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Isolan GR, Bark SA, Monteiro JM, Mattei TA, Yağmurlu K, Gonçalves RF, Malafaia O, Roesler R, Filho JMR. Porto Alegre Line predicts lenticulostriate arteries encasement and extent of resection in insular gliomas. A preliminary study. Front Surg 2025; 12:1414302. [PMID: 39996150 PMCID: PMC11847845 DOI: 10.3389/fsurg.2025.1414302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 01/07/2025] [Indexed: 02/26/2025] Open
Abstract
Object In insular glioma surgery, lenticulostriate arteries (LSTa) tumoral encasement increases neurological deficits risk despite intensive efforts to preserve the internal capsule's integrity. In this study, we focus on the LSTa relationships with the medial aspect of the insular tumors. We propose a new non-invasive method for LSTa involvement prediction in preoperative MRI (Porto Alegre Line). We compare it with direct intraoperative encased LSTa visualization. Methods A retrospective review of our database of 52 patients of insular glioma was performed. In cases with no tumor located medial to Porto Alegre line, our medial resection limit, mainly for the tumor part located next to the limen insula, was the inferior fronto-occipital fasciculus (IFOF), identified through altered speech patterns during electric subcortical stimulation. In cases with no assumed LSTa involvement, the parameter used to stop resection was the confirmation of the corticospinal tract with 10-mA stimulus. The resection limit of tumors placed medially to the Porto Alegre line was intraoperative direct LSTa visualization. Results The LSTa involvement was the most critical medial limiting factor in more aggressive tumor resection and an excellent overall survival (P = 0.022). In cases in which there were direct intraoperative LSTa encasement visualization, Porto Alegre Line was employed as an MRI preoperative landmark for prediction of LSTa involvement in those patients with Sensitivity, Specificity, Positive Predictive Values of 1, 0.975 and 0.923, respectively. Conclusion We have found that LSTa encasement is a limiting factor to reach a satisfactory extent of resection and that Porto Alegre Line can predict it.
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Affiliation(s)
- Gustavo Rassier Isolan
- Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba, Brazil
- National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology—INCT BioOncoPed, Porto Alegre, Brazil
- The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre, Brazil
| | - Samir Ale Bark
- Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba, Brazil
- The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre, Brazil
| | - Jander Moreira Monteiro
- Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba, Brazil
- The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre, Brazil
| | - Tobias A. Mattei
- Division of Neurological Surgery, St. Louis University, St. Louis, MO, United States
| | - Kaan Yağmurlu
- Department of Neurosurgery, University of Virginia, Charlottesville, VA, United States
| | - Rafaela Fernandes Gonçalves
- Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba, Brazil
- The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre, Brazil
| | - Osvaldo Malafaia
- The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre, Brazil
| | - Rafael Roesler
- National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology—INCT BioOncoPed, Porto Alegre, Brazil
- Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
- Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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West TR, Mazurek MH, Perez NA, Razak SS, Gal ZT, McHugh JM, Choi BD, Nahed BV. Navigated Intraoperative Ultrasound Offers Effective and Efficient Real-Time Analysis of Intracranial Tumor Resection and Brain Shift. Oper Neurosurg (Hagerstown) 2025; 28:148-158. [PMID: 38995025 DOI: 10.1227/ons.0000000000001250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 05/01/2024] [Indexed: 07/13/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Neuronavigation is a fundamental tool in the resection of intracranial tumors. However, it is limited by its calibration to preoperative neuroimaging, which loses accuracy intraoperatively after brain shift. Therefore, surgeons rely on anatomic landmarks or tools like intraoperative MRI to assess the extent of tumor resection (EOR) and update neuronavigation. Recent studies demonstrate that intraoperative ultrasound (iUS) provides point-of-care imaging without the cost or resource utilization of an intraoperative MRI, and advances in neuronavigation-guided iUS provide an opportunity for real-time imaging overlaid with neuronavigation to account for brain shift. We assessed the feasibility, efficacy, and benefits of navigated iUS to assess the EOR and restore stereotactic accuracy in neuronavigation after brain shift. METHODS This prospective single-center study included patients presenting with intracranial tumors (gliomas, metastasis) to an academic medical center. Navigated iUS images were acquired preresection, midresection, and postresection. The EOR was determined by the surgeon intraoperatively and compared with the postoperative MRI report by an independent neuroradiologist. Outcome measures included time to perform the iUS sweep, time to process ultrasound images, and EOR predicted by the surgeon intraoperatively compared with the postoperative MRI. RESULTS This study included 40 patients consisting of gliomas (n = 18 high-grade gliomas, n = 4 low-grade gliomas, n = 4 recurrent) and metastasis (n = 18). Navigated ultrasound sweeps were performed in all patients (n = 83) with a median time to perform of 5.5 seconds and a median image processing time of 29.9 seconds. There was 95% concordance between the surgeon's and neuroradiologist's determination of EOR using navigated iUS and postoperative MRI, respectively. The sensitivity was 100%, and the specificity was 94%. CONCLUSION Navigated iUS was successfully used for EOR determination in glioma and metastasis resection. Incorporating navigated iUS into the surgical workflow is safe and efficient and provides a real-time assessment of EOR while accounting for brain shift in intracranial tumor surgeries.
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Affiliation(s)
- Timothy R West
- Department of Neurosurgery, Massachusetts General Hospital, Boston , Massachusetts , USA
| | | | | | | | - Zsombor T Gal
- Harvard Medical School, Boston , Massachusetts , USA
| | - Jeffrey M McHugh
- Department of Neurosurgery, Massachusetts General Hospital, Boston , Massachusetts , USA
| | - Bryan D Choi
- Department of Neurosurgery, Massachusetts General Hospital, Boston , Massachusetts , USA
- Harvard Medical School, Boston , Massachusetts , USA
| | - Brian V Nahed
- Department of Neurosurgery, Massachusetts General Hospital, Boston , Massachusetts , USA
- Harvard Medical School, Boston , Massachusetts , USA
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Himstead AS, Chen JW, Chu E, Perez-Rosendahl MA, Zheng M, Mathew S, Yuen CA. Expanded Use of Vorasidenib in Non-Enhancing Recurrent CNS WHO Grade 3 Oligodendroglioma. Biomedicines 2025; 13:201. [PMID: 39857783 PMCID: PMC11762706 DOI: 10.3390/biomedicines13010201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 12/31/2024] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Anaplastic oligodendrogliomas (AOs) are central nervous system (CNS) World Health Organization (WHO) grade 3 gliomas characterized by isocitrate dehydrogenase (IDH) mutation (m)IDH and 1p/19q codeletion. AOs are typically treated with surgery and chemoradiation. However, chemoradiation can cause detrimental late neurocognitive morbidities and an accelerated disease course. The recently regulatory-approved vorasidenib, a brain-penetrating oral inhibitor of IDH1/2, has altered the treatment paradigm for recurrent/residual non-enhancing surgically resected CNS WHO grade 2 mIDH gliomas. Though vorasidenib can delay the time to chemoradiation for grade 2 gliomas, the implications for vorasidenib in non-grade 2 mIDH gliomas are not well understood. Results: We present a case of a 71-year-old male with a grade 3 non-enhancing oligodendroglioma successfully treated with vorasidenib with an 11% reduction in residual tumor volume. Vorasidenib was well tolerated in our patient with a mild elevation in his liver transaminases that resolved following a brief interruption in treatment. Conclusions: Our case suggests that vorasidenib may impart therapeutic benefits in this setting. This case illustrates the need for further investigation into these less commonly addressed scenarios and treatment strategies that extend beyond current guidelines.
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Affiliation(s)
- Alexander S. Himstead
- Department of Neurological Surgery, University of California, Irvine, CA 92697, USA; (A.S.H.); (J.W.C.)
| | - Jefferson W. Chen
- Department of Neurological Surgery, University of California, Irvine, CA 92697, USA; (A.S.H.); (J.W.C.)
| | - Eleanor Chu
- Department of Radiological Sciences, University of California, Irvine, CA 92697, USA;
| | - Mari A. Perez-Rosendahl
- Department of Pathology & Laboratory Medicine, University of California, Irvine, CA 92697, USA;
| | - Michelle Zheng
- UC Irvine Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA 92697, USA
| | - Sherin Mathew
- Department of Research, University of California, Irvine, CA 92697, USA
| | - Carlen A. Yuen
- Department of Neurology, Division of Neuro-Oncology, University of California, Irvine, CA 92697, USA
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Mahootiha M, Tak D, Ye Z, Zapaishchykova A, Likitlersuang J, Climent Pardo JC, Boyd A, Vajapeyam S, Chopra R, Prabhu SP, Liu KX, Elhalawani H, Nabavizadeh A, Familiar A, Mueller S, Aerts HJWL, Bandopadhayay P, Ligon KL, Haas-Kogan D, Poussaint TY, Qadir HA, Balasingham I, Kann BH. Multimodal deep learning improves recurrence risk prediction in pediatric low-grade gliomas. Neuro Oncol 2025; 27:277-290. [PMID: 39211987 PMCID: PMC11726244 DOI: 10.1093/neuonc/noae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Postoperative recurrence risk for pediatric low-grade gliomas (pLGGs) is challenging to predict by conventional clinical, radiographic, and genomic factors. We investigated if deep learning (DL) of magnetic resonance imaging (MRI) tumor features could improve postoperative pLGG risk stratification. METHODS We used a pretrained DL tool designed for pLGG segmentation to extract pLGG imaging features from preoperative T2-weighted MRI from patients who underwent surgery (DL-MRI features). Patients were pooled from 2 institutions: Dana Farber/Boston Children's Hospital (DF/BCH) and the Children's Brain Tumor Network (CBTN). We trained 3 DL logistic hazard models to predict postoperative event-free survival (EFS) probabilities with (1) clinical features, (2) DL-MRI features, and (3) multimodal (clinical and DL-MRI features). We evaluated the models with a time-dependent Concordance Index (Ctd) and risk group stratification with Kaplan-Meier plots and log-rank tests. We developed an automated pipeline integrating pLGG segmentation and EFS prediction with the best model. RESULTS Of the 396 patients analyzed (median follow-up: 85 months, range: 1.5-329 months), 214 (54%) underwent gross total resection and 110 (28%) recurred. The multimodal model improved EFS prediction compared to the DL-MRI and clinical models (Ctd: 0.85 (95% CI: 0.81-0.93), 0.79 (95% CI: 0.70-0.88), and 0.72 (95% CI: 0.57-0.77), respectively). The multimodal model improved risk-group stratification (3-year EFS for predicted high-risk: 31% versus low-risk: 92%, P < .0001). CONCLUSIONS DL extracts imaging features that can inform postoperative recurrence prediction for pLGG. Multimodal DL improves postoperative risk stratification for pLGG and may guide postoperative decision-making. Larger, multicenter training data may be needed to improve model generalizability.
