Lymphatic Valves and Lymph Flow in Cancer-Related Lymphedema

Drishya Iyer †, Melanie Jannaway †, Ying Yang and Joshua P. Scallan *. Cancers 2020, 12, 2297.

Lymphedema is a complex disease caused by the accumulation of fluid in the tissues resulting from a dysfunctional or damaged lymphatic vasculature. In developed countries, lymphedema most commonly occurs as a result of cancer treatment. Initially, impaired lymph flow causes edema, but over time this results in inflammation, fibrotic and fatty tissue deposition, limited mobility, and bacterial infections that can lead to sepsis. While chronically impaired lymph flow is generally believed to be the instigating factor, little is known about what pathophysiological changes occur in the lymphatic vessels to inhibit lymph flow. Lymphatic vessels not only regulate lymph flow through a variety of physiologic mechanisms, but also respond to lymph flow itself. One of the fascinating ways that lymphatic vessels respond to flow is by growing bicuspid valves that close to prevent the backward movement of lymph. However, lymphatic valves have not been investigated in cancer-related lymphedema patients, even though the mutations that cause congenital lymphedema regulate genes involved in valve development. Here, we review current knowledge of the regulation of lymphatic function and development by lymph flow, including newly identified genetic regulators of lymphatic valves, and provide evidence for lymphatic valve involvement in cancer-related lymphedema.

New Insights into the Pathophysiology of Primary and Secondary Lymphedema: Histopathological Studies on Human Lymphatic Collecting Vessels

Virginia Barone, PhD,1,* Annalisa Borghini, PhD,1,* Erica Tedone Clemente, MD,2 Margherita. Lymphatic Research Biology, 2020. 

Background: Lymphedema is characterized by an accumulation of interstitial fluids due to inefficient lymphatic drainage. Primary lymphedema is a rare condition, including congenital and idiopathic forms. Secondary lymphedema is a common complication of lymph node ablation in cancer treatment. Previous studies on secondary lymphedema lymphatic vessels have shown that after an initial phase of ectasia, worsening of the disease is associated with wall thickening accompanied by a progressive loss of the endothelial marker podoplanin.

Methods and Results: We enrolled 17 patients with primary and 29 patients with secondary lymphedema
who underwent lymphaticovenous anastomoses surgery. Histological sections were stained with Masson’s trichrome, and immunohistochemistry was performed with antibodies to podoplanin, smooth muscle a-actin (a-SMA), and myosin heavy chain 11 (MyH11). In secondary lymphedema, we found ectasis, contraction, and sclerosis vessel types. In primary lymphedema, the majority of vessels were of the sclerosis type, with no contraction vessels. In both primary and secondary lymphedema, not all a-SMA-positive cells were also positive for MyH11, suggesting transformation into myofibroblasts. The endothelial marker podoplanin had a variable expression unrelatedly with the morphological vessel type.

Conclusions: Secondary lymphedema collecting vessels included all the three types described in literature, that is, ectasis, contraction, and sclerosis, whereas in primary lymphedema, we found the ectasis and the sclerosis but not the contraction type. Some cells in the media stained positively for a-SMA but not for MyH11. These cells, possibly myofibroblasts, may contribute to collagen deposition.

Overview of Lymphedema for Physicians and Other Clinicians: A Review of Fundamental Concepts

Oscar J. Manrique, MD, FACS; Samyd S. Bustos, MD; Pedro Ciudad, MD, PhD; Kian Adabi, MD; Wei F. Chen, MD; Antonio J. Forte, MD, PhD, MS; Andrea L. Cheville, MD; James W. Jakub, MD; Sarah A. McLaughlin, MD;
and Hung-Chi Chen, MD, PhD. Mayo Clin Proceedings, 2020.

Lymphedema has historically been underrated in clinical practice, education, and scholarship to the detriment of many patients with this chronic, debilitating condition. The mechanical insufficiency of the lymphatic system causes the abnormal accumulation of protein-rich fluid in the interstitium, which triggers a cascade of adverse consequences such as fat deposition and fibrosis. As the condition progresses, patients present with extremity heaviness, itchiness, skin infections, and, in later stages, dermal fibrosis, skin papillomas, acanthosis, and other trophic skin changes. Correspondingly, lymphedema results in psychological morbidity, including anxiety, depression, social avoidance, and a decreased quality of life, encompassing emotional, functional, physical, and social domains. For this review, we conducted a literature search using PubMed and EMBASE and herein summarize the evidence related to the fundamental concepts of lymphedema. This article aims to raise awareness of this serious condition and outline and review the fundamental concepts of lymphedema.

