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Page 2 of 12             Pandey et al. Plast Aesthet Res 2021;8:47  https://dx.doi.org/10.20517/2347-9264.2021.61

                                                                                                       [1,2]
               early surgical intervention for lymphedema can delay, prevent, and even reverse lymphatic degeneration .
               Supermicrosurgical lymphaticovenular anastomosis (LVA) and vascularized lymph node transplant
                                                                                                       [3,4]
               (VLNT) are established physiologic techniques for the treatment of fluid-predominant lymphedema .
               While VLNT is efficacious in the treatment of advanced, fluid-predominant lymphedema, its risk of
               iatrogenic donor-site lymphedema makes the procedure undesirable to many. Vascularized lymph vessel
               transplant (VLVT) has recently been introduced as a less-invasive alternative to VLNT for these advanced
               cases . LVA is traditionally reserved for early-stage, fluid-predominant lymphedema. However, recent
                   [5-7]
               technical refinements have shown that the efficacy of LVA in advanced disease has been underestimated.
               With this expanded potential, there is now an overlap between the indications for LVA and VLVT/VLNT.
               This paper aims to share the technical and decision-making pearls for improving outcomes of LVA and
               VLVT, both of which are safe and powerful procedures to treat fluid-predominant lymphedema.

               History of LVA and VLNT
               Supermicrosurgical lymphaticovenular anastomosis and its precursor, microsurgical lymphovenous bypass
                                                                                                [8]
               (LVB), re-route native lymphatic vessels into the venous circulation of the affected extremity . LVB was
                                                                                                 [10]
               first described by Jacobson and Suarez  in a canine model in 1962. Simultaneously, Chang et al.  adapted
                                                [9]
               this canine model to study lymphovenous bypass, lymph node-to-vein anastomosis, lymphatic vessel
               interposition grafts, and vein interposition grafts to bridge lymphatic defects. Techniques were refined by
               various others using canine and rat models [11-14] . In 1977, O’Brien et al.  published their series of
                                                                                [15]
               microsurgical LVB in human proximal upper limbs. Because microsurgical techniques were still in
               development, the anastomoses were created in the proximal limb, which contains larger veins but more
               functionally impaired lymphatics. The combination of these high-pressure veins with lower-quality
               lymphatics resulted in inconsistent surgical outcomes [16-18] . Subsequent advances in pre- and intra-operative
               imaging, operating microscopes, and surgical instruments facilitated the anastomosis of vessels smaller than
                                                                   [2]
               0.8 mm in diameter, ushering in the era of supermicrosurgery . First described by Koshima et al.  in 2000,
                                                                                                 [19]
               supermicrosurgical LVA allowed for the anastomosis of smaller lymphatics with venules ranging from 0.1-
               0.6 mm in diameter. The ability to use smaller vessels allowed surgeons to operate in the distal extremity,
               where lymph vessel function was more likely to be intact and to select small, low-pressure venules that
               offered more favorable pressure gradients [19,20] .


               In 1979, Shesol performed a pedicled flap transfer of groin lymphatic tissues for popliteal fossa defects in
                                                              [21]
               rats, showing lymph flow reestablishment at 7 days . It set the groundwork for the development of
               VLNT  [22,23] . The mechanism of action of VLNT is believed to be due to: (1) bridging lymphangiogenesis
               mediated by lymphatic growth factors, particularly vascular endothelial growth factor C  secretion from
                                                                                           [24]
               the transplanted lymphatic tissue; and (2) “pumping” action-driven by perfusion gradients between arterial
               inflow and venous outflow [22-29] . However, there is no clear evidence that these mechanisms rely on the
               lymph nodes contained in these flaps. It has not been consistently demonstrated that different VLNT flap
               donor sites - which often contain different numbers of nodes - produce different outcomes [30-32] . The sole
               study comparing different VLNT flaps within a single institution did not demonstrate a significant
               difference , and studies attempting to establish a correlation between the number of LNs and the
                        [33]
               effectiveness of the flap have yielded mixed results [34,35] . Moreover, while it is difficult to compare VLNT
               flaps with and without skin paddles in a controlled manner, increasing understanding of the dermal and
               subcutaneous lymphatic system strongly suggests that lymphadiposal tissue is essential for the efficacy of the
               flap [36,37] . Additionally, lymphatic vessels are likely the main drivers of lymph pumping, as evidenced by their
               smooth muscle lining and peristaltic action. Now that advancements in lymphography allow precise pre-
               and intra-operative visualization of superficial lymph vessels, their pumping action can be harnessed with
               intentional inclusion in flaps and proper orientation in recipient sites . Combined with lymphatic
                                                                               [38]
               channels’ abilities to absorb lymph and stimulate lymphangiogenesis, it supports the hypothesis that vessels
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