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Affiliation(s)
- Maryamalsadat Mahootiha
- Faculty of Medicine, University of Oslo, Oslo, Norway
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Divyanshu Tak
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Zezhong Ye
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Zapaishchykova
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Jirapat Likitlersuang
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Juan Carlos Climent Pardo
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Aidan Boyd
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Sridhar Vajapeyam
- Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rishi Chopra
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Sanjay P Prabhu
- Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kevin X Liu
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Hesham Elhalawani
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Ali Nabavizadeh
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Center for Data-Driven Discovery in Biomedicine (D3b), Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Ariana Familiar
- Department of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Center for Data-Driven Discovery in Biomedicine (D3b), Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Sabine Mueller
- Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
- Department of Neurology, University of California San Francisco, San Francisco, California, USA
| | - Hugo J W L Aerts
- Radiology and Nuclear Medicine, CARIM & GROW, Maastricht University, Maastricht, The Netherlands
- Department of Radiology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
| | - Pratiti Bandopadhayay
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Keith L Ligon
- Department of Pathology, Dana-Farber Cancer Institute, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Daphne Haas-Kogan
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Tina Y Poussaint
- Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Hemin Ali Qadir
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
| | - Ilangko Balasingham
- Department of Electronic Systems, Norwegian University of Science and Technology, Trondheim, Norway
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
| | - Benjamin H Kann
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA
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Diaz M, Pan PC. Management of Low-Grade Gliomas. Cancer J 2025; 31:e0760. [PMID: 39841424 PMCID: PMC11801446 DOI: 10.1097/ppo.0000000000000760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
ABSTRACT The term "low-grade glioma" historically refers to adult diffuse gliomas that exhibit a less aggressive course than the more common high-grade gliomas. In the current molecular era, "low-grade" refers to World Health Organization central nervous system grade 2 gliomas almost always with an isocitrate dehydrogenase (IDH) mutation (astrocytomas and oligodendrogliomas). The term "lower-grade gliomas" has emerged encompassing grades 2 and 3 IDH-mutant astrocytomas and oligodendrogliomas, to acknowledge that histological grade is not as important a prognostic factor as molecular features, and distinguishing them from grade 4 glioblastomas, which lack an IDH mutation. These grades 2 and 3 IDH-mutant tumors are characterized by indolent growth but are ultimately incurable in most cases, presenting significant management challenges. Physicians must carefully weigh all available evidence to balance improvements in survival from new treatments against treatment toxicities. This review summarizes the evidence guiding the treatment of these patients.
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Rana R, Devi SN, Bhardwaj AK, Yashavarddhan MH, Bohra D, Ganguly NK. Exosomes as nature's nano carriers: Promising drug delivery tools and targeted therapy for glioma. Biomed Pharmacother 2025; 182:117754. [PMID: 39731936 DOI: 10.1016/j.biopha.2024.117754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 11/28/2024] [Accepted: 12/09/2024] [Indexed: 12/30/2024] Open
Abstract
Exosomes, minute vesicles originating from diverse cell types, exhibit considerable potential as carriers for drug delivery in glioma therapy. These naturally occurring nanocarriers facilitate the transfer of proteins, RNAs, and lipids between cells, offering advantages such as biocompatibility, efficient cellular absorption, and the capability to traverse the blood-brain barrier (BBB). In the realm of cancer, particularly gliomas, exosomes play pivotal roles in modulating tumor growth, regulating immunity, and combating drug resistance. Moreover, exosomes serve as valuable biomarkers for diagnosing diseases and assessing prognosis. This review aims to elucidate the therapeutic and diagnostic promise of exosomes in glioma treatment, highlighting the innovative advances in exosome engineering that enable precise drug loading and targeting. By circumventing challenges associated with current glioma treatments, exosome-mediated drug delivery strategies can enhance the efficacy of chemotherapy drugs like temozolomide and overcome drug resistance mechanisms. This review underscores the multifaceted roles of exosomes in glioma pathogenesis and therapy, underscoring their potential as natural nanocarriers for targeted therapy and heralding a new era of hope for glioma treatment.
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Affiliation(s)
- Rashmi Rana
- Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India.
| | | | - Amit Kumar Bhardwaj
- Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - M H Yashavarddhan
- Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Deepika Bohra
- Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Nirmal Kumar Ganguly
- Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India
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Huo JF, Zheng JJ, Helmy M, Liu MD, Zhang XJ, Song DL, Sun W. Minimally invasive neurosurgery: application of burr-hole technique across a spectrum of brain lesions. Neurosurg Rev 2024; 47:903. [PMID: 39690286 DOI: 10.1007/s10143-024-03151-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/15/2024] [Accepted: 12/08/2024] [Indexed: 12/19/2024]
Abstract
OBJECTIVE The burr-hole technique is a minimally invasive transcranial approach designed to minimize the surgical incision size and reduce disruption to brain tissue. We aimed to share our experience with the burr-hole technique for removing brain lesions and to evaluate its effectiveness in treating appropriately sized intra-axial brain lesions. METHODS In this retrospective cohort study, we analyzed the clinical features, radiological characteristics, surgical techniques, and outcomes of patients who underwent burr-hole surgery for intra-axial brain lesions between January 2019 and December 2023. RESULTS A total of 81 patients were included in the study. Gross total resection was achieved in 74 patients (91.4%), whereas subtotal resection was performed in 7 patients (8.6%). There were no perioperative deaths, cerebrospinal fluid leaks, or wound infections. The median follow-up duration was 40.5 months (range, 4.1-63.7 months). At the end of the follow-up period, 14 patients (17.3%) experienced recurrence, including 6 with glioma and 8 with primary cerebral lymphoma. Among these patients, 10 died due to lesion recurrence. CONCLUSIONS The burr-hole approach using a retractable tubular device is a safe and effective method for the removal of brain lesions. As a novel minimally invasive technique, it significantly facilitates and accelerates the evolution of microsurgical outcomes.
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Affiliation(s)
- Jun-Feng Huo
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Jia-Jia Zheng
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Mohamed Helmy
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Min-Di Liu
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Xue-Jun Zhang
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Dong-Lei Song
- Department of Neurosurgery, Shanghai Donglei Brain Hospital, No. 988# Road Huaxu, Qingpu Area, 201702, Shanghai, China
| | - Wei Sun
- Department of Neurosurgery, China Rehabilitation Research Center Beijing Boai Hospital, No. 10 Jiaomen North Road, Fengtai District, Beijing, China.
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Vaz-Salgado MÁ, García BC, Pérez IF, Munárriz BJ, Domarco PS, González AH, Villar MV, Caro RL, Delgado MLV, Sánchez JMS. SEOM-GEINO clinical guidelines for grade 2 gliomas (2023). Clin Transl Oncol 2024; 26:2856-2865. [PMID: 38662171 PMCID: PMC11467015 DOI: 10.1007/s12094-024-03456-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2024] [Indexed: 04/26/2024]
Abstract
The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.
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Affiliation(s)
- María Ángeles Vaz-Salgado
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis) CIBERONC, Madrid, Spain.
| | - Belén Cigarral García
- Medical Oncology Department, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain
| | - Isaura Fernández Pérez
- Medical Oncology Department, Hospital Alvaro Cunqueiro-Complejo Hospitalario Universitario de Vigo, Pontevedra, Spain
| | | | - Paula Sampedro Domarco
- Medical Oncology Department, Complexo Hospitalario Universitario de Ourense (CHUO), Orense, Spain
| | - Ainhoa Hernández González
- Medical Oncology Department, Hospital Germans Trias I Pujol(ICO)-Badalona, Instituto Catalán de Oncología, Barcelona, Spain
| | - María Vieito Villar
- Medical Oncology Department, Hospital Universitario Vall D'Hebron, Barcelona, Spain
| | - Raquel Luque Caro
- Medical Oncology Department, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria Ibs.Granada, Granada, Spain
| | | | - Juan Manuel Sepúlveda Sánchez
- Neuro-Oncology Unit, HM Universitario Sanchinarro-CIOCC, Madrid, Spain.
- Medical Oncology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación 12 de Octubre (I+12), Madrid, Spain.
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Boccuni L, Roca-Ventura A, Buloz-Osorio E, Leno-Colorado D, Delgado-Gallén S, Cabello-Toscano M, Perellón-Alfonso R, Villalba-Martínez G, Martínez-Ricarte F, Martín-Fernández J, Buxeda-Rodriguez M, Conesa-Bertrán G, Illueca-Moreno M, Lladó-Carbó E, Perla Y Perla C, Garrido C, Pariente JC, Laredo C, Muñoz-Moreno E, Bargalló N, Trompetto C, Marinelli L, Bartrés-Faz D, Abellaneda-Pérez K, Pascual-Leone A, Tormos-Muñoz JM. Non-invasive prehabilitation to foster widespread fMRI cortical reorganization before brain tumor surgery: lessons from a case series. J Neurooncol 2024; 170:185-198. [PMID: 39044115 PMCID: PMC11447047 DOI: 10.1007/s11060-024-04774-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 07/08/2024] [Indexed: 07/25/2024]
Abstract
PURPOSE The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings. METHODS Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery. RESULTS Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data. CONCLUSION This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.
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Affiliation(s)
- Leonardo Boccuni
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain
| | - Alba Roca-Ventura
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
| | - Edgar Buloz-Osorio
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - David Leno-Colorado
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Selma Delgado-Gallén
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - María Cabello-Toscano
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Ruben Perellón-Alfonso
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Gloria Villalba-Martínez
- Department of Neurosurgery, Hospital del Mar, Barcelona, Spain
- Systems Neurologic and Neurotherapeutic Group at Research Institute Hospital del Mar, Barcelona, Spain
- Universitat Pompeu Fabra, Barcelona, Spain
| | | | - Jesús Martín-Fernández
- Department of Neurosurgery, Hôpital Gui de Chauliac, Montpellier, France
- Department of Neurosurgery, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
- Universidad de La Laguna, Tenerife, Spain
| | | | | | | | | | | | - César Garrido
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain
- Neuroradiology Section, Radiology Department, Diagnostic Image Centre, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - José Carlos Pariente
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain
| | - Carlos Laredo
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain
| | - Emma Muñoz-Moreno
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain
| | - Núria Bargalló
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Magnetic Resonance Image Core Facility (IDIBAPS), Barcelona, Spain
- Neuroradiology Section, Radiology Department, Diagnostic Image Centre, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain
| | - Carlo Trompetto
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Lucio Marinelli
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - David Bartrés-Faz
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Kilian Abellaneda-Pérez
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain.
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Bellaterra, Spain.
- Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
| | - Alvaro Pascual-Leone
- Wolk Center for Memory Health and Marcus Institute for Aging Research, Hebrew Senior Life, Boston, MA, USA
- Department of Neurology, Harvard Medical School, Boston, MA, USA
| | - Josep María Tormos-Muñoz
- Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain.
- Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain.
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10
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Li PC, Yun DB, Huang YX, Huang QY. Prognostic significance of oligodendrocyte transcription factor 2 expression in glioma patients: A systematic review and meta-analysis. World J Clin Cases 2024; 12:5739-5748. [PMID: 39247740 PMCID: PMC11263059 DOI: 10.12998/wjcc.v12.i25.5739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 05/27/2024] [Accepted: 06/24/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Gliomas are the most common primary central nervous system neoplasm. Despite recent advances in the diagnosis and treatment of gliomas, patient prognosis remains dismal. Therefore, it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes. AIM To investigate the association between oligodendrocyte transcription factor 2 (Olig2) expression and the outcomes of glioma patients. METHODS The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were searched for studies (published up to October 2023) that investigated the relationship between Olig2 expression and prognosis of glioma patients. The quality of the studies was assessed using the Newcastle Ottawa Scale. Data analyses were performed using Stata Version 12.0 software. RESULTS A total of 1205 glioma patients from six studies were included in the meta-analysis. High Olig2 expression was associated with better outcomes in glioma patients [hazard ratio (HR): 0.81; 95% (confidence interval) CI: 0.51-1.27; P = 0.000]. Furthermore, the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients (HR: 1.34; 95%CI: 0.79-2.27) and better prognosis in Asian patients (HR: 0.43; 95%CI: 0.22-0.84). The sensitivity analysis showed that no single study had a significant effect on pooled HR, and there was also no indication of publication bias according to the Egger's and Begger's P value test or funnel plot test. CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients, and should be investigated further as a prognostic biomarker and therapeutic target for glioma.
