Lymphat Res Biol
· 2025 Aug · PMID 40384434
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The education need of health care professionals (HCP) to provide good quality care to children and young people with lymphedema (CYPwL) was unknown. While understanding of pediatric lymphedema grows, families still repor...The education need of health care professionals (HCP) to provide good quality care to children and young people with lymphedema (CYPwL) was unknown. While understanding of pediatric lymphedema grows, families still report delays in accessing appropriate treatment and HCP have reported being ill-prepared. A questionnaire was designed by phased process of literature search, focus group, and online consensus with international experts. The online survey, available in six languages, was distributed to HCP working with CYPwL by professional groups. Questionnaires were received from 507 responders from 33 countries. Specific education on the treatment of CYPwL is needed, even when HCP are adult lymphedema trained according to 80% of respondents. Greatest consensus on best practice was that a multidisciplinary team (MDT) with specialist knowledge is required to treat CYPwL, but almost one in five HCP working with CYPwL have no, or rare, access to such a team. Reducing infections and adapting compression/treatment for age and development were deemed most essential. A variety of learning resources are needed including films, videos, and webinars from clinical experts. This is the first international survey of the education need of HCP regarding CYPwL which include pathology, treatment, psychosocial care, and education of other professionals. Uppermost was knowing how to reduce infections and adapt compression and other treatments for age and development. Access to an experienced MDT was considered essential to support good clinical decision-making. Multimodal approaches are needed to address identified education need. Further research in individual countries and professions is recommended.
Fry L, Roys H, Bowlin A
… +5 more, Venugopal G, Bird JT, Weaver A, Byrum SD, Weinkopff T
Lymphat Res Biol
· 2025 Aug · PMID 40279249
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Cutaneous leishmaniasis (CL) is a significant public health problem leading to permanently disfiguring skin lesions caused by parasites. Lesion severity stems from an excessive host inflammatory response that prevents h...Cutaneous leishmaniasis (CL) is a significant public health problem leading to permanently disfiguring skin lesions caused by parasites. Lesion severity stems from an excessive host inflammatory response that prevents healing. Here, we characterized the transcriptional and translational responses of lymphatic endothelial cells (LECs) during murine CL using single-cell RNA sequencing data combined with flow cytometry and puromycin incorporation to assess translational activity. We identified upregulation of antigen presentation pathways including MHC-I, MHC-II, and immunoproteasome transcripts in dermal LECs from -infected mice compared to naive controls. LECs also exhibited increased expression of guanylate binding proteins and interferon-inducible genes, indicative of immune activation. Moreover, our findings demonstrate that LECs in leishmanial lesions displayed heightened translational activity relative to LECs from uninflamed ears, and LEC translational activity was highest in activated LECs. Furthermore, LEC translational activity exceeded that of other cell types within the lesion microenvironment. Validating the transcriptomic data, LECs in lesions expressed elevated MHC-II and programmed death-ligand 1 (PDL-1), supporting their potential role in antigen presentation. Functional assays using DQ-ovalbumin confirmed that LECs from leishmanial lesions efficiently uptake and process antigens, highlighting their capability as antigen presenting cells in the inflamed dermal microenvironment. Overall, our study reveals the activation status of LECs in leishmanial lesions, shedding light on their potential role in shaping local immunity and inflammation in a variety of skin diseases.
Ozturk G, Akpinar P, Silte Karamanlioglu D
… +3 more, Akan Begoğlu F, Unlu Ozkan F, Aktas I
Lymphat Res Biol
· 2025 Jun · PMID 40235450
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Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropat...Pain is a prevalent symptom in patients with lipedema predominantly impacting the lower extremities. This study aimed to evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] and vitamin B12 levels and neuropathic pain (NP) in patients diagnosed with lipedema. A total of 243 patients with lipedema who had 25(OH)D and B12 levels measured in the past 6 months were included in this study. Participants were divided into two groups: Group 1 ( = 78) with NP scores ≥13 and Group 2 ( = 165) with NP scores <13. The Turkish version of the painDETECT questionnaire was used to assess the patients' NP symptoms. Pain levels were measured using the Visual Analog Scale (VAS) and pain threshold through algometric measurement. Group 1 had significantly higher palpation and spontaneous VAS scores, and pain threshold through algometric measurements than Group 2 ( < 0.05). No statistically significant difference was found between the groups regarding vitamin D levels being below 30 ng/mL or vitamin B12 levels being below 400 pg/mL ( > 0.05). No association was found between NP and 25(OH)D or B12 levels in patients with lipedema.
