Lymphedema Research Articles

Short term treatment of secondary lymphedema with hyaluronidase injections reduces mouse hindlimb lymphedema.

Lymphedema is a common complication following breast cancer treatment with axillary lymphadenectomy and radiotherapy. Currently, there is no curative treatment for this disease, hence there is a need for new therapeutic suggestions. The aim of this study was to investigate the effect of hyaluronidase (HYAL) injections after inducing hindlimb lymphedema in 36 female C57BL/6 mice. HYAL injections were administered every second day for 14 days in three groups: (1) HYAL for 1 week followed by saline for 1 week, (2) HYAL for 2 weeks, and (3) saline injections for 2 weeks. Volume of the lymphedema limb was weekly assessed with micro-computed tomography (μ-CT) scans for a total course of 6 weeks. Lymph vessel morphometry was assessed in the end of the study after staining cross-sections of the hindlimb for anti-LYVE-1 blindly. Lymphatic function was assessed by lymphoscintigraphy to assess lymphatic clearance. There was a significant reduction of the volume of lymphedema in mice treated with HYAL-7 compared with mice treated with HYAL-14 (p < 0.05) and saline (p < 0.05). No differences were detected in lymph vessel morphometry and the lymphoscintigraphy between groups. Short-term treatment with HYAL-7 might be a potential therapeutic suggestion for secondary lymphedema induced in mouse hindlimbs. In the future, clinical studies are needed to investigate the potential of HYAL treatment in human beings.

Current Research on the Use of the Omental Flap in Breast Reconstruction and Post-Mastectomy Lymphedema: A Focus on Omental-Vascularized Lymph Node Transfer.

The novel use of the omental flap in breast reconstruction has been increasing in research popularity within the last few decades. This technique has its roots in the early 20th century as surgeons explored the use of the omentum for a variety of reconstructive purposes across various surgical subspecialties. The current literature shows evidence of the benefits of using the omentum in autologous breast reconstruction compared to the more traditional abdominal, flank, thigh, and gluteal donor flap reconstruction. This method introduces a viable option for patients that do not meet the criteria for the traditional autologous reconstruction techniques allowing for the restoration of more natural appearing breasts without the added complication of donor-site mortality. Additionally, the omentum, with its rich source of vascularized lymph nodes, has been studied as a potential source for lymph node transfer in the treatment of mastectomy-associated lymphedema. In this review, we highlight the most recent research on the current practices of omental-based breast reconstruction techniques and their use in postmastectomy lymphedema. We discuss the history and natural progression of the development of omental-based reconstruction as an autologous breast reconstruction technique, highlight the latest advances and challenges for the utility of the omental flap in current surgical procedures, and present future directions for the potential role of omental-based breast reconstruction in postmastectomy breast surgery.

Stage-Dependent Increase of Systemic Immune Activation and CCR5+CD4+ T Cells in Filarial Driven Lymphedema in Ghana and Tanzania.

Chronic lymphedema caused by infection of Wuchereria bancrofti is a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1-2), intermediate (stage 3-4), or advanced (stage 5-7) lymphedema to determine CD4+ T cell activation patterns and markers associated with immune cell exhaustion. A flow cytometry-based analysis of peripheral whole blood revealed different T cell phenotypes within participants with different stages of filarial lymphedema. In detail, increased frequencies of CD4+HLA-DR+CD38+ T cells were associated with higher stages of filarial lymphedema in patients from Ghana and Tanzania. In addition, significantly increased frequencies of CCR5+CD4+ T cells were seen in Ghanaian participants with advanced LE stages, which was not observed in the Tanzanian cohort. The frequencies of CD8+PD-1+ T cells were augmented in individuals with higher stage lymphedema in both countries. These findings show distinct activation and exhaustion patterns in lymphedema patients but reveal that immunological findings differ between West and East African countries.

Recent Advances in Therapeutic Modalities Against Breast Cancer-Related Lymphedema: Future Epigenetic Landscape.

Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.

The Future of Lymphedema: Potential Therapeutic Targets for Treatment.

This review aims to summarize the current knowledge regarding the pharmacological interventions studied in both experimental and clinical trials for secondary lymphedema. Lymphedema is a progressive disease that results in tissue swelling, pain, and functional disability. The most common cause of secondary lymphedema in developed countries is an iatrogenic injury to the lymphatic system during cancer treatment. Despite its high incidence and severe sequelae, lymphedema is usually treated with palliative options such as compression and physical therapy. However, recent studies on the pathophysiology of lymphedema have explored pharmacological treatments in preclinical and early phase clinical trials. Many potential treatment options for lymphedema have been explored throughout the past two decades including systemic agents and topical approaches to decrease the potential toxicity of systemic treatment. Treatment strategies including lymphangiogenic factors, anti-inflammatory agents, and anti-fibrotic therapies may be used independently or in conjunction with surgical approaches.

Investigation of physical activity, fear of falling, and functionality in individuals with lower extremity lymphedema.

To investigate the fear of falling, physical activity, and functionality in patients with lymphedema in the lower extremities. Sixty-two patients who developed stage 2-3 lymphedema in the lower extremities due to primary or secondary causes (age: 56.03 ± 7.83 years) and 59 healthy controls (age: 54.61 ± 5.43 years) were included in the study. The sociodemographic and clinical characteristics of all individuals included in the study were recorded. In both groups, fear of falling was evaluated with the Tinetti Falls Efficacy Scale (TFES), lower extremity functionality with the Lower Extremity Functional Scale (LEFS), and physical activity with the International Physical Activity Questionnaire-Short Form (IPAQ-SF). There was no statistically significant difference between the demographic characteristics of the groups (p > 0.05). The primary and secondary lymphedema groups had similar LEFS (p = 0.207, d = 0.16), IPAQ (p = 0.782, d = 0.04), and TFES (p = 0.318, d = 0.92) scores. However, the TFES score of the lymphedema group was significantly higher than that of the control group (p < 0.01, d = 0.52), while the LEFS (p < 0.01, d = 0.77) and IPAQ scores (p = 0.001, d = 0.30) were significantly higher in the latter. There was a negative correlation between LEFS and TFES (r = -0.714, p < 0.001) and between TFES and IPAQ (r = -0.492, p < 0.001). LEFS and IPAQ were positively correlated (r = 0.619, p < 0.001). It was determined that individuals with lymphedema developed a fear of falling, and their functionality was negatively affected. This negative effect on functionality can be attributed to reduced physical activity and an increased fear of falling.

Efficacy of Lymphaticovenular Anastomosis for Secondary Upper Extremity Lymphedema: Treatment Strategies with Effects of Compression Therapy Discontinuation and Site-Specific Evaluation of the Upper Extremity.

Background: Lymphaticovenular anastomosis (LVA) has recently become a mainstream surgical treatment for lymphedema and is a useful treatment option in addition to conservative therapies such as compression therapy, exercise therapy, and lymphatic drainage. We performed LVA with the goal of stopping compression therapy and report the effect of LVA on secondary lymphedema of the upper extremities. Methods and Results: The participants were 20 patients with secondary lymphedema of the upper extremities categorized as stage 2 or 3 according to the International Society of Lymphology classification. We measured and compared the upper limb circumference at six locations before and 6 months after LVA. Significant decreases in circumference after surgery were observed at 8 cm proximal to the elbow, the elbow joint, 5 cm distal to the elbow, and the wrist joints, but not at 2 cm distal to the axilla or the dorsum of the hand. At more than 6 months postoperatively, eight patients who had been wearing compression gloves were no longer required to wear them, and three patients who had been wearing both sleeves and gloves were no longer required to wear them. Conclusions: LVA is effective in the treatment of secondary lymphedema of the upper extremities, particularly in improving elbow circumference, and is one of the treatments that contributes significantly to the improvement of quality of life. For severe cases with limited range of motion of the elbow joint, LVA should be performed first. Based on these results, we present an algorithm for upper extremity lymphedema treatment.

