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      Eloquent Lower Grade Gliomas, a Highly Vulnerable Cohort: Assessment of Patients’ Functional Outcome After Surgery Based on the LoG-Glio Registry

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          Abstract

          Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, while occurrence was only 14% at 9-12-month follow up. 6/7 patients with mild aphasia recovered after 9-12 months, while motor deficits present at 3-month follow up were persistent in majority of patients. Eastern oncology group functional status (ECOG) significantly decreased by surgery (p < 0.001) in 31% of cases. Between 3-month and 9-12-months follow up no significant improvement was seen. In the multivariable model CTR (p=0.019, OR 31.9), and ECOG>0 (p=0.021, OR 8.5) were independent predictors for permanent postoperative deficit according to NIHSS at 3-month according to multivariable regression model. Patients harboring eloquently located LGG are highly vulnerable for permanent deficits. Almost one third of patients have a permanent reduction of their functional status based on ECOG. Risk of an extended resection has to be balanced with the respective oncological benefit. Especially, patients with impaired pre-operative status are at risk for new permanent deficits. There is a relevant improvement of neurological symptoms in the first year after surgery, especially for patients with slight aphasia.

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          Most cited references42

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          The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

          The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.
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            Glioma extent of resection and its impact on patient outcome.

            There is still no general consensus in the literature regarding the role of extent of glioma resection in improving patient outcome. Although the importance of resection in obtaining tissue diagnosis and alleviating symptoms is clear, a lack of Class I evidence prevents similar certainty in assessing the influence of extent of resection. We reviewed every major clinical publication since 1990 on the role of extent of resection in glioma outcome. Twenty-eight high-grade glioma articles and 10 low-grade glioma articles were examined in terms of quality of evidence, expected extent of resection, and survival benefit. Despite persistent limitations in the quality of data, mounting evidence suggests that more extensive surgical resection is associated with longer life expectancy for both low- and high-grade gliomas.
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              Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.

              It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan-Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered. Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered. The observations in this study indicate the usefulness of 5-ALA-induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                03 March 2022
                2022
                : 12
                : 845992
                Affiliations
                [1] 1Department of Neurosurgery, University of Ulm , Günzburg, Germany
                [2] 2Department of Neurosurgery, Charité - University of Berlin , Berlin, Germany
                [3] 3Department of Neurosurgery, University of Würzburg , Würzburg, Germany
                [4] 4Department of Neurosurgery, University of Göttingen , Göttingen, Germany
                [5] 5Department of Neurosurgery, Katharinenhospital Stuttgart , Stuttgart, Germany
                [6] 6Department of Neurosurgery, University of Frankfurt , Frankfurt am Main, Germany
                [7] 7Department of Neurosurgery, Helios Hospital Erfurt , Erfurt, Germany
                [8] 8Department of Neurosurgery, University of Tübingen , Tübingen, Germany
                [9] 9Department of Neurosurgery, KRH Klinikum Region Hannover , Hannover, Germany
                [10] 10Institute of Epidemiology and Medical Biometry, University of Ulm , Ulm, Germany
                Author notes

                Edited by: Alireza Mansouri, The Pennsylvania State University (PSU), United States

                Reviewed by: Pierre Robe, University Medical Center Utrecht, Netherlands; Asgeir S. Jakola, Sahlgrenska University Hospital, Sweden

                *Correspondence: Jan Coburger, jan.coburger@ 123456uni-ulm.de

                This article was submitted to Neuro-Oncology and Neurosurgical Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.845992
                8927728
                35311092
                a8581cb0-2d08-4bf2-873b-af34c2cb6c0d
                Copyright © 2022 Coburger, Onken, Rueckriegel, von der Brelie, Nadji-Ohl, Forster, Gerlach, Unteroberdörster, Roder, Kniese, Schommer, Rothenbacher, Nagel, Wirtz, Ernestus, Nabavi, Tatagiba, Czabanka, Ganslandt, Rohde, Löhr, Vajkoczy and Pala

                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
                : 30 December 2021
                : 31 January 2022
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 43, Pages: 10, Words: 5693
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                lgg,neurological deficit,awake surgery,imri = intraoperative mri,ius = intraoperative ultrasound,intraoperative monitoring (iom),eloquent area tumours,eloquent area surgery

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