Elephantiasis Nostras Verrucosa in a Patient With Lymphedema Tarda.

This case report presents a rare and complex clinical scenario of a 42-year-old male diagnosed with elephantiasis nostras verrucosa in the context of lymphedema tarda. The patient's seven-year history of insidious and progressively worsening swelling over the left lower limb, inguino-scrotal region, and left upper limb posed diagnostic challenges, leading to a multidisciplinary evaluation. Clinical examination, imaging studies, and laboratory investigations were integral in confirming the diagnosis. The manifestation of elephantiasis nostras verrucosa, characterized by extensive hyperkeratosis, added a unique dimension to the clinical presentation. A comprehensive treatment approach involving nutritional supplementation and pharmacological interventions was initiated to address the multifaceted aspects of lymphatic dysfunction. This case underscores the importance of a collaborative and holistic approach to managing complex lymphatic disorders, contributing valuable insights to the medical literature.

Characteristic Single Photon Emission Computed Tomography-Computed Tomography Findings in Lower Extremity Lymphedema: Comparison to Indocyanine Green Lymphography.

Introduction: Evaluation of lymph circulation is significant in lower extremity lymphedema (LEL) management. Single-photon emission computed tomography-computed tomography (SPECT-CT) has been introduced for lymphedema evaluation, but its characteristic findings are yet fully clarified. The purpose of this study was to reveal typical SPECT-CT findings in secondary LEL by contrasting with indocyanine green (ICG) lymphography findings. Methods: This is a single-center retrospective case-control study. Medical charts of cancer survivors who underwent SPECT-CT and ICG lymphography for secondary LEL were reviewed. Lymphedematous limbs were defined as ICG lymphography stage I-V and non-lymphedematous limbs were defined as ICG lymphography stage 0. Characteristic SPECT-CT findings were identified in early phase and delay phase, and prevalence of the findings was compared between lymphedematous limbs and non-lymphedematous limbs. Results: Thirty-four limbs of 17 patients were included in this study; 6 (17.6%) non-lymphedematous limbs and 28 (82.4%) lymphedematous limbs. Four characteristic SPECT-CT findings were identified; delayed enhancement of the main lower leg lymphatic pathway (DML), few delayed inguinal lymph nodes enhancement (FDN), early phase discontinuous enhancement of the main lymphatic pathway (EDM), and nonenhancement of the deep lymphatic pathways in early phase (NDE). Between lymphedematous and non-lymphedematous limbs, there were statistically significant differences in FDN (64.3% vs. 0%, p = 0.004) and EDM (67.9% vs. 0%, p = 0.002). Conclusions: FDN and EDM are characteristic SPECT-CT findings in secondary LEL.

Arm lymphedema after vascularized lymph node harvest following Covid-19 vaccination.

There is evidence that COVID-19 vaccines may affect the lymphatic system. We report a case of a 40-year-old female who had undergone lymph node transfer for treating primary lymphedema of the legs. Six months later, the patient developed lymphedema of the right arm closely related to mRNA vaccination against COVID-19.

Positive Impact of a New Compressive Garment in Patients with Genital Lymphedema: OLYMPY Study.

Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multicenter study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: Thirty-two patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (visual analog scale, Lymphedema Quality of Life Inventory [LyQLI], and EQ-5D questionnaires), lymphedema severity (genital lymphedema score [GLS]), and physician assessment (Clinical Global Impression-Improvement [CGI-I]). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort (p = 0.02) and swelling (p = 0.01). Significant declines in the mean global GLS (p < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling, or urinary dysfunction (p < 0.05 for all), were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial (p = 0.05), and practical domains. The compressive garment was well tolerated with high compliance, and adverse events (due to swelling or discomfort) led to permanent discontinuation in only three patients. Conclusion: The use of a new genital compression garment over 12 weeks improves the QoL and clinical measures in patients with genital lymphedema (ClinicalTrials.gov ID: NCT04602559; Registration: October 20, 2020).

Time-Dependent Changes of Extremity Volume and Tissue Alterations in Swollen Arms Caused by Taxanes.

