Please wait a minute...
浙江大学学报(医学版)  2017, Vol. 46 Issue (1): 44-51    DOI: 10.3785/j.issn.1008-9292.2017.02.07
原著     
国产载药微球经动脉化疗栓塞治疗不可切除原发性肝癌的临床研究
陈刚1,2(),张鼎2,应亚草2,王志峰2,陶伟2,朱皓2,张景峰1,*(),彭志毅1,*()
(1) 浙江大学医学院附属第一医院放射科, 浙江 杭州 310003
(2) 宁波市中医院放射科, 浙江 宁波 315010
Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma
CHEN Gang1,2(),ZHANG Ding2,YING Yacao2,WANG Zhifeng2,TAO Wei2,ZHU Hao2,ZHANG Jingfeng1,*(),PENG Zhiyi1,*()
(1) Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
(2) Department of Radiology, Traditional Chinese Medicine Hospital of Ningbo, Ningbo 315010, China
 全文: PDF(1197 KB)   HTML( 7 ) HTML
摘要: 目的

比较国产CalliSpheres?载药微球经动脉化疗栓塞(DEB-TACE)与常规经动脉化疗栓塞(cTACE)治疗不可切除原发性肝癌的近期临床疗效和安全性。

方法

42例不可切除原发性肝癌患者接受经导管动脉化疗栓塞(TACE)中使用CalliSpheres? DEB-TACE或cTACE治疗,在介入前1周及介入后1个月、3个月、6个月行MRI检查,对患者的随访影像资料和临床资料等进行汇总和分析,采用国际通用的改良实体瘤评价标准进行评价,比较两种方法在患者肿瘤反应、复发情况、并发症及不良反应发生率的差异。

结果

DEB-TACE组与cTACE组在介入治疗后1个月、3个月、6个月疾病缓解率、疾病控制率、治疗后并发症发生及肿瘤复发情况差异均无统计学意义(均P>0.05),且DEB-TACE组局部胆道损伤和胆汁瘤发生率以及瘤体外新发病灶发生率差异均无统计学意义(均P>0.05)。

结论

DEB-TACE与cTACE治疗用于不可切除原发性肝癌患者在肿瘤反应、治疗后并发症及肿瘤复发方面等结果相似。DEB-TACE治疗较cTACE治疗可能更易发生肝脏局部的并发症。

关键词: 癌, 肝细胞/药物疗法肝肿瘤/药物疗法药物洗脱支架化学栓塞, 治疗性肝动脉微球体治疗结果病例对照研究    
Abstract: Objective

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).

Methods

The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres?) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.

Results

There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra-or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.

Conclusion

There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.

Key words: Carcinoma, hepatocellular/drug therapy    Liver neoplasms/drug therapy    Drug-eluting stents    Chemoembolization, therapeutic    Hepatic artery    Microspheres    Treatment outcome    Case-control studies
收稿日期: 2016-12-20 出版日期: 2017-07-06
CLC:  R735.7  
基金资助: 国家卫计委—浙江省共建重大科研计划(WSK2014-2-009)
通讯作者: 张景峰,彭志毅     E-mail: chengang09@126.com;jingfengzhang73@163.com;pengzhiyi2010@163.com
作者简介: 陈刚 (1987-), 男, 硕士研究生, 主要从事胸腹部疾病的影像诊断和介入治疗; E-mail: chengang09@126.com|张景峰 (1973-), 男, 博士, 副主任医师, 主要从事肿瘤影像诊断和介入治疗. E-mail: jingfengzhang73@163.com|彭志毅 (1961-), 男, 硕士, 主任医师, 硕士生导师, 主要从事医学影像诊断和外周肿瘤以及脑血管介入治疗. E-mail: pengzhiyi2010@163.com
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
陈刚
张鼎
应亚草
王志峰
陶伟
朱皓
张景峰
彭志毅

引用本文:

陈刚,张鼎,应亚草,王志峰,陶伟,朱皓,张景峰,彭志毅. 国产载药微球经动脉化疗栓塞治疗不可切除原发性肝癌的临床研究[J]. 浙江大学学报(医学版), 2017, 46(1): 44-51.

