Comparison of fluid and body composition measures in women with lipoedema, lymphoedema, and control participants.

Lipoedema is the disproportionate accumulation of adipose tissue in the lower body, often associated with hormonal changes in women. Lipoedema is commonly misdiagnosed as lymphoedema or obesity due to similarities in appearance. The aim of this study is to compare body composition and fluid measures of women with lipoedema, lymphoedema, and matched control participants, to determine differences that may help distinguish between each condition. One hundred and eleven participants aged over 18, who presented with the complaint of leg swelling and underwent indocyanine green lymphography were included in this study. Our analysis showed that the individuals with lymphoedema had a significantly higher overall total body water (lymphoedema: 9.6 ± 4.2 L, lipoedema: 7.4 ± 2.3 L, control: 7.5 ± 1.8 L; p < .001) and extracellular fluid (lymphoedema: 4.6 ± 1.6, lipoedema: 3.4 ± 1.0 L, control: 3.5 ± 0.7 L; p < .001) in the legs when compared to individuals with lipoedema and matched control participants. Individuals with lipoedema had a significantly higher overall fat mass as a percentage of body weight when compared to individuals with lymphoedema (lymphoedema: 33.1% ± 9.5%, lipoedema: 39.4% ± 6.5%; p = .003). We are unable to distinguish between individuals with lipoedema and control participants, therefore further research needs to be conducted to help reduce misdiagnosis.

Liposuction for Advanced Lymphedema in a Multidisciplinary Team Setting in Australia: 5-Year Follow-Up.

BACKGROUND: Liposuction for International Society of Lymphology late stage 2 or 3 limb lymphedema is an established surgical option to remove excessive adipose tissue deposition and has been performed in Australia since 2012 at the Australian Lymphoedema Education, Research, and Treatment (ALERT) Program of Macquarie University. METHODS: Between May of 2012 and May of 2017, 72 patients with unilateral primary or secondary lymphedema of the arm or leg underwent suction-assisted lipectomy using the Brorson protocol. This prospective study presents 59 of these patients who had consented to research with a 5-year follow-up. RESULTS: Of the 59 patients, 54 (92%) were women, 30 (51%) had leg lymphedema, and 29 (49%) had arm lymphedema. For patients with arm lymphedema, the median preoperative volume difference between the lymphedematous and the contralateral arm was 1061 mL, which was reduced to 79 mL 1 year after surgery and to 22 mL 5 years after surgery. For patients with leg lymphedema, the median preoperative volume difference was 3447 mL, which was reduced to 263 mL 1 year after surgery but increased to 669 mL 5 years after surgery. CONCLUSION: Suction-assisted lipectomy is a long-term option for the management of selected patients with International Society of Lymphology late stage 2 or 3 limb lymphedema when conservative management can offer no further improvement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Breast lymphedema following breast-conserving treatment for breast cancer: current status and future directions.

PURPOSE: To examine the current evidence on breast lymphedema (BL) diagnosis and treatment after breast-conserving surgery, identify gaps in the literature, and propose future research directions. METHODS: A comprehensive literature review was conducted using Ovid, PubMed, and Cochrane, including studies published between 2000 and 2023. References were reviewed manually for eligible studies. Inclusion criteria were as follows: patients who underwent breast conserving treatment (surgery ± radiation) for breast cancer, goals of the paper included analyzing or reviewing BL measurement with ultrasound or tissue dielectric constant, or BL treatment. Twenty-seven manuscripts were included in the review. RESULTS: There is variation in incidence, time course, and risk factors for BL. Risk factors for BL included breast size, primary and axillary surgery extent, radiation, and chemotherapy but require further investigation. Diagnostic methods for BL currently rely on patient report and lack standardized criteria. Tissue dielectric constant (TDC) and ultrasound (US) emerged as promising ambulatory BL assessment tools; however, diagnostic thresholds and validation studies with ICG lymphography are needed to establish clinical utility. The evidence base for treatment of BL is weak, lacking high-quality studies. CONCLUSION: The natural history of BL is not well defined. TDC and US show promise as ambulatory assessment tools for BL; however, further validation with lymphatic imaging is required. BL treatment is not established in the literature. Longitudinal, prospective studies including pre-radiation measurements and validating with lymphatic imaging are required. These data will inform screening, diagnostic criteria, and evidence-based treatment parameters for patients with BL after breast-conserving surgery and radiation.

