The newly introduced endoscopic system can is a helpful approach for endonasal endoscopic surgery, because it allows good visualization of the pituitary adenoma, and viability confirmation of the mucosa.
The emission and the absorption spectra of ICG make it useful in endoscopic surgery. The peak emission and absorption of ICG is in a range of 800-850nm. ICG has already been used in many fields and has been applied in various approaches. In the field of neurosurgery, it was used to check re-filling after aneurysm clipping, or to check vessel patency after anastomosis surgery. It has also been used to identify feeding arteries and draining veins in hyper-vascular lesions such as arteriovenous malformations or hemangioblastomas.[15, 16] The effect was sufficiently proven in vascular surgery, but there have been concerns about using ICG in tumor staining. In glioma surgery, the use of 5-aminolevulinic acid increased the gross total resection rate and improved survival. However, in pituitary surgery, the effectiveness of 5-aminolevulinic acid was very limited.[18-20] Previously, there have been many efforts to stain the pituitary adenoma using ICG.[21-23] However, in previous endoscopic systems, the ICG was detected using xenon as a light source. ICG has an excitation range from 800-850nm, however, the effective detection range of filtered xenon is 845-870nm. Therefore, xenon had low excitation for ICG and only a very dark and blurry images were obtained which limited the applications for ICG in surgery. Recently, Chang et al. published a review article on the use of optical fluorescence agents during pituitary adenoma surgeries and indicated that ICG and folate receptors could be used clinically to differentiate pituitary adenomas from normal tissue, which aligns with the results of our study. Some papers have reported that tumor staining with ICG is possible.[21, 25] However, other papers reported that tumor staining with ICG was difficult and the clinical effects could only be obtained by uptake of other structures around the tumor.[22, 23, 26-28] Lee et al. introduced the second-window ICG method as a new ICG approach to overcome these limitations. They used a folate analog conjugated to a near-infrared fluorescent dye (OTL38). Patients were infused with OTL38 2-4 hours prior to surgery. They reported that this approach was highly specific for nonfunctioning adenomas did not have utility in functioning adenomas. Lee et al. assessed a study group and used ICG for various intracranial tumors, which showed impressive results. However, this method was problematic due the timing for injecting a high dose of ICG which should be injected 24 hours before operation. Although ICG is a relatively safe drug with few side effects, using high doses is bound to be a burden for patients and clinicians. The endoscopic system in the present study used low-dose ICG, which is very convenient and can be used just before or during the surgery. Previously, this fusion-fluorescence imaging system that used ICG was applied in laparoscopic surgery. In these studies, tumors, such as hepatomas, were well visualized.[14, 32, 33] For cases of meningioma, reports have indicated that the uptake is can be confirmed using the second window ICG method mentioned above, which is in agreement with our study results and observations. However, other papers have not yet reported on uptake for meningioma.[16, 22, 34] With the study design, it was not possible to confirm whether the uptake was due to the tumor characteristics or the endoscopic system or the difference in the ICG injection protocol. In this study, GH-releasing pituitary adenoma showed weaker ICG uptake compared to other nonfunctioning pituitary adenomas. It is hypothesized that this occurs due to the difference in angiogenesis between tumor types as angiogenesis is essential for tumor growth. In contrast to other tumors, pituitary adenomas are less vascular than the normal pituitary gland. There is also a difference in angiogenesis between functioning pituitary adenomas and non-functioning pituitary adenomas.
Pituitary adenomas exhibit relatively high long-term recurrence rates and delayed intervention is often required. The overall risk of recurrence after pituitary tumor surgery is reported to be between 7-33% at 5-10 years.[36-40] O’Sullivan et al. reported a recurrence rate of 0% in the gross total resection group. In comparison, based on the presence of intrasellar and extrasellar remnants, the recurrence rates after 5 years were reported as 15.4% and 51.4%, respectively. Therefore, if tumor staining becomes clearer using ICG, it is expected that the recurrence rate can be reduced.
A nasoseptal flap is a surgical technique that is applied in skull base reconstruction following anterior skull base tumor removal. Knowledge of the anatomical variations of the sphenopalatine artery and the surrounding structures is crucial when preparing nasoseptal flaps. Because of its specific septal branch blood supply, the nasoseptal flap provides reliable revascularization and robust coverage for skull base reconstruction. It is difficult to find the exact run of the artery when preparing nasoseptal flaps. However, it would be very helpful if the approximate run of the artery could be estimated. As in this study, it is expected that ICG can be applied to overcome the limitations of what can be visualized in white light and applied as an improved tool for more complete surgery.
This study is a preliminary result and the number of cases is very small. Therefore, it will be necessary to build a proper usage protocol with more experience and additional studies and observations.