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Affiliation(s)
- Peng-Cheng Li
- Department of Neurosurgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - De-Bo Yun
- Department of Neurosurgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Ya-Xin Huang
- Department of Transfusion, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Qian-Yi Huang
- Department of Transfusion, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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11
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Shi S, Liang H, Huang Q, Sun X. Identification of Novel Prognostic Signature of Recurrent Low-Grade Glioma. World Neurosurg 2024:S1878-8750(24)01287-7. [PMID: 39069129 DOI: 10.1016/j.wneu.2024.07.147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/18/2024] [Accepted: 07/20/2024] [Indexed: 07/30/2024]
Abstract
OBJECTIVES The prognosis of patients with recurrent low-grade glioma (rLGG) varies greatly. Some patients can survive >10 years after recurrence, whereas other patients have <1 year of survival. METHODS To identify the related risk factors affecting the prognosis of patients with rLGG, we performed a series of bioinformatics analyses on RNA sequencing data of rLGG based on the Chinese Glioma Genome Altas database. RESULTS We constructed a 12-gene prognostic signature, dividing all the patients with rLGG into high- and low-risk subgroups. The result showed an excellent predictive effect in both the training cohort and the validation cohort using LASSO-Cox regression. Moreover, multivariate Cox analysis identified 4 independent prognostic factors of rLGG; among them, ZCWPW1 is identified as a high-value protective factor. CONCLUSIONS In all, this prognostic model displayed robust predictive capability for the overall survival of patients with rLGG, providing a new monitoring method for rLGG. The 4 independent prognostic factors, especially ZCWPW1, can be potential targets for rLGG, bringing new possibilities for the treatment of patients with rLGG.
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Affiliation(s)
- Shenbao Shi
- Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Hui Liang
- Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Qinhong Huang
- Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xinlin Sun
- Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
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12
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Santillán-Guaján SM, Shahi MH, Castresana JS. Mesenchymal-Stem-Cell-Based Therapy against Gliomas. Cells 2024; 13:617. [PMID: 38607056 PMCID: PMC11011546 DOI: 10.3390/cells13070617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 03/29/2024] [Accepted: 03/31/2024] [Indexed: 04/13/2024] Open
Abstract
Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they come. In this work, the possibility of using MSCs to deliver therapeutic genes, oncolytic viruses, and miRNA is presented, as well as strategies that can improve their therapeutic efficacy against glioblastoma, such as CAR-T cells, nanoparticles, and exosomes.
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Affiliation(s)
- Sisa M. Santillán-Guaján
- Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain;
| | - Mehdi H. Shahi
- Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India;
| | - Javier S. Castresana
- Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain;
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13
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Koay JM, Michaelides L, Moniz-Garcia DP, Quinones-Hinojosa A, Chaichana K, Almeida JP, Gruenbaum BF, Sherman WJ, Sabsevitz DS. Repeated surgical resections for management of high-grade glioma and its impact on quality of life. J Neurooncol 2024; 167:267-273. [PMID: 38349476 DOI: 10.1007/s11060-024-04600-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 02/06/2024] [Indexed: 04/18/2024]
Abstract
PURPOSE High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. METHODS Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. RESULTS There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. CONCLUSIONS These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.
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Affiliation(s)
- Jun Min Koay
- Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
- Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
| | | | | | | | - Kaisorn Chaichana
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA
| | | | - Benjamin F Gruenbaum
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Wendy J Sherman
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
| | - David S Sabsevitz
- Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA
- Department of Neurological Surgery, Mayo Clinic, Jacksonville, FL, USA
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14
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Shimizu T, Tanaka S, Kitagawa Y, Sakaguchi Y, Kamiya M, Takayanagi S, Takami H, Urano Y, Saito N. Advancement of fluorescent aminopeptidase probes for rapid cancer detection-current uses and neurosurgical applications. Front Surg 2024; 11:1298709. [PMID: 38516394 PMCID: PMC10954885 DOI: 10.3389/fsurg.2024.1298709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 02/22/2024] [Indexed: 03/23/2024] Open
Abstract
Surgical resection is considered for most brain tumors to obtain tissue diagnosis and to eradicate or debulk the tumor. Glioma, the most common primary malignant brain tumor, generally has a poor prognosis despite the multidisciplinary treatments with radical resection and chemoradiotherapy. Surgical resection of glioma is often complicated by the obscure border between the tumor and the adjacent brain tissues and by the tumor's infiltration into the eloquent brain. 5-aminolevulinic acid is frequently used for tumor visualization, as it exhibits high fluorescence in high-grade glioma. Here, we provide an overview of the fluorescent probes currently used for brain tumors, as well as those under development for other cancers, including HMRG-based probes, 2MeSiR-based probes, and other aminopeptidase probes. We describe our recently developed HMRG-based probes in brain tumors, such as PR-HMRG, combined with the existing diagnosis approach. These probes are remarkably effective for cancer cell recognition. Thus, they can be potentially integrated into surgical treatment for intraoperative detection of cancers.
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Affiliation(s)
- Takenori Shimizu
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shota Tanaka
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yosuke Kitagawa
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Yusuke Sakaguchi
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mako Kamiya
- Department of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan
| | - Shunsaku Takayanagi
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirokazu Takami
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasuteru Urano
- Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Nobuhito Saito
- Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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15
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Quiñones-Hinojosa A, Basil A, Moniz-Garcia D, Suarez-Meade P, Ramos A, Jentoft M, Middlebrooks E, Grewal S, Abode-Iyamah K, Bydon M, Sarkaria J, Dickson D, Swanson K, Rosenfeld S, Schiapparelli P, Guerrero-Cazares H, Chaichana K, Meyer F. From the Operating Room to the Laboratory: Role of the Neuroscience Tissue Biorepository in the Clinical, Translational, and Basic Science Research Pipeline. Mayo Clin Proc 2024; 99:229-240. [PMID: 38309935 PMCID: PMC10842257 DOI: 10.1016/j.mayocp.2023.10.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 10/05/2023] [Accepted: 10/25/2023] [Indexed: 02/05/2024]
Abstract
OBJECTIVE To establish a neurologic disorder-driven biospecimen repository to bridge the operating room with the basic science laboratory and to generate a feedback cycle of increased institutional and national collaborations, federal funding, and human clinical trials. METHODS Patients were prospectively enrolled from April 2017 to July 2022. Tissue, blood, cerebrospinal fluid, bone marrow aspirate, and adipose tissue were collected whenever surgically safe. Detailed clinical, imaging, and surgical information was collected. Neoplastic and nonneoplastic samples were categorized and diagnosed in accordance with current World Health Organization classifications and current standard practices for surgical pathology at the time of surgery. RESULTS A total of 11,700 different specimens from 813 unique patients have been collected, with 14.2% and 8.5% of patients representing ethnic and racial minorities, respectively. These include samples from a total of 463 unique patients with a primary central nervous system tumor, 88 with metastasis to the central nervous system, and 262 with nonneoplastic diagnoses. Cerebrospinal fluid and adipose tissue dedicated banks with samples from 130 and 16 unique patients, respectively, have also been established. Translational efforts have led to 42 new active basic research projects; 4 completed and 6 active National Institutes of Health-funded projects; and 2 investigational new drug and 5 potential Food and Drug Administration-approved phase 0/1 human clinical trials, including 2 investigator initiated and 3 industry sponsored. CONCLUSION We established a comprehensive biobank with detailed notation with broad potential that has helped us to transform our practice of research and patient care and allowed us to grow in research and clinical trials in addition to providing a source of tissue for new discoveries.
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Affiliation(s)
| | - Aleeshba Basil
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL
| | | | | | - Andres Ramos
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL
| | - Mark Jentoft
- Department of Pathology, Mayo Clinic, Jacksonville, FL
| | | | - Sanjeet Grewal
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL
| | | | - Mohamad Bydon
- Department of Neurosurgery, Mayo Clinic, Rochester, MN
| | - Jann Sarkaria
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | | | | | | | | | | | | | - Fredric Meyer
- Department of Neurosurgery, Mayo Clinic, Rochester, MN
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16
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Kim TH, Cho J, Kang SG, Moon JH, Suh CO, Park YW, Chang JH, Yoon HI. High Radiation Dose to the Fornix Causes Symptomatic Radiation Necrosis in Patients with Anaplastic Oligodendroglioma. Yonsei Med J 2024; 65:1-9. [PMID: 38154474 PMCID: PMC10774647 DOI: 10.3349/ymj.2023.0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 08/09/2023] [Accepted: 09/06/2023] [Indexed: 12/30/2023] Open
Abstract
PURPOSE Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN). MATERIALS AND METHODS A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed. RESULTS The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, p=0.005). CONCLUSION The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
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Affiliation(s)
- Tae Hyung Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
| | - Jaeho Cho
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Seok-Gu Kang
- Department of Neurosurgery, Brain Tumor Center, Yonsei University College of Medicine, Seoul, Korea
| | - Ju Hyung Moon
- Department of Neurosurgery, Brain Tumor Center, Yonsei University College of Medicine, Seoul, Korea
| | - Chang-Ok Suh
- Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Yae Won Park
- Department of Radiology and Research Institute of Radiological Science and Center for Clinical Image Data Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Hee Chang
- Department of Neurosurgery, Brain Tumor Center, Yonsei University College of Medicine, Seoul, Korea.
| | - Hong In Yoon
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
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17
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De Simone M, Conti V, Palermo G, De Maria L, Iaconetta G. Advancements in Glioma Care: Focus on Emerging Neurosurgical Techniques. Biomedicines 2023; 12:8. [PMID: 38275370 PMCID: PMC10813759 DOI: 10.3390/biomedicines12010008] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/08/2023] [Accepted: 12/09/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Despite significant advances in understanding the molecular pathways of glioma, translating this knowledge into effective long-term solutions remains a challenge. Indeed, gliomas pose a significant challenge to neurosurgical oncology because of their diverse histopathological features, genetic heterogeneity, and clinical manifestations. Relevant sections: This study focuses on glioma complexity by reviewing recent advances in their management, also considering new classification systems and emerging neurosurgical techniques. To bridge the gap between new neurosurgical approaches and standards of care, the importance of molecular diagnosis and the use of techniques such as laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) are emphasized, exploring how the integration of molecular knowledge with emerging neurosurgical approaches can personalize and improve the treatment of gliomas. CONCLUSIONS The choice between LITT and FUS should be tailored to each case, considering factors such as tumor characteristics and patient health. LITT is favored for larger, complex tumors, while FUS is standard for smaller, deep-seated ones. Both techniques are equally effective for small and superficial tumors. Our study provides clear guidance for treating pediatric low-grade gliomas and highlights the crucial roles of LITT and FUS in managing high-grade gliomas in adults. This research sets the stage for improved patient care and future developments in the field of neurosurgery.