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.

Differentiation of lipoedema from bilateral lower limb lymphoedema by imaging assessment of indocyanine green lymphography.

Lipoedema is characterized by disproportionate painful fat accumulation mostly in the lower limbs. The presence of lymphoedema in lipoedema remains controversial. This study aimed to assess the presence or absence of lymphoedema in the lower limbs of women with lipoedema using indocyanine green (ICG) lymphography. A cross-sectional retrospective study was undertaken in women with a clinical diagnosis of lipoedema whose lower limbs were examined with ICG lymphography. MD Anderson Cancer Center (MDACC) ICG staging was used to determine lymphoedema presence and severity. Patient characteristics, ICG lymphography findings, Stemmer sign, body mass index, waist-to-hip ratio, limb volume and bioimpedance spectroscopy measures were recorded. Forty women with lipoedema underwent ICG lymphography for the lower limbs from January 2018 to July 2022. Thirty-four women (85.0%) were determined by ICG lymphography as MDACC ICG Stage 0 representing normal lymphatics. Of the six women who demonstrated dermal backflow on ICG lymphography, all were determined as ICG Stage 1, four had localized traumatic dermal backflow area at their ankles, one had previously diagnosed with primary lymphoedema and one was classified as lipoedema stage 4. ICG lymphography findings suggested the absence of lymphoedema in a clear majority of women with lower limb lipoedema.

A new indocyanine green fluorescence lymphography protocol for diagnostic assessment of lower limb lymphoedema.

INTRODUCTION: The lower limbs are a common body site affected by chronic edema. Imaging examination of the lymphatic system is useful to diagnose lymphoedema, identify structural changes in individuals, and guide interventional strategies. In this study, we used a protocol combining indocyanine green (ICG) lymphography and ICG-guided manual lymphatic drainage (MLD) for the diagnostic assessment of lower limb lymphoedema. MATERIALS AND METHODS: Patients with lower limb lymphoedema were divided into three groups by their medical history: primary, secondary cancer-related, or secondary non-cancer-related. ICG lymphography was conducted in three phases: initial observation, MLD to accelerate ICG dye transit and reduce imaging time, and imaging data collection. Lymphatic drainage regions were recorded, and the MD Anderson Cancer Center ICG staging was applied. We collected routine lymphoedema assessment data, including limb volume and bioimpedance spectroscopy measurements. RESULTS: Three hundred and twenty-six lower limbs that underwent ICG lymphography were analyzed. Eight drainage regions were identified. The ipsilateral inguinal and popliteal were recognized as the original regions, and the remaining six regions were considered compensatory regions that occur only in lymphoedema. More than half of the secondary cancer-related lower limb lymphoedema (57.6%) continued to drain to the ipsilateral inguinal region. The incidence of drainage to the ipsilateral inguinal region was even higher for the primary (82.8%) and secondary non-cancer-related (87.1%) groups. Significant associations were observed between cancer-related lymphoedema and the presence of compensatory drainage regions. CONCLUSIONS: We proposed a prospective ICG lymphography protocol for the diagnostic assessment of lower limb lymphoedema in combination with MLD. Eight drainage regions were identified, including two original and six compensatory regions.

Retrograde lymph flow in the lymphatic vessels in limb lymphedema.

