Hot off the Press May 2024

We have collated some great articles and material published over the last month. Click on the links below to read the  abstract or download the full paper.

Anatomy / Physiology /Pathophysiology

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention

Catharine Bowman, Stanley G. Rockson. Int J Mol Sci. 2024 Mar 31.

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Lower Limb Lymphedema Awareness among Gynecological Cancer Patients: An International Survey Supported by the European Network of Gynecological Cancer Advocacy Groups (ENGAGe) Group

Dimitrios Haidopoulos, Vasilios Pergialiotis, Maria Papageorgiou, Michael J. Halaska, Katerina Maxova, Elena Ulrich, Ignacio Zapardiel, Alexandros Rodolakis, Murat Gultekin, Christina Fotopoulou Cancers (Basel). 2024 Apr 18

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Pathogenic variants in HGF give rise to childhood-to-late onset primary lymphoedema by loss of function - click for abstract

Pathogenic variants in HGF give rise to childhood-to-late onset primary lymphoedema by loss of function

Murat Alpaslan, Elodie Fastré, Sandrine Mestre, Arie van Haeringen, Gabriela M. Repetto, Kathelijn Keymolen, Laurence M. Boon, Florence Belva, Guido Giacalone, Nicole Revencu, Yves Sznajer, Katie Riches, Vaughan L. Keeley, Sahar Mansour, Kristiana Gordon, Silvia Martin-Almedina, Sara Dobbins, Pia Ostergaard, Isabelle Quere, Pascal Brouillard, Miikka Vikkula. Hum Mol Genet. 2024 Apr 26.

Developmental and functional defects in the lymphatic system are responsible for primary lymphoedema (PL). PL is a chronic debilitating disease caused by increased accumulation of interstitial fluid, predisposing to inflammation, infections and fibrosis. There is no cure, only symptomatic treatment is available. Thirty-two genes or loci have been linked to PL, and another 22 are suggested, including Hepatocyte Growth Factor (HGF). We searched for HGF variants in 770 index patients from the Brussels PL cohort. We identified ten variants predicted to cause HGF loss-of-function (six nonsense, two frameshifts, and two splice-site changes; 1.3% of our cohort), and 14 missense variants predicted to be pathogenic in 17 families (2.21%). We studied co-segregation within families, mRNA stability for non-sense variants, and in vitro functional effects of the missense variants. Analyses of the mRNA of patient cells revealed degradation of the nonsense mutant allele. Reduced protein secretion was detected for nine of the 14 missense variants expressed in COS-7 cells. Stimulation of lymphatic endothelial cells with these 14 HGF variant proteins resulted in decreased activation of the downstream targets AKT and ERK1/2 for three of them. Clinically, HGF-associated PL was diverse, but predominantly bilateral in the lower limbs with onset varying from early childhood to adulthood. Finally, aggregation study in a second independent cohort underscored that rare likely pathogenic variants in HGF explain about 2% of PL. Therefore, HGF signalling seems crucial for lymphatic development and/or maintenance in human beings and HGF should be included in diagnostic genetic screens for PL.:10.1093/hmg/ddae060

Prevalence and Risk Factors

The Impact of Sleep on the Lives of Women Who Have Breast Cancer-Related Lymphedema: A Qualitative Exploration - click for abstract

The Impact of Sleep on the Lives of Women Who Have Breast Cancer-Related Lymphedema: A Qualitative Exploration

Karen Bock, Kristen Kelly, Delainey R. Pospichal, Catherine F. Siengsukon, Jill Peltzer. Lymphat Res Biol. 2024 Apr 22.

Background: Breast cancer survivors (BCSs) have many lifelong symptoms of anxiety, depression, lymphedema, and fatigue that can be exacerbated by sleep disturbance. However, little is known about unique factors contributing to sleep disturbance among BCSs with lymphedema; this requires further investigation to offer appropriate support and treatment to these individuals. Therefore, the objective of this study was to capture perceptions and experiences of lymphedema and sleep among BCSs with lymphedema.

Methods and Results: Qualitative description guided data collection and analysis as part of a mixed- methods investigation to characterize sleep disturbance among BCSs with and without lymphedema. The participants were interviewed one-on-one using a semistructured interview guide. Inductive content analysis was completed using an iterative coding approach, condensing, and categorizing to develop four themes. Seven BCSs with lymphedema participated. From their narratives, four themes were developed: (1) mind and body fatigue are exacerbated by sleep disturbance; (2) fatigue impacted fragile coping and support systems; (3) fatigue influenced self-identity and roles in society; and (4) self-management strategies were used for sleep health.

