Breast cancer–related lymphedema affects approximately 20 to 45 percent of breast cancer survivors after surgical intervention.1–7 This surgical sequela is associated with decreased patient quality-of-life measures, increased susceptibility to infection, and increased medical expenditure.8,9 Treatment for breast cancer–related lymphedema is largely palliative in nature and focused on reducing symptoms and preventing disease progression. Conservative measures require strict patient adherence to lifelong therapies, including manual lymphatic drainage, compression bandaging/garments, pneumatic pump use, and physical therapy.1,10,11 Despite improvements in microsurgical techniques such as vascularized lymph node transfer and lymphovenous bypass for the treatment of chronic lymphedema, none of these options has proven curative. As long-term overall survival increases in tandem with advancements in treatment, efforts toward minimizing or eliminating breast cancer–related lymphedema are paramount. The advent of the lymphatic microsurgical preventive healing approach has introduced the concept of surgical prevention for lymphedema.
大约 20% 到 45% 的乳腺癌幸存者在接受手术治疗后会出现乳腺癌相关淋巴水肿。1-7 这种手术后遗症与患者生活质量下降、易感染和医疗支出增加有关。89 乳腺癌相关淋巴水肿的治疗主要是姑息性的，侧重于减轻症状和防止疾病进展。保守措施要求患者严格遵守终身疗法，包括人工淋巴引流、加压包扎/穿衣、使用气动泵和物理疗法。11011 尽管用于治疗慢性淋巴水肿的显微外科技术有所改进，如血管化淋巴结转移和淋巴静脉搭桥、但这些方法均未被证明具有治疗效果。随着治疗技术的进步，长期总生存率也在不断提高，因此最大限度地减少或消除与乳腺癌相关的淋巴水肿至关重要。淋巴显微外科预防性治疗方法的出现引入了手术预防淋巴水肿的概念。
In the seminal study by Boccardo et al., lymphedema rates were 4 percent with 4 years’ follow-up in a high-risk patient cohort where the majority of patients underwent axillary lymph node dissection with regional lymph node radiotherapy.12 This finding has been replicated at other institutions, where similar decreases in rates of lymphedema after immediate lymphatic reconstruction were found in comparable patient cohorts.13,14 Some criticisms of these studies include variation in the criteria used to diagnose “lymphedema,” heterogeneity of measurement modalities used, and varying follow-up periods.15
在 Boccardo 等人的开创性研究中、在高危患者群中，大多数患者都接受了腋窝淋巴结清扫术和区域淋巴结放疗，随访4年后，淋巴水肿发生率为4%。12 其他机构也重复了这一发现，在类似的患者群中，立即淋巴重建后的淋巴水肿率也有类似的下降。1314 这些研究受到的一些批评包括诊断 "淋巴水肿 "的标准不同、"使用的测量模式不一致，以及随访时间长短不一。15
At our institution, the lymphatic microsurgical preventive healing approach is termed “immediate lymphatic reconstruction,” as divided lymphatics are reconstructed at the time of tumor extirpation.16 We use multiple lymphedema measurement modalities preoperatively and during postoperative surveillance. Moreover, we impose follow-up criteria to capture the long-term effects of this technique.
在我院，淋巴显微外科预防性愈合方法被称为 "即时淋巴重建"，因为分裂的淋巴管是在肿瘤切除时重建的。此外，我们还规定了随访标准，以了解该技术的长期效果。
Our present study aims to introduce and review our institutional experience with immediate lymphatic reconstruction in a node-positive breast cancer patient population undergoing axillary surgery. To this end, we performed a retrospective review of a quality improvement database to identify all patients who underwent axillary surgery with immediate lymphatic reconstruction at our institution and describe our surgical outcomes.
本研究旨在介绍和回顾我院在接受腋窝手术的结节阳性乳腺癌患者中进行即时淋巴重建的经验。为此，我们对质量改进数据库进行了回顾性审查，以确定本机构所有接受腋窝手术并立即进行淋巴重建的患者，并描述我们的手术结果。
PATIENTS AND METHODS 患者和方法
A retrospective review of our lymphatic surgery Research Electronic Data Capture database was performed. Institutional review board approval was obtained (protocol no. 2019P-000190). Consecutive patients with a diagnosis of node-positive unilateral breast cancer who underwent attempted immediate lymphatic reconstruction after axillary surgery from September of 2016 through February of 2019 were identified. No patients with a history of breast cancer or breast and/or axillary surgery were eligible for inclusion. Furthermore, no patients undergoing sentinel lymph node biopsy alone were eligible for immediate lymphatic reconstruction. Patient demographics, cancer characteristics, intraoperative specifics, and surveillance measurements were extracted for analysis. The study design is illustrated in Figure 1.
我们对淋巴手术研究电子数据采集数据库进行了回顾性审查。研究获得了机构审查委员会的批准（方案编号：2019P-000190）。从 2016 年 9 月到 2019 年 2 月，我们对诊断为结节阳性单侧乳腺癌并在腋窝手术后尝试立即进行淋巴重建的连续患者进行了鉴定。没有乳腺癌或乳腺和/或腋窝手术史的患者符合纳入条件。此外，仅接受前哨淋巴结活检的患者也不符合即时淋巴重建的条件。研究人员提取了患者的人口统计学特征、癌症特征、术中具体情况和监测测量数据进行分析。研究设计见图1。
Fig. 1.: Study design. QI, quality improvement; ILR, immediate lymphatic reconstruction.
图 1：研究设计。QI，质量改进；IRR，即时淋巴重建。
Preoperative Evaluation 术前评估
Certified lymphedema therapists at our institution used multiple lymphedema measurement modalities to obtain comprehensive baseline data for all patients who presented for immediate lymphatic reconstruction. These measurement modalities included (1) circumferential arm measurements at 4-cm intervals that were converted to volumes using the truncated cone formula,17 (2) perometry, and (3) bioimpedance spectroscopy (L-Dex U400; ImpediMed, Carlsbad, Calif.).
我们医院的认证淋巴水肿治疗师采用多种淋巴水肿测量方法，为所有立即进行淋巴重建的患者获取全面的基线数据。这些测量方法包括：(1) 以4厘米为间隔测量手臂周径，并使用截顶锥公式将其转换为体积，17 (2) 周径测量法，以及 (3) 生物阻抗光谱法（L-Dex U400; ImpediMed, Carlsbad, Calif.）。
In addition, all patients were administered the 36-Item Short-Form Health Survey questionnaire at routine intervals.18,19 We administer the 36-Item Short-Form Health Survey to all patients preoperatively. This survey provides data on physical functioning (physical component scale) and mental health, emotional, and social functioning (mental component scale). Pertinent patient data including demographics, medical history, cancer characteristics and treatment, and baseline lymphedema measurements are entered into a Research Electronic Data Capture20 lymphedema quality improvement clinical database to facilitate surveillance.