The effects of postoperative treadmill exercise on rats with secondary lymphedema.

Cancer-related lymphedema (LE) is often caused by radiotherapy and surgery such as lymph node dissection (LND). Previous studies have reported that exercise is beneficial to relieve LE, but the changes in the lymphatic system following exercise are still unclear. This study aimed to examine the changes in lymphatic drainage pathways over the exercise period and beneficial effects of exercise in rats with LE. Twelve rats were randomly allocated into exercise and control groups (EG and CG; n = 6 each). To obtain LE, inguinal and popliteal LND followed by 20 Gy irradiation was performed. Treadmill exercise was 30 minutes/day, 5 days/week over the four-week period. Consecutive indocyanine green (ICG) lymphography images were collected and classified into five patterns: i) linear; ii) splash; iii) stardust; iv) diffuse, and v) none. Ankle thickness was measured weekly. Histopathological evaluation was performed to examine the skin thickness, collagen area fraction (%) and lymphatic vessel density in harvested tissue. ICG lymphography exhibited more linear and splash patterns in the EG at week 3. The difference of swelling between both groups was significantly different at week 4 (p = 0.016). Histopathologic data revealed a thinner epidermis (p = 0.041) and dermis (p = 0.002), lower collagen area fraction (%, p = 0.002), and higher lymph vessel density (p = 0.002) in the EG than the CG. In conclusion, we found that postoperative exercise can facilitate improvement in lymphatic fluid retention in the lymphedema rat model, resulting in improvement of pathological conditions in the lymphatic system.

Retrospective Analysis of Management of Zygomatic Complex Fractures

Introduction Zygomatic bone and its surrounding bony anatomy are essential for maintaining facial contour—cheek prominence and orbital integrity. Management of the zygomatic complex (ZMC) fractures are important in the maintenance of function and facial integrity. Aim and Objectives To analyze the incidence, aetiology, surgical management, and complications encountered in the treatment of ZMC fractures in our super-specialty hospital, and to compare the number and location of fixation points and surgical access in our patient cohort with the literature. Materials and Method Retrospective analysis of all operative cases (Open Reduction and Internal Fixation) of ZMC fractures over a 3-year period (2017-2021) were reviewed. Craniofacial maxillofacial trauma patient’s medical records were collected and out which only the ZMC fracture cases were reviewed. Only the medical records from the period from 2017 to 2021 were included. The parameters such as etiology, site of the ZMC fracture, type of fracture, associated injuries, clinical findings, treated with conservative or surgical intervention, type of incisions used, number of fixation used, and any complications encountered were reviewed and analyzed. Results Out of 428 cases of craniofacial injury, 96 cases were ZMC fractures, isolated ZMC fractures accounted for 43%, 33% with associated injuries, 13% isolated arch, while 11% accounted isolated infraorbital rim fracture. Most common clinical findings were subconjunctival ecchymosis (71%), flattening of cheek (39%), malocclusion (22%), and so on. Buccal sulcus incision (66%) was mainly used, followed by upper blepharoplasty incision (59%). Depending on degree of displacement of fracture 1-point fixation (8%), 2-point fixation (30%), or 3-point fixation (27%) was performed. About 33% of cases were conservatively managed and followed up on regular intervals. Lymph edema, infra orbital paresthesia, temporary blindness, diplopia, hemianopsia were some of the complications encountered which were managed successfully and followed up. Conclusion ZMC fractures are most commonly occurring midface fractures with variable etiologies. The most common ZMC fracture pattern was tripod type of fracture. Greater portion of the patient were treated with 2-point fixation. Most of the complications were due to the impact and velocity of trauma.

