Clinical Lymphedema Research Articles

Regulation of Adipogenesis by Lymphatic Fluid Stasis

Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goal of this study was to determine how lymphatic fluid stasis regulates adipogenic gene activation and fat deposition. Adult female mice underwent tail lymphatic ablation and were euthanied at 1, 3, or 6 weeks postoperatively (n = 8 per group). Samples were analyzed by immunohistochemistry and Western blot analysis. An alternative group of mice underwent axillary dissections or sham incisions, and limb tissues were harvested 3 weeks postoperatively (n = 8 per group). Lymphatic fluid stasis resulted in significant subcutaneous fat deposition and fibrosis in lymphedematous tail regions (p < 0.001). Western blot analysis demonstrated that proteins regulating adipose differentiation including CCAAT/enhancer-binding protein-α and adiponectin were markedly up-regulated in response to lymphatic fluid stasis in the tail and axillary models. Expression of these markers increased in edematous tissues according to the gradient of lymphatic stasis distal to the wound. Immunohistochemical analysis further demonstrated that adiponectin and peroxisome proliferator-activated receptor-γ, another critical adipogenic transcription factor, followed similar expression gradients. Finally, adiponectin and peroxisome proliferator-activated receptor-γ expression localized to a variety of cell types in newly formed subcutaneous fat. The mouse-tail model of lymphedema demonstrates pathologic findings similar to clinical lymphedema, including fat deposition and fibrosis. The authors show that lymphatic fluid stasis potently up-regulates the expression of fat differentiation markers both spatially and temporally. These studies elucidate mechanisms regulating abnormal fat deposition in lymphedema pathogenesis and therefore provide a basis for developing targeted treatments.

Regulation of Adipogenesis by Lymphatic Fluid Stasis

Although fat deposition is a defining clinical characteristic of lymphedema, the cellular mechanisms that regulate this response remain unknown. The goals of this two-part study were to determine the effect of lymphatic fluid stasis on adipogenesis and inflammation (part I) and how these changes regulate the temporal and spatial expression of fat differentiation genes (part II). Adult female mice underwent tail lymphatic ablation and were euthanized 6 weeks after surgery (n = 20). Fat deposition, fibrosis, and inflammation were then analyzed in the regions of the tail exposed to lymphatic fluid stasis as compared with normal lymphatic flow. Lymphatic fluid stasis in the tail resulted in significant subcutaneous fat deposition, with a 2-fold increase in fat thickness (p < 0.01). In addition, lymphatic stasis was associated with subcutaneous fat fibrosis and collagen deposition. Adipogenesis in response to lymphatic fluid stasis was associated with a marked mononuclear cell inflammatory response (5-fold increase in CD45 cells; p < 0.001). In addition, the authors noted a significant increase in the number of monocytes/macrophages as identified by F4/80 immunohistochemistry (p < 0.001). The mouse-tail model has pathologic findings that are similar to clinical lymphedema, including fat deposition, fibrosis, and inflammation. Adipogenesis in response to lymphatic fluid stasis closely resembles this process in obesity. This model therefore provides an excellent means with which to study the molecular mechanisms that regulate the pathophysiology of lymphedema.

Lymphatic Dysfunction in the Apparently Clinically Normal Contralateral Limbs of Patients With Unilateral Lower Limb Swelling

To determine how often lymphatic dysfunction is bilateral when, clinically, lymphedema appears unilateral. Lymphoscintigraphy was performed after subcutaneous Tc-99m-nanocolloid injection in the first webspaces of both feet. The percentage of injected radioactivity accumulating in the ilioinguinal regions was recorded in dedicated images separately acquired at 60 and 180 minutes after injection. Within a consecutive series of 204 patients, 74 had unilateral clinical lymphedema of whom 68 had abnormal scintigraphy. Of these 68 patients, 46 had unilateral abnormal scintigraphy affecting the clinically abnormal limb, but 20 patients had bilateral abnormal scintigraphy and 2 had unilateral abnormal scintigraphy in the clinically unaffected limb. Thus, 32% (22/68) of patients in whom clinical lymphedema appeared to be unilateral, nevertheless, had abnormal scintigraphy in the clinically normal limb. Twenty-nine patients had no clinical evidence of lymphedema in either limb and were scintigraphically normal bilaterally. Mean ilioinguinal nodal accumulation at 180 minutes in the 44 limbs of 22 of these clinically and scintigraphically normal patients (dedicated ilioinguinal imaging was not performed in all patients) was 13.1% (standard deviation, 8.8%), higher (P = 0.02) than the mean value of 9.3% (standard deviation, 5.0%) in the clinically and scintigraphically normal contralateral limbs of 39 patients with unilateral clinical lymphedema. In the presence of unilateral lymphedema, the contralateral limb is often also abnormal. On lymphoscintigraphy, therefore, care should be taken before diagnosing unilateral lymphatic dysfunction. Quantification should be included in routine lymphoscintigraphy, as reduced ilioinguinal nodal accumulation may be the only apparent abnormality.

