Viabahn覆膜支架与旁路途径治疗下肢动脉硬化闭塞症有效性的系统评价及Meta分析.pdf

作者单仁CorrespClinical rresearch:临床研究774介人放射学杂志2 0 2 3年8 月第32 卷第8 期J Intervent Radiol 2023,Vol.32,No.8Viabahn覆膜支架与旁路途径治疗下肢动脉硬化闭塞症有效性的系统评价及Meta分析林印胜，陈梅，郭坚东，伍思意，张艳，李承志【摘要】目的系统评价Viabahn覆膜支架与以人工血管为移植物的旁路途径治疗下肢动脉硬化闭塞症的有效性，并且探讨不同直径的Viabahn覆膜支架对股浅动脉通畅率的影响。方法检索数据库包括万方数据知识平台、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、EmBa s e、Cochrane Library和PubMed上有关肝素涂层覆膜支架治疗下肢动脉硬化闭塞症的临床研究。文献检索时间及语言无限制，文献筛选、质量评估、数据提取至少由2 位研究者独立完成并交叉核对，采用Cochrane软件和RevMan5.3软件完成结果分析。结果纳入文献共10 篇（对照研究7 篇、非对照研究3篇），肝素涂层覆膜支架与旁路途径疗效对比研究7 篇，不同肝素涂层覆膜支架直径疗效对比研究5篇。肝素涂层支架组（Viabahn组）患者7 92 例，旁路途经组（Bypass组）患者2 99例，Viabahn组行不同支架直径亚组分析(a组：5mm、b 组：6 mm、c 组：7 mm），a、b、c 组分别有6 1例、47 4例、8 4例患者。Bypass组不仅一期通畅率优于Viabahn组0 R0.47(0.23,0.94),P-0.03，而且技术成功率更高RR0.97(0.94,1.00）,P=0.0 2 ，但是Bypass组的住院时间明显长于Viabahn组MD-4.89(-5.29，-4.48）,P0.05)。a 组与b组通畅率没有统计学差异0 R0.63(0.31,1.28),P=0.20,c组的通畅率要优于b组(0 R0.57(0.33,0.98),P=0.04。结论与Viabahn相比，以人工血管作为移植物的旁路途经具有更好的一期通畅率及技术成功率，但是需要更长的住院时间；推荐置入7 mm直径的Viabahn会得到更高的通畅率，但是需要根据患者实际血管直径来选择。【关键词】下肢动脉硬化闭塞症；肝素涂层覆膜支架；旁路途径；有效性；Meta分析中图分类号：R543.5文献标志码：B文章编号：10 0 8-7 94X(2023)-08-0774-08Viabahn covered-stent and bypass approach for the treatment of lower extremity arteriosclerosisobliterans:a systematic review and meta-analysis of its effectivenessLINYinsheng,CHENMei,GUOJiandong,WU Siyi,ZHANG Yan,LI Chengzhi.Department of Interventional Radiology and VascularSurgery,First Affiliated Hospital of Jinan University,Guangzhou,Guangdong Province 510630,Chinaonding author:LI Chengzhi,E-mail:Abstract Objective To systematically evaluate the effectiveness of the Viabahn covered-stent andthe bypass approach by using artificial blood vessel as graft in the treatment of lower extremity arteriosclerosisobliterans(ASO),and to discuss the effect of different diameters of the Viabahn covered-stent on the patencyrate of the superficial femoral artery.Methods Computerized retrieval of academic papers concerning theclinical study of heparin-coated covered-stent for lower extremity AOS from the databases of Wanfang DataKnowledge Platform,China Journal Full-text Database(CNKI),China Biomedical Literature Database(CBM),EmBase,Cochrane Library,and PubMed was conducted.Both of the published time and language of thepapers are unrestricted.At least two researchers independently completed the literature screening,qualityassessment and data extraction,and the results were cross-checked.Cochrane software RevMan 