Chronic unilateral arm lymphedema correlates with increased intima-media thickness in the brachial artery

Summary: Drainage of the arterial wall via adventitial lymphatic vessels has been shown to play a pivotal role for vessel wall homeostasis. Also, retrograde cholesterol transport is ensured via this route, but no studies exist to demonstrate that lymphatic stasis would represent a mechanism to initiate atherosclerotic lesion formation in human arteries. To test this hypothesis, we embarked on a simple clinical experiment, assessing wall thickness in limb arteries with lymphedema after surgical intervention, with the contralateral limb serving as control. Using ultrasound imaging, the differential thickness was assessed separately for the three arterial wall layers. The potential of disease progression by lymphostasis was addressed by depiction of longitudinal results according to the time after lymph dissection.

Development and Clinical Validation of the LymphMonitor Technology to Quantitatively Assess Lymphatic Function

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.

The prevalence of arm lymphedema after radiation treatment in patients with breast cancer

Aim: To evaluate the prevalence and risk factors of arm lymphedema in patients with breast cancer. Materials and methods: Between 2006 and 2017, we investigated patients with breast cancer after breast surgery who received adjuvant radiotherapy at the breast or chest wall, and/or adjuvant radiotherapy at regional lymph nodes, and standard systemic chemotherapy depending on disease stage and risk factors. We assessed arm lymphedema using arm circumference measurement differences on the treated side compared with the opposite arm (≥2 cm measurements at any one position). Associations between arm lymphedema and potential risk factors were identified using statistical analysis. Results: In 308 patients, arm lymphedema prevalence was 6·2%. Patients having ≥20 lymph nodes removed (hazard ratio (HR) = 3·29; 95% confidence interval (CI): 1·12–8·87), undergoing regional lymph node irradiation (HR = 1·81; 95% CI: 1·09–13·28), and no arm and shoulder exercises after treatment (HR = 3·16; 95% CI: 1·89–5·26) had a higher risk of arm lymphedema. Findings: Arm lymphedema is a serious breast cancer complication and is a preventable morbidity. Planning arm and shoulder exercises in line with adjuvant treatments and increasing clinical awareness of early indications could help lower the risk of occurrence.

Development and Psychometric Validation of a Patient-Reported Outcome Measure for Arm Lymphedema: The LYMPH-Q Upper Extremity Module

Background A multiphased mixed-methods study was performed to develop and validate a comprehensive patient-reported outcome measure (PROM) for arm lymphedema in women with breast cancer (i.e., the LYMPH-Q Upper Extremity Module). Methods Qualitative interviews (January 2017 and June 2018) were performed with 15 women to elicit concepts specific to arm lymphedema after breast cancer treatment. Data were audio-recorded, transcribed, and coded. Scales were refined through cognitive interviews (October and Decemeber 2018) with 16 patients and input from 12 clinical experts. The scales were field-tested (October 2019 and January 2020) with an international sample of 3222 women in the United States and Denmark. Rasch measurement theory (RMT) analysis was used to examine reliability and validity. Results The qualitative phase resulted in six independently functioning scales that measure arm symptoms, function, appearance, psychological function, and satisfaction with information and with arm sleeves. In the RMT analysis, all items in each scale had ordered thresholds and nonsignificant chi-square p values. For all the scales, the reliability statistics with and without extremes for the Person Separation Index were 0.80 or higher, Cronbach’s alpha was 0.89 or higher, and the Intraclass Correlation Coefficients were 0.92 or higher. Lower (worse) scores on the LYMPH-Q Upper Extremity scales were associated with reporting of more severe arm swelling, an arm problem caused by cancer and/or its treatment, and wearing of an arm sleeve in the past 12 months. Conclusions The LYMPH-Q Upper Extremity Module can be used to measure outcomes that matter to women with upper extremity lymphedema. This new PROM was designed using a modern psychometric approach and, as such, can be used in research and in clinical care.

Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35–64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.