Impact of neoadjuvant chemotherapy on breast cancer-related lymphedema after axillary lymph node dissection: a retrospective cohort study.

PURPOSE: We aimed to evaluate whether neoadjuvant chemotherapy (NAC) could be a risk factor for breast cancer-related lymphedema (BCRL) associated with axillary lymph node dissection (ALND). PATIENTS AND METHODS: A total of 596 patients with cT0-4N0-3M0 breast cancer who underwent ALND and chemotherapy were retrospectively analyzed between March 2012 and March 2022. NAC was administered in 188 patients (31.5%), while up-front surgery in 408 (68.5%). Univariate and multivariable Cox regression analyses were performed to determine whether NAC was an independent risk factor for BCRL. With propensity score matching (PSM), the NAC group and up-front surgery group were matched 1:1 by age, body mass index (BMI), molecular subtypes, type of breast surgery, and the number of positive lymph nodes. Kaplan-Meier survival analyses were performed for BCRL between groups before and after PSM. Subgroup analyses were conducted to explore whether NAC differed for BCRL occurrence in people with different characteristics. RESULTS: At a median follow-up of 36.3 months, 130 patients (21.8%) experienced BCRL [NAC, 50/188 (26.60%) vs. up-front surgery, 80/408 (19.61%); P = 0.030]. Multivariable analysis identified that NAC [hazard ratio, 1.503; 95% CI (1.03, 2.19); P = 0.033] was an independent risk factor for BCRL. In addition, the hormone receptor-negative/human epidermal growth factor receptor 2-negative (HR-/HER2-) subtype, breast-conserving surgery (BCS), and increased positive lymph nodes significantly increased BCRL risk. After PSM, NAC remained a risk factor for BCRL [hazard ratio, 1.896; 95% CI (1.18, 3.04); P = 0.007]. Subgroup analyses showed that NAC had a consistent BCRL risk in most clinical subgroups. CONCLUSION: NAC receipt has a statistically significant increase in BCRL risk in patients with ALND. These patients should be closely monitored and may benefit from early BCRL intervention.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Incidence and predictors of axillary web syndrome and its association with lymphedema in women following breast cancer treatment: a retrospective study.

PURPOSE: Axillary web syndrome (AWS) presents as a common postsurgical complication in individuals with breast cancer. Breast cancer-related lymphedema (BCRL) contributes to the shoulder and arm morbidity common in breast cancer survivors and often associated to cancer treatment. A paucity of literature exists evaluating the risk factors for developing AWS and the association between AWS and BCRL. The purposes of this study were (1) to identify risk factors for AWS in individuals with breast cancer, (2) to examine the association between BCRL and AWS, and (3) to determine if AWS increases the risk for developing BCRL. METHODS: A retrospective study of 354 women who underwent breast cancer treatment and received physical therapy was included. RESULTS: Axillary web syndrome developed in a third of women and predominately occurred in the first 8 postoperative weeks. The odds of AWS development were 73% greater for participants over the age of 60 (OR = 1.73, CI 95% 1.05-2.84). Women with AWS had 44% greater risk to develop lymphedema during the first postoperative year (RR = 1.44, CI 95% 1.12-1.84, p = 0.002). If AWS developed within the first postoperative month, women were almost 3 times more likely to develop lymphedema within the first 3 postoperative months compared with other women with AWS (RR = 2.75, CI 95% 1.199-6.310, p = 0.007). CONCLUSIONS: Our findings suggest that 30% of breast cancer survivors will have AWS during the first year of survivorship. As institutions prioritize screening efforts, early postoperative prospective surveillance is needed for women over 60 due to high risk for AWS development and any women with AWS for increased risk of lymphedema development based on our findings.

Lymphatic Vasculature Requires Estrogen Receptor-α Signaling to Protect From Lymphedema.

