ThULEP与HoLEP治疗良性前列腺增生疗效比较的Meta分析.pdf

764临床研究ThULEP 与 HoLEP治疗良性前列腺增生疗效比较的 Meta 分析周英豪，余皖东，马杭彬，张雪虎，周程，施国伟（复旦大学附属上海市第五人民医院泌尿外科，上海2 0 0 2 40）Efficacy of ThULEP versus HoLEP in treating benign prostatic hyperplasia:a MetaanalysisZHOU Yinghao,YU Wandong,Ma Hangbin,ZHANG Xuehu,ZHOU Cheng,SHI Guowei(Department of Urology,The Fifth Peoples Hospital of Shanghai,Fudan University,Shanghai 200240,China)ABSTRACT:Objective To compare the efficacy and safety of thulium laser enucleation of the prostate(ThULEP)andholmium laser enucleation of the prostate(HoLEP)in the treatment of benign prostatic hyperplasia(BPH).MethodsRandomized controlled trials（RC T s)a n d c lin ic a l c o n t r o lle d t r ia ls （C C T s)w e r e s e a r c h e d in Pu b M e d,Em b a s e,C o c h r a n eLibrary,CNKI and Wanfang Database from Jan.1,2010 to May 30,2022.Two reviewers independently screened literature,extracted data,and assessed the risk of bias of included studies.All divergences were resolved by a third researcher.RevMan 5.4software was used for Meta analysis.Results A total of 7 studies were included,involving 1 726 patients,750 in the ThULEPgroup and 976 in the HoLEP group.Meta analysis showed that,compared with HoLEP group,the ThULEP group had shortercatheter indwelling time MD=-0.10,95%CI(-0.17-0.03),P=0.004,shorter hospital stay MD=-0.43,95%CI(-0.60-0.25),P0.000 01,lower IPSS score 12 months after surgery MD=-1.13,95%CI(-1.95-0.30),P=0.007,lower QoL score 12 months after surgery MD=-1.00,95%CI(-1.19-0.81),P0.001,lower transfusion rateOR=0.11,95%CI(0.03-0.36),P=0.000 3 and lower incidence of urinary incontinence OR=0.24,95%CI(0.09-0.66),P=0.006J.Conclusion ThULEP may have similar efficacy and safety as HoLEP in the treatment of BPH,and hasmore advantages in some aspects.KEY WORDS:thulium laser enucleation of the prostate;holmium laser enucleation of the prostate;benign prostatichyperplasia;Meta analysis;systematic review摘要：目的通过Meta分析比较激光前列腺刻除术(ThULEP)与铁激光前列腺切除术（HoLEP)治疗良性前列腺增生（BPH)的疗效和安全性。方法计算机检索PubMed、Em b a s e、C o c h r a n e Lib r a r y、中国知网、万方等数据库，收集比较ThULEP和HoLEP治疗BPH的随机对照试验及对照临床试验，检索时限从2 0 10 年1月1日一2 0 2 2 年5月30 日，由两位研究者独立进行文献的筛选、评价和数据提取，所有分歧均由第3位研究者解决，采用RevMan5.4软件进行统计学分析。