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Affiliation(s)
- Matteo De Simone
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (V.C.); (G.P.); (G.I.)
| | - Valeria Conti
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (V.C.); (G.P.); (G.I.)
- Clinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi, D’Aragona”, 84131 Salerno, Italy
| | - Giuseppina Palermo
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (V.C.); (G.P.); (G.I.)
| | - Lucio De Maria
- Unit of Neurosurgery, Department of Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, 25123 Brescia, Italy;
- Unit of Neurosurgery, Department of Clinical Neuroscience, Geneva University Hospitals (HUG), 1205 Geneva, Switzerland
| | - Giorgio Iaconetta
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Via S. Allende, 84081 Baronissi, Italy; (V.C.); (G.P.); (G.I.)
- Neurosurgery Unit, University Hospital “San Giovanni di Dio e Ruggi, D’Aragona”, 84131 Salerno, Italy
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18
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Banu MA, McKhann GM. Maximizing Extent of Resection for Noneloquent Glioblastoma: Fluorescent Dye or Intraoperative Magnetic Resonance Imaging? J Clin Oncol 2023; 41:5493-5496. [PMID: 37722089 DOI: 10.1200/jco.23.00963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 07/31/2023] [Accepted: 08/08/2023] [Indexed: 09/20/2023] Open
Affiliation(s)
- Matei A Banu
- Department of Neurological Surgery, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, NY
| | - Guy M McKhann
- Department of Neurological Surgery, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, NY
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Toader C, Eva L, Costea D, Corlatescu AD, Covache-Busuioc RA, Bratu BG, Glavan LA, Costin HP, Popa AA, Ciurea AV. Low-Grade Gliomas: Histological Subtypes, Molecular Mechanisms, and Treatment Strategies. Brain Sci 2023; 13:1700. [PMID: 38137148 PMCID: PMC10741942 DOI: 10.3390/brainsci13121700] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization's grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care.
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Affiliation(s)
- Corneliu Toader
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
- Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania
| | - Lucian Eva
- Department of Neurosurgery, Dunarea de Jos University, 800010 Galati, Romania
- Department of Neurosurgery, Clinical Emergency Hospital “Prof. Dr. Nicolae Oblu”, 700309 Iasi, Romania
| | - Daniel Costea
- Department of Neurosurgery, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Antonio Daniel Corlatescu
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Razvan-Adrian Covache-Busuioc
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Bogdan-Gabriel Bratu
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Luca Andrei Glavan
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Horia Petre Costin
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Andrei Adrian Popa
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
| | - Alexandru Vlad Ciurea
- Department of Neurosurgery, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.T.); (A.D.C.); (R.-A.C.-B.); (B.-G.B.); (L.A.G.); (H.P.C.); (A.A.P.); (A.V.C.)
- Neurosurgery Department, Sanador Clinical Hospital, 010991 Bucharest, Romania
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20
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Young JS, Morshed RA, Hervey-Jumper SL, Berger MS. The surgical management of diffuse gliomas: Current state of neurosurgical management and future directions. Neuro Oncol 2023; 25:2117-2133. [PMID: 37499054 PMCID: PMC10708937 DOI: 10.1093/neuonc/noad133] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Indexed: 07/29/2023] Open
Abstract
After recent updates to the World Health Organization pathological criteria for diagnosing and grading diffuse gliomas, all major North American and European neuro-oncology societies recommend a maximal safe resection as the initial management of a diffuse glioma. For neurosurgeons to achieve this goal, the surgical plan for both low- and high-grade gliomas should be to perform a supramaximal resection when feasible based on preoperative imaging and the patient's performance status, utilizing every intraoperative adjunct to minimize postoperative neurological deficits. While the surgical approach and technique can vary, every effort must be taken to identify and preserve functional cortical and subcortical regions. In this summary statement on the current state of the field, we describe the tools and technologies that facilitate the safe removal of diffuse gliomas and highlight intraoperative and postoperative management strategies to minimize complications for these patients. Moreover, we discuss how surgical resections can go beyond cytoreduction by facilitating biological discoveries and improving the local delivery of adjuvant chemo- and radiotherapies.
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Affiliation(s)
- Jacob S Young
- Department of Neurological Surgery, University of California, San Francisco, USA
| | - Ramin A Morshed
- Department of Neurological Surgery, University of California, San Francisco, USA
| | | | - Mitchel S Berger
- Department of Neurological Surgery, University of California, San Francisco, USA
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21
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Ramos-Fresnedo A, Al-Kharboosh R, Twohy EL, Basil AN, Szymkiewicz EC, Zubair AC, Trifiletti DM, Durand N, Dickson DW, Middlebrooks EH, Abarbanel DN, Tzeng SY, Almeida JP, Chaichana KL, Green JJ, Sherman WJ, Quiñones-Hinojosa A. Phase 1, Dose Escalation, Nonrandomized, Open-Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol. NEUROSURGERY PRACTICE 2023; 4:e00062. [PMID: 38464470 PMCID: PMC10923529 DOI: 10.1227/neuprac.0000000000000062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 02/18/2025]
Abstract
Background and Objectives Despite standard of care with maximal safe resection and chemoradiation, glioblastoma is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering, and before initiating concomitant chemoradiation. To assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent glioblastoma (GBM). Secondary objectives are to assess the toxicity profile and long-term survival outcomes of patients enrolled in the trial. Additionally, biospecimens will be collected to explore the local and systemic responses to this therapy. Methods We will conduct a phase 1, dose escalated, non-randomized, open label, clinical trial of GBM patients who are undergoing surgical resection for recurrence. Up to 18 patients will receive intra-cavitary application of AMSCs encapsulated in fibrin glue during surgical resection. All patients will be followed for up to 5 years for safety and survival data. Adverse events will be recorded using the CTCAE V5.0. Expected Outcomes This study will explore the maximum tolerated dose (MTD) of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM. Additionally, preliminary long-term survival and progression-free survival outcome analysis will be used to power further randomized studies. Lastly, CSF and blood will be obtained throughout the treatment period to investigate circulating molecular and inflammatory tumoral/stem cell markers and explore the mechanism of action of the therapeutic intervention. Discussion This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM. It will also provide additional survival metrics for future randomized trials.
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Affiliation(s)
| | | | - Erin L. Twohy
- Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Abba C. Zubair
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA
- Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Nisha Durand
- Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, Florida, USA
| | - Dennis W. Dickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA
| | - Erik H. Middlebrooks
- Department of Radiology, Neuroradiology Division, Mayo Clinic, Jacksonville, Florida, USA
| | - David N. Abarbanel
- Department of Neurology, Neuro-Oncology Division, Mayo Clinic, Jacksonville, Florida, USA
| | - Stephany Y. Tzeng
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA
| | | | | | - Jordan J. Green
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA
| | - Wendy J. Sherman
- Department of Neurology, Neuro-Oncology Division, Mayo Clinic, Jacksonville, Florida, USA
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22
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Mondal A, Kang J, Kim D. Recent Progress in Fluorescent Probes for Real-Time Monitoring of Glioblastoma. ACS APPLIED BIO MATERIALS 2023; 6:3484-3503. [PMID: 36917648 DOI: 10.1021/acsabm.3c00052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Treating glioblastoma (GBM) by resecting to a large extent can prolong a patient's survival by controlling the tumor cells, but excessive resection may produce postoperative complications by perturbing the brain structures. Therefore, various imaging procedures have been employed to successfully diagnose and resect with utmost caution and to protect vital structural or functional features. Fluorescence tagging is generally used as an intraoperative imaging technique in glioma cells in collaboration with other surgical tools such as MRI and navigation methods. However, the existing fluorescent probes may have several limitations, including poor selectivity, less photostability, false signals, and intraoperative re-administration when used in clinical and preclinical studies for glioma surgery. The involvement of smart fluorogenic materials, specifically fluorescent dyes, and biomarker-amended cell-penetrable fluorescent probes have noteworthy advantages for precise glioma imaging. This review outlines the contemporary advancements of fluorescent probes for imaging glioma cells along with their challenges and visions, with the anticipation to develop next-generation smart glioblastoma detection modalities.
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Affiliation(s)
- Amita Mondal
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Jisoo Kang
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, South Korea
| | - Dokyoung Kim
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, South Korea
- Center for Converging Humanities, Kyung Hee University, Seoul 02447, Republic of Korea
- Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul 02447, Republic of Korea
- Materials Research Science and Engineering Center, University of California at San Diego, 9500 Gilman Drive La Jolla, California 92093, United States
- Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
- KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea
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23
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Yuan Y, Su Y, Wu Y, Xue Y, Zhang Y, Zhang Y, Zheng M, Chang T, Qu Y, Zhao T. Knowledge structure and hotspots research of glioma immunotherapy: a bibliometric analysis. Front Oncol 2023; 13:1229905. [PMID: 37671057 PMCID: PMC10476340 DOI: 10.3389/fonc.2023.1229905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 08/03/2023] [Indexed: 09/07/2023] Open
Abstract
Background Glioma is the most common primary brain tumor. Traditional treatments for glioma include surgical resection, radiotherapy, chemotherapy, and bevacizumab therapy, but their efficacies are limited. Immunotherapy provides a new direction for glioma treatment. This study aimed to summarize the knowledge structure and research hotspots of glioma immunotherapy through a bibliometric analysis. Method Publications pertaining to glioma immunotherapy published during the period from 1st January 1990 to 27th March 2023 were downloaded from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, Online Analysis Platform of Literature Metrology, and R software. The hotspots and prospects of glioma immunotherapy research were illustrated via analyzing the countries, institutions, journals, authors, citations and keywords of eligible publications. Results A total of 1,929 publications pertaining to glioma immunotherapy in 502 journals were identified as of 27th March 2023, involving 9,505 authors from 1,988 institutions in 62 countries. Among them were 1,285 articles and 644 reviews. Most of publications were produced by the United States. JOURNAL OF NEURO-ONCOLOGY published the majority of publications pertaining to glioma immunotherapy. Among the authors, Lim M contributed the largest number of publications. Through analyzing keyword bursts and co-cited references, immune-checkpoint inhibitors (ICIs) were identified as the research focus and hotspot. Conclusion Using a bibliometric analysis, this study provided the knowledge structure and research hotspots in glioma immunotherapy research during the past 33 years, with ICIs staying in the current and future hotspot. Our findings may direct the research of glioma immunotherapy in the future.
