Endo Y, Sano M, Kayama T
… +9 more, Inuzuka K, Saito T, Katahashi K, Yamanaka Y, Tsuyuki H, Ishikawa N, Naruse E, Takeuchi H, Unno N
Lymphat Res Biol
· 2023 Aug · PMID 36802287
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Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle de...Indocyanine green (ICG) fluorescence lymphography is widely used to diagnose lymphedema. There is little consensus on the appropriate injection method for ICG fluorescence lymphangiography. We used a three-microneedle device (TMD) for skin injection of ICG solution and investigated its usefulness. Thirty healthy volunteers were injected with ICG solution using a 27-gauge (27G) needle in one foot and a TMD in the other foot. Injection-related pain was evaluated using the Numerical Rating Scale (NRS) and Face Rating Scale (FRS). The skin depth of the injected ICG solution was evaluated by injecting the solution into the skin of amputated lower limbs using a 27G needle or TMD using ICG fluorescence microscopy. The median and interquartile range of the NRS scores was 3 (3-4) and 2 (2-4) in the 27G needle and TMD groups, respectively; that of the FRS scores was 2 (2-3) and 2 (1-2) in the 27G needle and TMD groups, respectively. Injection-related pain was significantly lower with the TMD than with the 27G needle. The lymphatic vessels were similarly visible using both needles. The depth of the ICG solution varied for each injection with a 27G needle (400-1200 μm) and was consistent at ∼300-700 μm below the skin surface using the TMD. Injection depth was significantly different between the 27G needle and the TMD. Injection-related pain decreased using the TMD, and ICG solution depth was consistent on fluorescence lymphography. A TMD may be useful for ICG fluorescence lymphography. Clinical Trials Registry (UMIN-CTR; ID: UMIN000033425).
Zhou J, Guo L, Song D
… +4 more, Li J, Liu Z, Sun J, Niu Y
Lymphat Res Biol
· 2023 Aug · PMID 36780016
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Intracystic hemorrhage from lymphangiomas is a common phenomenon in lymphatic malformations (LMs); however, little is known about the associated compositional changes in the lymphatic fluid. We prospectively collected l...Intracystic hemorrhage from lymphangiomas is a common phenomenon in lymphatic malformations (LMs); however, little is known about the associated compositional changes in the lymphatic fluid. We prospectively collected lymphatic fluid from children with LMs. Lymphatic fluid was divided depending on the bleeding status into the bleeding and nonbleeding groups. The fluid was subjected to cytological and biochemical analyses to determine protein and cytokine levels. The Mann-Whitney test was used to compare the two groups. There were significant differences in the levels of interleukin (IL)-6, IL-10, and glucose, and the percentage of white blood cells between the bleeding and nonbleeding groups. There was no significant difference in chlorine and protein content; white blood cell count; and IL-2, IL-4, tumor necrosis factor α, and interferon γ levels between the two groups. Lymphatic fluid is less stable in bleeding LMs than in non-bleeding LMs and is prone to inflammatory reactions. The inflammatory reaction in lymphatic fluid does not stimulate the cytokine storm in blood. The inflammatory reaction due to LMs does not affect the contents of protein and chlorine in lymphatic cyst fluid.
Andreoti TA, Berg S, Holm A
… +7 more, Angerer M, Oberlin M, Foeldi E, Baumgartner I, Niemeyer CM, Rössler J, Kapp FG
Lymphat Res Biol
· 2023 Jun · PMID 36706428
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Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymph...Generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), kaposiform lymphangiomatosis (KLA), and central conducting lymphatic anomaly (CCLA) are rare, multisystem lymphatic disorders, referred to as complex lymphatic anomalies (CLAs). Their etiology remains poorly understood; however, somatic activating mutations have recently been discovered, and the results of targeted treatments are promising. This study aimed to elaborate on the phenotypic description of CLA. Thirty-six consecutive patients were recruited for the "GLA/GSD Registry" of the University Hospital of Freiburg, Germany (2015-2021). Clinical data were prospectively collected provided that a signed informed consent form was obtained. The latest proposed diagnostic guidelines were retrospectively applied. Thirty-two patients (38% males) were included in the study; 15 GLA, 10 GSD, 3 KLA, and 4 CCLA patients were identified. Eighty-four percent already had symptoms by the age of 15 years. Osteolysis and periosseous soft-tissue infiltration were associated with GSD ( < 0.001 and = 0.011, respectively), ascites and protein-losing enteropathy with CCLA ( = 0.007 and = 0.004, respectively), and consumption coagulopathy with KLA ( = 0.006). No statistically significant differences were found in organ involvement, distribution of osteolytic lesions, number of affected bones and fractures. Twenty-five patients had complications; one patient with GLA died despite multimodal treatment. Spontaneous regression was seen in one patient with untreated KLA. CLA are rare, and their overlapping clinical presentations make differential diagnosis difficult. The characterization of our case series contributes to the phenotypic description and differentiation of these four clinical entities. A further understanding of their pathogenesis is crucial for evaluating targeted therapies and optimizing medical care.