结果共纳入7 项研究共17 2 6 例患者，其中ThULEP组7 50 例，HoLEP组97 6 例；Meta结果显示，与HoLEP组相比，ThULEP组留置导尿时间M D=0.10,9 5%C I 0.17 0.0 3),P=0.0 0 4、住院时间MD=0.43,95%CI(0.600.2 5)，P 0.0 0 0 0 1更短，术后12 个月IPSS评分更低MD=1.13,95%CI（1.950.30），P=0.0 0 7 、术后12 月QoL评分更低MD=-1.00,95%CI（-1.190.8 1)，P 0.0 0 1，需要输血的患者更少OR=0.11,95%CI(0.030.36），P=0.0 0 0 3，发生尿失禁的概率更低OR=0.24,95%CI(0.090.6 6)，P=0.0 0 6 。结论ThULEP相较于HoLEP在治疗BPH上可能具有类似的疗效及安全性，并在某些方面更具有优势。关键词：激光前列腺刻除术；激光前列腺切除术；良性前列腺增生；Meta分析；系统评价中图分类号：R697良性前列腺增生（benign prostate hyperplasia，BPH)是一种老年男性常见的良性疾病，临床主要表现为不同程度的下尿路症状（lower urinarytract收稿日期：2 0 2 2-0 9-30基金项目：上海市重点专科基金项目（No.ZK2019A03)通信作者：施国伟，主任医师。E-mail：s g w 16 3.c o m作者简介：周英豪，硕士研究生在读，住院医师。研究方向：前列腺肿瘤。E-mail:J Mod Urol,Vol.28 No.9 Sep.2023文献标志码：AD0I:10.3969/j.issn.1009-8291.2023.09.007symptoms,LUTS)，它的发病率随着年龄的增长不断升高，据统计，中国大陆在198 9一2 0 14年，40 岁男性中BPH的总患病率为36.6%L1。针对需要接受手术的BPH患者，经尿道前列腺电切术修回日期：2 0 2 3-0 5-0 8(transurethral resection of prostate,TURP)存在诸多局限，加之近数十年激光技术的飞速发展，激光刻除术式，尤其是铁激光前列腺切除术（holmiumlaserhttp:/;zgmnwk.cug.top现代泌尿外科杂志enucleation of prostate,HoLEP)得到了广泛应用2 。HoLEP在术后恢复方面相较于TURP有显著的改善3,已经被指南强烈推荐为替代TURP或开放性前列腺切除术的选择4。激光可以有效地实现对组织的汽化切割以及凝固，WANI等5 研究证实激光前列腺刻除术（thulium laser enucleation ofprostate,ThULEP)相较于 TURP,多种术后指标均有明显改善。此外，许多研究表明，ThULEP可以达到与HoLEP相似的效果，具有相同的疗效及安全性6 。因此本研究通过Meta分析比较ThULEP与HoLEP治疗BPH 的优劣，旨在评价二者在临床上治疗BPH的安全性和有效性，为临床医师在术式的选择上提供循证学证据。1资料与方法1.1文献检索采用计算机搜索PubMed、Em b a s e、Cochrane Library、中国知网、万方等数据库，检索时限为2 0 10 年1月1日一2 0 2 2 年5月30 日。以PubMed为例，在Title/Abstract中检索，检索词为:thulium laser OR thulium OR thulium ORthulep OR thuvep、h o le p O R h o lm iu m la s e r O R H o-YAG OR holmium laser prostate OR hyperplasia ofprostate OR benign prostatic hyperplasia ORprostatic hyperplasia。1.2纳入与排除标准1.2.1纳入标准研究对象：接受 ThULEP与HoLEP治疗,且术后病理证实为BPH 的患者;研究类型：随机对照试验（randomized controlled trial，RCT）及对照临床试验（controlled clinical trial，CCT);干预措施：试验组采取ThULEP治疗，对照组采取HoLEP治疗；结局指标：围手术期结果包括手术时间、血红蛋白下降程度、切除组织重量、平均留置尿管时间、平均住院时间和手术并发症等；术后随访疗效指标包括国际前列腺症状评分(International Prostatic Symptomatic Score,IPSS),最大尿流率(maximum urinary flow rate,Qmax)、生活质量评分（quality of life，Q o L)和术后残余尿（postvoidresidualurine,PVR)等指标。1.2.2排除标准无法获得准确数据的研究；无合并分析数据的研究；在后续出版物中更新的研究。1.3文献筛选与数据提取由两位研究者独立进行文献的筛选、评价和数据提取，所有分歧均由第3位研究者解决。