5.3 was usedto complete the analysis of results.Results A total of 10 papers,including 7 randomized controlled trials(RCT)and 3 non-control studies,were enrlled in this study.There were 7 RCTs on the efficacy of heparin-coated covered-stent and bypass approach,and 3 comparative studies on the therapeutic effect of differentdiameter heparin-coated coated stents.There were 792 patients in the heparin-coated stent group(ViabahnD0I:10.3969/j.issn.1008-794X.2023.08.010立：510 6 30广东广州暨南大学附属第一医院介人血管外科通信作者：李承志志E-mail:775介人放射学杂志2 0 2 3年8 月第32 卷第8 期JIntervent Radiol 2023,Vol.32,No.8group)and 299 patients in the bypass group(Bypass group).According to the used stent diameter,the Viabahngroup was further divided into subgroup a(5 mm,n=61),subgroup b(6 mm,n=474),and subgroup c(7 mm,n=84).The primary patency rate in the Bypass group was better than that in the Viabahn group(OR:0.47(0.23,0.94),P=0.03),and the technical success rate in the Bypass group was remarkably higher than that in theViabahn group(RR:0.97(0.94,1.00),P=0.02),although the hospital stay in the Bypass group was obviouslylonger than that in the Viabahn group(MD:-4.89(-5.29,-4.48),P0.05).No statistically significant differences in the patency rate between subgroup a and subgroup b(OR:0.63(0.31,1.28),P=0.20),and the patency rate in subgroup c was better than that in subgroup b(0R:0.57(0.33,0.98),P=0.04).Conclusion Compared with the Viabahn covered-stent,in the treatment of lower extremity ASO thebypass approach by using artificial blood vessel as graft carries better primary patency rate and technicalsuccess rate,but it needs a longer hospital stay.Viabahn covered-stent of 7 mm diameter is recommended touse as it can get a higher patency rate,but,the selection of stent diameter should be on the specificcondition of a given patient.(J Intervent Radiol,2023,32:774-781)Key words lower extremity arteriosclerosis obliterans;heparin-coated covered-stent;bypass approach;effectiveness;meta-analysis股浅动脉是下肢动脉硬化闭塞症(arteriosclerosisobliterans)最常见的发病部位，根据2019年全球严重肢体威胁性缺血疾病的指南推荐，Glass期且具有良好膝下动脉流出道的严重肢体缺血患者首选旁路途经2 ,但是对于以间歇性跛行为主要症状的非严重肢体缺血患者，或没有自体静脉作为移植物的患者来说，旁路途径与血管腔内治疗对比研究仍较少。同时，随着介人器械的不断发展，肝素涂层覆膜支架随之产生，尽管有学者指出肝素涂层覆膜支架治疗下肢动脉硬化闭塞症具有良好的疗效3,但是不同直径的肝素涂层覆膜支架置入股浅动脉后的疗效仍存在争议3-4。因此，本文作者收集国内外相关文献，旨在对比Viabahn覆膜支架与以人工血管作为移植物的旁路途径治疗ASO的有效性及不同Viabahn直径对股浅动脉通畅率的影响，以期更好的指导临床。1材料与方法1.1纳人与排除标准纳人标准：包括肝素涂层覆膜支架及旁路途经两种方案的对照试验，且旁路途径是选用人工血管作为移植物，或包括不同直径的Viabahn治疗下肢动脉硬化闭塞症的临床研究；股浅、胭动脉狭窄或闭塞性病变。