Background: We aimed to determine the course of arm swelling caused by the use of taxanes and to identify valid predictors of persistent swelling. Methods and Results: A total of 15 patients with unilateral arm swelling that developed during the course, or within 3 months after termination, of postoperative taxane-based chemotherapy were included in the present study. The patients attended follow-up appointments every 3-6 months for 24 months after their initial visit. Their arm circumference was measured at each follow-up appointment, while ultrasonography of the skin and subcutaneous tissues was performed at the 0-, 6-, 12-, and 24-month follow-ups. Of the 15 patients, 12 (80%) saw their taxane-induced arm swelling resolved within a median of 12 months (range, 3-29 months) after their final taxane administration. Of the 12 patients whose swelling resolved, 9 did not use compression sleeves; however, their course of resolution did not differ from the other 3 patients who regularly used compression sleeves. In the three patients with persistent swelling, the excess subcutaneous thickness in the medial upper arm (median, 283%) was significantly greater than that in the patients whose swelling resolved (120%; p < 0.05) during their initial visits. Conclusions: Of the 15 patients included in the present study, 80% saw their taxane-induced arm swelling resolve within a median of 12 months after their final taxane administration, independent of the use of compression therapy. Persistent swelling may be predicted during the initial visit based on subcutaneous thickening of the medial upper arm.

High Pressure 3 × 30 Minute Compression Methods for Advanced Lower Limb Lymphedema Patients.

Introduction: In advanced lymphedema of lower limbs, stage III bandaging under the routinely applied pressure of 40-60 mmHg remains largely ineffective. This is caused by skin and subcutaneous tissue stiffness due to fibrosis. Edema fluid accumulates deep in the subcutaneous tissue. Evacuating this fluid requires a high external compression force to overcome the resistance of fibrous tissue. We aimed to investigate the effectiveness of the compression method, with high pressure lasting for 3 days. Methods and Results: Twenty-one patients with lower limb lymphedema, stage III, of the postinflammatory type were included. Patients with acute inflammatory symptoms, venous thrombosis, profuse varicose veins, diabetes, and cardiac insufficiency with edema were excluded. A 10-cm-wide rubber bandage was applied to the foot and calf. The interface pressure measured using PicoPress ranged from 58 to 120 mmHg. Skin and deep tissue tonometry, skin water concentration, leg circumference, and drop of interface pressure were measured. Ultrasound examination was done before and after each compression session. The calf circumference decreased by 15.9 ± 5.4%, deep tissue stiffness by 58.9 ± 18.9%, skin stiffness by 69.6 ± 13.5%, and skin water concentration by 43.8 ± 11.5%. Interface pressure dropped to 66.3 mmHg (28-110 mmHg); ultrasonography images showed less fluid in the tissue. Conclusions: High-pressure 30-minute leg compression can remove excess edema fluid within 3 days and enable adjustment of nonstretch compression stockings. This method is more effective in advanced lymphedema at the beginning of therapy than the standard 30-50-mmHg bandaging as it provides an immediate effect.

Sensitivity of Each Index of Doppler, Cross, Uncollapsible, Parallel, and Superficial Fascia in Lymphatic Ultrasound.

Background: Recently, the usefulness of lymphatic ultrasound has been reported. It is beneficial not only to identify lymphatic vessels but also to evaluate lymphatic degeneration and diagnose lymphedema. We previously proposed D-CUPS (Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia) to identify the lymphatic vessels on ultrasound. The purpose of this study was to clarify the sensitivity of each index of D-CUPS. Methods: We performed a retrospective study of 27 patients (44 limbs, 98 sites) with lower extremity lymphedema, who underwent lymphaticovenous anastomosis (LVA). We performed a lymphatic ultrasound the day before surgery. We used a linear probe commonly used for venous ultrasound (Noblus EUP-L65; Hitachi Medical Corp., Tokyo, Japan). We applied the D-CUPS index to identify the lymphatic vessels on ultrasound. We checked whether lymphatic vessels consistent with preoperative lymphatic ultrasound findings were observed during the LVA. We also calculated the sensitivity of each D-CUPS index. Results: All the 27 patients were women, with a mean age of 59.7 years. Totally, 98 incisions were made (59 incisions on the thigh and 39 incisions on the lower leg). During LVA, lymphatic vessels consistent with the preoperative lymphatic ultrasound findings were observed at all the sites. The sensitivities of each indicator of D-CUPS were 100.0%, 100.0%, 68.4%, 19.4%, and 100.0%, respectively. Conclusion: The sensitivity was 100.0% in D, C, and S. Although each index separately was not perfect, by combining them appropriately, we were able to identify lymphatic vessels with certainty.