Jeziorek M, Szuba A, Kujawa K
… +1 more, Regulska-Ilow B
Lymphat Res Biol
· 2023 Jun · PMID 36662587
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An adequate dietary energy supply is particularly important in patients with lipedema as it promotes weight and fat loss. Accurate estimation of resting metabolic rate (RMR) allows implementing a proper calorie restricti...An adequate dietary energy supply is particularly important in patients with lipedema as it promotes weight and fat loss. Accurate estimation of resting metabolic rate (RMR) allows implementing a proper calorie restriction diet in patients with lipedema. Our study aimed to compare actual resting metabolic rate (aRMR) with predicted resting metabolic rate (pRMR) in women with lipedema and to determine the association between individual body composition parameters, body mass index, and aRMR. A total of 108 women diagnosed with lipedema were enrolled in the study. aRMR was obtained by indirect calorimetry (IC) using FitMate WM metabolic system (Cosmed, Rome, Italy). pRMR was estimated with predictive equations and bioelectric impedance analysis (BIA). All body composition parameters were based on BIA. The mean aRMR in the study group was 1705.2 ± 320.7 kcal/day. This study found the agreement of predictive equations compared to IC is low (<60%). Most methods of predicted RMR measurement used in our study significantly underpredicted aRMR in patients with lipedema. Therefore, the most applied equations remain useless in clinical practice in this specific population due to large individual differences among the studied women. IC is the best tool to evaluate RMR in evaluated patients with lipedema. It is necessary to propose a new equation to RMR determination in clinical practice.
Lymphat Res Biol
· 2023 Jun · PMID 36622762
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The resurgence of space travel in the recent years, both through formally trained astronauts on the International Space Station and the civilian space race to send astrocivilians to Low Earth Orbit and beyond, beckons th...The resurgence of space travel in the recent years, both through formally trained astronauts on the International Space Station and the civilian space race to send astrocivilians to Low Earth Orbit and beyond, beckons the need to understand the role of the lymphatic system and role of endothelial glycocalyx when subjected to gravitational alterations. A comprehensive narrative review of the literature explores a call to action for research and countermeasure development to support the health and well-being of humans subjected to space flight, with particular attention to the role of the lymphatic system and endothelial glycocalyx. Emerging evidence suggests a link between the dysfunction experienced with various physiological processes in microgravity, highlighting the need for more research exploring the role of the lymphatic system in the extremes of gravity and countermeasure development to reduce dysregulation. The synergistic and interdependent relationship of these structures are fundamental to health in space and on Earth.