A Novel Handheld Spectroscopy Tool for Detection of Lymphedema

The abstract provides an overview of lymphedema, a chronic and progressive lymphatic disorder that affects millions of people globally. This condition is associated with high costs and comorbidity, with limited treatment options available. Phlebolymphedema, a common form of secondary lymphedema, is linked to the combined effects of lymphatic and chronic venous insufficiencies. Early intervention is crucial to managing the condition; however, early detection remains challenging due to the lack of reliable diagnostic tools. This case study evaluates the clinical utility of a portable tissue analytical tool in a subject with bilateral lower extremity lymphedema undergoing a 60-day self-management program. The study includes details of the subject's profile, the intervention, and the measurements taken with the novel tool.

148. Extravasated Lymph from Secondary Lymphedema Patients Increases Cellular Permeability and Decreases Lymphatic Endothelial Cell VEGFR3 Expression

148. Extravasated Lymph from Secondary Lymphedema Patients Increases Cellular Permeability and Decreases Lymphatic Endothelial Cell VEGFR3 Expression

Skin microbiome alterations in upper extremity secondary lymphedema.

Lymphedema is a chronic condition that commonly occur from lymphatic injury following surgical resection of solid malignancies. While many studies have centered on the molecular and immune pathways that perpetuate lymphatic dysfunction, the role of the skin microbiome in lymphedema development remains unclear. In this study, skin swabs collected from normal and lymphedema forearms of 30 patients with unilateral upper extremity lymphedema were analyzed by 16S ribosomal RNA sequencing. Statistical models for microbiome data were utilized to correlate clinical variables with microbial profiles. Overall, 872 bacterial taxa were identified. There were no significant differences in microbial alpha diversity of the colonizing bacteria between normal and lymphedema skin samples (p = 0.25). Notably, for patients without a history of infection, a one-fold change in relative limb volume was significantly associated with a 0.58-unit increase in Bray-Curtis microbial distance between paired limbs (95%CI = 0.11,1.05, p = 0.02). Additionally, several genera, including Propionibacterium and Streptococcus, demonstrated high variability between paired samples. In summary, we demonstrate high compositional heterogeneity in the skin microbiome in upper extremity secondary lymphedema, supporting future studies into the role of host-microbe interactions on lymphedema pathophysiology.

Breast cancer-related lymphedema and recurrence of breast cancer: Protocol for a prospective cohort study in China.

The primary aim is to determine the factors associated with breast cancer-related lymphedema and to identify new associated factors for the recurrence of breast cancer and depression. The secondary objective is to investigate the incidence of breast cancer-related events (breast cancer-related lymphedema, recurrence of breast cancer, and depression). Finally, we want to explore and validate the complex relationship among multiple factors influencing breast cancer complications and breast cancer recurrence. A cohort study of females with unilateral breast cancer will be conducted in West China Hospital between February 2023 and February 2026. Breast cancer survivors in the age range of 17-55 will be recruited before breast cancer surgery. We will recruit 1557 preoperative patients with a first invasive breast cancer diagnosis. Consenting breast cancer survivors will complete demographic information, clinicopathological factors, surgery information, baseline information, and a baseline depression questionnaire. Data will be collected at four stages: the perioperative stage, chemotherapy therapy stage, radiation therapy stage, and follow-up stage. Data including the incidence and correlation of breast cancer-related lymphedema, breast cancer recurrence, depression, and medical cost will be collected and computed through the four stages above. For every statistical analysis, the participants will be classified into two groups based on whether they develop secondary lymphedema. Incidence rates of breast cancer recurrence and depression will be calculated separately for groups. Multivariate logistic regression will be used to determine whether secondary lymphedema and other parameters can predict breast cancer recurrence. Our prospective cohort study will contribute to establishing an early detection program for breast cancer-related lymphedema and recurrence of breast cancer, which are both associated with poor quality of life and reduced life expectancy. Our study can also provide new insights into the physical, economic, treatment-related and mental burdens of breast cancer survivors.

Chronic Progressive Lymphedema in Belgian Draft Horses: Understanding and Managing a Challenging Disease.

