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Obesity-Induced Lymphedema
Abstract
The purpose of this study was to characterize obesity as a novel cause of lower extremity lymphedema. Fifty-one patients with a body mass index (BMI) >30 without any potential cause of lymphedema were evaluated by lymphoscintigraphy. Group 1 (n=33) was at their maximum BMI; individuals with lymphatic dysfunction had a greater BMI (72.0) compared to subjects with normal function (37.7) (p<0.0001). BMI predicted lymphoscintigram result: abnormal if BMI >60 and normal if BMI <50. Group 2 (n=18) had lost weight and was not at their maximum BMI: patients who reduced their BMI from >60 to <50 had normal (n=4) or abnormal (n=3) lymphatic function. Patients with obesity-induced lymphedema, or who are at risk for the condition, are referred to a surgical weight loss center.
... Greene et al. 44 performed a study that demonstrated a ''lymphedema-associated BMI threshold,'' an association between BMI and impaired lymphatic function (resulting in CO). The results of this study are compared with the study results for this article, to test the threshold alongside the study paper BMIs. ...
... Greene et al. 44 assessed 33 obese patients, with a BMI greater than 30 kg/m 2 , for the presence of lymphedema, using lymphoscintigraphy scans. The group consisted of patients who were at their maximum BMI (had not yet lost weight through bariatric surgery or diet), which is similar to the study article's patients. ...
... Investigating and comparing the results of both studies is not straightforward. Although 23 participants in our study had BMIs between 40 and 50 kg/m 2 and therefore would have had ''normal'' lymphoscintigrams according to the Greene et al. 44 study, 10 of the study participants had CO (Table 7). ...
Background: Chronic edema (CO) is a complex condition, arising from different factors, including immobility and obesity. Edema and obesity can have a significant impact on quality of life of patients and their families. Understanding how to manage edema in obese patients is an increasing challenge for both patients and clinicians. As effective treatment options are limited for this population, it is more cost-effective for patients to lose weight before starting treatment. When patients cannot maintain weight loss, one option is to have bariatric surgery. This study was part of LIMPRINT: Lymphedema IMpact and PRevalence INTernational, a study with the aim of identifying the prevalence and impact of CO in different countries and health care settings. Study Purpose: To evaluate the prevalence and impact of CO among patients in a United Kingdom bariatric surgical service. Methods and Results: The gold standard pitting test assessed the presence of edema. General (EuroQOL-5 Dimensions [EQ-5D], RAND 36-Item Short Form Health Survey, Version 1.0 [SF-36], Generalized Anxiety Disorder 7-Item Scale [GAD-7] and Patient Health Questionnaire-9 [PHQ-9]), and edema-specific (Lymphedema Quality of Life [LYMQOL]) quality-of-life questionnaires were used to evaluate impact of edema. The prevalence of edema was 52.1% (25 of 48 participants had edema), potentially linked to obesity, immobility, and medications. Most participants had International Society of Lymphology (ISL) Stage I edema. There were no statistically significant differences between the quality of life of participants with and without edema. However, comparing SF-36 results and normative population data indicated that quality of life was much lower than those in the normative population. Conclusions: This study highlights the high prevalence of edema and low quality of life of this bariatric population. ClinicalTrials.gov ID: NCT03154593.
... Individuals with a body mass index (BMI kg/m 2 ) > 30 are more likely to develop secondary upper extremity lymphedema after breast cancer treatment, [4][5][6] and extreme obesity (BMI>60) causes lower extremity disease. [7][8][9] The effects of obesity on patients with established lymphedema, however, is unknown. The purpose of this study was to compare obese individuals with lymphedema to patients with a normal BMI. ...
... Subjects with a BMI >45 were not included because of their risk of having obesity-induced lymphedema. 7,8 Demographic information that was recorded included: age, sex, type of lymphedema (primary or secondary), location (arm, leg), co-morbidities, nodes, presence of dermal backflow), and duration of the condition. One outcome variable was a history of cellulitis of the lymphedematous extremity and whether or not the patient had required hospitalization for an infection. ...
... Extreme obesity (BMI>60) can independently cause lymphedema. [7][8][9] Animal studies have shown that obesity impairs lymphatic transport, reduces the number of lymphatic vessels, abnormally dilates lymphatics, causes smaller lymph nodes, and increases inflammation. [13][14][15] Obese humans have reduced adipose tissue lymphatic drainage of macromolecules compared to lean individuals which promotes inflammation. ...
Background:
Obesity is a risk factor for the development of secondary lymphedema after axillary lymphadenectomy and radiation. The purpose of the study was to determine if obesity influences the morbidity of lymphedema in patients who have the condition.
Methods:
Two cohorts of patients were compared: Group 1 = normal weight, body mass index (BMI kg/m) ≤25; Group 2 = obese (BMI ≥30). Inclusion criteria were patients ≥ 21 years-old with lymphedema confirmed by lymphoscintigraphy. Covariates included age, sex, lymphedema type (primary or secondary), location, comorbidities, lymph node dissection, radiation, lymphoscintigram result, and disease duration. Outcome variables were infection, hospitalization, and degree of limb overgrowth. The cohorts were compared using the Mann-Whitney U-test, Fisher's exact test, and multivariable logistic regression.
Results:
Sixty-seven patients were included: Group 1 (n=33), Group 2 (n=34). Disease duration did not differ between groups (p=0.72). Group 2 was more likely to have an infection (59%), hospitalization (47%), and moderate or severe overgrowth (79%), compared to Group 1 (18%, 6%, and 40% respectively, p<0.001). Multivariable logistic regression showed that obesity was an independent risk factor for infection (OR 7.9, 95% CI 2.5-26.3; p<0.001), hospitalization (OR 30.0, 95% CI 3.6-150.8; p<0.001), and moderate to severe limb overgrowth (OR 6.7, 95% CI 2.1-23.0; p=0.003).
Conclusions:
Obesity negatively affects patients with established lymphedema. Obese individuals are more likely to have infections, hospitalizations, and larger extremities compared to subjects with a normal BMI. Patients with lymphedema should be counseled about the negative effects of obesity on their condition.
... The incidence of PLE has been estimated to be 10.0% in patients with electromyographic tube intubation after neurosurgery [12], 13.5% in patients undergoing thyroid surgery for benign thyroid disease [9], 22.0% for post-extubation laryngeal stridor [6], or 29% for stridor or hoarseness symptoms [20]. ...
... As a risk factor for PLE, high BMI was identified in our multivariable analyses. High BMI can cause greater accumulation of fluids in the peripheral tissue and more frequent edema in surgical patients [22]. Therefore, patients with high BMI should be monitored regularly for PLE occurrence in the postoperative period, although the optimal cut-off point of BMI was not determined in this study. ...
Purpose
Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated.
Methods
A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343).
Results
PLE occurred in 29.4% [95%CI 24.4–34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166–7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160–20.529]) were significant risk factors for PLE.
Conclusions
PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.
... External factors include skeletal muscle contractions, respiratory movements, changes in central venous pressure, pulsations of nearby arteries, and gravitational force [87,92,[95][96][97][98]. Although lymphatic vessels were described almost 400 years ago [99], the molecular and cellular studies of the lymphatic system have mostly occurred the last two decades [100][101][102]. In recent years, the discovery of specific markers for the lymphatic system, such as vascular endothelial growth factor receptor 3 (VEGFR-3), podoplanin (gp38), Lymphatic Vessel Endothelial Receptor 1 (LYVE-1), and the lymphatic system-specific transcription factor Prospero Homeobox 1 (Prox-1) [84,102] allowed for the unequivocal identification of lymph vessels and isolation of LEC for in vitro analyses [103]. ...
... The impaired removal of excess macromolecules such as lipids and proteins from the interstitial space, and the impaired transport of immune complexes, T cells or Langerhans cells have been shown. Additionally, the research pointed to the possible malfunction of antigen-presenting cells and the possible occurrence of abnormalities in the structure of the lymph nodes [100,129]. In a study by Nitti et al., a mouse model of diet-induced obesity was used to identify putative cellular mechanisms of obesity-induced lymphatic dysfunction and determine whether there is a correlation between these deleterious effects and increasing weight gain [91]. ...