Sahbaz Pirincci C, Cihan E, Borman P
… +1 more, Dalyan M
Lymphat Res Biol
· 2023 Jun · PMID 36580543
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The aim of our study was to determine the causes of lower extremity kinesiophobia (whether it is biological or psychological) in individuals with lower limb lymphedema (LLL), and to compare the changes in fatigue and act...The aim of our study was to determine the causes of lower extremity kinesiophobia (whether it is biological or psychological) in individuals with lower limb lymphedema (LLL), and to compare the changes in fatigue and activities of daily living with healthy individuals. The study included 74 unilateral LLL patients (study group) and 74 individuals (control subjects). Causes of fear of movement were assessed with the Causes of Fear of Movement questionnaire; fatigue, with the Functional Assessment of Chronic Disease Treatment-Fatigue Questionnaire; and quality of life (QoL) with the Lymphedema Quality of Life Questionnaire-Leg. One hundred forty-eight participants were included in the study, 74 of whom were in the study group and 74 in the control group. 63.5% of the lymphedema patients had primary lymphedema and 36.5% had secondary lymphedema. Fear of movement total score and QoL scores was higher in LLL group than control group. Total fear of movement score and biological subparameter score of fear of movement, fatigue, and some subparameters of QoL scores were found to be higher in primary LLL patients compared with secondary LLL. Fear of movement is common and QoL is impaired in patients with secondary LLL, more significant in primary LLL.
Ohhashi T, Kawai Y, Maejima D
… +2 more, Hayashi M, Watanabe-Asaka T
Lymphat Res Biol
· 2023 Jun · PMID 36577034
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It is known that nitric oxide (NO) is a gas and synthesized from l-arginine by the NO synthase (NOS) in vascular endothelial cells. The diffused NO activates the guanosine monophosphate, which initiates a series of intra...It is known that nitric oxide (NO) is a gas and synthesized from l-arginine by the NO synthase (NOS) in vascular endothelial cells. The diffused NO activates the guanosine monophosphate, which initiates a series of intracellular events, leading to physiological response such as vasodilation. There are three different types of NOS, namely endothelial constitutive NOS (ecNOS), neuronal NOS (nNOS), and cytokine-inducible NOS (iNOS). The ecNOS and nNOS are expressed constitutively at low levels and can be activated rapidly by an increase in cytoplasmic calcium ions. In contrast, the iNOS is induced when macrophages are activated by cytokine, resulting in the induction of pathophysiological effects. Lymph flow is known to stimulate the release of NO from lymphatic endothelial cells (LEC) and then produce the relaxation of lymphatic smooth muscle cells. The NO also plays a key role in the control of lymphatic pump activity . Many studies have shown the NO-mediated findings in various kinds of lymph vessels. However, there is no or little study to demonstrate the effects of lymph flow on the molecular expression of ecNOS mRNA and the protein. In addition, little study is available for clarifying the relationship between NO and sympathetic nerve fibers in the regulation of lymph transport and production. Therefore, in this review, the experimental findings of lymph flow-mediated increases in the ecNOS mRNA and the protein in LEC are demonstrated in detail. In addition, the roles of NO and aminergic nerve fibers in the physiological control system of lymph transport and production are discussed.
Haspolat M, Sakızlı Erdal E, Erturk B
… +2 more, Erpolat OP, Keser I
Lymphat Res Biol
· 2023 Jun · PMID 36449398
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Breast lymphedema is a common complication of breast cancer treatments but there are limited studies about the treatment of breast lymphedema. The aim of this study was to investigate the acute effects of manual lymphati...Breast lymphedema is a common complication of breast cancer treatments but there are limited studies about the treatment of breast lymphedema. The aim of this study was to investigate the acute effects of manual lymphatic drainage (MLD), compression with exercise on the local tissue water percentage, pain, and stiffness following breast-conserving surgery and radiotherapy. Twenty-two patients (52.54 ± 12.18 years, 28.55 ± 5.11 kg/m) were included. The sociodemographic and clinical information was recorded. The pain and stiffness severity were measured with Visual Analog Scale. Measurements of water percentages in local tissue were performed in all quadrants of the breast with the Moisture Meter D Compact device. All measurements were performed baseline, after MLD, and after compression with exercise. There was a significant difference in local tissue water percentages between the affected and unaffected sides before treatment. The percentage of water only in the lower outer quadrant of the affected breast increased significantly after acute treatment (: 0.002). In addition, pain (: 0.001) and stiffness (: 0.001) scores decreased. Local tissue water percentages increased with MLD and decreased with compression with exercise. In the treatment of breast lymphedema, MLD and compression bandage with exercise may be beneficial in the management of the symptoms of swelling, pain, and stiffness.