Ward LC, Gaitatzis K, Thompson B
… +2 more, Paramanandam VS, Koelmeyer LA
Lymphat Res Biol
· 2025 Aug · PMID 40230006
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Bioimpedance spectroscopy (BIS) is commonly used for the detection and monitoring of lymphedema and potentially lipedema. BIS measures limb electrical resistance, which decreases with fluid accumulation in these conditio...Bioimpedance spectroscopy (BIS) is commonly used for the detection and monitoring of lymphedema and potentially lipedema. BIS measures limb electrical resistance, which decreases with fluid accumulation in these conditions. R0, the index of extracellular fluid and lymph accumulation, is typically estimated using Cole modeling, but technical and biological factors can affect accuracy. Participants with clinically affirmed bilateral leg lymphedema, lipedema, self-ascribed swelling, and healthy controls were included in this study. Impedance measurements were taken using a stand-on BIS device, and R0 was estimated using both the Cole modeling method and a regression approach. Quality of data fitting was assessed visually and statistically. Control participants were younger and lighter compared with the clinical groups. The regression method was able to analyze 100% of participant data, whereas the Cole method was successful in only 80%-88% of cases in the lymphedema and lipedema groups. Additionally, the regression approach provided better curve fitting accuracy for all participants. The regression method offers a robust alternative for estimating R0 values in BIS data, especially in lower limb assessments where data analysis is challenging. The small difference between methods in absolute R0 values (2.5%) has minimal practical implications, suggesting interchangeability in data analysis. The Cole method showed poorer performance, particularly in participants with lymphedema, possibly due to differences in water proportions and limb size. Overall, the regression method can be effectively used in clinical practice for estimating R0 values in BIS data, offering a more accurate and reliable approach than traditional Cole plotting methods.
Sakizli Erdal E, Haspolat M, Erturk B
… +1 more, Keser I
Lymphat Res Biol
· 2025 Aug · PMID 40207374
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This study aimed to evaluate the effects of forearm bandaging techniques, muscle contraction, and additional compression pad use on sub-bandage pressure. Thirty-one individuals (26 females, 5 males) with no chronic or l...This study aimed to evaluate the effects of forearm bandaging techniques, muscle contraction, and additional compression pad use on sub-bandage pressure. Thirty-one individuals (26 females, 5 males) with no chronic or lymphatic-related conditions participated in the study. Sub-bandage pressure was measured using the Kikuhime device, with a standardized protocol applied to the wrist extensor muscle belly. Participants were evaluated under rest and wrist extension conditions using two bandaging techniques: spiral and figure-of-eight. Variations included single and double layers, 1/2 and 1/3 overlaps, and the presence or absence of additional compression pads. Certified physiotherapists trained performed all bandaging applications using short-stretch compression materials. The figure-of-eight wrapping technique consistently produced significantly higher sub-bandage pressures compared to the spiral technique in all conditions. Double bandaging generated 1.4 times more pressure than single-layer applications, while 1/3 overlap resulted in greater pressure than 1/2 overlap. The addition of compression pads increased resting pressure by approximately 5 mmHg, and wrist extension further augmented pressure by 4-8 mmHg. The highest pressures were observed with the figure-of-eight technique, double bandaging, and 1/3 overlap combined ( < 0.05). These findings highlight the critical role of forearm bandaging technique, layering, and additional materials in determining sub-bandage pressure.