排除标准：涉及Viabahn及旁路途经以外的治疗方式，如药物涂层球囊、斑块旋切、机械抽栓装置等；靶病变是主髂动脉或膝下动脉病变；以严重肢体缺血患者为研究对象的试验；旁路途径以自体静脉为移植物的试验；综述、个案报道。1.2检索策略检索数据库包括万方数据知识平台、中国期刊全文数据库（CNKI)、中国生物医学文献数据库(CBM）、EmBa s e、Co c h r a n e L i b r a r y 和PubMed。中文检索词：下肢动脉硬化闭塞症、股浅动脉、股胭动脉、肝素涂层覆膜支架、旁路途经、随机。英文检索词：occlusive diseasestenosis disease-peripheral arterialdisease femoral artery femoropopliteal artery heparin-bonded stent、Vi a b a h n、c o v e r e d s t e n t s。语言及检索时间无限制，由2 位研究人员独立完成1.3文献筛选、资料提取及偏倚风险评价文献筛选、资料提取及偏倚风险评价均由2 位研究者独立完成后交叉核对,并由第3位高年资研究者解决分歧。严格遵循CochraneHandbook的标准，在随机方法、分配隐藏、盲法、数据完整性、偏倚方面对所有试验进行质量评价。资料提取内容包括作者、研究时间、研究方法、基线特征、基础疾病、结局指标、随访结果等。1.4结局指标及结果分析12个月一期通畅率定义为：无影像学依据证实靶动脉狭窄 50%或闭塞且12 个月内无靶血管重建；二期通畅率定义为：靶动脉闭塞后进行了至少一次靶血管重建，无影像学依据证实狭窄 50%或闭塞；截肢率定义为：大面积截肢或不可避免的脚趾截肢，不包括清创引流治疗；技术成功率定义为：靶动脉治疗后残余狭窄 30%；住院时长定义为：人院日期与出院日期之差；采用RevMan5.3软件分776-介人放射学杂志2 0 2 3年8 月第32 卷第8 期JInterventRadiol2023,Vol.32,No.8析，采用“倒漏斗图”检测是否存在发表偏倚。技术成功率采用相对危险度（relativerisk,RR）、截肢率采用率差（riskdiference，R D)表示，其余二分类变量均采用比值比（oddsratio，O R），住院时间采用均数加权均数差值（meandeviation，M D）表示，二者均以95%可信区间(CI)表示。通过P判断异质性的大小，根据P值选择不同分析模式，若P50%，则采用随机效应模型，若P50%，采用固定效应模型。2结果2.1文献筛选、基线特征及质量评价符合纳人排除标准文献共10 篇(9篇国外文献3-11),1篇国内文献12 ）（图1）,基本基线特征（表1、表2)。3篇文献4,9-10 对比不同Viabahn直径,7 篇文献对比Viabahn与Bypass,其中2 篇文献3-11Viabahn 组也对比不同支架直径对股浅动脉的影响。所有文献均报道了一期通畅率,2 篇文献没有报道技术成功率1-12 ,2篇文献没有报道住院时间8-12 ,所有文献都报道了截肢率。肝素涂层支架组(Viabahn组)患者7 92 例,旁路途经组(Bypass组）患者2 99例,Viabahn组不同支架直径行亚组分析(a组：5mmb组：6 mmc组：7 mm)，a、b、c 组分别有6 1例、47 4例、8 4例患者。所有的旁路途经均使用人工血管。根据评估随机对照试验偏倚风险的Cochrane工具,所有研究都存在不明确或高盲的风险。由于结果不一致的风险和证据的间接性，根据等级评分，随机和比较研究结果的证据质量中等（图2）。数据库收集文献(n=1631)CNKI(303）、万方（36 5）、CBM（438）Pu b me d(313）、Embase(163),Cochane Library(49)查重后排除460篇剩余117 1篇阅读标题、摘要后排除不相关文献1161篇剩余15篇阅读全文后排除5篇最终纳人10 篇图1文献筛选流程图2.2分析结果Bypass组的12 个月一期通畅率优于Viabahn组0 R0.47（0.2 3,0.94）,P=0.0 3，两组的二期通畅率无统计学差异0 R0.62(0.30,1.28）,P=0.2 0 。Viabahn组住院时间短于Bypass 组MD-4.89(-5.29,-4.48),P0.05)，二次通畅率分别为8 3%和8 6%(P0.05)，两组没有统计学差异，因此认为对于无可用性自体静脉或高危人群,血管腔内治疗是一种可以替代旁路途经的治疗方式。2 0 13年一项Meta分析比较了血管腔内治疗介人放射学杂志2 0 2 3年8 月第32 卷第8 期JInterventRadiol2023,Vol.32,No.8表1纳人文献基线特征研究（年）国家研究时段设计患者数（例）男性（%）年龄（岁）Waezi(2018)1)德国2005-2011Viabahn/Bypass27/2570.4%/92%689.7/658.2Reijnen(2017)(8)荷兰2010.11-2015.06Viabahn/Bypass63/6280.6%/73%68.58.8/66.77.9Ohki(2017)3日本2012.4-2013.08Viabahn/Bypass103/6882.3%/75%74.27.0/72.58.0McQuade(2010)7)美国2004.03-2005.05Viabahn/Bypass72/6780%/78.2%729.9/6710.7Lepantalo(2009)(6)芬兰3年Viabahn/Bypass23/2157%/57%64(48-79)/66(53-80)Jebran(2013)5)德国2005-2010Viabahn/Bypass27/25一689.7/658宋庆宏(2 