CHEN Gang,ZHANG Ding,YING Yacao,WANG Zhifeng,TAO Wei,ZHU Hao,ZHANG Jingfeng,PENG Zhiyi. Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma. J Zhejiang Univ (Med Sci), 2017, 46(1): 44-51.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2017.02.07        http://www.zjujournals.com/med/CN/Y2017/V46/I1/44

[n(%)]
相关指标 cTACE组 DEB-TACE组 合计
性别?男性 17(85.0) 19(86.4) 36(85.7)
???女性 3(15.0) 3(13.6) 6(14.3)
肿瘤负荷
?单叶 8(40.0) 12(54.5) 20(47.6)
?双叶 12(60.0) 10(45.5) 22(52.4)
?多发结节 (≥4个病灶) 9(45.0) 13(59.1) 22(52.4)
Okuda分期?Ⅰ 10(50.0) 12(54.5) 22(52.4)
????? Ⅱ 10(50.0) 10(45.5) 20(47.6)
Child-Pugh分级?A 17(85.0) 15(68.2) 32(76.2)
??????? B 3(15.0) 7(31.8) 10(23.8)
巴塞罗那肝癌分期?A 2(10.0) 5(22.7) 7(16.7)
?????????B 12(60.0) 9(40.9) 21(50.0)
?????????C 6(30.0) 8(36.4) 14(33.3)
门脉癌栓或转移?有 5(25.0) 7(31.8) 12(28.6)
????????无 15(75.0) 15(68.2) 30(71.4)
表1  cTACE组与DEB-TACE组患者临床特征分析
[n(%)]
组别 随访时间 n CR PR SD PD CR+PR CR+PR+SD
cTACE组 1个月 16 2(12.5) 7(43.8) 4(25.0) 3(18.8) 9(56.3) 13(81.2)
3个月 16 0(0.0) 7(43.8) 5(31.3) 4(25.0) 7(43.8) 12(75.0)
6个月 16 0(0.0) 4(25.0) 6(37.5) 6(37.5) 4(25.0) 10(62.5)
DEB-TACE组 1个月 17 3(17.6) 9(52.9) 4(23.5) 1(5.9) 12(70.6) 16(94.1)
3个月 17 3(17.6) 7(41.2) 3(17.6) 4(23.5) 10(58.8) 13(76.5)
6个月 17 2(11.8) 2(11.8) 6(35.3) 7(41.2) 4(23.5) 10(58.8)
表2  cTACE组与DEB-TACE组患者治疗后肿瘤反应率比较
[n(%)]
组别 随访时间 n 局部复发 新发病灶或肝外转移
cTACE组 3个月 16 2(12.5) 2(12.5)
6个月 16 4(25.0) 5(31.2)
DEB-TACE组 3个月 17 0(0.0) 4(23.5)
6个月 17 2(11.8) 7(41.2)
表3  cTACE组与DEB-TACE组患者治疗后肿瘤复发率比较
[n(%) 或 ($\overline x$±s)]
组别 n 不良反应及并发症
体温大于38° 腹痛 使用止痛药 使用吗啡 恶心 呕吐 乏力 局部胆道损伤
cTACE组209(45.0)11(55.0)3(15.0)0(0.0)5(25.0)4(20.0)7(35.0)0(0.0)
DEB-TACE组228(36.4)8(36.4)5(22.7)1(4.5)3(13.6)3(13.6)3(13.6)2(9.1)
P0.5690.2260.8081.0000.5870.8900.2070.489
组别n肝功能指标
白蛋白
(g/L)
ALT
(U/L)
AST
(U/L)
总胆红素
(μmol/L)
胆碱酯酶
(U/L)
凝血酶原
时间 (s)
甲胎蛋白
(ng/mL)
cTACE组2037.2±3.7130.0±51.1167.0±118.722.0±3.55171.2±1181.112.0±0.796.6(42.2~7277.6)
DEB-TACE组2236.6±7.491.1±76.5104.5±89.324.5±13.94914.1±2031.513.0±2.066.1(15.1~4894.9)
P0.7490.1020.2480.5450.8230.3390.507
表4  cTACE组与DEB-TACE组治疗后不良反应、并发症发生率及肝功能指标比较
图1  一例患者胆道铸型的MRI表现 患者男性,54岁,乙型病毒性肝炎.患者治疗前T1WI (A) 显示胆管右后支未见异常 (箭头所示),首次DEB-TACE治疗后3个月T1WI (B) 呈高信号 (箭头所示),T2WI (C) 呈低信号 (箭头所示).
图2  一例患者胆汁瘤及胆管扩张的MRI表现 图 1同一患者.患者治疗前T2WI (A) 正常;治疗后3个月T2WI (B) 显示胆汁瘤形成 (蓝箭头所示) 及胆道铸型远端胆管扩张 (红箭头所示);增强扫描门静脉期 (C) 胆汁瘤未见强化 (蓝箭头所示),扩张胆管未见强化 (红箭头所示).
1 PARKIN D M, BRAY F, FERLAY J et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55(2): 74-108 doi: 10.3322/canjclin.55.2.74
