Page 52 - Read Online

Fasanella. Mini-invasive Surg 2024;8:5 https://dx.doi.org/10.20517/2574-1225.2023.79 Page 3 of 10

Fluorescence technology
Intraoperative fluorescence imaging employs special fluorescent dyes emitting light in the near-infrared
(NIR) range (700-1,000 nm) and a high-resolution fluorescence camera system to detect NIR light, which is
[17]
invisible to the human eye . The NIR fluorescent dye most used in urological surgery is indocyanine green
[18]
(ICG) . ICG can be used to allow the identification of major renal artery branches and perform selective
and super-selective clamping, reducing WIT and the portion of renal parenchyma subject to ischemia [19,20] ,
leading to preservation of postoperative upper estimated glomerular filtration rate (eGFR) [21,22] . The limit
value of WIT, during PN, to avoid damage to renal function, is commonly believed to be 20-25 min.
However, according to some authors, a WIT > 30 min may still not affect renal function, especially in
patients with both functioning kidneys after on-clamp PN . On the other hand, the off-clamp (OC)
[23]
approach would seem to best preserve postoperative functionality despite a greater risk of intraoperative
bleeding with reduced vision and greater surgical difficulty for the operator . ICG also allows the
[24]
differentiation of healthy kidney tissue from tumor tissue, as its binding to a transmembrane protein known
as bilitranslocase would allow ICG to spread within cells and into the proximal convoluted tubules of
healthy tissue but not into the tumor [Figure 1]. This particular distribution of ICG would make fluorescent
[18]
normal renal parenchyma under NIR light and hypofluorescent tumor tissue . The success rate in this
differentiation varies between 73% and 100% of cases . This variability would also seem to be linked to the
[19]
lack of standardization of the ICG dosage: in fact, an underdosage can be associated with hypofluorescence
of the normal parenchyma, and an overdosage can make the tumor fluorescent. In general, an ICG dose of
[25]
0.25-0.50 mL can ensure good differential fluorescence .

Simone et al. proposed a technique, “green light riding”, to simplify challenging RAPN based on ICG super-
selective transarterial tumor marking . They selected ten consecutive patients with total endophytic renal
[26]
masses and performed purely OC RAPN following super-selective transarterial delivery of ICG-lipiodol
mixture.

In this regard, in recent times, thanks to the widespread diffusion of robotic surgery and the high surgical
expertise acquired, the indications for RAPN have expanded, also including particularly complex cases, for
example, totally endophytic renal tumors (TERTs) . These tumors are surrounded by healthy renal
[27]
parenchyma without altering the external profile of the kidney. As highlighted by Tuderti et al., IOUS could
prove to be a useful tool, allowing the identification of the mass and the definition of its depth and margins
[28]
before proceeding to resection . In particular, the preoperative marking of the endophytic mass by super-
selective transarterial administration of the lipiodol-ICG mixture and the continuous real-time switching to
NIR fluorescent imaging and conventional white light allows for improving the vision of a surgeon during
enucleation, minimizing lesions of the healthy subject kidney parenchyma and offering a shorter operating
time.

Other emerging approaches consist of using a fluorescent dye conjugated to a specific tumor molecule, such
as OTL38 (On Target Laboratories LLC., West Lafayette, IN, USA), a folate-targeted, intraoperative
fluorescence agent, highly expressed in the healthy kidney tissue, as opposed to tumor tissue . Another
[29]
target under evaluation is carbonic anhydrase IX, which is highly expressed in clear cell RCC (ccRCC) but
not in normal renal tissue. In this case, girentuximab, a monoclonal antibody, can be used for targeting
carbonic anhydrase IX . Recently, a combination of radio-guided and fluorescence-guided surgery has
[30]
been proposed. Hekman et al. performed a study regarding ex vivo perfusion of renal tumors, evaluating the
feasibility and reproducibility of dual imaging modalities using ¹¹¹I-girentuximab IRDye800CW . The
[31]
synergy of the two techniques would allow for more precise intraoperative imaging of the tumor, but further
studies are needed to support its validity.