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Lymphedema is a condition characterized by abnormal accumulation of lymphatic fluid in the interstitial spaces. Fluid stasis results in progressive tissue swelling, inflammation, and fibrosis (). Globally, lymphedema affects an estimated 250 million individuals (), with secondary lymphedema caused by external factors, such as radiation therapy, tumors, infections, or trauma, which are more prevalent than primary lymphedema, which arises from inherent genetic mutations. Importantly, as the incidence of malignant tumors has increased, cancer-related secondary lymphedema has emerged as the most frequent type of lymphedema (, ). This condition significantly diminishes the quality of life (QOL) of patients, posing a clinical challenge that requires prompt and effective treatment. Despite advancements in treatment, challenges persist in managing lymphedema. Clinical strategies can generally be divided into two main types: nonsurgical and surgical. In cases of mild lymphedema, conservative management, especially complex decongestive therapy (CDT) (), continues to be the preferred treatment. Conversely, moderate to severe instances often necessitate surgical options, which can be classified into two groups: physiological techniques aimed at reestablishing normal lymphatic function and debulking techniques that concentrate on excising excess fibrotic and adipose tissue ().

Liposuction (LS) is a frequently used debulking technique that was initially introduced for the treatment of upper extremity lymphedema in 1989 (). Since then, LS has attracted considerable interest as a less invasive alternative to traditional excisional methods, such as the Charles procedure, which necessitates the complete removal of the diseased skin (). By preserving healthy tissue, LS mitigates tissue damage and decreases the likelihood of complications associated with more invasive surgical options (). Unlike physiological procedures that focus on reconstructing lymphatic pathways, LS is specifically aimed at eliminating fibrotic and hypertrophic adipose tissue in instances of chronic, non-pitting lymphedema. Numerous studies have demonstrated its effectiveness in achieving significant reductions in limb volume and enhancements in patient-reported QOL (–). Nonetheless, variability in study design, such as disparities in follow-up times, patient selection processes, and outcome indicators, restricts the ability to compare these results. Furthermore, LS alone does not address fundamental lymphatic dysfunction, and its long-term effectiveness typically depends on continuous compression therapy. This situation has sparked heightened interest in merging LS with physiological procedures to improve outcomes by addressing both lymphatic drainage and removal of fibroadipose tissue. In the last ten years, the investigation of LS-based integrated (LSI) treatments has expanded markedly. These strategies seek to leverage the complementary interactions between LS and physiological approaches, potentially creating synergistic effects. However, current research on LSIs frequently faces challenges, such as limited sample sizes, brief follow-up periods, and a deficit in standardized methods. These factors impede the establishment of consensus-driven guidelines and restrict the implementation of evidence-based practice.

Despite various systematic reviews and meta-analyses focusing on lymphedema treatments involving LS, the majority have emphasized improvements in quality of life (), neglecting significant factors, such as volume reduction, reliance on CDT, and infection improvement (, ). To date, no systematic review has thoroughly assessed the integration of LS with additional therapeutic approaches (LSIs), and no meta-analysis has identified volume reduction as the primary endpoint. To address these gaps, we conducted a systematic review and meta-analysis examining five key dimensions of LS-based interventions: (1) treatment efficacy, (2) dependence on postoperative compression, (3) infection incidence, (4) quality of life outcomes, and (5) treatment strategy variation and optimization. By gathering and evaluating the latest findings through a systematic review and meta-analysis, this study aims to deliver substantial data that clarifies the role of LS-based treatment in the wider context of lymphedema treatment. Through this methodology, we intend to fill current evidence gaps, establish standardized evaluation parameters, and offer practical insights for future clinical practice.

A thorough and independent literature search was carried out across several primary public databases, including PubMed, Embase, and Web of Science. This search encompassed studies published between January 1996 and November 2024, concentrating on original research concerning lymphedema, lipectomy, and liposuction. The keywords used in the search were “lymphedema”, “lymphoedema”, “lipectomy”, and “liposuction”. Detailed search methodologies, including keywords and Boolean logic combinations, can be found in (). Furthermore, beyond the database searches, manual examinations of reference lists and pertinent citations were conducted to uncover potentially eligible studies that may have been missed. During the initial search, no limitations were set aside from the requirement for publications to be in English.