Short-Term Effects Of Dry Heat Treatment (Fluidotherapy) In The Management Of Breast Cancer Related Lymphedema: A Randomized Controlled Study.

BACKGROUND: To investigate whether fluidotherapy added to complete decongestive therapy (CDT) would provide additional contribution to edema reduction in patients with breast cancer related lymphedema (BCRL). MATERIAL AND METHODS: Thirthy-two patients with unilateral BCRL were randomly divided into 2 groups: standard treatment with CDT only (Group 1) and CDT + fluidotherapy (Group 2). All patients underwent phase 1 CDT, which included manual lymphatic drainage, multilayer bandaging, supervised exercises and skin care for a total of 15 sessions, 5 times a week for 3 weeks. Only Group 2 received a total of 15 sessions application of fluidotherapy. Before and after CDT, patients were evaluated for extremity volumes and excess volumes, according to circumferencial measurements of the extremity. Arm pain was evaluated with Visual Analaogue Scale (VAS-Pain). RESULTS: Seventeen patients in Group 1 and 15 patients in Group 2 completed the study. Patients' demographic data and volume measurements were similar at the beginning of the treatment. Limb volumes of both groups were significantly reduced after treatment (P < .001 for both group). Pain significantly decreased (P = .001 for both group). No adverse reactions were recorded. The mean change in volume measurements and VAS-Pain scores of patients in CDT+fluidotherapy group before and after treatment were significantly higher than those in only CDT group (P = .028, P = .020 respectively). CONCLUSION: Fluidotherapy added to CDT reduced pain and edema severity more than standard CDT in the patients with BCRL. As a noninvasive, novel, and effective method, fluidotherapy may be a promising treatment modality for the treatment of lymphedema.

Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation.

Objective: The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. Materials and Methods: This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Results: Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. Conclusion: In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion.

Comparison of Volume Measurements and Bioimpedance Spectroscopy Using A Stand-on Device for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer related lymphedema (BCRL) may be assessed through objective measurement of limb swelling with common techniques including volumetric measurement using a tape measure or perometry, and measurement of extracellular water using bioimpedance spectroscopy (BIS). This study aimed to evaluate the performance of a stand-on BIS device for detection of BCRL, introduce a novel graphical method to compare volumetric and BIS methods alongside traditional specificity and sensitivity analysis, and determine and compare BIS thresholds with those published previously. Materials and Methods: Female participants with indocyanine green lymphography confirmed unilateral arm lymphedema (n = 197) and healthy controls (n = 267) were assessed using a cross-sectional study design. BIS and volumetric measures were obtained in a single session. Results: The BIS lymphedema index (L-Dex) method had a significantly higher sensitivity than the excess volume approach (area under the curve = 0.832 vs. 0.649, p = 0.0001). A threshold of L-Dex 6.5 had a higher true positive rate (70.6%) than L-Dex 10 (68.5%) although false positive rate increased from 0.4% to 2.6%. A threshold of 5% excess volume improved the true positive rate (68.5%) compared with 10% excess volume (49.7%) however the false positive rate increased to an unacceptable 47%. The L-Dex ranges in this study were not significantly different from previously published ranges. Conclusion: BIS was superior for identifying BCRL compared with volume measurements, reaffirming the value of this technique. However, it is recommended that BIS be used in conjunction with comprehensive evaluation of symptoms and clinical presentation. The proposed graphical method provides a simple and easily interpretable approach to compare and define concordance between the two commonly used methods for BCRL assessment namely limb volume and BIS L-Dex indices. The existing BIS (L-Dex) thresholds for presence of BCRL were also validated.