OBJECTIVE: Retrograde movement of lymph owing to damaged and/or incompetent valves in the lymphatic vessels has been considered a pathological feature of lymphedema. This study aimed to determine the prevalence of retrograde lymph flow and the characteristics of patients with this condition using indocyanine green (ICG) lymphography. METHODS: An audit of 679 patients with upper or lower limb swelling who underwent ICG lymphography was undertaken over a 4-year period. Harvey's technique was applied to identify retrograde flow in the lymph collecting vessel during ICG lymphography. The characteristics of patients with retrograde lymph flow were recorded. RESULTS: Twenty-one patients (3.7%; lower limb, n = 19; upper limb, n = 2) were identified as having retrograde flow in lymph collecting vessels out of 566 confirmed lymphedema patients (lower limb, n = 275; upper limb, n = 291). Of the two patients with upper limb lymphedema (ULLE), one had a short segment of retrograde lymph flow in the forearm. The other patient with ULLE and one patient with lower limb lymphedema (LLLE) were previously diagnosed with lymphedema-distichiasis syndrome. Of the remaining 18 patients with LLLE and retrograde lymph flow, nine had initiating insect bites with lymphangitis and three had palpable benign enlarged inguinal lymph nodes evident before lower limb swelling onset. None had cancer-related LLLE. CONCLUSIONS: Retrograde lymph flow with valve incompetence in the lymph-collecting vessels was a rare finding in ULLE and a relatively uncommon finding in LLLE, contradicting the conventional understanding of pathological changes in lymphedema. ICG lymphography identified anticipated retrograde lymph flow in two patients with lymphedema distichiasis. In the remaining patients, retrograde lymph flow may have resulted from toxic or asymptomatic lymphangitis but there was no association with secondary cancer-related lymphedema. These findings have implication for conservative management as well as lymphovenous anastomosis surgery where both ends of a transected lymph collecting vessel would be potential targets for anastomoses.

Usability evaluation of a novel compact pneumatic compression device for the treatment of lymphoedema: Pilot study.

OBJECTIVE: To perform a preliminary usability evaluation of a novel, compact pneumatic compression device in patients with lymphoedema. METHODS: This open-label, single-arm trial had two phases: the first focused on the fitting of the pneumatic compression device (Aria FreeTM, Aria Health, San Diego CA, USA) and the second focused on evaluating the comfort of the entire system during a 45-min usage period. Both phases were conducted in a monitored clinical environment. Patients aged ≥18 years with a diagnosis of lower limb lymphoedema who had used a pneumatic compression device for ≥3 months were eligible. Patients rated subjective fit, comfort and usability on an 11-point Likert scale (where higher scores indicate better fit/comfort/usability). The truncated cone method was used to infer limb volume before and after therapy in phase 2. RESULTS: Twenty-four patients were screened, and 15 were enrolled (80% female; mean age 62 years); all completed both study phases. Patients rated the garment as easy to set up and fit (median score 6.5), and all reported that the therapy was comfortable (median score 10; p < 0.001 vs. reference score of 6). There was a 1.85% reduction in limb volume after device use for 45 min (p = 0.018 vs. before therapy). No safety issues were identified. CONCLUSIONS: The new pneumatic compression device fitted well, was easy to use and reduced leg oedema.

Personalizing Conservative Lymphedema Management Using Indocyanine Green-Guided Manual Lymphatic Drainage.

Background: The Australian Lymphoedema Education, Research and Treatment Program (ALERT) at Macquarie University in Sydney, Australia is one of the flagship programs of Australia's first fully integrated academic health sciences centre, MQ Health. The aim of this study was to describe our findings of compensatory drainage demonstrated by indocyanine green (ICG) lymphography in cancer-related upper and lower limb lymphedema and how this may be translated into clinical practice. Methods and Results: Retrospective data from 339 patients aged between 18 and 90 years with secondary cancer-related unilateral or bilateral lymphedema of the upper or lower limb who underwent ICG lymphography assessment at the ALERT clinic between February 2017 and March 2020 were analyzed. In patients with upper limb lymphedema, the ipsilateral axilla was the most frequent drainage region (74.9%), followed by clavicular (41.8%) and parasternal (11.3%). For patients with mild upper limb lymphedema, 94.4% drained to the ipsilateral axilla. No patients drained to the ipsilateral inguinal region. For lower limb lymphedema, drainage to the ipsilateral inguinal was most common (52.3%), followed by contralateral inguinal (30.7%), popliteal (26.1%), and gluteal (21.6%) regions. Three main patterns of superficial lymphatic compensation were identified based on which anatomical structure carried lymph fluid. Manual lymphatic drainage (MLD) was used to facilitate movement of the dye. A light/effleurage technique was sufficient to move the dye through patent lymphatic vessels; a slow and firmer technique was required to move the dye through areas of bridging dermal backflow. Conclusion: The introduction of ICG lymphography to our program and its use in guiding personalized conservative management plans, including facilitative MLD techniques, has translated into clinical practice and changed research and educational priorities within the ALERT program.

