Breast Articles From 2023: Informing Practice Across the Continuum of Care.

With new investigations and clinical trials in breast oncology reported every year, it is critical that surgeons be aware of advances and insights into the evolving care paradigms and treatments available to their patients. This article highlights five publications found to be particularly impactful this past year. These articles report on efforts to select the minimal effective dose of tamoxifen for prevention, to challenge the existing age-based screening guidelines as they relate to race and ethnicity, to refine axillary management treatment standards, to optimize systemic therapy in multidisciplinary care settings, and to reduce the burden of breast cancer-related lymphedema after treatment. Taken together, these efforts have an impact on all facets of the continuum of care from prevention and screening through treatment and survivorship.

Immediate lymphatic reconstruction: Lessons learned over eight years.

Immediate lymphatic reconstruction (ILR) is recognized as a surgical approach used to reduce the risk of developing secondary lymphedema, and evidence demonstrating the efficacy of ILR is favorable. Our Lymphatic Center has become a centralized location offering ILR for the risk-reduction in breast cancer-related lymphedema (BCRL) in New England. Over the course of our experience, we made several modifications and adapted our approach to enhance the operative success of this procedure. These include advancements in our use of indocyanine green (ICG) imaging to identify baseline lymphatic anatomical variation, utilization of fluorescein isothiocyanate for lymphatic vessel visualization, application of the lymphosome concept to guide arm injection sites, verification of anastomotic patency (using ICG), localization of reconstruction to guide radiation therapy, incorporation of intraoperative tools to facilitate better anatomic visualization of the axilla, and addition of a lower extremity vein graft to mitigate venous-related complications. Collecting information from each surgery in a standardized manner, including intraoperative lymphatic channel measurements, and deploying clips for possible future radiation exposure, enables future studies on ILR patient outcomes. In this contribution, we aimed to share our institutional modifications with the surgical community to facilitate further adoption, conversation, and advancement of ILR for the risk-reduction in BCRL.

The Vascularized Omentum Lymph Node Transfer - A Key Point in the Lymphedema Management.

Background: As an increased number of women beat breast cancer worldwide, the breast cancer related lymphedema has gained more attention recently. The vascularized omentum lymph node transfer has been approached as an useful tool for advanced and recurrent cases. The purpose of the paper is to emphasize the advantages and disadvantages of this method. Materials and Methods: This retrospective study consists of 17 patients known with breast cancer related lymphedema who received vascularized omentum lymph node transfer. Data was recorded between January 2022 and January 2023. Patients diagnosed with secondary lymphedema stage II or III, unresponsive to previous microsurgical lymphovenous bypass were included. Results: The most prevalent affected site was the left upper limb (59%), where edema was mainly identified in the forearm (75%). Nevertheless, more than half of the subjects have previously received lymphaticovenous anastomosis. The correlation between the stage of lymphedema and the postoperative reduction of the volume of the affected limb was -0.26, the slope to reached -0.33, with an intercept value of 2.64. The follow-up period showed reduced upper limb volume and an improved quality of life. Conclusion: Through an experienced hand, this versatile flap brings hope to breast cancer survivors with lymphedema.

Abnormalities of the Eyelashes in Turner's Syndrome.

Turner's syndrome (TS) is a sex chromosome disorder caused by a partial loss, complete absence or structural abnormality of one X chromosome in females. Special ocular features are often found. Some of the abnormalities are only cosmetic, such as the abnormalities of the eyelashes. The present prospective study with 12 TS and 12 control patients demonstrates the higher number of eyelashes as well as the greater vertical distance between the roots of the eyelashes in patients with TS compared with the control group. Increased awareness of this ophthalmological abnormality could be an additional diagnostic tool for early clinical suspicion of TS diagnosis.

[Plasmacytoid urothelial carcinoma: a rare cause of localized lymphedema]. / Plasmazytoides Urothelkarzinom: eine seltene Ursache des lokalisierten Lymphödems.

Localized lymphedema of the genital region is a rare medical condition. It is named primary lymphedema if caused by a congenital malformation of the lymphatic system. Secondary lymphedemas might be induced by exogenous damage to lymphatic vessels as a result of surgical interventions, obesity, filariasis, radiotherapy or malignancy. We report a case of localized lymphedema of the genial region for which a previously unknown urothelial carcinoma turned out to be the underlying cause.