Pathophysiology of Breast Cancer-Related Lymphoedema

Neil B. Piller1. Current Breast Cancer Reports. 2020.

Purpose of Review To review the literature regarding the pathophysiological changes found in BCRL and to link them to the cancer and the type and sequencing of treatments and raise attention to the fact that not all parts of the arm at risk or with lymphoedema may have underlying changes which are similar or are progressing at the same rate.

Recent Findings There still remains a lack of awareness regarding BCRL-related pathophysiology and of the range of reasons for it. Linked to this is a lack of appropriate in-clinic assessment of these changes and of the use of this information to better target and sequence treatment. We are refining and improving our consensus documents related to lymphoedema and the impact of the pathophysiology on its staging which will help in this.

Summary We should link the pathophysiological changes we find and record with the functional changes which are signs of that underlying structural change through increased use of a range of assessment tools such as indurometry, bio-impedance spectroscopy, tissue dielectric constants, ICG, lympho-scintigraphy, etc. We must better target and sequence our treatments and relate them to our measures of pathophysiological and functional changes.

Axillary web syndrome in women after breast cancer surgery referred to an Oncological Rehabilitation Unit: which are the main risk factors? A retrospective case-control study

De Sire1,2, L. Losco3, C. Cisari1,4, A. Gennari5, R. Boldorini6, N. Fusco7,8, E. Cigna3, M. Invernizzi1.  European Review for Medical and Pharmacological Sciences 2. 2020; 24: 8028-8035.

OBJECTIVE: Axillary web syndrome (AWS) is a complication of surgical procedures in breast cancer (BC) patients. This condition with poorly understood incidence and etiology is characterized by the locoregional development of scar tissue, leading to subcutaneous cording, motion impairment and pain. The early identification of patients at risk for AWS would improve their clinical management. Here, we sought to characterize the prevalence of and the risk factors associated with AWS in BC women after surgery.

PATIENTS AND METHODS: All patients with BC that underwent axillary surgery referred to an Outpatient Service for Oncological Rehabilitation were retrospectively collected. These women were assessed two weeks after the surgical procedure for their clinicopathologic features, type of therapeutic interventions, and AWS presence, laterality, pain, localization, cords type, and number of cords.

RESULTS: Altogether, 177 patients (mean aged 60.65 ± 12.26 years) were included and divided into two groups: AWSPOS (n=52; 29.4%) and AWSNEG (n=125; 70.6%). Patients with tumor N ≥1 (OR=3.7; p<0.001), subjected to mastectomy, axillary lymph node dissection (ALND) and chemotherapy showed significant correlations with AWS onset (p<0.05). The range of shoulder motion limitation (OR=11.2; p<0.001) and the presence of breast cancer related lymphedema (OR=3.5; p=0.020) were associated with AWS. CONCLUSIONS: Mastectomy, ALND, chemotherapy, low staging tumors, shoulder range of motion limitations, and BCRL represent risk factors for AWS onset. Realizing new strategies for assessing the individual risk of AWS is a crucial clinical need to improve the health-related quality of life of BC survivors.

In Search of Risk Factors for Recurrent Erysipelas and Cellulitis of the Lower Limb: A Cross-Sectional Study of Epidemiological Characteristics of Patients Hospitalized due to Skin and Soft-Tissue Infections

Mariusz Sapuła , Dagny Krankowska , and Alicja Wiercin´ska-Drapało. Interdisciplinary Perspectives on Infectious Diseases. Volume 2020.

Background. Erysipelas and cellulitis are common, acute, bacterial infections of the skin and subcutaneous tissue. The incidence of these infections is growing, and the recurrence rate is high. Effective antibiotic prophylaxis is available, but insufficient data exist on the risks factors for recurrent infection.

Purpose. To compare comorbidities and laboratory findings in patients with single episode and recurrent erysipelas/cellulitis in order to identify risk factors for recurrent erysipelas/cellulitis. Methods. A cross sectional study, which included patients hospitalized in the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw due to erysipelas and cellulitis during 3 consecutive years (July 2016–June 2019).

Results. The study included 163 patients, of which 98 had a first episode of erysipelas/cellulitis and 65 had a recurrence. The recurrent infection was significantly associated with a history of lymphedema (12.3% in the recurrent group vs. 2.0% in the first-episode group, p = 0.015), a higher BMI (35.4 vs. 31.2, respectively, p = 0.002), chronic obstructive pulmonary disease (10.8% vs. 2.0%, p = 0.030), and a shorter history of symptoms prior to hospitalization (6.0 days vs. 11.8 days, p = 0.004). Patients with the first episode of infection were more likely to have had minor local trauma directly preceding the symptoms of infection (20.4% in the first-episode group vs. 1.5% in the recurrent group, p = 0.001).