OBJECTIVE: Estrogens exert beneficial effect on the blood vascular system. However, their role on the lymphatic system has been poorly investigated. We studied the protective effect of the 17ß estradiol-the most potent endogenous estrogen-in lymphedema-a lymphatic dysfunction, which results in a massive fluid and fat accumulation in the limb. APPROACH AND RESULTS: Screening of DNA motifs able to mobilize ERs (estrogen receptors) and quantitative real-time polymerase chain reaction analysis revealed that estradiol promotes transcriptional activation of lymphangiogenesis-related gene expression including VEGF (vascular endothelial growth factor)-D, VEGFR (VEGF receptor)-3, lyve-1, and HASs (hyaluronan synthases). Using an original model of secondary lymphedema, we observed a protective effect of estradiol on lymphedema by reducing dermal backflow-a representative feature of the pathology. Blocking ERα by tamoxifen-the selective estrogen modulator-led to a remodeling of the lymphatic network associated with a strong lymphatic leakage. Moreover, the protection of lymphedema by estradiol treatment was abrogated by the endothelial deletion of the receptor ERα in Tie2-Cre; ERαlox/lox mice, which exhibit dilated lymphatic vessels. This remodeling correlated with a decrease in lymphangiogenic gene expression. In vitro, blocking ERα by tamoxifen in lymphatic endothelial cells decreased cell-cell junctions, inhibited migration and sprouting, and resulted in an inhibition of Erk but not of Akt phosphorylation. CONCLUSIONS: Estradiol protection from developing lymphedema is mediated by an activation of its receptor ERα and is antagonized by tamoxifen. These findings reveal a new facet of the estrogen influence in the management of the lymphatic system and provide more evidence that secondary lymphedema is worsened by hormone therapy.

Bone loss in the affected forearm in patients with breast cancer-related lymphedema: a controlled study.

PURPOSE: We aimed to investigate the association between lymphedema and bone mass density (BMD) of affected and unaffected forearms in patients with breast cancer-related lymphedema (BCRL). We also explored whether there was a relationship between any disability and BMD on the affected side. METHODS: We evaluated 111 patients (53.75 ± 9.07) with unilateral lymphedema (group 1) and 61 patients (50.90 ± 12.44) without lymphedema (group 2) after breast cancer surgery. BMD was performed by dual-energy x-ray absorptiometry (DXA) in lumbar spine, femoral neck, and distal forearm on both sides. Functional situation was assessed by the Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire. RESULTS: The total Z score (p = 0.018), T score (p = 0.005), and BMD value (p = 0.014) were lower in the affected forearm than the unaffected forearm in group 1. There was no difference between the affected or unaffected sides in the total Z score (p = 0.394), T score (p = 0.518), and BMD value (p = 0.629) in group 2. The DXA measurements in terms of the total forearm Z, T scores, and BMD value on the affected side were statistically significantly different between the groups. There was no difference between groups in the femur neck and lumbar total Z and T scores. There was also a positive correlation between the QuickDASH scores and lymphedema stage (r = 0.469, p = 0.001) and the duration without treatment of lymphedema (r = 0.298, p = 0.02) in group 1. CONCLUSION: We recommend early diagnosis and treatment of lymphedema for the protection of upper extremity disability and localized osteoporosis in patients with BCRL.

Acupuncture for breast cancer-related lymphedema: a randomized controlled trial.

PURPOSE: Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL. METHODS: Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher's exact to determine the proportion of responders. RESULTS: Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between groups for arm circumference difference (0.38 cm greater reduction in AC vs. WL, 95% CI - 0.12 to 0.89, p = 0.14) or bioimpedance difference (1.06 greater reduction in AC vs. WL, 95% CI - 5.72 to 7.85, p = 0.8). There was also no difference in the proportion of responders: 17% AC versus 11% WL (6% difference, 95% CI - 10 to 22%, p = 0.5). No severe adverse events were reported. CONCLUSIONS: Our acupuncture protocol appeared to be safe and well tolerated. However, it did not significantly reduce BCRL in pretreated patients receiving concurrent lymphedema treatment. This regimen does not improve upon conventional lymphedema treatment for breast cancer survivors with persistent BCRL.

Effects of physical exercise on breast cancer-related secondary lymphedema: a systematic review.

PURPOSE: The aim of this systematic review is to assess the effect of different types of exercise on breast cancer-related lymphedema (BCRL) in order to elucidate the role of exercise in this patient group. METHODS: A systematic data search was performed using PubMed (December 2016). The review is focused on the rehabilitative aspect of BCRL and undertaken according to the PRISMA statement with Levels of Evidence (LoE) assessed. RESULTS: 11 randomized controlled trials (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in aftercare were included. The different types of exercise consisted of aqua lymph training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive exercise. Four of the studies measured a significant reduction in BCRL status based on arm volume and seven studies reported significant subjective improvements. No study showed adverse effects of exercise on BCRL. CONCLUSION: The evidence indicates that exercise can improve subjective and objective parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise appearing to provide the most positive effects.

Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: an observational retrospective study with long-term follow-up.

BACKGROUND: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. METHODS: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. RESULTS: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. CONCLUSIONS: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification.

Prospective study of shoulder strength, shoulder range of motion, and lymphedema in breast cancer patients from pre-surgery to 5 years after ALND or SLNB.