0 14)12 中国2013Viabahn/Bypass22/31一63.728.64Saxon(2013)9)美国2007.10-2010.4Viabahn11361%679.6Kruse(2015)4)荷兰2001-2014Viabahn31575.1%6910.1Schneider(2011)10)美国2005.11-2007.4Viabahn2748.1%71.710.8表2基础疾病特征及病变特点基础疾病病变特点研究（年）分组DMHLHTSMKRICADCOPD长度/cmTASCII:C、DRf4Waezi(2018)()Viabahn22%70%96%26%11%63%15%1911.0637%37%Bypass44%92%96%24%32%60%20%24.391.9786%8%Reijnen(2017)8)Viabahn34.9%74.6%68.3%49.2%9.5%38.1%17.5%23.67.194%38%Bypass33.9%71%74.2%51.6%16.1%38.7%27.4%23.38.398%32%Ohki(2017)3)Viabahn60.2%62.1%88.3%50.5%一40.8%9.7%21.85.884%3%Bypass50%47.1%86.8%41.2%一30.9%5.9%21.65.8一一McQuade(2010)7)Viabahn19.4%31.4%41.7%30.6%一18.1%2.8%25.61515%12.5%Bypass29.9%31.3%62.7%40.2%一32.8%11.9%一22%28.3%Lepantalo(2009)6)Viabahn35%一68%70%5%18%14%一13%一Bypass14%一57%71%10%10%29%24%一Jebran(2013)5)Viabahn22.2%19%96.3%25.9%11.1%63%14.8%1911.1一37%Bypass44%23%96%24%32%60%20%24.42一宋庆宏(2 0 14)12)Viabahn45.5%一54.5%72.7%一45.5%一一一一Bypass38.7%一54.8%61.3%一45.2%一一一一Saxon(2013)9)Viabahn33%76%87%88%一49%11%1963.7%13.3%Kruse(2015)4)Viabahn36.8%57.1%70.2%57%16.2%46%一11.78.849.1%34.3%Schneider(2011)10)Viabahn33.3%一88.9%一一51.9%一一100%一DM：糖尿病；HL：高脂血症；HT：高血压SMK：抽烟;RI:肾脏病;CAD：冠心病；COPD：慢性阻塞性肺疾病；Rf:Rutherford分级随机序列产生（选择偏倚）分配隐藏（选择偏倚）对研究者和受试者施盲（实施偏奇）研究结果施盲（测量偏倚）结果数据的完整性（随访偏倚）选择性研究报告结果（报告偏倚）其他偏倚0%25%50%75%100%低度偏倚风险不清晰性偏倚风险高度偏倚风险图2纳人文献偏倚风险评估和旁路途径治疗严重肢体缺血患者的疗效，纳人4项随机对照研究，6 项观察研究，结果表明两者效果无统计学差异，但是在住院时长、手术创伤、术后并发症方面来说，血管腔内治疗更具有优势13。朱宋庆宏等12 做的一项研究同样支持该观点。不同学者对Viabahn及旁路途经治疗股胭动脉闭塞疾病的疗效存在争议，为了更好地指导临床及区分以往的研究，本研究所纳人的文献中存在以下778-介入放射学杂志2 0 2 3年8 月第32 卷第8 期J Intervent Radiol 2023,Vol.32,No.8ViabahnBypassOdds RatioOdds RatioStudyor SubgroupEventsTotalEventsTotalWeightM-H,Random,95%CIM-H,Random,95%CIJebran 20131227162516.7%0.450.15,1.37Lepantalo 2009112320217.6%0.050.01,0.40McQuade 20105272516721.5%0.820.38,1.75Ohki 201790103636817.1%0.550.19,1.62Reijnen 20174163396222.0%1.100.53,2.28Waezi 20181127202515.1%0.170.05,0.60Total(95%CI)315268100.0%0.470.23,0.94Total events217209Heterogeneity:Tau=0.44;Chi?=12.96,df=5(P=0.02);P=61%T0.010.1110100Test for overall effect:Z=2.13(P=0.03)1.一期通畅率森林图ViabahnBypassOdds RatioOdds RatioStudy_orSubgroupEventsTotalEventsTotalWeightM-H.Random,95%CIM-H.Random.95%CIJebran 20132227232514.4%0.380.07,2.18McQuade20106072586736.2%0.780.30,1.98Ohki 201710110368685.2%0.300.01,6.27Reijnen 20175463526234.3%1.150.43,3.07Waezi2018192724259.8%0.100.01,0.86Total(95%CI)292268100.0%0.620.30,1.28Total events256209Heterogeneity:Tau?