Safety and Effectiveness of Liposuction Modalities in Managing Lipedema: Systematic Review and Meta-analysis

Background  Lipedema is a chronic, incurable disorder characterized by painful fat accumulation in the extremities. While the application of liposuction in lipedema management has become increasingly popular, the safety and effectiveness of this approach remain contentious. Our systematic review and meta-analysis aimed to assess various liposuction modalities in lipedema management to verify their safety and efficacy. Methods  In-line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a comprehensive literature review from inception until March 2023 using the following electronic databases: CENTRAL, MEDLINE, Google Scholar, and EMBASE. Results  From the 562 initially identified articles, 20 met our inclusion/exclusion criteria for evaluation. Our review encompassed 14 prospective cohort studies, 3 retrospective studies, 2 case series, and 1 cross-sectional study. A meta-analysis of nine articles revealed a notable improvement in the quality of life, pain, pressure sensitivity, bruising, cosmetic impairment, heaviness, walking difficulty, and itching among lipedema patients who underwent liposuction. Although complications such as inflammation, thrombosis, seroma, hematoma, and lymphedema-related skin changes were reported, severe complications were rare. Crucially, no instances of shock, recurrence, or mortality were reported. Conclusion  Liposuction is a safe and beneficial therapeutic intervention for managing lipedema symptoms and enhancing quality of life. However, the impact of liposuction on secondary lymphedema remains unreported in the literature. Further high-quality, large-scale trials are necessary to assess the safety and effectiveness of different liposuction modalities. These studies will contribute valuable insights to optimize liposuction as a therapeutic option for individuals with lipedema. Level of Evidence  I, risk/prognostic study.


Introduction
Lipedema is a chronic, symmetric, and incurable disorder impacting adipose tissue. 1,2It typically manifests as a disproportionate, painful accumulation of fat in the extremities. 3Commonly, it presents as bilateral enlargement of the lower limbs, including the buttocks, thighs, knees, and legs, while upper limbs are less frequently involved, and hands and feet are always spared. 4 The exact pathophysiology driving this unusual fat deposition is not yet fully understood 5 ; however, previous studies indicate potential roles for genetic and hormonal influences. 6,7Lipedema primarily affects women, often related to their state of constant hormonal changes. 8,9Often, patients with lipedema experience feelings of shame due to frequent misdiagnosis as obesity, 10 which can erode their trust in the health care system. 11Furthermore, distressing symptoms such as disfigurement and pain can significantly impair quality of life, psychological health, and self-confidence. 12As of now, lipedema remains incurable, prompting the development of different modalities to manage its symptoms. 13However, the efficacy of conservative management is hotly debated, with most patients reportedly unresponsive to such treatment. 14,15Thus, liposuction and its various modalities have recently gained traction as a potential means to manage lipedema's painful and disfiguring symptoms. 9,15Nonetheless, the safety and effectiveness of liposuction modalities for lipedema management remain controversial, with limited evidence to support their use.As such, we structured this systematic review and meta-analysis to evaluate the safety and effectiveness of different liposuction modalities in managing lipedema.This study assesses the outcomes of liposuction interventions, such as tumescent liposuction, laser-assisted liposuction, ultrasound-assisted liposuction, and water-assisted liposuction, regarding their safety and efficacy in managing lipedema.The findings of this study could help guide clinical practice and inform the development of standardized protocols for liposuction interventions in lipedema management.Through this study, we aim to provide valuable insights into lipedema management and contribute to ongoing efforts to improve the quality of life for patients with this condition.A secondary objective of this research is to assess and compare the different techniques to discern the most effective approach for lipedema outcomes.

Methods Search Strategy
This systematic review was designed following the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) guidelines. 16A comprehensive literature search was conducted from database inception until March 2023, across CENTRAL, MEDLINE, Google Scholar, and EMBASE, without any timeframe restrictions.To ensure a comprehensive result, the search employed the following key terms: "lipedema OR lipoedema" AND "liposuction OR lipoplasty OR liposculpture OR fat removal OR adipose suction OR suction-assisted lipectomy OR fat removal" AND "complications OR outcomes OR patient-reported outcomes OR techniques."The review has been registered with the International Prospective Register of Systematic Reviews (ID: CRD42023411664).