Popliteal Node Visualization During Standard Pedal Lymphoscintigraphy for a Swollen Limb Indicates Impaired Lymph Drainage

The objective of our study was to examine the frequency and significance of visualization of popliteal nodes during lymphoscintigraphy for the investigation of lower extremity swelling. Technetium-99m-labeled nanocolloid was injected subcutaneously in the first web spaces of both feet of 204 consecutive patients (69 males, 135 females; age range, 11-79 years) undergoing routine, clinically indicated lymphoscintigraphy; imaging was performed 5, 45, and 150 minutes after injection. The patients were asked not to undertake any vigorous exercise between the injection and completion of imaging. No popliteal nodes were visualized in 29 patients in whom there was no evidence of lymphedema on clinical or lymphoscintigraphic examination (group 1). Unilateral or bilateral popliteal nodes were visualized in 10 of 39 patients (25.6%) with clinical evidence of lymphedema but normal lymphoscintigraphy findings (group 2) (p < 0.005 vs group 1). In 136 patients with clinical evidence of lymphedema and abnormal lymphoscintigraphy findings (group 3), unilateral or bilateral popliteal nodes were visualized in 59 (43.4%) (p < 0.0001 vs group 1). Popliteal nodes were visualized in 40 of 73 limbs with "dermal backflow" (54.8%) and 42 of 335 limbs without dermal backflow (12.5%) (p < 0.0001). Popliteal node visualization after subcutaneous foot web space injection is an important sign of abnormal lymphatic function in patients with clinical lymphedema of the lower extremities.

Exercise in patients with lymphedema: a systematic review of the contemporary literature

Controversy exists regarding the role of exercise in cancer patients with or at risk for lymphedema, particularly breast. We conducted a systematic review of the contemporary literature to distill the weight of the evidence and provide recommendations for exercise and lymphedema care in breast cancer survivors. Publications were retrieved from 11 major medical indices for articles published from 2004 to 2010 using search terms for exercise and lymphedema; 1,303 potential articles were selected, of which 659 articles were reviewed by clinical lymphedema experts for inclusion, yielding 35 articles. After applying exclusion criteria, 19 articles were selected for final review. Information on study design/objectives, participants, outcomes, intervention, results, and study strengths and weaknesses was extracted. Study evidence was also rated according to the Oncology Nursing Society Putting Evidence Into Practice® Weight-of-Evidence Classification. Seven studies were identified addressing resistance exercise, seven studies on aerobic and resistance exercise, and five studies on other exercise modalities. Studies concluded that slowly progressive exercise of varying modalities is not associated with the development or exacerbation of breast cancer-related lymphedema and can be safely pursued with proper supervision. Combined aerobic and resistance exercise appear safe, but confirmation requires larger and more rigorous studies. Strong evidence is now available on the safety of resistance exercise without an increase in risk of lymphedema for breast cancer patients. Comparable studies are needed for other cancer patients at risk for lymphedema. With reasonable precautions, it is safe for breast cancer survivors to exercise throughout the trajectory of their cancer experience, including during treatment.