OBJECTIVE: Determine the changes in shoulder strength, shoulder range of motion, and arm volume in breast cancer patients treated with sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) METHOD: Sixty-eight SLNB and 44 ALND patients were followed up from pre-surgery to 5 years after surgery. Primary outcomes were the differences between affected and non-affected sides for the following: shoulder strength measured by dynamometry, shoulder range of motion measured by goniometry, and lymphedema measured by volume. As a secondary outcome, health-related quality of life (HRQL) was assessed by the Short Form-36 Health Survey (SF-36) and the Functional Assessment of Cancer Therapy for breast cancer (FACT-B+4) questionnaires. Changes over time were tested for SLNB and ALND using univariate repeated measures analysis of variance. Generalized estimating equation models were constructed to assess the effect of SLNB and ALND over time. RESULTS: After 5 years, the ALND group had significant loss of strength for internal rotators (1.39 kg, p = 0.001) and significant arm volume increase (132.45 mL, p = 0.031). The ALND group had a greater number of patients with clinically relevant internal rotator strength loss (38.7 vs. 13.6%, p = 0.012) and a greater number of lymphedema requiring treatment (33.3 vs. 3.4%, p < 0.001) than the SLNB group. A loss of strength for shoulder external rotators, shoulder range of motion, and HRQL in physical and arm domains persisted at 5 years in both SLNB and ALND groups. CONCLUSION: These results could help understand and plan the prevention, needs, and long-term care of breast cancer patients.

Effects of resistance exercise in women with or at risk for breast cancer-related lymphedema.

ᅟ: Breast cancer survivors (BCS) have been told in the past to avoid strenuous repetitive activities in order to decrease the risk of lymphedema development. Recent evidence suggests that exercise may be beneficial to decrease the signs/symptoms and development of lymphedema. PURPOSE/METHODS: This study assessed the arm circumferences of 27 BCS (64 ± 7 years) at baseline and every 2 weeks thereafter during a 6-month resistance exercise training (RT) intervention. RT consisted of 2 days/week of 10 exercises including two sets of 8-12 repetitions at 52-69 % of the participants' one-repetition maximum. RESULTS: A repeated measure analysis of variance revealed no significant changes in percent difference of arm circumferences at any assessment point (pre, 1.31 ± 6.21 %; post, 0.62 ± 6.55 %), nor were there any adverse lymphedema-related events reported during the study. CONCLUSIONS: These findings imply that RT can be a safe activity for women with or at risk for breast cancer-related lymphedema.

A randomized control study of treating secondary stage II breast cancer-related lymphoedema with free lymph node transfer.

Microsurgical techniques are increasingly used for treating severe lymphoedema cases. The purpose of this study was to evaluate the effectiveness of free vascularized lymph node transfer (LNT) in stage II breast cancer-related lymphoedema patients in comparison with non-surgical management. During the last 3 years, 83 female patients were examined at our lymphoedema clinic. Finally, 36 cases were included in this study and randomly divided in two groups: group A patients (n = 18, mean age 47 years) underwent microsurgical LNT; followed by 6 months of physiotherapy and compression, while group B patients (n = 18, mean age 49 years) were managed by physiotherapy and compression alone for 6 months. Patients of both groups removed their elastic garments after 6 months and were re-examined 1 year later. All the 36 patients had detailed evaluation of the affected extremity including limb volume measurement, infection episodes and scale scoring of pain, feeling of heaviness and functional status both at baseline and 18 month. Limb volume reduction was observed in both groups; mean reduction was greater in group A (57 %) than in group B (18 %). Infection episodes in group A were significantly reduced compared to those in group B patients. All group A patients reported painless and feeling of heaviness-free extremities with overall functional improvement, while the corresponding changes in group B patients were no more than marginal. Moreover, the LNT procedure was estimated as cost effective compared to conservative treatment alone. LNT represents an effective therapeutic approach for stage II lymphoedema patients; it significantly reduces limb volume, decreases recurrent infections and improves the overall function.

Risk of secondary lymphedema in breast cancer survivors is related to serum phospholipid fatty acid desaturation.