Progression of fluid infiltration on non-contrast magnetic resonance imaging in breast cancer-related lymphedema: A comparative analysis with indocyanine green lymphography.

BACKGROUND: Non-contrast magnetic resonance imaging (NMRI) has been reported as valuable for the assessment of lymphedema. However, the correlation between NMRI findings and indocyanine green lymphography (ICG-L) findings remains elusive. METHODS: This single-center retrospective study included 26 patients diagnosed with breast cancer-related lymphedema. We examined the prevalence of fluid infiltration in eight regions of the upper extremity, the type of fluid distribution, and the dominant segment of edema on NMRI in comparison to the ICG-L stage. Statistical analysis was performed using the Cochran-Armitage trend test, Spearman's rank correlation test, and Fisher's exact test. RESULTS: The regional fluid infiltration significantly increased with the progression of the ICG-L stage (hand, forearm, elbow, and upper arm: p = 0.003, <0.001, <0.001, and <0.001, respectively). The fluid distribution significantly advanced with the progression of the ICG-L stage as follows (rs = 0.80; p < 0.001): no edema in ICG-L stage 0, edema in either the hand or elbow in ICG-L stage I, edemas in both the elbow and hand in ICG-L stage II, three segmental edemas centered on the forearm or elbow in ICG-L stage III, and edema encompassing the entire upper limb in ICG-L stage IV-V. Additionally, the dominant segment of edema tended to shift from the hand to the elbow and further to the forearm as the ICG-L stage progressed (p < 0.001). CONCLUSIONS: Fluid infiltration observed on NMRI exhibited distinct patterns with the progression of the ICG-L stage. We believe that anatomical information regarding fluid distribution would potentially contribute to optimizing surgical efficacy.

Four-Year Follow-Up of a Case of Yellow Nail Syndrome With IgM Deficiency.

Yellow nail syndrome is a rare condition occurring sporadically, with an extremely low prevalence rate. This syndrome classically presents with a triad of lower extremity edema, yellow nails, and mucosal issues such as pleural effusion and/or chronic sinusitis. Two out of the three features are deemed sufficient to diagnose a person with yellow nail syndrome. We present a rare case of yellow nail syndrome that began with chronic leg swelling and later progressed to the development of an asymptomatic pleural effusion and finally discoloration of nails. In our case, the patient did have a significant recent history of a total knee replacement with a titanium implant. Of note was the chronology of events including leg edema and asymptomatic pleural effusion which were present even before the titanium knee implant. The third feature of the hardening and yellow discoloration of the nails was found to have developed following the knee replacement. Interestingly, on further evaluation, he was found to have IgM deficiency.

Digital volumetric measurements based on 3D scans of the lower limb: A valid and reproducible method for evaluation in lymphedema therapy.

INTRODUCTION: Exact quantification of volumetric changes of the extremities is difficult and often error prone. The aim of this study was to establish a standardized method based on 3D scans. Furthermore, this study tests the method in terms of reproducibility and evaluates volume changes after surgical therapy in patients suffering from lymphedema on the lower extremity. METHODS: 3D-scans of the lower limb were performed with a mobile 3D-scanner. "repeatability" and "inter-observer reliability" of digital volumetry were tested. Furthermore, the method was applied on 31 patients suffering from chronic lymphedema. RESULTS: Calculations of repeatability of the volume based on 20 3D-scans of the same lower leg showed a mean volume of 2.488 ± 0,011 liters (range: 2.470 - 2.510). The mean volume of the different examiners did not differ significantly (F(2,18) = 1.579, p = .233). The paired t-Test showed a significant mean volume decrease of 375ml (95% CI = 245/505ml) between pre and post treatment (t (30) =5.892, p < .001). CONCLUSIONS: 3D-Volumetry is a noninvasive, easy and quick method to assess volume changes of the lower leg. Other than the low costs, it is reproducible and precise and therefore ideal for evolution of therapy in lymphedema.

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

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.

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

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

Psychometric Evaluation of the Bahasa Malaysia Version of the Lymphedema Functioning, Disability, and Health Questionnaire for Upper Limb Lymphedema in Patients with Breast Cancer-Related Lymphedema.