Study Selection
The Rayyan collaboration platform was used for the initial screening of articles by title and abstract.Inclusion criteria encompassed (1) studies reporting on patients who underwent liposuction for lipedema; (2) case series and original articles; (3) studies involving adult patients aged 18 years and above; (4) studies reporting on outcomes relevant to the clinical questions; (5) studies written in English.Exclusion criteria included (1) non-English language studies; (2) editorials, letters, commentaries, or reviews; (3) studies not employing liposuction for managing lipedema; (4) studies reporting on outcomes not relevant to the study objectives; (5) studies with a high risk of bias or improper methods.

Data Extraction
Data extraction was independently performed by two authors from the text, tables, and figures of the included studies using a predesigned, standardized extraction form.To ensure the reliability and accuracy of the extracted data, a second author independently reviewed the data extraction process, cross-checking all extracted data points against the original source materials to identify any discrepancies or missing information.This encompassed crucial data such as study characteristics (author, year of publication, study design, country of origin, and sample size), participant characteristics (age, sex, body mass index [BMI; kg/m 2 ], disease severity, and disease duration), liposuction Conclusion Liposuction is a safe and beneficial therapeutic intervention for managing lipedema symptoms and enhancing quality of life.However, the impact of liposuction on secondary lymphedema remains unreported in the literature.Further high-quality, large-scale trials are necessary to assess the safety and effectiveness of different liposuction modalities.These studies will contribute valuable insights to optimize liposuction as a therapeutic option for individuals with lipedema.Level of Evidence I, risk/prognostic study.
techniques were systematically categorized by fluid instillation (dry, wet, tumescent) and suction technology (conventional, power-assisted, laser-assisted, ultrasound-assisted), specialized techniques were also noted, intervention characteristics (type of liposuction modality used, volume of aspirate, number of procedures, and duration of follow-up), and outcome measures.The latter included safety outcomes such as the incidence of adverse events, and effectiveness outcomes including pain, edema, mobility, quality of life, secondary lymphedema, necrosis, and recurrence.The type of statistical analysis used to evaluate study outcomes was also noted.When data were unclear or incomplete, corresponding authors were contacted for clarification.If missing data could not be obtained, a thorough explanation was provided concerning it and its potential impact on the reported results.Data management was handled by the first author, in consultation with the second author.

Bias Assessment
Two authors independently used the methodological index for nonrandomized studies (MINORS) to assess the risk of bias in retrospective and prospective nonrandomized studies. 17For case series, the methodological quality and synthesis of case series and case report assessment tool was utilized. 18Potential bias was evaluated through funnel plots using the Egger's test.

Statistical Analysis
All analyses were conducted using RevMan (version 5.4.1;The Nordic Cochrane Centre, The Cochrane Collaboration, 2020, Copenhagen).We extracted the means and standard deviations (SDs) of the scores for the questions evaluating improvements in quality of life from the included studies, both pre-and postliposuction.In our study's quantitative analysis, we excluded studies that reported median and interquartile range values, in certain analysis.This exclusion was due to the necessity of mean and SD values for certain statistical calculations, including standardized mean differences (SMDs).A weighted mean difference with 95% confidence intervals (CIs) was pooled using a fixed-effects model.Forest plots were created to evaluate the results of pooling.p-value less than 0.05 was considered significant.Heterogeneity between trials was assessed using the Higgin I 2 test according to the Cochrane Handbook.

Quality Assessment and Level of Evidence
The quality of the 20 included articles was assessed by the authors, with 18 being nonrandomized noncomparative studies evaluated using the MINORS tool. 17The remaining two case series articles were assessed using the methodological quality and synthesis assessment tool. 18Two independent reviewers analyzed the risk of bias.This tool contains eight questions divided into four main domains: selection, ascertainment, causality, and reporting.Additionally, the MINORS tool, featuring eight items for noncomparative studies and scored on a scale of 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate), was used.The maximum score for noncomparative studies was 16.

