Lymphedema Research Articles

Transcriptional, developmental, and functional parallels of lymphatic and venous smooth muscle.

Lymphatic muscle cells (LMCs) are indispensable for lymphatic vessel contraction and their aberrant recruitment or absence is associated with both primary and secondary lymphedema. Despite their critical role in lymphatic vessel function, the transcriptomic and developmental basis that confer the unique contractile properties to LMCs are largely undefined. In this study, we employed single-cell RNA sequencing (scRNAseq), lineage tracing and in vivo imaging to investigate the basis for the hybrid cardiomyocyte and blood vascular smooth muscle cell (SMC) characteristics that have been described for LMCs. Using scRNAseq, the transcriptomes of LMC and venous SMCs from the murine hindlimb exhibited more similarities than differences, although both were markedly distinct from that of arteriole SMCs in the same tissue. Functionally, both lymphatic vessels and blood vessels in the murine hindlimb displayed pulsatile contractility. However, despite expressing genes that overlap with the venous SMC transcriptome, through lineage tracing we show that LMCs do not originate from Myh11+ SMC progenitors. Previous studies have shown that LMCs express cardiac-related genes, whereas in our study we found that arteriole SMCs, but not LMCs, expressed cardiac-related genes. Through lineage tracing, we demonstrate that a subpopulation of LMCs and SMCs originate from WT1+ mesodermal progenitors, which are known to give rise to SMCs. LMCs, however, do not derive from Nkx2.5+ cardiomyocyte progenitors. Overall, our findings suggest that venous SMCs and LMCs and may derive from a related mesodermal progenitor and adopt a similar gene expression program that enable their contractile properties.

Identification of Potential Factors Associated with Cellulitis Following Lymphovenous Bypass Surgery in Breast Cancer Survivors.

Breast cancer is one of the most common types of cancer, with around 2.3 million cases diagnosed in 2020. One in five cancer patients develops chronic lymphedema caused by multifactorial triggers and treatment-related factors. This can lead to swelling, skin infections, and limb dysfunction, negatively affecting the patient's quality of life. This retrospective cohort study aimed to determine the associations between demographic and breast cancer characteristics and postoperative cellulitis in breast cancer survivors who underwent lymphovenous bypass surgery (LVB) at Mayo Clinic, Florida. We performed a retrospective chart review. Data were collected retrospectively from 2016 to 2022. Sixty adult breast cancer survivors who underwent LVB were included in the final analysis based on specific inclusion and exclusion criteria. Patients were excluded if they did not meet the inclusion criteria or had incomplete follow-up data. Demographic and surgical data were extracted, including body mass index (BMI), type of anastomosis, number of anastomoses, and preoperative cellulitis status. Lymphedema measurements were performed using tape measurements. Fisher's exact test was used to determine statistically significant associations between variables and postoperative cellulitis. Postoperative cellulitis was more common in patients aged 60 to 69 years (43.2%), whites (75.0%), overweight or obese (90.9%), with one to four anastomoses (81.8%), and nonsmokers (79.5%). The mean International Society of Lymphology (ISL) criteria for both postoperative cellulitis and no postoperative cellulitis was 1.93. Statistically significant associations with postoperative cellulitis were found for the number of anastomoses (p = 0.021), smoking status (p = 0.049), preoperative cellulitis (p = 0.04), and the length of years with lymphedema diagnosis variable (p = 0.004). Our results suggest that a greater number of anastomoses, smoking, preoperative cellulitis, and years with lymphedema are significantly associated with an increased risk of postoperative cellulitis. Awareness of these risk factors is crucial for monitoring and early treatment of infections following surgery.

Vascular Endothelial Growth Factor C (VEGF-C) Sensitizes Lymphatic Endothelial Cells to Oxidative-Stress-Induced Apoptosis through DNA Damage and Mitochondrial Dysfunction: Implications for Lymphedema.

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.

Effect of Adding a Six-Week Course of Doxycycline to Intensive Hygiene-Based Care for Improving Lymphedema in a Rural Setting of Mali: A Double-Blind, Randomized Controlled 24-Month Trial.