Chronic progressive lymphedema (CPL) in draft horses is characterized by increased dermal thickness and fibrosis, with the development of skinfolds and nodules, hyperkeratosis, and ulcerations on the distal limbs of affected horses. Secondary bacterial, fungal, or parasitic infections frequently complicate and aggravate the lesions, as well as the progression of this disease. CPL has a particularly high prevalence of up to 85.86% in the Belgian draft horse breed. Due to the disease's progressive and incurable nature, affected horses are often euthanized prematurely. The treatment options are solely symptomatic, aimed at improving the horse's quality of life. Despite the severity of this condition, many uncertainties about its etiology and pathogenesis still remain to date. The established scientific research on CPL is rather limited, although there is an urgent need for strategies to tackle this disease. This review summarizes the available knowledge, serving as a guideline for practitioners, and provides perspectives for future research programs.

Recurrent Nonimmune Fetal Hydrops Due to a Novel Pathogenic Variant in PIEZO1 Gene: A Case Report from South India

AbstractNonimmune fetal hydrops (NIFH) has underlying diverse etiology with generalized lymphatic dysplasia being one such cause. Lymphatic malformation-6 is a type of lymphatic dysplasia that is due to homozygous or compound heterozygous variants in the PIEZO1 gene. The clinical features associated with this condition during fetal life are nonimmune fetal hydrops that manifests with widespread lymphatic edema, with other systemic manifestations like pericardial/pleural effusions, chylothorax along with lymphangiectasia seen primarily in lungs and intestines. We present a case of recurrent NIFH in a family due to a novel pathogenic mutation in PIEZO1 gene. This variant was identified in homozygous state in all the three affected fetuses and in heterozygous state in both the parents. The couple were counseled regarding recurrence of this condition and given reproductive options for future pregnancies.

Current Concepts in the Management of Primary Lymphedema.

Primary lymphedema is a heterogeneous group of conditions encompassing all lymphatic anomalies that result in lymphatic swelling. Primary lymphedema can be difficult to diagnose, and diagnosis is often delayed. As opposed to secondary lymphedema, primary lymphedema has an unpredictable disease course, often progressing more slowly. Primary lymphedema can be associated with various genetic syndromes or can be idiopathic. Diagnosis is often clinical, although imaging can be a helpful adjunct. The literature on treating primary lymphedema is limited, and treatment algorithms are largely based on practice patterns for secondary lymphedema. The mainstay of treatment focuses on complete decongestive therapy, including manual lymphatic drainage and compression therapy. For those who fail conservative treatment, surgical treatment can be an option. Microsurgical techniques have shown promise in primary lymphedema, with both lymphovenous bypass and vascularized lymph node transfers demonstrating improved clinical outcomes in a few studies.

Retrospective study on the trajectories of lower limb volume after outpatient-based complex decongestive therapy in post-operative gynecological cancer patients with lymphedema

PurposeTo determine the effect of outpatient-based complex decongestive therapy in patients with secondary lower limb lymphedema (LLL) after gynecologic cancer surgery using group-based trajectory modeling (GBTM), and to examine factors predictive of the treatment course.MethodsThis retrospective study included participants who underwent surgery for gynecological cancer with pelvic lymph node dissection and subsequently visited the outpatient clinic for the treatment of stage II LLL according to the International Society of Lymphology. The improvement rate of edema at the initial visit and 3, 6, and 12 months later was assessed by calculating the volume of the lower extremity using the circumferential method. For evaluation of the patterns of treatment course, logistic regression analysis was performed after group estimation by the trend of the treatment course using GBTM.ResultsA total of 148 women (mean age 60.6 years (standard deviation: 13.4 years)) were analyzed. Three improvement trajectories were identified: (1) no response group, with worsening rather than improvement (n = 26); (2) moderate response group, with a slow improvement rate (n = 89); and (3) high response group, with a high improvement rate (n = 33). In addition, adherence to compression therapy at 3 months post-intervention was found to be a predictor in the no response group.ConclusionsGBTM estimated that there are three patterns of the treatment course in patients with LLL after gynecologic cancer surgery. Adherence to compression therapy at 3 months post-intervention is a predictor of the treatment effectiveness.

