Primary Lymphedema Research Articles

Therapeutic Efficacy of Complex Decongestive Therapy in the Treatment of Elephantiasis of the Lower Extremities

ABSTRACT Objective To evaluate the therapeutic efficacy of complex decongestive therapy in the treatment of elephantiasis of the lower extremities. Methods Seventeen patients with unilateral lower limb elephantiasis were included in the study (5 with primary lymphedema and 12 with secondary lymphedema). All patients were treated with one course (4 weeks) of complex decongestive therapy. Changes inextracellular fluid (ECF), BMI, circumferences, and skin properties including skin stiffness (SF), percent water content (PWC), and trans-epidermal water loss (TEWL) were measured before and after treatment. Results The “elephantiasis-like” appearance of the affected limb was greatly improved after treatment. The ECF, BMI, and circumferences were significantly decreased after treatment (P Conclusion Complex decongestive therapy is effective in the treatment of advanced stages of chronic lymphedema.

Systematic Review of Patient-Reported Outcomes following Surgical Treatment of Lymphedema.

Introduction: Analysis of quality of life (QOL) outcomes is an important aspect of lymphedema treatment since this disease can substantially impact QOL in affected individuals. There are a growing number of studies reporting patient-reported outcomes (PROMs) for patients with lymphedema. The purpose of this study was to conduct a systematic review of outcomes and utilization of PROMs following surgical treatment of lymphedema. Methods: A literature search of four databases was performed up to and including March, 2019. Studies included reported on QOL outcomes after physiologic procedures, defined as either lymphovenous bypass (LVB) or vascularized lymph node transplant (VLNT), to treat upper and/or lower extremity primary or secondary lymphedema. Results: In total, 850 studies were screened—of which, 32 studies were included in this review. Lymphovenous bypass was the surgical intervention in 16 studies, VLNT in 11 studies, and both in 5 studies. Of the 32 total studies, 16 used validated survey tools. The most commonly used PROM was the lymph quality of life measure for limb lymphedema (LYMQOL) (12 studies). In the remaining four studies, the upper limb lymphedema 27 scale (ULL27), the short form 36 questionnaire (SF-36), the lymphedema functioning, disability and health questionnaire (Lymph-ICF), and lymphedema life impact scale (LLIS) were each used once. QOL improvement following surgical treatment was noted in all studies. Conclusions: Physiologic surgical treatment of lymphedema results in improved QOL outcomes in most patients. The use of validated PROM tools is increasing but there is no current consensus on use. Future research to evaluate the psychometric properties of PROMs in lymphedema is needed to guide the development and use of lymphedema-specific tools.

61: Complex labioplasty in patient with congenital primary lymphedema

This video summarizes the diagnosis, evaluation, underlying anatomy, surgical intervention, and follow-up in a patient with congenital primary lymphedema undergoing complex labioplasty. We present a case of a 17 year old female with a history of congenital primary lymphedema who underwent complex labioplasty. At birth the patient had thigh and labial swelling increasing in size over time. Imaging was unremarkable. No intervention was felt possible by vascular surgery. After puberty, the left labia minora enlarged to 9 x 7 x 4 cm, the left labia majora to 7 x 3 x 3 cm. This interfered with ADL's including dressing, walking, and pain on sitting. Patient had significant mental stress. Primary lymphedema affects 1 in 100,000 individuals, caused by abnormal development of the lymphatic system (primary) or an insult after birth (secondary). The majority have lower limb involvement, the left leg more often involved. This patient had no prior history of infection, radiation, surgery, or trauma. An awareness of the blood supply of the labia was critical in creating flaps. The initial flap extended from the introitus in a narrow to wider configuration, the lateral portion of labia minora tissue was included to match the color and texture of the right, the pedicle coming from 5 to 7 o'clock with deep dissection 3.5 cm at the base preserving the blood supply. Dissection to the level of the left frenulum. Underlying excess tissue excised allowing the skin flap to be placed in a normal configuration. Left labia majora reduced with an elliptical incision and underlying tissue excised to reduce the bulk. Postoperatively the patient had minimal separation of the superior aspect of labia minora resutured in the office setting with marked improvement in the overall appearance. This case illustrates the importance of conserving the blood supply to the labia in the creation of viable flaps in complex labioplasty.