Lymphedema (LE) is one the most disfiguring chronic manifestations of lymphatic filariasis. Its management relies primarily on limb hygiene and local care. A previous study in Ghana demonstrating a beneficial effect of doxycycline on LE led to the current multicenter trial on the efficacy of doxycycline in filarial LE. A randomized placebo-controlled trial was initiated in two rural health districts in Mali. Patients with LE stages 1-3 were randomized to receive either doxycycline (200 mg/day) or placebo over a 6-week monitored treatment period and were then followed every 6 months for 2 years. Both groups received materials for limb hygiene that was carried out daily for the entire 2-year study. The primary endpoint was lack of progression in LE stage at 24 months. One hundred patients were enrolled in each study arm. The baseline sociodemographic characteristics of each group were largely similar. There was no significant difference at month 24 after treatment initiation in the number of subjects showing progression in LE stage between the two treatment arms (P = 0.5921). Importantly, however, the number of attacks of acute adenolymphangitis (ADLA) was reduced in both arms, but there was no significant difference between the two groups at any follow-up time point (all P >0.23). Doxycycline was well tolerated in those receiving the drug. When added to daily self-administered limb hygiene, a 6-week course of doxycycline (200 mg) was not superior to placebo in increasing the improvement associated with hygiene alone in LE volume, stage, or frequency of ADLA attacks over a 24-month period.

Lymphedema: Current Strategies for Diagnostics and Management.

Lymphedema (LE) is characterized by the accumulation of lymph in the extremities, impairing functionality and quality of life. Despite its prevalence, accurate diagnoses and management remains complex because of inconsistencies in diagnostic criteria and limited epidemiological studies. This review aims to address this gap by providing a comprehensive overview of LE classifications, diagnostic approaches, and current management strategies. By synthesizing existing knowledge, this study seeks to contribute to a deeper understanding of LE for improvement of clinical consistency and education.

The impact of obesity on chronic oedema/lymphoedema of the leg – an international multicenter cross-sectional study (LIMPRINT)

Background/ObjectivesObesity and chronic oedema/lymphoedema are two distinct but related conditions, rarely investigated together. The aim was to study the impact of increased weight on chronic oedema and related factors.Subjects/MethodsA cross-sectional study, 38 centers, nine countries. Patients with clinically confirmed chronic oedema/lymphoedema of the leg were included. Weight category was estimated as: normal weight (BMI 20–30), class I-II obesity (BMI 30–40), or class III obesity (BMI > 40). Factors were tested for an association with increased weight, using a multivariable model.ResultsA total of 7397 patients were included; 43% with normal weight, 36% class I-II obesity and 21% class III obesity. Increased weight was associated with more advanced stages of chronic oedema (ISL stage III; the most advanced form); affecting 14% in normal weight, 18% class I-II obesity and 39% class III obesity (p < 0.001). Ten factors were independently associated with increased weight: diabetes (OR 2.4), secondary lymphoedema (OR 2.7), cellulitis/erysipelas within 12 months (OR 1.2), bilateral lymphoedema (OR 3.6), compression therapy (OR 2.1), increased swelling duration (1–2 years OR 1.3, 2–5 years OR 2.5, 5–10 years OR 3.6, >10 years OR 3.5) decreased mobility (walking with aid OR 1.9, being chair bound OR 1.2) and age (reference<45 years; 45–64 years OR 1.5, 75–84 years OR 0.6, 85+ years OR 0.2). Increased weight was associated with a lower presentation of peripheral arterial disease (OR 0.7) and poorer chronic oedema control (OR 0.8). Patients with obesity had lower function, appearance and more severe symptoms (LYMQOL) and lower quality of life (EuroQol).ConclusionsObesity negatively impacts chronic oedema, leading to more advanced stages. Achieving good control of swelling with compression is more difficult in these patients. Increased awareness of chronic oedema/lymphoedema as a complication of obesity is important for early detection and for developing effective strategies to prevent and manage them.

Polymorphism of angiogenesis regulation factor genes (VEGF/VEGFR), and extracellular matrix remodeling genes (MMP/TIMP), and the levels of their products in extracellular tissues of patients with primary and secondary lymphedema.

