Isocitrate Dehydrogenase Wild-type Glioblastoma Resection Under Fluorescein Sodium and White Light Guidance Based on Response Assessment in Neuro-Oncology Resect Criteria

Operative Neurosurgery 30:861–869, 2026

This study evaluates sodium fluorescein–guided resection versus white‑light surgery in isocitrate dehydrogenase wild‑type glioblastoma, using RANO resection classes and quantitative MRI volumes to compare residual contrast‑enhanced tumor burden. The retrospective analysis of 162 patients shows significantly lower postoperative CE residual volume and higher complete CE resection rates with fluorescein guidance.

The paper also correlates molecular markers with resection outcomes, finding MGMT promoter methylation associated with higher complete CE resection rates and suggesting fluorescein guidance may particularly improve CE resection across molecular subgroups, while survival differences require longer follow‑up and larger cohorts.

Objective Increase extent of resection of the contrast-enhanced (CE) portion of IDH–wild-type glioblastoma, using the RANO absolute residual-volume resection classes to quantify what sodium fluorescein guidance achieves vs white light (WL) surgery.

Design/measurement Retrospective comparative study of 162 patients (fluorescein 82 vs WL 80), with pre/post-op MRI volumetrics outlined in Brainlab and categorized by RANO EOR classes.

Key EOR result Residual CE tumor volume was lower with fluorescein guidance than WL (median 0.0 cm³ vs 0.5 cm³, P = .023).

Complete CE resection rate Proportion with 0 cm³ residual CE (RANO I + IIA) was higher with fluorescein (62.2%) than WL (42.5%), P = .012.

RANO distribution shift RANO class distribution differed between groups (P = .015), with more IIA and fewer IIB resections under fluorescein guidance.

Non-CE resection No significant between-group differences were found in preoperative CE/NCE volumes or postoperative NCE residual volumes, consistent with fluorescein primarily highlighting BBB-disrupted (enhancing) tissue.

MGMT association MGMT promoter methylation was associated with higher likelihood of achieving nonresidual CE (complete CE resection), P = .005; fluorescein guidance and MGMT status were significant predictors of nonresidual CE.

Survival Overall survival did not significantly differ between fluorescein-guided and WL groups (log-rank P = .15), while MGMT-methylated patients had significantly better survival than unmethylated (P = .019; HR = 0.52).

Brain metastasis resection: the impact of fluorescence guidance (MetResect study)

Neurosurg Focus 55(2):E10, 2023

Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection.

METHODS Analyzing their institution’s prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences.

RESULTS In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival.

CONCLUSIONS Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy

Acta Neurochirurgica (2018) 160:317–324

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions.

Methods This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis.

Results Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%.

Conclusions Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

Fluorescein-Guided Neuroendoscopy for Intraventricular Lesions

Operative Neurosurgery 13:173–181, 2017

The benefits of neuroendoscopy in the pathological diagnosis of intraand paraventricular tumors have already been shown in many neurosurgical studies. However, most authors agree that neuroendoscopic biopsies are not infrequently inconclusive due to small or inadequate samples, prompting the need for new diagnostic strategies.

OBJECTIVE: To describe a technique not previously reported in the literature, combining neuroendoscopy with angiofluorescein guidance for the pathological diagnosis of intraand paraventricular tumors.

METHODS: The 4-mm steerable fiberscope used was equipped with dual observation modes for white light and fluorescein. Access was by the classical precoronal burr hole. After inspecting the ventricular system in white light, a 10-mg/kg dose of fluorescein sodium (FS) was administered intravenously to the patient. The endoscope was then switched to the blue light fluorescent mode to better localize the pathological tissue. The protocol had been submitted to the local ethics committee.

RESULTS: From September 2011 to March 2015, 9 consecutive patients (aged 1-56 yr) harboring intra- and paraventricular lesions prospectively underwent angiofluoresceinguided endoscopy. In all cases, a pathological diagnosis was obtained without complications. In 5 patients, an endoscopic third ventriculostomy, and, in 1 patient, a septostomy was performed during the same procedure. Fluorescein guidance definitely modified our site of biopsy in 4 cases.

CONCLUSION: In our experience, FS has proven to be a strong enhancer of all ventricular lesions presentingwith a disrupted blood–brain barrier, including inflammatory processes. Fluorescein-guided neuroendoscopy appears to be a safe, economic method to improve diagnostic potential in ventricular lesions.

