Extremity Lymphedema Research Articles

The utility of computed tomography venography in the routine evaluation of patients who present to a lymphedema center with lower extremity edema

ObjectiveComputed tomography venography (CTV) is not routinely used to screen patients presenting with a presumed lower extremity lymphedema diagnosis for left iliac vein obstruction (IVO) or May-Thurner syndrome (MTS). The objective of this study is to determine the utility of routine CTV screening for these patients by evaluating the proportion presenting with clinically significant CTV-identified left IVO. MethodsWe retrospectively reviewed 121 patients who had presented to our lymphedema center with lower extremity edema between November 2020 and May 2022. Information regarding demographics, comorbidities, lymphedema characteristics, and imaging reports was collected. Cases of IVO present on CTV were reviewed by a multidisciplinary team to determine the clinical significance of the CTV findings. ResultsOf the patients with complete imaging studies, 49% (n = 25) had abnormal lymphoscintigraphy findings, 45% (n = 46) had reflux on ultrasound, and 11.4% (n = 9) had IVO on CTV. Seven patients (6%) had CTV findings of IVO and edema of either the isolated left (n = 4) or bilateral (n = 3) lower extremities. Cases of IVO on CTV were determined by the multidisciplinary team to be the predominant cause of lower extremity edema for three of these seven cases (43%; or 2.5% of all 121 patients). ConclusionsSix percent of patients presenting to a lymphedema center with lower extremity edema had left-sided IVO on CTV suggestive of MTS. However, the cases of IVO were determined to be clinically significant <50% of the time or for 2.5% of all patients. CTV should be reserved for patients with isolated left-sided or bilateral lower extremity edema with a greater left-sided component and a history of findings that raise clinical suspicion for MTS.

Tissue Dielectric Constant and Skin Stiffness Relationships in Lower Extremity Lymphedema.

Background: Lower extremity lymphedema or edema (LELE) may progressively transition from a state of excess tissue fluid to increased fat accumulation and collagen deposition, with tissue fibrosis and hardening. Such changes may lead to altered tissue water holding and thereby impact tissue dielectric constant (TDC). This study seeks to evaluate the relationship between TDC and tissue indentation force (TIF) in patients with LELE and assess the utility of the leg/arm TDC ratio (LAR) as an indicator of LELE. Methods and Results: Thirty females (49-91 years) with previously diagnosed LELE were evaluated during a scheduled session. TDC and TIF were measured 8 cm proximal to the medial malleolus on the medial and lateral aspects of both legs and on one forearm 8 cm distal to the antecubital fossa. The TDC-TIC relationship and the LAR were subsequently determined. Main results showed an absence of a significant correlation between TDC and TIF on medial or lateral leg sites but a positive correlation on the normal forearm site. Further, LAR values exceeded the published proposed threshold of 1.35 for 29/30 patients when using medial-side TDC values and 28/30 patients when using lateral-side TDC values. Conclusions: Findings suggest that for patients with LELE, TDC values are significantly elevated on medial and lateral standardized sites. The LAR determined using either medial or lateral sites that are similar to each other and have values consistent with a lymphedema threshold of 1.35. In edematous legs of the type evaluated herein, there is no apparent relationship between TDC values and indentation force.

Variation in Leg Tissue Dielectric Constant Values of Healthy Young Adult Females With and Without Compression Bandaging.