此外，所有患者都在常规时间间隔内接受了 36 项短式健康调查问卷。1819 我们在术前对所有患者进行36项短式健康调查。该调查提供有关身体功能（身体部分量表）和心理健康、情感及社会功能（心理部分量表）的数据。患者的相关数据，包括人口统计学、病史、癌症特征和治疗以及淋巴水肿的基线测量值，都会被输入研究电子数据采集20 淋巴水肿质量改进临床数据库，以方便监测。
Surgical Technique 手术技术
At our institution, sentinel lymph node biopsies are performed as permanent sections and axillary lymph node dissections occur in a staged manner. A single surgeon with fellowship training in lymphatic surgery (D.S.) performed all attempted immediate lymphatic reconstructions from September of 2016 through February of 2019 at the time of nodal extirpation. The type of axillary nodal intervention performed was determined by the lymphatic surgeon intraoperatively. Following axillary surgery, the lymphatic surgeon attempted to visualize the boundaries of a level I and II dissection including the axillary vein superiorly, serratus anterior medially, thoracodorsal vessels posteriorly, and latissimus muscle laterally.21 If all structures were visible, the procedure was termed an axillary lymph node dissection. If any of these structures was not visible, the procedure was termed an axillary sampling procedure.
在我们医院，前哨淋巴结活检是作为永久切片进行的，而腋窝淋巴结切除则是分阶段进行的。从 2016 年 9 月到 2019 年 2 月，由一名接受过淋巴手术研究培训的外科医生（D.S.）在结节切除时进行了所有尝试过的即时淋巴重建手术。腋窝结节干预的类型由淋巴外科医生在术中决定。腋窝手术后，淋巴外科医生尝试观察I级和II级解剖的边界，包括腋窝静脉上侧、前锯肌内侧、胸背血管后侧和阔筋肌外侧。21 如果所有结构都可见，则称为腋窝淋巴结清扫术。如果其中任何结构不可见，则称为腋窝取样手术。
Immediately before the initiation of the axillary intervention by the breast surgical oncology service, 0.25 cc of fluorescein isothiocyanate mixed with albumin was injected into the upper medial operative extremity as described previously.22 Following completion of the axillary lymph node dissection, using the same exposure provided by the breast surgeon, the axillary bed was evaluated, and any major venous branches draining into the axillary vein were identified. Tributaries of the axillary vein were then evaluated for adequate length and the presence of a proximal intact valve. In cases of inadequate vein length or significant venous back-bleeding, the lymphatic reconstruction was aborted.
在乳腺肿瘤外科开始进行腋窝介入治疗之前，按照之前的描述，将 0.25 cc 异硫氰酸荧光素与白蛋白混合液注入手术肢体的上内侧。22 在完成腋窝淋巴结清扫后，使用乳腺外科医生提供的相同暴露方式，对腋窝床进行评估，并确定排入腋窝静脉的主要静脉分支。然后评估腋窝静脉的支流是否有足够的长度，近端是否有完整的瓣膜。如果静脉长度不足或静脉回流明显，则放弃淋巴重建。
Using a Mitaka MM51 microscope equipped with a 560-nm filter (Mitaka Kohki Co., Ltd., Mitaka, Tokyo), divided lymphatic channels were visualized and their location mapped from the axillary vein. Each lymphatic channel was isolated and measured using high magnification and fluorescent technology for visualization. The distal ends of lymphatic channels were cut to confirm active lymphatic flow using filter technology. Afferent lymphatic vessels not suitable for anastomosis were clipped. A U stitch was then passed through the prepared tributary vein and lymphatic channels to facilitate parachuting the lymphatic channels into the vein using the technique described by Boccardo and Campisi.23 The lymphatic reconstruction was then secured using 9-0 nylon sutures (Ethicon, Inc., Somerville, N.J.), which were passed full thickness through the tributary vein into the perilymphatic tissues in a simple, interrupted manner. The initial U stitch was then cut to allow lymphatic flow into the vein. Confirmation of lymphatic flow and anastomotic patency was visualized using the Mitaka MM51 microscope, as documented in a previous study.22 A fat graft was then harvested from the axilla that was then wrapped around the anastomotic site to secure it. [See Video (online), which demonstrates the surgical technique used in immediate lymphatic reconstruction of the left axillary nodal bed.] The axillary incision was closed in standard fashion and a no. 15 Blake drain was placed exiting the dependent portion of the axillary bed away from the anastomotic site.
使用配备了 560 纳米滤光片的 Mitaka MM51 显微镜（Mitaka Kohki Co., Ltd., Mitaka, Tokyo），从腋窝静脉开始观察并绘制淋巴管的位置图。利用高倍放大镜和荧光技术对每条淋巴管进行分离和测量。利用过滤技术切割淋巴管远端，以确认活跃的淋巴流动。剪断不适合吻合的传入淋巴管。23 然后使用 9-0 尼龙缝线（Ethicon, Inc、Somerville, N.J.）缝合，以简单、间断的方式将缝线全厚度穿过支流静脉进入淋巴周围组织。然后切断最初的 U 形缝线，让淋巴液流入静脉。22 然后从腋窝抽取脂肪移植到吻合部位，将其包裹固定。[请参阅视频（在线），该视频展示了左侧腋窝结节床即时淋巴重建的手术技巧。］以标准方式缝合腋窝切口，并在腋窝外侧放置No.15 Blake引流管从远离吻合部位的腋窝依赖部分引出。
Video.
This video demonstrates the surgical technique used in immediate lymphatic reconstruction of the left axillary nodal bed.