The World Health Organization (WHO) has recognised obesity as one of the top ten threats to human health. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of an increased release of biologically active metabolites. Moreover, obesity predisposes the development of metabolic syndrome and increases the incidence of type 2 diabetes (T2DM), increases the risk of developing insulin resistance, atherosclerosis, ischemic heart disease, polycystic ovary syndrome, hypertension and cancer. The lymphatic system is a one-directional network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells that provides a unidirectional conduit to return filtered arterial and tissue metabolites towards the venous circulation. Recent studies have shown that obesity can markedly impair lymphatic function. Conversely, dysfunction in the lymphatic system may also be involved in the pathogenesis of obesity. This review highlights the important findings regarding obesity related to lymphatic system dysfunction, including clinical implications and experimental studies. Moreover, we present the role of biological factors in the pathophysiology of the lymphatic system and we propose the possibility of a therapy supporting the function of the lymphatic system in the course of obesity.
... 13 Several other studies described the negative effects of morbid obesity on the lymphatic system and suggested extreme obesity as a novel cause of LE, so-called ''obesity-induced LE.'' 14,15 Finally, several intervention studies targeting LE by weight management and dieting demonstrated positive results. [16][17][18][19][20] Bariatric surgery offers the most effective and durable treatment for obesity and exhibits positive effects on obesityrelated diseases, such as type 2 diabetes and cardiovascular risk factors. ...
... A small number of publications have described these results or have hypothesized about the potential benefits of weight loss by bariatric surgery in LE patients. Greene et al. 15 described the negative effects of morbid obesity on the lymphatic system, based on lymphoscintigrams. They suggested that extreme obesity could be a novel cause of LE, so-called ''obesity-induced LE,'' with the existence of a BMI threshold between 50 and 60 kg/m 2 , at which point lymphatic dysfunction could occur for the lower extremities. ...
Background:
Lymphedema (LE) is a chronic condition of swelling due to lymphatic impairment and is characterized by edema and fibro-adipose tissue deposition. LE may be caused by an anomalous development of the lymphatic system, known as primary LE, or may develop secondary to traumatic, infectious, or other external events. Knowledge is increasing about the plural and bidirectional relationship between LE and obesity. The rate of obesity is increasing worldwide, and bariatric surgery offers the most effective and durable treatment, as this surgery exhibits positive effects on many obesity-related diseases. We explored whether bariatric surgery could improve leg volumes in morbidly obese LE patients.
Patients:
Between 2013 and 2019, 829 patients were hospitalized in our Center of Expertise for Lymphovascular Medicine for intensive treatment of their LE. Nine patients with end-stage primary, secondary, or obesity-induced LE underwent a bariatric procedure related to their morbid obesity.
Methods and Results:
Data concerning age, gender, medical diagnosis, LE stage, type of bariatric treatment, body weight, body mass index (BMI), and limb volumes were retrospectively collected from the patient files. At the individual patient level, body weight, BMI, leg volumes, and their percent reduction between presurgery and postsurgery were calculated. At the group level, paired sample t-tests were conducted to compare the mean body weight, BMI, and volumes of both legs between postsurgery and presurgery. The data demonstrate a significant decrease in body weight, BMI, and leg volumes in morbidly obese end-stage primary, secondary, and obesity-induced LE patients following bariatric surgery.
Conclusions:
Our multiple case study indicates that bariatric surgery provides a good indication for concomitant treatment of morbid obesity and LE.
... In fact, several studies have shown that some very obese patients spontaneously develop lower extremity lymphedema even without antecedent injury [57]. In a retrospective study of 51 patients with lower extremity swelling, patients with a body mass index (BMI) ≥ 30kg/m 2 were more likely to have abnormal lymphoscintigrams findings as compared with patients with a BMI <30kg/m 2 [58]. In this study, a threshold BMI of 50kg/m 2 was identified as predictive of an abnormal lymphoscintigram result [58]. ...
... In a retrospective study of 51 patients with lower extremity swelling, patients with a body mass index (BMI) ≥ 30kg/m 2 were more likely to have abnormal lymphoscintigrams findings as compared with patients with a BMI <30kg/m 2 [58]. In this study, a threshold BMI of 50kg/m 2 was identified as predictive of an abnormal lymphoscintigram result [58]. The mechanism of obesity-induced lymphatic dysfunction is not well understood; one possibility is that increased lymphatic fluid in an enlarging limb overwhelms the draininage capacity of the existing lymphatic system. ...
An estimated 5 million people in the United States are affected by secondary lymphedema, with most cases attributed to malignancies or malignancy-related treatments. The pathogenesis of secondary lymphedema has historically been attributed to lymphatic injury or dysfunction; however, recent studies illustrate the complexity of lymphedema as a disease process in which many of its clinical features such as inflammation, fibrosis, adipogenesis, and recurrent infections contribute to on-going lymphatic dysfunction in a vicious cycle. Investigations into the molecular underpinning of these features further our understanding of the pathophysiology of this disease and suggests new therapeutics.
... [21][22][23][24] Affecting one-quarter of Canadian adults, 25 obesity is a major health concern around the world, and it has been identified as an important risk factor for lym phedema and an independent cause of non-cancer related lymphedema. 23,[26][27][28] People with severe obesity who have chronic leg edema demonstrate functional and medical concerns, such as cellulitis and venous thromboembolism. 29 The mechanisms linking obesity and lymphedema are not yet well delineated but are thought to involve a cascade of pathological events characterized by lymphatic vessel dysfunction, adipo cyte hypertrophy and dysfunction, and chronic inflam matory processes. ...
... 23 Among 51 patients with non-cancer-related leg lymphedema, Greene and colleagues found that a higher BMI predicted abnormal lymphatic dysfunction on lymphoscintigraphy. 27 ...
Purpose: Physiotherapists have an important role to play in the early detection and treatment of lymphedema, a chronic inflammatory condition characterized by excess interstitial protein-rich fluid, which is estimated to affect more than one million Canadians. Obesity has been identified both as an important cause of and as a risk factor for developing lymphedema of various aetiologies. Little is currently known about obesity in Canadians affected by lymphedema. The objective of this study was to report on the prevalence of overweight and obesity in a Canadian lymphedema clinic population and the relationships among BMI; demographic, medical, and lymphedema characteristics; and cellulitis history. Method: We conducted a retrospective electronic record review of the clinical data collected from new patients evaluated for suspected lymphedema at a specialized Canadian hospital-based clinic over a 2-year period. We used descriptive analyses to characterize the sample and one-way analysis of variance and χ ² tests for comparative analyses. Results: Of the 178 patients whose records were reviewed, 36.5% were classified as overweight and 39.3% as obese. Patients with non-cancer diagnoses had a higher mean BMI than those with cancer-related diagnoses ( p < 0.001). A higher BMI was associated with a longer time since lymphedema onset ( p < 0.001), bilateral lymphedema ( p = 0.010), and history of cellulitis ( p < 0.001). Conclusions:Obesity is prevalent in the Canadian population with lymphedema and is associated with delayed referral and increased cellulitis rates. Early detection and tailored management strategies are needed to address obesity in patients with lymphedema and the complexities associated with these two related conditions.
... A related topic relevant to the health of both the venous and lymphatic systems is obesity. Obesity can cause 'obesity-induced lymphedema' or OIL, and a body mass index (BMI) threshold exists between 50 and 60 where lymphatic dysfunction occurs [32,33]. Adipose tissue, an endocrine organ, produces the hormone adipokinase. ...
The foot and calf muscle pump, collectively known as the venous muscle pump, plays a crucial role in the circulatory system (veins, arteries, and lymphatics), particularly in the return of blood from the lower extremities to the heart. Further, the venous muscle pump is crucial to lymphatic health and essential in chronic edema/lymphedema management. This article will highlight the significance of the venous pump and review the functional anatomy and physiology of the foot and calf, integrating the connection to venous and lymphatic health. The complementary importance of mobility, exercise, and breathing will also be explored.