The clinical characteristics of lower extremity lymphedema in 440 patients

BackgroundLower extremity lymphedema is frequently encountered in the vascular clinic. Established dogma purports that cancer is the most common cause of lower extremity lymphedema in Western countries, whereas chronic venous insufficiency (CVI) is often overlooked as a potential cause. Moreover, lymphedema is typically ascribed to a single cause, yet multiple causes can coexist. MethodsA 3-year retrospective analysis was conducted of demographic and clinical characteristics of 440 eligible patients with lower extremity lymphedema who presented for lymphatic physiotherapy to a university medical center's cancer-based physical therapy department. ResultsThe four most common causes of lower extremity lymphedema were CVI (phlebolymphedema; 41.8%), cancer-related lymphedema (33.9%), primary lymphedema (12.5%), and lipedema with secondary lymphedema (11.8%). The collective cohort was more likely to be female (71.1%; P < .0001), to be white (78.9%; P < .0001), to demonstrate bilateral distribution (74.5%; P < .0001), and to have involvement of the left leg (bilateral, 69.1% [P < .0001]; unilateral, 58.9% [P = .0588]). Morbid obesity was pervasive (mean weight and body mass index, 115.8 kg and 40.2 kg/m2, respectively) and significantly correlated with a higher International Society of Lymphology lymphedema stage (stage III mean weight and body mass index, 169.2 kg and 57.3 kg/m2, respectively, vs stage II, 107.8 kg and 37.5 kg/m2, respectively; P < .0001). Approximately one in three (35.7%) of the population sustained one or more episodes of cellulitis, but patients with stage III lymphedema had roughly twice the rate of soft tissue infection as patients with stage II, 61.7% vs 31.8%, respectively (P < .001). Multifactorial lymphedema was present in 25%. Approximately half of the patients with lipedema with secondary lymphedema (48.1%) or primary lymphedema (45.5%) had a superimposed cause of swelling that was usually CVI. Total knee arthroplasty was the most common cause of noncancer surgery-mediated worsening of pre-existing lymphedema. ConclusionsIn a large cohort of patients treated in a cancer-affiliated physical therapy department, CVI (phlebolymphedema), not cancer, was the predominant cause of lower extremity lymphedema. One in four patients had more than one cause of lymphedema. Notable clinical characteristics included a proclivity for female patients, bilateral distribution, left limb, cellulitis, and nearly universal morbid obesity.

MELILOTUS, RUTIN AND BROMELAIN IN PRIMARY AND SECONDARY LYMPHEDEMA

As reported in the literature, benzopyrones (alpha and gamma) have important effects on the microcirculation through various mechanisms. Coumarins are an alpha-benzopyrone as derivatives of Melilotus Officinalis, while bioflavonoids are a gamma-benzopyrone and include Rutin. Alpha-benzopyrones have two fundamental pharmacological effects: they have pro-lymphokinetic action by activating contractility of lymphangions; and the activation of macrophages to provide a proteolytic effect. Gamma-benzopyrones, such as Rutin, have an important anti-exuding and membrane stabilizing effect. Bromelain is known for its anti-inflammatory effect. The present study enrolled 52 patients with primary and/or secondary lymphedema in clinical stages I or II (according to the ISL classification) with 31 cases involving the lower limbs and 21 cases involving the upper limbs. All subjects were given for six months a natural compound consisting of 100 mg of natural Melilotus, that contains 20 grams of Coumarin, 300 mg of Rutin and 100 mg of Bromelain. The following parameters were studied at zero time (T0), after three months (T1), and after six months of treatment (T2): pitting, Stemmer's sign, measurement of limb circumferences, measurement of superficial tissue thickness in the affected limbs using ultrasound, and blood tests to evaluate hepatic function (ALT, AST, GGT, total and fractional bilirubin). At the end of the treatment (T2), the following results were observed: disappearance of pitting in 72% of the cases; unchanged Stemmer's sign; average decrease in limb circumferences of 4.2 cm; and average reduction of the superficial thickness of 29%. There was no variation in the liver function parameters examined. The combination of natural compounds (Melilotus, Rutin, and Bromelain) has been shown to be a valuable aid in the clinical control of both primary and secondary lymphedema of clinical stages I and II as well as in control of inflammatory phenomena related to chronic stasis. There were no side effects and no alteration of liver function parameters found.