提取内容包括：第一作者，发表年份，各组患者的数量、年龄、随访时间、前列腺体积，术后随2023年9 月第2 8 卷第9 期http:/jmurology.xjtu.edu,cn;zgmnwk.cug.top765访疗效指标（包括术后IPSS、术后Qmax、术后QoL和PVR），围手术期指标（包括手术时间、切除组织重量、血红蛋白下降程度、留置导尿时间、住院时间及并发症指标包括输血率、尿路感染、尿道狭窄、尿失禁、尿潴留等）。1.4质量评价两位研究者分别按照Cochrane系统评价员手册5.0 中的质量评价工具独立进行风险偏倚评估，包括：随机分配方法；分配隐藏；盲法；数据的完整性；有无选择性报告偏倚；其他偏倚。1.5统计学方法使用RevMan5.4软件进行统计学分析，连续性变量应用加权均数差（meandeviation，M D）及9 5%可信区间（confidenceinterval,CI），二分类变量采用比值比（odds ratio，OR)及95%CI,对上述研究进行异质性分析，异质性I?50%,P0.10时采用随机效应模型。2结 果2.1文献检索及筛选结果通过数据库筛选出文献643篇，手工纳入文献12 篇，剔除重复文献后得到238篇文献，阅读文献标记及摘要初筛后剩余54篇文献，排除无关文献2 0 篇，阅读全文并严格按照纳人和排除标准，最终纳人7 篇文献。2.2纳入文献基本特征与质量评价共7 篇文献，1726例患者纳入此次Meta分析，其中ThULEP组750例,HoLEP组9 7 6 例，随访时间6 18 个月。纳人文献中2 篇纳入体积 12 0 mL（12 0 g），可列为体积 12 0 mL(120g)组；1篇纳入标准为小于8 0 mL（8 0 g），4篇未详细叙述前列腺体积范围，此5篇文献列为非 12 0 mL（12 0 g）组。在所有纳人研究中，4篇研究地区位于欧洲，3篇位于亚洲，详见表1。纳入文献质量评价见图1。随机序列的产生（选择偏倚）分配隐藏（选择偏倚）参与者和受试者双盲（实施偏倚）研究结局盲法评价（测量偏倚）结局数据不全（随访偏倚）选择性结局报告（报告偏倚）其他偏倚0%25%50%75%100%低风险中风险高风险图1纳入文献质量评价766表1纳入文献的基本特征手术纳人文献例数年龄/岁方式BECKER7 2018*#ThULEP25366.77.6HoLEP48967.37ENIKEEVEs1 2022#ThULEP77HoLEP86ZHANGE91 2012*ThULEP71HoLEP62PIROLAL101 2018#ThULEP117HoLEP117BOZZINIL11 2021*#ThULEP115HoLEP121ZHANG121 2020*ThULEP58HoLEP58陈志强13 2 0 2 2*ThULEP5069.2515.8080.5636.4717.026.64HoLEP5268.3217.8383.2043.4216.955.67*随机对照试验(RCT),其他文献为对照临床试验（CCT)；#研究地区来自欧洲,其他文献研究地区来自亚洲。ThULEP：激光前列腺劑除术；HoLEP：铁激光前列腺切除术。2.3Meta分析结果2.3.1围手术期结果围手术期结果包括手术时间、切除组织重量、血红蛋白下降程度、留置导尿时间、住院时间，均为连续性变量，除切除组织重量外，均采用固定效应分析。与HoLEP相比，ThULEP留置导尿ThULEP组StudyorSubgroupMeanSDTotalMeanSDTotalBECKER20183.50.8BOZZINI1120211.92.81ENIKEEVi81202210.3ZHANG(920122.4陈志强132 0 2 21.52.82Total(95%c)Heterogeneity:x*=0.00,df=4(P=1.00):12=0%Testforoveralleffect:Z=2.87(P=0.004)StudyorSubgroupBOZZINI112021ENIKEEV(82022PIROLA1102018陈志强1312 0 2 2Total(95%cI)Heterogeneity:x*=0.57,df=3(P=0.90);I=0%Testforoverall effect:Z=4.71(P0.00001)2.3.2术后随访疗效结果与 HoLEP 相比,ThULEP 在术后 12 月 IPSSMD=一1.13,9 5%CI（1.950.30),P=0.0 0 7 、术后12 月QoL评分J Mod Urol,Vol.28 No.9 Sep.2023前列腺Qmax/IPSS/分体积/mL92.139.822.91.891.437.322.91.664.36.266.218.965.07.064.717.576.29.746.625.273.4 10.343.523.0707.417525.93716.677529.6367.117.8390.242.769.515.5486.346.772.73.191.86.971.83.993.07.2HoLEP组2533.611523.55121861.11712.5501.63.2252575801ThULEP组HoLEP组MeanSDTotalMeanSDTotal2.24.051152.83.891212.2 