GLP-1 receptor agonist as an effective treatment for breast cancer-related lymphedema: a case report.

Introduction: Lymphedema is a major public health issue for many women undergoing breast cancer treatment. Although weight loss has been reported to be beneficial in the treatment of lymphedema, no studies to date have examined the use of GLP-1RAs for the treatment of secondary lymphedema. This case report describes a patient who experienced significant resolution of her breast cancer-related lymphedema after initiation of a GLP-1RA for weight loss. Main symptoms and/or important clinical findings: Nine months postoperatively the patient developed arm swelling and disability. While on adjuvant chemo and hormonal therapy, her weight increased dramatically and peaked 4 years later. Corresponding to her weight gain was significant worsening of her symptoms. The main diagnoses therapeutic interventions and outcomes: Due to adjuvant cancer-related weight gain and inability to lose weight with diet and exercise, she was referred for evaluation and diagnosed with lymphedema. The patient started treatment with a Glucagon-like peptide 1 receptor agonist and lost 24% of her body weight over the next 13 months. The improvement in her lymphedema mirrored her weight loss. Her limb volume difference dropped from 10.3% down to 3.4% and she no longer required a compression garment. Her imaging demonstrated return of lymphatic pumping and she experienced a significant improvement in quality of life, assessed by a validated lymphedema-specific patient reported outcome (PROM). She remains on hormonal therapy, no longer needs compression and is back to regular exercise without impairment. Conclusions: GLP-1 RAs provide a potential medical option for many patients struggling with weight gain and lymphedema. We have observed by all objective measures a significant reduction in lymphedema and the elimination of compression in the case presented as a direct result of GLP-1 RA. This may also reduce a patient's BMI to the point where they become a good candidate for lymphovenous bypass or vascularized lymph node transplant when indicated.

Lower limb lymphedema disrupts both static and dynamic balance.

BACKGROUND: The impact of lower-limb-lymphedema on quality of life of patients regarding balance is unclear due to the scarcity of literature. The aim of this study was to determine the static and dynamic balance of patients with lower-limb-lymphedema in comparison with healthy subjects. METHODS: This case-control designed study included 30 lymphedema patients and 30 healthy individuals, of whom were 52 female and 8 male with a mean age of 50.63 ± 9.72 years. Static balance stability and anterior-posterior with lateral sway parameters on four conditions (eyes-opened-stable-ground, eyes-closed-stable-ground, eyes-opened-unstable-ground, eyes-closed-unstable-ground) and dynamic stability of all participants were evaluated. FINDINGS: The demographic variables were similar between the groups. Majority of the patients had lymphedema due to cancer surgery with a stage of 2. Dynamic stability was significantly disrupted in lymphedema group in comparison with controls (P = 0.049). Static balance parameters were impaired on all conditions except the eyes opened-stable ground in lymphedema patients (P = 0.048,P = 0.043,P = 0.017). The dynamic with static balance and lateral sway parameters were correlated with the duration of lymphedema(P = 0.046,P = 0.002,P = 0.005). Anterior-posterior sway on eyes-closed-unstable-ground condition was correlated with functional status (P = 0.02). Static balance on eyes-opened-unstable-ground condition and anterior-posterior sway parameters were correlated with physical activity level (P = 0.015,P = 0.016,P < 0.05). INTERPRETATION: Closing eyes and the deterioration of ground caused significant alteration of the static and dynamic balance both separately and together in patients with lower-limb-lymphedema compared to healthy subjects. Regarding the static and dynamic imbalance, we suggest the evaluation of balance and inclusion of balance exercises in routine lymphedema rehabilitation program, especially in the early period of disease.

Quantification of Lymphangiogenesis in the Murine Lymphedema Tail Model Using Intravital Microscopy.

Background: Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects an estimated five million Americans. There is no cure for this disease. Assessing lymphatic growth is essential in developing novel therapeutics. Intravital microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous nonviral vector gene delivery using a chip with nanochannel poration in a rapid (<100 ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics in the live mice model. Methods and Results: The murine tail model of lymphedema was utilized. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: TNTpCMV6 group receives pCMV6 (expression vector backbone alone) (n = 6); TNTProx1 group receives pCMV6-Prox1 (n = 6). Lymphatic vessels (fluorescein isothiocyanate [FITC]-dextran stained) and lymphatic branch points (indicating lymphangiogenesis) were analyzed with the confocal/multiphoton microscope. The experimental group TNTProx1 exhibited reduced postsurgical tail lymphedema and increased lymphatic distribution compared to TNTpCMV6 group. More lymphatic branching points (>3-fold) were observed at the TNT site in TNTProx1 group. Conclusions: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. IVM can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.

