吲哚菁绿联合亚甲蓝双示踪法在国内乳腺癌前哨淋巴结活检中应用价值的Meta分析
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刘晓,Email: liuxiaowuxi@126.com;秦安,Email: annie2k@163.com

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Application value of dual-tracer method of indocyanine green plus methylene blue in sentinel lymph node biopsy of breast cancer in China: a Meta-analysis
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    摘要:

    背景与目的:手术切除是乳腺癌的首选治疗,以前哨淋巴结活检(SLNB)代替腋窝淋巴结清扫术(ALND),可降低术后并发症的发生率。SLNB成功与否,和示踪剂的选用密切相关,目前临床上最常应用的示踪剂是亚甲蓝和99mTc硫胶体,或将两者联合应用,但各有其弊端。有多项研究对新型示踪剂进行了临床试验,如吲哚菁绿(ICG)、超顺磁氧化铁(SPIO)、靛胭脂、纳米炭等,其中对ICG作为示踪剂的研究较多。然而,目前对联用多种示踪剂临床价值的汇总研究较少,故本研究旨在以Meta分析的方式评价ICG联合亚甲蓝双示踪法在国内乳腺癌SLNB中的应用价值。
    方法:检索中国知网数据库、万方数据库、维普数据库、PubMed和Cochrane Library中公开发表的并由中国的医疗机构开展的在乳腺腺癌SLNB中ICG联合亚甲蓝双示踪法与亚甲蓝单示踪法比较的研究文献,检索时间均为自建库至2019年8月,按照纳入和排除标准筛选文献,对纳入文献进行数据提取和文献质量评价,用Meta分析的方法比较两种示踪法前哨淋巴结(SLN)检出率、SLN检出数、假阴性率、敏感度和特异度的差异,用漏斗图检测发表偏倚。
    结果:最终纳入15篇文献,其中中文文献12篇,英文文献3篇,均为国内研究,Meta分析结果显示,与亚甲蓝示单踪法比较,ICG联合亚甲蓝双示踪法的SLN检出率(OR=5.39,95% CI=3.46~8.39,P<0.000 01)、SLN检出数(SMD=1.06,95% CI=0.76~1.36,P<0.000 01)、灵敏度(OR=5.31,95% CI= 2.68~10.55,P<0.000 01)和特异度(OR=2.71,95% CI=1.35~5.45,P=0.005)均明显增加,而假阴性率明显降低(OR=0.15,95% CI=0.08~0.29,P<0.000 01)。采用15篇文献报道的检出率进行发表偏倚评估,漏斗图显示,存在发表偏倚的可能性较小。
    结论:ICG联合亚甲蓝双示踪法在国内乳腺癌SLNB中具有较高的应用价值。随着研究的深入,未来将纳入更多临床研究进行汇总分析,使该法能够广泛应用于临床。

    Abstract:

    Background and Aims: Surgical resection is the preferred treatment for breast cancer. The use of sentinel lymph node biopsy (SLNB) in place of axillary lymph node dissection (ALND) can reduce the incidence of postoperative complications. The success (or not) of SLNB is closely related to the selection of tracer. At present, methylene blue and 99mTc sulfur colloid or the combination of the two are the most commonly used in clinical practice, however, both tracer agents have their drawbacks. A number of clinical trials have been performed to assess the new tracer agents, such as indocyanine green (ICG), superparamagnetic iron oxide (SPIO), indigocarmine, carbon nanoparticles, among which ICG has been most extensively studied. Nevertheless, there are few Meta-analysis on the clinical value of combining multiple tracers. Therefore, this study was designated to evaluate the application value of dual-tracer method of ICG combined with methylene blue in SLNB of breast cancer in China by Meta-analysis.  
    Methods: The publicly published studies comparing using dual-tracer method of ICG combined with methylene blue and single-tracer method of methylene blue performed by Chinese medical institutes were searched in China National Knowledge Infrastructure, Wanfangdata, VIP database, PubMed and Cochrane Library, encompassing the time period from the dates of inception to August 2019. The search results were screened in accordance with exclusion criteria, and the methodological qualities of the included studies were assessed. The differences in detection rate of sentinel lymph nodes (SLNs), number of detected SLNs, false negative rate, sensitivity and specificity between the two tracer methods were compared. Publication bias analysis was assessed by funnel plot. 
    Results: A total of 15 studies were finally included, including 12 articles in Chinese and 3 articles in English, and all of them were domestic studies. Meta-analysis results showed that the detection rate of SLNs (OR=5.39, 95% CI=3.46–8.39, P<0.000 01), number of detected SLNs (SMD=1.06, 95% CI=0.76–1.36, P<0.000 01), sensitivity (OR=5.31, 95% CI=2.68–10.55, P<0.000 01) and specificity (OR=2.71, 95% CI=1.35–5.45, P=0.005) were significantly increased and the false negative rate (OR=0.15, 95% CI=0.08–0.29, P<0.000 01) was significantly decreased by using dual -tracer method of ICG plus methylene blue compared with single-tracer method of methylene blue. The detection rates of SLNs reported in the 15 articles were used to assess publication bias, and the funnel plot showed that the possibility of publication bias was low. 
    Conclusion: The dual-tracer method of ICG combined with methylene blue has a high application value in SLNB of breast cancer in China. With the progress of research, more clinical studies will be included for Meta-analysis in the future, so that this method can be expected to be widely used in clinical practice.

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王骥, 吴瑞, 刘晓, 秦安.吲哚菁绿联合亚甲蓝双示踪法在国内乳腺癌前哨淋巴结活检中应用价值的Meta分析[J].中国普通外科杂志,2020,29(5):532-542.
DOI:10.7659/j. issn.1005-6947.2020.05.003

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  • 收稿日期:2019-12-05
  • 最后修改日期:2020-04-25
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  • 在线发布日期: 2020-05-25