1.20.50.592.53.6图2 激光前列腺刻除术(ThULEP)组与钦激光前列腺切除术(HoLEP)组围手术期结果的Meta分析随访前列腺PVR/mLQoL/分mL s-1时间月分组/mL7.42.790.345.66.81.688.342.523.36.08.73.224.35.18.62.624.63.26.83.922.8 2.67.33.7204.2672.22215.9373.26103.5104.818.2 7.317.98.05115.5130.517.9 6.958.26.7122.83.76.62.323.93.97.12.8172.739.48.956.03385.2139.038.345.6580.2536.66时间MD=-0.10,95%CI(-0.17 0.0 3),P=0.004更短、住院时间MD=-0.43,95%CI(-0.60一0.2 5),P 0.0 5)。WeightMeanDifference/%IV,fixed,95%cl0.54890.377162Weight/%3.1862.71170.9502.63683.80.74.11.376.5 70.25.10.875.5 77.35.01.064.632.564.633.49059.2690.4120.4165.546.240.00.100.21,0.010.7-0.10-0.91,0.71 54.90.100.19,-0.014.0-0.10-0.44,0.24 0.30.10-1.27,1.071000.10-0.17,-0.03MeanDifferenceIV,fixed,95%cl0.60-1.61,0.411.17725.21.011173.1752367100A：留置导尿时间；B：住院时间。更低MD=-1.00,95%CI(-1.19-0.8 1),P0.05），661850.741250.741269MeanDifferenceIV,fixed,95%cl-1-0.500.5ThULEP组HoLEP组MeanDifferenceIV,fixed,95%cl0.500.85,0.1569.90.400.61,0.19 1.8-0.10-1.42,1.220.430.60,0.25非 12 0120120非 12 0非 12 0非 12 0非 12 01?-1-0.500.51ThULEP组HoLEP组http:/;zgmnwk.cug.top现代泌尿外科杂志提示对于术后中短期疗效方面，ThULEP疗效不劣于HoLEP。尽管在术后早期，两者在IPSS及QoL评分StudyorSubgroupMeanSDTotalMeanSDTotalBOZZINI1120215.456.881156.123.75PIROLA1020184陈志强1312 0 2 29.155.82Total(95%cI)282Heterogeneity:Tau=1,19;x*=5.99,df=2(P=0.05);I2=67%Testforoveralleffect:Z=0.99(P=0.32)ThULEP组StudyorSubgroupMeanSDTotalBECKERI1201810.82.9253PIROLA110201844.44117Total(95%cI)370Heterogeneity:x*=1.19;df=1(P=0.17);I=48%Testforoveralleffect:Z=0.89(P=0.37)ThULEP组StudyorSubgroupMeanSDTotalMeanSDTotalBOZZINI1120216.81 4.921157.345.43121PIROLA1020183.54.44117Total(95%cI)232Heterogeneity:x=1.27;df=1(P=0.26);r=21%Test foroverall effect:Z=2.69(P=0.007)图3激光前列腺刻除术(ThULEP)组与激光前列腺切除术(HoLEP)组术后国际前列腺症状(IPSS)评分的Meta分析ThULEP组StudyorSubgroupMeanSDTotalBOZZINI11202140.915.22115陈志强1312 0 2 243.0511.24Total(95%cl)Heterogeneity:x*=0.47,df=1(P=0.49);I2=0%Testforoveralleffect:Z=1.70(P=0.09)ThULEP组StudyorSubgroupMeanSDTotalBECKER20181.5ENIKEEVIl820221.8ZHANG020122.1Total(95%cI)Heterogeneity:Tau*=0.04;x*=38.57;df=2(P0.000 01);I2=95%Testforoveralleffect:Z=0.93(P=0.35)ThULEP组StudyorSubgroupMeanSDTotalBOZZINI11202143.612.49115PIROLA101201800.74117Total(95%cI)232Heterogeneity:x*=0.40;df=1(P=0.53);r=0%Testforoveralleffect:Z=10.39(P0.05)。