Nomura Y, Naganishi H, Ando Y
… +2 more, Akita S, Mitsukawa N
Lymphat Res Biol
· 2025 Aug · PMID 40192529
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Lower extremity lymphedema (LEL) is a common complication following gynecological cancer treatment, characterized by the accumulation of protein-rich fluid owing to lymphatic system insufficiency. This condition manifest...Lower extremity lymphedema (LEL) is a common complication following gynecological cancer treatment, characterized by the accumulation of protein-rich fluid owing to lymphatic system insufficiency. This condition manifests as in skin thickening, soft tissue swelling, and other complications. Therefore, this study proposes an automatic method for measuring skin thickness in lower extremity computed tomography (CT) images and assessing its effectiveness in diagnosing LEL. We selected 56 patients with unilateral LEL based on specific diagnostic criteria, including clinical evaluation, lymphoscintigraphy, indocyanine green lymphography, and a noncontrast CT scan, which included the entire lower extremities. The CT images had a pixel spacing ranging from 0.723 to 0.976 mm, with a slice thickness of 10.0 mm. Our skin thickness measurement method involves preprocessing, such as extracting the leg, bone, muscle, and subcutaneous fat regions, defining the target slice range, and measuring the skin thickness. The lower extremity was divided into eight subregions, and the skin thickness was measured across these subregions. The overall median skin thicknesses were 0.883 ± 0.201 and 1.536 ± 0.487 mm in normal and positive subregions, respectively. The classification of LEL was based on the -score calculated for each subregion, with the median skin thickness from normal legs serving as a reference. Our classification method demonstrated an overall accuracy of 0.839, sensitivity of 0.703, and specificity of 0.937. Our automated method for measuring skin thickness in CT images shows promise in diagnosing LEL, with high accuracy and specificity. This approach enables a comprehensive evaluation of the entire leg, potentially enhancing the diagnostic process for LEL.
Yaman A, Borman P, Koyuncu EG
… +3 more, Aslan AB, Karasu AU, Pirinççi CŞ
Lymphat Res Biol
· 2025 Aug · PMID 40080396
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Lymphedema and lipedema are chronic conditions significantly impacting psychosocial status and quality of life (QOL). However, comparative studies on depression, life satisfaction, functional status, and QoL in these con...Lymphedema and lipedema are chronic conditions significantly impacting psychosocial status and quality of life (QOL). However, comparative studies on depression, life satisfaction, functional status, and QoL in these conditions are lacking. This study aims to fill this gap by providing a comparative evaluation of functional status, depression, life satisfaction, and QoL in patients with lymphedema and lipedema. Over 12 months, 73 female patients diagnosed with pure lymphedema or lipedema were recruited according to inclusion/exclusion criteria. A range of demographic variables, including age, body mass index (BMI), disease duration, stage of disease, and exercise/smoking conditions, were recorded. The lower-extremity functional scale (LEFS), life satisfaction index (LSI), patient health questionnaire (PHQ-9), and Lymphedema QOL Questionnaire for Legs were used to assess functional status, life satisfaction, depression, and QoL, respectively, in both groups. The relationship between questionnaire scores and demographic variables was carefully evaluated. Thirty-six individuals with lymphedema (mean age: 55.1 years) and 37 patients with lipedema (mean age: 50.7 years) were included in the study. Demographical variables were statistically similar between the groups ( > 0.05). Duration of disease was longer (mean: 159.3 months vs. 39.6 months) in a lipedema group than in lymphedema patients. PHQ-9 (mean:11.4 vs. 10.4) and overall QoL scores (mean: 5.06 vs. 5.47) were similar between groups, while LEFS (mean: 44 vs. 62) and LSI scores (mean: 11.5 vs. 14.3) were worse in patients with lymphedema than in a lipedema group. There were correlations between age and LEFS ( = 0.014, = -0.40) and LSI ( = 0.013, = -0.41) in the lymphedema group; and between BMI and LEFS ( = 0.013, = -0.041) and QoL ( = 0.034, = 0.37) scores; and duration of disease and PHQ-9 scores ( = 0.028, = -0.41) in the lipedema group. Patients with lipedema have similar depression and impaired QoL as lymphedema patients. However, lymphedema patients experience more functional disability and less life satisfaction. As the BMI and duration of illness are correlated with depression and QoL, early diagnosis and early management are essential to improve disability and QoL in patients suffering from lipedema.