Conclusions. Patients with lymphedema and obesity should be viewed at high risk of developing recurrence of erysipelas and thus should be considered as candidates for antibiotic prophylaxis and other prevention methods. Minor local trauma directly preceding the skin infection does not by itself confer a higher risk for erysipelas recurrence. More research is needed to assess the association of recurrent skin and soft-tissue infection to preceding minor local trauma,individual components of the metabolic syndrome, and COPD.

Drugs and Breast Cancer–Related Lymphoedema (BCRL): Incidence and Progression

Vaughan Keeley1,2. Current Breast Cancer Reports. 2020.

Purpose of Review What is the current evidence for the role of drugs as risk factors for the development of breast cancer–related lymphoedema (BCRL) and in exacerbating existing BCRL? What are the mechanisms by which these effects occur?

Recent Findings There is now evidence that taking calcium channel blockers (CCBs) during and after breast cancer treatment and receiving docetaxel chemotherapy are risk factors for the development of BCRL. CCBs cause oedema by increasing capillary filtration and docetaxel by inhibiting lymphatic vessel contractions.

Summary Ideally, CCBs should be avoided during and after treatment for breast cancer, but alternative options include changing to CCBs with a lower risk of causing oedema. An awareness of the potential role of medications in increasing the risk of BCRL and exacerbating existing BCRL is important in the appropriate management of patients treated for breast cancer.

Prognostic factors for lymphedema in patients with locally advanced head and neck cancer after combined radio(chemo)therapy- results of a longitudinal study

Silke Tribiusa,⁎, Henning Pazdykaa, Pierre Tennstedtb, Chia-Jung Buschc, Henning Hankend, Andreas Krülla, Cordula Petersen. Oral Oncology 109 (2020) 104856.

Aim: Treatment-associated lymphedema is a common side effect after multimodal therapy for locally advanced head and neck cancer (LAHNC). This study aims to evaluate potential prognostic factors for head and neck lymphedema (HNL) and its potential impact on clinical outcome.

Methods: This is a prospective data registry analysis on 280 patients treated for locally advanced head and neck cancer (LAHNC). All patients received surgery and risk-adapted platinum-based adjuvant intensity modulated radio(chemo)therapy (R(C)T, IMRT). Treatment- related toxicity was prospectively registered in a data base in regular intervals (baseline 3 months after R(C)T, every 3 months for 3 years, and every 6 months thereafter) and documented according to RTOG/EORTC toxicity criteria.

Results: Predictive for any grade HNL 3 months after R(C)T were age, BMI, number of removed nodes and RT modality. Multivariable logistic regression analysis showed that in the acute toxicity phase (3 months after R (C)T) higher body mass index (BMI), extracapsular spread (ECE), linac-based IMRT, bilateral treatment to the neck (surgery and RT), and the addition of chemotherapy increase the risk for grade 2 HNL. For chronic HNL, higher BMI, linac-based IMRT and ECE were predictive for grade 2 HNL. Higher BMI is associated with better local control rates. Advanced age and ECE had a negative impact on OS.

Conclusion: HNL is a common acute and late side effect after multimodal therapy for LAHNC. Knowing risk factors for HNL prior to therapy enables caregivers and patients to take measures prior to treatment to prevent or limit the effects of HNL.

The clinical characteristics of lower extremity lymphedema in 440 patients

Steven M. Dean, DO, FSVM, RPVI,a Elizabeth Valenti, APRN-CNP, CWS,a Karen Hock, MS, PT, CLT-LANA,b
Julie Leffler, PT, CLT-LANA,b Amy Compston, PT, DPT CRT, CLT-LANA,b and William T. Abraham, MD, FACP, FACC, FAHA, FESC, FRCPE,a Columbus, Ohio. Journal of Vascular Surgery: Venous and Lymphatic Disorders
September 2020.

Background: Lower extremity lymphedema is frequently encountered in the vascular clinic. Established dogma purports that cancer is the most common cause of lower extremity lymphedema in Western countries, whereas chronic venous insufficiency (CVI) is often overlooked as a potential cause. Moreover, lymphedema is typically ascribed to a single cause, yet multiple causes can coexist.