doi: 10.3322/canjclin.55.2.74
2 CUCCHETTI A, TREVISANI F, CESCON M et al. Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population. J Hepatol. 2012, 56(5): 1089-1096 doi: 10.1016/j.jhep.2011.11.022
doi: 10.1016/j.jhep.2011.11.022 pmid: 22245900
3 BRUIX J, SHERMAN M . Management of hepatocellular carcinoma. Hepatology. 2005, 42(5): 1208-1236 doi: 10.1002/hep.v42:5
4 European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer . EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. J Hepatol. 2012, 56(4): 908-943 doi: 10.1016/j.jhep.2011.12.001
doi: 10.1016/j.jhep.2011.12.001 pmid: 22424438
5 MARELLI L, STIGLIANO R, TRIANTOS C et al. Transarterial therapy for hepatocellular carcinoma:which technique is more effective? a systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 2007, 30(1): 6-25 doi: 10.1007/s00270-006-0062-3
6 VARELA M, REAL M I, BURREL M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007, 46(3): 474-481 doi: 10.1016/j.jhep.2006.10.020
doi: 10.1016/j.jhep.2006.10.020
7 POON R T, TSO W K, PANG R W et al. A phase Ⅰ/Ⅱ trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol. 2007, 5(9): 1100-1108 doi: 10.1016/j.cgh.2007.04.021
doi: 10.1016/j.cgh.2007.04.021 pmid: 17627902
8 LENCIONI R, PETRUZZI P, CROCETTI L . Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol. 2013, 30(1): 3-11 doi: 10.1055/s-00000068
9 DHANASEKARAN R, KOOBY D A, STALEY C A et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol. 2010, 101(6): 476-480
10 VOGL T J, LAMMER J, LENCIONI R et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads:results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011, 197(4): W562-W570 doi: 10.2214/AJR.10.4379
doi: 10.2214/AJR.10.4379 pmid: 21940527
11 FORNER A, REIG M E, DE LOPE C R et al. Current strategy for staging and treatment:the BCLC update and future prospects. Semin Liver Dis. 2010, 30(1): 61-74 doi: 10.1055/s-0030-1247133
doi: 10.1055/s-0030-1247133 pmid: 20175034
12 LEWIS A L, TAYLOR R R, HALL B et al. Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol. 2006, 17(8): 1335-1343 doi: 10.1097/01.RVI.0000228416.21560.7F
doi: 10.1097/01.RVI.0000228416.21560.7F pmid: 16923981
13 HONG K, KHWAJA A, LIAPI E et al. New intra-arterial drug delivery system for the treatment of liver cancer:preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res. 2006, 12(8): 2563-2567 doi: 10.1158/1078-0432.CCR-05-2225
doi: 10.1158/1078-0432.CCR-05-2225 pmid: 16638866