Cells of various organs and systems perform their functions and intercellular interactions not in an inert environment, but in the microenvironment of tissue fluids. Violations of the normal drainage of tissue fluids accompany lymphedema. An important mechanism of angiogenesis and vasculogenesis regulation in tissue fluids is the production and reception of vascular endothelial growth factors in combination with the regulation of matrix metalloproteinases. The aim of the work was to perform: a comparative analysis of some polymorphisms of vascular endothelial growth factor and their receptors and the genes encoding matrix metalloproteinases in two forms of lymphedema; an analysis of the relationship of these genes' polymorphisms with the levels of vascular endothelial growth factor and matrix metalloproteinases and their inhibitors in serum and affected tissues. Polymorphism of VEGF (rs699947, rs3025039), KDR (rs10020464, rs11133360), NRP2 (rs849530, rs849563, rs16837641), matrix metalloproteinases MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), Timp1 (rs6609533) and their combinations were analyzed by the Restriction Fragment Length Polymorphism method and TaqMan RT-PCR. The serum and tissue fluid levels were determined using the ELISA test system. Changes in the frequency distribution of MMP2 genotypes in primary and MMP3 in secondary lymphedema are shown. Significant frequency differences in NRP2 genotypes were revealed by comparing primary and secondary lymphedema. Features of the distribution of complex genotypes in primary and secondary lymphedema were revealed. The correlation analysis revealed the interdependence of the concentrations of the MMP, TIMP and VEGF products and differences in the structure of the correlation matrices of patients with both forms of lymphedema. It was shown that, in primary lymphedema, genotypes associated with low MMP2 and TIMP2 in serum and tissue fluid are detected, while in secondary lymphedema, other associations of the production levels with combined genetic traits are observed.

Comparison of the rate of concomitant proximal venous stenosis between the upper and lower extremities in patients with secondary lymphedema undergoing lymphaticovenous anastomosis

BackgroundConcomitant iatrogenic proximal venous stenosis increases venous pressure and can be a risk factor for unfavorable outcomes of lymphaticovenular anastomosis (LVA) in extremities with secondary lymphedema. This study investigated the frequency and relevant factors of venous stenosis in patients diagnosed with secondary lymphedema who underwent LVA. MethodsPatients who underwent preoperative computed tomographic venography (CTV) and LVA for secondary lymphedema of the extremities from October 2018 to March 2022 were included. The incidence of proximal venous stenosis in the affected limb on preoperative CTV and the rate of endovascular intervention were compared between upper and lower extremities. Factors affecting proximal venous stenosis were identified through multivariable analysis using independent variables, including patient age, body mass index, comorbidities, smoking history, radiation therapy, duration of lymphedema, and location of lymphedema. ResultsA total of 211 patients were analyzed, including 83 patients with upper extremity and 128 patients with lower extremity lymphedema. The incidence of proximal venous stenosis in the preoperative CTV was 32.5% and 7.8% in upper extremity, and lower extremity lymphedema, respectively (P < .001). The incidence of venous stenosis requiring endovascular intervention was significantly higher in the upper extremity compared with the lower extremity (16.9% vs 6.3%; P = .014). In multivariable analysis, risk factors affecting incidence of venous stenosis requiring endovascular intervention was the patient age (P = .007) and upper extremity (P = .009). ConclusionsPreoperative evaluation and treatment of venous stenosis in extremities with secondary lymphedema are necessary before LVA surgery, particularly in upper extremity lymphedema.

Primary Lymphovenous Anastomosis After Extended Soft Tissue Resection in the Medial Thigh for Reduction of Lymphocele and Lymphedema.