Methods: A 3-year retrospective analysis was conducted of demographic and clinical characteristics of 440 eligible patients with lower extremity lymphedema who presented for lymphatic physiotherapy to a university medical center’s cancer-based physical therapy department.

Results: The four most common causes of lower extremity lymphedema were CVI (phlebolymphedema; 41.8%), cancer related lymphedema (33.9%), primary lymphedema (12.5%), and lipedema with secondary lymphedema (11.8%). The collective cohort was more likely to be female (71.1%; P < .0001), to be white (78.9%; P < .0001), to demonstrate bilateral distribution (74.5%; P < .0001), and to have involvement of the left leg (bilateral, 69.1% [P < .0001]; unilateral, 58.9% [P ¼ .0588]). Morbid obesity was pervasive (mean weight and body mass index, 115.8 kg and 40.2 kg/m2, respectively) and significantly correlated with a higher International Society of Lymphology lymphedema stage (stage III mean weight and body mass index, 169.2 kg and 57.3 kg/m2, respectively, vs stage II, 107.8 kg and 37.5 kg/m2, respectively;P< .0001). Approximately one in three (35.7%) of the population sustained one or more episodes of cellulitis, but patients with stage III lymphedema had roughly twice the rate of soft tissue infection as patients with stage II, 61.7% vs 31.8%, respectively (P < .001). Multifactorial lymphedema was present in 25%. Approximately half of the patients with lipedema with secondary lymphedema (48.1%) or primary lymphedema (45.5%) had a superimposed cause of swelling that was usually CVI. Total knee arthroplasty was the most common cause of noncancer surgery-mediated worsening of pre-existing lymphedema. Conclusions: In a large cohort of patients treated in a cancer-affiliated physical therapy department, CVI (phlebolymphedema), not cancer, was the predominant cause of lower extremity lymphedema. One in four patients had more than one cause of lymphedema. Notable clinical characteristics included a proclivity for female patients, bilateral distribution, left limb, cellulitis, and nearly universal morbid obesity. (J Vasc Surg: Venous and Lym Dis 2020;8:851-9.)

Assessment of Upper Limb Lymphedema: A Qualitative Study Exploring Clinicians’ Clinical Reasoning

Robyn Sierla, PhD,1,2 Elizabeth S. Dylke, PhD,1 Tim Shaw, PhD,1, Simon Poon, PhD,3 and Sharon L. Kilbreath, PhD1. Lymphatic Research Biology, 2020.  

Background: A variety of objective and subjective assessments are available for clinical assessment of lymphedema. The aim of this study was to explore the clinical reasoning underpinning the assessment of upper limb lymphedema by experienced lymphedema clinicians.

Methods and Results: Semistructured, individual, interviews were conducted with lymphedema therapists (n = 14) from a variety of treatment settings. These interviews were conducted after observations of these therapists assessing patients with lymphedema and focused on: (1) the therapists’ rationale for the assessments selected, (2) how the data were analyzed, and (3) how the information was then used. Assessment selection was guided by the purpose of the visit, patient preference, resources, and time available. Subjective measures of visible and palpated tissue changes were used to target treatment, and objective measures of circumference and bioimpedance spectroscopy and patient report of symptoms informed treatment evaluation and disease progression. Objective data collected were primarily analyzed for interlimb difference and change between appointments.

Conclusions: A range of clinical assessments were used in the evaluation of lymphedema to detect the presence of lymphedema, estimate the extent of soft tissue change, understand the patient experience of lymphedema, and evaluate treatment response. A primary determinant for the collection of objective measures was the appointment duration. Current methods of data analysis and reporting do not facilitate the review of change over time.

Monitoring Leg Lymphedema Over the Course of Therapy Using an Infrared System

Iris M. Lu, MS,1 Michael J. Weiler, PhD,2 Nathan D. Frank, MBA,2, John Jordi, PTA, BS, CLT-LANA, CI,3 and J. Brandon Dixon, PhD1,2,4,5. Lymphatic Research Biology, Volume 18, Number 4, 2020.

Background: There are many techniques of monitoring leg lymphedema during physical therapy. Taking
volumetric measurements with a tape measure is among the most common clinically, and changes in volume are typically used to measure therapy efficacy. This study shows how the Kinect infrared (IR) sensor with custom algorithms can assess leg circumferences and volumes comparable with tape measurements taken by a trained therapist while exploring regional leg changes to determine uniformity of change.