Does Lymphovenous Anastomosis Effect Mammalian Target of Rapamycin Inhibitor-associated Lymphedema Patients?

The mammalian target of rapamycin (mTOR) inhibitors are used to prevent organ transplant rejection and are preferred over other immunosuppressants due to its low nephrotoxicity. However, mTOR inhibitors have been associated with various adverse effects including lymphedema. Although rare in incidence, previously known treatments for mTOR inhibitor-induced lymphedema were limited to discontinuation of related drugs and complex disruptive therapy with variable results. In this article, three patients who developed lymphedema in their lower limbs after using mTOR inhibitors, including two bilateral and one unilateral case, were treated with physiologic surgery methods such as lymphovenous anastomosis (LVA) and lymph node transfer. The efficacy of the treatment was evaluated. In the three cases described, cessation of the drug did not lead to any reduction in edema. The use of LVA and lymph node transfer resulted in early reductions in volume but failed to sustain over time. All patients underwent secondary nonphysiologic surgery such as liposuction resulting in sustained improvement. This series presents the first physiologic approach to mTOR inhibitor-induced lymphedema. Although further study is warranted, the physiologic surgical options may have limited success and nonphysiologic options may offer better sustainable results.

Conservative medical intervention as a complement to CDT for BCRL therapy: a systematic review and meta-analysis of randomized controlled trials.

Background: The effect of first-line complex decongestive therapy (CDT) for breast cancer-related lymphedema (BCRL) depending on various factors forces patients to seek additional treatment. Therefore, this meta-analysis was conducted to evaluate the effect of different conservative medical interventions as a complement to CDT. This is the first meta-analysis that includes various kinds of conservative treatments as adjunctive therapy to get broader knowledge and improve practical application value, which can provide recommendations to further improve BCRL patients' health status. Methods: RCTs published before 18 December 2023 from PubMed, Embase, Cochrane Library, and Web of Science databases were searched. RCTs that compared the effects of conservative medical intervention were included. A random-effects or fixed-effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool. Results: Sixteen RCTs with 690 participants were included, comparing laser therapy, intermittent pneumatic compression (IPC), extracorporeal shock wave therapy (ESWT), electrotherapy, ultrasound, diet or diet in combination with synbiotic supplement, traditional Chinese medicine (TCM), continuous passive motion (CPM), and negative pressure massage treatment (NMPT). The results revealed that conservative medical intervention as complement to CDT had benefits in improving lymphedema in volume/circumference of the upper extremity [SMD = -0.30, 95% CI = (-0.45, -0.15), P < 0.05, I 2 = 51%], visual analog score (VAS) for pain [SMD = -3.35, 95% CI (-5.37, -1.33), P < 0.05, I 2 = 96%], quality of life [SMD = 0.44, 95% CI (0.19, 0.69), P < 0.05, I 2 = 0], and DASH/QuickDASH [SMD = -0.42, 95% CI (-0.70, -0.14), P < 0.05, I 2 = 10%] compared with the control group. Subgroup analysis revealed that laser therapy and electrotherapy are especially effective (P < 0.05). Conclusion: Combining conservative medical interventions with CDT appears to have a positive effect on certain BCRL symptoms, especially laser therapy and electrotherapy. It showed a better effect on patients under 60 years old, and laser therapy of low to moderate intensity (5-24 mW, 1.5-2 J/cm2) and of moderate- to long-term duration (≥36-72 sessions) showed better effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354824, identifier CRD42022354824.

Efficacy of Airbo·Wave in Nighttime Compression for Leg Lymphedema.