视频。
本视频演示了左侧腋窝结节床即时淋巴重建的手术技巧。
Postoperative Surveillance
术后监控
On discharge, patients are advised to follow routine incisional care. When drain outputs are less than 20 cc/day for 2 consecutive days, the drain is removed, and this is usually accomplished by 14 days postoperatively. Our surveillance protocol for immediate lymphatic reconstruction patients included postoperative visits at 4 weeks, 3 months, and then every 3 months postoperatively for 2 years. During each surveillance visit, certified lymphedema therapists assessed and documented any signs or symptoms consistent with lymphedema (e.g., heaviness, swelling, numbness). All objective measurements from the preoperative evaluation were repeated at each surveillance visit. Studies have shown the success and cost-effectiveness of postoperative surveillance programs in patients at high risk for the development of breast cancer–related lymphedema.24–26 We monitor patients closely using three measurement modalities (i.e., perometry, bioimpedance spectroscopy, and volumetry by circumferential measurements). If the patient did not develop any signs or symptoms consistent with lymphedema or objective findings (any positive quantitative change by volumetry, L-Dex, or circumferential measurements) consistent with lymphedema during this time frame, patients were then surveilled every 6 months for the subsequent 2 years. In total, patients are actively surveilled for 4 years. The need for additional surveillance is determined on a case-by-case basis. Bioimpedance spectroscopy is a sensitive modality championed for postoperative patient surveillance, as it can noninvasively detect changes in lymph fluid by assessing the “impedance,” or opposition to current traveling through the body.27
出院时，建议患者进行常规切口护理。当引流管排出量连续两天少于 20 毫升/天时，引流管将被移除，这通常在术后 14 天内完成。我们对即刻淋巴重建患者的监控方案包括术后 4 周、3 个月和术后 2 年内每 3 个月的复诊。在每次监测访视期间，经认证的淋巴水肿治疗师都会评估并记录任何与淋巴水肿相符的体征或症状（如沉重、肿胀、麻木）。术前评估中的所有客观测量结果都会在每次复查时重复进行。研究表明，对于乳腺癌相关淋巴水肿的高危患者，术后监测计划是成功且具有成本效益的。24-26 我们使用三种测量方法（即周径测量法、生物阻抗光谱法和周径体积测量法）对患者进行密切监测。如果患者在此期间没有出现任何与淋巴水肿相一致的体征或症状，也没有任何与淋巴水肿相一致的客观检查结果（体积测量法、L-Dex 或周径测量法的任何积极定量变化），那么在随后的 2 年中，我们将每 6 个月对患者进行一次监测。患者总共要接受 4 年的主动监测。是否需要进行额外的监测要根据具体情况而定。生物阻抗光谱是一种用于术后患者监测的灵敏模式，因为它可以通过评估 "阻抗 "或电流通过人体时的阻抗，无创检测淋巴液的变化。27
All surveillance data were entered into a lymphatic surgery database by trained staff. The 36-Item Short-Form Health Survey questionnaires were sent to patients by automated e-mails from the database at 3, 6, and 12 months, and then annually following immediate lymphatic reconstruction. All results from completed online surveys were automatically populated within the Research Electronic Data Capture20 database.
所有监测数据均由经过培训的工作人员输入淋巴手术数据库。在淋巴重建手术后的3、6、12个月，以及每年的3、6、12个月，数据库会自动向患者发送36项短式健康调查问卷。所有在线调查的结果都会自动输入研究电子数据采集20 数据库。
Lymphedema is defined at our institution as having both (1) any positive quantitative measurement meeting criteria for lymphedema and the (2) presence of symptoms (i.e., tightness, heaviness, swelling) consistent with lymphedema as determined by a certified lymphedema therapist. Objective measurements consistent with a lymphedema diagnosis included a 10-point increase in bioimpedance (L-Dex) value from baseline; a 10 percent volume increase in the dominant, affected extremity; or a 7 percent increase in the nondominant affected extremity using volumetry. If the patient met these criteria while undergoing adjuvant treatment, with the exclusion of hormone therapy and immunotherapy, or within 6 months of their last oncologic treatment, lymphedema was classified as transient (i.e., “transient lymphedema”). A diagnosis of lymphedema was given if the patient met the above-specified criteria 6 months after their last oncologic treatment (surgery, adjuvant radiation therapy, or chemotherapy). Regional lymph node radiation was defined at our institution as targeted treatment to the internal mammary, supraclavicular, and/or axillary regions.28,29
我院对淋巴水肿的定义是：(1) 任何符合淋巴水肿标准的阳性定量测量值；(2) 经认证的淋巴水肿治疗师判断，出现与淋巴水肿相符的症状（即紧绷、沉重、肿胀）。符合淋巴水肿诊断的客观测量值包括：生物阻抗（L-Dex）值比基线值增加 10 个点；主要受累肢体的体积增加 10%；或使用容积测量法测量非主要受累肢体的体积增加 7%。如果患者在接受辅助治疗（不包括激素治疗和免疫治疗）期间或最后一次肿瘤治疗后 6 个月内符合上述标准，则淋巴水肿被归类为短暂性淋巴水肿（即 "短暂性淋巴水肿"）。如果患者在最后一次接受肿瘤治疗（手术、辅助放疗或化疗）6个月后符合上述标准，则可诊断为淋巴水肿。我院将区域淋巴结放射定义为乳腺内、锁骨上和/或腋窝区域的靶向治疗。2829
Statistical Analysis 统计分析
Descriptive statistics of the data were performed. Continuous data were represented using mean and standard deviation or median and range or first and third quartiles. Frequencies and percentages were used to summarize categorical variables. We used t tests for continuous variables and chi-square tests for categorical variables to compare demographics between the cohort who underwent successful immediate lymphatic reconstruction with 6-month minimum follow-up (n = 32) and all other patients who underwent attempted immediate lymphatic reconstruction (n = 65). R 3.5.3 (R Development Core Team, 2019) was used for statistical analyses.
对数据进行了描述性统计。连续数据用均值和标准差或中位数和范围或第一和第三四分位数表示。频率和百分比用于总结分类变量。我们对连续变量采用t检验，对分类变量采用卡方检验，以比较成功接受即时淋巴重建且随访时间至少为6个月的患者（n = 32）和其他所有尝试接受即时淋巴重建的患者（n = 65）的人口统计学特征。统计分析使用R 3.5.3 (R Development Core Team, 2019)。
RESULTS 结果
Ninety-seven women with unilateral node-positive breast cancer underwent attempted immediate lymphatic reconstruction at our institution during the study period. Forty-one patients had a minimum 6-month follow-up. Nine of these cases (22 percent) were excluded, as immediate lymphatic reconstruction was aborted intraoperatively. Inadequate recipient vein (e.g., lack of vein availability or back-bleeding) occurred in five of the aborted cases; lack of identifiable divided lymphatic channel occurred in four cases. A total of 18 patients had preoperative baseline measurements but did not present for 6-month follow-up and were thus ineligible for study inclusion at the time of analysis. Thirty patients underwent successful immediate lymphatic reconstruction with a mean patient age of 54 years and body mass index of 28 ± 6 kg/m2. Patients in this cohort had similar demographics when compared to the entire patient population (Table 1).