Patient Profile and Basic Characteristics
The total number of patients with lipedema was reported to be 1,785.The mean age of the study participants was 39.987 years.The ages of the patients included in the studies ranged from 16 to 81 years.Among the studies that provided information on gender, a total of 1,133 participants were identified as females.Various comorbidities were identified in the included data extracted from the articles.Most commonly included hypothyroidism (75 cases), allergies (72 cases), depression (48 cases), migraine (47 cases), sleep disorders (45 cases), arterial hypertension (28 cases), and asthma and bowel disorders (27 cases) were also noted.It is important to consider potential overlaps, as individual patients may have had multiple conditions.The overall mean BMI of the included patients preintervention was 33.3 AE 5.4.One study provided data on postintervention BMI, which showed a mean of 26.1 AE 5.4, as it was 28.4 AE 4.5. 14Additionally, another study reported a preintervention mean BMI of 35.3 and a postintervention mean BMI of 33.9. 22Among the included studies, the most commonly reported onset trigger was puberty, documented in 65 cases.Pregnancy was identified as the trigger in 22 cases, while contraceptives and menopause were reported in 4 and 2 cases, respectively.Among the included patients, all 1,034 cases exhibited lower extremity lipedema, with 504 cases reporting involvement in the outer legs and 504 cases in the inner legs.A subset of 65 patients (6.3%) also showed upper extremity involvement in the arms.In specific cases, the affected areas were identified as arms and legs, hips and thighs, or arms, thighs, hips, knees, and calves to ankle.For the lower extremities, the most commonly affected areas were the thighs, calves, and buttocks.The thighs were further categorized into complete thighs, frontal parts, lateral sides, backside, and inside of thighs.Other affected areas included the frontal calves, calves, upper arms, forearms, back, and abdomen.In terms of leg involvement, 111 patients had lipedema, with the upper legs predominantly affected in 108 patients (97.3%) and more significant involvement in the lower legs observed in only 2 patients (1.8%).Among the 65 patients with upper extremity involvement, the arms were affected.A positive family history of lipedema was reported in the included data.About 17.44% (316 out of 1,812) of patients had a positive family history of lipedema, without specifying which family members were affected.

Patients and Clinical Characteristics
In our analysis of the liposuction techniques across the included studies, a predominant preference for the tumescent method of fluid instillation was observed.Of the 20 studies examined, 17 (81%) used the tumescent technique.Regarding the technology used for suction, the most commonly mentioned method was power-assisted liposuction, used in 35% of the cases (7 out of 20 articles).Water-assisted liposuction was employed either solely or in combination in six studies, accounting for 29%.►Tables 2 and 3 provides a summary of the liposuction techniques used in each study.In our review, 14 articles provided detailed information on the stages of lipedema in their patient cohorts.However, it is noteworthy that six articles did not specify the lipedema stages.The stage and grade distribution of lipedema among the included patients were as follows: 64 cases were classified as Stage I, 503 cases as Stage II, and 467 cases as Stage III, based on the staging system mentioned by Langendoen et al and Katzer et al. 3,6 Notably, there were no documented cases classified as Stage IV.The analysis of the data revealed that the overall mean number of treatment sessions was approximately 2.88 AE 1.30, ranging from one to five sessions per patient.The overall mean volume of aspirate removed per session was approximately 4,429.16mL.However, it is important to note that the included studies did not consistently report the infiltrated volume, which is crucial for interpreting the volume of lipoaspirate.The duration of each liposuction session varied, ranging from 1 to 2.5 hours.Among the 20 studies included, 11 of them reported the use of compression garments postoperatively.

