Lymphatic failure and lymphatic interventions: Knowledge gaps and future directions for a new frontier in congenital heart disease.

Lymphatic failure is a broad term that describes the lymphatic circulation's inability to adequately transport fluid and solutes out of the interstitium and into the systemic venous circulation, which can result in dysfunction and dysregulation of immune responses, dietary fat absorption, and fluid balance maintenance. Several investigations have recently elucidated the nexus between lymphatic failure and congenital heart disease, and the associated morbidity and mortality is now well-recognized. However, the precise pathophysiology and pathogenesis of lymphatic failure remains poorly understood and relatively understudied, and there are no targeted therapeutics or interventions to reliably prevent its development and progression. Thus, there is growing enthusiasm towards the development and application of novel percutaneous and surgical lymphatic interventions. Moreover, there is consensus that further investigations are needed to delineate the underlying mechanisms of lymphatic failure, which could help identify novel therapeutic targets and develop innovative procedures to improve the overall quality of life and survival of these patients. With these considerations, this review aims to provide an overview of the lymphatic circulation and its vasculature as it relates to current understandings into the pathophysiology and pathogenesis of lymphatic failure in patients with congenital heart disease, while also summarizing strategies for evaluating and managing lymphatic complications, as well as specific areas of interest for future translational and clinical research efforts.

Lymphoscintigraphy of the Lower Extremities: Discrepancies Between Superficial and Deep Lymphatic Systems.

ABSTRACT: We describe a 57-year-old man with prostate cancer. A radical prostatectomy with a pelvic lymphadenectomy was performed. After 2 years, a mild swelling of the lower extremities appeared, and the patient was referred for lower-limb lymphoscintigraphy. A lymphoscintigraphy of the superficial lymphatic system in the limbs showed prominent, dermal backflow in the area of the right hypogastrium. Lymphoscintigraphy of the deep lymphatic system showed reflux in the left hypogastrium. This discrepancy between the findings in the superficial and deep lower-limb lymphatic systems was explained by asymmetric sampling of the lymph nodes during the lymphadenectomy.

The Lymphatic System: A Sometimes-Forgotten Compartment in Pharmaceutical Sciences.

The uniqueness of structure and physiology of the lymphatic system make it challenging to delineate all its contributions in the maintenance of our health. However, in the past two decades, the understanding of the importance of the function of this system has evolved and more appreciation has been drawn to the distinctive role it plays in health and disease. The lymphatic system has been linked to the pathophysiology of numerous ailments including cancer, various metabolic diseases, inflammatory conditions, and infections. Moreover, it has also been revealed that lymphatic targeted formulations can enhance the delivery of drugs through the lymphatic system to the bloodstream, bypassing the hepatic first-pass metabolism if taken orally, thus increasing the bioavailability, and improving the pharmacokinetic and toxicological profiles in general. Engineering lymphotropic preparations requires the understanding of many factors, the most important one being that of the physiological environment which they will encounter. Therefore, in this review, we detail the basic structure of the lymphatic system, then highlight the therapeutic and the pharmacokinetic benefits of drug delivery into the lymphatic system. The criteria for drugs and formulations used for lymphotropic delivery are also detailed with a contemporary overview of various studies undertaken in this field.

Association of Lymphatic Abnormalities with Early Complications after Fontan Operation.

BACKGROUND: Increased central venous pressure is inherent in Fontan circulation but not strongly related to Fontan complication. Abnormalities of the lymphatic circulation may play a crucial role in early Fontan complications. METHODS: This was a retrospective, single-center study of patients undergoing Fontan operation from 2008 to 2015. The primary outcome was significant early Fontan complication defined as secondary in-hospital treatment due to peripheral edema, ascites, pleural effusions, protein-losing enteropathy, or plastic bronchitis. All patients received T2-weighted magnetic resonance images to assess abdominal and thoracic lymphatic perfusion pattern 6 months after Fontan completion with respect to localization, distribution, and extension of lymphatic perfusion pattern (type 1-4) and with application of an area score (0-12 points). RESULTS: Nine out of 42 patients developed early Fontan complication. Patients with complication had longer chest tube drainage (mean 28 [interquartile range [IQR]: 13-60] vs. 13 [IQR: 2-22] days, p = 0.01) and more often obstructions in the Fontan circuit 6 months after surgery (56 vs. 15%, p = 0.02). Twelve patients showed little or no abnormalities of lymphatic perfusion (lymphatic perfusion pattern type 1). Most frequently magnetic resonance imaging showed lymphatic congestion in the supraclavicular region (24/42 patients). Paramesenteric lymphatic congestion was observed in eight patients. Patients with early Fontan complications presented with higher lymphatic area score (6 [min-max: 2-10] vs. 2 [min-max: 0-8]), p = 0.001) and greater distribution and extension of thoracic lymphatic congestion (type 3-4: n = 5/9 vs. n = 1/33, p = 0.001). CONCLUSION: Early Fontan complication is related to hemodynamic factors such as circuit obstruction and to the occurrence and extent of lymphatic congestion.