在研究期间，本院为 97 名单侧结节阳性乳腺癌患者尝试进行了即时淋巴重建。有 41 名患者接受了至少 6 个月的随访。其中九例（22%）因术中放弃即刻淋巴重建而被排除。其中五例因受体静脉不足（如缺乏可用静脉或背部出血）而流产；四例因缺乏可识别的分割淋巴通道而流产。共有 18 名患者在术前进行了基线测量，但没有进行 6 个月的随访，因此在分析时不符合纳入研究的条件。30名患者成功接受了即刻淋巴重建术，患者平均年龄为54岁，体重指数为28 ± 6 kg/m2。与所有患者相比，该组患者的人口统计学特征相似（表1）。
Table 1. -
Patient Demographics
表 1。- 患者人口统计数据
|
| Patients Who Underwent Attempted ILR (%)
尝试过 ILR 的患者 (%) |
Patient Who Underwent Successful ILR wtih 6-Mo Minimum Follow-Up (%)
接受至少 6 个月随访并成功进行 ILR 的患者（%）。 |
p
|
| No. 不 |
97 |
32 |
|
Mean age at surgery ± SD, yr
手术时的平均年龄（± SD），年 |
54.0 ± 13 |
54.1 ± 12 |
0.94 |
Mean BMI at surgery ± SD, kg/m2
手术时的平均体重指数（± SD），千克/米2
|
27.5 ± 6 |
27.7 ± 6 |
0.81 |
| Female sex 女性性别 |
97 (100) |
32 (100) |
|
| Race 竞赛 |
|
| 0.26 |
| White 白色 |
58 (59) |
23 (72) |
|
| Black 黑色 |
20 (21) |
7 (22) |
|
| Asian 亚洲 |
7 (8) |
1 (3) |
|
| Other/unknown 其他/未知 |
12 (13) |
1 (3.1) |
|
| Ethnicity, non-Hispanic 种族，非西班牙裔 |
95 (98) |
32 (100) |
0.99 |
ILR, immediate lymphatic reconstruction; BMI, body mass index.
ILR，即刻淋巴重建；BMI，体重指数。
Of the 32 patients who met study eligibility criteria, 88 percent of women in this cohort underwent adjuvant radiotherapy of whom 93 percent received regional lymph node irradiation. Furthermore, 59 percent of women had adjuvant chemotherapy, with the majority (74 percent) undergoing a taxane-based regimen (Table 2).
在符合研究资格标准的32名患者中，88%的女性接受了辅助放疗，其中93%接受了区域淋巴结照射。此外，59%的女性接受了辅助化疗，其中大多数（74%）接受了以类固醇为基础的方案（表 2）。
Table 2. -
Patient Cancer Treatment Characteristics
*
表 2.- 患者癌症治疗特征*
| Characteristic 特征 |
No. (%) 数量（%） |
| Tumor grade 肿瘤等级 |
|
| I |
0 (0) |
| II |
16 (50) |
| III |
16 (50) |
| Neoadjuvant chemotherapy 新辅助化疗 |
15 (47) |
| Taxane-based 基于类黄酮的 |
13 (87) |
| Adjuvant radiotherapy 辅助放射治疗 |
28 (88) |
Chest wall, breast, or intrabeam
胸壁、乳房或波束内 |
2 (7) |
RLNR with or without chest wall, breast, or intrabeam
带或不带胸壁、乳房或波束内的 RLNR |
26 (93) |
| Adjuvant chemotherapy 辅助化疗 |
19 (59) |
| Taxane-based 基于类黄酮的 |
14 (74) |
RLNR, regional lymph node radiotherapy.
RLNR，区域淋巴结放射治疗。
*n = 32.
*n = 32。
Intraoperatively, the median number of positive lymph nodes for both the axillary sampling and axillary lymph node dissection groups was one, with the total lymph nodes removed during these interventions being 10 and 13, respectively. All immediate lymphatic reconstructions were performed by a single lymphatic surgeon (D.S.) at our institution. Three breast surgeons performed 88 percent of all nodal dissections. A median of three divided lymphatic channels were visualized in each case (range, one to six). Of these, a median of one lymphatic channel was bypassed (range, one to three). The median distance of the bypassed channel to the distal aspect of the visualized axillary vein was 3.00 cm (range, 0.25 to 5.5 cm). The median bypass time after completion of axillary intervention was 85 minutes (range, 54 to 205 minutes). Table 3 reports the intraoperative data by axillary sampling versus axillary lymph node dissection cases. The median patient follow-up time was 11.4 months (range, 6.2 to 26.9 months). There was no statistical difference between the mean number of bypasses performed in the group of patients who underwent axillary sampling (n = 1.57) compared to those who underwent an axillary lymph node dissection (n = 1.48) (p = 0.79). A summary of surveillance measurements is provided in Table 4. No intraoperative or postoperative complications were observed in this cohort.
术中，腋窝取样组和腋窝淋巴结清扫组阳性淋巴结的中位数均为1个，这两组切除的淋巴结总数分别为10个和13个。本院所有即时淋巴重建手术均由一名淋巴外科医生（D.S.）完成。在所有结节切除术中，88%由三名乳腺外科医生完成。在每个病例中，可观察到的分裂淋巴管中位数为三条（范围为一到六条）。其中，中位数为一条淋巴管被绕过（范围为一到三条）。被旁路的淋巴管到可视腋静脉远端的中位距离为 3.00 厘米（范围为 0.25 至 5.5 厘米）。完成腋窝干预后的中位旁路时间为85分钟（范围为54至205分钟）。表3报告了腋窝取样与腋窝淋巴结清扫病例的术中数据。患者随访时间的中位数为11.4个月（6.2至26.9个月）。与接受腋窝淋巴结清扫术（n = 1.48）的患者相比，接受腋窝取样术（p = 0.79）的患者组所进行的旁路平均次数没有统计学差异。表4中提供了监控测量的摘要。该组患者未观察到术中或术后并发症。
Table 3. -
Intraoperative Specifics
*
表 3.- 术中具体情况*
| Characteristic 特征 |
Value (%) 数值 (%) |
| Axillary sampling 腋窝取样 |
7 (22) |
No. of positive nodes removed
切除的阳性结节数量 |
|
| Median 中位数 |
1 |
| IQR |
0–2.5 0-2.5 |
| No. of nodes removed 切除的结节数量 |
|
| Median 中位数 |
10 |
| IQR |
7–12 7-12 |
No. of divided lymphatics visualized
可视化分割淋巴管数量 |
|
| Median 中位数 |
3 |
| IQR |
1–3 1-3 |
No. of bypasses performed
旁路手术次数 |
|
| Median 中位数 |
1 |
| IQR |
1–3 1-3 |
Axillary lymph node dissection
腋窝淋巴结清扫 |
25 (78) |
No. of positive nodes removed
切除的阳性结节数量 |
|
| Median 中位数 |
1 |
| IQR |
1–3 1-3 |
| No. of nodes removed 切除的结节数量 |
|
| Median 中位数 |
13 |
| IQR |
10–17 10-17 |
No. of divided lymphatics visualized
可视化分割淋巴管数量 |
|
| Median 中位数 |
3 |
| IQR |
2–3 2-3 |
No. of bypasses performed
旁路手术次数 |
|
| Median 中位数 |
1 |
| IQR |
1–2 1-2 |
IQR, interquartile range.