EFFECT OF PREGNANCY ON LOWER LIMB LYMPHEDEMA IN PATIENTS TREATED WITH MULTISITE LYMPHATICOVENULAR ANASTOMOSES (MLVAS)

Lymphaticovenular anastomosis (LVA) using supermicrosurgical techniques is effective for treating and preventing progression of lymphedema. We analyzed the influence of pregnancy on LVA in five patients from a total 2179 LVA cases. Previous studies offer conflicting reports on whether pregnancy worsens pre-existing lymphedema. This is the first report on the influence of pregnancy on lower limb lymphedema previously treated by multisite LVA (mLVA). Five patients with primary (n=4) and secondary (n=1) lower leg lymphedema were analyzed for this study. Patient age ranged from 18 to 31 (average 22.6) years old with 4 right and 1 left extremities involved. Duration of symptoms ranged from one to 19 (average 7.4) years and the periods of compression therapy were from 1 to 19 years (6.6 years). Four patients had single pregnancies and one patient was multiparous with 3 pregnancies. Final follow-up ranged from 5.8 to 18 years (average 8.9 years) after the primary mLVA. All patients had normal pregnancy, birth, and no serious complications after surgeries. Following pregnancy three patients had complete functional recovery (limb volume reduction and no compression requirement), one with functional improvement (limb volume reduction but required compression), and one with no change in symptoms (not worse and continued need for compression). There were no occurrences of infection following pregnancy. Based on this case series, it is suggested that pregnancy does not worsen the pre-existing lymphedema in patients who had previously undergone mLVA. Further studies with larger number of patients are needed to confirm these results.

Multilymphosome injection indocyanine green lymphography can detect more lymphatic vessels than lymphoscintigraphy in lymphedematous limbs

Sometimes, injecting indocyanine green (ICG) or isotope at distal limbs is insufficient especially in cases with low lymphatic function. The purpose of this study was to elucidate the usefulness of multi-lymphosome injection ICG lymphography. Two hundred and six lower limbs of 103 patients were included. ICG lymphography was performed by injecting ICG in three lymphosomes per limb: dorsum of foot (saphenous lymphatics), the proximal side of the lateral condyle (lateral calf lymphatics), and the lateral side of the superior edge of the knee (lateral thigh lymphatics). We observed the presence or absence of a linear pattern at each injection site with a near-infrared camera. Lymphoscintigraphy was performed by injecting an isotope in the first web space, conventionally. Whole body scintigrams were taken 60 min after injection. In multi-lymphosome ICG lymphography, the lateral thigh lymphatics were observed as a linear pattern in 75.2% of patients, the lateral calf lymphatics in 72.8%, and the saphenous lymphatics in 84.5% of patients. There was not a significant difference between secondary and primary lymphedema (p = 0.57, 0.77, and 0.56 in the lateral thigh, the lateral calf, and the saphenous lymphatics, respectively). Among the 12 limbs classified as Type 5, at least one linear pattern was found in 10 limbs (83.3%). We observed a linear pattern in 83.3% of the limbs that were lymphoscintigraphic Type 5 by using multi-lymphosome ICG lymphography. There is a possibility that the results of this study can increase the number of patients eligible for lymphatico-venous anastomosis (LVA) and increase the success rate of LVA.

Clinical and Scintigraphic Predictors of Primary Lower Limb Lymphedema-Volume Reduction During Complete Decongestive Physical Therapy.

