Reliability of L-Dex Scores for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer-related lymphedema (BCRL) is a common complication of breast cancer treatment that may result in swelling of the affected arm due to compromised lymphatic function. Implementing a screening program and early intervention for BCRL are important for effective management. Bioimpedance spectroscopy (BIS) is a commonly used tool for assessing BCRL. This study aimed to compare different normative ranges for BIS L-Dex scores in the detection of BCRL. Materials and Methods: Data from 158 women with clinically ascribed and indocyanine green confirmed BCRL were analysed. BIS measurements were obtained using an ImpediMed standing device, and L-Dex scores were calculated using published normative ranges for healthy individuals. Statistical analysis was performed to compare the concordance between different reference ranges in classifying individuals with lymphedema. Results: The study found that L-Dex scores calculated using different normative ranges were highly correlated and essentially interchangeable in detecting BCRL. Approximately 90% of participants exceeded the L-Dex threshold for lymphedema, with minimal discrepancies between reference ranges. False negative rates were observed in some participants, likely due to early-stage BCRL with minimal lymph accumulation. Conclusion: The findings suggest that BIS L-Dex scores are a valid indicator of BCRL, regardless of specific normative ranges used. Detection rates of clinically confirmed BCRL were consistent across different reference ranges, with minimal discrepancies. BIS remains a valuable tool for early detection and monitoring of BCRL. Future research should focus on longitudinal assessments and use of change in L-Dex scores for lymphedema monitoring and progression.

Patient-reported outcome measures and physical function following head and neck lymphedema - a systematic review.

PURPOSE: Head and neck cancer (HNC) treatments often lead to significant morbidity, including lymphedema. This systematic review aims to comprehensively explore the prevalence and impact of head and neck lymphedema (HNL) following treatment. METHODS: A systematic literature search was conducted up to September 2023. Studies evaluating HNL prevalence, associated factors, impact, patient-reported outcomes (PROMs), and physical assessments were included. Methodological quality assessment was performed, and data were synthesised narratively. RESULTS: Twelve studies met the inclusion criteria, with methodological quality ranging from moderate to high. Internal lymphedema prevalence was consistently higher than external lymphedema, with varying rates attributed to treatment modalities and assessment methods. PROMs such as the Lymphedema Symptom Intensity and Distress-Head and Neck and physical assessments including Patterson's Rating Scale were commonly utilised. HNL significantly impacted quality of life and physical function, with reported symptoms including discomfort, tightness, swallowing difficulties, and psychological distress. CONCLUSION: HNL is a common sequela of HNC treatment with significant implications for individuals' QoL. Standardised assessment protocols and tailored interventions are needed to address the needs of individuals with HNL and improve overall outcomes. IMPLICATIONS FOR CANCER SURVIVORS: This systematic review highlights a significant prevalence of lymphedema, particularly internal lymphedema in the larynx and pharynx, following treatment. Swallowing difficulties, nutritional issues, anxiety, depression, and body image concerns were associated with both internal and external lymphedema. The impact on quality of life is substantial, with survivors experiencing physical symptoms and psychosocial challenges, emphasising the importance of integrated care approaches tailored to both aspects of well-being.

Current diagnostic and quantitative techniques in the field of lymphedema management: a critical review.

Lymphedema evaluation entails multifaceted considerations for which options continue to evolve and emerge. This paper provides a critical review of the current status of diagnostic and quantitative measures for lymphedema, from traditional and novel bedside assessment tools for volumetric and fluid assessment, to advanced imaging modalities. Modalities are contrasted with regard to empirical support and feasibility of clinical implementation. The manuscript proposes a grid framework for comparing the ability of each modality to quantify specific lymphedema characteristics, including distribution, dysmorphism, tissue composition and fluid content, lymphatic anatomy and function, metaplasia, clinical symptoms, and quality of life and function. This review additionally applies a similar framework approach to consider how well assessment tools support important clinical needs, including: (1) screening, (2) diagnosis and differential diagnosis, (3) individualization of treatment, and (4) monitoring treatment response. The framework highlights which clinical needs are served by an abundance of assessment tools and identifies others that have problematically few. The framework clarifies which tools have greater or lesser empirical support. The framework is designed to assist stakeholders in selecting appropriate diagnostic and surveillance modalities, gauging levels of confidence when applying tools to specific clinical needs, elucidating overarching patterns of diagnostic and quantitative strengths and weaknesses, and informing future investigation.