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Affiliation(s)
- Yexin Yuan
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yue Su
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yingxi Wu
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yafei Xue
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yunze Zhang
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yangyang Zhang
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Min Zheng
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Ting Chang
- Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Yan Qu
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
| | - Tianzhi Zhao
- Department of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, China
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24
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Mofatteh M, Mashayekhi MS, Arfaie S, Adeleye AO, Jolayemi EO, Ghomsi NC, Shlobin NA, Morsy AA, Esene IN, Laeke T, Awad AK, Labuschagne JJ, Ruan R, Abebe YN, Jabang JN, Okunlola AI, Barrie U, Lekuya HM, Idi Marcel E, Kabulo KDM, Bankole NDA, Edem IJ, Ikwuegbuenyi CA, Nguembu S, Zolo Y, Bernstein M. Awake Craniotomy in Africa: A Scoping Review of Literature and Proposed Solutions to Tackle Challenges. Neurosurgery 2023; 93:274-291. [PMID: 36961213 PMCID: PMC10319364 DOI: 10.1227/neu.0000000000002453] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/10/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Awake craniotomy (AC) is a common neurosurgical procedure for the resection of lesions in eloquent brain areas, which has the advantage of avoiding general anesthesia to reduce associated complications and costs. A significant resource limitation in low- and middle-income countries constrains the usage of AC. OBJECTIVE To review the published literature on AC in African countries, identify challenges, and propose pragmatic solutions by practicing neurosurgeons in Africa. METHODS We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review guidelines across 3 databases (PubMed, Scopus, and Web of Science). English articles investigating AC in Africa were included. RESULTS Nineteen studies consisting of 396 patients were included. Egypt was the most represented country with 8 studies (42.1%), followed by Nigeria with 6 records (31.6%). Glioma was the most common lesion type, corresponding to 120 of 396 patients (30.3%), followed by epilepsy in 71 patients (17.9%). Awake-awake-awake was the most common protocol used in 7 studies (36.8%). Sixteen studies (84.2%) contained adult patients. The youngest reported AC patient was 11 years old, whereas the oldest one was 92. Nine studies (47.4%) reported infrastructure limitations for performing AC, including the lack of funding, intraoperative monitoring equipment, imaging, medications, and limited human resources. CONCLUSION Despite many constraints, AC is being safely performed in low-resource settings. International collaborations among centers are a move forward, but adequate resources and management are essential to make AC an accessible procedure in many more African neurosurgical centers.
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Affiliation(s)
- Mohammad Mofatteh
- School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK
| | | | - Saman Arfaie
- School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK
- Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
| | - Amos Olufemi Adeleye
- Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Nathalie C. Ghomsi
- Neurosurgery Department, Felix Houphouet Boigny Unversity Abidjan, Cote d’Ivoire
| | - Nathan A. Shlobin
- Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Ahmed A. Morsy
- Department of Neurosurgery, Zagazig University, Zagazig, Egypt
| | - Ignatius N. Esene
- Neurosurgery Division, Faculty of Health Sciences, University of Bamenda, Bambili, Cameroon
| | - Tsegazeab Laeke
- Neurosurgery Division, Department of Surgery, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ahmed K. Awad
- Faculty of Medicine, Ain-shams University, Cairo, Egypt
| | - Jason J. Labuschagne
- Department of Neurosurgery, University of the Witwatersrand, Johannesburg, South Africa
| | - Richard Ruan
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, USA
| | - Yared Nigusie Abebe
- Department of Neurosurgery, Haramaya University Hiwot Fana Comprehensive Specialized Hospital, Harar, Ethiopia
| | | | - Abiodun Idowu Okunlola
- Department of Surgery, Federal Teaching Hospital Ido Ekiti and Afe Babalola University, Ado Ekiti, Nigeria
| | - Umaru Barrie
- Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Hervé Monka Lekuya
- Department of Neurosurgery, Makerere University/Mulago Hospital, Kampala, Uganda
| | - Ehanga Idi Marcel
- Department of Neurosurgery, College of Surgeons of East, Central and Southern Africa/Mulago Hospital, Kampala, Uganda
| | - Kantenga Dieu Merci Kabulo
- Department of Neurosurgery, Jason Sendwe General Provincial Hospital, Lubumbashi, Democratic Republic of the Congo
| | - Nourou Dine Adeniran Bankole
- Department of Neurosurgery, Hôpital Des Spécialités, WFNS Rabat Training Center For Young, African Neurosurgeons, Faculty of Medicine, Mohammed V University, Rabat, Morocco
| | - Idara J. Edem
- Department of Surgery, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | | | - Stephane Nguembu
- Department of Neurosurgery, Higher Institute of Health Sciences, Université des Montagnes, Bangangté, Cameroon
| | - Yvan Zolo
- Global Surgery Division, University of Cape Town, Cape Town, South Africa
| | - Mark Bernstein
- Division of Neurosurgery, Department of Surgery, University of Toronto, University Health Network, Toronto, Ontario, Canada
- Temmy Latner Center for Palliative Care, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
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25
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Tran S, Thomas A, Aliouat I, Karachi C, Lozano F, Mokhtari K, Dehais C, Feuvret L, Carpentier C, Giry M, Doukani A, Lerond J, Marie Y, Sanson M, Idbaih A, Carpentier A, Hoang-Xuan K, Touat M, Capelle L, Bielle F. A threshold for mitotic activity and post-surgical residual volume defines distinct prognostic groups for astrocytoma IDH-mutant. Neuropathol Appl Neurobiol 2023; 49:e12928. [PMID: 37503540 DOI: 10.1111/nan.12928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 07/13/2023] [Accepted: 07/22/2023] [Indexed: 07/29/2023]
Abstract
AIMS The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow-up and adjuvant treatment for resected astrocytomas IDH-mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre-IDH era. METHODS Maximal mitotic activity in consecutive high-power fields corresponding to 3 mm2 was examined for 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumour volume, multilobar involvement, post-surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation. RESULTS Seventy-one per cent of the samples had <6 mitoses per 3 mm2 . Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm2 identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm3 also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm2 and a residual volume <1 cm3 had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours. CONCLUSIONS Mitotic activity and post-surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH-mutant. Patients with <6 mitoses per 3 mm2 and a residual volume <1 cm3 were the best candidates for observational follow-up.
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Affiliation(s)
- Suzanne Tran
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neuropathology, Paris, France
| | - Alice Thomas
- Department of Radiation Oncology, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France
| | - Ilyes Aliouat
- Department of Neurosurgery, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Paris, France
| | - Carine Karachi
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Department of Neurosurgery, Paris, France
| | - Fernando Lozano
- AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Karima Mokhtari
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neuropathology, Paris, France
| | - Caroline Dehais
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Loïc Feuvret
- AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Department of Radiotherapy, Paris, France
| | - Catherine Carpentier
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Marine Giry
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
| | - Abiba Doukani
- Sorbonne Université, Inserm, UMS Production et Analyse des données en Sciences de la vie et en Santé, PASS, Plateforme Post-génomique Pitié-Salpêtrière, P3S, Paris, France
| | - Julie Lerond
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
- Sorbonne Université, AP-HP, Paris, France
| | - Yannick Marie
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
| | - Marc Sanson
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
- Sorbonne Université, AP-HP, Paris, France
- Department of Neuropathology, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
| | - Ahmed Idbaih
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Alexandre Carpentier
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Department of Neurosurgery, Paris, France
| | - Khê Hoang-Xuan
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Mehdi Touat
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neurology 2, Paris, France
| | - Laurent Capelle
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, Department of Neurosurgery, Paris, France
| | - Franck Bielle
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Universitaire Pitié-Salpêtrière, DMU Neurosciences, Department of Neuropathology, Paris, France
- Sorbonne Université, AP-HP, Paris, France
- Department of Neuropathology, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
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Peters DR, Halimi F, Ozduman K, Levivier M, Conti A, Reyns N, Tuleasca C. Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome-a systematic review and meta-analysis. Neurosurg Rev 2023; 46:185. [PMID: 37498398 PMCID: PMC10374773 DOI: 10.1007/s10143-023-02064-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 07/28/2023]
Abstract
Independently, both 5-aminolevulinic acid (5-ALA) and intraoperative neuromonitoring (IONM) have been shown to improve outcomes with high-grade gliomas (HGG). The interplay and overlap of both techniques are scarcely reported in the literature. We performed a systematic review and meta-analysis focusing on the concomitant use of 5-ALA and intraoperative mapping for HGG located within eloquent cortex. Using PRISMA guidelines, we reviewed articles published between May 2006 and December 2022 for patients with HGG in eloquent cortex who underwent microsurgical resection using intraoperative mapping and 5-ALA fluorescence guidance. Extent of resection was the primary outcome. The secondary outcome was new neurological deficit at day 1 after surgery and persistent at day 90 after surgery. Overall rate of complete resection of the enhancing tumor (CRET) was 73.3% (range: 61.9-84.8%, p < .001). Complete 5-ALA resection was performed in 62.4% (range: 28.1-96.7%, p < .001). Surgery was stopped due to mapping findings in 20.5% (range: 15.6-25.4%, p < .001). Neurological decline at day 1 after surgery was 29.2% (range: 9.8-48.5%, p = 0.003). Persistent neurological decline at day 90 after surgery was 4.6% (range: 0.4-8.7%, p = 0.03). Maximal safe resection guided by IONM and 5-ALA for high-grade gliomas in eloquent areas is achievable in a high percentage of cases (73.3% CRET and 62.4% complete 5-ALA resection). Persistent neurological decline at postoperative day 90 is as low as 4.6%. A balance between 5-ALA and IONM should be maintained for a better quality of life while maximizing oncological control.
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Affiliation(s)
- David R Peters
- Department of Neurosurgery, Atrium Health, Charlotte, NC, USA.
- Neurosurgery Service and Gamma Knife Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - Floriana Halimi
- Neurosurgery Service and Gamma Knife Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Koray Ozduman
- Department of Neurosurgery, School of Medicine, Acibadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Marc Levivier
- Neurosurgery Service and Gamma Knife Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology and Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Alfredo Conti
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy
- Dipartimento Di Scienze Biomediche E Neuromotorie (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Nicolas Reyns
- Neurosurgery and Neurooncology Service, Centre Hospitalier Regional Universitaire de Lille, Roger Salengro Hospital, Lille, France
| | - Constantin Tuleasca
- Neurosurgery Service and Gamma Knife Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology and Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
- Ecole Polytechnique Fédérale de Lausanne (EPFL, LTS-5), Lausanne, Switzerland
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da Costa MDS, Sarti THM, Vaz H, Dastoli PA, Nicácio JM, Silva FAB, Cappellano AM, Silva NS, Cavalheiro S. Risk for hydrocephalus, hygroma, and tumor dissemination after ventricular opening during resection of supratentorial neoplasms in children. Childs Nerv Syst 2023; 39:1881-1887. [PMID: 36715744 DOI: 10.1007/s00381-023-05861-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 01/22/2023] [Indexed: 01/31/2023]
Abstract
PURPOSE The possibility that ventricular opening generates postoperative complications after surgical tumor treatment often restricts the degree of tumor resection. This study aims to determine whether the ventricular opening is associated with more complications in surgeries for resectioning supratentorial intra-axial brain tumors in the pediatric population. METHODS A retrospective review analysis was performed of patients treated at IOP/GRAACC between 2002 and 2020 under 19 years of age and underwent surgery for supratentorial intra-axial primary brain tumor resection. Data were collected from 43 patients. RESULTS Glial tumor was more common than non-glial (65% vs. 35%, p = 0.09). The ventricular opening was not related to neoplastic spreads to the neuroaxis (6% vs. 0, p > 0.9) or leptomeningeal (3% vs. 0, p > 0.9). Of the patients whose ventricle was opened, 10% developed hydrocephalus requiring treatment, while none of the patients in the group without ventricular opening developed hydrocephalus (p = 0.5). There was also no statistical difference regarding ventriculitis. Postoperative subdural hygroma formation correlated with the ventricular opening (43% vs. 0, p = 0.003). The survival at 1, 5, and 10 years of cases with the ventricular opening was 93.2%, 89.7%, and 75.7%, respectively, while in cases without ventricular opening, it was 100%, 83%, and 83%, respectively, respectively, with no statistical difference between the mortality curves. CONCLUSION Our study demonstrated that ventricular violation was not associated with the occurrence of significant complications. It was related to the formation of subdural hygroma, which did not require additional treatment.
