Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood–brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported. Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18). Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm³ (range, 1.3–87.8 cm³). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%. Conclusion: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 1–10. ©2017 AACR.

Object: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. Methods: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45–74 years), enrolled in the study since September 2011. In all cases fluorescein (5–10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. Results: The median preoperative tumor volume was 30.3 cm ³ (range 2.4–87.8 cm ³ ). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Conclusions: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

OBJECTIVE: Anterior skull base meningiomas are benign lesions that cause neurological symptoms through mass effect on adjacent neurovascular structures. While traditional transcranial approaches have proven to be effective at removing these tumors, minimally invasive approaches that involve using an endoscope offer the possibility of reducing brain and nerve retraction, minimizing incision size, and speeding patient recovery; however, appropriate case selection and results in large series are lacking. METHODS: The authors developed an algorithm for selecting a supraorbital keyhole minicraniotomy (SKM) for olfactory groove meningiomas or an expanded endoscopic endonasal approach (EEA) for tuberculum sella (TS) or planum sphenoidale (PS) meningiomas based on the presence or absence of olfaction and the anatomical extent of the tumor. Where neither approach is appropriate, a standard transcranial approach is utilized. The authors describe rates of gross-total resection (GTR), olfactory outcomes, and visual outcomes, as well as complications, for 7 subgroups of patients. Exceptions to the algorithm are also discussed. RESULTS: The series of 57 patients harbored 57 anterior skull base meningiomas; the mean tumor volume was 14.7 ± 15.4 cm ³ (range 2.2–66.1 cm ³ ), and the mean follow-up duration was 42.2 ± 37.1 months (range 2–144 months). Of 19 patients with olfactory groove meningiomas, 10 had preserved olfaction and underwent SKM, and preservation of olfaction in was seen in 60%. Of 9 patients who presented without olfaction, 8 had cribriform plate invasion and underwent combined SKM and EEA (n = 3), bifrontal craniotomy (n = 3), or EEA (n = 2), and one patient without both olfaction and cribriform plate invasion underwent SKM. GTR was achieved in 94.7%. Of 38 TS/PS meningiomas, 36 of the lesions were treated according to the algorithm. Of these 36 meningiomas, 30 were treated by EEA and 6 by craniotomy. GTR was achieved in 97.2%, with no visual deterioration and one CSF leak that resolved by placement of a lumbar drain. Two patients with tumors that, based on the algorithm, were not amenable to an EEA underwent EEA nonetheless: one had GTR and the other had a residual tumor that was followed and removed via craniotomy 9 years later. CONCLUSIONS: Utilizing a simple algorithm aimed at preserving olfaction and vision and based on maximizing use of minimally invasive approaches and selective use of transcranial approaches, the authors found that excellent outcomes can be achieved for anterior skull base meningiomas.

OBJECT: The Milan Complexity Scale—a new practical grading scale designed to estimate the risk of neurological clinical worsening after performing surgery for tumor removal—is presented. METHODS: A retrospective study was conducted on all elective consecutive surgical procedures for tumor resection between January 2012 and December 2014 at the Second Division of Neurosurgery at Fondazione IRCCS Istituto Neurologico Carlo Besta of Milan. A prospective database dedicated to reporting complications and all clinical and radiological data was retrospectively reviewed. The Karnofsky Performance Scale (KPS) was used to classify each patient’s health status. Complications were divided into major and minor and recorded based on etiology and required treatment. A logistic regression model was used to identify possible predictors of clinical worsening after surgery in terms of changes between the preoperative and discharge KPS scores. Statistically significant predictors were rated based on their odds ratios in order to build an ad hoc complexity scale. For each patient, a corresponding total score was calculated, and ANOVA was performed to compare the mean total scores between the improved/unchanged and worsened patients. Relative risk (RR) and chi-square statistics were employed to provide the risk of worsening after surgery for each total score. RESULTS: The case series was composed of 746 patients (53.2% female; mean age 51.3 ± 17.1). The most common tumors were meningiomas (28.6%) and glioblastomas (24.1%). The mortality rate was 0.94%, the major complication rate was 9.1%, and the minor complication rate was 32.6%. Of 746 patients, 523 (70.1%) patients improved or remained unchanged, and 223 (29.9%) patients worsened. The following factors were found to be statistically significant predictors of the change in KPS scores: tumor size larger than 4 cm, cranial nerve manipulation, major brain vessel manipulation, posterior fossa location, and eloquent area involvement (Nagelkerke R ² = 0.286). A grading scale was obtained with scores ranging between 0 and 8. Worsened patients showed mean total scores that were significantly higher than the improved/unchanged scores (3.24 ± 1.55 vs 1.47 ± 1.58; p < 0.001). Finally, a grid was developed to show the risk of worsening after surgery for each total score: scores higher than 3 are suggestive of worse clinical outcome. CONCLUSIONS: Through the evaluation of the 5 aforementioned parameters—the Big Five—the Milan Complexity Scale enables neurosurgeons to estimate the risk of a negative clinical course after brain tumor surgery and share these data with the patient. Furthermore, the Milan Complexity Scale could be used for research and educational purposes and better health system management.