Primary lower limb lymphedema is a chronic debilitating disorder without curative treatment. The initial treatment phase is dedicated to reducing lymphedema volume, whereas the second aims to stabilize that volume. The objective of this study was to analyze clinical and lymphoscintigraphic characteristics during complete decongestive physical therapy as predictors of primary unilateral lower limb lymphedema-volume reduction. This observational, retrospective study included 222 consecutive patients (January 2009-January 2017; median age: 45.8years) with lymphedema affecting the entire lower limb, who received complete decongestive physical therapy for the first time in a specialized lymphedema management center. Complete decongestive physical therapy consisted of low-stretch bandaging, manual lymph drainage, exercises, and skin care for all patients. Lymphoscintigraphy preceded treatment. Median lymphedema evolution was 73months, and median excess volume was 34%. Median (interquartile range) lymphedema volumes were 2845 (1038-3487) mL before and 1276 (601-2195) mL after a median of 11days of complete decongestive physical therapy, with 34% median reduction. Multivariate analyses retained age, body mass index >40kg/m2, and previous cellulitis, as independently associated with lymphedema volume reduction. For each additional year of age, volume reduction increased 0.16%. Unexpectedly, log-transformed initial lymphedema volumes indicated a negative impact, that is, 4.95%, for each log-unit gain. Patients with previous cellulitis episode(s) obtained 6.9% and those with BMI>40kg/m2 17.1% higher lymphedema volume reductions. Lower limb lymphoscintigraphy was available for 150 (67.6%) patients. Having dermal back flow was associated with greater lymphedema volume reduction than not (respectively, 39% vs 31%). This study was retrospective, and only 67.6% of patients underwent lymphoscintigraphy. Our analysis identified clinical and scintigraphic predictors of primary lymphedema volume reduction for patients with unilateral disease. Lymphoscintigraphy helps confirm lymphedema and predict volume reduction. Further study is required to confirm these observations.

Study of a supplement and a genetic test for lymphedema management.

Malformations in the lymphatic vasculature, injury, surgery, trauma or toxic damage may lead to swelling of the limbs caused by inefficient lymphatic uptake and flow (lymphedema). Lymphedema can be congenital or acquired. Primary lymphedema is rare and caused by mutations in single genes, secondary lymphedema is more common and caused by a trauma in association with a genetic predisposition. We decided to develop a genetic test that would determine the genetic predisposition to the onset of lymphedema and to predict the course of the disease by analyzing polymorphisms involved in leukotriene B4 (LTB4) synthetic pathway, and variants involved in the onset of secondary lymphedema. There are not many compounds available for the treatment of the negative effects of lymph accumulation, we therefore designed a food supplement based on the hydroxytyrosol, that has anti-oxidant, anti-bacterial and anti-inflammatory activities.(www.actabiomedica.it)

Clinical aspects of congenital primary lymphedema.

Lymphedema is a specific type of edema with a chronic, progressive nature. The aim of the present study is to report clinical findings related to edema and its location in children with primary lymphedema. Sixty-eight children with congenital primary lymphedema were evaluated at the Godoy Clinic in São Jose do Rio Preto, Brazil, between 2014 and 2017. A retrospective, cross-sectional study was conducted involving the analysis of clinical data on the location of edema in 68 children with congenital primary lymphedema. We evaluated the charts of all children with this condition in the period analyzed, recording the affected limbs and conditions associated with lymphedema. Sixty-eight children, 37 girls (54.41%) and 31 boys (45.58%), were evaluated. We found that congenital primary lymphedema predominantly affects the lower limbs and is more prevalent in girls than boys.

Clinical Profile and Cost of Treatment among Patients with Lymphedema in Philippine Heart Center from 2018-2020