Background The clinical efficacy of acompression application has been often limited to the assessment of the change in limb volume, change in clinical symptoms (i.e., wound size, pain, range of motion, incidence of cellulitis), or vascular hemodynamics of the whole limb.Assessing compression-related biophysical changes of a localized area, such as around a wound, or in an area outside of an extremity cannot be objectively assessed by these measurements.Tissue dielectric constant (TDC) values, which provide a measure of the local tissue water (LTW) content, offer an alternative method to document variation in the LTW content of the skin in a specific location. The goals of the present research were (1) to characterize TDC values, expressed as percentage tissue water, from multiple areas along the medial aspect of the lower leg of healthy volunteers and (2) to explore the potential utilization of the TDC values to assess change in tissue water content in a localized area following compression applications. Methods TDC was measured at 10, 20, 30, and 40 cm proximal to the medial malleolus on the medial aspect of the right leg of 18 young adult healthy women with an age range of 18-23 years and a body mass index of 18.7 to 30.7kg/m2.. TDC was measured at baseline and after 10 minutes of exercise with compression in place on three separate days during which three different compression applications were assessed: a longitudinal elastic stockinette, a two-layer cohesive compression kit, and a combination of the two.Leg circumferences and compression-related interface pressures were also measured. Results Test-Retest Reliability of circumferential measurements and TDC values evaluated using Intraclass correlation coefficient (ICC 3,1) revealed excellent and moderate-to-good reliability, respectively.Analysis of TDC values along the length of the limb using Friedman's test, revealed a small but statistically significant overall difference among baseline TDC values attributable to a smaller value at 40 cm. The largest difference in cumulative average was 7.7% which occurred between 20 and 40 cm, with all other differences between locations less than 1%.No significant differences between the compression applications were observed. Conclusion The present findings demonstrate the utility of TDC measurements as a modality to assess compression-related changes in the legs of healthy women as a foundation for their potential use in assessing outcomes of compression treatments for persons with lower extremity edema or lymphedema. The absence of a significant change in TDC values in these healthy non-edematous conditions and the demonstrated reliability of the TDC measurements on three different days provides further support for the utility of such applications of TDC measurements. The extension to patients with lower extremity edema or lymphedema needs to be evaluated.

A Prospective Preliminary Study Examining the Physiological Impact of Pneumatic Compression Dosing in the Treatment of Lower Extremity Lymphedema.

Background: Optimal frequency and duration of pneumatic compression device (PCD) therapy for lymphedema is undetermined. This prospective, randomized preliminary study evaluated the impact of different PCD dosing protocols on physiological and patient-reported outcomes (PROs) to estimate treatment effects, assess the responsiveness of various measurement techniques, and identify endpoints for a definitive PCD dosing trial. Methods and Results: Twenty-one patients with lower extremity lymphedema were randomized into three groups for treatment with the Flexitouch advanced PCD: (A) once per day for 1 hour, 12 consecutive days; (B) twice per day in 1-hour treatments, 5 consecutive days; or (C) twice per day in 2-hour treatments, 5 consecutive days. Outcomes measured were changes in limb volume (LV), tissue fluid, tissue tone, and PROs. Those in group A experienced mean (standard deviation) LV reductions of 109 (58) mL (p = 0.003) on day 1 and of 97 (86) mL (p = 0.024) on day 5. Group A also showed possible single-treatment decreases in extracellular fluid volume by bioimpedance spectroscopy (BIS) on day 5. There were no consistent changes in groups B and C. Long-term assessment of LV and BIS showed no clear change. Tonometry, ultrasound, local tissue water, and PROs showed wide variation among participants. Conclusions: LV measurements showed potential benefit for 1-hour daily PCD treatment. A definitive dosing trial should include LV, BIS, and PROs in a comparison of 1- and 2-hour daily treatment protocols conducted over a study period of 4 weeks. These data may inform appropriate outcome measures for other intervention studies in lymphedema.

PROMs after Lymphatic Reconstructive Surgery: Is There a Correlation between Volume Reduction and Quality of Life?

We conducted a prospective single center study patients receiving lymphatic reconstructive surgery. Patients received volume measurements preoperatively and at standardized postoperative intervals. To evaluate patient-reported outcomes, patients completed the following questionnaires: LYMPH-Q Upper Extremity Module, quickDASH, SF 36, Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema, and Lower Extremity Functional Scale at the aforementioned intervals. We included 55 patients with upper limb lymphedema (24%) and lower limb lymphedema (73%) of lymphedema grades I-III. Patients received lymphovenous anastomosis only (23%), free vascularized lymph node transfer (35%) or a combination of both (42%). Analysis of patient-reported outcome measurements revealed improvements with respect to a broad range of complaints, particularly physical function, symptoms, and psychological well-being. There was no correlation between the extent of volume reduction and improvement in quality of life (Pearson correlation coefficient below ±0.7; P > 0.05). Based on a broad range of outcome measurements, we observed an improved quality of life in almost all patients, even in those without measurable volume loss of the extremity operated on, which emphasizes the need for a standardized use of patient-reported outcome measures to evaluate the benefits of lymphatic reconstructive surgery.