Conclusion: The participants’ perceptions of sleep disturbances’ impact on their lives endorse further investigation into optimal interventions to improve sleep quality and modify these impactful findings to create a higher quality of life for survivorship.:10.1089.0034

Factors Influencing the Self-management of Breast Cancer-Related Lymphedema: A Meta-synthesis of Qualitative Studies - click for abstract

Factors Influencing the Self-management of Breast Cancer-Related Lymphedema: A Meta-synthesis of Qualitative Studies

Ying Wang, Tingting Wei, Miaomiao Li, Peipei Wu, Wanmin Qiang, Xian Wang, Aomei Shen. Cancer Nurs. 2024 May 5.

BACKGROUND: Patients with breast cancer have an estimated 14% to 60% risk of developing lymphedema after treatment. Self-management behavior strategies regarding lymphedema are essential in preventing and alleviating the severity of lymphedema.
OBJECTIVE: The aim of this study was to evaluate qualitative research evidence on the potential influencing factors for self-management behaviors of lymphedema in patients with breast cancer.
METHODS: A systematic search of 10 electronic databases was conducted to identify qualitative studies on patient experience of lymphedema self-management. The following databases were included and appraised using the Joanna Briggs Institute Critical Appraisal Checklist: Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Med Online, and Chinese Biomedical Database. RESULTS: The literature search yielded 5313 studies, of which only 22 qualitative studies fulfilled the eligibility criteria. Five synthesized findings were derived encompassing personal characteristics, personal knowledge and experience, personal health beliefs, self-regulation skills and abilities, and social influences and support.
CONCLUSIONS: Patients with breast cancer are confronted with many challenges when performing self-management of lymphedema. Therefore, it is important to recognize potential facilitators and barriers to further offer practical recommendations that promote self-management activities for lymphedema.
IMPLICATIONS FOR PRACTICE: Healthcare professionals should receive consistent training on lymphedema management. On the basis of individual patient characteristics, tailored education and support should be provided, including transforming irrational beliefs, and improving related knowledge and skills, with the aim to promote self-management behaviors with respect to lymphedema.:10.1097

Time trend of breast cancer-related lymphedema according to body mass index - click for abstract

Time trend of breast cancer-related lymphedema according to body mass index

Ogiya, Akiko ; Kimura, Kiyomi ; Ueno, Takayuki ; Iwase, Takuji ; Ohno, Shinji. European journal of surgical oncology, 2024-06, Vol.50 (6), p.108350-108350, Article 108350.


To clarify how body mass index (BMI) affects the development and temporal trend of breast cancer-related lymphedema (BCRL).


This is a prospective study in which patients with operable breast cancer were registered in a single institute between November 2009 and July 2010. The incidence of lymphedema at 1, 3, and 5 years after surgery was assessed according to BMI, and the trend of newly developed BCRL was examined. Obesity was defined as BMI ≥25 in accordance with the Japan Society for the Study of Obesity.


A total of 368 patients were included in this study. The multivariate analysis of the whole population showed that high BMI, axillary dissection, and radiotherapy remained as risk factors for BCRL. Patients with high BMI showed a significantly higher incidence of new lymphedema than those with low BMI at 1 year (p < 00.001) regardless of axillary procedures (39.1 % vs 16.3 % for axillary dissection; 15.6 % vs 1.5 % for sentinel lymph node biopsy) but not at 3 and 5 years. Once BCRL developed, patients with high BMI showed slow recovery and 50.0 % of the patients retained edema at 5 years while patients with low BMI showed rapid recovery and 26.7 % retained after 3 years (p = 0.04).


The preoperative BMI affected the incidence and temporal trend of BCRL regardless of axillary procedures or radiotherapy. Patients with high BMI should be given appropriate information about BCRL before surgery with careful follow-up for BCRL after treatment.


Development of New Predictive Equations for the Resting Metabolic Rate (RMR) of Women with Lipedema

Małgorzata Jeziorek, Jakub Wronowicz, Łucja Janek, Krzysztof Kujawa, Andrzej Szuba. Metabolites. 2024 Apr 19

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Limb Volume Measurements: A Comparison of Circumferential Techniques and Optoelectronic Systems against Water Displacement

Farina, Giovanni ; Galli, Manuela ; Borsari, Leonardo ; Aliverti, Andrea ; Paraskevopoulos, Ioannis Th ; LoMauro, Antonella. Bioengineering (Basel), 2024-04, Vol.11 (4), p.382

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Lower limb lymphedema disrupts both static and dynamic balance - click for abstract

Lower limb lymphedema disrupts both static and dynamic balance

Karasimav, Özlem ; Borman, Pınar ; Dalyan, Meltem ; Yalçin, Elif ; Eliuz, Zahide Betül ; Poyraz, İpek ; Türk, Seren. Clinical biomechanics (Bristol), 2024-04, Vol.115, p.106241-106241

