Lymphedematous Limbs Research Articles

Lymphatic Mapping with Multi-Lymphosome Indocyanine Green Lymphography in Legs with Lymphedema.

It is observed that the locations of the most functional lymphatic vessels in the lymphedematous limbs can differ significantly from those in healthy limbs. The aim of this study was to elucidate the lymphatic map of lymphedematous limbs. We retrospectively analyzed 59 patients (118 limbs) with lower limb lymphedema. Fifty-five were women and four were men. The mean age and duration of lymphedema was 62.4 and 7.7 years, respectively. For the lateral thigh lymphosome, we injected indocyanine green (ICG) at the lateral knee and measured the distance (Dt) between the anterior superior iliac spine (ASIS) and the point where the lymphatic vessels crossed the reference line (the line connecting the ASIS and the patellar center). For the lateral calf lymphosome, we injected ICG at the lateral ankle and measured the distance (Dc) between the inferior patellar border and the point where the lymphatic vessels crossed the reference line (the anterior border of the tibia). In the lateral thigh, the mean Dt was 30.4 ± 0.6 cm (range, 0-41 cm) and the distribution peaked at approximately 30 cm from the ASIS. In the calf, the mean Dc was 13.1 ± 0.9 cm (range, -11 to 32 cm). The distribution of lymphatic vessel locations was highly variable. We could establish the lymphatic map in the lymphedematous legs. The distribution of lymphatic vessels in the thigh and lower legs had one and two peaks, respectively.

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.

Evaluation of the Superficial Collecting Lymph Vessels’ Vasa Vasorum in Lymphoedematous Limbs Using Video Capillaroscopy

The pre-collecting and collecting lymph vessels have smooth muscle cells, and sufficient perfusion is vital to maintain their function. Although the vasa vasorum of the collecting lymph vessels (VVCL) have been histologically investigated, little is known about their physiology. This study aimed to investigate the relationship between morphology and blood flow of the VVCL in lymphoedematous limbs. Medical records of lower extremity lymphoedema patients who underwent video capillaroscopy observation during supermicrosurgical lymphaticovenous anastomosis (LVA) surgery were reviewed. The collecting lymph vessels, dissected for LVA, were examined under video capillaroscopy (GOKO Bscan-ZD, GOKO Imaging Devices Co., Japan) with a magnification of 175x and 620x. Blood flow velocity of the VVCL was calculated by measuring the red blood cell movement using software (GOKO-VIP ver. 1.0.0.4, GOKO Imaging Devices Co., Japan). Based on the video capillaroscopy findings, the VVCL were grouped according to their morphology; the VVCL morphology types and blood flow velocity were then compared according to lymphosclerosis severity grade. Sixty-seven lymph vessels in 20 lower extremity lymphoedema patients were evaluated, including s0 in 19 (28.4%), s1 in 34 (50.7%), s2 in 10 (14.9%), and s3 in four (6.0%) lymph vessels. The VVCLs were grouped into four types: type 1 (n = 4), type 2 (n = 37), type 3 (n = 19), and type 4 (n = 7). Blood flow velocity of the VVCL ranged 0 - 189.3 μm/sec (average 26.40 μm/sec). There were statistically significant differences in VVCL morphology (p < .001) and blood flow velocity (p < .001) according to lymphosclerotic severity. Vasa vasorum of the collecting lymph vessels could be grouped into four types with different characteristics. Morphological and physiological changes of the VVCL were related to sclerotic changes of the collecting lymph vessels.

