Endoscopic-assisted ICG (EASI) technique for sentinel lymph node biopsy in breast cancer

Sentinel lymph node biopsy is currently the standard of care for axillary staging in early breast cancer patients with no clinical or radiological evidence of axillary lymph node involvement. Novel techniques studied in recent years include the use indocyanine green (ICG) fluorescence imaging, which was reported in a recent network meta-analysis to be comparable to standard dual modality in terms of false negative as well as detection rate. However, there have been no standardized operative methods leading to the underutilization of this modality in clinical practice. In addition, technical limitations such as the difficulty in tracing ICG flow in obese patients further restrict the use of ICG fluorescence in sentinel lymph node biopsy. In this article, we describe in detail the use of the endoscopic-assisted ICG technique in performing sentinel lymph node biopsy, which addresses limitations associated with conventional use of ICG fluorescence imaging. The technical novelty of this technique lies in the fact that it has not been previously described in the literature and it allows for the identification of sentinel lymph nodes with minimal incision and tissue disruption as well.


INTRODUCTION
The most widely used technique for sentinel lymph node (SLN) identification is the dual-modality method involving the injection of technetium-99m-labeled nanocolloid and blue dye into the peritumoral or periareolar region [1] . The dual technique has its shortcomings, including radiation exposure to healthcare professionals and patients, issues with radiotracer availability, dependency on availability of nuclear medicine units and allergic reactions to blue dye. New techniques have been developed to improve the clinical value of SLN biopsy with similar accuracy, but avoiding irradiation and risks of allergy [2] . Novel techniques studied in recent years include those using indocyanine green (ICG) fluorescence imaging, which was reported in a 2019 network meta-analysis by Mok et al. [3] , showed ICG to be superior to the blue dye technique alone and comparable to that of the standard dual-modality method. There was, however, technical difficulties with the use of ICG [4] especially in obese patients, thereby limiting the widespread use of this modality. In this article, we describe a minimally invasive technique which is effective in overcoming limitations and at the same time minimizes tissue dissection or disruption in the axilla.

TECHNIQUE
Detailed description of this technique as attached in Video 1.

ICG PREPARATION AND INJECTION
ICG VERDYE (Diagnostic Green, Bavaria) solution of 1.25 mg/0.5 mL (vial of 25 mg added to 10 mL of water for injection) was prepared, and 1 mL of ICG was injected intradermally over 12 o' clock and 9 or  to aid in determining the most optimal placement of the axillary incision. Alternatively, a direct axilla incision could be made within the axillary skin crease without prior identification of lymphatic flow.

ENDOSCOPIC-ASSISTED ICG TECHNIQUE AND IDENTIFICATION OF SENTINEL LYMPH NODES
The endoscopic-assisted ICG (EASI) technique involved the use of an optical trocar (Endopath Xcel® Bladeless Trocar, Johnson & Johnson, USA), a 5-or 10-mm 0° or 30° endoscope and ICG system (Olympus Visera Elite II, Olympus, Tokyo, Japan) in performing the SLN biopsy. A 5-or 10-mm stab incision  (depending on the endoscope used) was placed along the axillary skin crease. In our institution, blue dye was used concomitantly with ICG as a second modality. Direct optical entry was performed with slow and controlled movement while looking for lymphatic flow, either blue or green (under fluorescence imaging) [ Figure 6]. Direction of entry was then guided by lymphatic flow until the first SLN was identified.

RETRIEVAL OF SENTINEL LYMPH NODES
Once the first SLN was identified, the camera was then removed. With the optical trocar still in place, minimal extension of the skin incision to 1.5 or 2 cm was then performed to allow retrieval of the SLN. A focused and directed dissection towards the SLN as guided by the optical trocar resulted in minimal tissue/ lymphatic disruption or damage [ Figures 7 and 8]. After retrieval of the first SLN, fluorescence imaging was then used to trace the lymphatic flow beyond the first SLN and detect further SLNs, if any [ Figures 9 and 10]. In cases where dual modality was used, the second technique could be used to detect SLNs that were not ICG-avid. Nodes were sent for intraoperative frozen section analysis and axillary dissection performed as deemed necessary if the frozen section analysis returned positive for metastatic carcinoma.

CONCLUSION
The EASI technique for SLN biopsy is an innovative approach to utilize ICG in SLN biopsy with the potential to overcome the difficulty of visualizing ICG flow especially in obese patients as well as resulting in minimal tissue/lymphatic disruption.  Figure 9B, as the axilla showed an area of indocyanine green fluorescence without any clinically palpable nodes, the area was excised to ensure that it was just lymphatic flow (false positive) rather than sentinel nodes