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Page 4 of 15 Friedman et al. Plast Aesthet Res 2023;10:23 https://dx.doi.org/10.20517/2347-9264.2022.100

thereby restoring a novel afferent route for lymphatic fluid. In 2009, Boccardo et al. applied this innovation
for the prevention of BCRL by rerouting arm lymphatics to an axillary vein tributary at the time of
[64]
ALND . This procedure, originally termed Lymphatic Microsurgical Preventative Healing Approach
[66]
(LYMPHA) [64,65] , has more recently been referred to as immediate lymphatic reconstruction . A growing
body of evidence has demonstrated promising results of ILR for the prevention of BCRL, including a recent
meta-analysis which reported a BCRL incidence of 5.7% in patients who underwent ILR compared to 34%
in those who underwent ALND alone .
[13]

An overview of the steps of immediate lymphatic reconstruction is outlined in Figure 1. Immediately prior
to ALND, a lymphatic-specific dye is injected intradermally for lymphatic channel identification. In order to
ensure comprehensive visualization of lymphatic channels, we perform intradermal injections of 0.25cc of
st
th
2% fluorescein isothiocyanate (FITC) mixed with albumin at the 1 and 4 dorsal hand web spaces and at
the radial and ulnar aspects of the volar wrist crease. Additionally, 1cc of isosulfan blue is injected
intradermally over the course of the cephalic vein, identified by ultrasound, in the lateral upper arm. The
anatomic location of these injections can vary, with some opting for upper arm injections as originally
described [67,68] . Once the ALND is complete, the dye allows for visualization of disrupted lymphatic channels
within the axilla and the channels can then be prepared for the LVB.

Various dyes have been utilized for identification of lymphatic channels, including isosulfan blue,
indocyanine green (ICG), and FITC . Isosulfan blue dye was initially used for ILR, but this dye is also
[67]
frequently utilized for the oncologic mapping of sentinel lymph nodes; therefore, this presented challenges
in distinguishing sentinel lymph nodes from peripheral arm lymphatics. This necessitated the adoption of
novel dyes for lymphatic channel identification, such as ICG, which remains a favorable option as it is not
consistently used during the oncologic portion of the procedure. However, the use of ICG is limited by the
inability to visualize the dye without a near-infrared camera and can compromise the surgeon’s view of the
surrounding structures under the surgical microscope. Additionally, some oncologic surgeons will utilize
ICG for breast sentinel lymph node biopsy, though this is institution dependent. Some groups have utilized
FITC as an effective alternative, given the ability of FITC to be visualized with a fluorescence filter applied
to the microscope that does not limit the visibility of surrounding anatomical structures . Therefore, both
[69]
lymphatic channel visualization and microsurgical reconstruction can be carried out without interference.
Notably, each of these techniques allows for visualization of superficial structures 1-2 cm below the skin and
therefore, deep lymphatic channels are not currently able to be readily identified during ILR.

While each dye has distinct advantages and disadvantages, further research is necessary to develop
standardized methods for lymphatic channel identification . For example, increasing dye uptake in
[70]
lymphatic vessels and improved visualization of deep lymphatic channels are notable obstacles in the
application of newer dyes. Conjugating a fluorophore to a larger compound, such as to dextran, albumin, or
polyethylene glycol (PEG), may have potential utilization, as any particle too small (< 5 nm) or too large (>
[71]
100 nm) precludes dye uptake into the lymphatic channels . Prior investigations determined that the
optimal size for lymphatic uptake is 10-100 nm; therefore, these dyes may aid in optimizing lymphatic
uptake. Furthermore, near-infrared (NIR) dyes and upconverting nanoparticles (UCNPs) are other
potential methods to enhance lymphatic visualization .
[72]

Following the identification of the transected lymphatic channels, a target vein for the lymphovenous bypass
is identified. There are multiple recipient venous candidates in the axilla, including the accessory vein
(thoracoepigastric vein), lateral thoracic vein, medial pectoral vein, circumflex scapular vein, thoracodorsal
vein, or other unnamed adjacent venous tributaries [Figure 2] [67,73] . The accessory vein, which is the most