Jönsson C, Johansson K, Bjurberg M
… +1 more, Brogårdh C
Lymphat Res Biol
· 2023 Jun · PMID 36449394
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Circumferential measurements (CMs) every 4th cm are commonly used to assess lower limb volume (LLV), but fewer measurements would be less time-consuming. The aim of this study was therefore to establish the agreement bet...Circumferential measurements (CMs) every 4th cm are commonly used to assess lower limb volume (LLV), but fewer measurements would be less time-consuming. The aim of this study was therefore to establish the agreement between LLV measurements derived from CM every 4th cm (V4), 8th cm (V8), and 12th cm (V12), and to evaluate the intrarater test-retest reliability for each of the three measurement methods in persons with lower limb lymphedema (LLL). Forty-two persons with unilateral or bilateral LLL were measured twice, 2 weeks apart. Volume measurements for the V4, V8, and V12 methods were derived using CM. The agreement was evaluated using intraclass correlation coefficient (ICC) and Bland-Altman graphs including 95% limits of agreement (LOA). The reliability was evaluated using ICC and standard error of measurement (SEM%) and smallest real difference (SRD%). The agreement was high for the V4 and V8 methods (ICC 0.999), and for the V4 and V12 methods (ICC 0.998). The graphs revealed slightly higher agreement between the V4 and V8 than between the V4 and V12 methods visualized by the 95% LOA (-117 to 62 and -236 to 132 mL, respectively). For all three measurement methods, the test-retest reliability was high (ICC 0.993-0.995) and the measurement error low (SEM%: 1.2%-1.4% and SRD%: 3.4%-3.8%). The higher agreement between the V4 and V8 methods than between V4 and V12, and the high test-retest reliability in LLV measurements support the V8 method to replace the V4 method in persons with LLL.
Lymphat Res Biol
· 2023 Jun · PMID 36178954
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Breast cancer-related lymphedema (BCRL) is a serious health condition negatively affecting psychological state, sleep quality, and quality of life (QOL) of patients. These complications of BCRL can be overlooked in routi...Breast cancer-related lymphedema (BCRL) is a serious health condition negatively affecting psychological state, sleep quality, and quality of life (QOL) of patients. These complications of BCRL can be overlooked in routine clinical practice. The aim of this study is to evaluate sleep quality, depression, and QOL in patients with different stages of BCRL. This cross-sectional study included 111 consecutive women patients with BCRL attending to lymphedema unit of Physical Medicine and Rehabilitation Hospital in Ankara City Hospital. Demographical and clinical data of patients were noted. Sleep quality was assessed with Pittsburgh Sleep Quality Index, day-time sleepiness was assessed with Epworth Sleepiness Scale, depression was assessed with Beck Depression Questionnaire, and QOL was assessed with Lymphedema Quality of Life Questionnaire-arm. Median age of patients was 57 (49-63) (25%-75% interquartile range). Nearly 58.8% of the patients had sleep disturbances, and 29.7% of the patients had depression. Presence of both sleep disturbance and depression was associated with increased age. Patients with sleep disturbance were found to be more depressive and vice versa, ( < 0.001, < 0.001, respectively). Sleep disturbance, depression and day-time sleepiness, and higher body mass index were all associated with lower QOL scores. Presence of sleep disturbances and depression should be evaluated in every patient with BCRL with special attention to elderly. Rehabilitative management of BCRL should include psychiatric evaluation and interventions. Future studies should intend to assess the risk factors that affect psychological state, sleep quality, and QOL in patients with BCRL.
