"The Uncertainty Principle"- studying immediate lymphatic reconstruction impacts the natural history of breast cancer related lymphedema.

Breast cancer-related lymphedema (BCRL) following axillary lymph node dissection (ALND) is a life-altering sequela for patients and a challenging problem for their surgeons. In order to prevent BCRL, immediate lymphatic reconstruction (ILR) is a surgical technique that has been devised to restore lymphatic drainage to the operative limb. Although ILR is becoming popular in the literature, we have identified several challenges within our own ILR research, including a lack of a clear definition of lymphedema, a lack of common outcome measures and possible alteration of the natural history of lymphedema through early compression therapy. Given these challenges, we must move forward with caution, while striving to develop clear and universally agreed upon definitions and outcomes, so that we can advance the body of evidence in support of ILR.

Prevención quirúrgica del linfedema del miembro superior relacionado con la cirugía axilar en el cáncer de mama / Surgical prevention of upper limb lymphoedema related to axillary surgery in breast cancer

El linfedema (LE) es una de las secuelas más graves e incapacitantes secundarias al tratamiento en el cáncer de mama debido a las limitaciones funcionales, implicaciones estéticas y riesgo de infección que conlleva. Se estima que entre el 29 y 39% de las pacientes que se sujetan a una linfadenectomía axilar desarrollan LE, frente a entre 5 y 7% de los que casos que se realiza una biopsia selectiva de ganglio centinela. Para intentar reducir su incidencia, se ha desarrollado el mapeo axilar inverso. El objetivo de esta técnica es diferenciar las distintas vías de drenaje linfático axilar y del brazo mediante la inyección de un colorante azul en el brazo ipsilateral, para poder respetar los linfáticos que drenan la extremidad superior durante la disección linfática axilar. Otra posibilidad es usar verde de indocianina y así combinar el procedimiento de mapeo axilar inverso con el trazador dual estándar en la biopsia selectiva de ganglio centinela. Gracias a la microcirugía se han desarrollado técnicas como la anastomosis linfático-venosa para la prevención secundaria de LE, de manera que los linfáticos aferentes del brazo se pueden redirigir a ramas colaterales de la vena axilar para restaurar el flujo linfático fisiológico. Este procedimiento es más eficaz en las etapas precoces de LE. En los últimos años se está llevando a cabo la técnica LYMPHA, que consiste en anastomosar los vasos linfáticos del brazo a una rama colateral de la vena axilar en el momento de la disección ganglionar. Esta se ha demostrado útil en la prevención primaria de LE y en la reducción de complicaciones tempranas. (AU)

Lymphoedema (LE) is one of the most serious and disabling sequelae secondary to breast cancer treatment due to the functional limitations, cosmetic implications and risk of infection it entails. Twenty-nine to thirty-nine per cent of patients who undergo axillary lymphadenectomy (AL) are estimated to develop LE, compared to 5-7% in those who undergo selective sentinel lymph node biopsy (SLNB). In an attempt to reduce its incidence, Reverse Axillary Mapping (ARM) has been developed. The aim of this technique is to differentiate the different axillary and arm lymphatic drainage pathways by injecting a blue dye into the ipsilateral arm, in order to respect the lymphatics draining the upper extremity during axillary lymphatic dissection. Another possibility is to use indocyanine green and thus combine the ARM procedure with the standard dual tracer in SLNB. Thanks to microsurgery, techniques such as lymphatic-venous anastomosis (LVA) have been developed for secondary prevention of lymphoedema, so that afferent lymphatics in the arm can be redirected to collateral branches of the axillary vein to restore physiological lymphatic flow. In recent years, the LYMPHA technique, which involves anastomosing the lymphatic vessels of the arm to a collateral branch of the axillary vein at the time of lymph node dissection, has been implemented. This has been shown to be useful in the primary prevention of LE and in the reduction of early complications. (AU)

Non-Linear Lymphatic Anatomy in Breast Cancer Patients Prior to Axillary Lymph Node Dissection: A Risk Factor For Lymphedema Development.

Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has become increasingly utilized for the prevention of breast cancer related lymphedema. Preoperative indocyanine green (ICG) lymphography is routinely performed prior to an ILR procedure to characterize baseline lymphatic anatomy of the upper extremity. While most patients have linear lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017-June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study's findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND.

Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-related Lymphedema: Preliminary Results of Randomized Controlled Trial.

