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      Fluorescein Application in Cranial and Spinal Tumors Enhancing at Preoperative MRI and Operated With a Dedicated Filter on the Surgical Microscope: Preliminary Results in 279 Patients Enrolled in the FLUOCERTUM Prospective Study

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          Abstract

          Objective: Sodium fluorescein, a green, water soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier (BBB) disruption. The authors report the preliminary results of a prospective observational study regarding the use of fluorescein-guided technique for the resection of suspected malignant neoplasms of the central nervous system (CNS), contrast enhancing at preoperative magnetic resonance imaging (MRI), using a dedicated filter on the surgical microscope.

          Methods: In March 2016 the authors started a prospective, observational trial to evaluate intraoperative fluorescence's characteristics of CNS tumors, the percentage of extent of resection thanks to fluorescein aid and side effects related to fluorescein administration. This report is based on a preliminary analysis of the results of first 279 enrolled patients. Fluorescein was intravenously injected after intubation or immediately at the entrance in the operating room for awake procedures; the tumor was removed using a dedicated filter on the surgical microscope in an inside-out fashion until all fluorescent tissue was removed, as considered feasible by the surgeon.

          Results: The 279 patients finally enrolled in the trial, both firstly diagnosed and recurrent, were categorized according to WHO pathological classification and there were 212 neuroepithelial tumors, 25 brain metastases, 10 cerebral lymphomas, 7 hemangioblastomas, or hemangioendotheliomas and 25 other tumors and conditions. No adverse reaction related to the administration of fluorescein or to the combined use of fluorescein with other fluorophores was registered. Fluorescein accumulated in cerebral regions where the BBB was damaged, representing a significant surgical aid in most of the CNS tumors with contrast enhancement. In cases of complete removal of all fluorescent tissue, as intraoperatively judged by the surgeon, postoperative MRI revealed a gross total resection in 181/198 patients (91.4%).

          Conclusions: Based on these preliminary results, fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration.

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          Most cited references53

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          European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas.

          The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
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            Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

            Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.
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              Prospective Randomized Trial of Post-operative Stereotactic Radiosurgery versus Observation for Completely Resected Brain Metastases

              SUMMARY Background After brain metastasis resection, whole-brain radiation therapy (WBRT) decreases local recurrence but may cause cognitive decline. We performed this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved local tumor tumor-free recurrence rates compared to surgical resection alone as an alternative to the need for immediate WBRT. Methods The main entry criteria for the study included patients >3 years of age, with a Karnofsky Performance Score ≥ 70, who were able to undergo an MRI scan and who had a complete resection of 1–3 brain metastases (the maximum diameter of the resection cavity had to be ≤4cm). Patients were assigned randomly to either SRS treatment of the resection cavity (within 30 days of surgery) or observation (OBS). Patients were stratified by histology, tumor size, and number of metastases. Patients were recruited at a single tertiary cancer center. The primary endpoint was time to local recurrence in the resection cavity assessed by blinded central review of brain MRI scans in the intention-to-treat population. The trial was registered at clinicaltrials.gov (Trial NCT00950001, status: closed to new participants). Findings Between 8/13/2009 and 2/16/2016, 132 patients were randomized to OBS (N=68) or SRS (N=64), with 128 patients available for analysis. We stratified by metastasis size (maximum diameter of ≥3 cm vs. <3 cm), histology (melanoma vs. other), and number of metastases (one vs. two or three). The 12-month local tumor recurrence-free rate was 43% (OBS) (95% CI 31%–59%) and 72% (SRS) (95% CI 60%–87%) (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24–0.88, p=0.015). Interpretation This prospective randomized trial of patients undergoing surgical resection for 1–3 brain metastases indicates that SRS administered to the resection cavity significantly lowers local recurrence compared to observation alone. Thus, the use of SRS after brain metastasis resection is an alternative to WBRT.
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                Author and article information

                Contributors
                Journal
                Front Surg
                Front Surg
                Front. Surg.
                Frontiers in Surgery
                Frontiers Media S.A.
                2296-875X
                13 August 2019
                2019
                : 6
                : 49
                Affiliations
                [1] 1Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta , Milan, Italy
                [2] 2Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center , Phoenix, AZ, United States
                Author notes

                Edited by: Vernard S. Fennell, Capital Institute for Neurosciences, United States

                Reviewed by: Jorge Marcelo Mura, Instituto de Neurocirugía, Chile; Hiroki Toda, Fukui Red Cross Hospital, Japan

                *Correspondence: Francesco Acerbi francesco.acerbi@ 123456istituto-besta.it

                This article was submitted to Neurosurgery, a section of the journal Frontiers in Surgery

                †These authors have contributed equally to this work

                Article
                10.3389/fsurg.2019.00049
                6705221
                31475153
                382feb44-e2f8-4e08-8b24-42092fcda66d
                Copyright © 2019 Falco, Cavallo, Vetrano, de Laurentis, Siozos, Schiariti, Broggi, Ferroli and Acerbi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 February 2019
                : 29 July 2019
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 62, Pages: 13, Words: 8895
                Categories
                Surgery
                Original Research

                biopsy,brain tumors,central nervous system,fluorescein,neuro-oncology,spinal tumors,yellow 560

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