Methods and Results: Leg volumes were measured in 38 lymphedema patients using the tape measure circumference method and the Kinect IR system. Changes in circumferences in various leg regions over the course of therapy were analyzed in 23 patients. The leg circumferences (R2 = 0.9522) and volumes ( R2 = 0.9847) strongly correlated between the two methods. The Bland–Altman analysis indicated a circumference percent different bias of 1.6 (6.2%), requiring a minor correction factor between the two methods. Over the course of therapy, patients with a reduction in leg volume, defined as a change >6.5% have greater reduction most distal to the body.

Conclusion: The Kinect IR system explored can be used clinically for leg volume measurements to monitor leg lymphedema patients over the course of their therapy. Implementing analysis of regional leg changes can better inform physical therapy to improve efficacy of treatment.

Psychosocial Issues Associated with Breast Cancer-Related Lymphedema: a Literature Review

L. H. Eaton1 & N. Narkthong2 & J. M. Hulett 2. Current Breast Cancer Reports, 2020.

Purpose of Review Breast cancer-related lymphedema (BCRL) is a chronic disease affecting breast cancer survivors. The purpose of this article is to update the scientific literature regarding psychosocial issues associated with BCRL.

Recent Findings Reports describe economic burdens, social support, sexuality, BCRL patient-education needs, and interventions to reduce BCRL symptoms and improve QOL among women with breast cancer. The psychosocial impact of BCRL may differ between younger and older women which has implications for age-related interventions to reduce the adverse psychosocial experiences of women with BCRL. We did not locate studies reporting the psychosocial impact of BCRL on male breast cancer survivors.

Summary More psychosocial-based interventions are needed that target the concerns of those with BCRL, including age-related needs, sexual concerns, body image, and social support. Future research is indicated to study the psychosocial impact of BCRL among men. Researchers may consider how pandemic-driven health care policies affect the psychosocial needs of those with BCRL

The reaching movement in breast cancer survivors: Attention to the principles of rehabilitation

Paolucci Teresa a, Serena Vincenza Capobianco b, Arianna Valeria Bai b, Bonifacino Adriana c, Agostini Francesco b, Bernetti Andrea b, Paoloni Marco b, Cruciani Arianna d, Santilli Valter b, Padua Luca d, e, Mangone Massimiliano. Journal of Bodywork & Movement Therapies 24 (2020) 102e108.

Introduction: Breast-cancer is leading cause of morbidity and mortality in women. The prognosis and
survival rate of women with breast-cancer have significantly improved worldwide; more attention needs
to be paid to rehabilitative interventions after surgery. This paper describes use of reaching movement to
assess upper limb motor control and functional ability after breast-cancer surgery (BC).

Material and methods: We conducted a cross-sectional observational study consisting of biomechanical
evaluation of upper limb limitations in women BC, versus a control group (CG). Thirty breast-cancer
survivors and thirty healthy women participated in this study. Both groups were subjected to clinical
evaluation of the shoulder joint ROM on the operated side, as an assessment of the muscular-strength of
the shoulder with the MRC-scale. The Functional-Assessment was evaluated by the DASH and Constant Murley-Score. The EORTC QLQ-C30 and VAS were used to measure the quality of life assessment and pain
respectively. A Biomechanical evaluation was performed, using Reaching-Task and Surface-EMG.

Results: Normal Jerk for BC was higher than CG. Target approaching velocity and movement duration BC
was lower than CG. Synergy Anterior Deltoid/Triceps Brachii muscles in CG was higher than BC.

Tissue Dielectric Constant Measures in Women With and Without Clinical Trunk Lymphedema Following Breast Cancer Surgery: A 78-Week Longitudinal Study

Linda A. Koehler, Harvey N. Mayrovitz. Physical Therapy Volume 100 Number 8, 2020.

Objective. Following breast cancer surgery with lymph node removal, women are at risk of developing lymphedema in the upper extremity or trunk. Currently, trunk lymphedema diagnosis relies on a clinical assessment because no quantifiable standard method exists. Tissue dielectric constant (TDC) values are quantifiable measures of localized skin tissue water and may be able to detect trunk lymphedema. The goal of this study was to (1) compare parameters derived from TDC measurements with those derived from clinically accepted criteria for trunk lymphedema in women following breast cancer surgery and (2) explore the potential utility of TDC to detect trunk lymphedema early in its progression.

Methods. This prospective longitudinal study, a secondary analysis from a larger study, observed women with and without clinically determined truncal lymphedema following breast cancer surgery. TDC was measured on the lateral trunk wall at post-surgery weeks 2, 4, 12, and 78 in women who had surgical breast cancer treatment with lymph node removal. Clinical assessment for trunk lymphedema was determined at 78 weeks by a lymphedema expert. Comparison of TDC measurements in women with and without clinical trunk lymphedema was analyzed.