... 21,22,26 Lastly, obesity has been identified as a significant risk factor for the development and progression of lymphedema. 27,28 Thus, maintaining a healthy weight through diet and exercise can aid patients in reducing the risk of lymphedema-related complications. Although these strategies can be beneficial, they necessitate behavioral modifications and substantial patient effort. ...
Background
Immediate lymphatic reconstruction (ILR) has traditionally required a fluorescent-capable microscope to identify lymphatic channels used to create a lymphaticovenous bypass (LVB). Herein, a new alternative method is described, identifying lymphatic channels using a commercially available handheld fluorescence imaging device.
Methods
This was a single-center study of consecutive patients who underwent ILR over a 1-year period at a tertiary medical center. Intradermal injection of fluorescent indocyanine green dye was performed intraoperatively after axillary or inguinal lymphadenectomy. A handheld fluorescent imaging device (SPY-PHI, Stryker) rather than a fluorescent-capable microscope was used to identify transected lymphatic channels. Data regarding preoperative, intraoperative, and outcome variables were collected and analyzed.
Results
The handheld fluorescent imaging device was successfully able to identify transected lymphatic channels in all cases (n = 15). A nonfluorescent-capable microscope was used to construct the LVB in 14 cases. Loupes were used in one case. In 13 cases, ILR was unilateral. In two cases, bilateral ILR was performed in the lower extremities. All upper extremity cases were secondary to breast cancer (n = 7). Lower extremity cases (n = 8) included extramammary Paget disease of the penis, ovarian cancer, vulvar squamous cell carcinoma, squamous cell carcinoma of unknown origin, soft tissue sarcomas, cutaneous melanoma, and porocarcinoma.
Conclusions
ILR, using indocyanine green injection with a handheld fluorescent imaging device, is both safe and effective. This method for intraoperative identification of lymphatic channels was successful, and LVB creation was completed in all cases. This approach makes ILR feasible when a fluorescent-capable microscope is unavailable, broadening access to more patients.
... Maintaining a healthy lifestyle and appropriate weight is important as obesity is associated with an increased risk of developing lymphedema and an increase in adipose tissue may decrease the effectiveness of other therapies such as compression pumps or sleeves [23, 23]. Severe obesity (BMI > 50 kg/m 2 ) can also be the primary driver of lymphatic dysfunction, and in such patients, significant weight loss can have dramatic improvement in the degree of edema [25]. Even in patients with non-obesity-induced lymphedema, weight loss may lessen lymphedema-associated symptoms and provide other, global health benefits to improve overall patient well-being. ...
Purpose of review
This review provides a practical, evidence-based summary of lymphedema with a focus on its clinical management to guide clinicians in providing the most current treatment options for their patients.
Recent findings
The cornerstone of the management of lymphedema is adherence to appropriate general care measures and high-quality compression. There have been advances in invasive options using highly specialized operative techniques that either facilitate lymphatic drainage or bring new lymphatic growth to an area otherwise devoid of viable lymph tissue. For patients with more advanced disease, operative debulking can decrease limb girth and improve limb mobility.
Summary
Lymphedema centers involving multi-disciplinary care teams are equipped to provide patients with advanced diagnostic imaging, comprehensive non-invasive management strategies, and specialized surgical options to address their condition. Early referral to dedicated lymphatic centers with microsurgical expertise can provide patients with nuanced conservative and surgical options that have the potential to improve limb outcomes and overall quality of life.
... [13][14][15][16] Other risk factors such as obesity also promote the development of lymphedema. 2,17,18 The increase in volume in lymphedema is not only relevant from a cosmetic point of view, but also from an orthopaedic point of view due to its weight. Movement restrictions can be a consequence of lymphedema. ...
Background Untreated lymphedema of an extremity leads to an increase in volume. The therapy of this condition can be conservative or surgical.
Methods “Lymphological liposculpture” is a two-part procedure consisting of resection and conservative follow-up treatment to achieve curative volume adjustment of the extremities in secondary lymphedema. This treatment significantly reduces the need for complex decongestive therapy (CDT). From 2005 to 2020, 3,184 patients with secondary lymphedema after breast cancer and gynecological tumors were treated in our practice and clinic. “Lymphological liposculpture” was applied to 65 patients, and the data were recorded and evaluated by means of perometry and questionnaires.
Results The alignment of the sick to the healthy side was achieved in all patients. In 58.42% (n = 38), the CDT treatment could be completely stopped postoperatively; in another 33.82% (n = 22) of the patients, a permanent reduction of the CDT was achieved. In 7.69% (n = 5) patients, the postoperative CDT could not be reduced. A total of 92.30% (n = 60) of the patients described a lasting significant improvement in their quality of life.
Conclusion “Lymphological liposculpture” is a standardized curative sustainable procedure for secondary lymphedema for volume adjustment of the extremities and reduction of postoperative CDT with eminent improvement of the quality of life.
... One of the most straightforward links between the lymphatics and obesity is lymphedema. Work by Green et al. in 2012 and 2015 suggested that obesity (notably in scenarios where a patient's BMI exceeds 50-60) could be a cause of lymphedema due to buildup of adipose tissue disrupting lymphatic flow [98,99]. Additional work by the same group using lymphoscintigraphy to visualize flow demonstrated sustained impairment in a severely obese patient following a sleeve gastrectomy [100]. ...
Study of the lymphatic system, compared to that of the other body systems, has been historically neglected. While scientists and clinicians have, in recent decades, gained a better appreciation of the functionality of the lymphatics as well as their role in associated diseases (and consequently investigated these topics further in their experimental work), there is still much left to be understood of the lymphatic system. In this review article, we discuss the role lymphatic imaging techniques have played in this recent series of advancements and how new imaging techniques can help bolster this wave of discovery. We specifically highlight the use of lymphatic imaging techniques in understanding the fundamental anatomy and physiology of the lymphatic system; investigating the development of lymphatic vasculature (using techniques such as intravital microscopy); diagnosing, staging, and treating lymphedema and cancer; and its role in other disease states.
... Much has been reported in the past regarding obesity as a risk factor for the origin of lymphedema. [6][7][8][9][10][11][12][13] There are also reports of surgical treatments for obesity-related lymphedema. 14,15 LVA, along with fat reduction procedures such as liposuction, has been well documented. ...
Much has been reported in the past regarding obesity as a risk factor for the origin of lymphedema. There are also reports of surgical treatments for obesity-related lymphedema. We have previously reported on the effectiveness of lymphaticovenular anastomosis in reducing chronic inflammation, and we believe that lymphaticovenular anastomosis is a very useful surgical approach in patients with recurrent cellulitis. In this report, we describe a case of a severely obese patient with a body mass index over 50 who developed lymphedema in both lower extremities due to pressure from sagging abdominal fat accompanied by frequent episodes of cellulitis.
... [5][6][7][8] The damage of lymphatics can result from various causes such as cancer treatment, injury trauma, venous disease, obesity, inflammation, skin infection, drug abuse, or infection of parasites, and so on, but the cancer treatments including the surgical process, radiotherapy, and chemotherapy are the leading causes. 9 The surgical procedure, particularly lymph node dissection, physically disconnects the lymphatic pathway because lymphatic vessels and lymph nodes serve as a draining channel for returning lymphatic fluid from interstitial tissue spaces to the venous system. 1,10,11 The absence or removal of lymph nodes is like losing a major drainage pathway since lymph nodes are located at strategic positions along with the lymphatic system. ...
Secondary lymphedema is a severe complication of cancer treatment, but there is no effective curative method yet. Lymph node dissection and radiation therapy for cancer treatment may lead to secondary lymphedema, which is a chronic disease induced by malfunction of lymphatic flow. The lymphatic channel sheet (LCS) is an artificial micro‐fluidic structure that was fabricated with polydimethylsiloxane to maintain lymphatic flow and induce lymphangiogenesis. The structure has two‐dimensional multichannels that increase the probability of lymphangiogenesis and allow for relatively easy application. We verified the efficacy of the lymphatic channel sheet through macroscopic and microscopic observation in small animal models, which underwent brachial lymph node dissection and irradiation. The lymphatic channel sheet enabled the successful transport of lymphatic fluid from the distal to the proximal area in place of the removed brachial lymph nodes. It prevented swelling and abnormal lymphatic drainage during the follow‐up period. Lymphangiogenesis was also identified inside the channel by histological analysis after 8 weeks. According to these experimental results, we attest to the roles of the lymphatic channel sheet as a lymphatic pathway and scaffold in the rat upper limb model of secondary lymphedema. The lymphatic channel sheet maintained lymphatic flow after lymph node dissection and irradiation in an environment where lymph flow is cut off. It also relieved symptoms of secondary lymphedema by providing a lymph‐friendly space and inducing lymphangiogenesis.
