Markkula Silja P, Leung Nelson, Allen Victoria B, Furniss Dominic
Department of Plastic Surgery, Helsinki University Hospital, PL 266, Helsinki, Finland, FIN-00029 HUS.
Cochrane Database Syst Rev. 2019 Feb 19;2(2):CD011433. doi: 10.1002/14651858.CD011433.pub2.
Breast cancer is the most common type of cancer amongst women worldwide, and one distressing complication of breast cancer treatment is breast and upper-limb lymphoedema. There is uncertainty regarding the effectiveness of surgical interventions in both the prevention and management of lymphoedema affecting the arm after breast cancer treatment.
We searched the Cochrane Breast Cancer Group's Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for all prospectively registered and ongoing trials on 2 November 2017. Reference lists of included studies were also handsearched by three review authors for additional eligible trials.
All randomised controlled trials (RCTs) comparing a surgical intervention for the prevention or treatment of lymphoedema of the arm after breast cancer treatment to either standard intervention, placebo intervention, or another surgical intervention were included. Patients of both sexes and all ages who have had treatment for their breast cancer were considered. No limits were applied to language or study location. Three authors independently determined the eligibility of each study.
Three authors independently extracted data for each included study using a pre-designed data extraction pro forma and used Cochrane's 'risk of bias' tool for assessing risk of bias. Dichotomous variables were analysed using the Mantel-Haenszel method to estimate risk ratios (RRs). Differences in continuous variables were expressed as mean differences (MDs). GRADE was used to assess the certainty of the evidence provided by the included studies.
Two studies involving 95 participants examined surgical interventions for preventing breast cancer-related lymphoedema. Both studies evaluated the efficacy of the lymphaticovenular anastomosis technique as part of a preventative management protocol. Both studies were deemed to be at unclear risk of bias overall. Statistical variation between the studies was low, which increases the reliability of the evidence. However, the two studies were conducted in the same centre. Lymphaticovenular anastomosis appears to result in a reduction in the incidence of lymphoedema compared to nonoperative management with a risk ratio of 0.20 (95% CI 0.06 to 0.63, P = 0.006; 95 participants; low-certainty evidence). The RCTs did not evaluate any of the secondary outcomes.One study involving 36 participants evaluated the effectiveness of vascularised lymph node transfer for treating breast cancer-related lymphoedema. The trial was deemed to be at unclear risk of bias. For participants suffering from stage 2 lymphoedema, the evidence suggested reductions in limb volume (MD -39.00%, 95% CI -47.37% to -30.63%, very low-certainty evidence), pain scores (MD -4.16, 95% CI -5.17 to -3.15, very low-certainty evidence), heaviness sensation (MD -4.27, 95% CI -5.74 to -2.80, very low-certainty evidence), mean number of infections/year (MD -1.22, 95% CI -2.00 to -0.44, very low-certainty evidence), and an improvement in overall function scores (MD -3.77, 95% CI -4.89 to -2.65, very low-certainty evidence) for those who had undergone vascularised lymph node transfer compared to those who had undergone no treatment.
AUTHORS' CONCLUSIONS: There is low-certainty evidence that lymphaticovenular anastomosis is effective in preventing the development of lymphoedema after breast cancer treatment based on the findings from two studies. One study providing very low-certainty evidence found that vascularised lymph node transfer is an efficacious option in the treatment of established stage 2 lymphoedema related to breast cancer. Important secondary outcomes in this review were rarely reported in the included studies. More high-quality RCTs are required to further elucidate the effectiveness of surgical interventions in the prevention and treatment of lymphoedema after breast cancer treatment. At the time of this review, no ongoing trials on this topic were identified.
乳腺癌是全球女性中最常见的癌症类型，乳腺癌治疗中一个令人苦恼的并发症是乳房及上肢淋巴水肿。对于乳腺癌治疗后影响手臂的淋巴水肿，手术干预在预防和管理方面的有效性存在不确定性。
我们检索了Cochrane乳腺癌小组专业注册库、Cochrane对照试验中央注册库、MEDLINE、Embase、护理及相关健康文献累积索引（CINAHL）、世界卫生组织国际临床试验注册平台（ICTRP）和ClinicalTrials.gov，以查找2017年11月2日所有前瞻性注册及正在进行的试验。三位综述作者还对纳入研究的参考文献列表进行了手工检索，以寻找其他符合条件的试验。
纳入所有将乳腺癌治疗后预防或治疗手臂淋巴水肿的手术干预与标准干预、安慰剂干预或另一种手术干预进行比较的随机对照试验（RCT）。考虑所有接受过乳腺癌治疗的男女患者，年龄不限。对语言或研究地点不设限制。三位作者独立确定每项研究的合格性。
三位作者使用预先设计的数据提取表格，为每项纳入研究独立提取数据，并使用Cochrane的“偏倚风险”工具评估偏倚风险。二分变量采用Mantel-Haenszel方法进行分析，以估计风险比（RRs）。连续变量的差异以平均差（MDs）表示。采用GRADE评估纳入研究提供的证据的确定性。
两项涉及95名参与者的研究探讨了预防乳腺癌相关淋巴水肿的手术干预措施。两项研究均评估了淋巴静脉吻合技术作为预防性管理方案一部分的疗效。两项研究总体上被认为偏倚风险不明确。研究之间的统计差异较小，这增加了证据的可靠性。然而，这两项研究在同一中心进行。与非手术管理相比，淋巴静脉吻合术似乎可降低淋巴水肿发生率，风险比为0.20（95%CI 0.06至0.63，P = 0.006；95名参与者；低确定性证据）。RCT未评估任何次要结局。一项涉及36名参与者的研究评估了带血管蒂淋巴结转移治疗乳腺癌相关淋巴水肿的有效性。该试验被认为偏倚风险不明确。对于患有2期淋巴水肿的参与者，证据表明与未接受治疗的参与者相比，接受带血管蒂淋巴结转移的参与者肢体体积减少（MD -39.00%，95%CI -47.37%至-30.63%，极低确定性证据）、疼痛评分降低（MD -4.16，95%CI -5.17至-3.15，极低确定性证据）、沉重感降低（MD -4.27，95%CI -5.74至-2.80，极低确定性证据）、每年平均感染次数降低（MD -1.22，95%CI -2.00至-0.44）以及总体功能评分改善（MD -3.77，95%CI -4.89至-2.65，极低确定性证据）。
基于两项研究的结果，有低确定性证据表明淋巴静脉吻合术在预防乳腺癌治疗后淋巴水肿的发生方面有效。一项提供极低确定性证据的研究发现，带血管蒂淋巴结转移是治疗已形成的与乳腺癌相关的2期淋巴水肿的有效选择。纳入研究中很少报告本综述中的重要次要结局。需要更多高质量的RCT来进一步阐明手术干预在预防和治疗乳腺癌治疗后淋巴水肿方面的有效性。在本次综述时，未发现关于该主题的正在进行的试验。