Fearn N, Meybodi F, Kilbreath S
… +4 more, Dylke E, Llanos C, Swanton C, Stuart K
Lymphat Res Biol
· 2023 Jun · PMID 36154463
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Breast lymphedema after breast cancer is challenging to quantify. Three-dimensional (3D) surface imaging is one available technique to measure breast volume, however, the measurement properties of available software prog...Breast lymphedema after breast cancer is challenging to quantify. Three-dimensional (3D) surface imaging is one available technique to measure breast volume, however, the measurement properties of available software programs have not been fully determined. The aim of this study was to determine equivalency of measurements with two software programs as well as reliability, standard error of measurement (SEM), and smallest detectable change (SDC). Retrospective three-dimensional surface imaging (3D-SI) of 100 breasts taken before or after breast conserving surgery for breast cancer were retrieved for reliability analysis. Three assessors followed a standardized measurement technique using two software programs, Vectra 3D Analysis Module (VAM) and Breast Sculptor. Mean breast volume was 489.9 ± 206 cc using VAM and 480.1 ± 229.1 cc using Breast Sculptor. Lin's concordance showed poor agreement between programs (0.81-0.88). Measurements using VAM had excellent intra- and inter-rater reliability with SEM = 4.1% for one assessor and 8.7% for multiple assessors. Breast Sculptor also had excellent intra-rater and substantial inter-rater reliability but the SEM was much larger at 14.5% (intra-rater) and 19.1% (inter-rater). The SDC value was lowest for VAM and a single rater with 56 cc indicating a meaningful change beyond measurement error. Breast volume measurements captured with 3D-SI using VECTRA-XT are highly reliable, but the volumes, SEM, and SDC varied between the two software programs. Measurement error was lowest with VAM software. Although the usefulness of VECTRA-XT and VAM software to detect change in breast volume is promising, further solutions to reduce measurement error are required to improve clinical utility to measure breast lymphedema.
Dietrich MS, Gaitatzis K, Koelmeyer L
… +11 more, Boyages J, Abramson VG, McLaughlin SA, Ngui N, Elder E, French J, Hsu J, Hughes TM, Stolldorf DP, Shah C, Ridner SH
Lymphat Res Biol
· 2023 Jun · PMID 36126315
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Patients underwent a compression (sleeve and gauntlet) intervention for subclinical breast cancer-related lymphedema (S-BCRL). Physical, emotional, and quality-of-life (QoL) outcomes were examined. Associations of change...Patients underwent a compression (sleeve and gauntlet) intervention for subclinical breast cancer-related lymphedema (S-BCRL). Physical, emotional, and quality-of-life (QoL) outcomes were examined. Associations of change in extracellular fluid alone through bioimpedance spectroscopy (BIS) or change in whole-arm volume through tape measure with the outcomes at time of S-BCRL were explored. We enrolled newly diagnosed nonmetastatic breast cancer patients for surveillance up to 36 months postoperatively. Upon detection of S-BCRL, a 28-day compression intervention was initiated. Data were obtained through physical examination/measurement and self-report instruments: skin examination, Lymphedema Symptom Intensity and Distress Survey-Arm, and Functional Assessment of Cancer Therapy General (FACT-G), Breast (FACT-B), and FACT-B+4. Improvements with intervention were observed in the proportion of patients reporting symptom scores ≥3 in function (Cohen's = -0.46, < 0.01), in biobehavioral (Cohen's = -0.30, < 0.05), maximum number of skin conditions (Cohen's = -0.34, < 0.05. 3), FACT-B (Cohen's = 0.52, < 0.01), and FACT-B + four (Cohen's = -0.42, < 0.01). At the study endpoint, compared with those who did not progress, chronic breast cancer-related lymphedema (C-BCRL) progressing patients had higher overall symptom scores ( = 0.037), more skin conditions ( = 0.009), and lower total FACT-G and FACT-B scores ( < 0.05). At the time of S-BCRL, detection of greater BIS unit change correlated with higher symptom, skin condition, and QoL values. Greater whole-arm volume change correlated with higher FACT-B+4 scores (all < 0.05). Prospective surveillance, symptom assessment, and compression intervention promote low progression rates from S-BCRL to C-BCRL and as such reduce symptom burden. This closed study is registered with ClinicalTrials.gov NCT02167659.