... deren Behandlung (Bestrahlung, Lymphknotenresektion). Adipositas besitzt einen induzierenden und aggravierenden Einfluss [22,28,29]. ...
Zusammenfassung
Hintergrund und Ziele
Medizinische Kompressionsstrümpfe (MKS) sind bei chronischer venöser Insuffizienz (CVI) aller Stadien indiziert und beim Lymphödem eine unverzichtbare Therapiekomponente; 8 % der deutschen Bevölkerung tragen vom Arzt verordnete MKS, Frauen häufiger als Männer (12 % vs. 5 %) und insbesondere Personen ab 60 Jahren (17 %). Die Adhärenz der Patienten ist relevant für eine erfolgreiche Behandlung mit MKS. Untersucht wurde die Versorgung mit MKS aus Patientensicht.
Patienten und Methodik
Die vorliegende Studie untersuchte 2019 die Versorgungsqualität durch strukturierte Interviews mit 414 repräsentativ ausgewählten Nutzern. Die Erkenntnisse werden vor dem Hintergrund wissenschaftlicher Evidenz zur Wirkung der MKS diskutiert.
Ergebnisse
Venenprobleme sind der häufigste Verordnungsgrund (44 %), gefolgt von Lymphödemen (22 %) bzw. Mehrfachindikationen (27 %). Patienten tragen MKS zumeist täglich und durchschnittlich 11 h/Tag; 89 % der Patienten waren zufrieden bzw. sehr zufrieden mit den MKS und berichteten je nach Indikation ein differenziertes Wirkprofil. Dieses reflektiert die umfangreiche wissenschaftliche Evidenz zur klinischen Wirksamkeit der MKS. Ein wichtiger Faktor für die Patientenadhärenz ist die ärztliche Schulung und Aufklärung.
Schlussfolgerungen
MKS werden von Patienten sehr gut akzeptiert. Bei der Verordnung sollen praktischen Aspekte wie An- und Ausziehen, empfohlene Tragedauer und -häufigkeit sowie der Wirkmechanismus der MKS vermittelt werden.
Graphic abstract
... Our analysis confirmed the clustering between obesity and breast cancer in the lymphatic cohort, thus correctly underscoring the co-occurrence of these two conditions in acquired lymphedema, as prior studies have demonstrated. [40][41][42] Obesity is often considered a risk factor for breast cancer, possibly through the promotion of breast tissue tumorigenesis through obesity-induced local inflammation. 9,43 Because inflammation is heavily fostered through mechanisms associated with lymphatic immune traffic, any form of undetected, underlying lymphatic dysfunction or structural abnormality could serve as a potential mechanistic link for the clustering of breast cancer and obesity. ...
Background:
The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies.
Methods:
We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise co-occurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships.
Results:
Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population.
Conclusions:
The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.
... The mechanisms via which obesity impairs lymphatic function and the outcome of liposuction are not known. However, it is suspected that the amount of lymph produced by the body increases as BMI increases, and that the greater amount of lymph may interfere with the ambulation/muscle contraction in the lower limbs required to transport the fluid [51]. ...
Objective:
There is limited information on postoperative care after liposuction for lymphedema limb. The aim of this retrospective study was to identify the threshold compression pressure and other factors that lead liposuction for lower limb lymphedema to success.
Materials and methods:
Patients were divided according to whether they underwent compression therapy with both stockings and bandaging (SB group), stockings alone (S group), or bandaging alone (B group) for 6 months after liposuction. The postoperative compression pressure and rate of improvement were compared according to the postoperative compression method. We also investigated whether it was possible to decrease the compression pressure after 6 months. Liposuction was considered successful if improvement rate was >15.
Results:
Mean compression pressure was significantly lower in the S group than in the SB group or B group. The liposuction success rate was significantly higher in the SB group than in the B group or S group. There was not a significant difference between the values at 6 months after liposuction and at 6 months after a decrease in compression pressure in the successful group.
Conclusion:
Our results suggest that stable high-pressure postoperative compression therapy is key to the success of liposuction for lower limb lymphedema and is best achieved by using both stockings and bandages. The postoperative compression pressure required for liposuction to be successful was >40 mmHg on the lower leg and >20 mmHg on the thigh. These pressures could be decreased after 6 months.
... 134 There is evidence that obesity itself can be a precipitating cause of human lymphedema. [135][136][137][138] Mechanistic support for this observation can be derived from dietinduced, obese K14-VEGF-C mice, where adipose hypertrophy induces a functional impairment in the lymphatic collecting vasculature, with concomitant structural alterations. 139 In a model of diet-induced adiposity, obese mice have impaired baseline lymphatic function that is exacerbated by lymphatic injury and is accompanied by increased chronic inflammation, fibrosis, and adipose deposition. ...
Lymphedema is a common, complex, and inexplicably underappreciated human disease. Despite a history of relative neglect by health care providers and by governmental health care agencies, the last decade has seen an explosive growth of insights into, and approaches to, the problem of human lymphedema. The current review highlights the significant advances that have occurred in the investigative and clinical approaches to lymphedema, particularly over the last decade. This review summarizes the progress that has been attained in the realms of genetics, lymphatic imaging, and lymphatic surgery. Newer molecular insights are explored, along with their relationship to future molecular therapeutics. Growing insights into the relationships among lymphedema, obesity, and other comorbidities are important to consider in current and future responses to patients with lymphedema.
... En el presente estudio todos los participantes tenían sobrepeso u obesidad y presentaron una reducción volumen del linfedema y del peso corporal total, postintervención; la presencia de obesidad es un factor desencadenante de linfedema y agravante los cuadros de linfedema prexistentes, empeorando la calidad de vida y aumentando las complicaciones propias del linfedema 26,27 ; no obstante, no era objetivo del estudio es importante abordar este asunto, tal como propone el estudio de Winkels et al. es necesario evaluar los resultados asociados a un control nutricional paralelo 28 . ...
Resumen
Introducción
El ejercicio físico es un pilar en el tratamiento conservador del linfedema; sin embargo, normalmente no se realiza un programa de ejercicio terapéutico enfocado a mejorar la funcionalidad.
Objetivo
Analizar los cambios en la funcionalidad y la marcha de pacientes con linfedema de extremidad inferior aplicando un protocolo de ejercicio terapéutico progresivo supervisado.
Materiales y método
Pacientes adultos, portadores de linfedema de extremidad inferior, fueron tratados mediante un plan de ejercicios progresivo mixto, aeróbico y de resistencia, durante 8 semanas. Se registraron datos sociodemográficos, clínicos y antropométricos, funcionalidad de la extremidad inferior, marcha, fuerza isométrica de piernas y prensión de agarre, al inicio y final del programa. Para el análisis de datos se utilizó el t-test y Wilcoxon.
Resultados
Diecisiete mujeres y 5 hombres fueron reclutados, edad promedio 45,5 años (23-68), 12 participantes presentaron linfedema unilateral y 10 bilaterales, 20 estaban en etapas clínicas i o ii y 16 tenían linfedema secundario. Postintervención, la funcionalidad de miembros inferiores según el Lower Extremity Functional Scale mejoró 11 puntos promedio (p < 0,005); la distancia recorrida promedio, aumentó de 474 m a 503 m, con p < 0,005 solo para el grupo de mujeres. Hubo mejoras en la fuerza isométrica de piernas y fuerza de prensión de agarre sin significación estadística. Además, se observó reducción del peso corporal y del volumen de extremidad afectada (p < 0,005).