The study selection process is summarized in , which follows the PRISMA flow-diagram format. Inclusion Criteria:1. The original studies used randomized controlled trials, prospective cohort studies, retrospective cohort studies, cross-sectional designs, or case series designs. Studies evaluating the outcomes of LS either as a standalone treatment or in combination with physiological procedures such as LVA or VLNT. 3.Studies reporting volume changes and improvement in quality of life as primary outcome measures. 4.Studies with a sample size of at least eight patients. 5.Articles published in English. Exclusion Criteria: 1. Studies focusing solely on surgical treatments other than LS (e.g., VLNT, LVA, RRPP, VLVT, and Charles procedure) without incorporating LS. 2.Studies that did not report relevant outcomes such as volume changes or quality-of-life measures. 3.Review articles, editorials, letters, abstracts, non-original research, and animal studies.

Data were collected based on the inclusion and exclusion criteria. Two reviewers independently examined all identified articles to ensure a thorough evaluation. In instances where discrepancies arose, the reviewers engaged in discussions to reach agreement. If disagreements continued, a third experienced reviewer was brought in to facilitate mediation and finalize the consensus. Essential information, such as publication year, study design, first author, and surgical techniques, was systematically recorded for each included study. The risk of bias in case series and retrospective studies was assessed using the JBI quality assessment tool for non-controlled trials. Additionally, the Newcastle-Ottawa Scale (NOS) () was used to evaluate the quality of the non-controlled trials.

The process for selecting studies is depicted in the PRISMA flow diagram (). An initial search of the databases yielded 1220 entries from PubMed (286), Embase (508), and Web of Science (426), after which 893 duplicates were eliminated. After reviewing the titles and abstracts of the remaining entries, 257 studies were discarded because of their lack of relevance. A full-text eligibility evaluation of 70 studies resulted in the removal of 18 studies for reasons such as insufficient outcome data, absence of pertinent interventions, or flawed study design. Ultimately, 52 studies were incorporated into the systematic review (, , –), and 21 studies involving 929 participants were used in the meta-analysis ().

The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies included in the non-randomized studies, while the JBI Critical Appraisal Checklist was utilized for the case series. Details regarding the quality assessment are shown in .

A total of 2,334 patients were included in the 52 studies reviewed, with the publication period ranging from 1989 to 2024. The number of patients in each study varied from 10 to 158, resulting in an average of 45.3 patients per study. Sex data were available for 49 of the studies (representing 2,299 patients), revealing that 7.8% were male (179 individuals) and 92.2% were female (2,120 individuals). Anatomical review indicated that 59.3% of the cases involved the upper extremities, 40.3% involved the lower extremities, and 0.4% involved neck lymphedema. The average follow-up was found to be 26.6 months. The study design comprised six prospective cohorts, 14 retrospective cohorts, six prospective case series, and 26 retrospective case series. Regarding surgical techniques, the studies analyzed included 33 that investigated LS as a standalone treatment, 11 examining LS in combination with LVA, 6 studying LS together with VLNT, 4 examining LS along with either VLNT or LVA, 1 that included LS, LVA, and VLNT, and 1 that combined LS with VLVT. The detailed characteristics of all included studies are presented in , .

Among the 25 studies that documented alterations in excess volume(affected limb volume − healthy limb volume)/healthy limb volume × 100%), 17 (encompassing 798 patients) provided adequate data for inclusion in the meta-analysis. Of these 17 investigations, two examined LS in conjunction with LVA or VLNT, one explored LS combined with LVA, and two focused on LS paired with VLNT. Studies were excluded if they did not provide sufficient statistical details or reported only medians without ranges or interquartile ranges (IQRs). A random-effects model was employed because of the significant heterogeneity (I² = 93.2%). The overall reduction in excess circumference across the 17 studies was 92.44% [95% CI: 91.33 to 93.5] (). In the subgroup analysis, LS alone resulted in nearly complete reduction in excess volume (99.74%, 95% CI: 98.03 to 101.46; I² = 91.2%). Conversely, LS combined with physiological interventions yielded slightly lower pooled reductions (87.31%, 95% CI: 84.75 to 89.86; I² = 29.8%), but showed decreased heterogeneity (). The diminished effect size and reduced heterogeneity observed with LSI therapies might be attributable to variations in the combination of interventions used.