Background: The impact of lower-limb-lymphedema on quality of life of patients regarding balance is unclear due to the scarcity of literature. The aim of this study was to determine the static and dynamic balance of patients with lower-limb-lymphedema in comparison with healthy subjects.
Methods: This case-control designed study included 30 lymphedema patients and 30 healthy individuals, of whom were 52 female and 8 male with a mean age of 50.63 ± 9.72 years. Static balance stability and anterior- posterior with lateral sway parameters on four conditions (eyes-opened-stable-ground, eyes-closed-stable- ground, eyes-opened-unstable-ground, eyes-closed-unstable-ground) and dynamic stability of all participants were evaluated.
Findings: The demographic variables were similar between the groups. Majority of the patients had lymphedema due to cancer surgery with a stage of 2. Dynamic stability was significantly disrupted in lymphedema group in comparison with controls (P = 0.049). Static balance parameters were impaired on all conditions except the eyes opened-stable ground in lymphedema patients (P = 0.048,P = 0.043,P = 0.017). The dynamic with static balance and lateral sway parameters were correlated with the duration of lymphedema(P = 0.046,P = 0.002,P = 0.005). Anterior-posterior sway on eyes-closed-unstable-ground condition was correlated with functional status (P = 0.02). Static balance on eyes-opened-unstable-ground condition and anterior-posterior sway parameters were correlated with physical activity level (P = 0.015,P = 0.016,P < 0.05). I
nterpretation: Closing eyes and the deterioration of ground caused significant alteration of the static and dynamic balance both separately and together in patients with lower-limb-lymphedema compared to healthy subjects. Regarding the static and dynamic imbalance, we suggest the evaluation of balance and inclusion of balance exercises in routine lymphedema rehabilitation program, especially in the early period of disease.

Management Strategies

The Effect of Exercise on Reducing Lymphedema Severity in Breast Cancer Survivors

Yanxue Lian, Simran Sandhu, Yamikani Asefa, Ananya Gupta. Cancers (Basel). 2024 Mar 30.

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Surgical Treatment for Primary Lymphedema: A Systematic Review of the Literature

Miguel Angel Gaxiola-García, Joseph M. Escandón, Oscar J. Manrique, Kristin A. Skinner, Beatriz Hatsue Kushida-Contreras. Arch Plast Surg. 2024 Apr 8. Mar.

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Longitudinal Assessment of Health-Related Quality of Life and Clinical Outcomes with At Home Advanced Pneumatic Compression Treatment of Lower Extremity Lymphedema

Frank T. Padberg, Areck Ucuzian, Hasan Dosluoglu, Glenn Jacobowitz, Thomas F. O’Donnell. J Vasc Surg Venous Lymphat Disord. 2024 Apr 16

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Lymphoedema specialists embedded into community nurse and wound services: impacts and outcomes - click for abstract

Lymphoedema specialists embedded into community nurse and wound services: impacts and outcomes

Melanie J. Thomas, Karen Morgan, Ioan Humphreys. Br J Nurs. 2024 Apr 18.

BACKGROUND: Lymphoedema is a progressive condition causing significant alterations to life, exerting pressures on unscheduled care from complications including cellulitis and wounds. An on the ground education programme (OGEP) was implemented to raise knowledge, competence and confidence in lymphoedema management in community clinical services. The aim of this study was to explore the impact and outcomes of the OGEP intervention. METHODS: Data were captured before and after OGEP on 561 lymphoedema patients in the community setting. Data recorded included resource use, costs and outcomes (EQ-5D-5L and LYMPROM). RESULTS: Data demonstrated statistically significant reductions in resource allocations including staff visits (P<..001), cellulitis admissions (P<..001), compression consumables and wound dressing costs (P<..001). Overall, the total mean per patient cost decreased from £1457.10 to £964.40 (including intervention) with outcomes significantly improved in EQ-5D-5L/LYMPROM scores. CONCLUSION: The analysis suggests the OGEP intervention may offer reductions in resource costs and improvements in patient outcomes. OGEP may therefore provide an innovative solution in future care delivery.:10.12968.33.8.360

Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial- click for abstract

Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial

Lundanes, Julianne ; Sandnes, Frida ; Gjeilo, Kari Hanne ; Hansson, Patrik ; Salater, Sissel ; Martins, Catia ; Nymo, Siren.  Obesity (Silver Spring, Md.), 2024-04.

Objective: The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis.

Methods: Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention.

Results: A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m2) were included. The LCD group had greater weight loss (-2.8 kg; 95% CI: -4.1 to -1.0; p < 0.001) and larger reduction in pain now (-1.1; 95% CI: -1.9 to -0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions. Conclusions: Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain.