Vascularized Lymph Node Transfer for Patients with Breast Cancer-Related Lymphedema Can Potentially Reduce the Burden of Ongoing Conservative Management.

Background: Vascularized lymph node transfer (VLNT) microsurgery is conducted in selected specialist lymphatic programs as a surgical treatment option for breast cancer-related lymphedema (BCRL) with variation in treatment outcomes. Methods and Results: Ten patients with BCRL underwent VLNT from 2012 to 2015. Donor sites were the inguinal (n = 6) or supraclavicular fossa/neck (n = 4) regions and recipient sites were the axilla (n = 6) or elbow regions (n = 4). Outcomes included changes in limb volume and extracellular fluid ratios, postoperative garment use, number of cellulitis episodes, and self-reported symptom improvement. At a mean follow-up of 46 months from surgery (range: 28-66 months), the excess volume in the affected arm had reduced (n = 4) or remained stable (n = 1) for 5 of 10 patients (50%) (mean change: -106.4 mL, range: -515.5 to +69.6 mL). Four of these five patients had also reduced (n = 3) or discontinued (n = 1) wearing compression garments and three reported a reduction in episodes of cellulitis. The remaining five patients had an increase of over 100 mL in postoperative excess volume (mean change: 295.8 mL, range: 142.1-382.8 mL). Three of these five patients reported noncompliance with compression garments. Despite the increase in limb volume, some patients reported softness in swelling (n = 3) and better response to conservative treatment (n = 1). Conclusion: Our results warrant continuation of VLNT as a surgical treatment option for patients with BCRL and show that the burden of conservative management such as wearing garments can be reduced over time for some patients. Longer term follow-up with standardized measures across all centers is required to further investigate VLNT.

A new indocyanine green fluorescence lymphography protocol for identification of the lymphatic drainage pathway for patients with breast cancer-related lymphoedema.

BACKGROUND: Breast cancer related lymphoedema (BCRL) is a common side effect of cancer treatment. Recently indocyanine green (ICG) fluorescent lymphography has become a popular method for imaging the lymphatics, however there are no standard protocols nor imaging criteria. We have developed a prospective protocol to aid in the diagnosis and therapeutic management of BCRL. METHODS: Lymphatic imaging procedures were conducted in three phases. Following initial observation of spontaneous movement of ICG in phase one, manual lymphatic drainage (MLD) massage was applied to facilitate ICG transit via the lymphatics in phase two. All imaging data was collected in phase three. Continuous lymphatic imaging of the upper limb was conducted for approximately an hour and lymphatic drainage pathways were determined. Correlations between the drainage pathway and MD Anderson Cancer Centre (MDACC) ICG lymphoedema stage were investigated. RESULTS: One hundred and three upper limbs with BCRL were assessed with this new protocol. Despite most of the patients having undergone axillary node dissection, the ipsilateral axilla drainage pathway was the most common (67% of upper limbs). We found drainage to the ipsilateral axilla decreased as MDACC stage increased. Our results suggest that the axillary pathway remained patent for over two-thirds of patients, rather than completely obstructed as conventionally thought to be the case for BCRL. CONCLUSIONS: We developed a new ICG lymphography protocol for diagnosing BCRL focusing on identification of an individual patient's lymphatic drainage pathway after lymph node surgery. The new ICG lymphography protocol will allow a personalised approach to manual lymphatic drainage massage and potentially surgery.