Eason HE, Kilbreath SL, Fearn N
… +1 more, Dylke ES
Lymphat Res Biol
· 2025 Jun · PMID 40042124
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Lipedema diagnosis is heavily reliant on patient history. Various objective assessments have been suggested; however, a standardized measurement process is lacking. A systematic review was undertaken to identify which im...Lipedema diagnosis is heavily reliant on patient history. Various objective assessments have been suggested; however, a standardized measurement process is lacking. A systematic review was undertaken to identify which imaging and measurement tools are used in lipedema quantification and to review their protocols. Six databases were searched with two reviewers screening citations for inclusion. Full peer-reviewed publications that included defined lipedema diagnosis criteria, no male cases within comparative cohorts, and used an imaging or measurement tool to quantify lipedema were included. Twenty studies met the inclusion criteria using 13 different tools to quantify individual physical lipedema characteristics to either enable differential diagnosis, and/or quantify treatment effect: tape measure, perometry, durometry, tonometry, bioimpedance spectroscopy, tissue di-electric constant, ultrasound, Dual-Energy X-ray Absorptiometry, magnetic resonance imaging (MRI), noncontrast MRI lymphangiography, Indocyanine green lymphography, lymphoscintigraphy, and dynamic lymphangiography. Eight imaging and five measurement tools assessed lymphatic transport disturbances ( = 8), limb size/volume ( = 4), adipose tissue thickness/mass/volume ( = 3), and tissue fluid presence ( = 2). Multiple tools were only used in studies completed in 2020 or later. A lack of consistency exists in tool protocols, measurement locations, and outcome analysis. Limited reporting of clinimetrics with data derived from small cohorts and heterogenous populations impacted the ability to recommend tools for clinical practice and research. Various tools were used for objective lipedema assessment; however, consistency in approach was lacking. Further investigations are required to establish the validity and reliability of measurement and imaging tools, protocols, measurement points, and outcome reporting/interpretation to quantify the physical attributes of lipedema.
Lymphat Res Biol
· 2025 Aug · PMID 40042112
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To determine the efficacy of therapeutic ultrasound (TUS) added to complex decongestive therapy (CDT) in patients with breast cancer-related lymphedema (BCRL). Thirty female volunteer patients who developed stage 2-3 BC...To determine the efficacy of therapeutic ultrasound (TUS) added to complex decongestive therapy (CDT) in patients with breast cancer-related lymphedema (BCRL). Thirty female volunteer patients who developed stage 2-3 BCRL were included in the study. The patients were randomly assigned to one of two groups: standard treatment with CDT alone and CDT + TUS. Before the study, both groups were given a training and home program consisting of remedial exercises and skin care. All patients received 15 sessions of treatment over 3 weeks. Circumferential and ultrasonographic (USG) measurements of all patients were performed before and after treatment. Treatment efficacy was evaluated based on extremity volume and soft tissue thickness. The demographic data and volume measurements of the patients were similar at the beginning of treatment. There was a statistically significant decrease in the affected extremity in both groups in posttreatment circumferential measurements. However, the reductions in volume difference and volume difference percentage were significantly higher in the CDT + TUS group ( = 0.001 and = 0.002, respectively). In the USG measurements, a greater decrease was observed in the soft tissue thickness below the elbow in the CDT + TUS group compared with the CDT alone group ( = 0.003). In the treatment of BCRL, TUS added to CDT resulted in a reduction in lymphedema. We consider that when added to CDT, TUS can increase the efficacy of treatment by reducing lymphedema in stages 2 and 3 lymphedema cases.