=0.14;Chi?=5.05,df=4(P=0.28);P=21%0.010.1110100Test for overall effect:Z=1.29(P=0.20)2.二期通畅率森林图ViabahnBypassOdds RatioRisk RatioStudyorSubgroupEventsTotalEventsTotalWeightM-H,Random,95%CIM-H,Fixed,95%CIJebran 20132727252510.0%1.000.93,1.08Lepantalo 2009212321218.5%0.920.79,1.07McQuade 20107272676726.5%1.000.97,1.03Ohki 2017101103686831.2%0.980.95,1.02Reijnen 20175863626223.8%0.920.85,1.00Total(95%CI)288243100.0%0.970.94,1.00Total events279243Heterogeneity:Chi?2=8.34;df=4(P=0.08);P=52%0.850.911.11.2Test for overall effect:Z=2.29(P=0.02)3.技术成功率森林图ViabahnBypassMeanDifferenceMean DifferenceStudyor SubgroupMeanSDTotalMeanSDTotalWeightIV,Fixed,95%CIIV,Fixed,95%CIJebran20134.84.05279.835.53252.4%-5.03-7.68,2.38Lepantalo 20091.71.75234.522113.4%-2.803.91,-1.69Ohki 20173.4 2.910312.75.3688.8%9.30-10.68,-7.92Reijinen 20173.73.46364.4628.7%2.303.68,0.92Waezi20184.770.75279.831.052566.7%5.065.56,4.56Total(95%CI)243201100.0%-4.89-5.29,-4.48Heterogeneity:Chi?=66.79;df=4(P0.00001);P=94%H-10-50510Test for overall effect:Z=23.47(P 50%（53.3%比2 7.5%），2 年的生存率单发与多发（30.9%比2 3.1%）、单叶分布与双叶分布（31.4%比17.1%）、有包膜与无包膜（43.5%比2 4.5%）、肿瘤体积肝脏体积50%与 50%（32.0%比5.5%），差异均有统计学意义（均P 肝脏体积50%、合并门脉癌栓、肿瘤包膜是治疗后患者生存的影响因素。结论DEB-TACE治疗大肝癌安全、有效；肿瘤占肝脏体积 50%、门脉癌栓是DEB-TACE治疗大肝癌预后的独立危险因素，而肿瘤包膜是预后的保护因素。【关键词】大肝癌；化疗栓塞；肿瘤形态；介人治疗中图分类号：R735.7文献标志码：B文章编号：10 0 8-7 9 4X(2023)-08-0781-05Factors influencing the effect of drug-eluting beads transarterial chemoembolization for large livercancer LI Zhen,LI Yifan,YU Peng,LI Xin,ZHANGT Yuyuan,WU Bailu,LI Jie,YE Shuwen,XIEBingcan,HU Hongtao,WU Gang,REN Kewei,DUAN Xuhua,HAN Xinwei.Department of InterventionalRadiology,First Afiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province 450052,ChinaCorreauthorLIZhen.t620163.c01AbstractObjectiveTo investigate the factors that influence the effect of drug-eluting beadstransarterial chemoembolization(DEB-TACE)for large liver cancer(maximum diameter 5 cm).Methods Theclinical data of 228 patients with large liver cancer,who received DEB-TACE at the First Affiliated Hospitalof Zhengzhou University of China between December 2016 and May 2020,were retrospectively analyzed.TheD0I:10.3969/j.issn.1008-794X.2023.08.011基金项目：国家自然科学基金项目（U1904143），省部共建重点项目（SBGJ202102099），河南省重大公益专项(201300310400)作者单位：450 0 52河南郑州1河南省肿瘤微创介人工程技术研究中心、郑州大学第一附属医院放射介入科（李臻、李一帆、余鹏、李鑫、张玉元、吴白露、李杰、叶书文、谢炳灿、吴刚、任克伟、段旭华、韩新巍）；河南省肿瘤医院放射科（胡鸿涛）通信作者：李臻E-mail：l z l y c t 6 2 0 16 3.c o m