Work experiences of Australian cancer survivors with lymphoedema: A qualitative study.

Our qualitative study addresses a significant gap in the scholarship on return-to-work after cancer by examining the impact of secondary lymphoedema on individuals in paid employment. We undertook an Interpretive Phenomenological Analysis of interviews with 14 cancer survivors (13 women) with secondary lymphoedema in Sydney, Australia. Our interviewees were engaged in paid employment during and after their lymphoedema diagnosis. In addition to difficulties with tasks involving manual or repetitive labour, interviewees highlighted the importance of work for maintaining their identity. They also outlined the critical role that significant others at work, such as supervisors and colleagues, play in maintaining that identity. At the same time, their need for privacy and control over to whom they disclosed their lymphoedema diagnosis emerged strongly from our interviews. Finally, we present the coping mechanisms that our interviewees utilised to manage their lymphoedema in the workplace, including covering the affected limb with long sleeves, changing the tasks they completed, or even changing employers. In addition to our contribution to the scholarship, we highlight implications for employers, future research, and policy makers.

Patterns of lymphatic drainage after axillary node dissection impact arm lymphoedema severity: A review of animal and clinical imaging studies.

Upper extremity lymphoedema after axillary node dissection is an iatrogenic disease particularly associated with treatment for breast or skin cancer. Anatomical studies and lymphangiography in healthy subjects identified that axillary node dissection removes a segment of the lymphatic drainage pathway running from the upper limb to the sub-clavicular vein, creating a surgical break. It is reasonable to infer that different patterns of lymphatic drainage may occur in the upper limb following surgery and contribute to the various presentations of lymphoedema from none to severe. Firstly, we reviewed animal imaging studies that investigated the repair of lymphatic drainage pathways from the limb after lymph node dissection. Secondly, we examined clinical imaging studies of lymphatic drainage pathways after axillary node dissection, including lymphangiography, lymphoscintigraphy and indocyanine green fluorescence lymphography. Finally, based on the gathered data, we devised a set of general principles for the restoration of lymphatic pathways after surgery. Lymphoscintigraphy shows that restoration of the original lymphatic pathway to the axilla after its initial disruption by nodal dissection was not uncommon and may prevent lymphoedema. We found that regenerated lymphatic vessels and dermal backflow (the reflux of lymph to the skin) contributed to either restoration of the original pathway or rerouting of the lymphatic pathway to other regional nodes. Variation in the lymphatic drainage pathway and the mechanisms of fluid drainage itself are the foundation of new lymphatic drainage patterns considered to be significant in determining the severity with which lymphoedema develops.

Reducing Body Image-Related Distress in Women With Breast Cancer Using a Structured Online Writing Exercise: Results From the My Changed Body Randomized Controlled Trial.

Purpose Breast cancer treatment adverse effects result in one in three survivors experiencing body image-related distress (BID) that negatively impacts on a woman's ability to recover after cancer and into survivorship. My Changed Body (MyCB) is a Web-based psychological intervention to alleviate BID and improve body appreciation in survivors of breast cancer (BCSs) through a single-session, self-compassion focused writing activity. This randomized controlled trial evaluated the impact of MyCB on BID and body appreciation in BCSs. The moderating effect of lymphedema status (affected or unaffected) and appearance investment (self-importance placed on personal appearance) and the mediating effect of self-compassion were evaluated. Patients and Methods Women (disease-free stage I to III BCSs who had experienced at least one negative event related to bodily changes after breast cancer) were randomly assigned to MyCB (n = 149) or an expressive writing control arm (n = 155). Primary outcomes were reduction in BID and improvement in body appreciation 1 week after intervention. Secondary outcomes included psychological distress (depression and anxiety) and self-compassion. Follow-up assessments occurred 1 week, 1 month, and 3 months after writing. Results Compliance with the MyCB intervention was 88%, and attrition was 9.2%. Intent-to-treat linear mixed models indicated that participants who received MyCB reported significantly less BID ( P = .035) and greater body appreciation ( P = .004) and self-compassion ( P < .001) than expressive writing participants. Intervention effects on BID were moderated by lymphedema status ( P = .007) and appearance investment ( P = .042). Self-compassion mediated effects on both primary outcomes. Therapeutic effects were maintained at 1 month (BID and body appreciation) and 3 months (body appreciation) after intervention. Significant reductions in psychological distress (1-month depression, P = .001; 1-week and 1-month anxiety, P = .007) were evident for MyCB participants with lymphedema. Conclusion This study supports the efficacy of MyCB for reducing BID and enhancing body appreciation among BCSs.