Patient-reported Outcomes and Complications
Among the patient satisfaction evaluation methods used in the studies, the Visual Analogue Scale was employed in six    Liposuction's Efficacy in Lipedema Mortada et al.
p-value < 0.0001; ►Fig.5), cosmetic appearance (SMD 2.07, p-value <0.0001; ►Fig. 6),and heaviness (SMD 2.01, p-value <0.0001; ►Fig.7).Lastly, the improvement in difficulty in walking after liposuction was reported in only two studies, showing a significant effect with a p-value <0.00001, SMD ¼ 1.34 (95% CI: 1.12-1.56),and I 2 ¼ 86% (►Fig.8).We com-pared pre-and postliposuction data, revealing notable improvements in lipedema symptoms following the procedure.Pain levels decreased by 72.39%, sensitivity to pressure by 68.13%, bruising by 52.32%, cosmetic impairment by 57.36%, and the sensation of heaviness by 50.85%.Additionally, there was a significant reduction in difficulty in walking, Fig. 2 Forest plot showing the quality of life levels before and after liposuction in patients with lipedema.The standardized mean difference and corresponding 95% confidence intervals (CIs) are presented for each study.The diamond represents the overall effect size.SD, standard deviation.
Fig. 3 Forest plot illustrating the pain outcomes before and after liposuction in patients with lipedema.The standardized mean difference and its 95% confidence intervals (CIs) are displayed for each study.The diamond symbol represents the overall effect size.SD, standard deviation.which decreased by 78.47%.Overall, the reported complications included inflammation in 25 cases and thrombosis in 1 case.Individual cases presented specific complications such as skin changes consistent with lymphedema, foot and ankle swelling, dermal fibrosis, dermal sclerosis, hyperkeratosis, and persistent pigment irregularities.Other reported complications included mild arm-vein phlebitis in two patients, an episode of postsurgical anemia requiring a blood transfusion in one patient, and a microscopic pulmonary fat embolism in another patient.Some cases did not report complications, while one case reported deep vein thrombosis.Among the patients included in the study, a total of 14 individuals developed seroma (0.82%), 10 experienced infections (0.59%), 12 had hematoma (0.71%), 2 encountered bleeding (0.12%), 2 had skin necrosis (0.12%), and 3 developed secondary lymphedema (0.18%).The mean follow-up duration for the patients was 15.14 months, ranging from 1 to 96 months (8 years).

Quality Assessment and Bias Evaluation
The included studies in this analysis had varying levels of evidence.Out of the total studies, 15 were classified as Level II evidence.The MINORS tool was employed to gauge the quality of the nonrandomized studies included in this systematic review. 1 Total scores varied from 6 to 14, averaging 10.Items scoring the least included unbiased assessment of the study endpoint (a score of 0 in all studies), prospective calculation of the study size (a score of 0 in most studies), and a less than 5% loss to follow-up (a score of 0 in over half of the studies).Items with the highest scores were endpoints appropriate to the study's aim (a score of 2 in nearly all studies), clearly stated study aims (a score of 2 in most studies), and a follow-up period appropriate to the study's aim (a score of 2 in most studies; ►Table 4).The methodological quality and synthesis assessment tools were used to evaluate the risk of bias in case studies. 2 Both included case series scored 10.62 in terms of quality (►Table 5).

Discussion
Complex decongestive therapy is typically the initial treatment choice for lipedema in many countries.The aim of this treatment is to stop the progression of the condition and alleviate swelling.However, many patients continue to experience an increase in subcutaneous fat and a worsening of symptoms. 37The tumescent technique for liposuction,   Liposuction's Efficacy in Lipedema Mortada et al.6][37][38][39][40][41] Consequently, liposuction started to be considered a potential approach for treating lipedema and reducing fat tissue.This systematic review evaluated the effectiveness and safety of liposuction in individuals diagnosed with lipedema.A total of 20 articles, encompassing 1,785 patients, were included in the review.Among these, 1,133 patients were identified as females, with no males reported in the data extracted from the articles.The majority of these patients were classified as stage 2 (503 individuals), followed by stage 3 (467 individuals), and a smaller subgroup of stage 1 (64 individuals).The most frequently identified comorbidities were hypothyroidism and allergies, followed by depression, migraine, sleep disorders, arterial hypertension, asthma, and bowel disorders.Lipedema was predominantly observed in the outer and inner legs, and arms.Tumescent liposuction was the most commonly used technique, followed by Powerassisted liposuction and Water-assisted liposuction.
The meta-analysis of nine articles showed a significant improvement in patients' overall well-being, indicating considerable positive outcomes.Liposuction was found to effectively alleviate a range of symptoms associated with lipedema, such as pain, sensitivity to pressure, bruising, Table 4 Methodological index for nonrandomized studies assessment tool for nonrandomized noncomparative studies (N ¼ 18)