Lymphatic ultrasound (D-CUPS) and multi-point ICG lymphography for successful LVA

Securing dilated lymphatic vessels with good function is challenging when performing lymphaticovenous anastomosis (LVA). To achieve this, we propose multi-point indocyanine green (ICG) lymphography and lymphatic ultrasound (D-CUPS; Doppler, Cross, Uncollapsible, Parallel, and Superficial fascia). With multi-point ICG lymphography, more lymphatic vessels can be found than with conventional ICG lymphography, which leads to better surgical results. Lymphatic ultrasound is more useful because it allows the observation of cross-sections of lymphatic vessels. It is known that lymphatic degeneration occurs in the lymphatic vessels in lymphedematous limbs, and LVA is most effective when dilated lymphatic vessels are anastomosed. The degree of lymphatic degeneration can be diagnosed with lymphatic ultrasound, and the proximity of dilated lymphatic vessels and veins suitable for anastomosis can be reliably identified and selected as the skin incision site for LVA. Lymphatic ultrasound is a safe, versatile and useful imaging technique that does not require a contrast agent and can be performed by anyone. By mastering multi-point ICG lymphography and lymphatic ultrasound (D-CUPS), the operation time can be shortened, and more effective LVA can be performed. In this Technical Note article, we comprehensively describe lymphatic function examinations that we have developed so far.

The relationship between the degree of subcutaneous fluid accumulation and the lymphatic diameter

The relationship between the fluid accumulation in the subcutaneous tissue and the lymphatic degeneration in the lymphedematous limbs has not been elucidated, and we have evaluated it in the current study. Twenty-five patients (50 limbs) were included in this retrospective study. We performed lymphatic ultrasound by separating the limbs into four lymphosomes: the saphenous (medial) thigh, saphenous (medial) calf, lateral thigh, and lateral calf. In each lymphosome, the lymphatic diameter, the degree of lymphatic degeneration, and the fluid accumulation in the subcutaneous tissue were evaluated. The lymphatic vessels were detected based on the index of D-CUPS (Doppler, Crossing, Uncollapsibe, Parallel, and Superficial fascia). Lymphatic degeneration was diagnosed based on the NECST (Normal, Ectasis, Contraction, and Sclerosis Type) classification. All patients were women with a mean age of 62.7 years. Lymphatic vessels were detected using lymphatic ultrasonography in 50 saphenous (medial) thigh lymphosomes, 43 saphenous (medial) calf lymphosomes, 34 lateral thigh lymphosomes, and 22 lateral calf lymphosomes. The fluid accumulation tended to be more acute in the more severe stages of lymphedema. As for the NECST classification, the normal type was observed only in the areas without fluid accumulation. Among the other areas, the percentage of contraction type was the largest in the area with slight edema and decreased in the areas with severe edema. The lymphatic vessels were dilated to a greater extent in legs with more severe fluid accumulation. Therefore, there is no hesitation needed to perform lymphaticovenous anastomosis because of severe lymphedema.

A retrospective analysis of Stewart-Treves syndrome in the context of chronic lymphedema

BackgroundStewart-Treves syndrome (STS) is an angiosarcoma associated with chronic lymphedema. ObjectivesThis article analyses the characteristics of twenty-two patients and proposes active intervention in lymphedema and the early diagnosis of STS. MethodsTwenty-two patients with STS were diagnosed at the centre over an 11-year period. Clinical manifestations, a series of conventional analyses, and histopathology were used to study these cases retrospectively. ResultsThe age range of 22 patients with STS was 15 to 78 years. The main clinical manifestations included multiple skin and subcutaneous nodules and scattered red or purplish-red rashes in the lymphoedematous limbs. These patients often showed clinical symptoms such as lymphedema, weakness, emaciation, pain, mass, lymphadenopathy and so on. The positive rates of ultrasonography, MRI and radionuclide imaging were 66.7% (6/9), 92.3% (12/13) and 18.2% (2/11), respectively. The main points regarding active intervention in lymphedema and early diagnosis of STS were summarized. Study limitationsSince this was a retrospective study, the main points summarized by the author need to be further quantified in clinical work to guide the diagnosis of this kind of disease more conveniently. In addition, further clinical trials are needed to evaluate the role of lymphedema in the occurrence and development of malignant tumors. ConclusionsSTS can appear in lymphoedematous tissue many years after lymphedema onset. To avoid delays in the diagnosis and therapy of STS, physicians should actively look for signs or symptoms of malignant lymphedema during the follow-up period and promptly manage patients developing problems.