The Fluoropen: a simple low-cost device to detect intraoperative fluorescein fluorescence in stereotactic needle biopsy of brain tumors

Acta Neurochir (2017) 159:371–375

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas. We developed a device (Fluoropen) for detecting fluorescence in brain tumor tissues obtained by fluorescein fluorescence-guided stereotactic needle biopsy.

Methods: The Fluoropen is a device consisting of a light source fitted with color filters to create the required emission and visualization wavelengths. The proof-of-concept study consisted of four consecutive patients who underwent fluorescein fluorescence-guided frameless stereotactic biopsy of brain tumor. Each sample was examined for the presence of fluorescence using the Fluoropen and compared with a microscope with fluorescence visualization capability.

Results: A total of six samples were obtained from four stereotactic needle biopsy procedures. Four out of five samples (80%) taken from the contrast-enhancing part of the tumors were shown to be fluorescent under the microscope fitted with fluorescence module and the Fluoropen. One non-contrast enhancing lesion was non-fluorescent using both the microscope fitted with fluorescence module and the Fluoropen. The Fluoropen was shown to have 100% concordance with the microscope fitted with fluorescence module.

Conclusions: The Fluoropen is a low-cost and simple standalone device for the detection of fluorescein fluorescence that can expedite stereotactic needle biopsy by providing instant confirmation of the diagnostic sample and therefore avoid the need for an intraoperative frozen section. In patients with non-contrast enhancing tumors and those who were pre-treated with dexamethasone prior to surgery, fluorescein fluorescence-guided stereotactic needle biopsy will need to be used with caution.

Fluorescein sodium-guided resection of cerebral metastases

Acta Neurochir (2017) 159:363–367

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identifi- cation of tumor tissue. In 2012, we started evaluating fluores- cein (FL) with the dedicated microscope filter in cerebral me- tastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients.

Methods: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intrave- nously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events.

Results: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL stain- ing. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course.

Conclusions: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Fluorescein sodium-guided resection of cerebral metastases — experience with the first 30 patients

Fluorescein sodium-guided resection of cerebral metastases — experience with the first 30 patients

Acta Neurochir (2015) 157:899–904

Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW560 nm (ZeissMeditec, Germany) in patients with CM.

Methods Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects.

Results Most patients (90.0 %, n=27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0 %) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0 %) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3 % (n=25) of patients. No adverse effects were registered over the postoperative course.

Conclusions FL and the YELLOW560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Use of intraoperative fluorescein sodium fluorescence to improve the accuracy of tissue diagnosis during stereotactic needle biopsy of high-grade gliomas

stereotactic biopsy specimen obtained under the YELLOW560

Acta Neurochir (2014) 156:1071–1075

Stereotactic needle biopsy is valuable for tissue diagnosis of suspected high-grade gliomas, but limited by a sampling error that can lead to inappropriate grading of the tumor or failure to provide diagnosis. Increasing the number of biopsy attempts can increase morbidity. The authors designed a protocol to increase safety and efficiency of the procedure.

Methods Six consecutive patients with suspected high-grade gliomas who were not candidates for cytoreductive surgery underwent fluorescein-guided stereotactic needle biopsy. All received an injection of 3 mg/kg fluorescein sodium during anesthesia induction. Samples were obtained and observed under a microscope-integrated fluorescent module. If the initial specimens were fluorescent, the procedure was complete if the pathologist confirmed diagnostic tissue. Additional specimens were obtained only at the pathologist’s request. An independent neuropathologist later analyzed and graded samples for diagnostic value, tumor, and necrosis. This information was correlated to the degree of intraoperative fluorescent signal in biopsy samples.

Results During six biopsy procedures, 26 specimens were obtained: 15 (58 %) fluorescent and 11 (42%) nonfluorescent. All fluorescent specimens contained diagnostic tissue appropriate for tumor grading. Of 11 nonfluorescent specimens, four (36 %) did not contain tumor, three (27 %) contained minor hypercellularity or gliosis, and four (36 %) contained tumor with a high proportion of necrosis. All six tumors were diagnosed as glioblastoma multiforme. The sensitivity and specificity for fluorescein fluorescence was 79 % and 100 %, respectively.

Conclusions Fluorescein fluorescence may improve diagnostic accuracy and expedite stereotactic biopsy procedures.