Timing of Breast Cancer Related Lymphedema Development Over 3 Years: Observations from a Large, Prospective Randomized Screening Trial Comparing Bioimpedance Spectroscopy (BIS) Versus Tape Measure.

BACKGROUND: The PREVENT randomized control trial monitored progression to chronic breast cancer-related lymphedema (cBCRL) following intervention for subclinical breast cancer-related lymphedema (sBCRL) assessed by bioimpedance spectroscopy (BIS) versus tape-measure (TM). This multi-institutional trial demonstrated a 92% risk reduction of developing cBCRL. This secondary analysis reviews the timing of sBCRL and cBCRL following breast cancer (BC) treatment. PATIENTS AND METHODS: Women at risk of cBCRL (n = 919) were screened regularly up to 36 months after BC treatment using either BIS or TM. Following diagnosis of sBCRL, patients underwent a 4-week compression sleeve intervention. The time in months from BC treatment to detection was reviewed at 3-month intervals. RESULTS: In total 209 patients developed sBCRL (BIS: n = 89, TM: n = 120) and were eligible for intervention. 30 progressed to cBCRL postintervention (BIS: 7, TM: 23). More than half of patients had measurements consistent with sBCRL within 9 months of BC treatment. Patients continued to have initial detections of sBCRL, regardless of screening method, with rates remaining consistent in years two and three (p > 0.242) post surgery. Additionally, 39 patients progressed to cBCRL without developing sBCRL or receiving intervention across the 3-year period. CONCLUSIONS: The timing of sBCRL detection demonstrates that patients continue to be at risk years after treatment and may continue to progress to cBCRL years after surgery. Early detection of sBCRL allows for early intervention decreasing the likelihood of progression to cBCRL. Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important.

Comparison of Volume Measurements and Bioimpedance Spectroscopy Using A Stand-on Device for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer related lymphedema (BCRL) may be assessed through objective measurement of limb swelling with common techniques including volumetric measurement using a tape measure or perometry, and measurement of extracellular water using bioimpedance spectroscopy (BIS). This study aimed to evaluate the performance of a stand-on BIS device for detection of BCRL, introduce a novel graphical method to compare volumetric and BIS methods alongside traditional specificity and sensitivity analysis, and determine and compare BIS thresholds with those published previously. Materials and Methods: Female participants with indocyanine green lymphography confirmed unilateral arm lymphedema (n = 197) and healthy controls (n = 267) were assessed using a cross-sectional study design. BIS and volumetric measures were obtained in a single session. Results: The BIS lymphedema index (L-Dex) method had a significantly higher sensitivity than the excess volume approach (area under the curve = 0.832 vs. 0.649, p = 0.0001). A threshold of L-Dex 6.5 had a higher true positive rate (70.6%) than L-Dex 10 (68.5%) although false positive rate increased from 0.4% to 2.6%. A threshold of 5% excess volume improved the true positive rate (68.5%) compared with 10% excess volume (49.7%) however the false positive rate increased to an unacceptable 47%. The L-Dex ranges in this study were not significantly different from previously published ranges. Conclusion: BIS was superior for identifying BCRL compared with volume measurements, reaffirming the value of this technique. However, it is recommended that BIS be used in conjunction with comprehensive evaluation of symptoms and clinical presentation. The proposed graphical method provides a simple and easily interpretable approach to compare and define concordance between the two commonly used methods for BCRL assessment namely limb volume and BIS L-Dex indices. The existing BIS (L-Dex) thresholds for presence of BCRL were also validated.