Low-intensity pulsed ultrasound reduces lymphedema by regulating macrophage polarization and enhancing microcirculation.

Background: Conventional therapies reduce lymphedema but do not cure it because they cannot modulate the pathophysiology of secondary lymphedema. Lymphedema is characterized by inflammation. We hypothesized that low-intensity pulsed ultrasound (LIPUS) treatment could reduce lymphedema by enhancing anti-inflammatory macrophage polarization and microcirculation. Methods: The rat tail secondary lymphedema model was established through the surgical ligation of lymphatic vessels. The rats were randomly divided into the normal, lymphedema, and LIPUS treatment groups. The LIPUS treatment (3min daily) was applied 3days after establishing the model. The total treatment period was 28days. Swelling, fibro adipose deposition, and inflammation of the rat tail were evaluated by HE staining and Masson's staining. The photoacoustic imaging system and laser Doppler flowmetry were used to monitor microcirculation changes in rat tails after LIPUS treatment. The cell inflammation model was activated with lipopolysaccharides. Flow cytometry and fluorescence staining were used to observe the dynamic process of macrophage polarization. Results: After 28days of treatment, compared with the lymphedema group, the tail circumference and subcutaneous tissue thickness of rats in the LIPUS group were decreased by 30%, the proportion of collagen fibers and the lymphatic vessel cross-sectional area was decreased, and tail blood flow was increased significantly. Cellular experiments revealed a decrease in CD86+ macrophages (M1) after LIPUS treatment. Conclusion: The transition of M1 macrophage and the promotion of microcirculation could be responsible for the beneficial effect of LIPUS on lymphedema.

Lymphological Liposculpture for Secondary Lymphedema after Breast Cancer and Gynecological Tumors: Long-Term Results after 15 Years.

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.

Outcomes after microsurgical treatment of lymphedema: a systematic review and meta-analysis.

Microsurgical treatment options for lymphedema consist mainly of lymphovenous anastomosis (LVA) and vascularized lymph node transfers (VLNTs). There are no standard measurements of the effectiveness of these interventions and reported outcomes vary among studies. A systematic review and meta-analysis were performed based on a structured search in Embase, Medline, PubMed, Cinahl, Cochrane, and ProQuest in October 2020, with an update in February 2022. Firstly, a qualitative summary of the main reported outcomes was performed, followed by a pooled meta-analysis of the three most frequently reported outcomes using a random effects model. Randomized controlled trials, prospective cohorts, retrospective cohorts, and cross-sectional and case-control studies that documented outcomes following microsurgery in adult patients were included. Studies of other surgical treatments (liposuction, radical excision, lymphatic vessel transplantation) or without reported outcomes were excluded. The study protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42020202417). No external funding was received for this review. One hundred fifty studies, including 6496 patients, were included in the systematic review. The qualitative analysis highlighted the three most frequently reported outcomes: change in circumference, change in volume, and change in the number of infectious episodes per year. The overall pooled change in excess circumference across 29 studies, including 1002 patients, was -35.6% [95% CI: -30.8 to -40.3]. The overall pooled change in excess volume across 12 studies including 587 patients was -32.7% [95% CI: -19.8 to -45.6], and the overall pooled change in the number of cutaneous infections episodes per year across 8 studies including 248 patients was -1.9 [95% CI: -1.4 to -2.3]. The vast majority of the studies included were case series and cohorts, which were intrinsically exposed to a risk of selection bias. The currently available evidence supports LVA and vascularized lymph node transfers as effective treatments to reduce the severity of secondary lymphedema. Standardization of staging method, outcomes measurements, and reporting is paramount in future research in order to allow comparability across studies and pooling of results.