Conclusión
El protocolo de ejercicio terapéutico progresivo aplicado mostró efectos positivos en todas las variables estudiadas, principalmente funcionalidad y marcha, y puede ser recomendable y seguro en esta población.
... The legs are enlarged, out-of-proportion to the rest of the body, with relative sparing of the distal extremity. Obesity [body mass index (BMI > 30)] can cause leg enlargement and edema [3,9]. ...
Background/objectives:
Patients with obesity and lipedema commonly are misdiagnosed as having lymphedema. The conditions share phenotypic overlap and can influence each other. The purpose of this study was to delineate obesity-induced lymphedema, obesity without lymphedema, and lipedema in order to improve their diagnosis and treatment.
Subjects/methods:
Our Lymphedema Center database of 700 patients was searched for patients with obesity-induced lymphedema (OIL), obesity without lymphedema (OWL), and lipedema. Patient age, sex, diagnosis, cellulitis history, body mass index (BMI), and treatment were recorded. Only subjects with lymphoscintigraphic documentation of their lymphatic function were included.
Results:
Ninety-eight patients met inclusion criteria. Subjects with abnormal lymphatic function (n = 46) had a greater BMI (65 ± 12) and cellulitis history (n = 30, 65%) compared to individuals with normal lymphatic function [(BMI 42 ± 10); (cellulitis n = 8, 15%)] (p < 0.001). Seventeen patients had a history of lipedema and two exhibited abnormal lymphatic function (BMI 45, 54). The risk of having lower extremity lymphedema was predicted by BMI: BMI < 40 (0%), 40-49 (17%), 50-59 (63%), 60-69 (86%), 70-79 (91%), ≥80 (100%). Five patients with OIL (11%) underwent resection of massive localized lymphedema (MLL) or suction-assisted lipectomy. Three individuals (18%) with lipedema were treated with suction-assisted lipectomy.
Conclusions:
The risk of lymphedema in patients with obesity and lipedema can be predicted by BMI; confirmation requires lymphoscintigraphy. Individuals with OIL are at risk for cellulitis and MLL. Patients with a BMI > 40 are first managed with weight loss. Excisional procedures can further reduce extremity size once BMI has been lowered.
... Lower extremity lymphedema can be seen once a patient's BMI is greater than 50 kg/m 2 and may be ubiquitous in patients with a BMI over 60 [4]. Lymphedema in obese patients is commonly diagnosed with lymphoscintigraphy [10]. The primary treatment for obesity-induced lymphedema is weight loss. ...
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.
... MetSyn is now one of the most prevalent diseases globally and increases the risk for all causes of mortalities, including cardiovascular diseases 1,2 . Clinical studies have established the link between obesity and lymphatic dysfunction, which is associated with increased susceptibility for developing lymphedema [3][4][5][6] . Mice heterozygous for Prox1, a master lymphatic endothelial transcription factor, consistently develop adult onset obesity coupled with increased chyle accumulation in the thoracic cavity 7,8 . ...
The intrinsic lymphatic contractile activity is necessary for proper lymph transport. Mesenteric lymphatic vessels from high-fructose diet-induced metabolic syndrome (MetSyn) rats exhibited impairments in its intrinsic phasic contractile activity; however, the molecular mechanisms responsible for the weaker lymphatic pumping activity in MetSyn conditions are unknown. Several metabolic disease models have shown that dysregulation of sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump is one of the key determinants of the phenotypes seen in various muscle tissues. Hence, we hypothesized that a decrease in SERCA pump expression and/or activity in lymphatic muscle influences the diminished lymphatic vessel contractions in MetSyn animals. Results demonstrated that SERCA inhibitor, thapsigargin, significantly reduced lymphatic phasic contractile frequency and amplitude in control vessels, whereas, the reduced MetSyn lymphatic contractile activity was not further diminished by thapsigargin. While SERCA2a expression was significantly decreased in MetSyn lymphatic vessels, myosin light chain 20, MLC20 phosphorylation was increased in these vessels. Additionally, insulin resistant lymphatic muscle cells exhibited elevated intracellular calcium and decreased SERCA2a expression and activity. The SERCA activator, CDN 1163 partially restored lymphatic contractile activity in MetSyn lymphatic vessel by increasing phasic contractile frequency. Thus, our data provide the first evidence that SERCA2a modulates the lymphatic pumping activity by regulating phasic contractile amplitude and frequency, but not the lymphatic tone. Diminished lymphatic contractile activity in the vessels from the MetSyn animal is associated with the decreased SERCA2a expression and impaired SERCA2 activity in lymphatic muscle.
... The negative role of weight excess in lymphatic and venous diseases has been discussed in a few recent publications. [34][35][36][37] Some literature data refer to morbid obesity as a relevant aggravating, or generating factor of LYM, 34, 35 while a BMI over 30 kg/m 2 proved an extremely important predictive factor (HR=1.52) of breast cancer-related LYM onset. 38 Overweight and especially obesity result in a series of documented negative repercussions effects in LYM patients, which can be summarized as follows: 32 1) onset of metabolic syndrome and increase of the biochemical factors which generate cardiac/renal edema; 2) fat deposition in the tissues, which recalls fluids in the limb; 3) accompanying liver steatosis, which relates to systemic fluid retention; 4) hypertension and the frequent intake of anti-hypertensive drugs, which may generate venulodilation and limb edema ultimately; 5) hormonal changes which induce edema (higher cortisol, insulin etc.); 6) possible dysfunction of plantar/calf pump and especially of diaphragmatic pump, with a reduction of veno-lymphatic return. ...
Lymphology is evolving in search of a better management of lymphedema patients, both as to the diagnostic pathway and as to the therapeutic options. Similarly, lymphatic system is involved in a wide spectrum of pathophysiologic processes of most chronic degenerative diseases. Translational medicine integrates the interdisciplinary scientific knowledge to improve diagnostic and therapeutic options in the biomedical field. Inflammation and lymphatic function are regarded as the connecting biochemical factors in most diseases. This review focuses on the scientific publications regarding lymphatic system in connection to psychoneuroendocrineimmunology, hormesis, epigenetics and more generally nutrition and lifestyle. The interaction between lymphology and translational medicine may play a relevant role to improve management of LYM on one side, and of chronic degenerative diseases on the other side.
... Many studies have focused on the negative impact of obesity on lymphatic system, both in terms of LYM onset and in terms of LYM course and prognosis. 35,36 Lymphoscintigraphic studies have proven significant changes in lymphatic vessels/nodes in obese patients, which may explain the great influence of weight control in LYM patients. Overweight and, more relevantly, obesity proved to be a few of the most significant risk factors for the onset of LYM in patients subjected to cancer-related surgery (especially breast cancer). ...
Nutrition is considered a basic component in the management of any vascular disease. Lymphedema is characterised by an increase of interstitial fluid due to a lymphatic system morphological and/or functional alteration. Therapeutic management of lymphedema includes a multi-faceted approach based on compression and physiotherapy mainly. Weight control and antiinflammatory and anti-edema diet are two additional necessary components of the holistic therapy in presence of primary or secondary limb lymphedema. This narrative review provides the available information derived from the scientific literature on nutrition in lymphedema, which anyway lacks robust evidence. Additional information and speculations are provided on the role of food, diet, nutraceuticals and fasting on the basic processes at the root of the chronic progressive degeneration of tissue lymph stasis, i.e. weight excess, inflammation, edema, fibroadiposis. More targeted and randomized studies are needed in order to assess and standardise the obvious, so far neglected, role of nutrition in lymphedema patients.
... [1] Moreover, studies have associated obesity with both upper and lower limb lymphedema. [2] During routine electrical bioimpedance analyses, Godoy & Godoy recently identified an important change in the quantity of intracellular and extracellular liquid as well as liquid in the limbs and trunk, but without meeting bioimpedance criteria for clinical lymphedema, which the authors denominated subclinical systemic lymphedema. [3] When monitoring the evolution of lymphedema in obese patients using bioimpedance, the authors detected a well-defined clinical progression, which they classified into four clinical stages ranging from subclinical lymphedema to clinical systemic lymphedema meeting bioimpedance criteria. ...