Additionally, subgroup analysis based on the affected limb location revealed no major disparity in treatment efficacy between upper and lower limb cases. Pooled reduction in excess volume for lower limb lymphedema was 91.08% (95% CI: 89.57 to 92.59; I² = 94.3%), while that for upper limb cases was slightly higher at 92.83% (95% CI: 91.44 to 94.22; I² = 93.2%). These results suggest that LS may be similarly effective in managing both upper and lower limb lymphedema, though substantial heterogeneity remained across studies ().

Fewer episodes of skin infections were observed in 24 of the 52 studies, while 20 of these studies supplied adequate data regarding annual changes in infection occurrences. Among these, 4 studies encompassing a total of 339 patients were included in the meta-analysis. The overall decrease in the frequency of infection episodes was found to be 0.95 [95% CI: 0.85 to 1.05], accompanied by notable heterogeneity. Following the removal of two outlier studies, the recalculated pooled reduction among 131 patients was 1.30 [95% CI: 1.00 to 1.60], exhibiting low heterogeneity (I² = 0%) (see ). This underscores the potential of interventions based on LS to significantly decrease infection rates in individuals with lymphedema. These findings should be interpreted cautiously given the limited number of eligible studies and variability in definitions and follow-up.

The possibility of publication bias was evaluated using Egger’s and Begg’s tests, neither of which indicated significant evidence of bias. Visual inspection of the funnel plots revealed symmetrical distributions, which further validated the strength of the findings.

Across the included studies, reliance on compression following liposuction-based interventions was heterogeneously defined and reported. Therefore, we synthesized these outcomes narratively and present study-level details in . In general, LS maintained a requirement for long-term compression to preserve volume control, whereas combined approaches were consistently associated with a reduction in compression burden. Specifically, multiple cohorts reported down-titration of garment class/pressure and fewer daily wearing hours after combined procedures, with a proportion of patients discontinuing compression entirely. These patterns were observed across both upper- and lower-extremity lymphedema, although between-study variability in definitions, follow-up windows, and perioperative protocols precluded a single pooled estimate.

Quality of life outcomes were assessed using validated instruments but varied across studies (LYMQOL, LLIS, SF-36 and LyQLi), limiting quantitative aggregation. We therefore provide a structured narrative synthesis and detailed tabulation in . Overall, LS-based interventions were associated with clinically meaningful improvements from baseline, most commonly in appearance, symptoms, function and emotional domains. Studies employing combined procedures frequently demonstrated sustained gains at mid- to longer-term follow-up, aligning with reduced compression dependence and improved limb function. appearance (P = 0.019), function (P = 0.046), and symptoms (P = 0.014). Emotional improvement was observed but did not

This meta-analysis provides comprehensive insights into the effectiveness of treatments based on LS for lymphedema, highlighting significant reductions in limb volume, reliance on compression therapy, and frequency of infection episodes. Standalone LS effectively reduces the volume almost completely by directly removing fibrotic and hypertrophic adipose tissues. When combined with techniques such as VLNT or LVA, LSI enhances lymphatic regeneration and drainage restoration, thereby alleviating both physical and immune-related challenges. However, comparisons indicate that LSI achieves slightly less volume reduction than standalone LS. These results primarily support our initial hypothesis that LSI is less effective than standalone LS in achieving volume reduction within a short time frame. There are two key reasons for this discrepancy. First, LSI techniques require the preservation of additional tissue to perform LVA or VLNT, which is essential for maintaining blood flow and sustaining functional lymphatic structures in the affected area (–). Consequently, the total amount of tissue removed was less than that in standalone LS. Second, VLNT results in a gradual decline over several months, dependent upon recovery of the lymphatic drainage system. Therefore, the relatively short follow-up periods in these studies may not adequately capture the long-term outcomes of the volume reduction.