Dysfunction of dermal initial lymphatics of the arm and upper body quadrant causes congenital arm lymphedema.

OBJECTIVE: The objective of this study was to explore the pathologic process underlying primary lymphedema. METHODS: Twenty-seven patients with unilateral congenital arm lymphedema who visited our clinic from January 1, 2014, to May 30, 2019, were enrolled. The patients' clinical signs and the findings of indocyanine green (ICG) lymphography, skin tissue immunohistochemical staining, and whole exome sequencing of tissue and blood were evaluated. RESULTS: Among the 27 patients, 11 were diagnosed with stage II and 16 were diagnosed with stage III lymphedema. No lymphatic vessels were visualized in the affected arm in 25 of 27 (93%) patients who underwent ICG lymphography; likewise, no lymphatics were found in the territories of axillary lymph node drainage in the trunk, irrespective of any anomalies of the axillary lymph nodes. In only two (7%) patients, an unclear lymphatic trunk gradually appeared in the dorsum of the affected hand. The number of initial lymphatics was increased in the skin specimens of all nine patients in whom lymphatics were not demonstrated by ICG lymphography. Among 14 tested patients, we found compound heterozygote variants in the PIEZO1 gene in only one (7%) patient. Two missense variants, c.4072C>T; p.Arg1358Cys and c.5033C>T; p. Ala1678Val, were identified and found to have been inherited from the father and mother, respectively. No other pathogenic or likely pathogenic variants of currently known lymphedema-related genes were identified in the remaining 13 patients. No genetic difference was found between the lymphedematous and nonedematous healthy skin tissue of the same person. CONCLUSIONS: Segmental or regional dysfunction of the dermal initial lymphatics causes congenital arm lymphedema and may have implications for clinical treatment.

Degradation of lymphatic anatomy and function in early venous insufficiency.

OBJECTIVE: We used near-infrared fluorescence lymphatic imaging in a pilot study to assess the lymphatics in preulcerative (C2-C4) venous insufficiency and determine whether involvement and/or degradation of lymphatic anatomy or function could play a role in the progression of chronic venous insufficiency. We also explored the role of lymphatics in early peripheral arterial disease. METHODS: After informed consent and intradermal injections of indocyanine green for rapid lymphatic uptake, near-infrared fluorescence lymphatic imaging was used to assess the lymphatic anatomic structure and quantify the lymphatic propulsion rates in subjects with early venous insufficiency. The anatomic observations included interstitial backflow, characterized by the abnormal spreading of indocyanine green from the injection site primarily into the surrounding interstitial tissues; dermal backflow, characterized by the retrograde movement of dye-laden lymph from collecting lymphatics into the lymphatic capillaries; and lymphatic vessel segmentation and dilation. RESULTS: Ten subjects with venous insufficiency were enrolled, resulting in two legs with C2 disease, nine legs with C3 disease, eight legs with C4 disease, and one leg with C5 disease. Interstitial and/or dermal backflow were observed in 25%, 33%, and 41% of the injection sites in each limb with C2, C3, and C4 disease, respectively. Distinct vessel segmentation and dilation were observed in limbs with a C3 and higher classification, and dermal backflow proximal to the injection sites was observed in two legs with C4 disease and in the inguinal region of the C5 study subject. The overall average lymph propulsion rates were 1.3 ± 0.4, 1.2 ± 0.7, and 0.8 ± 0.5 contractile events/min for limbs with C2, C3, and C4 disease, respectively. One subject with peripheral arterial disease, who had previously undergone bypass surgery, presented with extensive dermal backflow and lymphatic reflux. CONCLUSIONS: Near-infrared fluorescence lymphatic imaging demonstrated that, compared with normal health subjects, the lymphatic anatomy and contractile function generally degrade with the severity of venous insufficiency. Lymphatic abnormalities mimic those in early cancer-acquired lymphedema subjects, as previously observed by us and others. Additional studies are needed to decipher the relationship, including any causality, between lymphatic dysfunction and peripheral vascular disease and venous insufficiency.