14 Varela M, Real M I, Burrel M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007, 46(3): 474-481 doi: 10.1016/j.jhep.2006.10.020
doi: 10.1016/j.jhep.2006.10.020
15 MALAGARI K, ALEXOPOULOU E, CHATZIMICHAIL K et al. Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments:midterm results of doxorubicin-loaded DC bead. Abdom Imaging. 2008, 33(5): 512-519 doi: 10.1007/s00261-007-9334-x
doi: 10.1007/s00261-007-9334-x pmid: 17938995
16 SONG M J, PARK C H, KIM J D et al. Drug-eluting bead loaded with doxorubicin versus conventional Lipiodol-based transarterial chemoembolization in the treatment of hepatocellular carcinoma:a case-control study of Asian patients. Eur J Gastroenterol Hepatol. 2011, 23(6): 521-527 doi: 10.1097/MEG.0b013e328346d505
doi: 10.1097/MEG.0b013e328346d505 pmid: 21537127
17 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 PRECISION V study. Cardiovasc Intervent Radiol. 2010, 33(1): 41-52 doi: 10.1007/s00270-009-9711-7
doi: 10.1007/s00270-009-9711-7 pmid: 2816794
18 GOLFIERI R, GIAMPALMA E, RENZULLI M et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014, 111(2): 255-264 doi: 10.1038/bjc.2014.199
doi: 10.1038/bjc.2014.199 pmid: 24937669
19 FACCIORUSSO A, MARIANI L, SPOSITO C et al. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Gastroenterol Hepatol. 2016, 31(3): 645-653 doi: 10.1111/jgh.2016.31.issue-3
doi: 10.1016/j.dld.2016.02.005 pmid: 26965785
20 BAUR J, RITTER C O, GERMER C T et al. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma. Hepat Med. 2016, 8: 69-74
21 SCARTOZZI M, BARONI G S, FALOPPI L et al. Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma:efficacy and safety results from a large mono-institutional analysis. J Exp Clin Cancer Res. 2010, 29: 164 doi: 10.1186/1756-9966-29-164
22 VOGL T J, LAMMER J, LENCIONI R et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads:results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011, 197(4): W562-W570 doi: 10.2214/AJR.10.4379
doi: 10.2214/AJR.10.4379 pmid: 21940527
23 GOLFIERI R, GIAMPALMA E, RENZULLI M et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014, 111(2): 255-264 doi: 10.1038/bjc.2014.199
doi: 10.1038/bjc.2014.199 pmid: 24937669
24 WALDRAM R, WILLIAMS R, CALNE R Y . Bile composition and bile cast formation after transplantation of the liver in man. Transplantation. 1975, 19(5): 382-387 doi: 10.1097/00007890-197505000-00004
doi: 10.1097/00007890-197505000-00004 pmid: 168674