Non-Invasive Assessment of Human Clinical Lymphedema: The Progress Continues

Lymphatic Research and BiologyVol. 9, No. 1 EditorialNon-Invasive Assessment of Human Clinical Lymphedema: The Progress ContinuesStanley G. RocksonStanley G. RocksonSearch for more papers by this authorPublished Online:19 Mar 2011https://doi.org/10.1089/lrb.2011.9102AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Non-Invasive Assessment of Human Clinical Lymphedema: The Progress Continues." , 9(1), p. 1FiguresReferencesRelatedDetailsCited byThe Hydromechanics of Edema Fluid in Lymphedematous Lower Limb During Intermittent Pneumatic Compression18 December 2015 | Lymphatic Research and Biology, Vol. 13, No. 4 Volume 9Issue 1Mar 2011 InformationCopyright 2011, Mary Ann Liebert, Inc.To cite this article:Stanley G. Rockson.Non-Invasive Assessment of Human Clinical Lymphedema: The Progress Continues.Lymphatic Research and Biology.Mar 2011.1-1.http://doi.org/10.1089/lrb.2011.9102Published in Volume: 9 Issue 1: March 19, 2011PDF download

Lymphoscintigraphy As an Imaging Modality in Lymphatic System

Lymphedema is a chronic debilitating disease that results from chronic lymphatic insufficiency. Lymphoscintigraphy forms an authentic yet simple diagnostic and screening procedure in patients with preclinical and clinical lymphedema of different etiologies. Our study population consisted of 540 patients with diagnosed lymphedema of different etiologies and grading. Here we highlight our experience of lymphoscintigraphy in different clinical situations and staging of lymphedema. Lymphoscintigraphy is a simple, noninvasive procedure, which documents clinical diagnosis and guides the management of Lymphedema

Abstract 3830: Inhibition of IL-4 function decreases fibrosis and lymphatic dysfunction in a mouse model of lymphedema

Abstract Background: Lymphedema, commonly encountered in cancer survivors, is characterized by chronic swelling and fibrosis. Previous studies have shown that fibrotic disorders involving other organ systems are dependent on T-helper 2 (Th-2) chronic inflammatory changes. The purpose of these experiments was therefore to evaluate the role of Th-2 cells in the pathological changes associated with lymphedema. Methods: We developed a surgical mouse model that results in tail lymphedema for prolonged periods (&amp;gt;9 weeks) and is histologically is similar to clinical lymphedema. Using this model in wild-type and athymic nude mice we evaluated the role of T-cells in general on the development of lymphedema and fibrosis. Furthermore, using a specific monoclonal neutralizing antibody against IL-4, a molecule necessary for Th-2 differentiation, we evaluated the role of Th2 cells in the initiation and maintenance of chronic lymphedema. Results: Lymphedema in wild-type mice resulted in a chronic inflammation consisting predominantly of CD-4+cells with a mixed Th1-Th2+ differentiation. Interestingly, application of this model to athymic nude mice resulted in markedly decreased tail edema and fibrosis, demonstrating that these outcomes are T-cell dependent. While inhibition of Th2 differentiation immediately after surgery did not prevent initiation of lymphedema, it did result in early resolution, with a marked reduction in fibrosis and improved lymphatic function 6 weeks post-operatively. Consistent with this, inhibition of Th2 cell function in mice with established lymphedema resulted in resolution of lymphedema and fibrosis with just 3 weekly treatments. In contrast, lymphedema was sustained in animals treated with isotype control. Conclusions: We have shown that Th2 differentiation is necessary for maintenance of the pathologic changes associated with lymphedema. Inhibition of Th2 differentiation completely reversed the fibrosis and lymphatic dysfunction in animals with established lymphedema, with resultant resolution of swelling. These results indicate that similar approaches may be clinically useful in patients with chronic lymphedema. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3830.

Lymph Edema of the Lower Extremities after Lymphadenectomy and Radiotherapy for Cervical Cancer

To assess the incidence of clinical lymph edema after lymphadenectomy and postoperative radiotherapy (RT). From 1994-2002 192 patients with risk factors for recurrence received radiotherapy with FIGO I (58.8%), II (35.4%), III (4.2%) or IV (1.6%). RT consisted of teletherapy (10.4%), brachytherapy of the vaginal vault (20.8%) or a combination of both (68.8%). Additional chemotherapy was given in 69 patients (35.9%). Surgery comprised laparoscopically assisted radical vaginal hysterectomy (LARVH) (35.4%), radical abdominal hysterectomy (RAH) (48.4%), simple hysterectomy (HE) (11.5%) or exenteration (4.7%). 73 patients had lymph node metastases, 119 had negative lymph nodes. In patients with LARVH 6-74 (median 30) lymph nodes were removed, with RAH 3-70 (median 21 lymph nodes), and after HE or exenteration 5-50 (median 13 lymph nodes). 90 patients had 25 or less lymph nodes removed, 83 patients more than 25 lymph nodes removed. Prognostic factors, such as age, FIGO stages, histologic grading and type of histology were well balanced in these cohorts. 45 (23.4%) of all patients developed clinically relevant lymph edema of the lower limb with a median latency of 11 (1-121) months. When 25 or less lymph nodes were removed 17.8% of patients developed leg edema, when more than 25 lymph nodes were removed 32.5% of patients were diagnosed with lymph edema (p = 0.025). Radiotherapy and chemotherapy had no influence on the incidence of leg edema. Overall survival at 5 (10) years was independent of number of lymph nodes removed. The data suggest increasing rates of leg edema with increasing number of lymph nodes dissected independent of the type of radiotherapy and chemotherapy performed. The lymph node sampling policy should be planned carefully in respect to minimize the risk of leg lymph edema.