Despite these variations, LSI offers significant advantages by reducing dependence on compression therapy and enhancing long-term QOL. Although earlier research indicated that lymphangiogenesis occurs following LS treatment, the immediate effects of LS remain incompletely understood (). A primary limitation of LS is its reliance on continuous compression therapy to maintain results. By contrast, as illustrated in , , the integration of LS with physiological procedures provides distinct benefits by substantially reducing the need for postoperative compression therapy. This improvement is further corroborated by the restoration of lymphatic function, which contributes to enduring outcomes. Analyses of subgroups revealed that a notable proportion of patients undergoing LS in conjunction with LVA or VLNT achieved complete cessation of compression therapy within 3–12 months, with most of approximately 6 months (–). Among the remaining patients, the majority experienced significant reductions in both pressure and frequency of compression garment use. Importantly, these combined strategies resulted in marked improvements in the QOL scores, demonstrating enhanced functional outcomes and reduced physical burden.

Recent advances in liposuction techniques reflect both procedural refinements and expanded conceptual roles within combined surgical strategies. Initially limited to ISL stage II due to concerns about its efficacy in fibrotic limbs, liposuction has evolved significantly with the introduction of power-assisted liposuction (PAL) (, ). This innovation—using vibrating cannulas—has demonstrated the ability to partially disrupt fibrotic and adipose tissues, thereby enhancing fat removal efficiency and reducing surgical time. As a result, PAL has broadened practical use in fibrotic limbs; however, effectiveness varies and appears to depend on strict compression adherence and careful case selection, with limited high-certainty evidence in advanced fibrosis (, –). This broader applicability has been supported by clinical evidence, with some studies documenting sustained volume reduction lasting up to 15 years. Moreover, incorporating agents such as hyaluronidase into tumescent solutions has improved tissue compliance and reduced the duration of postoperative compression therapy, further facilitating enhanced recovery and long-term outcomes (). However, since LS alone does not restore lymphatic drainage, it is increasingly performed in combination with LVA or VLNT to achieve more lasting outcomes. The optimal combination strategy should be tailored to disease characteristics. Given the risk of damaging residual lymphatics, particularly in late-stage disease, selective liposuction techniques have emerged. These involve sparing lymphatic-rich areas identified by preoperative indocyanine green (ICG) mapping (, , ). LS and physiological reconstructions may be performed in a single session or staged depending on the lymphatic architecture. Some studies suggest that LVA remains effective with deep lymphatic system, when superficial lymphatic structures are not preserved, allowing for more aggressive fat removal where necessary. In patients lacking functional lymphatics, LS combined with VLNT is generally preferred (, , , , , ). Triple-combination strategies (LS + LVA + VLNT) have shown potential superiority over dual combinations in reducing limb volume, skin tension, and infection recurrence (). However, robust comparative data remain limited, and high-quality randomized controlled trials are needed to establish clear indications and refine procedural sequencing. The choice between single-stage and staged approaches remains an area of active debate. Staged procedures offer the advantage of targeting dominant disease components—starting with LS for solid-predominant cases or physiological surgery for fluid-predominant ones (). One-stage surgery may be preferable in mixed presentations or when minimizing hospitalizations is a priority (). Nonetheless, performing multiple procedures in the same anatomical area poses challenges: LVA requires intact superficial lymphatics, while VLNT depends on preserved vascular supply and minimal postoperative compression. Segmental or compartment-based strategies and standardized surgical protocols are essential to mitigate these risks and improve outcomes.

Importantly, this meta-analysis revealed that LS-based interventions demonstrated similarly high efficacy in both upper and lower limb lymphedema. Despite prior concerns that gravitational effects and tissue characteristics might lead to weaker responses in the lower extremities, subgroup analysis showed nearly equivalent volume reductions—91.08% for lower limb cases and 92.83% for upper limb cases. These findings suggest that LS-based surgical approaches, whether standalone or combined with physiological techniques, can be broadly effective across anatomical locations. This reinforces the clinical versatility of LS and supports its application as a robust intervention for managing lymphedema, regardless of limb involvement.