Hisano F, Watanabe S, Niwa S
… +7 more, Nakanishi K, Mawaki A, Takeno Y, Murota K, Honda I, Fujimoto E, Oshima C
Lymphat Res Biol
· 2023 Apr · PMID 36112357
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Lymphedema often affects the trunk after breast cancer surgery. Measuring volume baseline can help detect lymphedema-related changes early, thereby allowing for early intervention efforts. However, there is no quantitati...Lymphedema often affects the trunk after breast cancer surgery. Measuring volume baseline can help detect lymphedema-related changes early, thereby allowing for early intervention efforts. However, there is no quantitative method for detecting truncal lymphedema. As a preliminary investigation into the development of a new method for measuring truncal lymphedema, this study aimed to investigate the reliability and define the minimal detectable change (MDC) in posterior truncal thickness using a three-dimensional (3D) scanning system. This observational study included 21 women who had undergone a mastectomy for breast cancer. The 3D images of every subject's trunk were captured by a handheld 3D scanner at two time points. The acquired 3D images were used to calculate the differences in thickness between the affected and unaffected sides at eight points on the trunk. The reliability was determined by checking for agreement between the trials (intraclass correlation coefficient) and by investigating the presence of systematic bias between the measurement error and true value (Bland-Altman analysis). Then, the MDC was calculated. For 14 of the 21 participants, 3D images without missing data at both time points were obtained. Analysis indicated that there was no systematic bias regarding the mean value at the seven body points. Fair-to-excellent reliability was shown at the five points in the middle of the trunk (MDC: 4.14-9.79 mm). The other three points (at the top and bottom of the trunk) had limited reliability. The 3D scanning system effectively measured the differences in thickness between the affected and unaffected sides of participants' posterior trunks, with fair-to-excellent reliability in the middle of the trunk.
This study aimed to investigate the possible relationship between breast cancer-related lymphedema and central obesity, which is known to be effective in metabolic syndrome and chronic inflammation. Thirty-six patients...This study aimed to investigate the possible relationship between breast cancer-related lymphedema and central obesity, which is known to be effective in metabolic syndrome and chronic inflammation. Thirty-six patients (18 lymphedemas, 18 control) enrolled in the study. There was no statistically significant difference in demographic data between the two groups except body mass index (BMI) distribution ( = 0.008). Although 50% of the patients in the study group were obese, this rate was 5.6% in the control group. Although there was a significant difference between the study and control groups in terms of abdominal circumference measurement, there was no significant difference between total and abdominal fat amount and ratios. When BMI and abdominal circumference measurements were evaluated together to predict lymphedema, the area under the curve in abdominal circumference measurement was higher than BMI (0.715 vs. 0.659). In receiver operating characteristic curve analysis, 107 cm of abdominal circumference measurement was determined as cutoff value for lymphedema, with 55% sensitivity and 89% specificity (Youden index: 0.44). Abdominal circumference measurement can be evaluated together with BMI in determining the risk of lymphedema.
Webb E, Bissett B, Neeman T
… +3 more, Bowden F, Preston E, Mumford V
Lymphat Res Biol
· 2023 Apr · PMID 35997601
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Cellulitis is a common and often recurrent infection that causes substantial financial burden and morbidity. Compression therapy reduces the risk of recurrent cellulitis episodes for adults with chronic edema; however, l...Cellulitis is a common and often recurrent infection that causes substantial financial burden and morbidity. Compression therapy reduces the risk of recurrent cellulitis episodes for adults with chronic edema; however, little is known about the cost-effectiveness of the intervention. A cost analysis was undertaken during a randomized controlled trial (RCT) involving 84 participants with lower limb chronic edema and a history of recurrent cellulitis. The intervention group received compression therapy and education, while the control group received education only. A clinical audit and survey were used to measure health service and patient resource use for (1) the most recent episode of cellulitis, and (2) compression therapy over 18 months. Australian reference costs were used to calculate cellulitis and compression therapy costs, and the mean expenditure in both the RCT groups. Of the 84 RCT participants, 43 were surveyed and audited on the cost of cellulitis, and 40 on the cost of compression therapy. The mean cost of a hospitalized and nonhospitalized episode of cellulitis was $9071 and $506 from a health service perspective, and $4496 and $1320 from a patient perspective. The mean cost of compression therapy per participant over 18 months was $1905 and $421 from health service and patient perspectives, respectively. During the RCT, the mean annual cost per participant was $4972 in the experimental group and $26,382 in the control group, giving a cost-saving of $21,483 (95% confidence interval, 3136-48,176) per participant. For patients with lower limb chronic edema and recurrent cellulitis, compression therapy is both efficacious and cost-saving. Trial Registration: ACTRN12617000412336.