OBJECTIVE: To conduct a randomized controlled trial (RCT) on the efficacy of immediate lymphatic reconstruction (ILR) for decreasing the incidence of breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). BACKGROUND: Despite encouraging results in small studies, an appropriately powered RCT on ILR has not been performed. METHODS: Women undergoing ALND for breast cancer were randomized in the operating room 1:1 to either ILR, if technically feasible, or no ILR (control). The ILR group underwent lymphatic anastomosis to a regional vein using microsurgical techniques; control group had no repair and cut lymphatics were ligated. Relative volume change (RVC), bioimpedance, quality of life (QoL), and compression use were evaluated at baseline and every 6 months postoperatively up to 24 months. Indocyanine green (ICG) lymphography was performed at baseline and 12 and 24 months postoperatively. The primary outcome was the incidence of BCRL, defined as ≥10% RVC from baseline in the affected extremity at 12-, 18-, or 24-month follow-up. RESULTS: Of 72 patients randomized to ILR and 72 to control from January 2020 to March 2023, our preliminary analysis includes 99 patients with 12-month follow-up, 70 with 18-month follow-up, and 40 with 24-month follow-up. The cumulative incidence of BCRL was 9.5% in the ILR group and 32% in the control group ( P =0.014). The ILR group had lower bioimpedance values, decreased compression usage, better lymphatic function on ICG lymphography, and better QoL than the control group. CONCLUSIONS: Preliminary results of our RCT show that ILR after ALND decreases BCRL incidence. Our goal is to finish the accrual of 174 patients with 24-month follow-up.

Impact on Health-Related quality of life after wearing compression garment or not for six months in women with mild breast cancer-related arm lymphedema. A cross-sectional study.

BACKGROUND: Women with mild breast cancer-related arm lymphedema (BCRAL) mostly receive treatment with compression garments and instructions in self-care to prevent the progression of lymphedema. However, wearing a compression garment may be experienced as negative and may affect health-related quality of life (HRQOL) more than the lymphedema itself. The aim of this study was to investigate if there is a difference in lymphedema-specific HRQOL, between women with mild BCRAL wearing compression garments or not for 6 months. MATERIAL AND METHODS: Participants with mild BCRAL (Lymphedema relative volume <10%) rated their HRQOL by the Lymphedema Quality of Life Inventory (LyQLI), 6 months after diagnosis and being randomized to compression group (CG) or non-compression group (NCG). Both groups received self-care instructions, and the CG was treated with a standard compression garment, compression class 1. Data from 51 women (30 in the CG and 21 in the NCG), were analyzed. RESULTS: Both the CG and the NCG experienced a low negative impact on HRQOL in physical, psychosocial, and practical domains (score <1). However, the CG experienced a higher negative impact on median HRQOL in the practical domain compared to the NCG, 0.23/0.08 respectively, (p = 0.026). In the specific items, more participants in the CG reported a negative impact on HRQOL compared to the NCG in employment activities 23%/0%, (p = 0.032), embarrassment by lymphedema/compression garments 33%/5%, (p = 0.017), feeling discomfort/embarrassment while doing sports and hobbies 30%/5%, (p = 0.034) and having to answer questions about the lymphedema 27%/0% (p = 0.015). CONCLUSION: Overall, the lymphedema-specific HRQOL was high after 6 months in women with mild lymphedema, with only a minor difference between the groups. Some women may however perceive practical and emotional issues with the compression garment. These aspects should be considered in patient education and when planning/evaluating treatment. Trial registration: ISRCTN51918431.

Advances in the prevention and treatment of breast cancer-related lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies. FINDINGS: Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful. CONCLUSION: Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.

Efficacy of Immediate Lymphatic Reconstruction in Prevention of Breast Cancer-Related Lymphedema.

INTRODUCTION: Breast cancer-related lymphedema (BCRL) is a chronic condition that can negatively affect the quality of life of breast cancer survivors. Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection is emerging as a technique for the prevention of BCRL. This study compared the incidence of BRCL in patients who received ILR and those who were not amenable to ILR. METHODS: Patients were identified through a prospectively maintained database between 2016 and 2021. Some patients were deemed nonamenable to ILR due to a lack of visualized lymphatics or anatomic variability (eg, spatial relationships or size discrepancies). Descriptive statistics, independent t test, and Pearson χ 2 test were used. Multivariable logistic regression models were created to assess the association between lymphedema and ILR. A loose age-matched subsample was created for subanalysis. RESULTS: Two hundred eighty-one patients were included in this study (252 patients who underwent ILR and 29 patients who did not). The patients had a mean age of 53 ± 12 years and body mass index of 28.6 ± 6.8 kg/m 2 . The incidence of developing lymphedema in patients with ILR was 4.8% compared with 24.1% in patients who underwent attempted ILR without lymphatic reconstruction ( P = 0.001). Patients who did not undergo ILR had significantly higher odds of developing lymphedema compared with those who had ILR (odds ratio, 10.7 [3.2-36.3], P < 0.001; matched OR, 14.2 [2.6-77.9], P < 0.001). CONCLUSIONS: Our study showed that ILR was associated with lower rates of BCRL. Further studies are needed to determine which factors place patients at highest risk of developing BCRL.

