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Chang et al. Mini-invasive Surg 2024;8:15 https://dx.doi.org/10.20517/2574-1225.2023.137 Page 3 of 7

The epidermal growth factor receptor (EGFR) is another target that has been the focus of study in sinonasal
surgery. EGFR is commonly overexpressed in head and neck cancer, and several trials utilizing
Panitumumab-IRDye800 have demonstrated utility in intraoperative margin assessment, residual tumor
identification, and mapping of nodal disease. A preclinical study of Pan800 in a sinonasal tumor model was
able to demonstrate the feasibility of endoscopic targeted NIR imaging; further translational studies are
necessary to evaluate the utility of Pan800 in sinonasal cancer .
[10]
The 5-aminolevulinic acid (5-ALA) has been investigated as another potential agent for fluorescence-guided
surgery. Administered orally 2-4 h preoperatively, 5-ALA is absorbed by cells and transformed into
protoporphyrin IX (PpIX), a fluorescent compound. PpIX has been shown to have an affinity for rapidly
dividing cells, such as those found in cancer . Intraoperatively, PpIX can be visualized using 405 nm
[11]
wavelength blue light. The compound 5-ALA has Food and Drug Administration (FDA) approval for use in
high-grade gliomas and has recently been shown to have utility in head and neck squamous cell
[11]
[12]
carcinoma for identifying positive margins, perineural invasion, and metastatic nodal disease . However,
in endonasal surgery, the utility of 5-ALA may be limited. A recent multicenter study of sinonasal tumors
investigating 28 sinonasal benign and malignant tumors found that SCC, esthesioneuroblastoma, and
plasmacytoma did not demonstrate any 5-ALA fluorescence [13,14] . This fluorescence was only observed in
two of the tumors (7%): a pituicytoma and a meningioma.

PRESERVATION OF CRITICAL STRUCTURES
Sinonasal cancers often encroach upon critical neurovascular structures of the skull base. Intraoperative use
of fluorescent agents can allow for real-time enhanced visualization of structures, allowing surgeons to
navigate and preserve them more effectively.

The internal carotid artery can be reliably identified in endoscopic sinonasal and skull base surgery within a
[15]
few seconds after intraoperative administration of ICG, with a strong fluorescent signal . ICG can also be
used to assess patency of the cavernous sinus. Furthermore, angiography can also aid in identification of
critical perforators of the brain, optic apparatus, and pituitary gland . In resection of skull base tumors,
[16]
ICG has been utilized to assess and preserve vascular perfusion of the optic nerve with excellent vision
outcomes [17,18] .

Intravenous administration doses can range from 12.5 to 50 mg. A NIR endoscope can then be used to
visualize vascular structures within one minute of administration. Examples of ICG administration to
visualize skull base vascular anatomy can be seen in Figure 1.

PERFUSION ASSESSMENT IN RECONSTRUCTIVE FLAPS
ICG fluorescence angiography provides real-time feedback on blood flow dynamics, enabling surgeons to
make informed decisions regarding tissue viability and the potential need for vascularized flaps in
reconstructive procedures.

Necrosis of a reconstructive flap poses the potential complication of meningitis. While MRI with
gadolinium contrast is considered the standard method to assess for flap perfusion, this can often only be
performed in the postoperative setting. Flap necrosis can potentially be avoided through utilization of
intraoperative ICG angiography to assess viability of reconstructive flaps [19-21] . A systematic review assessed
104 cases of patients undergoing skull base reconstruction with nasoseptal flaps, lateral nasal wall flaps,
pericranial flaps, and microvascular free flaps, and found that intraoperative ICG perfusion was strongly
associated with flap perfusion as assessed by postoperative MRI . Intraoperative administration of ICG can
[22]
help confirm the perfusion of nasoseptal flap pedicles in real time, through fluorescence in the region of the
posterior septal artery [Figure 2].