Assessing the Influence of Unstable Footwear on Lower Limb Lymphedema: A Comparative Clinical Trial l- click for abstract

Assessing the Influence of Unstable Footwear on Lower Limb Lymphedema: A Comparative Clinical Trial

Robledo-Donascimento, Yolanda PhD; López-Mesa, Mario Manuel; Rubio-Alonso, Margarita; Varela-Donoso, Enrique; Abuín-Porras, Vanesa PhD; Romero-Morales, Carlos PhD; de-la-Cueva-Reguera, Mónica; Villafañe, Jorge Hugo PhD. Topics in Geriatric Rehabilitation 40(2):p 158-164, April/June 2024.


Unstable shoes may benefit lower limb lymphedema patients by reducing foot volume and relieving symptoms.


The objective of this study was to evaluate and compare the effectiveness of unstable shoes versus conventional sports shoes in managing lower limb lymphedema, focusing on changes in foot volume, circumference, and symptom relief.


We conducted an 8-week clinical trial, recruiting patients with lower limb lymphedema. Participants were divided into 2 groups: one using unstable shoes and the other using conventional sports shoes. Measurements of foot volume and circumference were taken at the beginning and end of the trial. Additionally, participants were asked to report any changes in leg cramps and paraesthesia during the study period.


The results indicated a nonstatistically significant tendency toward a decrease in foot volume and circumference in the intervention group using unstable shoes. In contrast, the control group using conventional sports shoes showed a tendency toward an increase in foot volume and a statistically significant increase in foot circumference. Moreover, participants in the unstable shoes group reported a decrease in leg cramps and paraesthesia, indicating potential symptom relief.


This study suggests that unstable shoes have the potential to offer benefits to individuals with lower limb lymphedema, particularly in terms of foot volume reduction and symptom relief. The use of unstable shoes may be suitable for activities such as walking and extended periods of standing. However, further research is necessary to explore their full potential and effectiveness in managing lymphedema symptoms comprehensively.

Comparison of intermittent pneumatic compression pump as adjunct to decongestive lymphatic therapy against decongestive therapy alone for upper limb lymphedema after breast cancer surgery: A systematic review and meta-analysis - click for abstract

Comparison of intermittent pneumatic compression pump as adjunct to decongestive lymphatic therapy against decongestive therapy alone for upper limb lymphedema after breast cancer surgery: A systematic review and meta-analysis

Background: Breast cancer is among the most prevalent malignancies in women worldwide, with substantial morbidity and mortality. Upper limb lymphedema (ULL) is a common complication after breast cancer surgery that affects patients’ daily activities and quality of life. Decongestive lymphatic therapy (DLT) and intermittent pneumatic compression (IPC) therapy are two primary treatment methods for ULL.
Objectives: This study aims to compare the efficacy of DLT with IPC versus DLT alone in the management of ULL following breast cancer surgery.
Method: PubMed Central, SCOPUS, EMBASE, MEDLINE, Cochrane trial registry, Google Scholar, and databases were comprehensively searched for randomized controlled trials (RCTs) comparing DLT with IPC and DLT alone in patients with breast cancer-related ULL. Risk of bias was evaluated using the RoB 2 tool. Pooled effect sizes were calculated using random-effects models.
Results: A total of 1894 citations were identified by the systematic search. Of them, 9 RCTs were included in the analysis. The pooled SMD for percentage volume reduction was 0.63 (95%CI: -0.24 to 1.50; I2=90.9%), showing no significant difference between the DLT alone and DLT combined with IPC (p=0.15). Pain and heaviness scores were also comparable between the groups. However, there was a significant difference in external rotation joint mobility (SMD=0.62; 95%CI: 0.08-1.16; I2=23.8%), favouring DLT with IPC.
Conclusions: Our findings suggest that DLT with IPC and DLT alone showed similar findings in managing ULL after breast cancer surgery, with DLT with IPC showing a greater impact on external rotation joint mobility. Healthcare providers should consider patient preferences and individual factors when selecting the most appropriate treatment modality for ULL management.

Effect of kinesiology taping on breast cancer-related lymphedema: A systematic review and meta-analysis of randomized controlled trials- click for abstract

Effect of kinesiology taping on breast cancer-related lymphedema: A systematic review and meta-analysis of randomized controlled trials

Smykla A; Walewicz K; Trybulski R; Halski T; Kucharzewski M; Kucio C; Mikusek W; Klakla K; Taradaj J, BioMed research international [Biomed Res Int], ISSN: 2314-6141, 2013; Vol. 2013, pp. 767106; Publisher: Hindawi Pub. Co; PMID: 24377096


The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema.


We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort.


Information was extracted from 14 randomized controlled trials. The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (SMD = −0.88, 95% CI: [−1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]).


The findings suggest that kinesiology taping could be considered as a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed randomized controlled trials.