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Affiliation(s)
- Marcos Devanir Silva da Costa
- Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Division of Neurosurgery, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | | | - Herison Vaz
- Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Division of Neurosurgery, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | - Patricia Alessandra Dastoli
- Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Division of Neurosurgery, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | - Jardel Mendonça Nicácio
- Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Division of Neurosurgery, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | | | - Andrea Maria Cappellano
- Division of Neuro-Oncology, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | - Nasjla Saba Silva
- Division of Neuro-Oncology, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
| | - Sergio Cavalheiro
- Department of Neurology and Neurosurgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Division of Neurosurgery, Instituto de Oncologia Pediatrica (IOP/GRAACC), Sao Paulo, Brazil
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28
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Mazzucchi E, Hiepe P, Langhof M, La Rocca G, Pignotti F, Rinaldi P, Sabatino G. Automatic rigid image Fusion of preoperative MR and intraoperative US acquired after craniotomy. Cancer Imaging 2023; 23:37. [PMID: 37055790 PMCID: PMC10099637 DOI: 10.1186/s40644-023-00554-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 04/05/2023] [Indexed: 04/15/2023] Open
Abstract
BACKGROUND Neuronavigation of preoperative MRI is limited by several errors. Intraoperative ultrasound (iUS) with navigated probes that provide automatic superposition of pre-operative MRI and iUS and three-dimensional iUS reconstruction may overcome some of these limitations. Aim of the present study is to verify the accuracy of an automatic MRI - iUS fusion algorithm to improve MR-based neuronavigation accuracy. METHODS An algorithm using Linear Correlation of Linear Combination (LC2)-based similarity metric has been retrospectively evaluated for twelve datasets acquired in patients with brain tumor. A series of landmarks were defined both in MRI and iUS scans. The Target Registration Error (TRE) was determined for each pair of landmarks before and after the automatic Rigid Image Fusion (RIF). The algorithm has been tested on two conditions of the initial image alignment: registration-based fusion (RBF), as given by the navigated ultrasound probe, and different simulated course alignments during convergence test. RESULTS Except for one case RIF was successfully applied in all patients considering the RBF as initial alignment. Here, mean TRE after RBF was significantly reduced from 4.03 (± 1.40) mm to (2.08 ± 0.96 mm) (p = 0.002), after RIF. For convergence test, the mean TRE value after initial perturbations was 8.82 (± 0.23) mm which has been reduced to a mean TRE of 2.64 (± 1.20) mm after RIF (p < 0.001). CONCLUSIONS The integration of an automatic image fusion method for co-registration of pre-operative MRI and iUS data may improve the accuracy in MR-based neuronavigation.
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Affiliation(s)
- Edoardo Mazzucchi
- Unit of Neurosurgery, Mater Olbia Hospital, Olbia, Italy.
- Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University, Rome, Italy.
| | | | | | - Giuseppe La Rocca
- Unit of Neurosurgery, Mater Olbia Hospital, Olbia, Italy
- Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University, Rome, Italy
| | - Fabrizio Pignotti
- Unit of Neurosurgery, Mater Olbia Hospital, Olbia, Italy
- Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University, Rome, Italy
| | | | - Giovanni Sabatino
- Unit of Neurosurgery, Mater Olbia Hospital, Olbia, Italy
- Institute of Neurosurgery, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Catholic University, Rome, Italy
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Hervey-Jumper SL, Zhang Y, Phillips JJ, Morshed RA, Young JS, McCoy L, Lafontaine M, Luks T, Ammanuel S, Kakaizada S, Egladyous A, Gogos A, Villanueva-Meyer J, Shai A, Warrier G, Rice T, Crane J, Wrensch M, Wiencke JK, Daras M, Oberheim Bush NA, Taylor JW, Butowski N, Clarke J, Chang S, Chang E, Aghi M, Theodosopoulos P, McDermott M, Jakola AS, Kavouridis VK, Nawabi N, Solheim O, Smith T, Berger MS, Molinaro AM. Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma. J Clin Oncol 2023; 41:2029-2042. [PMID: 36599113 PMCID: PMC10082290 DOI: 10.1200/jco.21.02929] [Citation(s) in RCA: 75] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 08/18/2022] [Accepted: 11/14/2022] [Indexed: 01/06/2023] Open
Abstract
PURPOSE In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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Affiliation(s)
- Shawn L. Hervey-Jumper
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Yalan Zhang
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Joanna J. Phillips
- Department of Pathology, University of California, San Francisco, San Francisco, CA
| | - Ramin A. Morshed
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Jacob S. Young
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Lucie McCoy
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Marisa Lafontaine
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Tracy Luks
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Simon Ammanuel
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Sofia Kakaizada
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Andrew Egladyous
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Andrew Gogos
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Javier Villanueva-Meyer
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Anny Shai
- Department of Pathology, University of California, San Francisco, San Francisco, CA
| | - Gayathri Warrier
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Terri Rice
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Jason Crane
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Margaret Wrensch
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - John K. Wiencke
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Mariza Daras
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
- Department of Neurology, University of California, San Francisco, San Francisco, CA
| | - Nancy Ann Oberheim Bush
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
- Department of Neurology, University of California, San Francisco, San Francisco, CA
| | - Jennie W. Taylor
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
- Department of Neurology, University of California, San Francisco, San Francisco, CA
| | - Nicholas Butowski
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Jennifer Clarke
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
- Department of Neurology, University of California, San Francisco, San Francisco, CA
| | - Susan Chang
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
- Department of Neurology, University of California, San Francisco, San Francisco, CA
| | - Edward Chang
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Manish Aghi
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Philip Theodosopoulos
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Michael McDermott
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Asgeir S. Jakola
- Department of Neurological Surgery, St Olavs University Hospital, Trondheim, Norway
- Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
| | | | - Noah Nawabi
- Department of Neurological Surgery, Brigham and Women's Hospital, Boston, MA
| | - Ole Solheim
- Department of Neurological Surgery, St Olavs University Hospital, Trondheim, Norway
- Norwegian University of Science and Technology, Trondheim, Norway
| | - Timothy Smith
- Department of Neurological Surgery, Brigham and Women's Hospital, Boston, MA
| | - Mitchel S. Berger
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
| | - Annette M. Molinaro
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA
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30
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Demetz M, Krigers A, Moser P, Kerschbaumer J, Thomé C, Freyschlag CF. Same but different. Incidental and symptomatic lower grade gliomas show differences in molecular features and survival. J Neurooncol 2023; 162:397-405. [PMID: 37043120 PMCID: PMC10167120 DOI: 10.1007/s11060-023-04301-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 03/20/2023] [Indexed: 04/13/2023]
Abstract
PURPOSE Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate differences between patients with iLGG and sLGG. METHODS All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors' institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients' charts. If IDH1, ATRX and EGFR were not routinely assessed, they were re-determined. RESULTS Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n = 12), trauma(n = 2), MRI indicated by other departments(n = 7), staging examination for cancer(n = 1), volunteering for MRI sequence testing(n = 1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p = 0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p = 0.008), FLAIR (p = 0.038) and DWI (p = 0.028). Incidental LGG demonstrated significantly lower incidence of anaplasia (p = 0.004) and lower expression of MIB-1 (p = 0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p = 0.024). Incidental LGG showed a significantly longer OS (mean 212 vs. 70 months, p = 0.005) and PFS (mean 201 vs. 61 months, p = 0.001) compared to sLGG. CONCLUSION Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG.
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Affiliation(s)
- Matthias Demetz
- Department of Neurosurgery, Medical University of Innsbruck, Anichstr. 35, Innsbruck, AT-6020, Austria
| | - Aleksandrs Krigers
- Department of Neurosurgery, Medical University of Innsbruck, Anichstr. 35, Innsbruck, AT-6020, Austria
| | - Patrizia Moser
- Department of Neuropathology, University Hospital Innsbruck, Tirol Kliniken, Innsbruck, Austria
| | - Johannes Kerschbaumer
- Department of Neurosurgery, Medical University of Innsbruck, Anichstr. 35, Innsbruck, AT-6020, Austria
| | - Claudius Thomé
- Department of Neurosurgery, Medical University of Innsbruck, Anichstr. 35, Innsbruck, AT-6020, Austria
| | - Christian F Freyschlag
- Department of Neurosurgery, Medical University of Innsbruck, Anichstr. 35, Innsbruck, AT-6020, Austria.
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31
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Current Trends in Neurosurgical Management of Adult Diffuse Low-Grade Gliomas in Canada. Can J Neurol Sci 2023; 50:278-281. [PMID: 35510291 DOI: 10.1017/cjn.2022.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
There is considerable variability in the management of diffuse low-grade gliomas (LGGs). To characterize treatment paradigms, a survey of Canadian neurosurgeons was performed with forty neurosurgeons responding. Their responses show that the management of patients with LGGs has evolved in the past decade and findings from the RTOG9802 trial have been integrated into the practice of Canadian neurosurgeons. Most respondents stated that the patient selection and treatment strategy advocated by the RTOG9802 trial needs further evaluation. Overall, there is a trend toward more aggressive surgical resections, and future investigations will have to more accurately stratify patient risk profiles.
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32
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Lavalle L, D'Elia A, Ciavarro M, Esposito V. Subpial technique in supratentorial glioma resection: state of the art and analysis of costs and effectiveness in a single institute experience. J Neurosurg Sci 2023; 67:73-82. [PMID: 32989970 DOI: 10.23736/s0390-5616.20.05046-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Many neurosurgeons advocate subpial technique as the best technique to remove supratentorial gliomas. However, few authors clearly defined advantages and features of this technique. The aim of our study is to describe microsurgical subpial technique related to glioma surgery, with regard to its safety and cost effectiveness. METHODS We analyzed retrospectively all consecutive patients surgically treated for supratentorial glioma from January 2017 to April 2018 at Neurosurgery Department of Neuromed Institute. All patients underwent to surgical glioma resection performing microsurgical subpial technique. Extent of resection and neurological complications were evaluated as primary outcomes; Karnofsky Performance Status and postoperative edema extent were secondary outcomes. Statistical analysis was obtained. RESULTS The study included 70 patients. Gross Total Removal was obtained in 91.3% of patients with low grade glioma (LGG) and in 81% of patients with high grade glioma. Neurological complications amounted to 34% at early assessment in LGG patients, which were permanent at 3 months in 17% of patients. In high grade glioma patients, neurological complications amounted to 51% at early assessment, which were permanent at 3 months in 25% of them. CONCLUSIONS We obtained good postoperative results with regard to the extent of tumor resection using this technique. Subpial resection is an effective surgical technique to get a safer and more complete tumor resection. It should be combined with other modern neurosurgical tools such as neuronavigation, ultrasound and cortical mapping to obtain the best tumor resection and functional neurological preservation.