The Impacts of Lymph on the Adipogenesis of Adipose-Derived Stem Cells.

The pathophysiology of adipose proliferation or differentiation in extremity lymphedema has not been thoroughly studied. This study investigated the impacts of the lymph harvested from lymphedematous limbs on the adipogenesis of adipose-derived stem cells (ASCs). ASCs were isolated from the adipose tissue of normal extremities and cultured with lymph collected from Cheng lymphedema grade III to IV patients or adipogenic differentiation medium (ADM) and further subjected to differentiation and proliferation assay. The expression of adipogenesis genes was examined by real-time polymerase chain reaction to investigate the effect of lymph on ASCs. The level of adipogenic cytokines in the lymph was also evaluated. The adipocytes were significantly larger in lymphedema fat tissue compared with that in normal fat tissues ( P < 0.00). The adipogenesis of ASCs cultured in lymph was significantly enhanced compared with in ADM ( P = 0.008) on day 10, suggesting that the adipogenesis of ASCs was promoted under the lymph-cultured environment. The expression of adipogenesis genes, peroxisome proliferator-activated receptor ( P = 0.02), CAAT/enhancer-binding protein α ( P = 0.008); fatty-acid binding protein ( P = 0.004), and lipoprotein lipase ( P = 0.003), was statistically elevated when the ASCs were cultured with lymph. The insulin content in lymph was statistically higher in lymph ( P < 0.001) than in plasma. The adipogenesis of ASCs was promoted under the lymph-cultured environment with statistically increased adipogenesis genes of peroxisome proliferator-activated receptor, CAAT/enhancer-binding protein α, fatty-acid binding protein, and lipoprotein lipase. The excess lymph accumulated in the lymphedematous extremity contained a greater insulin/insulin-like growth factor-2. These adipogenic factors promoted the expression of early adipogenesis genes and led ASCs to undergo adipogenesis and differentiated into adipocytes. The accumulation of adipose tissue in the lymphedema region was contributed from the content of excess lymph.

Investigations on the donor limb after harvest of lymphatic vessels for lymphedema surgery

ObjectiveMicrosurgical lymphatic vessel transplantation is one of the well-established therapies for lymphedema. Lymphatic vessels are harvested from a healthy thigh and transplanted into lymphedematous limbs to create a lymphatic bypass. Its benefit on lymphatic drainage has already been proven. However, to the best of our knowledge, the effect on the lymphatic function of the donor site has not yet been studied. Our aim was to evaluate the long-term postoperative lymphatic function in the donor site by clinical and scintigraphic examinations and a patient questionnaire. MethodsA consecutive series of 25 women (mean age, 57.2 years) who had undergone follow-up after lymph vessel transplantation to treat secondary lymphedema of the arm comprised the study group. Lymphatic vessel function of the donor site was evaluated by circumferential measurements of the limb and, in nine cases, by lymphatic scintigraphy. Additionally, a questionnaire was used to assess the patients’ pre- and postoperative complaints for the donor limb and quality of life. Separately, the medical records of 100 patients who had undergone lymphatic harvest and been followed up were reviewed for documented signs of lymphatic function of the donor limb. ResultsThe lymphatic grafts were harvested from the thigh (left, n = 9; right, n = 16) and transplanted to bridge the region of lymphatic obstruction in the axilla. The mean follow-up period was 4.5 years after surgery. None of the patients had shown significant changes in the circumference of the donor limb or pathologic findings via lymphatic scintigraphy. None of the patients had reported any impairment in the donor leg or showed symptoms of postoperative lymphedema or erysipelas. ConclusionsOur results have shown that harvesting lymphatic vessels from the thigh for lymphatic vessel transplantation is possible without significant donor site morbidity.

Bacterial diversity significantly reduces towardthe late stages among filarial lymphedema patients in the Ahanta West District of Ghana: A cross-sectional study.