MO-0215 Incidence and predictors of lower extremity lymphedema after post-prostatectomy radiotherapy

MO-0215 Incidence and predictors of lower extremity lymphedema after post-prostatectomy radiotherapy

D25. Alternative Patterns of Superficial Lymphatic Drainage in the Breast and Trunk after Breast Cancer Surgery

PURPOSE: Changes in superficial lymphatic drainage from the chest wall/trunk after breast cancer treatment are not well described. This study examines alternative lymphatic flow in the post-mastectomy lymphedema population to identify risks associated with truncal and upper extremity lymphedema. METHODS: Patients undergoing revision breast surgery with suspicion of lymphedema from 2014-2020 were offered lymphangiography. Breasts and trunks were visualized and blindly evaluated for alternative drainage. Summary statistics were computed, and linear Cohen’s Kappa statistic was used to compare rater agreement. Binomial regression was used to compute relative risks (RR). RESULTS: 86 sides (46 patients) were included. 12 sides underwent no treatment and were considered controls. 88% of the non-controls had alternative lymphatic flow. This was seen in ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen’s Kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage reduced risk of truncal lymphedema (RR 0.78, CI 0.63-0.97, p=0.04; RR 0.32, CI 0.13-0.79, p=0.01, respectively). Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, p=0.02; RR 1.92, CI 1.09-3.39, p=0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, p=0.01; RR 2.83, CI 1.23-6.52, p=0.01, respectively). CONCLUSION: This study highlights several risk/protective factors for truncal and upper extremity lymphedema. Ipsilateral axillary and contralateral inguinal drainage are protective against truncal lymphedema. Patients with radiation, axillary lymph node dissection and contralateral axillary drainage are at highest risk of upper extremity lymphedema.

D138. A 28-year Single Institutional Experience of Complete Reduction of Extremity Lymphedema Using Suction Assisted Lipectomy

D138. A 28-year Single Institutional Experience of Complete Reduction of Extremity Lymphedema Using Suction Assisted Lipectomy

D84. Pre-operative Lymphedema Risk Factors in Patients with Inflammatory Breast Cancer: Optimizing Patient Selection for LYMPHA

PURPOSE: LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) is increasingly offered for prevention of upper extremity lymphedema after breast cancer treatment, which develops in up to 47% of breast cancer patients. Prior studies have focused on intraoperative and postoperative lymphedema risk factors. This study aimed to identify preoperative risk factors, when the decision to perform LYMPHA must be made. METHODS: Retrospective review of a dedicated inflammatory breast cancer (IBC) program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on final pathology, and need for adjuvant chemotherapy. RESULTS: Of 356 patients with IBC, 134 (mean age 51 years, range 22-89 years) had complete data. Forty-seven percent developed lymphedema. Obesity (BMI>30) (OR 2.7, CI 1.2-6.4, p=0.02) and non-white race (OR 4.5, CI 1.2-23, p=0.04) were preoperative risk factors for lymphedema development. CONCLUSION: Patients with IBC are at high risk for developing lymphedema, due to their need for ALND, radiation, and neoadjuvant chemotherapy. This study identified non-white race and obesity as additional risk factors. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with inflammatory breast cancer. Larger prospective studies should evaluate potential racial disparities in lymphedema development.

Reliability and validity testing of the Korean translation of lymphedema quality of life questionnaire (LYMQOL) for lower limb lymphedema

Purpose This study aimed to translate the Lymphedema Quality of Life Questionnaire-leg into Korean (K-LYMQOL-leg) and test its reliability and validity. Materials and methods The LYMQOL-leg was translated forward and backward from English to Korean. Fifty-five patients with lower limb lymphedema completed the K-LYMQOL-leg and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at the first visit, and the K-LYMQOL-leg was re-administered within a week. Reliability was tested by calculating the intraclass correlation coefficient (ICC) and the Cronbach’s alpha for each domain. Face validity was evaluated, and concurrent validity was verified by comparing the K-LYMQOL-leg domain scores with the corresponding EORTC-QLQ-C30 and limb volume scales. The known-group construct validity was then assessed. Results Excellent reliability was confirmed by internal consistency (Cronbach’s alpha coefficient, 0.851–0.878) and test-retest reliability (ICC, 0.901–0.936) in the four domains. A significant correlation was confirmed in the appearance domain with limb volume (r = 0.424) and in the other domains [function, symptom, and mood], with the EORTC-QLQ-C30 scales (r = −0.779, 0.712, and −0.783). Known-group validity was confirmed in all four domains. Conclusions The K-LYMQOL-leg verified in this study can be used in clinical practice to evaluate the Quality of Life (QOL) of patients with lymphedema or in research as an outcome. IMPLICATIONS FOR REHABILITATION Among cancer treatment-related complications, lymphedema of the lower extremities severely and persistently reduces the health-related quality of life of cancer survivors. The Korean version of the Lymphedema Quality of Life Questionnaire-leg (K-LYMQOL-leg) is an easy, reliable and valid questionnaire for patients with lower limb lymphedema. K-LYMQOL-leg will be useful in assessing the quality of life of patients with lower limb lymphedema in a clinical setting or for research purposes.