Objectives: This study aimed to clarify the efficacy of Airbo·Wave EV1 in nighttime compression therapy as part of complex decongestive therapy (CDT) for leg lymphedema. Patients and Methods: We retrospectively reviewed 33 patients with leg lymphedema who used Airbo·Wave EV1 between April 2021 and September 2022. In these patients, the changes in leg volume and skin hardness were assessed using a scale ranging from 1 (softest) to 7 (hardest), and dermal thickness before and after the use of Airbo·Wave EV1 was evaluated. Results: Twenty-two patients used Airbo·Wave EV1 for nighttime compression in CDT. Their skin hardness in the lower calf decreased mildly (mean scale: before, 3.9; after, 3.6 [p <0.05]), but the leg volume and skin thickness were unchanged. Eleven patients who were nonadherent could restart compression therapy by using Airbo·Wave EV1. Their skin hardness in the medial lower calf (before, 5.1; after, 4.3 [p <0.05]), leg volume (before, 8412 mL; after, 8191 mL [p <0.01]), and skin thickness in the medial and lateral lower leg were reduced. Conclusion: Airbo·Wave EV1 could improve skin hardness in the calf area. Moreover, it is a safe procedure for the nonadherent while reducing leg volume reasonably.

Time trend of breast cancer-related lymphedema according to body mass index.

PURPOSE: To clarify how body mass index (BMI) affects the development and temporal trend of breast cancer-related lymphedema (BCRL). METHODS: This is a prospective study in which patients with operable breast cancer were registered in a single institute between November 2009 and July 2010. The incidence of lymphedema at 1, 3, and 5 years after surgery was assessed according to BMI, and the trend of newly developed BCRL was examined. Obesity was defined as BMI ≥25 in accordance with the Japan Society for the Study of Obesity. RESULTS: A total of 368 patients were included in this study. The multivariate analysis of the whole population showed that high BMI, axillary dissection, and radiotherapy remained as risk factors for BCRL. Patients with high BMI showed a significantly higher incidence of new lymphedema than those with low BMI at 1 year (p < 00.001) regardless of axillary procedures (39.1 % vs 16.3 % for axillary dissection; 15.6 % vs 1.5 % for sentinel lymph node biopsy) but not at 3 and 5 years. Once BCRL developed, patients with high BMI showed slow recovery and 50.0 % of the patients retained edema at 5 years while patients with low BMI showed rapid recovery and 26.7 % retained after 3 years (p = 0.04). CONCLUSION: The preoperative BMI affected the incidence and temporal trend of BCRL regardless of axillary procedures or radiotherapy. Patients with high BMI should be given appropriate information about BCRL before surgery with careful follow-up for BCRL after treatment.

Improving quality of life after breast cancer: a comparison of two microsurgical treatment options for breast cancer-related lymphedema (BCRL).

PURPOSE: Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). METHODS: A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. RESULTS: A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. CONCLUSIONS: Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications.

Lymphaticovenous Anastomosis and Vascularized Lymph Node Transfer for the Treatment of Lymphedema-A Canadian Case Series.

Introduction: Lymphedema is a chronic and debilitating condition. This study aims to assess the efficacy and safety of lymphaticovenous anastomosis (LVA) and vascularized lymph node transfers (VLNT) for the treatment of patients suffering from lymphedema, mainly by comparing pre- and postoperative daily compression use, limb volumes, and occurrence of cellulitis. Methods: We performed a retrospective analysis of patients who were treated by a single surgeon for lymphedema with LVA and/or VLNT between March 2018 and February 2020. Eighteen limbs met the inclusion criteria. The severity of lymphatic dysfunction was assessed by indocyanine green lymphangiography. Patients with patent vessels were offered LVA, whereas those without were offered VLNT. Pre- and postoperative circumferential limb measurements, use of compression garments, and postoperative complications were compared. Results: Nine limbs underwent LVA, 8 underwent VLNT, and one both. The minimum follow-up was 12 months. Postoperatively, all but 3 patients (83%) were able to cease daily compression. When considering excess limb volumes, the average reduction was 58%. This reduction was achieved despite compression weaning. Forty-four percent of patients (8) reported episodes of recurrent cellulitis preoperatively, while postoperatively, only 3 of those patients (17%) experienced cellulitis, which was statistically significant (P = .018). No surgical complications occurred. Conclusions: Patients with lymphedema can benefit from LVA and VLNT surgery. An important effect of surgery is decreased dependence on daily compression garments to maintain a stable and reasonable limb volume. The reduction of limb circumference after 1 year was similar to LVA and VLNT. Episodes of cellulitis were significantly lower after the intervention.