The influence of axillary surgery and radiotherapeutic strategy on the risk of lymphedema and upper extremity dysfunction in early breast cancer patients.

PURPOSE: To explore the risk factors for breast cancer-related lymphedema (BCRL) and upper extremity dysfunction (UED) in patients with early breast cancer after modern comprehensive treatment and to compare the toxicity of different treatment strategies. METHODS: From 2017 to 2020, a total of 1369 female patients with pT1-3N0-1M0 breast cancer who underwent adjuvant radiotherapy in our centre were retrospectively reviewed. BCRL and UED were identified by the Norman and QuickDASH questionnaires. The incidence, severity and risk factors for BCRL and UED were evaluated. RESULTS: After a median follow-up of 25 months, a total of 249 patients developed BCRL; axillary lymph node dissection (ALND), increased number of dissected nodes, right-sided and hypofractionated radiotherapy containing RNI were found to be significant risk factors (all p values < 0.05). The sentinel lymph node biopsy (SLNB)+ regional nodal irradiation (RNI) group had a significantly lower BCRL risk than the ALND + RNI group (10.8% vs. 32.5%, HR = 0.426, p = 0.020), while there was no significant difference between ALND vs. ALND + RNI or SLNB vs. SLNB + RNI. A total of 193 patients developed UED, and ALND (p = 0.02) was the only significant risk factor. The SLNB + RNI group had a significantly decreased risk of UED compared with the ALND + RNI group (7.5% vs. 23.9%, HR = 0.260, p = 0.001), and there was no significant difference between SLNB vs. SLNB + RNI or ALND vs. ALND + RNI. CONCLUSION: Aggressive ALND remains the primary risk factor for BCRL and UED while RNI does not. Thus, replacing ALND with tailored radiotherapy would be an effective preventive strategy in early breast cancer patients.

Current Diagnostic Tools for Breast Cancer-Related Lymphedema.

PURPOSE OF REVIEW: Breast cancer-related lymphedema (BCRL) can have a significant impact on breast cancer survivors quality of life. The purpose of this review is to evaluate diagnostic tools for the assessment of BCRL. RECENT FINDINGS: Multiple BCRL diagnostic tools are available, though older diagnostic tools have low sensitivity, limiting the ability for sub-clinical BCRL diagnosis while BIS and perometry have increased sensitivity and the ability to diagnose BCRL sub-clinically. Prospective studies have demonstrated such an approach coupled to early intervention is associated with low rates of chronic BCRL while a recently published randomized trial demonstrated that prospective surveillance with BIS coupled with early intervention reduced rates of chronic BCRL as compared to circumference measurements with compression garments. Prospective and randomized data support the use of prospective surveillance for BCRL. The strongest data available comes from the PREVENT trial and supports prospective BCRL surveillance with bioimpedance spectroscopy coupled to early intervention with a compression sleeve.

Multidisciplinary preventive intervention for breast cancer-related lymphedema: An international consensus.

OBJECTIVE: To establish a consensus regarding the multidisciplinary prevention of breast cancer-related lymphedema (BCRL), taking into account the expert opinion of professional groups from across the world involved in the identification and treatment of breast cancers. METHODS: International consensus study involving a modified nominal group and Delphi process. A total of 50 preventive strategies representing those used by a range of health disciplines involved in breast cancer care were identified by the nominal group. These strategies were categorised into four subgroups (general recommendations, therapeutic approach, rehabilitation medicine and physiotherapy and dietary recommendations) and presented in survey format to a multidisciplinary panel of experts in a two-round Delphi process. Eleven specialist areas and 15 countries were represented on the panel. RESULTS: Twenty-seven experts responded to both Delphi rounds, and the mean overall agreement after Round 2 was 85.7%. Of the 50 proposed strategies for preventing BCRL, 48 yielded consensus among experts. CONCLUSION: We report an international consensus for the multidisciplinary prevention of BCRL, setting out recommendations aimed at systematising the care of women with breast cancer. The consensus could provide a platform for the development of standardised clinical guidelines.

Early intervention with compression garments prevents progression in mild breast cancer-related arm lymphedema: a randomized controlled trial.