BackgroundLymphatic Filariasis (LF), a neglected tropical disease, has been speculated to be complicated by secondary bacteria, yet a systematic documentation of these bacterial populations is lacking. Thus, the primary focus of this study was to profile bacteria diversity in the progression of filarial lymphedema among LF individuals with or without wounds.MethodsA cross‐sectional study design recruited 132 LF individuals presenting with lymphedema with or without wounds from eight communities in the Ahanta West District in the Western Region, Ghana. Swabs from the lymphedematous limbs, ulcers, pus, and cutaneous surfaces were cultured using standard culture‐based techniques. The culture isolates were subsequently profiled using Matrix‐assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry.ResultsOf the 132 LF participants recruited, 65% (85) had filarial lymphedema with no wounds. In total, 84% (235) of the bacterial isolates were identified. The remaining 16% (46) could not be identified with the method employed. Additionally, 129(55%) of the strains belonged to the phylum Firmicutes, while 61 (26%) and 45 (19%) represented Proteobacteria and Actinobacteria, respectively. Generally, irrespective of the samples type (i.e., wound sample and non‐wound samples), there was a sharp increase of bacteria diversity from Stages 1 to 3 and a drastic decrease in these numbers by Stage 4, followed by another surge and a gradual decline in the advanced stages of the disease. The Shannon Diversity Index and Equitability for participants with and without wounds were (3.482, 0.94) and (3.023, 0.75), respectively. Further, Staphylococcus haemolyticus and Escherichia coli showed resistance to tetracycline, chloramphenicol, and penicillin.ConclusionThe present study reveals a sharp decline in bacterial load at the late stages of filarial lymphedema patients. In addition, we report an emerging antimicrobial resistance trend of S. haemolyticus and E. coli against commonly used antibiotics such as tetracycline, chloramphenicol, and penicillin in communities endemic for LF in the Ahanta West District, Ghana. This could pose a huge challenge to the management of the disease; particularly as current treatments are not quite effective against the infection.

The Lymphatic Pump Technique for the Treatment of the Lower Limb Lymphedema

Lymphedema is a condition occurring when the lymphatic system fails to efficiently transport the lymph, thus creating a fluid accumulation in the interstitial space. As of today, the rehabilitation treatment for lymphedema relies on the principles of Complete Decongestive Therapy (CDT), a series of treatments designed to favor the reabsorption of the lymph by the lymphatic system and to restore the functionality of the affected limb. From an osteopathic point of view, interesting results have been obtained through Lymphatic Pump Technique (LPT), a series of oscillatory techniques applied to different areas of the body such as chest, abdomen and feet. A few LPT studies on animals have shown a significant improvement not only in the lymphatic system efficiency (an increase of 271% in lymph flow) but also in the immune system. Aim. From the scientific evidence derived from such studies, in this paper we propose a clinical trial aiming to demonstrate the benefits that this technique can bring to human beings in a specific rehabilitation process following a lower limb lymphoedema. Material and methods. An indirect volumetric measurement of lymphedematous limbs according to the segmental technique was performed on six subjects having a history of CDT treatments with different clinical histories, age, gender, work and sport characteristics.The results of the study group treated with the LPT were compared to the results of the same subjects who previously underwent CDT treatment only. The LPT was applied in 8 sessions for two weeks, i.e. for the period of time scheduled for normal physiotherapy rehabilitation including CDT. Results. The average volume before CDT was 9470.6 ml while after treatment was 8429 ml. The mean volume before CDT associated with LPT was 9608.5 ml, whereas after treatment the mean was 8267 ml with a significant reduction in lymphoedema. Conclusions. Despite the small number of cases examined, the treatment described in this project has led to positive and statistically significant results, in terms of absorption of lymphedema, especially reducing the volume of the limb. LPT is safe as it is a non-invasive technique, performed with the application of light forces, and integrates perfectly with the CDT.