... Animal studies have demonstrated that obesity and its progression are associated with a set of alterations, such as a reduction in contractile mechanisms of the lymphatic system, the inflammatory process as well as changes in capillary permeability and the immune response [4,5]. Therefore, such findings in humans allow posing the hypothesis of subclinical systemic lymphedema similar to what has been seen in animals [6]. ...
The aim of the study was to report an improvement in clinical lymphedema in a patient who went from morbid obesity to overweight following bariatric surgery. A 52-year-old female patient reported having undergone bariatric surgery with a body mass index (BMI) of 51.2 kg/m², losing 40 kg and arriving at her current BMI of 37.1 kg/m². She would previously awake with bilateral edema that involved her feet and worsened throughout the day, corresponding to clinical stage II lymphedema, and currently no longer had this problem. Eight years after the surgery and weight loss, the patient was submitted to electrical bioimpedance analysis, which revealed an increase in total intracellular and extracellular fluids in the limbs and trunk. Active exercise and further weight loss were recommended. This study paves a path for a new line of investigation in the treatment of obesity and changes in the lymphatic system caused by obesity.
... [6][7][8][9] Adults with obesity exhibit structural lymphatic abnormality, and in some cases, the lymphatic damage may be irreversible. 10 Venous insufficiency, 11 cellulitis, 12 and chronic wounds 13 as well as other comorbidities common with obesity create additional challenges for lymphedema management. ...
This study investigated whether a lifestyle modification program that encouraged a ketogenic diet (KD) for participants with lymphedema and obesity would reduce weight and limb volume and improve quality of life. A total of 12 participants with lymphedema and obesity (mean body mass index = 38.38; SD = 7.02) were enrolled in a lifestyle modification group. The timespan from baseline data collection to 30-day follow-up was 18 weeks. Retention rate was 83.3%. Data were analyzed with repeated-measures ANOVA and Pearson correlation. Participants demonstrated statistically significant improvement in most outcome measures. Mean weight loss was 5.18 kg—F(4, 36) = 11.17; P < .001—or 4.8% of mean baseline weight. The average limb volume reduction was 698.9 ml—F(4, 36) = 9.4; P < .001—and was positively correlated with weight loss (r = 0.8; P = .005). There appeared to be a tendency for participants who used a KD (n = 6) to demonstrate superior results in most outcome measures compared with those who did not use the diet (n = 4), although the sample size of the 2 groups was too small to report definitive results. This lifestyle modification program provided insight into the possible value of a KD for obesity and lymphedema management.
Background/Objectives: Obesity and chronic oedema/lymphoedema are two distinct but related conditions, rarely investigated together. The aim was to study the impact of increased weight on chronic oedema and related factors.
Subjects/Methods: A cross-sectional study (2014-2017), in 38 centers, nine countries. Patients with clinically confirmed chronic oedema/lymphoedema of the leg were included. Normal weight was judged as BMI 20-30, obesity BMI 30-40 or morbidly obese BMI >40. Factors were tested for an association with increased weight, using a multivariable model.
Results: In total 7397 patients were included; 43% being normal weight, 36% obese and 21% morbidly obese. Patients with increased weight had significantly more advanced stages of chronic oedema (ISL stage III; the most advanced form); affecting 14% of normal weight, 18% in obesity and 39% in morbid obesity (p<0.001). Ten factors were independently associated with increased weight: diabetes (OR 2.4), secondary lymphoedema (OR 2.7), cellulitis/erysipelas within 12 months (OR 1.2), bilateral lymphoedema (OR 3.6), compression therapy (OR 2.1), increased swelling duration (1-2 years OR 1.3, 2-5 years OR 2.5, 5-10 years OR 3.6, >10 years OR 3.5) decreased mobility (walking with aid OR 1.9, being chair bound OR 1.2) and age (reference <45 years; 45-64 years OR 1.5, 75-84 years OR 0.6, 85+ years OR 0.2). Increased weight was associated with a lower presentation of peripheral arterial disease (OR 0.7) and poorer chronic oedema control (OR 0.8). Patients with obesity/morbid obesity had a lower function, appearance and more severe symptoms as assessed by LYMQOL and lower quality of life using EuroQol.
Conclusions: Obesity negatively impacts chronic oedema, leading to more advanced stages. Achieving good control of swelling with compression is more difficult in these patients. Increased awareness of chronic oedema/lymphoedema as a complication of obesity is important for early detection and for developing effective strategies to prevent and manage them.
Das Lymphödem ist eine pathologische Ansammlung und Veränderung der interstitiellen Flüssigkeit als Folge einer primären (angeborenen) oder sekundären (erworbenen) Schädigung des Lymphdrainagesystems. Meist sind die Extremitäten betroffen, jedoch kann es auch in anderen Regionen auftreten. Gutachtlich ist von Bedeutung, dass es sich um eine chronische, ohne Behandlung schnell progrediente Krankheit mit sichtbarer Volumenvermehrung bzw. Volumenveränderung einer Körperregion, meistens an einer oder mehreren Extremitäten handelt. Insbesondere die dadurch eintretenden Einschränkungen in der Gebrauchsfähigkeit können sowohl im Schwerbehindertenrecht, sozialen Entschädiungsrecht und in der Unfallversicherung relevant sein und einen GdS/GdB bzw. eine MdE in nicht unerheblichem Maße bedingen. Der lebenslange Therapiebedarf stellt zudem eine erhebliche Belastung für den Patienten dar und hat oftmals einen relevanten psychosozialen Einfluss auf dessen Lebensqualität.
Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.
Purpose:
While vascularized lymph node transplant (VLNT) has gained popularity, there is a lack of prospective long-term studies and standardized outcomes. The purpose of this study was to evaluate the safety and efficacy of VLNT using all available outcome measures.
Methods:
This was a prospective study on all consecutive patients who underwent VLNT. Outcomes were assessed with two patient-reported outcome metrics, limb volume, bioimpedance, need for compression, and incidence of cellulitis.
Results:
There were 89 patients with the following donor sites: omentum (73%), axilla (13%), supraclavicular (7%), groin (3.5%). Mean follow-up was 23.7±12 months. There was a significant improvement at 2 years post-op across all outcome measures: 28.4% improvement in the Lymphedema Life Impact Scale (LLIS), 20% average reduction in limb volume, 27.5% improvement in bioimpedance score, 93% reduction in cellulitis, and 34% of patients no longer required compression. Complications were transient and low without any donor site lymphedema.
Conclusion:
VLNT is a safe and effective treatment for lymphedema with significant benefits fully manifesting at 2 years post-op. Omentum does not have any donor site lymphedema risk making it an attractive first choice.
Surgery to treat lymphedema has been shown to be effective in multiple studies, is not experimental, and has long been held as the standard of care for patients with lymphedema. When integrated into a comprehensive lymphedema treatment program for patients, surgery can provide effective and long-term improvements that nonsurgical management alone cannot achieve. Such a lymphedema treatment program can provide tremendous improvements for many problems including recurring cellulitis infections, inability to wear appropriate clothing, loss of arm or leg function, and reductions in the amount of lymphedema therapy and compression garment use needed.This chapter reports the use of a two-phase approach to treat patients with chronic, solid-predominant lymphedema who have maximized the use of conservative lymphedema therapies. Suction-assisted protein lipectomy (SAPL) is used to address the excess lymphedema solids first. After patient healing is complete, vascularized lymph node transfer (VLNT) and/or lymphaticovenous anastomosis (LVA) surgery can be used to further reduce dependence on conservative treatment methods.KeywordsSuction-assisted protein lipectomy (SAPL)Vascularized lymph node transplant (VLNT)Lymphaticovenous anastomosis (LVA)
Comprehensive evaluation of the patient presenting with extremity swelling is essential for accurate diagnosis and treatment. For patients with lymphedema, a detailed history and clinical examination are supported by multiple metrics to correctly support the diagnosis and for staging. Lymphedema may be complicated by a complex interplay with insufficiency of the venous system, in particular when affecting the lower extremity, and specific imaging may be indicated for further evaluation. Measurement of the relative lymphatic fluid/adipose tissue composition is important to guide the optimal sequence of lymphedema treatment. This chapter presents a practical evidence-based approach for the evaluation of the patient with limb swelling.KeywordsLymphedemaEvaluationPerometerLDexIndocyanine green (ICG) lymphographyLymphoscintigraphyMagnetic resonance angiography/lymphangiography (MRA/MRL)
Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.