IQR，四分位数区间。
*n = 32.
*n = 32。
Table 4. -
Patient Surveillance and Outcomes
*
表 4.- 患者监测和结果*
|
| Value (%) 数值 (%) |
Follow-up from time of ILR, mo
从 ILR 开始的随访，月 |
|
| Median 中位数 |
11.4 |
| Range 范围 |
6.2–26.9 6.2-26.9 |
Mean unit change of L-Dex from baseline ± SD
L-Dex 与基线相比的平均单位变化 ± SD |
2.9 ± 8.4 |
Absolute change in circumferential measurements from baseline ± SD, %
周长测量值与基线相比的绝对变化（± SD），百分比 |
–1.7 ± 7.1 -1.7 ± 7.1 |
Absolute change in perometry values from baseline ± SD, %
与基线相比，周长测量值的绝对变化±标度（%）。 |
1.3 ± 6.7 |
No. of patients diagnosed with transient lymphedema
确诊为一过性淋巴水肿的患者人数 |
4 (12.5) |
No. of patients whose transient lymphedema resolved
一过性淋巴水肿消退的患者人数 |
3 (9.4) |
No. of patients with ongoing transient lymphedema
一过性淋巴水肿患者人数 |
1 (3.1) |
ILR, immediate lymphatic reconstruction.
ILR，即刻淋巴重建。
*n = 32.
*n = 32。
Four patients developed transient lymphedema during postoperative surveillance (Fig. 2 and Table 4). All four patients underwent axillary lymph node dissection and not an axillary sampling. Three patients had disease resolution within 6 months and were not using any compression or therapy at the time of analysis. In one patient, symptoms occurred at the first follow-up visit and resolved at the 6-month visit. In the other two patients, lymphedema symptoms began at months 3 and 6, respectively, and resolved at the 9-month follow-up visit. One patient developed transient lymphedema at 3 months and has had persistent signs and symptoms at her 6-, 9-, and 12-month visits. She was still undergoing oncologic treatment at the time of analysis. This patient is currently in compression and has an elevated risk-factor profile, including axillary lymph node dissection, adjuvant regional lymph node radiation therapy including targeted treatment to the axilla, elevated body mass index (38.4 kg/m2), and neoadjuvant taxane-based chemotherapy. In this cohort of patients who presented with transient lymphedema, L-Dex was the most sensitive measurement modality and was the first presenting abnormal quantitative measurement for all four patients. Furthermore, in patients where immediate lymphatic reconstruction was aborted, transient lymphedema developed in three of the nine patients, for a 33 percent overall rate. In these patients, lymphedema resolved in two patients and persisted in one patient, for a transient lymphedema rate of 22 percent on conclusion of the study period.
四名患者在术后观察期间出现一过性淋巴水肿（图2和表4）。所有四名患者都进行了腋窝淋巴结清扫，而不是腋窝取样。三名患者的病情在 6 个月内得到缓解，分析时未使用任何压迫或治疗手段。一名患者在首次随访时出现症状，6 个月后症状缓解。另外两名患者分别在第 3 个月和第 6 个月出现淋巴水肿症状，并在 9 个月的随访中缓解。一名患者在 3 个月时出现一过性淋巴水肿，并在 6 个月、9 个月和 12 个月的随访中出现持续的体征和症状。在进行分析时，她仍在接受肿瘤治疗。该患者目前正在接受压迫治疗，风险因素较高，包括腋窝淋巴结清扫术、辅助区域淋巴结放疗（包括腋窝靶向治疗）、体重指数升高（38.4 kg/m2）和新辅助类固醇化疗。在这组出现一过性淋巴水肿的患者中，L-Dex是最敏感的测量方式，也是所有四名患者首次出现的异常定量测量结果。此外，在放弃立即进行淋巴重建的患者中，9 名患者中有 3 名出现了一过性淋巴水肿，总发生率为 33%。在这些患者中，有两名患者的淋巴水肿得到缓解，一名患者的淋巴水肿持续存在，在研究结束时，一过性淋巴水肿率为 22%。
Fig. 2.: Graphic of patients and follow-up during the study period. Four patients developed transient lymphedema during the study period, which resolved in three patients.
图 2：研究期间患者和随访情况图。四名患者在研究期间出现了一过性淋巴水肿，其中三名患者的水肿得到了缓解。
DISCUSSION 讨论
Our study found that immediate lymphatic reconstruction was effective in a high-risk patient cohort with an overall lymphedema rate of 3.1 percent. Moreover, we found that quantitative measurements and symptoms consistent with transient lymphedema resolved within 6 months of initial onset in three of four patients (75 percent). In these patients, L-Dex was the first measurement to indicate lymphedema. Throughout the entire study period, immediate lymphatic reconstruction was attempted in 97 cases. Of those, 41 had a minimum of 6-month follow-up, and immediate lymphatic reconstruction was successful in 32 (78 percent) and aborted in nine. The rate of lymphedema in the aborted cohort was 22 percent. In the aborted cases, venous issues were the most common reasons for terminating the reconstruction. Finally, all four patients who developed transient lymphedema underwent axillary lymph node dissection and not axillary sampling.
我们的研究发现，对于淋巴水肿发生率为 3.1% 的高危患者群体来说，立即进行淋巴重建是有效的。此外，我们还发现，四名患者中有三名（75%）的定量测量结果和与一过性淋巴水肿相符的症状在发病后 6 个月内得到缓解。在这些患者中，L-Dex 是首次显示淋巴水肿的测量值。在整个研究期间，有 97 例患者尝试过立即进行淋巴重建。其中，41 例患者接受了至少 6 个月的随访，32 例（78%）成功进行了即时淋巴重建，9 例流产。失败病例的淋巴水肿发生率为 22%。在流产的病例中，静脉问题是终止重建的最常见原因。最后，出现一过性淋巴水肿的四名患者均接受了腋窝淋巴结清扫术，而非腋窝取样。
Our most notable finding was the low rate of postoperative lymphedema in a patient population with multiple independent risk factors for its development. Our group’s 2019 meta-analysis including over 3000 patients reported a 15.5 percent pooled incidence of lymphedema after axillary lymph node dissection.7 This value increased to 26.5 percent with the addition of regional lymph node irradiation. In the same meta-analysis, the addition of a lymphatic microsurgical preventive healing approach or immediate lymphatic reconstruction decreased these rates to 4.6 percent and 10.6 percent, respectively. Furthermore, the seminal study by Boccardo et al. reported a lymphedema rate of 4.05 percent with 4-year follow-up.12 These data align with our current institutional lymphedema rate of 3.1 percent. Most patients in our cohort were high risk, undergoing axillary lymph node dissection and adjuvant regional lymph node radiotherapy. Most patients also underwent chemotherapy in either the neoadjuvant (47 percent) or adjuvant setting (59 percent), with the majority undergoing taxane-based regimens. Although controversial, this risk factor has been independently associated with development of lymphedema in some studies.30–32 The success of immediate lymphatic reconstruction in this high-risk population is promising and points to the need to determine appropriate patient selection criteria to broaden its application.