25 BRANDSAETER B, SCHRUMPF E, CLAUSEN O P et al. Recurrent sclerosing cholangitis or ischemic bile duct lesions-a diagnostic challenge?. Liver Transpl. 2004, 10(8): 1073-1074 doi: 10.1002/lt.20192
doi: 10.1002/lt.20192
26 PFAU P R, KOCHMAN M L, LEWIS J D et al. Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc. 2000, 52(1): 55-63 doi: 10.1067/mge.2000.106687
doi: 10.1067/mge.2000.106687 pmid: 10882963
27 CLERMONTS S H, VAN DAM R M . Obstructive putty-like cast of the biliary tree. Hepatobiliary Surg Nutr. 2014, 3(1): 47-49
28 BENNINGER J, GROBHOLZ R, OEZTUERK Y et al. Sclerosing cholangitis following severe trauma:description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms. World J Gastroenterol. 2005, 11(27): 4199-4205 doi: 10.3748/wjg.v11.i27.4199
doi: 10.1055/s-2005-858505 pmid: 16015689
29 GELBMANN C M, RUMMELE P, WIMMER M et al. Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically ill patients. Am J Gastroenterol. 2007, 102(6): 1221-1229 doi: 10.1111/ajg.2007.102.issue-6
doi: 10.1111/j.1572-0241.2007.01118.x pmid: 17531010
30 MONIER A, GUIU B, DURAN R et al. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma:comparison between drug-eluting beads and lipiodol emulsion. Eur Radiol. 2017, 27(4): 1431-1439 doi: 10.1007/s00330-016-4488-y
doi: 10.1007/s00330-016-4488-y pmid: 27436016
[1] 丁元 等. 腹腔镜胰体尾切除术患者围手术期加速康复管理及效果评估[J]. 浙江大学学报(医学版), 2017, 46(6): 625-629.
[2] 祝子逸 等. 内镜引导下吻合口瘘冲洗治疗食管胃吻合口瘘合并瘘旁脓肿临床疗效观察[J]. 浙江大学学报(医学版), 2017, 46(6): 637-642.
[3] 陆薇 等. 改良侧壁开窗式上颌窦底提升术治疗上颌后牙区缺牙伴重度骨萎缩患者临床观察[J]. 浙江大学学报(医学版), 2017, 46(6): 630-636.
[4] 张思影 等. CT和磁共振参数反应图在肿瘤精准疗效评估中的研究进展[J]. 浙江大学学报(医学版), 2017, 46(5): 468-472.
[5] 潘静颖 等. PET-CT与乳腺癌分子病理分型、治疗反应及预后的相关性研究进展[J]. 浙江大学学报(医学版), 2017, 46(5): 473-480.
[6] 邹丽霞 等. 人源化白细胞介素-6受体抗体治疗全身型幼年特发性关节炎的疗效及安全性[J]. 浙江大学学报(医学版), 2017, 46(4): 421-426.
[7] 张美霞 等. 静脉溶栓获益的最大梗死体积阈值与急性缺血性卒中患者发病时间的关系[J]. 浙江大学学报(医学版), 2017, 46(4): 384-389.
[8] 张晓群 等. 不同药物洗脱支架对冠状动脉小血管病变患者预后影响的meta分析[J]. 浙江大学学报(医学版), 2017, 46(3): 305-314.
[9] 陈益明 等. 中孕期母血清甲胎蛋白和游离β-hCG筛查胎儿腹裂和脐膨出的效率[J]. 浙江大学学报(医学版), 2017, 46(3): 268-273.
[10] 翁露茜 等. 腭中缝骨皮质切开辅助快速扩弓矫治15~25岁上颌横向宽度不足患者临床研究[J]. 浙江大学学报(医学版), 2017, 46(2): 198-205.
[11] 翁露茜,宋晓佳,李娟,刘彭若峰,林军. 腭中缝骨皮质切开辅助快速扩弓矫治15~25岁上颌横向宽度不足患者临床研究[J]. 浙江大学学报(医学版), 2017, 46(2): 198-205.
[12] 李文波 等. 手术和非手术治疗老年人肱骨近端三、四部分骨折疗效的meta分析[J]. 浙江大学学报(医学版), 2016, 45(6): 641-647.
[13] 夏光发 等. 新辅助化疗前后激素受体变化的乳腺癌患者辅助内分泌治疗的疗效[J]. 浙江大学学报(医学版), 2016, 45(6): 614-619.
[14] 方敏波 等. 瞬时受体电位通道M2外显子单核苷酸多态性rs1556314与脓毒症的相关性分析[J]. 浙江大学学报(医学版), 2016, 45(4): 410-415.
[15] 何斌 等. 贝伐珠单克隆抗体在难治性子宫颈癌中的应用进展[J]. 浙江大学学报(医学版), 2016, 45(4): 395-402.