BACKGROUND: Early diagnosis and compression treatment are important to prevent progression in breast cancer-related arm lymphedema (BCRAL). However, some mild BCRAL can be reversible, and therefore, compression treatment may not be needed. The aim of this study was to investigate the proportion of women with mild BCRAL showing progression/no progression of lymphedema after treatment with or without compression garments, differences in changes of lymphedema relative volume (LRV), local tissue water and subjective symptoms during 6 months. Also, adherence to self-care was examined. MATERIAL AND METHODS: Seventy-five women diagnosed with mild BCRAL were randomized to a compression group (CG) or noncompression group (NCG). Both groups received self-care instructions, and the CG were treated with a standard compression garment (ccl 1). Women in the NCG who progressed in LRV ≥2%, or exceeded 10% dropped out, and received appropriate treatment. The proportion showing progression/no progression of LRV, and changes in LRV was measured by Water Displacement Method. Changes in local tissue water were measured by Tissue Dielectric Constant (TDC), subjective symptoms by Visual Analogue Scale, and self-care by a questionnaire. RESULTS: A smaller proportion of LRV progression was found in the CG compared to the NCG at 1, 2 and 6 months follow-up (p ≤ 0.013). At 6 months, 16% had progression of LRV in the CG, compared to 57% in the NCG, (p = 0.001). Thus, 43% in the NCG showed no progression and could manage without compression. Also, CG had a larger reduction in LRV, at all time-points (p ≤ 0.005), and in the highest TDC ratio, when same site followed, at 6 months (p = 0.025). Subjective symptoms did not differ between the groups, except at 1 month, where the CG experienced more reduced tension (p = 0.008). There were no differences in adherence to self-care. CONCLUSION: Early treatment with compression garment can prevent progression in mild BCRAL. Trial registration: ISRCT nr ISRCTN51918431.

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy.

BACKGROUND: Lymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema. STUDY DESIGN: All patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA. RESULTS: 194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2-0.8]). CONCLUSION: SLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.

Reverse Lymphatic Mapping and Immediate Microsurgical Lymphatic Reconstruction Reduces Early Risk of Breast Cancer-Related Lymphedema.

BACKGROUND: Breast cancer-related lymphedema is a progressive disease that poses tremendous physical, psychosocial, and financial burden on patients. Immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection is emerging as a potential therapeutic paradigm to decrease the incidence of breast cancer-related lymphedema in high-risk patients. METHODS: Eighty-one consecutive patients underwent reverse lymphatic mapping and, when feasible, supermicrosurgical immediate lymphaticovenular anastomosis at the time of axillary lymph node dissection at a tertiary care cancer center. Patients were followed prospectively in a multidisciplinary lymphedema clinic (plastic surgery, certified lymphatic therapy, dietary, case management) at 3-month intervals with clinical examination, circumferential limb girth measurements, and bioimpedance spectroscopy. An institutional control cohort was assessed for the presence of objectively diagnosed and treated breast cancer-related lymphedema. Data were analyzed by a university statistician. RESULTS: Seventy-eight patients met inclusion, and 66 underwent immediate lymphaticovenular anastomosis. Mean follow-up was 250 days. When compared to a retrospective control group, the rate of lymphedema in patients who underwent immediate lymphaticovenular anastomosis was significantly lower (6 percent versus 44 percent; p < 0.0001). Patients with 6-month follow-up treated with combined adjuvant radiation therapy and chemotherapy had significantly greater risk of developing breast cancer-related lymphedema (p = 0.04) compared to those without combined adjuvant therapy. Arborized anastomotic technique had a statistically shorter operative time than end-to-end anastomosis (p = 0.005). CONCLUSIONS: This series of consecutive patients demonstrate a 6 percent incidence of early-onset breast cancer-related lymphedema with immediate lymphaticovenular anastomosis and an increased risk in those undergoing combined adjuvant treatment. These early data represent an encouraging and substantial decrease of breast cancer-related lymphedema in high-risk patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

[BREAST CANCER-RELATED LYMPHEDEMA: INCIDENCE AND RISK FACTORS, PREVENTIVE MEASURES AND TREATMENTS].

INTRODUCTION: Lymphedema is a pathological condition in which intercellular protein-rich fluid accumulates and leads over time to inflammation, adipose tissue hypertrophy and fibrosis. Secondary lymphedema is caused by injury or blockage of the lymphatic system and the main cause in the Western world is the treatment of a variety of cancers, the main one being breast cancer. Chronic arm edema after breast cancer surgery is a common problem with an estimated incidence of 1 in 5 patients after breast cancer treatment. In this article we review the main risk factors, approaches to reducing the risk of developing lymphedema after treatment for breast cancer and existing treatment protocols for lymphedema including the surgical innovations in this field and our experience in these innovative surgical approaches. To date, 26 physiological surgeries have been performed at the Tel Aviv Medical Center using the microsurgical approach for treating lymphedema. These surgeries had no significant complications and the improvement was observed to be greater in the group of patients with secondary lymphedema. Lymphovenous anastomosis and vascularized lymph node transfer offer promising solutions for the treatment of breast cancer related lymphedema. The introduction of additional techniques and the refinement of these procedures will probably continue to improve the results in the future.