Background: Breast cancer-related lymphedema (BCRL) is the most prevalent comorbidity that occurs following breast cancer treatments and has negative impact on the patients' quality of life (QoL). The Lymphedema Functioning, Disability, and Health Questionnaire for Upper Limb Lymphedema (Lymph-ICF-UL) is a valid and reliable instrument in assessing the QoL of patients with BCRL. However, the Bahasa Malaysia (BM) version is not available yet. This study aimed to translate the Lymph-ICF-UL into BM and to evaluate its validity and reliability. Methods and Results: A forward-backward translation was performed based on Sousa's guideline, and then, the face, content, construct validity, internal consistency, and test-retest reliability were tested. Face validity was assessed by five patients, and content validity was evaluated by six experts. Then, construct validity and internal validity were assessed in 107 patients. Finally, test-retest reliability was analyzed in 21 patients. Two items were eliminated following suggestions from the patients and experts. All patients found the scoring system and items clear and relevant. The results showed sufficient content validity index and modified kappa statistics value. Confirmatory factor analysis showed acceptable fit indices. Cronbach's alpha values ranged from 0.67 to 0.95, intraclass correlation coefficient ranged from 0.88 to 0.99, standard error measurement was 2.29-6.15, and the Bland-Altman plot showed an agreement between two test occasions. Conclusion: These results suggested that the Lymph-ICF-UL BM has good validity and reliability in evaluating the QoL of patients with BCRL in Malaysia.

Concordance between preoperative imaging methods in patients with limb lymphedema undergoing supermicrosurgical lymphaticovenular anastomosis.

OBJECTIVE: Supermicrosurgical lymphaticovenular anastomosis (LVA) is increasingly being recognized as a first-line treatment for limb lymphedema because it is minimally invasive and highly effective. Lymphoscintigraphy and indocyanine green (ICG) lymphography are the two most commonly performed diagnostic imaging examinations to establish the indication and plan the procedure in patients affected by limb lymphedema. In a small group of patients, the information between these two imaging tools can be discordant, showing different anatomical drainage pathways or showing absence of drainage and dermal backflow in one examination, and valid drainage pathways in the other. The purpose of this study is to examine the types of possible discrepancies between lymphoscintigraphy of the superficial system and ICG lymphography, and to describe the surgical outcome after LVA in patients presenting such discrepancies. METHODS: We retrospectively reviewed the data of all patients who underwent LVA for upper or lower limb lymphedema between July 2015 and July 2023. From this series, we identified a group of patients who had non-concordant imaging results from lymphoscintigraphy and ICG-L prior to lymphatic surgery. Non-concordant findings were described in terms of "pattern discordance" or "pathway discordance". Surgical outcome was measured by the change in mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. P values<0.05 were considered significant. RESULTS: A total of 28 patients with limb lymphedema exhibited inconsistencies between preoperative lymphoscintigraphy of the superficial system and ICG lymphography. Among these patients, 14 experienced "pattern discordance", while 13 had "pathway discordance", and 1 patient had both. After LVA, we observed a significant reduction in the average circumference of the affected limb in the analyzed group. CONCLUSIONS: The discrepancy of information between lymphoscintigraphy and ICG lymphography in the preoperative study of patients affected by limb lymphedema is rare but possible. This phenomenon is still not fully explained, but our results suggest that it does not correlate with the outcome of supermicrosurgical lymphovenous anastomoses.

Toxicity evaluation of dose-escalation in hypofractionated regional nodal irradiation for breast cancer: a retrospective study.