Ensuring patient centeredness in upper extremity lymphedema research: Identifying patient-prioritized agenda and preferences

To elicit a patient-prioritized agenda and preferences for upper extremity lymphedema (LE) research. Focus group sessions (FGs) were conducted with English-speaking, adult women (18 years and older) with breast cancer-related LE (BCRL) seeking conservative or surgical care at two tertiary cancer centers in Ontario, Canada. An interview guide was used; women were asked to describe health-related quality of life (HRQL) outcomes that mattered the most to them, followed by their preferences for research study design and for providing patient-reported outcomes measure (PROM) data. Inductive content analysis was used to identify themes and subthemes. A total of 16 women participated in 4 FG sessions (55±9.5 years) and described the impact of LE on their appearance, physical, psychosocial, and sexual well-being. Women emphasized that psychosocial well-being was often not discussed in clinical care and that they were poorly informed of LE risk and care options. Most women said that they would not be willing to be randomized to surgical versus conservative management of LE. They also expressed a preference to complete PROM data electronically. All women emphasized the value of having an open text option alongside PROMs to expand on their concerns. Patient centeredness is key to generating meaningful data and ensuring ongoing engagement in clinical research. In LE, comprehensive PROMs that measure a range of HRQL concerns, especially psychosocial well-being, should be considered. Women with BCRL are reluctant to be randomized to conservative care when a surgical option is available, resulting in implications for planning trial sample size and recruitment.

Re-examining content validity of the BREAST-Q more than a decade later to determine relevance and comprehensiveness

PurposeThe BREAST-Q is the most used patient-reported outcome measure (PROM) in breast cancer surgery. The purposes of this study were to re-examine the content validity of BREAST-Q cancer modules (mastectomy, lumpectomy and reconstruction) and to determine the need for new scales.MethodsInterviews were conducted with women with breast cancer (Stage 0–4, any treatment), and were audio-recorded and transcribed verbatim. Deductive (based on original BREAST-Q conceptual framework) and inductive (new codes from the data) content analysis approaches were used to analyze the data. The number of codes that mapped to BREAST-Q were recorded.ResultsDataset included 3948 codes from 58 participants. Most of the breast (n = 659, 96%) and all psychosocial (n = 127, 100%), sexual (n = 179, 100%) and radiation-related (n = 79, 100%) codes mapped to BREAST-Q Satisfaction with Breast, Psychosocial Wellbeing, Sexual Wellbeing and Adverse Effects of Radiation scales, respectively. For the physical wellbeing codes (n = 939) for breast/chest and arm, 34% (n = 321) mapped to the Physical Wellbeing-Chest scale. Most of the abdomen codes (n = 311) mapped to Satisfaction with Abdomen (n = 90, 76%) and Physical Wellbeing-Abdomen (n = 171, 89%) scales. Codes that did not map (n = 697, 30%) covered breast sensation and lymphedema. Concerns related to fatigue, cancer worry, and work impact were most reported and did not map to BREAST-Q.ConclusionThe BREAST-Q, which was developed using extensive patient input more than a decade ago, is still relevant. To ensure the BREAST-Q remains comprehensive, new scales for upper extremity lymphedema, breast sensation, fatigue, cancer worry, and work impact were developed.