Prophylactic Use of Compression Sleeves Reduces the Incidence of Arm Swelling in Women at High Risk of Breast Cancer-Related Lymphedema: A Randomized Controlled Trial.

PURPOSE: To determine whether prophylactic use of compression sleeves prevents arm swelling in women who had undergone axillary lymph node dissection for breast cancer surgery. METHODS: Women (n = 307) were randomly assigned to either a compression or control group. In addition to usual postoperative care, the compression group received two compression sleeves to wear postoperatively until 3 months after completing adjuvant treatments. Arm swelling was determined using bioimpedance spectroscopy (BIS) thresholds and relative arm volume increase (RAVI). Incidence and time free from arm swelling were compared using Kaplan-Meier analyses. Hazard ratios (HRs) were estimated from Cox regression models for BIS and RAVI thresholds independently. In addition, time to documentation of the first minimally important difference (MID) in four scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the breast cancer-specific (BR23) questionnaire was analyzed. RESULTS: The HR for developing arm swelling in the compression group relative to the control group was 0.61 (95% CI, 0.43 to 0.85; P = .004) on the basis of BIS and 0.56 (95% CI, 0.33 to 0.96; P = .034) on the basis of RAVI. The estimated cumulative incidence of arm swelling at 1 year was lower in the compression group than the control group on the basis of BIS (42% v 52%) and RAVI (14% v 25%). HRs for time from baseline to the first change of the minimally important difference were not statistically significant for any of the four scales of EORTC QLQ-30 and BR23 questionnaires. CONCLUSION: Prophylactic use of compression sleeves compared with the control group reduced and delayed the occurrence of arm swelling in women at high risk for lymphedema in the first year after surgery for breast cancer.

Immediate Lymphatic Reconstruction to Prevent Breast Cancer-Related Lymphedema: A Systematic Review.

Significance: Lymphedema is chronic limb swelling from lymphatic dysfunction. The condition affects up to 250 million people worldwide. In breast cancer patients, lymphedema occurs in 30% who undergo axillary lymph node dissection (ALND). Recent Advances: Immediate lymphatic reconstruction (ILR), also termed Lymphatic Microsurgical Preventing Healing Approach (LyMPHA), is a method to decrease the risk of lymphedema by performing prophylactic lymphovenous anastomoses at the time of ALND. The objective of this study is to assess the risk reduction of ILR in preventing lymphedema. Critical Issues: Lymphedema has significant effects on the quality of life and morbidity of patients. Several techniques have been described to manage lymphedema after development, but prophylactic treatment of lymphedema with ILR may decrease risk of development to 6.6%. Future Directions: Long-term studies that demonstrate efficacy of ILR may allow for prophylactic management of lymphedema in the patient undergoing lymph node dissection.

Utilisation des microchirurgies pour la prévention et le traitement du lymphœdème lié au cancer / Use of microsurgery for the prevention and treatment of cancer-related lymphedema