MeanDifferenceIV,Random,95%cl37.8-2.00-3.24,-0.760.83-1.15,2.810.77-2.28,0.75IV,fixed,95%Cl0.300.74,0.140.50-0.55,1.550.180.58,0.221.502.55,0.451.131.95,0.30MeanDifferenceIV,fixed,95%cl3.306.95,0.351.17-6.01,3.672.535.44,0.38Mean Difference6233.50.100.19,0.011000.100.33,0.12-4-1-0.5ThULEP组HoLEP组MeanDifferenceIV,fixed,95%cl-21-10ThULEP组HoLEP组MeanDifferenceIV,fixed,95%ci-2024-4ThULEP组HoLEP组MeanDifferenceIV,Random,95%cl-0.5-0.25ThULEP组HoLEP组MeanDifferenceIV,fixed,95%c/-4-2ThULEP组HoLEP组-2ThULEP组HoLEP组MeanDifferenceIV,fixed,95%cl100.500.250220120.54A4?C?http:/;zgmnwk.cug.top768Study orSubgroupBECKERI72018BOZZINI112021ZHANGl02012Total(95%cI)Total eventsHeterogeneity:x*=1.78,df=2(P=0.41);I=0%Test for overall effect:Z=3.65(P=0.000 3)Study orSubgroupBECKER2018BOZZINI112021ENIKEEVI812022Total(95%cI)TotaleventsHeterogeneity:x=0.04,df=2(P=0.98);I*=0%Test for overall effect:Z=2.77(P=0.006)2.4亚组分析和发表偏倚根据地区、发表时间及前列腺体积进行亚组分析，地区和发表时间亚组间I均50%，而前列腺体积的不同有可能是异质性来源之一,前列腺体积小于12 0 mL组的I2=0.0080 mL:18-monthfollow-up resultsJJ.World J Urol,2020,38(6):1555-1562.13陈志强，胡海义，章又云.HoLEP和ThuLEP临床疗效的前瞻性随机对照研究J.全科医学临床与教育，2 0 2 2，2 0（4）：32 2-324,343.14 RIEKEN M,EBINGER MUNDORFF N,BONKAT G,et al.Complications of laser prostatectomy:a review of recent dataJJ.World J Urol,2010,28(1):53-62.15J WENDT-NORDAHL G,HUCKELE S,HONECK P,et al.Systematic evaluation of a recently introduced 2-micromcontinuous-wave thulium laser for vaporesection of the prostateJJ.JEndourol,2008,22(5):1041-1045.16 BACHMANN A,MUIR GH,COLLINS EJ,et al.180-W XPSGreenLight laser therapy for benign prostate hyperplasia:earlysafety,efficacy,and perioperative outcome after 201 proceduresJJ.EurUrol,2012,61(3):600-607.17J HERRMANN TR,BACH T,IMKAMP F,et al.Thulium laserenucleation of the prostate(ThuLEP):transurethral anatomicalprostatectomy with laser support.Introduction of a noveltechnique for the treatment of benign prostatic obstructionJ.WorldJUrol,2010,28(1):45-51.18PARISER JJ,FAMAKINWAOJ,PEARCE SM,et al.High-power thulium laser vaporization of the prostate:short-termoutcomes of safety and effectivenessJ.J Endourol,2014,28(11):1357-1362.（编辑何宏灵）http:/;zgmnwk.cug.top