Stewart-Treves syndrome: a case report of lymphedema-related angiosarcoma

Stewart-Treves syndrome (STS) is an angiosarcoma associated with lymphedema deriving more often from radical mastectomy and longstanding lymphedema, first described in 1948. Irradiation is also commonly associated with chronic lymphedema of extremities. It generally occurs about 10 years after the mastectomy and/or radiotherapy. The prognosis is very poor with a mean survival of 20 months from the diagnosis especially when radical surgery is not possible. We present the case of STS in an 89-year-old female who underwent left upper outer quadrantectomy for invasive ductal carcinoma in 2009 followed by axillary lymphadenectomy, radiotherapy, and hormonal therapy until 2014. She presented swollen upper left limb associated with hemorrhagic red papular lesions. Skin biopsy revealed the presence of lymphedema-associated angiosarcoma. Radical surgery was not possible, so she underwent conservative therapy with pazopanib, a tyrosine kinase inhibitor, with benefit. Long-term follow-up of these patients is crucial to intercept this condition at an early stage.

The impact of cancer-related lower extremity lymphedema on patient quality of life: a qualitative meta-synthesis

Abstract Lower extremity lymphedema (LEL) is a common and potentially debilitating chronic condition associated with cancer treatment. Research has outlined the substantial psychosocial and quality-of-life (QOL) sequelae associated with lymphedema, primarily of the upper extremities and through the use of quantitative methods. The purpose of this systematic review was to summarize, synthesize, and appraise qualitative literature exploring the impact of LEL on patients' QOL and psychosocial well-being after cancer treatment. Nine databases were searched for qualitative research articles published before May 1, 2022. Six eligible articles were included. Four studies used individual semistructured interviews, one used open-ended survey questions, and one used structured interviews. There was a total of 248 participants (average age: 59.8 years) included in the reviewed articles, ranging from 13 to 178 participants. Most participants were women and had a history of gynecologic cancer. All studies described psychosocial challenges experienced by individuals with cancer-related LEL. Four key themes were identified: (1) physical burden and functional limitations, (2) psychologic and emotional impacts, (3) financial implications, and (4) relational and social sequelae. Despite available qualitative data suggesting that cancer-related LEL has negative consequences on patients' QOL, there is still a significant need for increased research to broaden our understanding of the cancer-related LEL experience to better inform policy and practical guideline development.

Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum

Lymphatic Research and BiologyVol. 21, No. 2 EditorialFree AccessBreast Cancer-Related Lymphedema: The Primary/Secondary ConundrumStanley G. RocksonStanley G. RocksonEditor-in-Chief, Stanford University School of Medicine, Stanford, California, USA.Search for more papers by this authorPublished Online:20 Apr 2023https://doi.org/10.1089/lrb.2023.29141.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail For quite some time, within the pages of this journal1–3 and elsewhere,4,5 there has been a persistent theory that there might be systemic and other predispositions to the secondary (or acquired) lymphedema that is encountered frequently as a sequela of breast cancer therapeutics. In addition, it has recently been observed that the presence of a lymphatic disorder such as breast cancer-associated lymphedema can alter the patterns of associated systemic disease expression that exist as comorbidities.6 These phenomena help to blur the distinction between “primary” and “secondary” lymphedema.In the current issue of Lymphatic Research and Biology, we provide three additional sets of original observations that help to expand insights into this hypothesis.In the first of these, Kim and colleagues have explored rates of incidental subclinical lymphedema in the contralateral arm of patients with unilateral postsurgical secondary upper extremity lymphedema. In their study, magnetic resonance imaging of the upper extremities was utilized to examine patients with unilateral upper extremity clinical lymphedema. Axial STIR MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded by the investigators. In these 78 examined subjects, contralateral abnormalities were detected in 14.1%. Although the direct conclusion was to emphasize the importance of evaluation of the contralateral limb, the interpretation, by extension, is that there is a disturbance in lymphatic anatomy or function that extends beyond the direct lymphatic trauma of cancer therapeutics.The second investigation, by Furlan and colleagues, examines the phenomenon of blood flow abnormalities in the limb that precede the development of overt lymphedema. In a cohort of 200 subjects, Doppler ultrasound was utilized to examine the axillary and brachial arteries. In these patients, there was detection of higher mean flow velocity and end-diastolic velocity as early as 1 month after surgery. The end-diastolic velocity demonstrated a 73.7% sensitivity and 71.2% specificity as a predictor of long-term lymphedema, with a negative predictive value of 57.6%.The third of these three new investigations proposed a pilot investigation of abdominal fat ratio in subjects with breast cancer-related lymphedema. Here, Nakipoğlu and colleagues investigated the impact of central obesity to the occurrence of this lymphedema presentation. They investigated cohorts of postsurgical subjects with a matched control cohort that differed only in the distribution of BMI. The abdominal circumference measurement demonstrated a modest predictive utility, with a predictive specificity of 89%.In aggregate, these three newly published investigations continue to tantalize us with the increasingly tenable hypothesis that the appearance of acquired lymphedema (in this case following breast cancer therapies) may, and likely does, depend upon systemic factors that predict the likelihood of disease evolution. Continued exploration of these phenomena will, ideally, result in enhanced risk factor stratification, diagnostic evaluation, and, with good fortune, improved risk factor reduction strategies.