Lymphat Res Biol
· 2025 Aug · PMID 40040430
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To evaluate the stiffness of the skin and subcutaneous tissues of the arm and forearm of patients with breast cancer-related lymphedema using shear-wave elastography (SWE) and to investigate the relationship between the...To evaluate the stiffness of the skin and subcutaneous tissues of the arm and forearm of patients with breast cancer-related lymphedema using shear-wave elastography (SWE) and to investigate the relationship between the patients' symptoms. Both lymphedematous and unaffected upper extremities of 72 patients (72 lymphedematous and 72 unaffected extremities) and 72 upper extremities of 36 controls (72 healthy extremities) were included in the study. The stiffness of the skin and subcutaneous tissues of all extremities was evaluated with SWE. The patients' pain, tension, weight, and stiffness symptoms associated with lymphedema were questioned using a numerical scale. The patients' functionality and participation in daily life activities were evaluated. The skin stiffness of the affected extremity was higher and the subcutaneous tissue stiffness was lower in patients than in controls ( < 0.05). The skin stiffness of the affected forearm was higher and the subcutaneous tissue stiffness of the affected arm and forearm was lower than their healthy extremities ( < 0.05). Quick Disabilities of Arm, Shoulder, and Hand and Life Impact Scale; were negatively correlated with arm and forearm subcutaneous tissue stiffness and positively correlated with forearm skin stiffness. The decrease in subcutaneous tissue stiffness of the arm was associated with heaviness sensation, the increase in skin stiffness of the forearm was associated with tightness, and the decrease in subcutaneous tissue stiffness of the forearm was associated with tightness, heaviness, and stiffness sensations. The results of this study suggest that SWE measurements can be useful for diagnosis and follow-up of patients.
Xing C, Sun J, Liu Y
… +4 more, Zhou J, Bai X, Li J, Zhao H
Lymphat Res Biol
· 2025 Jun · PMID 39964776
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Secondary chronic lymphedema is a complication that seriously affects the quality of life of cancers survivors which is urgent to be studied. However, the current animal models generally have some defects such as short d...Secondary chronic lymphedema is a complication that seriously affects the quality of life of cancers survivors which is urgent to be studied. However, the current animal models generally have some defects such as short duration that affect the research process. To acquire an animal model which is easier to accomplish as well as higher success rate is the main goal of our experiment. The hind limb model of rats with secondary chronic lymphedema was established by near infrared fluorescence-guided lymphatic system destruction combined with high-fat diet innovation. The model was evaluated by limb circumference, volume, near-infrared fluorescence imaging of lymphatic vessels, and a series of histopathological staining. The model was successfully established by operation combined with a high-fat diet and kept persistent effective lasting up to 16 weeks. Compared with the normal diet group, the high-fat group received a higher success rate (77.77% vs. 55.55%), a more obvious degree of limb swelling, and a more significant level of subcutaneous inflammatory factor infiltration at the edema site. Based on it, we kept research and found out that there was no significant difference in the process of subcutaneous fibrosis between the two groups. High-fat diet may improve secondary chronic lymphedema rat model success rate as well as effectiveness by changing the level of inflammatory infiltration in the site of lymphedema.
Sumiya R, Kageyama T, Sakai H
… +2 more, Tsukuura R, Yamamoto T
Lymphat Res Biol
· 2025 Jun · PMID 39937577
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Female genital lymphedema (FGL) is a challenging disease, and appropriate preoperative evaluation is crucial before surgical treatments. Computed tomography (CT) is expected useful for FGL evaluation, but little is known...Female genital lymphedema (FGL) is a challenging disease, and appropriate preoperative evaluation is crucial before surgical treatments. Computed tomography (CT) is expected useful for FGL evaluation, but little is known. This study aimed to clarify characteristic CT findings of FGL with a case report of CT findings-guided lymphaticovenous anastomosis (LVA). Medical charts of secondary lower extremity lymphedema patients who underwent CT and indocyanine green (ICG) lymphography were reviewed. Genital regions with dermal backflow patterns on ICG lymphography were diagnosed as FGL. Prevalence of characteristic CT findings of lymphedema was compared between genitalia regions with and without FGL. A case of genital lymphedema treated with LVA under the guidance of CT findings was presented. A total of 51 patients (32 with FGL, and 19 without FGL) were included in this study. Genital ICG included stages 0/I/II/III/IV/V in 19 (37.3%)/5 (9.8%)/11 (21.6%)/9 (17.6%)/7 (13.7%)/0 (0%) cases, respectively. Characteristic CT findings included thick skin in 14 (27.5%), thick fascia in 17 (33.3%), high density of the superficial fat in 11 (21.6%), high density of the deep fat in 13 (25.5%), fluid collection in 8 (15.7%), detectable inguinal lymph node in 42 (82.4%), and honeycomb appearance in 7 regions (13.7%). Between genital regions with and without FGL, there were statistically significant differences in all the characteristic CT findings ( < 0.05). Characteristic CT findings of secondary FGL were identified. Preoperative CT evaluation may be useful for selecting appropriate LVA sites for optimal results.