Introduction : Le lymphœdème est une affection chronique et débilitante. La présente étude vise à évaluer l'efficacité et l'innocuité de l'anastomose lymphaticoveineuse (ALV) et des transferts des ganglions lymphatiques vascularisés (TGLV) pour le traitement des patients ayant un lymphœdème, surtout en comparant l'utilisation quotidienne des vêtements compressifs, le volume des membres et l'occurrence de cellulites avant et après l'opération. Méthodologie : Les chercheurs ont procédé à une analyse rétrospective des patients chez qui le même chirurgien a procédé à une ALV ou à un TGLV à cause d'un lymphœdème entre mars 2018 et février 2020. Dix-huit membres ont respecté les critères d'inclusion. Les chercheurs ont évalué la gravité du dysfonctionnement lymphatique par lymphangiographie au vert d'indocyanine. Les patients ayant des vaisseaux perméables se sont fait offrir une ALV, et les autres, un TGLV. Les chercheurs ont comparé les mesures du périmètre des membres et l'utilisation de vêtements compressifs avant et après l'opération, de même que les complications postopératoires. Résultats : Une ALV a été effectuée sur neuf membres, des TGLV, sur huit membres, et les deux interventions, sur un membre. La période de suivi minimale était de 12 mois. Après l'opération, tous les patients, sauf trois (83%), ont pu cesser la compression quotidienne. En moyenne, le volume excessif des membres a diminué de 58%. Les chercheurs ont obtenu cette réduction malgré le sevrage de la compression. Au total, 44% des patients (huit) ont signalé des récurrences de la cellulite avant l'opération, mais après l'opération, seulement trois d'entre eux (17%) en ont souffert, ce qui est statistiquement significatif. Aucune complication chirurgicale n'a été signalée. Conclusions : Les patients ayant un lymphœdème peuvent profiter d'une ALV ou d'un TGLV. Parmi ses effets importants, l'opération réduit la dépendance au port quotidien de vêtements compressifs afin que les membres conservent un volume stable et raisonnable. La réduction du paramètre des membres au bout d'un an était semblable après l'ALV et les TGLV. Les épisodes de cellulite étaient considérablement moins fréquents après l'intervention.

Concordance between preoperative imaging methods in patients with limb lymphedema undergoing supermicrosurgical lymphaticovenular anastomosis.

OBJECTIVE: Supermicrosurgical lymphaticovenular anastomosis (LVA) is increasingly being recognized as a first-line treatment of limb lymphedema because it is minimally invasive and highly effective. Lymphoscintigraphy and indocyanine green (ICG) lymphography are the two most commonly performed diagnostic imaging examinations to establish the indication and plan the procedure for patients affected by limb lymphedema. In a small group of patients, the information between these two imaging tools can be discordant, showing different anatomical drainage pathways or the absence of drainage and dermal backflow in one examination and valid drainage pathways in the other. The purpose of this study is to examine the types of possible discrepancies between lymphoscintigraphy of the superficial system and ICG lymphography and to describe the surgical outcomes after LVA for patients presenting with such discrepancies. METHODS: We retrospectively reviewed the data of all patients who underwent LVA for upper or lower limb lymphedema between July 2015 and July 2023. From this series, we identified a group of patients with nonconcordant imaging results from lymphoscintigraphy and ICG lymphography before lymphatic surgery. Nonconcordant findings were described in terms of "pattern discordance" and "pathway discordance." The surgical outcome was measured by the change in the mean circumference of the limb after surgery. The changes between the preoperative and postoperative limb measures were analyzed using the Student t test. P values < .05 were considered significant. RESULTS: A total of 28 patients with limb lymphedema exhibited inconsistencies between preoperative lymphoscintigraphy of the superficial system and ICG lymphography. Among these patients, 14 experienced pattern discordance, 13 had pathway discordance, and 1 patient had both. After LVA, we observed a significant reduction in the average circumference of the affected limb in the analyzed group. CONCLUSIONS: The discrepancy in the information between lymphoscintigraphy and ICG lymphography in the preoperative study of patients affected by limb lymphedema is rare but possible. This phenomenon is still not fully explained; however, our results suggest that it does not correlate with the outcome of supermicrosurgical LVAs.