PURPOSE: Secondary lymphedema is a common irreversible side effect of breast cancer surgery. We investigated if risk of secondary lymphedema in breast cancer survivors was related to changes in serum phospholipid fatty acid composition. METHODS: Study subjects were voluntarily recruited into the following three groups: breast cancer survivors who had sentinel lymph node biopsy without lymphedema (SLNB), those who had auxillary lymph node dissection without lymphedema (ALND), and those who had ALND with lymphedema (ALND + LE). Body mass index (BMI), serum lipid profiles, bioimpedance data with single-frequency bioimpedance analysis (SFBIA), and serum phospholipid compositions were analyzed and compared among the groups. RESULTS: BMI, serum total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) and SFBIA ratios increased only in the ALND + LE. High polyunsaturated fatty acids (PUFAs) and high C20:4 to C18:2 n-6 PUFAs (arachidonic acid [AA]/linoleic acid [LA]) was detected in the ALND and ALND + LE groups compared to SLNB. The ALND + LE group showed increased activity indices for delta 6 desaturase (D6D) and D5D and increased ratio of AA to eicosapentaenoic acid (AA/EPA) compared to the ALND and SLNB groups. Correlation and regression analysis indicated that D6D, D5D, and AA/EPA were associated with SFBIA ratios. CONCLUSION: We demonstrated that breast cancer survivors with lymphedema had elevated total PUFAs, fatty acid desaturase activity indices, and AA/EPA in serum phospholipids. Our findings suggested that desaturation extent of fatty acid composition might be related to the risk of secondary lymphedema in breast cancer survivors.

Barcelona Lymphedema Algorithm for Surgical Treatment in Breast Cancer-Related Lymphedema.

Background Breast cancer-related lymphedema is a prevalent condition that has a major impact on quality of life. Surgical treatment has become an alternative to help affected patients with good results. However, there is no consensus on surgical procedure and protocol. Methods We analyzed our data in two periods: from June 2007 to December 2011 and from January 2012 to June 2014. Data included the analysis of the limb circumferences and the subjective symptoms felt by patients. Results Of the 200 patients treated in the study, 81 had lymphaticovenous anastomosis, 7 had autologous lymph node transfer, 16 had total breast anatomy restoration, 52 had vibroliposuction, and 44 had combined reconstructive procedures. In the first period, the circumference of the superior limb showed a decrease of 0.9 to 6.1 cm (average 2.75 cm). In the second period, the circumference of the superior limb showed a decrease of 2.9 to 6.1 cm (average 3.85 cm). Clinical results and data from the questionnaires confirmed the improvement and subjective benefits. Conclusion We have obtained considerable improvements in results of limb circumferences and subjective symptoms after incorporating several modifications into our surgical strategy for lymphedema treatment. A detailed preoperative assessment should be performed to determine whether reconstructive surgery or palliative surgery is indicated.

Invention and Clinical Application of an Oversleeve for Measuring Limb Volume in Postoperative Breast Cancer Patients.

BACKGROUND: Lymphedema is a common complication of breast cancer treatment, affecting 1/5 of breast cancer survivors, but there is no reliable way to detect subclinical lymphedema. OBJECTIVE: The purpose of this study was to determine the feasibility and reliability of using an oversleeve as a postoperative limb volume measurement tool in breast cancer patients. METHODS: Fifty patients were analyzed based on inclusion criteria. A body volume measurement kit was designed based on the drainage volume method and the circumference measurement method. Twenty-two normal healthy people were measured by the drainage volume (LV) and oversleeve measuring limb volume (OMLV) methods, so as to verify the accuracy of OMLV. Twenty-eight patients with lymphedema diagnosed by the circumdiameter measurement (CDM) method were measured with OMLV for comparison. The difference in measurements between OMLV and CDM was compared in 50 patients with early lymphedema diagnosed by the LV method. RESULTS: There was no significant difference between the sleeve method and the drainage volume method in the normal population (P = 0.74). All patients with lymphedema diagnosed by CDM met the diagnostic criteria by the OMLV method. In patients with early lymphedema diagnosed by LV, the diagnostic rate with OMLV was significantly higher than that with CDM (P = 0.008). CONCLUSION: Similar to LV in the diagnosis of lymphedema, OMLV can effectively improve the diagnostic rate of early lymphedema, providing a new option for the diagnosis and treatment of lymphedema.

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Feasibility of segmental bioelectrical impedance analysis for mild- to moderate-degree breast cancer-related lymphedema: Correlation with circumferential volume measurement and phase angle.