Simulation‐based reasoning of residual tissue deformations in a two‐chamber test of a lymphedematous leg

A two-chamber inflation-deflation test was recently proposed as a diagnostic method to determine parameters of the intermittent pneumatic compression used as an effective therapeutic modality for lymphedematous limbs. It is crucial that the recorded trends for residual tissue deformations are understood in terms of specific properties of subcutaneous tissue and skin to support diagnostic process. This paper presents a mechanical model of lymphedematous legs in two-chamber tests. The cylindrical geometry composed of layers of skin, modeled as hyperelastic medium, and subcutaneous tissue, modeled as fluid saturated hyperporoelastic medium, is assumed. The results of finite element simulations show the possibility of such combinations of the properties of skin (rigidity) and subcutaneous tissue (rigidity and permeability), which ensures that the model predictions resemble the evolution of tissue residual deformations observed in the two-chamber test. The stiffness and permeability appeared to be the most crucial tissue property determining trend lines of residual deformations. The analysis of the components of displacement of solid matrix and pore fluid pressure explains the mechanisms that are responsible for particular tissue behavior. The moderate role of skin and limitations related to the mechanical and geometrical model assumptions are indicated. Recommendations for treating lymphedema using intermittent compression therapy in relation to the results of the two-chamber test and properties of tissues are discussed.

LEVERAGING THOUSANDS OF POLYGENIC SCORES, FAMILY HISTORY, AND AGE-OF-ONSET INFORMATION TO OPTIMIZE RISK PREDICTION FOR PSYCHIATRIC AND NEUROLOGICAL DISORDERS

Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines ‘Liposuction for Chronic lymphoedema’, acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland.A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined.There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7–86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively.Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

METHODOLOGICAL AND PERFORMANCE IMPLICATIONS OF ADDING POLYGENIC RISK SCORES TO EHR-BASED PREDICTION MODELS

Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines ‘Liposuction for Chronic lymphoedema’, acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland.A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined.There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7–86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively.Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

POLYGENIC EMBRYO SCREENING: SCIENCE FICTION OR SCIENCE FACT?

Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines ‘Liposuction for Chronic lymphoedema’, acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland.A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined.There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7–86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively.Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

CLINICAL RELEVANCE OF GENOTYPE-PHENOTYPE ANALYSES WITHIN BIPOLAR DISORDER AND ACROSS THE MOOD AND PSYCHOSIS SPECTRUM

Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines ‘Liposuction for Chronic lymphoedema’, acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland.A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined.There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7–86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively.Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

IN VIVO PERTURB-SEQ: STUDY GENE FUNCTION AT SCALE IN DEVELOPING TISSUES

Liposuction for lymphoedematous limbs is an effective treatment for chronic lymphoedema, with excellent long-term results in well-selected patients. In 2008 NICE produced guidelines ‘Liposuction for Chronic lymphoedema’, acknowledging this treatment modality. However, there remain very few centers that provide this service in the United Kingdom. We aim to share our experience of our referral system at Ninewells Hospital, Dundee, Scotland.A 10 year prospective database from 2005 to 2014 was analysed. Referral sources, patient demographics, diagnosis and treatment offered were examined.There were 221 referrals in total, 190 (86%) female and 31 (14%) male. The mean age was 51 (range 7–86 years). 127 (58%) were referred via their general practitioners, 72 (33%) from a hospital consultant and 22 (10%) from a lymphoedema nurse specialist. 153 (69%) referrals were from Scotland, 61 (28%) from England and 7 (3%) from Northern Ireland. The majority of patients 165 (75%) were referred with lower limb swelling. Following assessment in clinic, 146 (66%) were found to have lymphoedema whilst the rest were deemed to have other non-lymphoedematous diagnoses which include lipoedema (47, 21%), dependent oedema (8, 4%) and obesity (5, 2%). 131 (59%) were offered liposuction- 74 (34%) have received liposuction, 18 (8%) are awaiting their procedure, 3 (1%) have declined surgery, 27 (12%) are awaiting funding approval and 9 (4%) have been declined funding by their primary care trust/clinical commissioning group (PCT/CCG). 4 (2%) are awaiting investigations to further evaluate the cause of their swelling, whilst the remaining 86 (39%) were felt unsuitable for surgery and were treated conservatively.Chronic lymphoedema is a challenging condition to treat, with few specialist centers offering surgical treatment. We hereby share our referral process, diagnosis and management.

Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema.

Simple SummaryLymphedema is a common complication of cancer, and patients with lymphedema have substantially decreased quality of life and suffer from lifelong symptoms. This study aimed to examine the effect of inhibition of Th2 inflammation in lymphedema by using QBX258, a combination of IL4/13 neutralizing antibodies. QBX258 treatment increased quality of life and reduced pathologic changes in skin including hyperkeratosis, cytokine production, fibrosis and immune cell recruitment. In conclusion, this study suggested that immunotherapy against IL4/13 improved patients’ daily life which might be related with reduced pathological skin changes.Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer–related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.

Lower Limb Lymphedema Patients Can Still Benefit from Supermicrosurgical Lymphaticovenous Anastomosis (LVA) after Vascularized Lymph Node Flap Transfer (VLNT) as Delayed Lymphatic Reconstruction-A Retrospective Cohort Study.

Background: For lymphedema patients who received a vascularized lymph node flap transfer (VLNT) as their primary treatment, what are the treatment options when they seek further improvement? With recent publications supporting the use of lymphaticovenous anastomosis (LVA) for treating severe lymphedema, we examined whether LVA could benefit post-VLNT patients seeking further improvement. Methods: This retrospective cohort study enrolled eight lymphedema patients with nine lymphedematous limbs (one patient suffered from bilateral lower limb lymphedema) who had received VLNT as their primary surgery. Patients with previous LVA, liposuction, excisional therapy, or incomplete data were excluded. LVA was performed on nine lower lymphedematous limbs. Demographic data and intraoperative findings were recorded. Preoperative and postoperative limb volumes were measured with magnetic resonance volumetry. The primary outcome was the limb volume measured 6 months post-LVA. Results: The median duration of lymphedema before LVA was 10.5 (4.9–15.3) years. The median waiting time between VLNT and LVA was 41.4 (22.3–97.9) months. The median volume gained in the lymphedematous limb was 3836 (2505–4584) milliliters (mL). The median post-LVA follow-up period was 18 (6–30) months. Significant 6-month and 1-year post-LVA percentage volume reductions were found compared to pre-LVA volume (both p < 0.001). Conclusion: Based on the results from this study, the authors recommend the use of LVA as a secondary procedure for post-VLNT patients seeking further improvement.

Two methods of extracorporeal shock-wave therapy in a rat model of secondary lymphedema: a pilot study.

ObjectivesTo compare the effectiveness of two methods of extracorporeal shock-wave therapy (ESWT) in a rat model of forelimb lymphedema, induced by axillary lymph node dissection.MethodsSprague–Dawley rats were randomly allocated to a group that received 500 ESWT shocks only in the lymphedematous forelimb (Forelimb/ESWT) and a group that received 300 ESWT shocks in the axilla and 200 shocks in the lymphedematous forelimb (Axilla+Forelimb/ESWT). The circumferences of each limb were then measured. Immunohistochemistry for a pan-endothelial marker (cluster of differentiation [CD]31) and lymphatic vessel endothelial hyaluronan receptor-1, and western blot analysis for vascular endothelial growth factor receptor-3 (VEGFR3) and VEGF-C were performed.ResultsThe circumferences of the limbs showed significant effects of group and time following surgery. The circumferences at the carpal joint and 2.5 cm above were smallest in the naïve limbs, larger in the Axilla+Forelimb/ESWT group, and the largest in the control group. VEGFR3 tended to be expressed at a higher level in the Axilla+Forelimb/ESWT group (1.96-fold) than in the Forelimb/ESWT group (1.20-fold) versus the opposite non-edematous forelimbs, although this difference was not statistically significant.ConclusionsThese data suggest that ESWT protocols have differential effects on angiogenesis and lymphangiogenesis in lymphedematous limbs.

Far Infrared Radiation Therapy for Gynecological Cancer-Related Lymphedema Is an Effective and Oncologically Safe Treatment: A Randomized-Controlled Trial.

Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference (p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.