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Page 12 of 16             Raman et al. Plast Aesthet Res 2023;10:6  https://dx.doi.org/10.20517/2347-9264.2022.62

               [Supplementary Table 2]. Studies evaluating volume typically used the truncated cones method [30,31,38,39]  - a
               method characterized by measuring the circumference at 4 cm intervals along the limb, and summating the
               volume segments calculated by the truncated cones formula to receive an estimated total volume of the
                   [40]
               limb . Another tool to calculate volume in studies was perometry, which utilized a specialized device to
               emit infrared beams to quantify volume [41,42] . Given the substantial variability in reporting limb size
               outcomes, future studies should aim to standardize the approach to measurement. The current
               International Society of Lymphology (ISL) recommendation is 4 cm incremental measurements from the
               ulnar styloid of the wrist to the axilla for upper extremity lymphedema, and 4 cm incremental
               measurements from the medial malleolus until the popliteal fossa or gluteal crease, depending on the extent
                                             [43]
               of the lower extremity lymphedema .

               For the studies that reported reduction or discontinuation of conservative therapy following the procedure,
               it appeared that patients could rely less heavily on these treatments postoperatively. Variations in
               postoperative conservative treatment protocols and follow-up time points restricted direct comparisons
               between  studies.  There  were  also  numerous  investigations  with  unclear  postoperative  therapy
               protocols [30,31,44] .


               Infection rates were another more commonly reported outcome. It has been previously established in the
               literature that lymphedema increases the risk of developing cellulitis in the affected limb [45,46] . Specifically,
               the obstruction of lymphatic flow and accumulation of protein-rich colloid in the interstitium results in
               localized immunosuppression and a subsequent increase in infections . Therefore, a procedure restoring
                                                                           [47]
               lymphatic flow within the affected limb would be expected to mitigate the mechanism that propagates
               infection . In this systematic review, only studies reporting the number of preoperative and postoperative
                       [47]
               episodes of cellulitis were included for meta-analysis purposes. All investigations reporting this outcome
               reported a successful reduction of postoperative infection following the VLNT. Particularly, patients who
               underwent intra-abdominal VLNT experienced a significant reduction in infectious episodes compared to
               those with an extra-abdominal donor site. Importantly, it should be noted that the majority of the intra-
               abdominal donor data regarding infection rate reduction was from omental VLNT. Therefore, more
               research is needed to clarify this advantage with intra-abdominal flaps, as ileocecal, appendiceal, and jejunal
               mesenteric VLNTs have especially limited evidence surrounding this outcome.


               Another interesting finding related to the reduction of annual infectious episodes was observed when
               stratifying the data based on upper and lower limb recipient sites. Patients with upper limb lymphedema
               had a trend toward greater reduction (83.8 ± 3.4 %) in postoperative infectious episodes than those with
               lower extremity lymphedema (77.4 ± 4.8 %). Though lower extremity lymphedema patients are more likely
               to experience infection, the exact mechanism behind this predisposition is unclear in the literature .
                                                                                                       [46]
               Potentially, given that the lower extremities are in the dependent region of the body, disruptions in
               lymphatic flow could result in more significant accumulations of lymph, with markedly poorer responses to
               infection. This postulation could explain why, even after VLNT, the reduction in infectious episodes would
               be less substantial in comparison to upper limb recipient sites.


               Intra-abdominal vs. extra-abdominal
               In recent years, additional donor sites for lymphatic tissue have been found. There are several benefits to
               obtaining lymph nodes and tissue from the abdominal cavity, as it can mitigate the risk for donor-site
               lymphedema-a major concern when it comes to VLNTs from extra-abdominal sites . Intra-abdominal
                                                                                         [48]
                                                                                      [48]
               sites also allow for the ability to harvest up to 3 vascularized flaps from 1 donor site . With the possibility
               of laparoscopic harvest, the risk of donor-site morbidity may be reduced and minimal donor-site scars can
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