Postoperative chronic lymphocele and lymphedema represent severe burdens for soft tissue sarcoma patients who are already physically handicapped after an extensive surgery and a long recovery time. Incidences are high in the upper medial thigh. We have shifted our focus to lymphedema and lymphocele risk reduction with immediate lymphovenous anastomosis (LVA) after sarcoma resection. We performed immediate lymphatic reconstruction in 11 patients after soft tissue sarcoma resection in the upper medial thigh. The postoperative course was followed up closely, and postoperative occurrence of lymphocele and lymphedema was clinically assessed. A literature search outlining the latest clinical data, current treatment strategy landscape, and their application into clinical practice was added to the investigation. A total of 19 LVA and 2 lympho-lymphatic anastomoses were performed in 11 patients immediately after tumor resection in an end-to-end manner. We found a postoperative lymphedema rate of 36% and a postoperative lymphocele rate of 27%. Mean follow-up time was 17 months. Average tumor volume was 749 cc. Our literature search yielded 27 articles reporting on immediate LVA in cancer patients. Incidences of secondary lymphedema after LVA for lymphedema prevention vary between 0% and 31.1%. Lymphocele prevention with LVA is poorly studied in sarcoma patients. Immediate lymphatic reconstruction improved the overall postoperative course of our patients. The current literature does not serve with high-quality studies about primary LVA preventing lymphedema and lymphocele formation. We conclude that this technique should be seen as an additional concept to achieve overall better postoperative outcomes in these challenging surgical settings. We strongly recommend to either anastomose or ligate severed lymphatics under the microscope primarily after sarcoma resection in the upper medial thigh area.

Comparing complex decongestive therapy in patients with lymphedema of different causes by measuring: extremity volume, quality of life, and functionality.

This study aimed to investigate the effects of complex decongestive therapy (CDT) applied to the lower extremities of patients with lymphedema of different causes on the extremity volume, quality of life (QoL), and functionality. The study included 90 patients, of whom 28 had primary lymphedema, 30 had secondary lymphedema, 18 had phlebolymphedema, and 14 had lipolymphedema. A total of 137 extremities were treated with CDT. The patients who received CDT for 5 days a week for 3 weeks (15 sessions in total) were included in the sample. Extremity volume was measured using a tape measure. The lymphedema QoL-Leg Questionnaire was used to evaluate QoL, and the lower extremity functional scale (LEFS) was administered to assess lower extremity functionality. The changes in QoL before and after treatment significantly differed in the primary lymphedema, phlebolymphedema, and lipolymphedema groups (p < 0.05). The post-treatment LEFS scores indicated a significant decrease in the phlebolymphedema and lipolymphedema groups compared to the pre-treatment scores (p < 0.05). The difference in appearance, which is one of the sub-parameters of QoL, significantly decreased in the comparisons performed between the groups, whereas the changes in the remaining parameters were not significant.

An arabinogalactan isolated from Cynanchum atratum promotes lymphangiogenesis and lymphatic vessel remodeling to alleviate secondary lymphedema

Secondary lymphedema is a chronic and incurable disease lacking satisfactory therapeutic drugs. It primarily results from lymphatic vessel dysfunction resulting from factors such as tumor-related surgery, injury, or infection. Promoting lymphangiogenesis and lymphatic vessel remodeling is crucial for restoring tissue fluid drainage and treating secondary lymphedema. In this study, we discovered that the oral administration of a type-II arabinogalactan (CAPW-1, molecular weight: 64 kDa) significantly promoted lymphangiogenesis and alleviated edema in mice with secondary lymphedema. Notably, the tail diameter of the CAPW-1200 group considerably decreased in comparison to that of the lymphedema group, with an average diameter difference reaching 0.98 mm on day 14. CAPW-1 treatment also reduced the average thickness of the subcutaneous area in the CAPW-1200 group to 0.37 mm (compared with 0.73 mm in the lymphedema group). It also facilitated the return of injected indocyanine green (ICG) from the tail tip to the sciatic lymph nodes, indicating that CAPW-1 promoted lymphatic vessel remodeling at the injury site. In addition, CAPW-1 enhanced the proliferation and migration of lymphatic endothelial cells. This phenomenon was associated with the activation of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, thereby promoting the expression of vascular endothelial growth factor-C (VEGF-C), which can be abolished using a TLR4 antagonist. Despite these findings, CAPW-1 did not alleviate the symptoms of lymphedema or restore lymphatic drainage in VEGFR3flox/flox/Prox1-CreERT2 mice. In summary, CAPW-1 alleviates secondary lymphedema by promoting lymphangiogenesis and lymphatic vessel remodeling through the activation of the TLR4/NF-κB/VEGF-C signaling pathway, indicating its potential as a therapeutic lymphangiogenesis agent for patients with secondary lymphedema.