Results. Clinical assessment identified trunk lymphedema in 15 out of 32 women at 78 weeks. These women had TDC ratios statistically higher than women without truncal lymphedema.

Conclusion. The overall findings indicate that TDC has the ability to quantify trunk lymphedema and might be valuable in early detection.

Impact. TDC may be a beneficial tool in the early detection of breast cancer–related trunk lymphedema, which could trigger intervention.

Lay Summary. A new device may help recognize trunk lymphedema in patients with breast cancer so they could receive appropriate treatment.

Surgical Approaches to the Prevention and Management of Breast Cancer–Related Lymphedema

Kristine C. Rustad1 & David W. Chang. Current Breast Cancer Reports (2020) 12:185–192.

Purpose of Review Upper extremity lymphedema is a much-feared complication of breast cancer treatment leading to significant impairments in patients’ quality of life. The mainstay of treatment for this debilitating chronic disease has been non-surgical modalities, namely complete decongestive therapies. Surgical treatment of lymphedema has emerged as an option for patients who have exhausted these conservative measures and consists of both physiologic procedures (vascularized lymph node transplant and lymphovenous bypass) which aim to reduce the burden of lymphatic fluid and reductive procedures to remove excess soft tissue.

Recent Findings Opinions vary among surgeons regarding the appropriate surgical indications in patients with different stages of lymphedema for each type of surgery, as well as the optimal donor site for lymph node transplant, and recent studies are beginning to address these questions. Additionally, there is growing data regarding the benefits of preventative lymphatic surgery at the time of axillary lymph node dissection, as well as the cost effectiveness of this approach.

Summary Surgical approaches for the prevention and treatment of breast cancer–related lymphedema are gaining popularity as a means of improving patients’ quality of life. There is an expanding body of literature demonstrating the effectiveness of these surgical procedures in terms of reduction in arm circumference, decreased cellulitis incidence, and overall quality of life, as well as emerging evidence of their cost effectiveness.

Resistance exercise and breast cancer–related lymphedema—a systematic review update and meta-analysis

Timothy Hasenoehrl1 & Stefano Palma1 & Dariga Ramazanova2 & Heinz Kölbl3 & Thomas E. Dorner4,5 &
Mohammad Keilani1 & Richard Crevenna1. Supportive Care in Cancer (2020) 28:3593–3603.

Background The purpose of this systematic review update and meta-analysis was to analyze resistance exercise (RE) intervention trials in breast cancer survivors (BCS) regarding their effect on breast cancer-related lymphedema (BCRL) status and upper and lower extremity strength.

Methods Systematic literature search was conducted utilizing PubMed, MEDLINE, and Embase databases. Any exercise intervention studies—both randomized controlled and uncontrolled—which assessed the effects of RE on BCRL in BCS in at least one intervention group published between 1966 and 31st January 2020 were included. Included articles were analyzed regarding their level of evidence and their methodological quality using respective tools for randomized and nonrandomized trials of the Cochrane collaboration. Meta-analysis for bioimpedance spectroscopy (BIS) values as well as upper and lower extremity strength was conducted.

Results Altogether, 29 studies were included in the systematic review. Results of six studies with altogether twelve RE intervention groups could be pooled for meta-analysis of the BCRL. A significant reduction of BCRL after RE was seen in BIS values (95% CI − 1.10 [− 2.19, − 0.01] L-Dex score). Furthermore, strength results of six studies could be pooled and meta-analysis showed significant improvements of muscular strength in the upper and lower extremities (95% CI 8.96 [3.42, 14.51] kg and 95% CI 23.42 [11.95, 34.88] kg, respectively).

Conclusion RE does not have a systematic negative effect on BCRL and, on the contrary, potentially decreases it.

Is the Effect of Complex Decongestive Therapy the Same for Primary and Secondary Lower Lymphedema?

Hanife Abakay, PT, MSc,1 Hanife Dog˘ and, PT, PhD,1 Havva Talay Cxalisx, MD,2 and Tu¨ rkan Akbayrak, PT, PhD3. Lymphatic Research Biology, 2020.  

Background: The aim was to compare edema and quality of life (QOL) after complex decongestive therapy (CDT) in two types of lymphedema: primary lower limb lymphedema (PLL) and secondary lower limb lymphedema (SLL).