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.

Body composition and chemotherapy toxicities in breast cancer: a systematic review of the literature.

PURPOSE: Breast cancer is the most diagnosed cancer in women with chemotherapy being a common treatment. Toxicities due to chemotherapy can result in dose reduction, delay, and early cessation of treatment, which along with causing distress for individuals during their cancer treatment might also reduce the therapeutic effect. The purpose of this systematic review is to examine the role of body composition on chemotherapy toxicities in women with breast cancer. METHODS: A systematic search of the literature was completed on electronic databases Pubmed, Embase, CINHAHL, and Cochrane. Studies were included if the direct effect of body composition on chemotherapy toxicities was reported and excluded if body composition could not be isolated. A critical appraisal of the studies included was performed using McMasters University Critical Review Form for Quantitative Studies. RESULTS: Eleven studies were included with a total of 2881 female participants. All studies reported significant relationships between body composition and chemotherapy toxicities; however, individual parameters differed between the studies. Adding to the heterogeneity, different thresholds were reported to determine both sarcopenia and myosteatosis, making it difficult to identify a common finding. CONCLUSION: This review suggests that body composition may be an important factor in predicting the severity of chemotherapy toxicities during treatment for breast cancer; however, the lack of international consensus as to thresholds in the literature for sarcopenia and myosteatosis may result in bias. The review supports the need for further prospective studies, allowing for more robust, pre-determined data collection, to better understand the implications of body composition on toxicities and benefits of using body composition to individualize chemotherapy dosing. IMPLICATIONS FOR CANCER SURVIVORS: Toxicities due to chemotherapy can result in treatment being unable to be completed as planned, potentially resulting in poorer survival outcomes. Improved knowledge in this area may give rise to a more reliable way of individualizing chemotherapy dosage to help mitigate this risk.

Effects of Body Positioning When Assessing Lymphedema of the Lower Limb Using Bioimpedance Spectroscopy.

Background: Bioimpedance spectroscopy (BIS) measurements are conventionally performed in supine position with a lead device attached to gel-backed electrodes, and more recently, with a stand-on device that uses fixed stainless-steel electrodes under the hands and feet. The aim of this study was to assess and compare BIS measurements made in supine, sitting, and standing positions using lead and stand-on impedance devices in participants with and without unilateral leg lymphedema. Materials and Methods: Participants with self-ascribed unilateral leg lymphedema (n = 24) and healthy controls (n = 71) were recruited using a cross-sectional study design. Triplicate BIS measurements were taken for each device in each position. Results: Impedance measurements with either device were reliable with coefficient of variation of 0.6% or lower. The magnitude of mean differences in absolute impedance values between devices were between 1% and 6% dependent on condition. L-Dex scores between the two devices were highly correlated (r = 0.82) and ∼70% of participants in the lymphedema group were classified as having lymphedema using the recommended cut-off with either device. There was no significant interleg difference of controls using the lead device; however, small, but significant differences (p = 0.0001) were found when using the stand-on device. Conclusion: The findings demonstrate that reliable impedance measurements of the legs can be made with either device in lying, sitting, or standing positions. However, data between the devices were not directly interchangeable. Although the risk of misidentification was small, reference ranges appropriate to the device and measurement position should be used when converting data to L-Dex scores.

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.

Axillary Treatment and Chronic Breast Cancer-Related Lymphedema: Implications for Prospective Surveillance and Intervention From a Randomized Controlled Trial.