Lymphatic abnormalities demonstrated by lymphoscintigraphy after lower limb cellulitis

Cellulitis is a common cause for admission to hospital, and repeated episodes are thought to damage the lymphatic system. Lymphoedema is recognized as a condition predisposing to cellulitis but there are no data to suggest its prevalence among a population presenting to hospital with acute cellulitis. To ascertain whether lymphatic abnormalities represent a common problem in patients with lower limb cellulitis. Patients admitted with cellulitis of the lower limb were invited to undergo clinical examination and lymphoscintigraphy. Thirty patients agreed to participate in the study. Fifteen underwent lymphoscintigraphy. Thirteen had abnormal scans indicating impaired lymph drainage (seven patients had clinical lymphoedema). Lymphatic abnormalities represent an important but unrecognized problem in patients with leg cellulitis.

Comparison of standardised lymphoscintigraphic function test and high resolution sonography of the lymphoedema of legs

SummaryPurpose: Comparison of qualitative and quantitative sonography with the lymphoscintigraphic function test and clinical findings in legs. Patients, methods: In 33 patients a lymphoscintigraphic function test of legs combined with measurement of lymph node uptake was performed and subsequently compared with sonography. Sonographic criteria were: Thickness of cutis, thickness of subcutanean fatty tissue and presence of liquid structures or fine disperse tissue structure of lower limbs, foots and toes. Results: In 51 legs uptake values lie in the pathologic area, in four legs in the grey area and in ten legs in the normal area. The cutis thickness in the lower leg shows no significant correlation with the uptake. The determination of the thickness of the subcutanean fatty tissue of the lower leg and of the cutis thickness of the feet turned out to be an unreliable method. In 47% of the medial lower legs and in 57% of the lateral lower legs with clinical lymphoedema sonography is falsely negative. Conclusion: Early lymphoedema is only detectable with the lymphoscintigraphic function test. In the case of clinical lymphoedema clinical examination is more reliable than sonography.

Lymph drainage studied by lymphoscintigraphy in the arms after sentinel node biopsy compared with axillary lymph node dissection following conservative breast cancer surgery

To investigate lymphatic drainage as measured by lymphoscintigraphy in the arms of patients undergoing either sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). From January 2001 to December 2002, 30 patients with unilateral invasive breast carcinoma underwent breast-conserving surgery with SNB and 30 patients with ALND. All patients received radiotherapy to the breast. Lymphoscintigraphy was performed, and skin circulation, skin temperature, and arm volume were measured 2-3 years after radiotherapy. None of the 30 patients who underwent SNB showed any clinical manifestation of lymphedema. Of the 30 patients undergoing ALND, six (20%) had clinical lymphedema, with an arm volume that was >10% larger on the operated than on the non-operated side (P<0.01). Scintigraphically, visual analysis revealed lymphatic dysfunction in three patients, manifested as forearm dermal back flow. Two of these patients also had an increased arm volume. Quantitative analysis showed no differences between the groups, apart from a smaller amount of isotope in the axilla in the ALND group. There was no difference in skin circulation or skin temperature. Our study shows that lymph drainage in the operated arm compared with the non-operated arm was less affected by SNB than by ALND, and that morbidity associated with SNB was lower than with ALND. However, the results do not confirm our hypothesis that lymphoscintigraphy can reveal differences in lymph circulation that are not evident clinically in the form of manifest lymphedema. The most sensitive clinical method of assessing lymph drainage seems to be measurement of arm volume.