OBJECT: The endoscopic endonasal approach (EEA) provides a minimally invasive corridor through which the cervicomedullary junction can be decompressed with reduced morbidity rates compared to those with the classic transoral approaches. The limit of the EEA is its inferior extent, and preoperative estimation of its reach is vital for determining its suitability. The aim of this study was to evaluate the actual inferior limit of the EEA in a surgical series of patients and develop an accurate and reliable predictor that can be used in planning endonasal odontoidectomies. METHODS: The actual inferior extent of surgery was determined in a series of 6 patients with adequate preoperative and postoperative imaging who underwent endoscopie endonasal odontoidectomy. The medians of the differences between several previously described predictive lines, namely the nasopalatine line (NPL) and nasoaxial line (NAxL), were compared with the actual surgical limit and the hard-palate line by using nonparametric statistics. A novel line, called the rhinopalatine line (RPL), was established and corresponded best with the actual limit of the surgery. RESULTS: There were 4 adult and 2 pediatric patients included in this study. The NPL overestimated the inferior extent of the surgery by an average (± SD) of 21.9 ± 8.1 mm (range 14.7-32.5 mm). The NAxL and RPL overestimated the inferior limit of surgery by averages of 6.9 ± 3.8 mm (range 3.7-13.3 mm) and 1.7 ± 3.7 mm (range −2.8 to 8.3 mm), respectively. The medians of the differences between the NPL and NAxL and the actual surgery were statistically different (both p = 0.0313). In contrast, there was no statistically significant difference between the RPL and the inferior limit of surgery (p = 0.4375). CONCLUSIONS: The RPL predicted the inferior limit of the EEA to the craniovertebral junction more accurately than previously described lines. The use of the RPL may help surgeons in choosing suitable candidates for the EEA and in selecting those for whom surgery through the oropharynx or the facial bones is the better approach.

OBJECTIVE: Surgical treatment of orbital lesions is challenging because complex approaches with a high risk of postoperative sequelae are required. Recently, minimally invasive endoscopic approaches through endonasal (EEA) and transpalpebral (ETP) routes have been proposed. The objective of this study was to assess outcomes of EEA and ETP in the authors’ series of patients with orbital lesions. METHODS: Data from all patients who underwent operations for an orbital tumor through an endoscopic approach at the authors’ institution from 2002 to 2018 were retrospectively collected. All patients underwent preoperative MRI and ophthalmological evaluation, which was repeated 3 months after surgery and then at regular follow-up intervals. A systematic review of the literature was also performed using Medline, Embase, and Web of Science databases. RESULTS: The series includes 23 patients (14 males); the mean patient age was 48 ± 23.9 years. Most of the lesions were intraconal (n = 19, 83%). The more frequent histotype was cavernous hemangioma (n = 5, 22%). Exophthalmos was the most common symptom (21 of 23 patients). EEA was performed in 16 cases (70%) and ETP in 7 (30%). The aim of the surgery was achieved in 94% of the cases after an EEA (successful biopsy in 5 of 6 cases and radical resection in all 10 remaining patients), and in 86% after an ETP (successful biopsy in 2 cases and radical tumor resection in 4 of 5 cases). Complications consisted of 3 cases (13%) of transitory diplopia. One recurrence (4%) was observed at follow-up (mean 59 ± 55 months). CONCLUSIONS: The EEA and ETP have demonstrated to be safe and effective for tumors located respectively in medial and lateral quadrants, permitting one to approach orbital lesions endoscopically at 360°. Innovative surgical tools, including intraoperative ultrasonography, may be useful to potentially reduce surgical morbidity. Larger series are needed to validate these preliminary suggestions.