PURPOSE: Regional nodal irradiation (RNI) to the axilla and supraclavicular area presents distinct toxicities, such as lymphedema and shoulder stiffness, compared to whole-breast irradiation. There is insufficient evidence on the safety of dose-escalation in hypofractionated RNI. We aimed to evaluate and compare toxicity rates in patients with breast cancer who received hypofractionated RNI with and without dose-escalation. METHODS: We retrospectively analyzed 381 patients with breast cancer treated with hypofractionated RNI between March 2015 and February 2017. Patients received either the standard-dose to the regional nodal area (43.2 Gy/16 fx; 48.7 Gy3.5 EQD2, 2 Gy equivalent dose with α/ß=3.5 Gy) or dose-escalation with a median dose of 54.8 Gy3.5 EQD2 (range, 51.7 - 60.9 Gy3.5 EQD2) depending on clinical and pathologic nodal stage. Toxicity rates of lymphedema and shoulder stiffness were assessed, and statistical analyses were conducted to identify associated factors. RESULTS: The median follow-up time was 32.3 months (5.7 - 47.0 months). After radiotherapy, 71 (18.6%) patients developed lymphedema, and 48 (12.6%) developed shoulder stiffness. Patients who received dose-escalation exhibited significantly higher rates of lymphedema (32.1% vs. 14.8%; Odds Ratio (OR): 2.72, p=0.0004) and shoulder stiffness (23.8% vs. 9.4%; OR: 2.01, p=0.0205) compared to the standard-dose group. Moreover, dose-escalation showed a tendency to increase the severity of lymphedema and shoulder stiffness. CONCLUSIONS: Patients who received dose-escalation in hypofractionated RNI face a higher risk of developing lymphedema and shoulder stiffness compared to those who received standard-dose hypofractionated RNI. Therefore, it is crucial to implement close and frequent monitoring for early detection, along with timely rehabilitation interventions for these patients.

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

Lymphedema is a chronic and progressive disease of the lymphatic system characterized by inflammation, increased adipose deposition, and tissue fibrosis. Despite early hypotheses identifying lymphedema as a disease of mechanical lymphatic disruption alone, the progressive inflammatory nature underlying this condition is now well-established. In this review, we provide an overview of the various inflammatory mechanisms that characterize lymphedema development and progression. These mechanisms contribute to the acute and chronic phases of lymphedema, which manifest clinically as inflammation, fibrosis, and adiposity. Furthermore, we highlight the interplay between current therapeutic modalities and the underlying inflammatory microenvironment, as well as opportunities for future therapeutic development.

Assessment Modalities for Lower Extremity Edema, Lymphedema, and Lipedema: A Scoping Review.

Lower extremity swelling may be broadly characterized as due to edema, lymphedema, or lipedema. Differentiation between these three conditions is important for providing appropriate treatment. This review analyzes and compares different clinical diagnostic modalities for these conditions, with the aim of assisting in the process of choosing the most appropriate diagnostic modality by highlighting the advantages and limitations of each. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for a systematic search of peer-reviewed literature, the following diagnostic methods for lower extremity swelling were investigated: (1) ultrasound (US), (2) lymphoscintigraphy (LSG), (3) computed tomography (CT), (4) bioimpedance spectroscopy (BIS), (5) tissue dielectric constant (TDC), and (6) magnetic resonance imaging (MRI), including magnetic resonance lymphangiography (MRL). The databases used in the search were PubMed, ProQuest, CINAHL Complete, Web of Science, Embase, and Biomedical Reference Collection. After retrieving 115 studies based on predetermined inclusion criteria, a total of 31 studies were critically evaluated. The main results indicate the following: duplex US is the modality of choice to initially identify lower extremity edema such as deep venous thrombosis (DVT) and venous reflux due to its high sensitivity and specificity. CT venography of the lower extremity appears to bethe preferred option for gynecologic cancer patients with lower extremity swelling post-treatment, as it measures subcutaneous tissue volumes to look for DVTs, lymphoceles, and cancer recurrence. TDC is a recommended modality for a variety of conditions, including edema and lymphedema, in part, due to its noninvasive localized assessment capabilities and ease of use. LSG emerges as an effective imaging modality for lymphedema characterization with minimal invasiveness and high sensitivity and specificity. BIS is widely used to identify and monitor lower extremity lymphedema but has been reported to have low sensitivity and lacks the ability to account for changes in tissue composition such as fibrosis. US and MRL are favored for lipedema diagnosis, with MRL providing comprehensive anatomical and functional insights, albeit with cost and accessibility limitations compared to US. While CT, MRI, US, and TDC are all useful for differentiating lymphedema from lipedema, MRI is the preferred modality due to its anatomical and functional diagnostic capabilities. However, US is a pragmatic alternative for use with obese patients or when MRI is not an option.