Reliability and Validity of Arm Volume Measurements for Assessment of Lymphedema

Arm lymphedema following breast cancer surgery is a continuing problem. In this study, we assessed the reliability and validity of circumferential measurements and water displacement for measuring upper-limb volume. Participants included subjects who had had breast cancer surgery, including axillary dissection--19 with and 22 without a diagnosis of arm lymphedema--and 25 control subjects. Two raters measured each subject by using circumferential tape measurements at specified distances from the fingertips and in relation to anatomic landmarks and by using water displacement. Interrater reliability was calculated by analysis of variance and multilevel modeling. Volumes from circumferential measurements were compared with those from water displacement by use of means and correlation coefficients, respectively. The standard error of measurement, minimum detectable change (MDC), and limits of agreement (LOA) for volumes also were calculated. Arm volumes obtained with these methods had high reliability. Compared with volumes from water displacement, volumes from circumferential measurements had high validity, although these volumes were slightly larger. Expected differences between subjects with and without clinical lymphedema following breast cancer were found. The MDC of volumes or the error associated with a single measure for data based on anatomic landmarks was lower than that based on distance from fingertips. The mean LOA with water displacement were lower for data based on anatomic landmarks than for data based on distance from fingertips. Volumes calculated from anatomic landmarks are reliable, valid, and more accurate than those obtained from circumferential measurements based on distance from fingertips.

Prevalence and risk factors for development of lymphedema following breast cancer treatment

Early detection and multimodality therapy has resulted in an overall improvement of survival among breast cancer patients. Despite a significant shift in the treatment approach from radical mastectomy to breast conservation a significant number of patients develop lymphedema. This study was conducted to evaluate the prevalence and risk factors for development of lymphedema. Retrospective analysis for prevalence of lymphedema in a tertiary care regional cancer centre. Three hundred treated breast cancer patients with a minimum follow up of one year were evaluated for the prevalence and risk factors for lymphedema. Lymphedema was assessed using a serial circumferential measurement method. More than 3 cm difference in circumference is considered as clinical significant lymphedema. Univariate and multivariate analysis were performed for evaluating the risk factors by using the Chi square test and Cox logistic regression analysis. The prevalence of clinically significant lymphedema was 33.5 % and 17.2 % had severe lymphedema. The prevalence of lymphedema was 13.4 % in patients treated with surgery only where as the prevalence was 42.4% in patients treated with surgery and radiotherapy. Stage of the disease, body surface area > 1. 5 m2, presence of co-morbid conditions, post operative radiotherapy and anthracycline based chemotherapy were significant risk factors in univariate analysis where as axillary irradiation and presence of co-morbid conditions have emerged as independent risk factors in multivariate analysis (P < 0.001). Post treatment lymphedema continues to be a significant problem following breast cancer therapy. Presence of co-morbid conditions and axillary radiation significantly increases the risk of lymphedema. A combination of axillary dissection and axillary radiation should be avoided whenever feasible to avoid lymphedema.

Compression prophylaxis may increase the potential for flight-associated lymphoedema after breast cancer treatment

This study aimed to assess exposure to flying in breast cancer survivors and assess the relationship of flying to lymphoedema. A total of 293 relapse-free breast cancer survivors with known pathology and treatment details and prospectively measured arm circumferences were surveyed for their flight exposure and precautions history. Of these, 287 responded, with a mean follow-up of 31.6 (4–111) months. A total of 50.5% had flown, and of these, 27% had travelled overseas. The mean number of flights was 5.3 (1–100); 24% had taken lymphoedema precautions, 90% of which utilized compression techniques. There was no significant difference in lymphoedema rates for fliers (11.2%) and non-fliers (8.3%). No woman reported permanent (new or increased) swelling after flying. Of the nine reporting temporary swelling, six reported 1–3 concurrent potential risk factors. On regression modelling for both measured and self-reported swelling endpoints the use of precautions (OR 5.6 for lymphoedema and 3.7 for flight-related temporary swelling) were statistically significant. For patient-reported swelling, the number of positive nodes (OR 1.2) and the number of overseas flights (OR 1.4) was also significant, whereas for clinical lymphoedema age (OR 1.07) was significant. We conclude that domestic air travel (<4.5 h) is low risk and that compression devices are possibly counterproductive.