Methods and Results: Participants with PLL (n = 20) and SLL (n = 20) were recruited in this prospective singleblinded study. Patients in both groups were treated with CDT for 4 weeks 5 days a week. The amount of edema in their lower extremities was assessed by circumference measurement. The QOL for the patients was evaluated by a Lymphedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphedema (LymphICF-LL) before and immediately following the therapy. There was no significant difference in the volume reductions between the two groups ( p > 0.05). Overall initial QOL was significantly lower in patients with PLL than in patients with SLL scores. Post-CDT differed significantly between PLL and SLL groups, QOL was significantly lower for patients with PLL than for patients with SLL scores ( p < 0.05). When the changes in both groups were examined, it was found that their QOL increased after the treatment ( p < 0.05). Conclusions: While there was no difference in the amount of edema in both groups, the results of patients with SLL were more positive than patients with PLL in terms of QOL. Lymphedema therapists should approach patients with different therapeutic considerations specific to each type of lymphedema before using CDT in clinical practice.

Reduction of breast lymphoedema secondary to breast cancer: a randomised controlled exercise trial

S. L. Kilbreath1, L. C. Ward2, G. M. Davis1, A. C. Degnim3, D. A. Hackett1, T. L. Skinner4, D. Black1. Breast Cancer Research and Treatment. 2020.

Background Breast lymphoedema can occur following surgical treatment for breast cancer. We investigated whether an exercise program reduced breast lymphoedema symptoms compared to a non-exercise control group.

Methods A single-blinded randomised controlled trial was conducted in which women with stable breast lymphoedema (n=89) were randomised into an exercise (n=41) or control (n=47) group. The intervention comprised a 12-week combined aerobic and resistance training program, supervised weekly by an accredited exercise physiologist. All participants completed a weekly symptoms diary and were assessed monthly to ensure that there was no exacerbation of their lymphoedema. Changes in the breast were captured physically with ultrasound and bioimpedance spectroscopy and changes in symptoms were captured using European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer (BR23) and Lymphoedema Symptom Intensity and Distress questionnaires.

Results The exercise group reported a greater reduction in breast-related symptoms than the control group, assessed by the EORTC BR23 breast symptom questions. Measures of extracellular fuid, assessed with bioimpedance spectroscopy ratio, decreased in the exercise group compared to the control group. No signifcant diference was detected in dermal thickness in the breast, assessed by ultrasound. Session attendance in the exercise sessions was high, with two musculoskeletal adverse events reported, but no exacerbations of lymphoedema observed.

Conclusion Combined resistance and aerobic exercise training is safe for women living with breast lymphoedema. Preliminary data suggest exercise training can reduce breast lymphoedema symptoms to a greater extent than usual care

Lymphatic treatments after orthopedic surgery or injury: A systematic review

Ifat Klein a, Dorit Tidhar b, Leonid Kalichman c. Journal of Bodywork and Movement Therapies. Published:July 10, 2020.

Background: Orthopedic injuries in conjunction with extensive damage to tissues, bones and blood
vessels, usually require a long recovery. Associated consequences are pain, movement limitations,
decreased function and occasionally, prolonged edema, which can delay or interfere with the healing
process. Lymphatic and compression therapy have become increasingly common, intending to reduce
edema and pain, thus, promoting the recovery process.

Aims: To examine the efficacy of methods commonly used to reduce edema after orthopedic injury or
surgery, i.e. decongestive therapy, manual lymphatic drainage, and compression bandaging.

Methods: English literature search was undertaken in January 2019, in the following databases: Cochrane
Library, MEDLINE, PEDro. Inclusion criteria: randomized controlled or quasi-controlled trials in adults
who have edema or pain after recent limb trauma or surgery. Two independent assessors rated study
quality and risk of bias using the PRISMA recommendations and PEDro score.

Results: We evaluated 71 papers. After excluding duplicated and irrelevant papers, 15 met the eligibility
criteria (6 on lymphatic treatment and 9 on compression). Quality of papers ranged from 3 to 7 on PEDro
score; of them, 13 were 1b Level of Evidence and two were 1c.

Conclusion: After elective surgeries, when the significant edema appears or persists beyond recovery
time, complex decongestive therapy and manual edema mobilization should be recommended in
addition to conventional physical therapy. In acute injuries such as ankle or distal radius fractures,
lymphatic treatments and compression bandaging should be considered as part of the therapeutic
protocol. Nine studies evaluated different compression modalities found that only multilayer and long
stretch compression significantly reduce edema.

Safety and effectiveness of early compression of free flaps following lower limb reconstruction: A systematic review

Juan Enrique Bernera,b, Patrick Willc,d, Luke Geoghegane, Luigi Troisif, Jagdeep Nanchahalg, Abhilash Jaine,h. Journal of Plastic, Reconstructive & Aesthetic Surgery (2020).