我们最显著的发现是，在有多种独立风险因素的患者群体中，术后淋巴水肿的发生率很低。我们小组在2019年进行的荟萃分析包括3000多名患者，结果显示腋窝淋巴结清扫术后淋巴水肿的总发生率为15.5%7 这一数值在增加区域淋巴结照射后增至26.5%。在同一项荟萃分析中，增加淋巴显微外科预防性愈合方法或立即淋巴重建后，上述比例分别降至4.6%和10.6%。12 这些数据与我们目前机构的淋巴水肿率 3.1% 相吻合。我们队列中的大多数患者都属于高危人群，接受了腋窝淋巴结清扫术和区域淋巴结辅助放疗。大多数患者还接受了新辅助化疗（47%）或辅助化疗（59%），其中大多数接受了以类固醇为基础的治疗方案。30-32立即淋巴重建术在这一高危人群中取得的成功令人鼓舞，同时也表明有必要确定适当的患者选择标准，以扩大其应用范围。
The rate of transient lymphedema observed in this cohort was 12.5 percent. This overall statistic is consistent with that reported by Boccardo et al., who found a 10.8 percent rate of transient lymphedema.12 The majority of postoperative transient lymphedema diagnoses resolved completely within 3 to 6 months of onset. Transient lymphedema has been defined differently across studies. Increases in arm girth after surgery have resolved spontaneously in 33 to 51 percent of patients, particularly in those undergoing adjuvant treatment. In fact, Kilbreath et al. suggest that swelling observed in the first postoperative year not be defined as lymphedema unless it persists for at least 6 months.33 This finding is the reason that we excluded all patients who did not have at least 6-month follow-up from analysis.
在该队列中观察到的短暂性淋巴水肿发生率为12.5%。12 大部分术后短暂性淋巴水肿在发病后3至6个月内完全消退。不同研究对一过性淋巴水肿的定义各不相同。33%至51%的患者在术后臂围增大，尤其是接受辅助治疗的患者，会自行消退。33 事实上，Kilbreath 等人建议，术后第一年观察到的肿胀除非持续至少 6 个月，否则不应定义为淋巴水肿。
We recommend that patients undergoing similar regimens be closely surveilled for 4 years and that patients with transient lymphedema be defined as those that developed quantitative signs and symptoms within 6 months of their last oncologic treatment (i.e., surgery, radiation, or chemotherapy). Our prospective surveillance regimen for this high-risk patient cohort allows for the early detection of at-risk patients to facilitate early intervention.24,34 For example, patients at our center who develop signs/symptoms and measurements consistent with lymphedema initiate a more intense regimen under certified lymphedema therapists that includes compression bandaging and heightened surveillance. In the future, standardizing the definition of transient lymphedema will not only facilitate the development of a shared, uniform vocabulary among lymphedema providers, but will also allow for better aggregation of data sets to identify particular risk factors associated with persistent lymphedema.
我们建议对接受类似治疗方案的患者进行为期 4 年的密切监测，并将一过性淋巴水肿患者定义为在最后一次肿瘤治疗（即手术、放疗或化疗）后 6 个月内出现定量体征和症状的患者。我们对这一高风险患者群的前瞻性监测方案可及早发现高风险患者，以便进行早期干预。2434 例如、我们中心的患者如果出现与淋巴水肿相符的体征/症状和测量结果，就会在经过认证的淋巴水肿治疗师的指导下接受更严格的治疗，包括加压包扎和加强监测。未来，对一过性淋巴水肿的定义进行标准化不仅能促进淋巴水肿医疗机构之间形成共享的统一词汇，还能更好地汇总数据集，以确定与持续性淋巴水肿相关的特殊风险因素。
We found bioimpedance spectroscopy to be the most reliable assessment modality that detected changes in postoperative limb girth consistent with lymphedema. In fact, in all patients who developed transient lymphedema, L-Dex was the first measurement modality to demonstrate lymphedema. The concomitant presence of symptoms, most frequently heaviness, was reported by these patients. Bioimpedance spectroscopy has an increased sensitivity to detect subtle changes in extracellular fluid volume and has been championed for its utility in lymphedema surveillance programs.25,35 Furthermore, this modality is operator-independent and more readably understandable, as set points are clear and findings do not necessitate interpretation of nondominant and dominant hands.36 Other modalities including serial circumferential measurements would be more susceptible to interrater measurement variations. Nonetheless, we continue to use circumferential measurements and perometry for assessment to best capture any change in volume in the affected extremity that would be concerning for lymphedema development.
我们发现，生物阻抗光谱仪是最可靠的评估方式，它能检测出与淋巴水肿一致的术后肢体周长变化。事实上，在所有出现一过性淋巴水肿的患者中，L-Dex 是第一种显示淋巴水肿的测量方式。据这些患者报告，他们同时还出现了一些症状，其中最常见的是沉重感。生物阻抗光谱仪在检测细胞外液容量的细微变化方面具有更高的灵敏度，因此在淋巴水肿监测项目中大显身手。2535 此外、这种模式与操作者无关，更易于阅读理解，因为设置点清晰明了，结果也无需对非惯用手和惯用手进行解释。36 其他测量方式（包括连续周径测量）更容易受到测量者间差异的影响。尽管如此，我们仍继续使用周径测量和周径测量法进行评估，以最好地捕捉患肢体积的任何变化，这些变化可能与淋巴水肿的发展有关。
Interestingly, one commonality among patients who developed transient lymphedema is that they all underwent axillary lymph node dissection. No patients who underwent axillary sampling developed signs or symptoms consistent with lymphedema. The one anatomical area where residual nodal tissue was most often noted, thereby qualifying the case as axillary sampling, was along the axillary vein. Interestingly, although our prior report and other existing articles focus on the number of nodes removed during axillary intervention,37–40 perhaps the extent of dissection is more clinically relevant. We do believe that, moving forward, researchers adapt a uniform definition for axillary lymph node dissection to best evaluate and distinguish outcomes (lymphedema) for this cohort compared to those who did not undergo full dissection. In breast cancer surgery, an optimal number of lymph nodes removed (i.e., >10) during axillary lymph node dissection has traditionally been proposed as a quality metric to confirm accurate staging.41–44 However, it may be more important to consider the extent of axillary lymph node dissection as paramount.