Potential therapeutic effect of a ketogenic diet for the treatment of lymphoedema: Results of an exploratory study.

Lymphoedema is a chronic and progressive disease characterised by excessive accumulation of lymph in the interstitial compartment, leading to tissue swelling and fibroadipose deposition. Lymphangiogenesis is partly regulated by ketone body oxidation, and a ketogenic diet (KD) has shown therapeutic efficacy in a preclinical mouse tail lymphoedema model. Therefore, we aimed to investigate the potential therapeutic effect of a KD in patients with secondary lymphoedema. Nine patients with unilateral stage 2 lymphoedema secondary to lymphadenectomy were included in this quasi-experimental exploratory study consisting of a short run-in phase to gradually induce ketosis, followed by a classic KD (CKD) and modified Atkins diet (MAD) phase during which patients consumed a CKD and MAD, respectively. Lymphatic function and oedema volume, the primary outcomes, were assessed at baseline and at the end of both the CKD and MAD phase. Secondary outcomes included health-related and lymphedema-specific quality of life (QoL). Seven out of nine patients completed the study protocol. Lymphatic function was improved upon consumption of both a CKD (dermal backflow score [mean ± SD]: 7.29 ± 2.98 vs. 10.86 ± 2.19 at baseline; p = 0.03) and MAD (6.71 ± 2.06; p = 0.02), whereas oedema volume did not decrease during the course of the study (excess limb volume [mean ± SD]: 20.13 ± 10.25% at end of CKD and 24.07 ± 17.77% at end of MAD vs. 20.79 ± 12.96% at baseline; p > 0.99 and p > 0.30, respectively). No changes were observed in health-related, nor lymphoedema-specific QoL at the end of CKD and MAD. The consumption of a KD improved lymphatic function and was associated with a clinically meaningful reduction in oedema volume in some patients (3/7 at end of CKD, 2/7 at end of MAD) with unilateral stage 2 secondary lymphoedema. These results highlight the potential of a KD to improve lymphatic function in patients with lymphoedema. However, further studies are required to substantiate our findings.

Characterization of Immune Cell Infiltration and Collagen Type III Disorganization in Human Secondary Lymphedema: A Case-control Study.

Secondary lymphedema (SL) affects 120 million people globally, posing a lifelong burden for up to 37% of cancer survivors. Chronic inflammation and progressive fibrosis are key drivers of SL, yet detailed characterization of immune cell subpopulations across lymphedema stages is lacking. This study aimed to investigate the immunologic profile of lymphedematous skin and its association with extracellular matrix changes, which could serve as clinical biomarkers or therapeutic targets. This case-control study analyzed the skin from 36 patients with and without SL, using immunofluorescence to quantify T cells, B cells, macrophages, and their subpopulations. Collagen quantity and composition were examined using picrosirius red staining, and mast cell infiltration was assessed with toluidine blue staining. Early and late SL stages were compared to identify histomorphological and immunologic correlates of stage progression. We found a predominance of CD4+ T cells and mast cells in SL skin (1.4/mm² versus 1.0/mm², P < 0.01; 1.2/mm² versus 0.2/mm², P < 0.0001) and a higher ratio of collagen III to collagen I fibers (51.6% versus 75.0%, P < 0.001). M2 macrophages were more abundant in late-stage than in early-stage lymphedema (1.7/mm² versus 1.0/mm², P = 0.02). This study demonstrated a shift toward CD4+ T cell and mast cell infiltration in SL skin, correlating with extracellular matrix disorganization and an altered collagen III/I ratio. These findings enhance our understanding of the cellular and morphological changes in SL, potentially guiding future diagnostic and therapeutic strategies.