Moderate risk
Selection: (Question 1).Does the patient(s) represent(s) the whole experience of the investigator (center) or is the selection method unclear to the extent that other patients with similar presentations may not have been reported?Ascertainment: (Question 2).Was the exposure adequately ascertained?(Question 3).Was the outcome adequately ascertained?Causality: (Question 4).Were other alternative causes that may explain the observation ruled out? (Question 5).Was there a challenge/rechallenge phenomenon?(Question 6).Was there a dose-response effect?(Question 7).Was follow-up long enough for outcomes to occur?Reporting: (Question 8).Is the case(s) described with sufficient details to allow other investigators to replicate the research or to allow practitioners to make inferences related to their own practice?cosmetic concerns, heaviness, and mobility difficulties.Additionally, the procedure provided relief from itchiness, a specific symptom experienced by patients.These findings are consistent with reviews conducted by Peprah and Mac-Dougall 42 and Kruppa et al, 5 further supporting liposuction as an effective treatment for improving symptoms and overall quality of life in individuals with lipedema.Despite a few reported complications including inflammation, thrombosis, seroma, hematoma, and lymphedema-related skin changes, severe complications were rare.Notably, no instances of shock, recurrence, or death were reported in the analyzed cases, underscoring the overall safety of the procedure.Other studies 5,42,43 corroborate these findings, reinforcing the safety of liposuction as an intervention.
The average follow-up period for patients included in the studies was approximately 15 months, with a range from 1 to 96 months (8 years), which adds to the credibility and applicability of the findings.These results strongly advocate for liposuction as a safe, effective treatment option for managing lipedema symptoms, significantly improving in patients' overall well-being.
To the best of our knowledge, this is the first systematic review and meta-analysis to evaluate the safety and efficacy of different liposuction modalities in managing lipedema.The study has several strengths, such as compliance with the PRISMA guidelines, strict inclusion and exclusion criteria, comprehensive literature review without specific time constraints, inclusion of studies with moderate to high levels of evidence, and providing ample data to support a metaanalysis.According to the MINORS assessment tool, most studies scored a mean of 9.7 for potential bias.The methodological quality and synthesis assessment tool showed a quality score of 7, and a moderate risk of bias for the two included case series.However, the study does have limitations.First, most of our results were based on prospective cohort studies, potentially leading to some publication bias.Second, some studies did not include all the necessary details in their reported data, which may have resulted in some deficits in comparison.Third, 14 out of the 20 studies included in the review were from Germany, suggesting an underrepresentation of other areas of practice.Further research should prioritize the need for randomized control trials to assess the safety and effectiveness of different liposuction modalities.This should be accomplished through high-quality, large-scale, and multicenter studies.While there are multiple liposuction techniques that may yield similar outcomes, the lack of comparative studies hinders any definitive conclusion about the superiority of one method over another.The tumescent technique is often regarded as highly efficient with the lowest complication rates.However, the meta-analysis highlighted significant heterogeneity in the techniques utilized across studies, making direct comparisons between water-assisted, ultrasound-assisted, and powerassisted liposuction challenging.The variable reporting on the use of tumescence and its potential implications, especially in secondary lymphedema, further muddies the waters.There is a pressing need for standardized liposuction protocols and clarity on tumescence's role.Specific recommendations for standardization could include defining the composition of the tumescent solution, establishing guidelines for infiltration volume and rate, setting precise timing and duration for tumescence, and refining patient selection criteria.Additionally, outlining surgical techniques, postoperative care strategies, and outcome measurement protocols could significantly enhance the efficacy and safety of liposuction procedures.It is imperative that future research must concentrate on these areas to discern the efficacy and safety of the various liposuction techniques.Our study's limitation includes the potential overlap of patient cohorts in longitudinal studies, such as those by Schmeller et al (2012), 37 Baumgartner et al (2016, 2021), 22,30 andRapprich et al (2011, 2015). 31,33This overlap could lead to some patients being counted multiple times in our reported total of 1,785.Such repeated inclusions may slightly overestimate the number of unique patients, a factor to consider when interpreting our findings on lipedema prevalence and treatment outcomes.Our study highlights the importance of preoperative imaging for assessing lymphatic dysfunction in liposuction patients.We recommend future research to explore the use of imaging techniques like lymphoscintigraphy or near-infrared fluorescence imaging in preoperative evaluations.Such investigations could reveal crucial insights into lymphatic involvement, influencing surgical strategies and improving patient outcomes in lipedema and related conditions.In addition, our analysis reveals a need for more research on postoperative care in liposuction, particularly regarding the use and impact of compression garments.The inconsistency in their usage across studies suggests a lack of standardized practice.Future studies should focus on the efficacy of compression garments and their role in patient recovery.This could inform standardized guidelines for postliposuction care, optimizing patient outcomes and minimizing postoperative complications.