有趣的是，出现一过性淋巴水肿的患者有一个共同点，即他们都接受了腋窝淋巴结清扫术。接受腋窝取样的患者均未出现与淋巴水肿相符的体征或症状。最常发现残留结节组织的解剖区域是沿腋窝静脉，因此可以确定为腋窝取样。有趣的是，尽管我们之前的报告和其他现有文章都关注腋窝介入时切除的结节数量，37-40 也许解剖的范围与临床更相关。我们确实认为，研究人员在今后的工作中应调整腋窝淋巴结清扫的统一定义，以最好地评估和区分与未进行全面清扫的患者相比，这部分患者的治疗效果（淋巴水肿）。在乳腺癌手术中，腋窝淋巴结清扫时切除淋巴结的最佳数量（即>10个）历来被认为是确认准确分期的质量指标41-44 然而，更重要的可能是考虑腋窝淋巴结清扫的范围。
Immediate lymphatic reconstruction was unable to be performed in nine of 41 patients (22 percent) who underwent immediate lymphatic reconstruction with at least 6-month follow-up. This was primarily secondary to venous issues, including inadequate vein length. Because immediate lymphatic reconstruction was first performed at our institution in 2016, we have noticed a decrease in rates of aborted procedures when a collaborative operative approach is used. Specifically, when able, both the breast and lymphatic surgeon are present for the axillary dissection. This provides the opportunity to facilitate dialogue between surgeons regarding preservation of appropriate and suitable veins.
在 41 位接受了即时淋巴重建且至少接受了 6 个月随访的患者中，有 9 位（22%）无法进行即时淋巴重建。这主要是因为静脉问题，包括静脉长度不足。我院于 2016 年首次开展即刻淋巴重建术，因此我们注意到，采用合作手术方式后，手术流产率有所下降。具体来说，在条件允许的情况下，乳腺外科医生和淋巴外科医生都会在场进行腋窝清扫。这为促进外科医生之间就保留适当和合适的静脉进行对话提供了机会。
There are noteworthy limitations to our study. Although our study has unique strengths, including multiple measurement modalities and a rigorous follow-up criterion for study inclusion, our study was not designed as a prospective randomized trial. Moreover, our lymphatic surgery database does not capture patients who exclusively underwent axillary lymph node dissection. Thus, we do not have a formal control group for comparison. We do acknowledge that our study was limited by the number of patients included in analysis. We restricted our eligibility criteria to include those who had sufficient follow-up and serial measurements for evaluation. Furthermore, our median follow-up time was 11.4 months. There were patients included in this cohort who met minimum follow-up criteria but did not present for surveillance measurements. Although we can contend that, in our experience, patients are less likely to present if asymptomatic, we are unable to comment on the entire cohort of patients, who theoretically met eligibility criteria. In light of this, we have modified our surveillance protocol to include direct outreach to patients to encourage adherence to appointments.
我们的研究存在一些值得注意的局限性。虽然我们的研究具有独特的优势，包括多种测量方式和严格的随访纳入标准，但我们的研究并没有设计成前瞻性随机试验。此外，我们的淋巴手术数据库并不包含只接受腋窝淋巴结清扫术的患者。因此，我们没有正式的对照组进行比较。我们承认，我们的研究受到了纳入分析的患者人数的限制。我们限制了我们的资格标准，只包括那些有足够的随访和连续测量结果可供评估的患者。此外，我们的中位随访时间为 11.4 个月。有些患者虽然符合最低随访标准，但却没有接受监测测量。虽然根据我们的经验，无症状的患者不太可能来就诊，但我们无法对理论上符合资格标准的所有患者进行评论。有鉴于此，我们修改了监测方案，包括直接联系患者，鼓励他们遵守预约。
CONCLUSIONS 结 论
Data from our experience support that immediate lymphatic reconstruction demonstrates significant promise in reducing rates of postoperative lymphedema in a high-risk patient cohort with a minimum 6-month follow-up. We used multiple measurement modalities to evaluate patients at prescribed time intervals and found L-Dex to be the most sensitive. Our study fills a gap in the literature by our rigid inclusion criteria, use of multiple measurement modalities, and mode of data entry and analysis where the operating surgeon was blinded. We look forward to continuing our studies in a larger, more diverse patient cohort.
我们的经验证明，在至少随访 6 个月的高风险患者群中，即时淋巴重建在降低术后淋巴水肿发生率方面大有可为。我们采用了多种测量方式，在规定的时间间隔内对患者进行评估，结果发现 L-Dex 的灵敏度最高。我们的研究通过严格的纳入标准、多种测量模式的使用以及手术医生盲法的数据录入和分析模式填补了文献空白。我们期待着在更大规模、更多样化的患者群体中继续开展研究。
REFERENCES 参考文献
1. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis. Lancet Oncol. 2013;14:500–515.
1.DiSipio T、Rye S、Newman B、Hayes S.乳腺癌术后单侧手臂淋巴水肿的发生率：系统回顾和荟萃分析。Lancet Oncol.2013;14:500-515.
2. Ozcinar B, Guler SA, Kocaman N, Ozkan M, Gulluoglu BM, Ozmen V. Breast cancer related lymphedema in patients with different loco-regional treatments. Breast 2012;21:361–365.
2.Ozcinar B, Guler SA, Kocaman N, Ozkan M, Gulluoglu BM, Ozmen V. 不同局部区域治疗患者的乳腺癌相关淋巴水肿。乳腺 2012；21：361-365。
3. Chang DT, Feigenberg SJ, Indelicato DJ, et al. Long-term outcomes in breast cancer patients with ten or more positive axillary nodes treated with combined-modality therapy: The importance of radiation field selection. Int J Radiat Oncol Biol Phys. 2007;67:1043–1051.
3.Chang DT、Feigenberg SJ、Indelicato DJ 等：《采用联合模式疗法治疗 10 个或 10 个以上腋窝结节阳性乳腺癌患者的长期疗效》：放射野选择的重要性。Int J Radiat Oncol Biol Phys.
4. Wernicke AG, Shamis M, Sidhu KK, et al. Complication rates in patients with negative axillary nodes 10 years after local breast radiotherapy after either sentinel lymph node dissection or axillary clearance. Am J Clin Oncol. 2013;36:12–19.