Abnormalities of the leg lymphatics are not specific for bancroftian filariasis

Studies using conventional angiography or non-invasive scintigraphy have revealed widespread abnormalities in the lymphatics of the legs of patients with bancroftian filariasis, regardless of whether clinical lymphoedema is present. To determine if the observed changes were specific for filarial infections, we imaged the lymphatics of both legs in native residents of an area in Brazil where filariasis is not endemic. Study participants were matched by age, socioeconomic status and physical activities to patients with filariasis in Recife, evaluated in parallel. Based on textbook criteria, only one of 15 study participants had a completely normal lymphoscintigram. Modest to severe pathology of the leg lymphatics was observed in the remaining 14 residents of the non-endemic area and in 49 of 50 patients with bancroftian filariasis. These results indicated that factors other than filarial worms are a common cause of subclinical pathology of the leg lymphatics in north-eastern Brazil, and that the latter is not specific for bancroftian filariasis.

Allograft survival prolongation after microsurgical lymphatic reconstruction in a short-term immunosuppressed rat small bowel transplantation model

“It is clear, however, that today's discovery by bacteriologists, immunologists, biochemists, pathologists and other specialists have their origin in the questions raised by early surgical pioneers, whose primary concern was adequate wound coverage and healing.” This quotation by Felix T. Rapaport and plastic surgeon John Marquis Converse represents the early history of transplantation. “It remains there to this day and did him lasting good in many ways.” This statement by Sir Winston Churchill of his donation of a skin allograft to a brother officer in 1899 illustrates an example of allogeneic grafting without immunosuppression. “Their vasculature is established by direct end-to-end anastomosis of some at least of vessels in the graft with the vessels of the bed.” A quotation from Sir Peter Medawar's classic Harvey Lecture of March 21, 1957, describes the importance of vessel connections between the graft and the host to prevent rejection of allografts described by others. “Nature presents us with her protests against removing lymphatics, with her protests against any lymphatic malfunctioning.” Leo Clodius, who spent his career studying lymphatics, opened with these words a congress on lymphology in 1987. He referred later to the clinical lymphedema treatment by plastic and microsurgical operations. These four quotations demonstrate that (1) grafts can be transplanted allogeneically without immunosuppression; (2) they will not be rejected if no connection to the vascular system of the host take place, like in the brain; (3) but will be rejected if vessels of the host shoot up to the allograft; and (4) lymphatics also belong to a vascular system that transports immunological circulating cells. Interestingly, the possibility of microsurgical reconstructions of the lymphatic system is not seen to be necessary in transplantation today. It is unclear why the actual state of the art of microneurolymphovascular transplantation in plastic surgery is not considered in today's transplantation research.

An Experimental Model for Chronic Lymphedema

Although a multitude of operations exist for the treatment of lymphedema, none is highly successful. An experimental model that reliably and easily produces chronic lymphedema in an extremity would be useful to study treatments in a controlled and comparative manner and would enhance our understanding of the physiology and treatment of lymphedema. Many models that simulate clinical lymphedema have been described, but they suffer from cumbersome protocols, high laboratory costs, and an inconsistent yield of permanent lymphedema. We describe an experimental model for chronic lymphedema in the lower extremity of the rat that creates a lymphatic block in the groin induced by radiation treatment and one operation--surgical division of the superficial and deep lymphatics. All animals develop stable chronic lymphedema of the lower extremity within days of operation, with swelling that persists for at least 9 months. A mortality rate of 8 percent was associated with this technique. Methods for quantification of limb swelling are described, as is analysis of the lymphatic block by lymphoscintigraphic imaging of lymph channels and nodes. This model has the advantages of simplicity of technique, cost-effective use of rodent subjects, reproducibility of lymphedema, and quantification of results.

Lymphatic hypoplasia without lymphoedema

A prospective study of lymph vessel abnormalities in the lower limbs of 744 adult patients without lymphoedema revealed seven patients with lymphatic hypoplasia, a prevalence rate of 0.94% (95% limits of confidence 0.24-1.64%). The prevalence was higher in males (1.1%) than in females (0.5%) but the difference is not statistically significant. This is much higher than any available estimate of the prevalence of primary lymphoedema of the lower limbs and suggests that lymphatic hypoplasia is merely one factor in the aetiology of clinical lymphoedema.