Hybrid fluorescein-guided surgery for pituitary adenoma resection: a pilot study

OBJECTIVEThe authors conducted a pilot study on hybrid fluorescein-guided surgery for pituitary adenoma resection and herein describe the feasibility and safety of this technique.METHODSIn this pilot study, the authors included all consecutive patients presenting with pituitary adenomas, functioning and nonfunctioning. They performed a hybrid fluorescein-guided surgical technique for tumor resection. An endonasal endoscopic approach was used; after exposure of the rostrum of the sphenoid sinus, they administered a bolus of 8 mg/kg of fluorescein sodium (FNa) intravenously, and during resection, they alternated between endoscopic and microscopic techniques to guide the resection under a YELLOW 560 filter.RESULTSThe study included 15 patients, 7 men (47%) and 8 women (53%). Of the pituitary adenomas, 7 (46%) were nonfunctioning, 6 (40%) were GH secreting, 1 (7%) was prolactin secreting, and 1 (7%) was ACTH secreting. There were no FNa-related complications (anaphylactic reactions); yellowish staining of urine, skin, and mucosa was seen in all patients and resolved in a maximum time of 24 hours. After color spectrophotometric analysis, the authors identified a statistical difference in fluorescence among tumor, gland, and scar tissue (p = 0.01).CONCLUSIONSThis is the first study of its kind to describe the feasibility and safety of using FNa to guide the resection of pituitary adenomas. The authors found this technique to be safe and feasible. It may be used to obtain better surgical results, especially for hormone-producing and recurring tumors, as well as for reducing the learning curve in pituitary adenoma surgery.

Fluorescein-guided removal of peripheral nerve sheath tumors: a preliminary analysis of 20 cases

OBJECTIVEBenign peripheral nerve sheath tumors (PNSTs) include mainly schwannomas—the most common tumors arising from peripheral nerves—and neurofibromas. Due to their origin, distinguishing between functional intact nerve and the fibers from whence the PNST arose may not always be easy to perform. The introduction of intraoperative tools to better visualize these tumors could be helpful in achieving a gross-total resection. In this study, the authors present a series of patients harboring PNST in which the surgery was performed under fluorescein guidance.METHODSBetween September 2018 and February 2019, 20 consecutive patients with a total of 25 suspected PNSTs underwent fluorescein-guided surgery performed under microscopic view with a dedicated filter integrated into the surgical microscope (YELLOW 560) and with intraoperative monitoring. All patients presented with a different degree of contrast enhancement at preoperative MRI. Fluorescein was intravenously injected after intubation at a dose of 1 mg/kg. Preoperative clinical and radiological data, intraoperative fluorescein characteristics, and postoperative neurological and radiological outcomes were collected and analyzed.RESULTSSix patients were affected by neurofibromatosis or schwannomatosis. There were 14 schwannomas, 8 neurofibromas, 1 myxoma, 1 reactive follicular hyperplasia, and 1 giant cell tumor of tendon sheath. No patient experienced worsening of neurological status after surgery. No side effects related to fluorescein injection were found in this series. Fluorescein allowed an optimal intraoperative distinction between tumor and surrounding nerves in 13 of 14 schwannomas and in all neurofibromas. In 6 neurofibromas and in 1 schwannoma, the final YELLOW 560 visualization showed the presence of small tumor remnants that were not visible under white-light illumination and that could be removed, obtaining a gross-total resection.CONCLUSIONSFluorescein was demonstrated to be a feasible, safe, and helpful intraoperative adjunct to better identify and distinguish PNSTs from intact functional nerves, with a possible impact on tumor resection, particularly in diffuse neurofibromas.

P.095 Novel use of fluorescein sodium in the resection of a pediatric posterior fossa tumor

Background: Gross total resection of pediatric posterior fossa tumors is paramount towards improving progression-free survival.Fluorescein accumulates in tumoral tissue, where the blood-brain barrier is disrupted. It can therefore potentially aid in differentiating tumoral versus normal tissue. We aimed to evaluate the efficacy of fluorescent-guidance (using fluorescein) towards the resection of a pediatric cerebellar tumor, as the index case at our institution using this technique. Methods: 5 mg/kg of IV fluorescein sodium was injected upon induction of general anesthesia. During tumor resection, a yellow 560-nm filter (Kinevo microscope, Zeiss) was employed for fluorescent-guidance. The extent of resection was assessed via post-operative MRI. Results: There were no adverse side effects experienced by the patient. Tumoral material was clearly visualized under the yellow 560-nm filter, allowing for satisfactory gross total resection of the lesion (confirmed on post-operative MRI). Preliminary pathology was consistent with medulloblastoma. Conclusions: Fluorescent-guided resection of pediatric posterior fossa tumors appears to be a safe and useful adjunct for gross total resection of these lesions. To the best of our knowledge, this is the first reported case in Canada wherein IV fluorescein was used under a yellow 560-nm filter for resection of a posterior fossa medulloblastoma in a child.

Dual-labeling with 5–aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note

OBJECTIVEFluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.METHODSThe authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).RESULTSFluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.CONCLUSIONSDual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance

OBJECTIVEExtent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins.METHODSThirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection.RESULTSBright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions.CONCLUSIONSIntraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal.

Sodium Fluorescein-Guided Resection under the YELLOW 560 nm Surgical Microscope Filter in Malignant Gliomas: Our First 38 Cases Experience

Objective. Sodium fluorescein (FL) had been safely used in fluorescence-guided microsurgery for imaging various brain tumors. Under the YELLOW 560 nm surgical microscope filter, low-dose FL as a fluorescent dye helps in visualization. Our study investigated the safety and efficacy of this innovative technique in malignant glioma (MG) patients. Patients and Method. 38 patients suffering from MGs confirmed by pathology underwent FL-guided resection under YELLOW 560 nm surgical microscope filter. We retrospectively analyzed the clinical characters, microsurgery procedure, extent of resection, pathology of MGs, progression-free survival (PFS), and overall survival (OS). Results. Thirty-eight patients had MGs (10 WHO grade III, 28 WHO grade IV). With YELLOW 560 nm surgical microscope filter combined with neuronavigation, sodium fluorescein-guided gross total resection (GTR) was achieved in 35 (92.1%) patients and subtotal resection in 3 (7.69%). The sensitivity and specificity of FL were 94.4% and 88.6% regardless of radiographic localization. Intraoperatively, 10 biopsies (10/28 FL[+]) showed “low” or “high” fluorescence in non-contrast-enhancement region and are also confirmed by pathology. Our data showed 6-month PFS of 92.3% and median survival of 11 months. Conclusion. FL-guided resection of MGs under the YELLOW 560 nm surgical microscope filter combined with neuronavigation was safe and effective, especially in non-contrast-MRI regions. It is feasible for improving the extent of resection in MGs especially during emergency cases.