INTRODUCTION: Le lymphœdème lié au cancer est une complication causée par un dysfonctionnement du système lymphatique à la suite de certains traitements oncologiques ou par le cancer lui-même, dont les plus communs sont les cancers du sein, gynécologiques, de la peau et uro-génitaux. Il peut apparaître après un traitement chirurgical d'un cancer comme une dissection ganglionnaire ou une biopsie du ganglion sentinelle, mais également à la suite de traitements de radiothérapie. Les principales manifestations sont l'enflure du membre ou de la zone atteinte pouvant être accompagnée d'une sensation de lourdeur, de raideur ou de douleur et d'une diminution de la mobilité. Le lymphœdème peut également induire une morbidité physique et causer de la détresse psychologique chez les patients, pouvant nuire de manière importante à leurs relations sociales et à leur qualité de vie. En outre, les personnes ont un risque plus élevé d'expérimenter des épisodes de cellulite et de lymphangite, pouvant ainsi augmenter la fréquence d'hospitalisation et les coûts associés aux traitements. Le traitement actuellement proposé aux personnes atteintes de lymphœdème est la thérapie décongestive complexe. Cette dernière implique, entre autres, des drainages manuels et le port de vêtements de compression, qui demeurent généralement nécessaires jusqu'à la fin de la vie du patient. Bien que cette thérapie puisse, dans certains cas, réduire et maintenir un volume réduit du membre atteint, elle ne permet pas de restaurer le réseau lymphatique lésé. Les microchirurgies pourraient représenter une alternative qui permettrait de restaurer le réseau lymphatique lésé et ainsi de prévenir et d'améliorer les symptômes des personnes atteintes de lymphœdème lié au cancer. Parmi ces microchirurgies, on retrouve la reconstruction lymphatique immédiate comme microchirurgie préventive. Celle-ci se pratique au même moment que la chirurgie oncologique, soit avant l'apparition du lymphœdème. L'anastomose lymphoveineuse et le transfert de ganglions lymphatiques vascularisés sont, pour leur part, des microchirurgies thérapeutiques réalisées chez des patients atteints de lymphœdème. CONTEXTE: Compte tenu des avantages que pourraient offrir la reconstruction lymphatique immédiate, l'anastomose lymphoveineuse et le transfert de ganglions lymphatiques vascularisés pour la prévention et le traitement du lymphœdème lié au cancer, l'INESSS s'est vu confier le mandat d'évaluer la pertinence clinique de ces microchirurgies dans les établissements de santé québécois, et le cas échéant, de formuler des recommandations relatives à l'organisation de cette offre de services au Québec. MÉTHODOLOGIE: Une revue systématique des données issues de la littérature a été réalisée afin de documenter l'efficacité et l'innocuité des différentes microchirurgies. La littérature considérée porte sur les personnes atteintes d'un cancer, de tous types et de tous stades, ayant subi une microchirurgie dans le but de prévenir ou de guérir un lymphœdème. Des consultations auprès des parties prenantes, comprenant des experts cliniques ainsi que des patients, ont été menées. Des données clinico-administratives ont également été analysées afin d'obtenir un portrait de la problématique au Québec, d'évaluer les coûts des microchirurgies ainsi que l'impact budgétaire que pourraient avoir ces microchirurgies si elles étaient implantées dans notre système de santé. L'ensemble des données a été intégré dans le but de produire des constats auxquels un niveau de preuve a été rattaché. Ces constats, ainsi que des propositions de recommandations, ont été soumis au Comité délibératif permanent ­ Modes d'intervention en santé, pour que celui-ci puisse délibérer en vue de la formulation des recommandations définitives. CONSTATS: L'intégration des données scientifiques, contextuelles et expérientielles a permis de formuler les constats suivants : Besoin de santé: Le lymphœdème lié au cancer est relativement fréquent et apparaît principalement à la suite du traitement chirurgical d'un cancer (dissection ganglionnaire ou biopsie du ganglion sentinelle), mais également de traitements de radiothérapie; La majorité des lymphœdèmes liés au cancer se produisent dans les 2 ans suivant l'intervention oncologique, mais l'expérience clinique a démontré que certains patients développent des symptômes jusqu'à 20 ans plus tard; Le lymphœdème est une source d'anxiété importante omniprésente chez les patients. Contrairement au cancer, les patients n'ont aucun espoir de guérison de leur lymphœdème; Le nombre de personnes pouvant être atteintes de lymphœdème au Québec est difficile à quantifier. Selon la littérature, le risque de développer un lymphœdème à la suite d'une