P252 Comparison of the Effectiveness of Complex Decongestive Therapy Components in the Treatment of Upper Extremity Lymphedema Associated with Breast Cancer

P252 Comparison of the Effectiveness of Complex Decongestive Therapy Components in the Treatment of Upper Extremity Lymphedema Associated with Breast Cancer

Unilateral lower extremity lymphedema as a first symptom of primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)

Unilateral lower extremity lymphedema as a first symptom of primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)

The Prevalence of the Axillo-Inguinal Lymphatic Pathway in Lymphedema of the Extremities and Potential Therapeutic Implications.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.

Lymphatic complex transfer as combined lymph vessel and node transfer for advanced stage upper extremity lymphedema

ObjectiveLymphedema, especially in the advanced stage, is a growing challenge in extremity reconstruction, with few applicable surgical methods. Despite its importance, no consensus has been reached regarding a single surgical method yet. Herein, the authors introduce a novel concept of lymphatic reconstruction yielding promising results. MethodsWe included 37 patients with advanced-stage upper extremity lymphedema who underwent lymphatic complex transfers, consisting of both lymph vessel and node transfers, from 2015 to 2020. We compared the preoperative and postoperative (last visit) mean circumferences and volume ratios between the affected and unaffected limbs. Changes in the Lymphedema Life Impact Scale scores and complications were also investigated. ResultsThe circumference ratio (affected to unaffected limbs) improved at all measuring points (P < .05), while the volume ratio showed a decrease from 1.54 to 1.39 (P < .001). The mean Lymphedema Life Impact Scale decreased from 48.1 ± 15.2 to 33.4 ± 13.8 (P < .05). No donor site morbidities, including iatrogenic lymphedema or any other major complications, were observed. ConclusionsA new technique for lymphatic reconstruction, lymphatic complex transfer, may be useful in cases of advanced stage lymphedema because of its effectiveness and the low possibility of donor site lymphedema.

Extracellular vesicles from adipose-derived stem cells relieve extremity lymphedema in mouse models.

Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has been reported to improve the severity of chronic lymphedema. Extracellular vesicles (EVs) derived from mesenchymal stem cells have been reported to exert effects such as the promotion of angiogenesis, suppression of inflammation, and regeneration of damaged organs. In this study, we showed that lymphangiogenesis was induced by EVs derived from ADSCs and revealed the therapeutic potential of these EVs for the treatment of lymphedema. We examined in vitro effects of ADSC-EVs to lymphatic endothelial cells (LECs). Next, we conducted in vivo analysis of ADSC-EVs to mouse lymphedema models. Furthermore, Bioinformatics analysis was also performed to evaluate the implications of the altered miRNA expression. We showed that ADSC-EVs promoted the proliferation, migration, and tube formation of LECs, and the gene expression of lymphatic markers was elevated in the ADSC-EV-treated group. Notably, a mouse lymphedema model revealed that legs treated with ADSC-EVs had markedly improved edema with increased numbers of capillary vessels and lymphatic channels. Bioinformatics analysis revealed that ADSC-EV-associated microRNAs, such as miR-199a-3p, miR-145-5p, miR-143-3p, miR-377-3p, miR-100-3p, miR-29a-3p, miR-495-3p, and miR-29c-3p, targeted MDM2, which contributed to the stability of HIF1 and resulted in angiogenesis and lymphangiogenesis in LECs. The present study showed lymphangiogenic effects of ADSC-EVs, which will lead to new treatment options for chronic lymphedema. Cell-free therapy with EVs has fewer potential risks, such as poor engraftment efficiency and potential tumor formation, than stem cell transplantation and could be a promising tool for patients suffering from lymphedema.