PURPOSE: The PREVENT randomized trial assessed progression to chronic breast cancer-related lymphedema (cBCRL) after intervention triggered by bioimpedance spectroscopy (BIS) or tape measurement (TM). This secondary analysis identifies cBCRL risk factors on the basis of axillary treatment. METHODS: Between June 2014 and September 2018, 881 patients received sentinel node biopsy (SNB; n = 651), SNB + regional node irradiation (RNI; n = 58), axillary lymph node dissection (ALND; n = 85), or ALND + RNI (n = 87). The primary outcome was the 3-year cBCRL rate requiring complex decongestive physiotherapy (CDP). RESULTS: After a median follow-up of 32.8 months (IQR, 21-34.3), 69 of 881 patients (7.8%) developed cBCRL. For TM, 43 of 438 (9.8%) developed cBCRL versus 26 of 443 (5.9%) for BIS (P = .028). The 3-year actuarial risk of cBCRL was 4.4% (95% CI, 2.7 to 6.1), 4.2% (95% CI, 0 to 9.8), 25.8% (95% CI, 15.8 to 35.8), and 26% (95% CI, 15.3 to 36.7). Rural residence increased the risk in all groups. For SNB, neither RNI (SNB, 4.1% v SNB + RNI, 3.4%) nor taxane (4.4%) increased cBCRL, but risk was higher for patients with a BMI of ≥30 (6.3%). For SNB + RNI, taxane use (5.7%) or supraclavicular fossa (SCF) radiation (5.0%) increased cBCRL. For ALND patients, BMI ≥25 or chemotherapy increased cBCRL. For ALND + RNI, most patients received SCF radiation and taxanes, so no additional risk factors emerged. CONCLUSION: The extent of axillary treatment is a significant risk factor for cBCRL. Increasing BMI, rurality, SCF radiation, and taxane chemotherapy also increase risk. These results have implications for a proposed risk-based lymphedema screening, early intervention, and treatment program.

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.

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.

Prospective Surveillance with Compression for Subclinical Lymphedema: Symptoms, Skin, and Quality-of-Life Outcomes.

Background: Patients underwent a compression (sleeve and gauntlet) intervention for subclinical breast cancer-related lymphedema (S-BCRL). Physical, emotional, and quality-of-life (QoL) outcomes were examined. Associations of change in extracellular fluid alone through bioimpedance spectroscopy (BIS) or change in whole-arm volume through tape measure with the outcomes at time of S-BCRL were explored. Methods and Results: We enrolled newly diagnosed nonmetastatic breast cancer patients for surveillance up to 36 months postoperatively. Upon detection of S-BCRL, a 28-day compression intervention was initiated. Data were obtained through physical examination/measurement and self-report instruments: skin examination, Lymphedema Symptom Intensity and Distress Survey-Arm, and Functional Assessment of Cancer Therapy General (FACT-G), Breast (FACT-B), and FACT-B+4. Improvements with intervention were observed in the proportion of patients reporting symptom scores ≥3 in function (Cohen's d = -0.46, p < 0.01), in biobehavioral (Cohen's d = -0.30, p < 0.05), maximum number of skin conditions (Cohen's d = -0.34, p < 0.05. 3), FACT-B (Cohen's d = 0.52, p < 0.01), and FACT-B + four (Cohen's d = -0.42, p < 0.01). At the study endpoint, compared with those who did not progress, chronic breast cancer-related lymphedema (C-BCRL) progressing patients had higher overall symptom scores (p = 0.037), more skin conditions (p = 0.009), and lower total FACT-G and FACT-B scores (p < 0.05). At the time of S-BCRL, detection of greater BIS unit change correlated with higher symptom, skin condition, and QoL values. Greater whole-arm volume change correlated with higher FACT-B+4 scores (all p < 0.05). Conclusions: Prospective surveillance, symptom assessment, and compression intervention promote low progression rates from S-BCRL to C-BCRL and as such reduce symptom burden. This closed study is registered with ClinicalTrials.gov NCT02167659.

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.

Risk factors for breast cancer-related lymphedema in patients undergoing 3 years of prospective surveillance with intervention.