5. Hayes S, Di Sipio T, Rye S, et al. Prevalence and prognostic significance of secondary lymphedema following breast cancer. Lymphat Res Biol. 2011;9:135–141.
6. Chang EI, Skoracki RJ, Chang DW. Lymphovenous anastomosis bypass surgery. Semin Plast Surg. 2018;32:22–27.
7. Johnson AR, Kimball S, Epstein S, et al. Lymphedema incidence after axillary lymph node dissection: Quantifying the impact of radiation and the lymphatic microsurgical preventive healing approach. Ann Plast Surg. 2019;82(Suppl 3):S234–S241.
8. Shih YC, Xu Y, Cormier JN, et al. Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: A 2-year follow-up study. J Clin Oncol. 2009;27:2007–2014.
9. Taghian NR, Miller CL, Jammallo LS, O’Toole J, Skolny MN. Lymphedema following breast cancer treatment and impact on quality of life: A review. Crit Rev Oncol Hematol. 2014;92:227–234.
10. Rockson SG. Lymphedema after breast cancer treatment. N Engl J Med. 2018;379:1937–1944.
11. Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: Risk factors, precautionary measures, and treatments. Gland Surg. 2018;7:379–403.
12. Boccardo F, Casabona F, De Cian F, et al. Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: Over 4 years follow-up. Microsurgery 2014;34:421–424.
13. Hahamoff M, Gupta N, Munoz D, et al. A lymphedema surveillance program for breast cancer patients reveals the promise of surgical prevention. J Surg Res. 2019;244:604–611.
14. Feldman S, Bansil H, Ascherman J, et al. Single institution experience with lymphatic microsurgical preventive healing approach (LYMPHA) for the primary prevention of lymphedema. Ann Surg Oncol. 2015;22:3296–3301.
15. Jørgensen MG, Toyserkani NM, Sørensen JA. The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema: A systematic review and meta-analysis. Microsurgery 2018;38:576–585.
16. Johnson AR, Singhal D. Immediate lymphatic reconstruction. J Surg Oncol. 2018;118:750–757.
17. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg. 2012;46:410–415.
18. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473–483.
19. Keeley V, Crooks S, Locke J, Veigas D, Riches K, Hilliam R. A quality of life measure for limb lymphoedema (LYMQOL). J Lymphoedema 2010;5:26–37.
20. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap): A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–381.
21. Page F, Hamnett N, Chadwick S, Nelson K, Jaffe W. Axillary lymph node dissection: Do you know your boundaries? J Plast Reconstr Aesthet Surg. 2015;68:597–599.
22. Spiguel L, Shaw C, Katz A, et al. Fluorescein isothiocyanate: A novel application for lymphatic surgery. Ann Plast Surg. 2017;78(Suppl 5):S296–S298.
23. Campisi C, Boccardo F. Microsurgical techniques for lymphedema treatment: Derivative lymphatic-venous microsurgery. World J Surg. 2004;28:609–613.
24. Stout NL, Binkley JM, Schmitz KH, et al. A prospective surveillance model for rehabilitation for women with breast cancer. Cancer 2012;118(Suppl):2191–2200.
25. Kilgore LJ, Korentager SS, Hangge AN, et al. Reducing breast cancer-related lymphedema (BCRL) through prospective surveillance monitoring using bioimpedance spectroscopy (BIS) and patient directed self-interventions. Ann Surg Oncol. 2018;25:2948–2952.
26. Stout NL, Pfalzer LA, Springer B, et al. Breast cancer-related lymphedema: Comparing direct costs of a prospective surveillance model and a traditional model of care. Phys Ther. 2012;92:152–163.
27. Fu MR, Cleland CM, Guth AA, et al. L-dex ratio in detecting breast cancer-related lymphedema: Reliability, sensitivity, and specificity. Lymphology 2013;46:85–96.
28. Whelan TJ, Olivotto IA, Parulekar WR, et al.; MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307–316.
29. Coen JJ, Taghian AG, Kachnic LA, Assaad SI, Powell SN. Risk of lymphedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys. 2003;55:1209–1215.
30. Zhu W, Li D, Li X, et al. Association between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema. Anticancer Drugs 2017;28:350–355.
31. Hugenholtz-Wamsteker W, Robbeson C, Nijs J, Hoelen W, Meeus M. The effect of docetaxel on developing oedema in patients with breast cancer: A systematic review. Eur J Cancer Care (Engl.) 2016;25:269–279.
32. Kim M, Kim SW, Lee SU, et al. A model to estimate the risk of breast cancer-related lymphedema: Combinations of treatment-related factors of the number of dissected axillary nodes, adjuvant chemotherapy, and radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86:498–503.
33. Kilbreath SL, Lee MJ, Refshauge KM, et al. Transient swelling versus lymphoedema in the first year following surgery for breast cancer. Support Care Cancer 2013;21:2207–2215.
34. Shah C, Arthur DW, Wazer D, Khan A, Ridner S, Vicini F. The impact of early detection and intervention of breast cancer-related lymphedema: A systematic review. Cancer Med. 2016;5:1154–1162.
35. Kaufman DI, Shah C, Vicini FA, Rizzi M. Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema. Breast Cancer Res Treat. 2017;166:809–815.
36. Fu MR. Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and management. World J Clin Oncol. 2014;5:241–247.
37. Abass MO, Gismalla MDA, Alsheikh AA, Elhassan MMA. Axillary lymph node dissection for breast cancer: Efficacy and complication in developing countries. J Glob Oncol. 2018;4:1–8.
38. Hahamoff M, Gupta N, Munoz D, et al. A lymphedema surveillance program for breast cancer patients reveals the promise of surgical prevention. J Surg Res. 2019;244:604–611.
39. Giuliano AE, Hunt KK, Ballman Karla V, et al. Sentinel lymph node dissection with and without axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial. JAMA 2011;305:569–575.
40. Schmidt-Hansen M, Astin M, Hasler E, Reed MW, Bromham N. Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev. 2017;1:CD004561.
41. Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674–681.
42. Somner JEA, Dixon JMJ, Thomas JSJ. Node retrieval in axillary lymph node dissections: Recommendations for minimum numbers to be confident about node negative status. J Clin Pathol. 2004;57:845–848.
43. Chagpar AB, Scoggins CR, Martin RC II, et al.; University of Louisville Breast Sentinel Lymph Node Study. Factors determining adequacy of axillary node dissection in breast cancer patients. Breast J. 2007;13:233–237.
44. Boughey JC, Donohue JH, Jakub JW, Lohse CM, Degnim AC. Number of lymph nodes identified at axillary dissection: Effect of neoadjuvant chemotherapy and other factors. Cancer 2010;116:3322–3329.
