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Raman et al. Plast Aesthet Res 2023;10:6 https://dx.doi.org/10.20517/2347-9264.2022.62 Page 3 of 16

(3) published before November 12, 2021; (4) involved original research; and (5) included at least one of the
following: (i) clinical outcomes (limb size differences, infection rate, or reduction in conservative
treatment); (ii) patient-reported outcomes using validated questionnaires/scales; or (iii) imaging outcomes.
Exclusion criteria were as follows: (1) any avascularized/non-vascular lymph node transfers; (2) published
in a language other than English; (3) included study designs with patients receiving only combination
procedures (i.e., LVA and VLNT); (4) did not include any original, extractable data (i.e., review articles,
commentaries, letters to the editor); (5) no full-text available; and (6) studies involving non-human subjects
or cadaveric models.

Three reviewers (Raman S, Sanka S, Ji J) independently screened investigations based on title/abstracts. Two
research personnel reviewed each full-text article. A third reviewer was used in each instance where there
was dissonance of opinion. Data from full-text articles were extracted and stored in Microsoft Excel
(Version 16.52).

After full-text articles were identified, duplicate studies which included patients from the same institution
from the same time period were removed to avoid confounding any meta-analysis. If multiple articles
included the same group of patients and reported the same clinical outcome variables, the investigation
reporting the most variety of clinical outcomes or greatest sample size was included in this systematic
review.

Data extracted from each article included study-specific information (author, year of publication, country,
study design, and inclusion/exclusion criteria of patients for the study); clinical outcomes (limb
circumference or volume differences postoperatively, infection rate reduction, and reduction in need for
conservative therapy); imaging outcomes; patient sample demographics [age, body mass index (BMI),
gender, comorbidities, etiology of lymphedema, duration of lymphedema]; number of patients in each
experimental arm; details of surgical intervention (procedure performed, donor and recipient site); staging
criteria utilized; method in which clinical outcome variables were obtained including the location in the
limb for circumference/volume measurements; clinical outcomes reported [limb circumference or volume
difference, infection rate reduction (annual episodes of infection), and reductions in conservative
treatment]; PROs for each investigation in which a validated questionnaire was utilized; complications
related to donor or recipient site; and length of follow-up. An American Society of Plastic Surgeons Level of
[16]
Evidence was assigned to each investigation . PROs were recorded for each domain in which a value was
reported.

Studies reporting infection rates were reviewed to identify those that presented this information in a
standard fashion (episodes of infection/year preoperatively and postoperatively) to encourage comparability
between studies. Due to significant variability in methodology and study design, outcomes related to
improvement in limb size and reductions in conservative treatment were qualitatively summarized in table
format. Patients were stratified based on donor and recipient site (upper or lower limb lymphedema) for
meta-analysis of infection rate reduction and PROs. Continuous variables were summarized with mean and
standard deviation. Categorical variables were summarized with frequencies or percentages.

Statistical analysis was performed using GraphPad Prism 9.2.0 (Dotmatics, Boston, MA, USA) with a
statistical significance set to 0.05. Weighted means and fixed-effects pooled variances were tabulated for
each variable, and these values were used to perform statistical analyses. To compare continuous variables,
Kruskall-Wallis or Mann-Whitney tests were performed, as appropriate. Meta-analysis heterogeneity was
[18]
[19]
[17]
calculated using the meta and metafor packages in R version 4.0.3 on the R Studio version 2022.02.3