dissection axillaire ou d'une radiothérapie pour le traitement du cancer du sein est estimé à 15 %, ce qui pourrait représenter entre 635 et 1 074 nouveaux cas de lymphoedème au Québec annuellement (lymphoedème lié au cancer du sein uniquement). La modification des pratiques chirurgicales pour le traitement du cancer du sein comme l'avènement de la biopsie du ganglion sentinelle tend à diminuer le nombre de nouveaux cas potentiels de lymphœdème depuis quelques années. Prise en charge: La prise en charge des patients atteints de lymphœdème lié au cancer semble compromise par le manque de connaissances de la part des professionnels de la santé et des autres intervenants, l'accès limité à l'information et l'absence de trajectoire de soins pour cette condition; La thérapie décongestive complexe est le traitement actuellement proposé aux patients atteints de lymphœdème lié au cancer de stade précoce à avancé. Elle représente un fardeau important pour les patients; L'accès à la thérapie décongestive complexe est restreint en raison d'un nombre limité de thérapeutes certifiés pratiquant cette intervention. Ceux-ci travaillent majoritairement en clinique privée, ce qui oblige un investissement financier important de la part du patient; Le degré d'observance des patients quant à la thérapie décongestive complexe semble être variable en raison du nombre important de soins au quotidien. Les autodrainages, le port de vêtements de compression, les soins de la peau ainsi que les exercices occupent une bonne partie de la journée des patients; La thérapie décongestive complexe pourrait permettre de maintenir un volume réduit du membre atteint sans toutefois restaurer le réseau lymphatique lésé; Les microchirurgies pourraient représenter une alternative, ou un complément, qui permettrait de prévenir ou d'améliorer les symptômes de certains patients atteints de lymphœdème lié au cancer en restaurant le réseau lymphatique lésé. État de la pratique des microchirurgies au Québec: Actuellement, aucun établissement n'offre la reconstruction lymphatique immédiate dans le but de prévenir les lymphœdèmes liés au cancer; Deux établissements de santé montréalais offrent la pratique de microchirurgies afin de traiter les patients atteints de lymphœdème au moyen de la technique d'anastomose lymphoveineuse ou du transfert de ganglions lymphatiques vascularisés; Un troisième établissement est actuellement en élaboration d'un projet afin d'acquérir l'équipement nécessaire pour pratiquer la reconstruction lymphatique immédiate, l'anastomose lymphoveineuse et le transfert de ganglions lymphatiques vascularisés; Trois chirurgiens plasticiens sont surspécialisés dans la pratique des microchirurgies à des fins de prévention et (ou) de traitement du lymphœdème. Le nombre de patients actuellement traités demeure minime à ce jour. Selon les experts consultés, une offre de service de microchirurgies thérapeutiques devrait être concentrée dans certains centres spécialisés disposant de l'expertise et de l'équipement nécessaires; Considérant la pratique des dissections ganglionnaires dans un nombre élevé de centres partout sur le territoire québécois et la difficulté de sélectionner les patients qui pourraient le plus en bénéficier, il serait difficilement envisageable d'offrir la reconstruction lymphatique immédiate à tous les patients potentiellement à risque de développer un lymphœdème; L'ajout de la reconstruction lymphatique immédiate aux patients atteints de cancer pourrait augmenter le temps opératoire et allonger les délais d'accès à la chirurgie aux patients atteints de cancer et même, à d'autres populations nécessitant une intervention chirurgicale. Appréciation du niveau de la preuve Scientifique: Bien qu'on retrouve quelques études sur le sujet, le niveau de preuve associé à l'évaluation de l'efficacité et de l'innocuité des microchirurgies pour la prévention ou le traitement du lymphœdème associé au cancer du sein est jugé faible. Plusieurs limites et variations méthodologiques rendent la généralisation des données disponibles extrêmement difficile; Les données disponibles sont insuffisantes pour évaluer l'efficacité des microchirurgies pour les lymphœdèmes liés aux autres types de cancer; Pour ces raisons, les constats qui suivent concernent uniquement les microchirurgies pour la prévention et le traitement du lymphœdème lié au cancer du sein. MISE À JOUR DES RECOMMANDATIONS: La pertinence de mettre à jour le présent avis sera évaluée et déterminée en fonction de l'apport de nouvelles données en soutien à l'une ou l'autre des dimensions abordées dans cet avis, notamment la publication des résultats des essais cliniques en cours ainsi que la collecte de données en contexte québécois.