Breast Cancer-Related Lymphedema: Differentiating Fat from Fluid Using Magnetic Resonance Imaging Segmentation.

BACKGROUND: Lymphedema is an iatrogenic complication after breast cancer treatment in which lymph fluid in the affected limb progresses to fat deposition and fibrosis that are amenable to liposuction treatment. Magnetic resonance imaging (MRI) for lymphedema can differentiate fat tissue from fluid, but estimating relative volumes remains problematic. METHODS AND RESULTS: Patients underwent routine bilateral arm MRI both before and after liposuction for advanced lymphedema. The threshold-based level set (TLS) segmentation method was applied to segment the geometric image data and to measure volumes of soft tissue (fat, muscle, and lymph fluid) and bone. Bioimpedance testing (L-Dex®) to detect extracellular fluid was also used. Volumes derived by using TLS or girth measurement were evaluated and showed consistent agreement, whereas L-Dex showed no significant reduction between pre- and postoperative measures. The percentage median volume difference between the affected and unaffected sides was 132.4% for girth measures compared with 137.2% for TLS (p = 0.175) preoperatively, and 99.8% and 98.5%, respectively (p = 0.600), postoperatively. MRI segmentation detected reductions in fat (median 52.6%, p = 0.0163) and lymph fluid (median 66%, p = 0.094), but the volumes of muscle and bone were relatively constant. CONCLUSIONS: MRI imaging with TLS technology may be a useful tool to quantitatively measure fat tissue and fluid for patients with advanced lymphedema and may assist in the selection of eligible liposuction candidates at initial assessment and follow-up of patients who proceed with surgery.

Financial cost of lymphedema borne by women with breast cancer.

OBJECTIVE: Our study examines the financial cost of lymphedema following a diagnosis of breast cancer and addresses a significant knowledge gap regarding the additional impact of lymphedema on breast cancer survivors. METHODS: An online national survey was conducted with 361 women who had either breast cancer without lymphedema (BC) (group 1, n = 209) or breast cancer with lymphedema (BC+LE) (group 2, n = 152). Participant recruitment was supported by the Breast Cancer Network Australia and the Australasian Lymphology Association. RESULTS: Both breast cancer and lymphedema result in significant out-of-pocket financial costs borne by women. Of patients with BC+LE, 80% indicated that their breast cancer diagnosis had affected them financially compared with 67% in the BC group (P < .020). For patients with lymphedema, over half (56%) indicated that this specific additional diagnosis to their breast cancer affected them financially and that costs increased with lymphedema severity. The cost of compression garments formed a large proportion of these costs (40.1%). The average number of attendances to a therapist each year was 5.8 (range, 0-45). Twenty-five patients (16.4%) had an episode of cellulitis in the past year. The incidence of cellulitis was 7.7% in 91 patients with subclinical or mild lymphedema compared with 29.5% of 61 patients with more extensive lymphedema (P < .001). The average out-of-pocket financial cost of lymphedema care borne by women was A$977 per annum, ranging from A$207 for subclinical lymphedema to over A$1400 for moderate or severe lymphedema. CONCLUSIONS: This study identifies an additional detrimental effect of lymphedema on women in terms of financial costs.