007,18(9):1691-1699.
[3]LEWIS AL,GONZALEZ MV,LLOYD AW,et al.DC bead:In vitro characterization of a drug-delivery device for transarterial chemoembolization[J].J Vase Interv Radiol,2006,17(2 Pt1):335-342.
[4]National Health and Family Planning Commission of the People's Republic of China.Diagnosis,management,andtreatment of hepatocellular carcinoma(V2017)[J].J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[5]DUFOUR DR,LOTT JA,NOLTE FS,et al.Diagnosis and monitoring of hepatic injury,I.Performance characteristics of laboratory tests[J].Clin Chem,2000,46(12):2027-2049.
[6]LAMMER J,MALAGARI K,VOGL T,et al.Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma:Results of the PRE-CISION V study[J].Cardiovasc Intervent Radiol,2010,33(1):41-52.
[7]RISSE JH,MENZEL C,GRYNWALD F,et al.Therapy of hepatocellular cancer with iodine-131-Lipiodol[J].Rom J Gastroenterol,2004,13(2):119-124.
[8]LI SY,WU S,CHEN TS,et al.Effect of portal venous perfusion cinobufacini injection combined with TACE in patients with intermediate hepatocellular carcinoma[J].Clin J Med Offic,2017,45(9):884-886.(in Chinese)李淑英,吴申,陈挺松,等.经导管肝动脉栓塞化疗联合华蟾素门静脉灌注治疗中期原发性肝癌疗效研究[J].临床军医杂志,2017,45(9):884-846.
[9]HIGASHIHARA H.Transcatheter arterial chemoembolization of hepatocellular carcinoma:A Japanese experience[J].Hepatogastroenterology,2002,49(43):72-78.
[10]de BAERE T,DUFAUX J,ROCHE A,et al.Circulatory alterations inducedby intra-arterial injection of iodized oil and emulsions of iodized oiland doxorubicin:experimental study[J].Radiology,1995,194(1):165-70.
[11]KAN Z,IVANCEV K,HAGERSTRAND I,et al.In vivo microscopy of the liverafter injection of Lipiodol into the hepatic artery and portal vein inthe rat[J].Acta Radiologica,1989,30(4):419-425.
[12]ZHAO BL,CUI XJ,XING H,et al.Clinical effect of transcatheter arterial chemoembolization with iodinated oil combined with microspheres in treatment of large hepatocellular carcinoma[J].Shandong Med J,2018,58(22):87-89.(in Chinese)赵邦利,崔新江,邢辉,等.碘化油联合微球经导管肝动脉化疗栓塞治疗大肝癌效果观察[J].山东医药,2018,58(22):87-89.
[13]LUO JJ,YAN ZP,WANG JH,et al.HCC embolized by microspheres and iodized oil compared with by iodized oil alone[J].Chin Comput Med Imag,2008,14(2):154-159.(in Chinese)罗剑钧,颜志平,王建华,等.微球+碘化油联合栓塞与碘化油单独栓塞治疗肝癌的比较研究[J].中国医学计算机成像杂志,2008,14(2):154-159.
[14]ZHANG JX,LI FZ,CHAI J,et al.Clinical and controlled trial of transcatheter arterial chemoembolization with polyvinyl alcohol particle in patients with advanced hepatocellular carcinoma[J].J Hepatopancreatobiliary Surg,2014,26(3):195-197,203.(in Chinese)张军喜,李发中,柴健,等.微球加碘化油栓塞治疗肝癌疗效的临床对照研究[J].肝胆胰外科杂志,2014,26(3):195-197,203.
[15]YOU JX,WANG JB,AI ST,et al.TACE by using microspheres and lipiodol for the treatment of hepatocellular carcinoma:Analysis of short-term efficacy[J].J Intervent Radiol,2017,26(6):531-534.(in Chinese)游建雄,王精兵,艾松涛,等.微球联合碘油栓塞治疗肝癌的近期疗效分析[J].介入放射学杂志,2017,26(6):531-534.
[16]NAKAO N,UCHIDA H,KAMINO K,et al.Determination of the optimum dose level of lipiodol in transcatheter arterial embolization of primary hepatocellular carcinoma based on retrospective multivariate analysis[J].Cardiovasc Intervent Radiol,1994,17(2):76-80.
[17]XIAO CJ,ZHENG LY.Clinical effect of transarterial chemoembolization in treatment of liver injury:An analysis of 100 cases[J].Chin J Radiol,1997,31(11):777-779.(in Chinese)肖承江,郑丽吟.肝动脉栓塞化疗对肝损害的观察(附100例分析)[J].中华放射学杂志,1997,31(11):777-779.
[18]DUFOUR DR,LOTT JA,NOLTE FS,et al.Diagnosis and monitoring of hepatic injury.I.Performance characteristics of laboratory tests[J].Clin Chem,2000,46(12):2027-2049.
[19]KAN XF,ZHENG CS,XIONG B,et al.Simple conventional hepatic artery chemoembolization for the treatment of Barcelona stage C liver cancer:A clinic analysis[J].J Intervent Radiol,2018,27(12):1182-1185.(in Chinese)阚雪锋,郑传胜,熊斌,等.单纯经典肝动脉化疗栓塞术治疗巴塞罗那C期肝癌的临床分析[J].介入放射学杂志,2018,27(12):1182-1185.
[20]WANG FS,FAN JG,ZHANG Z,et al.The global burden of liver disease:The major impact of China[J].Hepatology,2014,60(6):2099-2108.
[21]ZHANG MY,NIU JQ.Prevalence of primary liver cancer in Eastern countries and related influencing factors[J].J Clin Hepatol,2018,34(7):1399-1402.(in Chinese)张明媛,牛俊奇.东方国家原发性肝癌发病趋势及影响因素[J].临床肝胆病杂志,2018,34(7):1399-1402.
[22]CAO K,BAO ZM,ZHOU XY,et al.Effects and mechanisms of hepatitis B virus X protein on invasion and migration of hepatocellular carcinoma cells[J].Chin J Dig Surg,2017,16(2):177-182.(in Chinese)曹宽,鲍仲明,周新宇,等.乙型肝炎病毒X蛋白对肝癌细胞侵袭与迁移能力的作用及机制[J].中华消化外科杂志,2017,16(2):177-182.