INTRODUCTION: Cancer-related lymphedema is a complication caused by dysfunction of the lymphatic system following certain oncologic treatments or by the cancer itself, the most common of which are breast, gynecological, skin and urogenital cancers. It can occur after surgical treatment of cancer such as lymph node dissection or sentinel node biopsy, but also following radiotherapy treatments. The main manifestations are swelling of the affected limb or area, which may be accompanied by a feeling of heaviness, stiffness or pain and a decrease in mobility. Lymphedema can also induce physical morbidity and cause psychological distress in patients, which can significantly affect their social relationships and quality of life. In addition, individuals are at greater risk of experiencing episodes of cellulitis and lymphangitis, which can increase the frequency of hospitalization and the costs associated with treatment. The current treatment offered to people with lymphedema is complex decongestive therapy. This involves, among other things, manual drainage and the wearing of compression garments, which are generally necessary for the rest of the patient's life. Although this therapy can, in some cases, reduce and maintain a reduced volume of the affected limb, it does not restore the damaged lymphatic network. Microsurgery could be an alternative to restore the damaged lymphatic network and thus prevent and improve the symptoms of people with cancer-related lymphedema. Among these microsurgeries is Lymphatic Microsurgical Preventing Healing Approach (LYMPHA). This is performed at the same time as the oncology surgery, before the onset of lymphedema. Lymphaticovenous anastomosis and vascularized lymph node transfer are, for their part, therapeutic microsurgeries performed on patients with lymphedema. BACKGROUND: Given the potential benefits of LYMPHA, lymphaticovenous anastomosis, and vascularized lymph node transfer for the prevention and treatment of cancer-related lymphedema, INESSS was mandated to evaluate the clinical relevance of these microsurgeries in Quebec health care institutions and, if appropriate, to make recommendations regarding the organization of this service offering in Quebec. METHODOLOGY: A systematic review of data from the literature was conducted to document the efficacy and safety of various microsurgeries. The literature considered includes cancer patients of all types and stages who have undergone microsurgery to prevent or cure lymphedema. Stakeholder consultations, including clinical experts as well as patients were conducted. Clinical and administrative data were also analyzed to obtain a portrait of the problem in Quebec, to evaluate the costs of microsurgery and the budgetary impact that microsurgery could have if it were implemented in our health care system. All of the data were integrated to produce findings to which a level of evidence was attached. These findings, along with proposed recommendations, were submitted to INESSS Comité délibératif permanent ­ Modes d'intervention en santé (standing deliberative committee on health care interventions) for deliberation in order to formulate the final recommendations. FINDINGS: The integration of scientific, contextual, and experiential data resulted in the following findings: Health needs: Cancer-related lymphedema is relatively common and occurs primarily following surgical treatment of cancer (lymph node dissection or sentinel node biopsy), but also following radiation treatments. The majority of cancer-related lymphedema occurs within 2 years of cancer surgery, but clinical experience has shown that some patients develop symptoms up to 20 years later. Lymphedema is a pervasive and significant source of anxiety for patients. Unlike cancer, patients have no hope of recovery from lymphedema. The number of people who may have lymphedema in Quebec is difficult to quantify. According to the literature, the risk of developing lymphedema following axillary dissection or radiation therapy for breast cancer is estimated to be 15%, which could represent between 635 and 1074 new cases of lymphedema in Quebec annually (breast cancer-related lymphedema only). Changes in surgical practices for the treatment of breast cancer, such as the advent of sentinel node biopsy, have tended to decrease the number of potential new cases of lymphedema in recent years. MANAGEMENT: Management of patients with cancer-related lymphedema appears to be compromised by a lack of knowledge among health care professionals and other participants, limited access to information, and the absence of a care pathway for this condition. Complex decongestive therapy is the current treatment offered to patients with early to advanced cancer-related lymphedema. It represents a significant burden for patients. Access to complex decongestive therapy is limited due to a limited number of certified therapists performing this procedure. Most of them work in private clinics, which requires a significant financial investment from the patient. Patient compliance with complex decongestive therapy appears to be variable due to the large amount of daily care. Self-drainage, compression garments, skin care and exercise occupy a large part of the patient's day. Complex decongestive therapy could maintain a reduced volume of the affected limb without restoring the injured lymphatic network. Microsurgeries could be an alternative, or an adjunct, to prevent or improve symptoms in some patients with cancer-related lymphedema by restoring the injured lymphatic network. STATUS OF MICROSURGERY PRACTICE IN QUEBEC: Currently, no facilities offer LYMPHA to prevent cancer-related lymphedema. Two Montreal health care facilities offer microsurgeries to treat patients with lymphedema using the lymphaticovenous anastomosis or vascularized lymph node transfer. A third facility is currently developing a project to acquire the necessary equipment to perform LYMPHA, lymphaticovenous anastomosis and vascularized lymph node transfer. Three plastic surgeons are subspecialized in microsurgeries for the prevention and/or treatment of lymphedema. The number of patients currently treated remains minimal. According to the experts consulted, the provision of therapeutic microsurgeries services should be concentrated in certain specialized centres having the necessary expertise and equipment. Considering that the practice of lymph node dissections exists in a large number of centres throughout Quebec and the difficulty of selecting the patients who could most benefit from it, it would be difficult to consider offering LYMPHA to all patients potentially at risk of developing lymphedema. The addition of LYMPHA to cancer patients could increase operative time and lengthen surgery waiting time for cancer patients and even other populations requiring surgery. UPDATING THE RECOMMENDATIONS: The relevance of updating this advisory will be evaluated and determined based on the contribution of new data in support of any of the dimensions addressed in this advisory, particularly the publication of the results of ongoing clinical trials and the collection of data in the Quebec context.

Methods for quantifying breast cancer-related lymphedema in patients undergoing a contralateral prophylactic mastectomy.

Patients treated for breast cancer are at risk of developing breast cancer-related lymphedema (BCRL). A significant proportion of patients treated for breast cancer are opting to undergo a contralateral prophylactic mastectomy (CPM). Currently, it remains unclear as to whether the relative volume change (RVC) equation may be used as an alternative to the weight adjusted change (WAC) equation to quantify BCRL in patients who undergo CPM. In order to simplify BCRL screening, our cohort of patients who underwent a CPM (n=310) was matched by BMI to a subset of patients who underwent unilateral breast surgery (n=310). Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6-12 months. The correlation of ipsilateral RVC and WAC values for those who underwent bilateral surgery was calculated (r=0.60). Contralateral WAC values for patients in both cohorts were compared, and there was no significant difference between the two distributions in variance (p=0.446). The RVC equation shows potential to be used to quantify ipsilateral postoperative arm volume changes for patients who undergo a CPM. However, a larger trial in which RVC and WAC values are prospectively assessed is needed.