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Affiliation(s)
- Laura Lavalle
- Department of Neurosurgery, IRCCS Neuromed, Pozzilli, Isernia, Italy -
| | - Alessandro D'Elia
- Department of Neurosurgery, IRCCS Neuromed, Pozzilli, Isernia, Italy
| | - Marco Ciavarro
- Department of Neurosurgery, IRCCS Neuromed, Pozzilli, Isernia, Italy
| | - Vincenzo Esposito
- Department of Neurosurgery, IRCCS Neuromed, Pozzilli, Isernia, Italy
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33
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Golpayegani M, Edalatfar M, Ahmadi A, Sadeghi-Naini M, Salari F, Hanaei S, Shokraneh F, Ghodsi Z, Vaccaro AR, Rahimi-Movaghar V. Complete Versus Incomplete Surgical Resection in Intramedullary Astrocytoma: Systematic Review with Individual Patient Data Meta-Analysis. Global Spine J 2023; 13:227-241. [PMID: 35486519 PMCID: PMC9837510 DOI: 10.1177/21925682221094766] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
STUDY DESIGN Systematic reviewBackground: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome. OBJECTIVE To compare the overall survival (OS) and neurologic outcomes of complete vs incomplete surgical resection for patients with intramedullary astrocytoma. METHODS A comprehensive search of MEDLINE, CENTRAL and EMBASE was conducted by two independent reviewers. Individual patient data (IPD) analysis and multivariate Cox Proportional Hazard Model was developed to measure the effect of surgical strategies on OS, post-operative neurological improvement (PNI), and neurological improvement in the last follow up (FNI). RESULTS We included 1079 patients from 35 studies. Individual patient data of 228 patients (13 articles) was incorporated into the integrative IPD analysis. Kaplan-Meier survival analysis showed complete resection (CR) significantly improved OS in comparison with the incomplete resection (IR) (log-rank test, P = .004). In the multivariate IPD analysis, three prognostic factors had significant effect on the OS: (1) Extent of Resection, (2) pathology grade, and (3) adjuvant therapy. We observed an upward trend in the popularity of chemotherapy, but CR, IR, and radiotherapy had relatively stable trends during three decades. CONCLUSION Our study shows that CR can improve OS when compared to IR. Patients with spinal cord astrocytoma undergoing CR had similar PNI and FNI compared to IR. Therefore, CR should be the primary goal of surgery, but intraoperative decisions on the extent of resection should be relied on to prevent neurologic adverse events. Due to significant effect of adjuvant therapy on OS, PNI and FNI, it could be considered as the routine treatment strategy for spinal cord astrocytoma.
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Affiliation(s)
- Mehdi Golpayegani
- Sina Trauma and Surgery Research
Center, Tehran University of Medical
Sciences, Tehran, Iran
| | - Maryam Edalatfar
- Sina Trauma and Surgery Research
Center, Tehran University of Medical
Sciences, Tehran, Iran
| | - Ayat Ahmadi
- Knowledge Utilization Research
Center, Tehran University of Medical
Sciences, Tehran, Iran
| | - Mohsen Sadeghi-Naini
- Sina Trauma and Surgery Research
Center, Tehran University of Medical
Sciences, Tehran, Iran,Department of Neurosurgery, Lorestan University of Medical
Sciences, Khoram-Abad, Iran
| | - Farhad Salari
- Eye Research Center, Farabi Eye
Hospital, Tehran University of Medical
Sciences, Tehran, Iran
| | - Sara Hanaei
- Department of Neurosurgery, Imam
Khomeini Hospital Complex, Tehran University of Medical Sciences
(TUMS), Tehran, Iran,Universal Scientific Education and
Research Network (USERN), Tehran, Iran
| | - Farhad Shokraneh
- Cochrane Schizophrenia Group, The Institute of Mental
Health, Nottingham, UK
| | - Zahra Ghodsi
- Sina Trauma and Surgery Research
Center, Tehran University of Medical
Sciences, Tehran, Iran
| | - Alex R. Vaccaro
- Department of Orthopedics and
Neurosurgery, Thomas Jefferson University and the
Rothman Institute, Philadelphia, PA, USA
| | - Vafa Rahimi-Movaghar
- Sina Trauma and Surgery Research
Center, Tehran University of Medical
Sciences, Tehran, Iran,Universal Scientific Education and
Research Network (USERN), Tehran, Iran,Brain and Spinal Cord Injury
Research Center, Neuroscience Institute, Tehran University of Medical
Sciences, Tehran, Iran,Department of Neurosurgery,
Shariati Hospital, Tehran University of Medical
Sciences, Tehran, Iran,Institute of Biochemistry and
Biophysics, University of Tehran, Tehran, Iran,Visiting Professor, Spine
Program, University of Toronto, Toronto, ON, Canada,Vafa Rahimi-Movaghar, MD, Sina Trauma and
Surgery Research Center, Tehran University of Medical Sciences, Hassan-Abad
Square, Tehran 1136746911, Iran.
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34
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Pyroptosis-Related Genes as Markers for Identifying Prognosis and Microenvironment in Low-Grade Glioma. JOURNAL OF HEALTHCARE ENGINEERING 2023; 2023:6603151. [PMID: 36820395 PMCID: PMC9938775 DOI: 10.1155/2023/6603151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/11/2022] [Accepted: 04/15/2022] [Indexed: 02/13/2023]
Abstract
Low-grade glioma (LGG) is one of the most common brain tumors and often develops into the worst glioblastoma (GBM). Pyroptosis is related to inflammation and immunization. It has been demonstrated to influence the progression of a variety of cancers. However, the value of pyrosis-related genes (PRGs) in LGG remains unclear. Public TCGA-LGG data are used to analyze the differential expression and genetic variation of PRGs in LGG. Subsequently, this paper identifies pyroptosis-related subtypes and constructs prognostic models. This paper analyzes the expression and function of selected CASP5 in LGG and constructs a ceRNA regulatory network. Final CASP5-related immune infiltration analysis and methylation analysis are performed. Most PRGs are differentially expressed and altered in LGG. Subtypes and prognostic models based on PRGs not only have good functions but also have a great connection with immune infiltration. Enrichment analysis of PRGs with prognostic value of LGG also shows functions correlated mainly with immunity and inflammation. CASP5 is significantly differentially expressed in different grades of gliomas and different prognoses. Despite fewer mutations, CASP5 has a clear correlation for both immune cells and immune checkpoint molecules in the LGG microenvironment. Its methylation may also have a role in the prognosis of LGG. This paper shows the association of pyrosis-related subtypes, prognostic models, and genes, with immune infiltration.
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Yao S, Yang R, Du C, Jiang C, Wang Y, Peng C, Bai H. Maximal safe resection of diffuse lower grade gliomas primarily within central lobe using cortical/subcortical direct electrical stimulation under awake craniotomy. Front Oncol 2023; 13:1089139. [PMID: 36895476 PMCID: PMC9990258 DOI: 10.3389/fonc.2023.1089139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 02/07/2023] [Indexed: 02/23/2023] Open
Abstract
Background Diffuse lower-grade glioma (DLGG) in the central lobe is a challenge for safe resection procedures. To improve the extent of resection and reduce the risk of postoperative neurological deficits, we performed an awake craniotomy with cortical-subcortical direct electrical stimulation (DES) mapping for patients with DLGG located primarily within the central lobe. We investigated the outcomes of cortical-subcortical brain mapping using DES in an awake craniotomy for central lobe DLGG resection. Methods We performed a retrospective analysis of clinical data of a cohort of consecutively treated patients from February 2017 to August 2021 with diffuse lower-grade gliomas located primarily within the central lobe. All patients underwent awake craniotomy with DES for cortical and subcortical mapping of eloquent brain areas, neuronavigation, and/or ultrasound to identify tumor location. Tumors were removed according to functional boundaries. Maximum safe tumor resection was the surgical objective for all patients. Results Thirteen patients underwent 15 awake craniotomies with intraoperative mapping of eloquent cortices and subcortical fibers using DES. Maximum safe tumor resection was achieved according to functional boundaries in all patients. The pre-operative tumor volumes ranged from 4.3 cm3 to 137.3 cm3 (median 19.2 cm3). The mean extent of tumor resection was 94.6%, with eight cases (53.3%) achieving total resection, four (26.7%) subtotal and three (20.0%) partial. The mean tumor residue was 1.2 cm3. All patients experienced early postoperative neurological deficits or worsening conditions. Three patients (20.0%) experienced late postoperative neurological deficits at the 3-month follow-up, including one moderate and two mild neurological deficits. None of the patients experienced late onset severe neurological impairments post-operatively. Ten patients with 12 tumor resections (80.0%) had resumed activities of daily living at the 3-month follow-up. Among 14 patients with pre-operative epilepsy, 12 (85.7%) were seizure-free after treatment with antiepileptic drugs 7 days after surgery up to the last follow-up. Conclusions DLGG located primarily in the central lobe deemed inoperable can be safely resected using awake craniotomy with intraoperative DES without severe permanent neurological sequelae. Patients experienced an improved quality of life in terms of seizure control.
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Affiliation(s)
- Shujing Yao
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Ruixin Yang
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Chenggang Du
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Che Jiang
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Yang Wang
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Chongqi Peng
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
| | - Hongmin Bai
- Department of Neurosurgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China
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Steiner G, Galli R, Preusse G, Michen S, Meinhardt M, Temme A, Sobottka SB, Juratli TA, Koch E, Schackert G, Kirsch M, Uckermann O. A new approach for clinical translation of infrared spectroscopy: exploitation of the signature of glioblastoma for general brain tumor recognition. J Neurooncol 2023; 161:57-66. [PMID: 36509907 PMCID: PMC9886632 DOI: 10.1007/s11060-022-04204-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/01/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Infrared (IR) spectroscopy has the potential for tumor delineation in neurosurgery. Previous research showed that IR spectra of brain tumors are generally characterized by reduced lipid-related and increased protein-related bands. Therefore, we propose the exploitation of these common spectral changes for brain tumor recognition. METHODS Attenuated total reflection IR spectroscopy was performed on fresh specimens of 790 patients within minutes after resection. Using principal component analysis and linear discriminant analysis, a classification model was developed on a subset of glioblastoma (n = 135) and non-neoplastic brain (n = 27) specimens, and then applied to classify the IR spectra of several types of brain tumors. RESULTS The model correctly classified 82% (517/628) of specimens as "tumor" or "non-tumor", respectively. While the sensitivity was limited for infiltrative glioma, this approach recognized GBM (86%), other types of primary brain tumors (92%) and brain metastases (92%) with high accuracy and all non-tumor samples were correctly identified. CONCLUSION The concept of differentiation of brain tumors from non-tumor brain based on a common spectroscopic tumor signature will accelerate clinical translation of infrared spectroscopy and related technologies. The surgeon could use a single instrument to detect a variety of brain tumor types intraoperatively in future clinical settings. Our data suggests that this would be associated with some risk of missing infiltrative regions or tumors, but not with the risk of removing non-tumor brain.