Surgical Approach to Lymphedema Reduction.

PURPOSE OF REVIEW: For patients who have or may develop lymphedema due to oncologic resection, surgical options are available to prevent and treat this chronic disease. Here, we review the current pathophysiology, classification systems, surgical preventive techniques, and treatment options for lymphedema reduction. RECENT FINDINGS: Preventive surgical techniques, including de-escalation of axillary surgery, sentinel lymph node biopsy (SLNB), axillary reverse mapping (ARM), and lymphedema microsurgical preventive healing approach (LYMPHA), have been shown to reduce the incidence of lymphedema. Water displacement remains the gold standard for measuring limb volume and classification of lymphedema; however, lymphoscintigraphy and ICG lymphography are two novel imaging techniques that are now utilized to characterize lymphedema and guide management. Complete decongestive therapy (CDT) remains the mainstay of treatment. Vascularized lymph node transfer (VLNT) and lymphovenous bypass have shown promising results, particularly in advanced lymphedema stages. Combination therapy, incorporating both surgical and non-surgical approaches to lymphedema, yields best patient outcomes. Lymphedema is a chronic disease wherein management requires a combination of surgical and conservative treatments. Standardization in lymphedema staging, key outcome indicators, and quantitative data will be critical to establish the absolute best practices in lymphedema diagnosis and treatment.

Innominate Vein Turn-down Procedure for Failing Fontan Circulation.

After the Fontan, systemic venous hypertension induces pathophysiologic changes in the lymphatic system that can result in complications of pleural effusion, ascites, plastic bronchitis, and protein losing enteropathy. Advances in medical therapy and novel interventional approaches have not substantially improved the poor prognosis of these complications. A more physiological approach has been developed by decompression of the thoracic duct to the lower pressure common atrium with a concomitant increase of preload. Diverting the innominate vein to the common atrium increases the transport capacity of the thoracic duct, which in most patients enters the circulation at the left subclavian-jugular vein junction. Contrary to the fenestrated Fontan circulation, in which the thoracic duct is drained into the high pressure Fontan circulation, turn down of the innominate vein to the common atrium effectively decompresses the thoracic duct to the lower pressure system with "diastolic suctioning" of lymph. Innominate vein turn-down may be considered for medical-refractory post-Fontan lymphatic complications of persistent chylothorax, plastic bronchitis, and protein losing enteropathy. Prophylactic innominate vein turn-down may also be considered at time of the Fontan operation for patients that are higher risk for lymphatic complications.

Prevalence and Cause of Early Fontan Complications: Does the Lymphatic Circulation Play a Role?

Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein-losing enteropathy. However, the role of the lymphatic circulation in early post-Fontan outcomes is not well defined. Methods and Results This was a retrospective, single-center study of patients undergoing first-time Fontan completion from 2012 to 2017. The primary outcome was early Fontan complication ≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions in the absence of Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2-weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty-eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high-grade lymphatic abnormalities had 6 times greater odds of developing early complications (P=0.001). Conclusions There is substantial morbidity in the early post-Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher-grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.

Lymphedema: A Practical Approach and Clinical Update.