PURPOSE This is a local study conducted that describes the clinical profile and cost incurred of patients with lymphedema among Filipinos seen in our institution. METHODS A descriptive study using the data from the Philippine Heart Center Lymphedema clinic from 2018-2020. It consists of the patient’s name, age, sex, lymphedema onset, classification, type, stage, affected site, treatment modality, and the number of sessions. The cost incurred was based on the clinic’s costing list, treatment modality, and the number of sessions rendered. RESULTS The analysis included a total of 97 patients. The mean age was 60.3 (± 14.3) years old, with female predominance (74.2% versus 25.8%). The majority is classified as secondary (91.8%) versus primary (8.2%). The classification of primary lymphedema are praecox (62.5%), congenital (25%) and tarda (12.5%) while for secondary it is cancer related (53.9%), phlebolymphedema (34.8%), lipolymphedema (3.4%), obesity induced 3.4%, trauma related, infection (3.4%) and iatrogenic (1.1). The stage of severity is stage IIA (60.8%), III (17.6%), IIB (13.4%), and I (8.2%). The most affected site is bilateral lower extremities (30%), followed by left (18.5%) and right (17.5%) lower extremities. The right and left upper extremities showed equal (16.5%) with no bilateral upper extremities affectation. The majority of treatment is unilateral (68.8%) versus bilateral (31.2%) decompressive lymphatic therapy. The total cost incurred was an average of P17,753 per patient and mostly came from the private section (89.7%) versus (10.3%). CONCLUSION Lymphedema is a chronic and recurrent disease that carries a substantial cost to patients. Its exact incidence, treatment outcomes, and quality of life among Filipinos are yet to be explored. A clinical profile will be the first step to raise awareness and to identify the different subset of populations for prevention, support, and treatment. Keywords Clinical profile, Cost of treatment, Lymphedema

Lympho-scintigraphic localisation of obstructions in primary lymphodema of lower limbs in the Central Province of Sri Lanka from 1990 to 2003

Introduction: Primary lymphoedema constitutes the bulk of cases among those seeking treatment in the Central province1. The underlying pathophysiological mechanics at presentation have not yet been established in Sri Lanka. Objective: To describe the location of the sites of obstruction to lymphatic flow in primary lymphoedema among Sri Lankan patients related to their clinical level of lymphoedema at presentation. Method: Eighty consecutive patients with primary lymphoedema, with varied levels of clinical lymphoedema were studied by isotope lympho-scintigraphy to ascertain where the block occurred, for each level of clinical lymphoedema of the lower limb. Results: The location of scintigraphic obstruction was always located more proximal in the limb, to the level of clinical lymphoedema. The site varied for each clinical level. Sites were related to the anatomical location of lymph nodes except for, a very common site in the medial knee. Such blocks were associated with rapid entry to the blood stream suggestive of the existence of lympho-venous shunting at this level. In most, the presenting level of lymphoedema was reached within 24-months of onset. Conclusion: Lymph nodes are probably the site of obstruction in most cases of primary lymphoedema. Presenting clinical level of lymphoedema is a dynamic of, site of lymphatic blockage and the presence of lympho-venous shunting.

Volumetric analysis of Non-contrast Magnetic Resonance Lymphangiography in patients affected by lower extremities primary lymphedema.

Since the response to conservative and surgical treatments in lymphedema is based only on clinical evaluation, we want to propose a new technique for the volume calculation of lower extremities affected by lymphedema. Ten female patients affected by primary LE of the lower limbs (mean age 33 ± 5years; age range 16-42) underwent NCMRL in September 2019. Acquisition protocol included a STIR sequence (FOV 460 × 504mm; matrix 315 × 384 pixel; voxel size 1.1 × 1.1 × 1.0mm; TR 3000ms; TE 254ms; TI 160ms). Two readers independently performed a manual segmentation with ITK-SNAP open-source software to assess the volume of the lower limbs. The agreement for volumetric segmentation between the two operators was assessed through intraclass correlation coefficient (ICC). Mean segmentation time was 5 ± 0.3min. ICC demonstrated excellent intra-examiner agreements for both readers 1 (ICC = 0.9991, p < 0.0001) and 2 (ICC = 0.9989, p < 0.0001). Inter-reader agreement was excellent (ICC = 0.9991, p < 0.0001). Manual segmentation with ITK-SNAP of NCMRL examinations in patients affected by primary lower limb LE represents a reproducible procedure for an objective evaluation of volumes, useful for follow-up.

Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema

ObjectiveLymphedema is a chronic debilitating disease characterized by the accumulation of fluid in the extremities as a result of lymphatic system impairment. Current treatments fail to restore the functionality and structural integrity of the lymphatic vessels lost in this condition. In this study, autologous mobilized peripheral blood stem cell transplantation was used and its potential efficacy and safety were evaluated in treating this condition. MethodsTen patients with primary lymphedema in the lower extremity received granulocyte-colony stimulating factor subcutaneously for 4 days, to stimulate stem cell mobilization, after which 200 to 250 mL of blood was drawn from each patient and used to collect stem cells. Mobilized stem cells were counted by flow cytometry with International Society of Hematotherapy and Graft Engineering method. In two sessions, 3 weeks apart, these stem cells were injected subcutaneously in the affected limb at approximately 80 points, along the lymphatic vessels. Each patient was followed for 6 months, during which changes in the limb volume and circumference were measured. Lymphangiogenesis was evaluated by biopsy, the lymphoscintigraphic transport index was calculated using Lymphoscintigraphy, and quality of life was surveyed. ResultsIn this study, patients received on average 9.5 ± 6.8 × 108 mononuclear cells (which divided into 2 × 106 CD34+ cells for each session) in two sessions. The volume of the lower limbs decreased in 60% of patients. One patient showed a slight increase in the volume of lower limbs and three showed no change. The average limb volume was 4469.41 ± 1760.71 cm3, which on average differed from the average initial limb volume by 232.88 ± 392.53 cm3. Quality of life was reported as slightly increased in 60% of patients. The lymphoscintigraphic transport index suggested improvement in 60% of the patients. Likewise, tissue samples showed a 60% increase in lymphatic vessels. ConclusionsSubcutaneous injection of autologous hematopoietic stem cells harvested from peripheral blood into patients with primary lower limb lymphedema is feasible, potentially effective, and without serious adverse effects. However, a larger scale study with more patients is needed to validate our results. Last, to increase the effectiveness of this treatment, the optimal dose of cells injected and the requirement for additional growth factors need further study.

Novel Method of Liposuction in Primary Lymphedema

Chronic lymphedema is a devastating problem for the patient and major financial and social burden. There are various medical and surgical management options available. One of the methods of treatment of chronic lymphedema is liposuction. We have used a novel modification of liposuction adhering to the principles to help in better aspiration of fat and fluid.

Novel Method of Liposuction in Primary Lymphedema

Chronic lymphedema is a devastating problem for the patient and major financial and social burden. There are various medical and surgical management options available. One of the methods of treatment of chronic lymphedema is liposuction. We have used a novel modification of liposuction adhering to the principles to help in better aspiration of fat and fluid.

Characteristics and outcomes of lymphaticovenular anastomosis in older patients with bilateral involvement versus younger patients with unilateral involvement in lower extremity lymphedema

ObjectiveWe have previously reported that patients with idiopathic primary lymphedema of adult onset can be classified into an older group with bilateral involvement and a younger group with unilateral involvement and that there are significant differences in the characteristics of these groups. The aims of this study were to investigate the features of these two groups further by evaluating the lymphatics while performing lymphaticovenular anastomosis (LVA) and to compare the effectiveness of LVA between the two groups. MethodsThis study enrolled 74 patients (136 edematous legs) in whom indocyanine green (ICG) lymphography and LVA were performed. The rate of detection and the diameter of the lymphatic vessels were recorded. The lower extremity lymphedema index (the total sum of the squares of the circumference for five areas in each leg divided by the body mass index) was obtained before and 6 months after LVA. The rate of improvement in the affected lower limbs after LVA was also calculated. ResultsThe clinical lymphedema pattern was determined to be bilateral in 62 patients and unilateral in 12. Patients with bilateral lymphedema were significantly older than those with unilateral lymphedema (77.1 ± 7.8 years vs 55.5 ± 12.77 years; P < .01). A linear pattern was seen in 23 patients (46 legs), a low enhancement (LE) pattern in 12 patients (24 legs), a distal dermal backflow (dDB) pattern in 20 patients (40 legs), and an extended dermal backflow (eDB) pattern in 7 patients (14 legs). The lymphedema was unilateral in 12 patients (12 legs). There were significant between-group differences in lymphatic diameter in relation to lower leg area: linear (0.9 ± 0.1 mm) vs dDB (0.7 ± 0.2 mm), linear vs eDB (0.7 ± 0.2 mm), linear vs unilateral (0.5 ± 0.1 mm), LE (0.9 ± 0.2 mm) vs dDB, LE vs eDB, LE vs unilateral, and dDB vs unilateral, P < .01; and eDB vs unilateral, P < .05. There were also significant between-group differences in the rate of improvement in the lower extremity lymphedema index according to the ICG lymphography pattern and laterality: linear (10.5% ± 2.4%) vs unilateral (6.7% ± 0.6%), LE (10.4% ± 1.5%) vs unilateral, dDB (11.0% ± 1.3%) vs eDB (8.9% ± 1.5%), and dDB vs unilateral, P < .01; linear vs eDB, P < .05; and eDB vs unilateral, P < .05. ConclusionsThe lymphatic vessel diameter tended to be greater in older patients with bilateral lymphedema than in younger patients with unilateral lymphedema. The rate of detection and improvement tended to decrease with worsening of the ICG lymphography pattern. LVA is thought to be more effective in older patients with early-stage bilateral lower leg lymphedema than in their younger counterparts with late-stage unilateral lymphedema.