Head and neck cancer survivors’ perception of lymphedema care.

e24046 Background: Secondary lymphedema and fibrosis occurs in more than 90% of HNC survivors. Given the progressive nature of lymphedema, prompt identification and treatment are essential. Treatment of HNC related lymphedema is fraught by numerous barriers. Advanced pneumatic compression devices (APCD) may address critical barriers. We conducted a phase 3 randomized multi-site trial in HNC survivors with treatment naïve lymphedema comparing usual care to APCD. Here in we report a qualitative analysis of participants treatment experience. Methods: Semi-structured interviews were audio recorded and transcribed after participants completed the 6th-month visit (N = 14 usual care, N = 23 APCD). Questions addressed treatment experience, perceptions of care, barriers, and facilitators. A hierarchical coding system was developed and refined using the interview guide and preliminary review of the transcripts. Transcripts were coded by experienced qualitative researchers. The coded transcripts were analyzed using an iterative inductive-deductive approach and based on our theoretical framework. Results: Participants were 65% male, 35% female and identified as 92% white, 5% black, and 5% Hispanic. The average age was 62 with a range of 32-82. We identified two distinct and one common set of barriers and facilitators. For usual care, health system (care coordination, logistics) and therapist factors (perceived skills and demeanor) were important while device characteristics (fit, comfort) were important for the APCD. Cognitive affective factors (self-efficacy, knowledge, outcome expectations, frustration) were similar for both therapies and interacted with the device/system characteristics. Conclusions: We identified distinct treatment barriers and facilitators for usual lymphedema care and treatment with APCD. Barriers identified in this study highlight practice changing opportunities to address system issues and develop interventions to enhance care and quality of life. Utilization of both treatment strategies may allow tailoring of treatments thus optimizing outcomes. Clinical trial information: NCT04797390 .

Timeframe for lymphedema therapy for head and neck cancer survivors.

e13535 Background: More than 90% of head and neck cancer (HNC) survivors experience secondary head and neck lymphedema. Prompt identification and treatment are essential given the progressive nature of lymphedema and potential complications. Usual care includes complete decongestive therapy performed by a lymphedema therapist followed by lifelong home self-care. The ability to participate in lymphedema therapy (LT) is deleteriously impacted by numerous barriers. We are conducting a phase 3 multisite randomized trial involving HNC survivors with treatment-naïve lymphedema which compares usual lymphedema care to the use of an advanced pneumatic compression device (APCD). For patients treated on the usual care arm, data pertaining to LT delivery was collected prospectively. Herein we report the preliminary analysis from this dataset. Methods: Eligible patients were age ≥18 years, had pathologically confirmed HNC, completed curative intent cancer therapy with no evidence of active cancer, were diagnosed with internal or external head and neck lymphedema with at least one core lymphedema associated symptom and had not previously received treatment for lymphedema. Participants were randomized to either usual care with complete decongestive therapy directed by a lymphedema therapist followed by home self-care or daily self-directed use of APCD. Anatomic measurements and patient reported outcome measures were obtained at 2-, 4- and 6-month endpoints. The intervention phase lasted 6 months and therapy records were received for analysis. Key outcome measures included the time from referral to LT evaluation consultation, time from LT evaluation to treatment session and time from referral to treatment session. Results: At the time of this analysis, 87 participants randomized to usual care arm were eligible for inclusion in this assessment. Of the 87 patients, we were unable to document completion of LT consultation or therapy for 39 patients. Among the 48 participants who were referred for LT and received therapy, 72% were male and 28% were female, with 91% identifying as white, 7% as black, and 2% as other. The average age was 62. The mean time from referral by a health care provider to initial lymphedema consultation was 19.6 (σ 18.1) days. Of note, there was a wide-ranging timeframe from referral to LT treatment, varying from 0 to 93 days. The mean time from consultation to treatment was 1.7 days (σ 5.1) and referral to treatment was 21.3 (σ 17.8). Conclusions: A key finding of this study is the high rate (45%) of those referred for LT were not documented to complete a therapy consultation or to receive therapy. Of those patients who receive therapy, consultation and treatment were delay significantly in a high percentage of patients. These finding highlight the need for additional investigation into barriers to timely implementation of LT for head and neck cancer survivors. Guidelines and standards of care should be developed to guide practitioners. Clinical trial information: NCT04797390 .