Summary Introduction: Early postoperative compression of free flaps for lower limb reconstruction remains controversial. It may reduce venous congestion and promote the resolution of oedema. However, concerns remain regarding inadvertent pedicle compression, which may lead to flap failure. The aim of this systematic review was to determine the safety and effectiveness of this intervention.

Methods: A systematic review was designed in compliance with PRISMA. MEDLINE and EMBASE databases were searched. Parallel screening, selection of eligible studies, and data gathering were carried out by two independent authors. A formal risk of bias assessment was included along with the appraisal of outcomes.

Results: A total of 847 abstracts were retrieved and 262 free flaps for lower limb reconstruction were identified in ten eligible articles. The overall flap failure rate for patients who underwent early postoperative compression was 1.6%. Apart from flap failure rates, there were no other outcomes consistently reported and none of the studies included a no-compression group for comparison.

Discussion: All included studies had methodological flaws, resulting in a high risk of bias. Nevertheless, there was consistent reporting of flap failure as a postoperative outcome. Compression of free flaps in the context of lower limb reconstruction does not appear to be associated with a higher flap failure rate compared with other series. Compression bandages may reduce the pain associated with dangling regimes. However, there is no evidence to support that free flap compression in the context of lower limb reconstruction is associated with any other clinical benefit

Manual lymphatic drainage treatment for lymphedema: a systematic review of the literature

Belinda Thompson1 & Katrina Gaitatzis1 & Xanne Janse de Jonge2 & Robbie Blackwell1 & Louise A. Koelmeyer 1. Journal of Cancer Survivorship. August 2020.

Purpose Manual lymphatic drainage (MLD) massage is widely accepted as a conservative treatment for lymphedema. This systematic review aims to examine the methodologies used in recent research and evaluate the effectiveness of MLD for those atrisk of or living with lymphedema.

Methods The electronic databases Embase, PubMed, CINAHL Complete and Cochrane Central Register of Controlled Trials were searched using relevant terms. Studies comparing MLD with another intervention or control in patients at-risk of or with lymphedema were included. Studies were critically appraised with the PEDro scale.

Results Seventeen studies with a total of 867 female and two male participants were included. Only studies examining breast cancer-related lymphedema were identified. Some studies reported positive effects of MLD on volume reduction, quality of life and symptom-related outcomes compared with other treatments, while other studies reported no additional benefit of MLD as a component of complex decongestive therapy. In patients at-risk, MLD was reported to reduce incidence of lymphedema in some studies, while others reported no such benefits.

Conclusions The reviewed articles reported conflicting findings and were often limited by methodological issues. This review highlights the need for further experimental studies on the effectiveness of MLD in lymphedema. Implications for Cancer Survivors There is some evidence that MLD in early stages following breast cancer surgery may help prevent progression to clinical lymphedema. MLD may also provide additional benefits in volume reduction for mild lymphedema. However, in moderate to severe lymphedema, MLD may not provide additional benefit when combined with complex decongestive therapy.

Successful treatment of solid persistent facial edema with isotretinoin and compression therapy

Haley D. Heibel, MD,a Mark D. Heibel, MD,b and Clay J. Cockerell, MD, MBAc,d, Brooklyn, New York; Lincoln, Nebraska; and Dallas, Texas. JAAD Case Reports August 2020.

Solid persistent facial edema is a rare and poorly understood condition that is difficult to treat and can
lead to significant cosmetic disfigurement, adversely affecting a patient’s self-esteem and mental health.1 It can be a serious complication of acne vulgaris and rosacea, but also may be associated with other congenital, infectious, malignant, and inflammatory processes.2 It has also been referred to as Morbihan’s disease (referring to the French district where it was first described in 1957) and rosaceous lymphedema.3-5. The pathogenesis of solid persistent facial edema and definitive treatment remain unclear. Theories have suggested that Morbihan’s disease is an end-stage complication of rosacea and acne.4 The recurrent occurrences of vascular dilation and inflammation may lead to chronic inflammatory changes, including damage and remodeling of the vascular and lymphatic vessels.4 Persistent edema results from impaired lymphatic drainage. However, Morbihan’s disease has occurred in patients without rosacea, or as a first symptom of rosacea.4 Therefore, it is possible that solid persistent facial edema may represent a separate disease entity. Herein, we describe a patient who presented with solid persistent facial edema and responded well to isotretinoin and compression therapy.