Lymphedema results from inadequate lymphatic function. Extreme obesity can cause lower extremity lymphedema, termed "obesity-induced lymphedema (OIL)." OIL is a form of secondary lymphedema that may occur once an individual's body mass index (BMI) exceeds 40. The risk of lymphatic dysfunction increases with elevated BMI and is almost universal once BMI exceeds 60. Obesity has a negative impact on lymphatic density in subcutaneous tissue, lymphatic endothelial cell proliferation, lymphatic leakiness, collecting-vessel pumping capacity, and clearance of macromolecules. Lymphatic fluid unable to be taken up by lymphatic vessels results in increased subcutaneous adipose deposition, fibrosis, and worsening obesity. Individuals with OIL are in an unfavorable cycle of weight gain and lymphatic injury. The fundamental treatment for OIL is weight loss.
Complex Physical Decongestive Therapy (CDT) is the standard therapy for lymphedema. The aim of treatment is to cause the lymphedema to regress to a clinically edema-free stage or at least to decrease the stages of lymphedema. CDT as the basic therapy for lymphedema encompasses five elements as skin care, manual lymph drainage, compression therapy, decongestive exercise, and self-treatment education. The dosage, indications, and contraindications of individual components depend on the stage of lymphedema, the age of patient, and comorbidities. The long-term success of therapy depends on cooperation along the therapeutic chain of doctors, physiotherapists, and ensuring adequate medical compression garments.
Significance: Obesity affects one-third of the U.S. population and lymphedema is a chronic disorder without a cure. The relationship between obesity and lymphedema has important implications for public health. Recent Advances: Extreme obesity can cause lower extremity lymphedema, termed "obesity-induced lymphedema (OIL)." OIL is a form of secondary lymphedema that may occur once an individual's body mass index (BMI) exceeds 40. The risk of lymphatic dysfunction increases with elevated BMI and is almost universal once BMI exceeds 60. Patients with OIL also may develop areas of massive localized lymphedema (MLL). Critical Issues: Individuals with OIL are in an unfavorable cycle of weight gain and lymphatic injury. As BMI increases lymphedema worsens, ambulation becomes more difficult, and BMI further rises. The fundamental treatment for OIL is weight loss. Resection of areas of MLL and lower extremity volume reduction are performed when the BMI is lowered to <40 to reduce complications and recurrence. Future Directions: The mechanisms by which obesity causes lymphedema are still being elucidated. Although lymphatic function can improve following weight loss, it is unclear whether lymphedema may be completely reversed.
Background:
Lymphedema results from inadequate lymphatic function causing swelling in subcutaneous tissues. Lymph is transported proximally through valved lymphatic channels and muscle contraction. The purpose of this study was to determine lymphatic function in nonambulatory patients with lower extremity neuromuscular disease.
Methods and Results:
Our Lymphedema Program database of 700 patients was reviewed for nonambulatory patients with lower extremity neuromuscular disease. Patient age, gender, disease, body mass index (BMI), and lymphoscintigram result were recorded. Eight patients were included in the study: myelomeningocele (n = 6), spinal muscle atrophy type 2 (n = 1), Charcot Marie Tooth (n = 1). Patient ages were between 15 and 36 years; five were female. BMI range for patients without swelling or a normal lymphoscintigram (n = 4) was 22-27. Four subjects with lymphatic dysfunction by lymphoscintigram all were obese (BMI 36-74; p = 0.03).
Conclusions:
Nonambulatory patients with lower extremity neuromuscular dysfunction and swelling can exhibit normal lymphatic function. Obesity is associated with abnormal lymphoscintigram result and lymphedema in this patient population. Individuals should be advised to maintain a normal BMI.
Background:. Although patients with obesity-induced lymphedema can be treated by weight loss therapy, they find it difficult to lose the required amount of weight. The aims of this study were to clarify the characteristics of the lymphatic vessels in patients with obesity-induced lymphedema and to determine the feasibility and efficacy of lymphovenous anastomosis (LVA) in these patients.
Methods:. Twenty-two patients (44 edematous lower limbs) with a body mass index (BMI) >35 kg/m2 (obese group) and 91 patients with lymphedema (141 edematous lower limbs) and BMI
Lymphatic disorders are a group of congenital malformations that affect the lymphatic system. The lesions consist of: macrocystic/microcystic lymphatic malformation, primary lymphoedema, generalized lymphatic anomaly, Gorham–Stout disease, and overgrowth conditions associated with lymphatic malformations (CLOVES, Klippel–Trenaunay). Many lesions are caused by mutations in PIK3CA. Treatment is based on symptoms and the type of lymphatic disorder. Patients are typically best managed in an interdisciplinary centre focused on vascular anomalies.
Objective
To identify the extent that sex, age and body mass index (BMI) is associated with medical and pharmacy costs.
Design
Retrospective cohort.
Setting
A school district in the Western USA involving 2531 workers continuously employed during 2011–2014.
Main outcome measures
Medical and pharmacy costs and BMI.
Results
Approximately 84% of employees participated in wellness screening. Participants were 1.03 (95% CI 1.01 to 1.06) times more likely to be women and younger (M=47.8 vs 49.8, p<0.001). Median medical and pharmacy costs were higher for women than men, increased with age, and were greater in morbidly obese individuals (p<0.001). Annual pharmacy claims were 18% more likely to be filed by women than men, 23% more likely filed by those aged ≥60 versus <40 years, and 6% more likely filed by morbidly obese individuals than of normal weight (p<0.001) individuals. Greater medical and pharmacy costs in older age were most pronounced in underweight and morbidly obese groups. Higher use of medication among women than men was primarily because of drugs involving birth control, osteoporosis, thyroid disease and urinary tract infection. Higher medication use in older age was primarily related to medications used to treat gastrointestinal problems. Medication use was positively associated with BMI weight classifications for most of the 33 drug types considered, with exceptions involving birth control, herpes and osteoporosis. A J-shape relationship was observed between BMI and medication use for acne, antibiotic, cold/influenza/allergy, eye infection, oedema, muscle spasms, pain and ulcers.
Conclusions
Medications associated with higher medical and pharmacy costs among women, older age and underweight or obese individuals are identified. Lowering medical and pharmacy costs requires weight management in older ages, particularly for underweight and obese. Higher pharmacy costs for certain drugs among underweight individuals may be associated with poorer nutrition.
Background:
Primary lymphedema results from the anomalous development of the lymphatic system that typically presents during infancy, childhood, or adolescence. Adult-onset primary lymphedema is rare and has not been studied. The purpose of this investigation was to characterize patients with primary lymphedema that developed after the pediatric time period to better understand the condition.
Study Design:
Patients treated in our Lymphedema Program between 2009 and 2018 were reviewed. Diagnosis was determined based on history, physical examination, and imaging studies. Patients with primary lymphedema developing in adulthood (>21 years) were identified. Sex, age of onset, location, severity, morbidity, family history, associated features, and lymphoscintigraphy findings were documented.
Results:
Twenty-six patients (10%) of 259 with primary lymphedema developed the disease during adulthood. Sixteen individuals were female, and the disease occurred at an average age of 40 years (range, 24-72). It affected the lower extremity (85%) (unilateral 82%, bilateral 18%) or upper limb (15%) (unilateral 80%, bilateral 20%). Twenty-seven percent of patients suffered infections. Ninety-five percent of lymphoscintigrams exhibited delayed transit of radiolabeled tracer and 73% showed dermal backflow. None of the patients had systemic lymphatic involvement or associated vascular anomalies. One patient had a family history of lymphedema.