Infection presents a significant challenge in individuals with lymphedema. Our systematic review demonstrated that LS-based treatment markedly decreased the occurrence of episodes of infection. In the standalone LS group, the removal of inflammatory tissue resulted in a notable reduction in the recurrence of infections compared with the preoperative baseline, which aligns with previous research findings. Patients undergoing LSI also exhibited a considerable decline in infection rates, likely due to enhanced lymphatic drainage and immune system modulation through VLNT and LVA. However, it is essential to recognize that the limited number of studies adhering to the criteria for meta-analysis poses challenges in establishing definitive comparisons between LS and LSI. Among the studies that met the eligibility criteria, only two were suitable for meta-analysis, revealing a small yet clinically significant decrease in approximately one episode of infection following surgery. This highlights the need for future well-designed studies that use standardized reporting and consistent statistical techniques to further substantiate these promising findings.

This research offers several advantages, including a comprehensive examination of 52 studies involving 2,357 patients and a primary focus on volume reduction, compression therapy reliance, and infection rates. The subgroup analyses provided valuable insights into the comparative benefits of standalone LS versus LSI, elucidating their distinct clinical applications (, ). However, this study had several limitations. The notable heterogeneity observed in standalone LS studies (I² = 91.2%) reflects the variability in surgical techniques, patient demographics, and postoperative care protocols. Differences in follow-up duration and adherence to compression therapy likely influenced the results, underscoring the need for standardized methodologies (, ). Specifically, future studies should: (1) adopt a unified set of primary outcomes that includes a standardized definition of excess volume reduction; reports cellulitis as events per patient-year; specifies explicit metrics for “compression dependence” (e.g., garment class/pressure in mmHg and hours of wear per day); and uses validated quality-of-life instruments (e.g., LYMQOL, LLIS, or SF-36 at pre-specified timepoints); (2) standardize assessment windows at 3, 6, 12, 24, 36, and 48 months postoperatively; (3) stratify and report outcomes by ISL stage (II vs. III) and by limb (upper vs. lower); and (4) predefine and comprehensively report perioperative compression protocols (bandaging sequence, garment class/pressure, duration) as well as surgical parameters (e.g., PAL vs. SAL, cannula diameter, and tumescent composition including the hyaluronidase dose). Additionally, several of the included studies employed retrospective designs, which may introduce risks associated with selection and reporting biases. Moreover, to harmonize outcomes across studies, we converted medians (with IQRs or ranges) to means and standard deviations using established methods; while widely accepted, these transformations can introduce minor imprecision. The limited sample sizes of LSI therapy studies further constrain the generalizability of the findings. Finally, the long-term outcomes remain inadequately understood, particularly regarding the sustainability of volume reduction and the implications of discontinuing compression therapy, highlighting the necessity for future longitudinal research.

To address these deficiencies, future studies should prioritize standardization of methods that include consistent outcome measures and follow-up protocols. Conducting large-scale randomized controlled trials(RCTs) are essential to validate the effectiveness of lymphatic system interventions and establish clinical guidelines based on robust evidence. The absence of high-quality RCTs in the current literature limits strong causal inferences regarding treatment outcomes, as most studies rely on retrospective case series. Therefore, future research in this field should focus on filling this critical gap. Furthermore, additional research should explore the complex relationship between restoration of lymphatic drainage and volume reduction to enhance patient outcomes. Additionally, investigations should assess the long-term benefits of decreasing compression dependence, particularly in comprehensive procedures, in order to deepen the overall understanding of treatment effectiveness.

This systematic review and meta-analysis validated the efficacy of liposuction-based therapies in reducing limb volume and may reduce incidence of infection among patients with lymphedema. Independent LS results in a significant immediate decrease in volume, whereas the combination of LS with physiological approaches, such as LVA or VLNT, enhances long-term outcomes by addressing the underlying causes of lymphatic dysfunction. Future research should focus on improving the methodological consistency, exploring the long-term benefits of combined treatments, and establishing standardized clinical protocols to optimize patient outcomes and therapeutic strategies.

Edited by: Robert Fruscio , University of Milano Bicocca, Italy Reviewed by: Subramania Iyer , Amrita Vishwa Vidyapeetham University, India Michael Sorkin , The Ohio State University, United States Ying-Sheng Lin , National Taiwan Normal University, Taiwan

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