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Potential therapeutic treatment

This review aims to summarize the current knowledge regarding the pharmacological interventions studied in both experimental and clinical trials for secondary lymphedema. Recent findings: Lymphedema is a progressive disease that results in tissue swelling, pain, and functional disability. The most common cause of secondary lymphedema in developed countries is an iatrogenic injury to the lymphatic system during cancer treatment. Despite its high incidence and severe sequelae, lymphedema is usually treated with palliative options such as compression and physical therapy. However, recent studies on the pathophysiology of lymphedema have explored pharmacological treatments in preclinical and early phase clinical trials. Summary: Many potential treatment options for lymphedema have been explored throughout the past two decades including systemic agents and topical approaches to decrease the potential toxicity of systemic treatment. Treatment strategies including lymphangiogenic factors, anti-inflammatory agents, and anti-fibrotic therapies may be used independently or in conjunction with surgical approaches.

Source: The Future of Lymphedema: Potential Therapeutic Targets for Treatment. Curr Breast Cancer Rep. 2023 Jun: PMC10233555

Pneumatic compression dosing

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/Results:

21 patients with lower extremity lymphedema were randomized into 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. Longterm 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.

Source: A Prospective Preliminary Study Examining the Physiological Impact of Pneumatic Compression Dosing in the Treatment of Lower Extremity Lymphedema Lymphat Res Biol. 2023 May 4. PMID:37140559 | DOI:10.1089/lrb.2022.0087

Acupuncture for BCRL

Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing standardized clinical and patient-centered outcome measures. Methods/Results: Patients with BCRL were randomized to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of 3 of 3 measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patientcentered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. 14 patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. 93 percent of all participants completed all 3 measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred. Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.

Source: Acupuncture Treatment for Breast Cancer-Related Lymphedema: A Randomized Pilot Study. Lymphat Res Biol. 2023 Apr 20. PMID:37083501 | DOI:10.1089/lrb.2022.0001

Tracking symptoms after PAL

Lymphedema negatively impacts patients from a psychosocial standpoint and consequently affects patient’s quality of life. Debulking procedures using power-assisted liposuction (PAL) are currently deemed an effective treatment for fat-dominant lymphedema and improves anthropometric measurements as well as quality of life. However, there have been no studies specifically evaluating changes in symptoms related to lymphedema after PAL. An understanding of how symptoms change after this procedure would be valuable for preoperative counseling and to guide patient expectations. Methods: A cross-sectional study was performed in patients with extremity lymphedema who underwent PAL from Jan 2018 - Dec 2020 at a tertiary care facility. A retrospective chart review and follow-up phone survey were conducted to compare signs and symptoms related to lymphedema before and after PAL. Results: Of the 45 patients in the study, 60% underwent upper extremity PAL and 40% underwent lower extremity PAL. The mean follow-up time was 15.5±7.9 months. After PAL, patients with upper extremity lymphedema reported having resolved heaviness (44%), as well as improved achiness (79%) and swelling (78%). In patients with lower extremity lymphedema, they reported having improved all signs and symptoms, particularly swelling (78%), tightness (72%), and achiness (71%). Conclusions: In patients with fat-dominant lymphedema, PAL positively impacts patient-reported outcomes in a sustained fashion over time. Continuous surveillance of postoperative studies is required to elucidate factors independently associated with the outcomes found in our study. Moreover, further studies using a mixed method approach will help us better understand patient’s expectations to achieve informed decision and adequate treatment goals.

Source: Tracking Symptoms of Patients With Lymphedema Before and After Power-Assisted Liposuction Surgery. Ann Plast Surg. 2023 Feb 27. PMID:36881732 | DOI:10.1097/SAP.0000000000003430