The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the clinical approaches based on new knowledge and developments of the lymphatic system are covered. The lymphatic system has 3 major functions: (1) the preservation of fluid balance; (2) a nutritional function, as intestinal lymphatics are responsible for fat absorption; and (3) host defense. Lymph vessels return the capillary ultrafiltrate and escaped plasma proteins from most tissues back, ultimately, to the blood circulation. Hence, lymphatics are responsible for maintaining tissue (and plasma) volume homeostasis. Impaired lymph drainage results in peripheral edema (lymphedema) and may have more far-reaching effects on cardiovascular disease, in particular hypertension and atherosclerosis. Lymphatics have an important immune surveillance function, as they represent the principal route of transport from tissues for antigen and immune cells. Intestinal lymphatics (lacteals) are responsible for most fat absorption, first documented by Gaspare Aselli in 1627, when the lymphatic system was discovered. A relationship between fat and lymphatics may exist well beyond the gut alone. Fat deposition is a defining clinical characteristic of lymphedema. Suction-assisted lipectomy of lymphedema has shown the swelling is not just fluid but is dominated by fat. Lymphatics are the preferred route for the metastatic spread of cancer. Accordingly, the lymphatic system may be important for defense against cancer by generating immune responses to malignant cell antigens. Preventing lymphatic entry and propagation of malignant metastasis would effectively render the cancer nonfatal. As one can see, the lymphatic circulation is fundamentally important to cardiovascular disease, infection and immunity, cancer, and, in all likelihood, obesity - 4 of the major challenges to health care in the 21st century.

Sclerotherapy for lymphatic malformations of head and neck: Systematic review and meta-analysis.

BACKGROUND: Percutaneous sclerotherapy is a commonly used modality for treatment of lymphatic malformations (LMs) of the head, face, and neck. The safety and efficacy of sclerotherapy with various agents for diverse pathologic types of LMs have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for treatment of LMs of the head, face, and neck. METHODS: We searched PubMed, MEDLINE, and Embase from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy of head, face, and neck LMs. Two independent reviewers selected studies and abstracted data. The primary outcomes were complete and partial resolution of the LM. Data were analyzed using random-effects meta-analysis. RESULTS: There were 25 studies reporting on 726 patients included. The overall rate of complete cure of any pathologic type of LM after percutaneous sclerotherapy with any agent was 50.5% (95% confidence interval, 36.6%-64.3%). Macrocystic lesions had a cure rate of 53.1% compared with cure rates of 35.1% for microcystic lesions and 31.1% for mixed lesions. Regarding agents, doxycycline had the highest cure rate (62.4%) compared with all other agents. Overall permanent morbidity or mortality was 1.2% (95% confidence interval, 0.4%-2.0%) with no deaths. I2 values were >50% for most outcomes, indicating substantial heterogeneity. CONCLUSIONS: Our systematic review and meta-analysis of 25 studies and >700 patients found that percutaneous sclerotherapy is a safe and effective modality for treatment of LMs of the head, neck, and face.

The Concept of Chronic Edema-A Neglected Public Health Issue and an International Response: The LIMPRINT Study.

Lymphedema has always been a neglected global health care problem. A central requirement for the development of any chronic disease is the clear use of public health definitions that can be used internationally to define populations. The term "lymphedema" has historically been defined as either primary, resulting from failure of lymphatic development, or secondary, following damage to the lymphatics (e.g., cancer treatment, injury, or filariasis). Attempts to integrate causes of edema arising from damage to the venous system or the effects of gravity, immobility, and systemic disease have rarely been integrated. More recently, the prominent role of the lymphatics in tissue fluid homeostasis in all forms of chronic edema has been recognized. These advances led to the development of the term: "Chronic edema: a broad term used to describe edema, which has been present for more than three months." It can be considered an umbrella term that includes not only conventional "lymphedema" but also chronic swelling, which may have a more complex cause. This definition has been adapted in the international epidemiology study (LIMPRINT) that identified people throughout the health and social care systems in participating countries. Clearer definitions will allow for examination of this important public health problem that is likely to escalate given the projections of an aging population with multiple comorbidities. It will be possible to define both the hidden mortality and morbidity associated with complications, such as cellulitis and the impact on health-related quality of life. This evidence is urgently required to lobby for increased resource and effective health care in an increasingly competitive health care arena in which more established conditions have greater priority and funding.

LIMPRINT in Australia.