Conclusions:
Adult-onset primary lymphedema is typically unilateral, affects the lower extremity, and is not associated with systemic lymphatic anomalies; hereditary transmission is rare. Because adult-onset lymphedema is much less common than the pediatric condition, the disease should be confirmed with lymphoscintigraphy. Imaging of the axillary or inguinal nodes is also considered to rule out a lesion causing secondary lymphedema.
Background and Objectives
In the Robot Assisted Surgery for High Risk Endometrial Cancer (RASHEC) trial, patients with high-risk endometrial cancer were randomly assigned to robot-assisted laparoscopic surgery (RALS) or laparotomy for pelvic and infrarenal para-aortic lymph node dissection. We here report on self-reported lower limb lymphedema (LLL), lymphocyst formation, ascites, and long-term serious adverse events 12 months after surgery.
Patients and methods
Patients were enrolled between 2013 and 2016, and 96 patients were included in the per protocol analysis, evenly distributed between RALS and laparotomy. Self-reported LLL was recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for endometrial cancer—EN24, assessed before and 12 months after surgery. Computed tomography was assessed at baseline, 3, and 12 months. Medical charts were reviewed for serious adverse events and hospital admissions 31 to 365 days after surgery.
Results
At 12 months after laparotomy and RALS, 61% and 50% patients, respectively, reported LLL (p = 0.31). In univariate analysis, the mean score of LLL at 12 months was significantly higher for laparotomy than for RALS (p < 0.05) and for those without abdominal drainage (p = 0.02), but was not independently associated with LLL in the multivariate analysis. Imaging showed no significant difference in lymphocyst formation or ascites between surgical modalities. No difference was found in serious adverse events and admissions to hospital for any reason. There was no agreement between lymphocyst formation or ascites and self-reported LLL.
Conclusion
Follow-up 1 year after comprehensive surgical staging for high-risk endometrial cancer showed no differences in self-reported LLL, findings on imaging, or SAE between laparotomy and robot-assisted surgery.
Background:
Genetic mutations and obesity increase the risk of secondary lymphedema, suggesting that impaired lymphatic function before surgical injury may contribute to disease pathophysiology. Previous studies show that obesity not only decreases lymphatic function, but also markedly increases pathologic changes, such as swelling, fibroadipose deposition, and inflammation. However, although these reports provide circumstantial evidence supporting the hypothesis that baseline lymphatic defects amplify the effect of lymphatic injury, the mechanisms regulating this association remain unknown.
Methods:
Baseline lymphatic morphology, leakiness, pumping, immune cell trafficking, and local inflammation and fibroadipose deposition were assessed in wild-type and Prox1-haploinsufficient (Prox1) mice, which have previously been shown to have abnormal vasculature without overt evidence of lymphedema. In subsequent experiments, wild-type and Prox1 mice underwent popliteal lymph node dissection to evaluate the effect of lymphatic injury. Repeated testing of all variables was conducted 4 weeks postoperatively.
Results:
At baseline, Prox1 mice had dilated, leaky lymphatic vessels corresponding to low-grade inflammation and decreased pumping and transport function, compared with wild-type mice. Popliteal lymph node dissection resulted in evidence of lymphedema in both Prox1 and wild-type mice, but popliteal lymph node dissection-treated Prox1 mice had increased inflammation and decreased lymphatic pumping.
Conclusions:
Subclinical lymphatic dysfunction exacerbates the pathologic changes of lymphatic injury, an effect that is multifactorial and related to increased lymphatic leakiness, perilymphatic accumulation of inflammatory cells, and impaired pumping and transport capacity. These findings suggest that preoperative testing of lymphatic function may enable clinicians to more accurately risk-stratify patients and design targeted preventative strategies.
Objective: The objective of the present study is to compare intracellular and extracellular
fluid variations in patients with lymphedema and body mass indexes between 25 and 37 with
a control group. Subjects: A cross-sectional study was carried out of 30 consecutive patients
with grade III (elephantiasis) leg lymphedema and BMI between 25 and 37 treated at the
Clinica Godoy in São Jose do Rio Preto-Brazil. Variations in intracellular and extracellular
fluid were evaluated by bioelectrical impedance analysis. Diagnosis of lymphedema was
made by the clinical history, physical examination, and measurement of intracellular and
extracellular fluid levels. The unpaired t-test and Fisher's exact test were used for statistical
analysis with an alpha error greater than 5% (p-value <0.05) being considered significant.
Results: Obese patients with lymphedema have more intracellular and extracellular fluid
compared to obese patients without lymphedema. Conclusion: Subclinical systemic
lymphedema caused by obesity manifests earlier in patients with lymphedema and worsens
with the progression of obesity.
Copyright
Lymphedema often is confused with other causes of extremity edema and enlargement. Understanding the risk factors and physical examination signs of lymphedema can enable the health care practitioner to accurately diagnose patients ∼90% of the time. Confirmatory diagnosis of the disease is made using lymphoscintigraphy. It is important to correctly diagnose patients with lymphedema so that they can be managed appropriately. © 2018 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Beyond lymphedema, in its diverse manifestations, there is a spectrum of human disease that directly or indirectly alters lymphatic structure and function. Diagnosis and differential diagnosis pose distinct challenges. In this overview, various categories of lymphatic disease are enumerated and viewed through the prism of lymphatic embryological development.Defects in the growth and development of lymphatic vessels underlie the lymphatic clinical disorders, including lymphedema, vascular malformations, and lymphangiectasia.Lymphedema represents the most commonly encountered disease state of the lymphatics. It can present in both acquired and heritable forms.Clinical manifestations of primary lymphedema can be mistaken for secondary lymphedema if edema first appears after an apparent provoking secondary inciting event.A genetic predisposition for the development of lymphedema, even when the inciting secondary events are easy to identify.There are at least nine causal mutations known for inherited human lymphedema.Beyond peripheral lymphedema, the spectrum of lymphatic vascular disease is remarkably diverse. The pathological alterations can be isolated, regionalized, or diffuse and can occur in isolation or in concert with other complex vascular lesions.Lymphatic malformations are microcystic, macrocystic, or mixed; generalized lymphatic anomaly is a multifocal lymphatic malformation that can involve the skin, superficial soft tissues, bone, and abdominal and thoracic viscera.In protein-losing enteropathy, loss of lymphatic fluid and plasma protein within the lumen of the gastrointestinal tract can lead to edema and hypoproteinemia.
Introduction: Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity induced lymphatic dysfunction modulates the pathologic effects of lymphatic injury in a mouse model. Methods: We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals are fed a high fat diet and controls are fed a normal chow diet for 8-10 weeks. We then surgically ablated the superficial and deep lymphatics of the mid-portion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Results: Compared with lean controls, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45(+) and CD4(+) cell inflammation (p<0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. Conclusions: Obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury.
Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system.
Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up.
High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages.
Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.
Conventional oil-contrast lymphography has long been the mainstay for lymphatic imaging. However, the emergence of computed tomography (CT) and magnetic resonance (MR) imaging has severely curtailed its use. Because of recent improvements and refinements, lymphangioscintigraphy now permits high-resolution imaging of peripheral lymphatic vessels and provides insight into lymph flow dynamics. It is indispensable for patients with known or suspected lymphatic circulatory disorders in confirming the diagnosis and delineating the pathogenesis and evolution of lymphedema. In addition, lymphangioscintigraphy helps evaluate lymphatic truncal anatomy and radiotracer transport. It can also be used to evaluate the efficacy of various treatment options designed to facilitate lymph flow or reduce lymph formation. The procedure is essentially noninvasive, can easily be repeated, and does not adversely affect the lymphatic vascular endothelium. MR imaging complements lymphangioscintigraphy in the monitoring and treatment of more complex lymphatic circulatory disorders, whereas CT facilitates catheter-guided percutaneous sclerosis or obliteration of specific lymphangiectasia or lymphangioma syndromes. Ultrasonography has proved useful in the setting of filariasis. Patients with a provisional diagnosis of peripheral lymphatic dysfunction or idiopathic edema should undergo diagnostic lymphangioscintigraphy and, in some cases, MR imaging to verify diagnostic accuracy, pinpoint the specific abnormality, and help guide subsequent therapy.