Pharmacotherapy Agents in Lymphedema Treatment: A Systematic Review.

It is estimated that one in every six patients undergoing solid cancer treatment will develop secondary lymphedema. We conducted a systematic review of publications assessing the potential use of pharmacotherapy agents in lymphedema treatment. The search was conducted on PubMed and eligibility criteria excluded papers that investigated other therapies or focused on primary lymphedema. From 285 potential papers found in the literature, seven studies fulfilled the eligibility criteria. Different types of therapies were proposed, but all of them interfered with inflammation in the lymphedema tissue. Interestingly, the majority of publications were clinical, and three authors conducted randomized, placebo-controlled, double-blinded clinical studies. Promising results were observed for the oral administration of ketoprofen or selenium and topical tacrolimus. Pharmacotherapy agents were successfully described in lymphedema treatment in clinical and experimental studies. The benefits of delivering ketoprofen, selenium, or tacrolimus in lymphedema were noticed, and these therapies were easily delivered and well-tolerated.

Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation.

Background: Lymphedema includes primary lymphedema (P-LE) and secondary lymphedema (S-LE), which is a chronic progressive disease. The former group is further classified as congenital and acquired P-LE (AP-LE); its etiology is unclear, and only a few studies on its pathophysiology exist. We hypothesized that an autoimmune disease or self-inflammatory mechanism occurs in lymphatic vessels, leading to obstruction. Methods and Results: We enrolled 46 patients with lymphedema who underwent lymphaticovenous anastomosis (LVA) from January to October 2015. Collecting lymph ducts were obtained during LVA. We performed hematoxylin/eosin staining and immunostaining for LYVE-1, IL-1β, IL-6, and TNF-α. There were no substantial histological differences between the two types of lymphedema, whereas some differences in expression of inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were observed. Only a few inflammatory cells could be seen around the vessels. Although no significant differences in expression of IL-1β were found between AP-LE and S-LE, TNF-α was more highly expressed in the smooth muscle layer in AP-LE patients than in S-LE patients. There were no significant morphological differences in the collecting ducts of lymphatic vessels between S-LE and P-LE. Nevertheless, higher levels of TNF-α accumulation were found in the thick smooth muscle layer of P-LE patients than in that of S-LE patients. Conclusion: TNF-α-related inflammation in collecting ducts of lymphatic vessels is an important characteristic of the pathology of P-LE. TNF-α inhibitors might improve symptoms of AP-LE.

Giant primary lymphedema of the vulva in a young female

A 21-year-old single female with a large swelling of the vulva’s left labia majora was diagnosed with a case of primary lymphedema of the left lower limb and external genitalia. The giant labial swelling was excised, and the patient experiences no complications or recurrence for 7 months postoperatively. Following the surgical excision of the swelling, the left labia majora and minora were reconstructed successfully. The excised mass weighed 6.3 kg and measured 40 cm x 35 cm x 30 cm. There were no complications postoperatively, and the patient has not experienced recurrence during the 7-month follow-up period. The patient returned to her normal life. Level of evidence: Level V, therapeutic study.