Matsui C, Koide H, Mortada H
… +5 more, Tsukuura R, Miyazaki T, Sakai H, Mizuno H, Yamamoto T
Lymphat Res Biol
· 2025 Jun · PMID 39929174
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Lymphedema, characterized by abnormal lymph circulation, is a chronic debilitating condition often associated with chronic inflammation and hypoxia in lymphedematous tissue. Previously, using videocapillaroscopy, we foun...Lymphedema, characterized by abnormal lymph circulation, is a chronic debilitating condition often associated with chronic inflammation and hypoxia in lymphedematous tissue. Previously, using videocapillaroscopy, we found that the severity of lymphedema damages vasa vasorum vessels on the surface of lymph vessels, significantly compromising the oxygen supply environment to lymph endothelial cells. While previous research has indicated the inhibitory effects of hypoxic conditions on the proliferation of human dermal lymph endothelial cells (HDLECs), the impact on HDLEC migration remains unclear. This study aims to investigate the migration ability of HDLECs under hypoxic conditions, shedding light on the potential mechanisms underlying lymphedema progression and offering insights into therapeutic strategies. Purchased HDLECs were cultured under normoxic (2% O) and hypoxic (1% O) conditions. Migration assays were performed using a scratch assay to assess the migratory capabilities of HDLECs. The experiment monitored cell migration over a period of 6 hours. Experiments were performed in triplicate. HDLECs were cultured to full confluence before the scratch assay. The results revealed a significant reduction in HDLEC migration under hypoxic conditions compared to normoxic conditions after 6 hours ( < 0.001). This suggests that hypoxic environments directly impair HDLEC migration. Hypoxia negatively affects HDLEC migration, potentially exacerbating lymphedema. Protecting vasa vasorum may preserve HDLEC migration and lymphangiogenesis. Further exploration of hypoxia-HDLEC interactions is crucial for understanding lymphedema pathogenesis and developing therapies.
Lymphat Res Biol
· 2025 Jun · PMID 39879536
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We report the usefulness of a tapered cutting needle, which has a polyhedral tip similar to that of a square needle and transitions to a round tip in the middle, for super-microsurgery. We have performed more than 500 l...We report the usefulness of a tapered cutting needle, which has a polyhedral tip similar to that of a square needle and transitions to a round tip in the middle, for super-microsurgery. We have performed more than 500 lymphaticovenular anastomoses (LVAs) using tapered cutting needles. Therefore, we investigated the caliber of the anastomosed lymphatic vessels and veins, characteristics of the lymphatic vessels, the time required to perform the anastomosis, damage to the lymphatic vessels and veins during anastomosis, and patency of 30 recently performed consecutive anastomoses. The mean caliber of the anastomosed lymphatic vessels was 0.68 mm (range, 0.4-1.2 mm), and the mean caliber of the veins was 0.87 mm (range, 0.5-1.5 mm). Regarding the progression of fibrosis, 14 cases were classified as no degeneration, 13 cases were classified as mild degeneration, 2 cases were classified as moderate degeneration, and 1 case was classified as severe degeneration. The average time required to perform the anastomosis was 10.53 minutes (range, 8-13 minutes). No cases of lymphatic or venous injury or laceration occurred during the anastomosis procedure. After the anastomosis was created, intraoperative patency was observed in all patients. The tapered cutting needle is useful for LVAs because of its excellent thread-ability and protective properties for blood vessels. Furthermore, the tapered cutting needle is useful for short anastomoses, regardless of the diameter or condition of the lymphatic vessels. In the future, the tapered cutting needle is expected to become the needle of choice for LVAs.