Background and Study Objective: Australia was one of nine participating countries in the epidemiology Phase II Lymphoedema Impact and Prevalence - International (LIMPRINT) project to determine the number of people with chronic edema (CO) in local health services. Methods and Results: Data collection occurred through questionnaire-based interviews and clinical assessment with provided LIMPRINT tools. Four different types of services across three states in Australia participated. A total of 222 adults participated with an age range from 22 to 102 years, and 60% were female. Site 1 included three residential care facilities (54% of participants had swelling), site 2 was community-delivered aged care services (24% of participants had swelling), site 3 was a hospital setting (facility-based prevalence study; 28% of participants had swelling), and site 4 was a wound treatment center (specific patient population; 100% of participants had swelling). Of those with CO or secondary lymphedema, 93% were not related to cancer, the lower limbs were affected in 51% of cases, and 18% of participants with swelling reported one or more episodes of cellulitis in the previous year. Wounds were identified in 47% (n = 105) of all participants with more than half of those with wounds coming from the dedicated wound clinic. Leg/foot ulcer was the most common type of wound (65%, n = 68). Conclusions: Distances between services, lack of specialized services, and various state funding models contribute to inequities in CO treatment. Understanding the high number of noncancer-related CO presentations will assist health services to provide timely effective care and improve referral pathways.

The Development and Validation of the LIMPRINT Methodology.

The acronym Limprint stands for Lymphedema IMpact and PRevalence INTernational and was run under the auspices of the International Lymphedema Framework (ILF), a charity dedicated to improving provision of care globally. The primary aim was to identify the number of people with chronic edema (chronic edema present for >3 months and due to a range of underlying etiologies and associated risk factors) within diverse health services in nine participating countries and to determine its impact using validated methods. An international protocol and sampling framework, online data capture system, and standard operating procedures were adopted. An international consensus was used to create a core data tool that covered 13 domains. Specialist data on demographics and disability, details of swelling, wounds, cancer, and health-related quality of life were also available for sites. The study protocol was designed to allow flexibility in the types of studies undertaken within complex health care systems. All cases were confirmed using the modified pitting test. Sensitivity and specificity for this method were determined in Japanese and European populations. Following confirmation of a chronic edema case, Lymphologists defined whether it was a primary of a secondary form. The study was designed to provide robust evidence that chronic edema is an important and unrecognized public health problem in health services with significant morbidity. Without evidence of the size and complexity, it will remain considered a rare phenomenon and people affected will be denied access to appropriate treatment that would allow them to have fulfilled and productive lives.

Clinical and Ethical Challenges in Undertaking LIMPRINT in Vulnerable Populations.

Background and Study Objective: To estimate the prevalence of chronic edema (CO) and wounds within two vulnerable populations, a male high security prison in the East Midlands (United Kingdom) and residential and nursing homes in the United Kingdom and Australia. Methods and Results: Methods for screening for CO and wounds were adapted from the main LIMPRINT methodology. Prison Population: In total, 195 inmates were recruited with 22 (11%) having CO. While the majority were white Caucasian (156/83.4%) a further 20 (10.7%) were dark skinned with 11 (5.95%) from other minority populations. Comorbidities included 123 (63%) smokers, 22 (11%) alcohol dependant, 60 (31%) with mental health problems, and 35 (18%) a history of self-harm. Only three had a current wound with 30 (16%) having had a traumatic stab wound. Residential and Nursing Homes (United Kingdom and Australia): In the United Kingdom, the total population available for inclusion was 189 with only 137 (73%) recruited. Seventy-two of the 137 (52%) suffered from CO and a further 16 (23%) had a history of cellulitis. Results from the Australian residential care facilities have been published in full. In summary, of the 37 participants 20 (54%) experienced CO with 25 (68%) having comorbidities and 11 (30%) having a concurrent wound. Conclusion: Obtaining an accurate picture of the prevalence and impact of CO in vulnerable populations is extremely challenging due to issues of access and consent. Lack of reliable data for these populations will contribute to poor service provision.

Lymphedema Impact and Prevalence International Study: The Canadian Data.

Background: Chronic edema/lymphedema is defined as edema present for more than 3 months. It is underrecognized and undertreated. The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT), to estimate the prevalence and impact of chronic edema in heterogeneous populations. Canada participated in this study. Methods and Results: Participants were recruited from an outpatient chronic wound management clinic. At a study visit, the following tools were administered: The Core Tool, Demographics and Disability assessment (WHODAS 2.0), Quality-of-life assessment (LYMQOL + EQ-5D), Details of swelling, Wound assessment, and Cancer. Data were entered into an international database (Clindex), and country-specific data were analyzed. Sixty-eight subjects were enrolled. Fifty-seven percent were males and 43% females. More than 90% were older than 45 years. Only 7.35% had primary lymphedema. Most had lower extremity edema (65 of 68). Over half (47.06%) were morbidly obese with body mass index of >40. The most common underlying condition was venous disease. Only 8 of 68 had a history of cancer. While 72.06% had a history of cellulitis, only 10.2% had been hospitalized in the past year. 39.71% had an open wound. More than 75% had received multilayer bandaging, compression garments, wound dressings, and extensive counseling. Few had received manual lymphatic drainage, which is not funded. Disability was less than expected. Conclusion: Chronic edema/lymphedema is an underrecognized condition. These data and the wider LIMPRINT study are important tools to advocate for wider recognition and funding of treatment by health care systems.