Conclusion
Liposuction, especially the tumescent technique, is effective in treating lipedema, enhancing outcomes across different modalities.However, the literature lacks data on liposuction's impact on secondary lymphedema.Future research should focus on comprehensive trials with diverse designs, including long-term follow-up and cost-effectiveness studies, to evaluate the safety and effectiveness of liposuction in lipedema.Future work should also determine safe lipoaspirate volumes to minimize complications, furthering our understanding of liposuction's benefits for lipedema patients.Integral to this future research is the exploration of true lymph-preserving liposuction, guided by indocyanine green lymphangiography and the avoidance of lymphatics during the procedure, a promising approach that warrants further investigation.

Fig. 1
Fig.1PRISMA flowchart illustrating the study selection process.The diagram outlines the number of studies identified, screened, assessed for eligibility, and included in the systematic review and meta-analysis, along with the reasons for exclusion at each stage.PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Fig. 4
Fig.4Forest plot showing sensitivity to pressure levels before and after liposuction in patients with lipedema.The standardized mean difference and corresponding 95% confidence intervals (CIs) are presented for each study.The diamond represents the overall effect size.SD, standard deviation.

Fig. 5
Fig. 5 Forest plot showing bruising levels before and after liposuction in patients with lipedema.The standardized mean difference and corresponding 95% confidence intervals (CIs) are presented for each study.The diamond represents the overall effect size.SD, standard deviation.

Fig. 6
Fig.6Forest plot showing cosmetic impairment levels before and after liposuction in patients with lipedema.The standardized mean difference and corresponding 95% confidence intervals (CIs) are presented for each study.The diamond represents the overall effect size.SD, standard deviation.

Fig. 7 Fig. 8
Fig. 7 Forest plot showing the heaviness before and after liposuction in patients with lipedema.The standardized mean difference and corresponding 95% confidence intervals (CIs) are presented for each study.The diamond represents the overall effect size.SD, standard deviation.

Table 1
Basic demographics of the included articles Archives of Plastic Surgery © 2024.The Author(s).

Table 1 (
Continued) .One study utilized the Freiburg Life Quality Assessment for lymphatic diseases questionnaire, another used the Hanse-Klinik-approved questionnaire, and one employed the Body Shape Questionnaire/Lower Extremity Functional Scale.To overcome outcome measurement differences among the studies, we used the SMD as a summary statistic in our meta-analysis.This enabled us to compare the effects of the intervention on a consistent scale, despite variations in outcome measurement approaches.The meta-analysis consistently illustrated significant improvements postliposuction in patients with lipedema in areas like quality of life (SMD 2.48, p-value <0.0001; ►Fig. 2),pain (SMD 2.04, p-value <0.0001; ►Fig.3), pressure sensitivity (SMD 2.2, p < 0.0001; ►Fig. 4),bruising (SMD 1.61, IVArchives of Plastic Surgery © 2024.The Author(s).Liposuction's Efficacy in Lipedema Mortada et al.studies

Table 2
Comparison of intervention and control groups in a study assessing liposuction modalities for lipedema Abbreviations: LAL, laser-assisted liposuction; NM, not mentioned; PAL, power-assisted liposuction; UAL, ultrasound-assisted liposuction; WAL, water-assisted liposuction.Archives of Plastic Surgery © 2024.The Author(s).

Table 3
Overview of liposuction techniques in included studies

Table 5
The methodological quality and synthesis of case series and case reports assessment tool (N ¼ 2)