The Impact of Obesity on Success of Immediate Lymphatic Reconstruction for Prevention of Breast Cancer–Related Lymphedema

Background Breast cancer–related lymphedema (BRCL) is a potential sequela of high-risk breast cancer treatment. Preventive treatment with immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has emerged as the standard of care; however, there is relatively little known about factors that may contribute to procedural failure. Methods A retrospectively maintained, institutional review board–approved study followed patients who underwent ILR at the time of ALND at our tertiary care center between May 2018 and May 2023. Patients who presented for at least one follow-up visit in our multidisciplinary lymphedema clinic met the criteria for inclusion. Patients who developed lymphedema despite ILR and potential contributing factors were further explored. Results 349 patients underwent ILR at our institution between May 2018 and May 2023. 341 of these patients have presented for follow-up in our multidisciplinary lymphedema clinic. 32 (9.4%) patients developed lymphedema despite ILR. This cohort was significantly more likely to be obese (56% vs 35%, P = 0.04). Multivariate logistic regression demonstrates increased odds of procedural failure in patients with a body mass index (BMI) ≥30 kg/m2 (odds ratio 2.6 [1.2–5.5], P = 0.01). Conclusion These data comment upon our institutions outcomes following ILR. Patients who develop lymphedema despite ILR tend to have a higher BMI, with a significantly increased risk in patients with a BMI of 30 or greater. Consideration of these data is critical for preprocedural counseling and may support a BMI cutoff when considering candidacy for ILR going forward, as well as when optimizing failures for secondary lymphedema procedures.

Fatigue and sleep quality improvement through complete decongestive therapy in postmastectomy lymphedema: An investigative analysis

ObjectiveTo evaluate the effects of complete decongestive therapy (CDT) on cancer-related fatigue, sleep quality, and lymphedema-specific quality of life using validated and reliable questionnaires in cancer patients being commendable.Material and methodsThis prospective study includes 94 patients who had postmastectomy lymphedema syndrome. The demographic characteristics of the patients were recorded. The participants’ stages of lymphedema (The International Society of Lymphology), Hirai Cancer Fatigue Scale (HCFS) score, Pittsburgh Sleep Quality Index (PSQI) Global score, lymphedema-specific quality of life questionnaire (LYMQOL-ARM) score, and Global health status were recorded before and after CDT.ResultsThe mean age of the patients was 58.49 ± 10.96 years. Strong correlations were found between the severity of edema and global health status. There was a significant positive relationship between the HCFS score, PSQI Global score, LYMQOL-ARM score, and CDT. After decongestive physiotherapy, the majority of the lymphedema stages were downstaging (p < 0.05), respectively. There was also a trend toward improvement in general well-being (p < 0.05).ConclusionCancer-related fatigue and sleep disturbance can persist for years after surgery in women with breast cancer. This can negatively affect the patient physically, socially and cognitively. Our study, which is the first study to investigate the HCFS score in postmastectomy patients and the relationship between PSQI Global score and CDT. The findings identify the risk factors that affect these outcomes in women with lymphedema and can provide valuable insights for targeted interventions and improved patient care.

Effect of complex decongestive therapy on frailty and quality of life in women with breast cancer-related lymphedema: the before-and-after treatment study

ObjectiveTo investigate the impact of Complex Decongestive Therapy (CDT) on the severity of frailty and quality of life in individuals suffering from postmastectomy lymphedema syndrome.MethodsParticipants who met the inclusion criteria were informed about CDT and informed consent was obtained. Edmonton Frailty Scale (EFS), extremity volüme (EV), lymphedema stage(LS), EQ-5D General Quality of Life Scale (EQ-5D-5L), and Quick Disabilities of Arm, Shoulder, and Hand (DASH) scores were evaluated by the same physician before and after treatment. A total of 15 sessions of CDT were performed for 3 weeks, five days a week. During the treatment period, hospitalized patients received guidance from a nurse on protecting the affected arm in their daily routine.ResultsEighty patients with breast cancer-related lymphedema who met the inclusion criteria were included in the study. Following a period of 3 weeks of practice and training, the specialist physician conducted the final evaluation and assessments. All patients showed a statistically significant reduction in EV, and regression in LS, EFS, and Quick DASH score (p&amp;lt;0.001). Statistically significant improvement was also observed in quality of life and general health status. (p&amp;lt;0.001).ConclusionThe application of 15 sessions of CDT and educational interventions to women with postmastectomy lymphedema syndrome due to breast cancer yielded positive outcomes. This approach led to an enhancement in patients’ functional capacity, improving their quality of life and a subsequent reduction in the severity of frailty.