LIMPRINT: Estimation of the Prevalence of Lymphoedema/Chronic Oedema in Acute Hospital in In-Patients.

Background: To estimate the prevalence of lymphedema/chronic edema (CO) and wounds in acute hospital inpatients in five different countries. Methods and Results: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, and Australia) and one hospital oncology inpatient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphedema/CO was present in 723 of them (38%). Main risk factors associated with CO were age, morbid obesity, and heart failure, as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with CO and wounds (24.8%) and CO alone (14.1%) compared to the 1.5% prevalence in patients without CO. Conclusion: Lymphedema/CO is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency, and heart failure. Our results strongly suggest a hidden health care burden and cost linked to CO independently of chronic wounds.

LIMPRINT Study: The Turkish Experience.

Background: Lymphedema and chronic edema is a major health care problem in both developed and nondeveloped countries The Lymphoedema Impact and Prevelance - International (LIMPRINT) study is an international health service-based study to determine the prevalence and functional impact in adult populations of member countries of the International Lymphoedema Framework (ILF). Methods and Results: A total of 1051 patients from eight centers in Turkey were recruited using the LIMPRINT study protocol. Data were collected using the core and module tools that assess the demographic and clinical properties as well as disability and quality of life (QoL). Most of the Turkish patients were recruited from specialist lymphedema services and were found to be women, housewives, and having secondary lymphedema because of cancer treatment. The duration of lymphedema was commonly <5 years and most of them had International Society of Lymphology (ISL) grade 2 lymphedema. Cellulitis, infection, and wounds were uncommon. The majority of patients did not get any treatment or advice before. Most of the patients had impaired QoL and decreased functionality, but psychological support was neglected. Although most had social health security access to lymphedema centers, nevertheless access seemed difficult because of distance and cost. Conclusion: The study has shown the current status and characteristics of lymphedema patients, treatment conditions, the unmet need for the diagnosis and treatment, as well as burden of the disease in both patients and families in Turkey. National health policies are needed for the prevention, diagnosis, and treatment in Turkey that utilize this informative data.

LIMPRINT: Prevalence of Chronic Edema in Health Services in Copenhagen, Denmark.

Background: The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT), to estimate the prevalence and impact of chronic edema (CO) in heterogeneous populations. Methods and Results: A validation study using the LIMPRINT methodology was undertaken in Denmark. Participants with CO were identified from inpatient services and compared with those identified within a specialist lymphedema service and three primary care settings. Of 452 inpatients available for screening, CO was present in 177 (39%) and absent in 275 (61%). In addition, 723 participants were found from specialist and primary care services (LPCSs). Inpatients were significantly older and more likely to be underweight or normal weight. They were more likely to suffer from heart failure/ischaemic heart disease (44.6% vs. 23.4%, p < 0.001) and have neurological problems (18.1% vs. 10.9% p = 0.009). Patients in the inpatient group were nearly all suffering from secondary lymphedema and were less likely to have a cancer or venous diagnosis, but more likely to have immobility as the cause of CO (44.0% vs. 17.7%, p < 0.001). No inpatients had midline CO compared with 30 within LPCSs. Fewer in the inpatient group had standard CO treatment (17.1% vs. 73.5%, p < 0.001) and subjective control of swelling was worse (19.9% vs. 66.7%, p < 0.001). While the inpatient group experienced fewer acute infections, when they did so, they were more likely to be admitted to hospital for this (78.6% vs. 51.0%, p = 0.049). Conclusion: The prevalence of CO in inpatient facilities is high and those with CO have multiple comorbidities that vary according to setting. The feasibility study showed that the methodology could be adapted for use in different health systems.