ABSTRACT: Segmental multi-frequency bioelectrical impedance analysis (s-MFBIA) has been adopted recently to evaluate the volume of breast cancer-related lymphedema (BCRL). This procedure uses the segmental phase angle (s-PhA) as an indicator of cellular integrity. In the smaller-built Asian population, the BCRL often has a small volume difference and can be overlooked by tape circumference volume measurement (TVM). This study aimed to investigate the clinical feasibility of s-MFBIA for the assessment of lymphedema severity compared with TVM and evaluate the association between lymphedema severity and cellular integrity of the affected arm based on s-PhA values for a patient with mild- to moderate-degree BCRL.Segmental PhA and extracellular water (ECW)/total body water (TBW) ratio of bilateral arms were measured using InBody S10, an s-MFBIA device, in 128 BCRL patients. Inter-limb volume ratio was measured using TVM. The inter-limb ECW/TBW ratio was correlated with inter-limb volume ratio. Inter-limb ECW/TBW ratio and inter-limb volume ratio were then correlated with inter-limb PhA ratio to demonstrate the association between lymphedema severity and arm cellular integrity.The inter-limb ECW/TBW ratio and inter-limb volume ratio were positively correlated (r = 0.654, P < .001). The same result was obtained after adjusting for age, body mass index, postoperative survival, and duration of lymphedema (r = 0.636, 0.653, 0.652, and 0.648, P < .001). The inter-limb PhA ratio demonstrated significant negative correlation with inter-limb ECW/TBW ratio and inter-limb volume ratio (r = -0.896, -0.562, P < .001).s-MFBIA has high consistency with the conventional TVM method, and its relation to cellular integrity by segmental PhA enables better understanding of the cellular state of the affected limb in mild- to moderate-degree BCRL. Therefore, it is clinically feasible for severity assessment and monitoring of mild- to moderate-degree BCRL in smaller-built Asian patients.

Reverse Lymph Node Mapping Using Indocyanine Green Lymphography: A Step Forward in Minimizing Donor-Site Morbidity in Vascularized Lymph Node Transfer.

BACKGROUND: Reverse lymphatic mapping before harvesting a lymph node flap is crucial to avoid donor-site lymphedema; however, the technique is complex and unavailable in many centers. The authors introduce radioisotope-free reverse lymphatic mapping using indocyanine green and Patent Blue dye. METHODS: The authors conducted a prospective study in patients undergoing free vascularized groin lymph node transfer for postmastectomy upper extremity lymphedema. The day before surgery, 0.2 ml of technetium-99 was injected into the first and second web spaces of the ipsilateral foot. The following day, once the patient was anesthetized, indocyanine green was injected into the same web spaces of the same foot and Patent Blue dye was injected just proximal to the upper margin of the skin paddle of the lymph node flap. The main lymph nodes draining the limb were localized using indocyanine green lymphography and gamma probe. RESULTS: Thirty-nine patients underwent vascularized groin lymph node transfer with or without deep inferior epigastric artery perforator flap breast reconstruction. Navigation of the main lower extremity draining inguinal lymph nodes using the gamma probe and indocyanine green lymphography was identical in all patients. The blue-stained lymphatics in the skin paddle drained to the superficial proximal inguinal lymph node and were targeted for transfer. No donor-site lymphedema was reported, and lymphatic drainage of the lower extremity was preserved in all cases. CONCLUSIONS: Reverse lymphatic mapping using indocyanine green lymphography provides identical results to those using technetium-99 isotope scanning. However, indocyanine green is preferable in terms of safety and reproducibility and also avoids the complexity and hazards of radioisotope mapping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Correlation between superficial and deep lymphatic systems using magnetic resonance lymphangiography in breast cancer-related lymphedema: Clinical implications.

BACKGROUND: Magnetic resonance lymphangiography (MRL) has increased our knowledge of lymphatic anatomy and lymphedema pathophysiology and improved the efficacy of microsurgical procedures to manage peripheral lymphedema. The aim of this study is to investigate the ability of MRL to detect communications between superficial and deep lymphatic systems in breast cancer-related lymphedema (BRCL) and to investigate whether these communications could preserve lymphatic drainage of the hand. METHODS: Between 2008 and 2017 we used MRL imaging in 59 women with BCRL. Lymphedema of the arm and hand was detected in 30 patients while the hand was spared in 29. Using axial and coronal MRL reconstruction images we investigated the existence of any communication between the superficial and deep lymphatic systems. RESULTS: Among the 29 patients with spared hand, MRL revealed that 24 had at least one communicating lymphatic perforator at the wrist region (p < 0.001). Lymphatic flow at the axilla was clearly visualized in 16 of the 29 patients (55.2%), no perforating lymphatic vessels were detected in the group with lymphedema in the hand (30 patients). CONCLUSIONS: Communications between the deep and superficial lymphatic systems at the wrist region in BCRL patients without hand lymphedema should be considered when planning microsurgical lymphatic procedures at the wrist and in postoperative compression therapy.