Current Aspects of Medical Rehabilitation of Patients with Cancer Related Lymphedema of Extremities: a Narrative Review

INTRODUCTION. Over the past decades, in developed countries and in the Russian Federation, there has been an increase in the number of patients with secondary lymphedema who have undergone surgical treatment with dissection of regional lymph nodes and radiation therapy for various forms of gynecological cancer in women and prostate cancer in men, as well as breast cancer. AIM. Search and analysis of the results of previously published randomized controlled trials (RCTs) of the effectiveness of various non-drug rehabilitation methods in patients with lymphedema of the extremities who underwent radical treatment for cancer of various locations. MATERIALS AND METHODS. A search was conducted and studied publications in international scientific peer-reviewed publications (PEDro Database) on medical rehabilitation for cancer treatment-related lymphedema (LSPR) for the period from 1996 to December 2023 using the keywords “lymphedema”, “rehabilitation”. 145 RCTs focused on medical rehabilitation and conservative treatment of LSPR. DISCUSSION. Lifestyle correction and psychosocial interventions are recommended to improve the quality of life of patients. Studies have found that early activation, various physical exercises with a slow increase in loads under the supervision of a physical therapist are safe and help increase endurance, strength and range of motion in a limb with lymphatic edema. The clinical effectiveness of therapeutic exercises in the pool has been proven, manifested in the reduction of edema in patients with LSPR. The effectiveness of compression products with Velcro technology as an alternative to rigid low-stretch bandages in patients with LSPR has been confirmed. The anti-edematous and anti-inflammatory effects of low-intensity laser therapy and magnetic therapy in the rehabilitation of patients with LSLR have been proven. Alternating pneumatic compression (APC) is recommended as an adjuvant treatment in addition to comprehensive decongestant therapy. Preference should be given to the use of technologies of advanced hardware lymphatic drainage methods that imitate manual techniques. CONCLUSION. To improve the physical and socio-psychological functioning of patients with LSPR, an integrated approach is required, including lifestyle changes, psychological correction, compression therapy, modern exercise therapy techniques, and safe physiotherapeutic technologies. Conducted scientific research indicates the high effectiveness of the use of manual and hardware lymphatic drainage techniques, while the use of PPC is more economical and accessible, and does not require the involvement of specialists who know the expensive method of manual lymphatic drainage.

Exercise Therapy in Oncology.

The diagnosis and treatment of cancer are highly stressful. Exercise therapy is often used to mitigate the adverse effects of treatment. But how good is the evidence base, and what has changed in recent years? In this narrative review, we present the current data and what it implies for the care of adults with cancer. This review is based on data from meta-analyses and systematic reviews concerning 16 relevant clinical endpoints (outcomes) of exercise therapy for cancer patients. The literature evaluated for this paper reveals that targeted exercise therapy is feasible and safe under appropriate supervision. It is highly effective for improving eight endpoints (anxiety, depression, fatigue, quality of life, physical function, secondary lymphedema after breast cancer, urinary incontinence, post-mastectomy pain syndrome in breast cancer) and may also have a beneficial effect on sleep quality, cardiotoxicity, and cognitive function. Less conclusive studies are currently available with respect to chemotherapy-induced polyneuropathy, nausea/vomiting, and bone health. There is currently insufficient data to suggest any benefit with respect to sexual function and risk factors for falling. The data shows that exercise therapy for cancer patients is safe and has manifold effects on selected clinically relevant parameters. Further studies should be performed regarding the possible utility of exercise therapy against treatment-related side effects for which the evidence is currently insufficient. On the basis of the currently available and already existing recommendations, quality-assured exercise therapy can be recommended to cancer patients suffering from a wide range of neoplastic conditions.