BACKGROUND: To evaluate risk factors (treatment-related, comorbidities, and lifestyle) for breast cancer-related lymphedema (BCRL) within the context of a Prospective Surveillance and Early Intervention (PSEI) model of care for subclinical BCRL. METHODS: The parent randomized clinical trial assigned patients newly diagnosed with breast cancer to PSEI with either bioimpedance spectroscopy (BIS) or tape measurement (TM). Surgical, systemic and radiation treatments, comorbidities, and lifestyle factors were recorded. Detection of subclinical BCRL (change from baseline of either BIS L-Dex ≥6.5 or tape volume ≥ 5% and < 10%) triggered an intervention with compression therapy. Volume change from baseline ≥10% indicated progression to chronic lymphedema and need for complex decongestive physiotherapy. In this secondary analysis, multinomial logistic regressions including main and interaction effects of the study group and risk factors were used to test for factor associations with outcomes (no lymphedema, subclinical lymphedema, progression to chronic lymphedema after intervention, progression to chronic lymphedema without intervention). Post hoc tests of significant interaction effects were conducted using Bonferroni-corrected alphas of .008; otherwise, an alpha of .05 was used for statistical significance. RESULTS: The sample (n = 918; TM = 457; BIS = 461) was female with a median age of 58.4 years. Factors associated with BCRL risk included axillary lymph node dissection (ALND) (p < .001), taxane-based chemotherapy (p < .001), regional nodal irradiation (RNI) (p ≤ .001), body mass index >30 (p = .002), and rurality (p = .037). Mastectomy, age, hypertension, diabetes, seroma, smoking, and air travel were not associated with BCRL risk. CONCLUSIONS: Within the context of 3 years of PSEI for subclinical lymphedema, variables of ALND, taxane-based chemotherapy, RNI, body mass index >30, and rurality increased risk.

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.

A Comparison of Bioimpedance Spectroscopy or Tape Measure Triggered Compression Intervention in Chronic Breast Cancer Lymphedema Prevention.

Background: This study compared rates of progression to chronic breast cancer-related lymphedema (defined as ≥ 10% arm volume change from baseline requiring complex decongestive physiotherapy [CDP]) following an intervention for subclinical lymphedema (S-BCRL) triggered by bioimpedance spectroscopy (BIS) or by tape measurement (TM). Methods and Results: This stratified, randomized, international trial enrolled new breast cancer patients undergoing: mastectomy/partial mastectomy, axillary treatment (dissection, sentinel lymph node biopsy [SLNB] >6 nodes or radiation), radiation therapy (chest wall/breast, supraclavicular fossa), or taxane-based chemotherapy. Following postsurgery eligibility reassessment, centralized, 1:1 randomization to prospective surveillance by BIS or TM occurred. S-BCRL detection triggered a 4-week, 12-hour per day, compression sleeve, and gauntlet intervention. The primary outcome (n = 209), rates of postintervention progression to CDP, was assessed over 3 years. Between June 24, 2014 and September 11, 2018, 1200 patients were enrolled, 963 randomized (BIS n = 482; TM n = 481) and 879 analyzed (BIS n = 442; TM n = 437). Median follow-up was 32.9 months (interquartile range = 22, 35). BIS patients triggered an intervention at a lower rate than TM patients (20.1%, n = 89 vs. 27.5%, n = 120, p = 0.011). Median months to trigger were longer with BIS than TM (9.7; 95% confidence interval [CI], 8.2-12.6 vs. 3.9; 95% CI, 2.8-4.5, p = 0.001). Overall, 14.4% (n = 30) progressed post-intervention, with reduced likelihood for BIS patients than TM patients (7.9%, n = 7 vs. 19.2%, n = 23; relative risk = 0.41; 95% CI, 0.13-0.81; absolute reduction 11.3%; 95% CI, 2.3-20.3; p = 0.016). Conclusions: Compared to TM, BIS provides a more precise identification of patients likely to benefit from an early compression intervention. Clinical Trial Registration number: NCT02167659.