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Affiliation(s)
- Gerald Steiner
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Roberta Galli
- Medical Physics and Biomedical Engineering, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Grit Preusse
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Susanne Michen
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany
| | - Matthias Meinhardt
- Department of Pathology (Neuropathology), University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Achim Temme
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany ,National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany ,German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stephan B. Sobottka
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany
| | - Tareq A. Juratli
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany
| | - Edmund Koch
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Gabriele Schackert
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany ,National Center for Tumor Diseases (NCT), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany ,German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Ortrud Uckermann
- Department of Neurosurgery, University Hospital Carl Gustav Carus, TU, Dresden, Germany ,Division of Medical Biology, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany
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Kögl FV, Léger É, Haouchine N, Torio E, Juvekar P, Navab N, Kapur T, Pieper S, Golby A, Frisken S. A Tool-free Neuronavigation Method based on Single-view Hand Tracking. COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING. IMAGING & VISUALIZATION 2022; 11:1307-1315. [PMID: 37457380 PMCID: PMC10348700 DOI: 10.1080/21681163.2022.2163428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/19/2022] [Indexed: 12/30/2022]
Abstract
This work presents a novel tool-free neuronavigation method that can be used with a single RGB commodity camera. Compared with freehand craniotomy placement methods, the proposed system is more intuitive and less error prone. The proposed method also has several advantages over standard neuronavigation platforms. First, it has a much lower cost, since it doesn't require the use of an optical tracking camera or electromagnetic field generator, which are typically the most expensive parts of a neuronavigation system, making it much more accessible. Second, it requires minimal setup, meaning that it can be performed at the bedside and in circumstances where using a standard neuronavigation system is impractical. Our system relies on machine-learning-based hand pose estimation that acts as a proxy for optical tool tracking, enabling a 3D-3D pre-operative to intra-operative registration. Qualitative assessment from clinical users showed that the concept is clinically relevant. Quantitative assessment showed that on average a target registration error (TRE) of 1.3cm can be achieved. Furthermore, the system is framework-agnostic, meaning that future improvements to hand-tracking frameworks would directly translate to a higher accuracy.
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Affiliation(s)
- Fryderyk Victor Kögl
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
- Computer Aided Medical Procedures, Technische Universität München, Munich, Germany
| | - Étienne Léger
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Nazim Haouchine
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Erickson Torio
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Parikshit Juvekar
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Nassir Navab
- Computer Aided Medical Procedures, Technische Universität München, Munich, Germany
- Whiting School of Engineering, Johns Hopkins University, Baltimore, USA
| | - Tina Kapur
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Steve Pieper
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
- Isomics, Inc., Cambridge, MA, USA
| | - Alexandra Golby
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
| | - Sarah Frisken
- Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
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Chaulagain D, Smolanka V, Smolanka A, Munakomi S, Havryliv T. The role of extent of resection on the prognosis of low-grade astrocytoma: a systematic review and meta-analysis. EGYPTIAN JOURNAL OF NEUROSURGERY 2022. [DOI: 10.1186/s41984-022-00161-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Purpose
To investigate the predictor factors of mortality describing the prognosis of primary surgical resection of low-grade astrocytoma.
Materials and methods
A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to November 14, 2021. All statistical analysis was conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. A random-effect model was used when heterogeneity was seen to pool the studies, and the result were reported in the hazards ratio (HR) and corresponding 95% confidence interval.
Result
Five cohort studies were selected for meta-analysis. There was statistically significant effect of total resection on increase mortality after surgery in low-grade astrocytoma patients (HR = 0.70 [0.52, 0.94]; p = 0.02; I2 = Not applicable). On the other hand, there was statistically nonsignificant effect of patient’s age (HR = 1.27 [0.95, 1.68]; p = 0.11; I2 = 83%), tumor size (HR = 1.13 [0.94, 1.35]; p = 0.19; I2 = 73%), and increasing KPS (HR = 0.59 [0.20, 1.77]; p = 0.35; I2 = 86%) on prognosis of low-grade astrocytoma after surgery.
Conclusion
The results of meta-analysis showed significant relationship of extent of resection and mortality, while factors such age, KPS score, and tumor size were nonsignificant to determine mortality in patient diagnosed with low-grade astrocytoma. The gross total resection surgery should be preferred over subtotal resection since the incidence of malignant formation is low in gross total resection.
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Yahanda AT, Rich KM, Dacey RG, Zipfel GJ, Dunn GP, Dowling JL, Smyth MD, Leuthardt EC, Limbrick DD, Honeycutt J, Sutherland GR, Jensen RL, Evans J, Chicoine MR. Survival After Resection of Newly-Diagnosed Intracranial Grade II Ependymomas: An Initial Multicenter Analysis and the Logistics of Intraoperative Magnetic Resonance Imaging. World Neurosurg 2022; 167:e757-e769. [PMID: 36028106 DOI: 10.1016/j.wneu.2022.08.077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 08/17/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To identify factors, including the use of intraoperative magnetic resonance imaging (iMRI), impacting overall survival (OS) and progression-free survival (PFS) after resections of newly diagnosed intracranial grade II ependymomas performed across 4 different institutions. METHODS Analyses of a multicenter mixed retrospective/prospective database assessed the impact of patient, treatment, and tumor characteristics on OS and PFS. iMRI workflow and logistics were also outlined. RESULTS Forty-three patients were identified (mean age 25.4 years, mean follow-up 52.8 months). The mean OS was 52.8 ± 44.7 months. Univariate analyses failed to identify prognostic factors associated with OS, likely due to relatively shorter follow-up time for this less aggressive glioma subtype. The mean PFS was 43.7 ± 39.8 months. Multivariate analyses demonstrated that gross-total resection was associated with prolonged PFS compared to both subtotal resection (STR) (P = 0.005) and near-total resection (P = 0.01). Infratentorial location was associated with improved PFS compared to supratentorial location (P = 0.04). Log-rank analyses of Kaplan-Meier survival curves showed that increasing extent of resection (EOR) led to improved OS specifically for supratentorial tumors (P = 0.02) and improved PFS for all tumors (P < 0.001). Thirty cases (69.8%) utilized iMRI, of which 12 (27.9%) involved additional resection after iMRI. Of these, 8/12 (66.7%) resulted in gross-total resection, while 2/12 (16.7%) were near-total resection and 2/12 (16.7%) were subtotal resection. iMRI was not an independent prognosticator of PFS (P = 0.72). CONCLUSIONS Greater EOR and infratentorial location were associated with increased PFS for grade II ependymomas. Greater EOR was associated with longer OS only for supratentorial tumors. A longer follow-up is needed to establish prognostic factors for this cohort, including use of iMRI.
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Affiliation(s)
- Alexander T Yahanda
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
| | - Keith M Rich
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Ralph G Dacey
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Gregory J Zipfel
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Gavin P Dunn
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Joshua L Dowling
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Matthew D Smyth
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Eric C Leuthardt
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - David D Limbrick
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - John Honeycutt
- Department of Neurological Surgery, Cook Children's Medical Center, Fort Worth, Texas, USA
| | - Garnette R Sutherland
- Department of Neurological Surgery, University of Calgary School of Medicine, Calgary, Alberta, Canada
| | - Randy L Jensen
- Department of Neurological Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA
| | - John Evans
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - Michael R Chicoine
- Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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Jakola AS, Pedersen LK, Skjulsvik AJ, Myrmel K, Sjåvik K, Solheim O. The impact of resection in IDH-mutant WHO grade 2 gliomas: a retrospective population-based parallel cohort study. J Neurosurg 2022; 137:1321-1328. [PMID: 35245899 PMCID: PMC10193505 DOI: 10.3171/2022.1.jns212514] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/10/2022] [Indexed: 12/17/2022]
Abstract
OBJECTIVE IDH-mutant diffuse low-grade gliomas (dLGGs; WHO grade 2) are often considered to have a more indolent course. In particular, in patients with 1p19q codeleted oligodendrogliomas, survival can be very long. Therefore, extended follow-up in clinical studies of IDH-mutant dLGG is needed. The authors' primary aim was to determine results after a minimum 10-year follow-up in two hospitals advocating different surgical policies. In one center early resection was favored; in the other center an early biopsy and wait-and-scan approach was the dominant management. In addition, the authors present survival and health-related quality of life (HRQOL) in stratified groups of patients with IDH-mutant astrocytoma and oligodendroglioma. METHODS The authors conducted a retrospective, population-based, parallel cohort study with extended long-term follow-up. The inclusion criteria were histopathological diagnosis of IDH-mutant supratentorial dLGG from 1998 through 2009 in patients aged 18 years or older. Follow-up ended January 1, 2021; therefore, all patients had primary surgery more than 10 years earlier. In region A, a biopsy and wait-and-scan approach was favored, while early resections were advocated in region B. Regional referral practice ensured population-based data, since referral to respective centers was based strictly on the patient's residential address. Previous data from EQ-5D-3L, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and EORTC BN20 questionnaires were reanalyzed with respect to the current selection of IDH-mutant dLGG and to molecular subgroups. The prespecified primary endpoint was long-term regional comparison of overall survival. Secondarily, between-group differences in long-term HRQOL measures were explored. RESULTS Forty-eight patients from region A and 56 patients from region B were included. Early resection was performed in 17 patients (35.4%) from region A compared with 53 patients (94.6%) from region B (p < 0.001). Characteristics at baseline were otherwise similar between cohorts. Overall survival was 7.5 years (95% CI 4.1-10.8) in region A compared with 14.6 years (95% CI 11.5-17.7) in region B (p = 0.04). When stratified according to molecular subgroups, there was only a statistically significant survival benefit in favor of early resection for patients with astrocytomas. The were no apparent differences in the different HRQOL measures between cohorts. CONCLUSIONS In an extended follow-up of patients with IDH-mutant dLGGs, early resection was associated with a sustained and clinically relevant survival benefit. The survival benefit was not counteracted by any detectable reduction in HRQOL.
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Affiliation(s)
- Asgeir S Jakola
- 1Department of Neurosurgery, St. Olav's University Hospital, Trondheim, Norway
- 2Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- 3Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden
| | | | - Anne J Skjulsvik
- 5Department of Pathology, St. Olav's University Hospital, Trondheim, Norway
- 6Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
| | - Kristin Myrmel
- 7Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway; and
| | - Kristin Sjåvik
- 4Department of Neurosurgery, University Hospital of Northern Norway, Tromsø, Norway
| | - Ole Solheim
- 1Department of Neurosurgery, St. Olav's University Hospital, Trondheim, Norway
- 8Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
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Mosteiro A, Di Somma A, Ramos PR, Ferrés A, De Rosa A, González-Ortiz S, Enseñat J, González JJ. Is intraoperative ultrasound more efficient than magnetic resonance in neurosurgical oncology? An exploratory cost-effectiveness analysis. Front Oncol 2022; 12:1016264. [PMID: 36387079 PMCID: PMC9650059 DOI: 10.3389/fonc.2022.1016264] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 10/05/2022] [Indexed: 11/22/2022] Open
Abstract
Objective Intraoperative imaging is a chief asset in neurosurgical oncology, it improves the extent of resection and postoperative outcomes. Imaging devices have evolved considerably, in particular ultrasound (iUS) and magnetic resonance (iMR). Although iUS is regarded as a more economically convenient and yet effective asset, no formal comparison between the efficiency of iUS and iMR in neurosurgical oncology has been performed. Methods A cost-effectiveness analysis comparing two single-center prospectively collected surgical cohorts, classified according to the intraoperative imaging used. iMR (2013-2016) and iUS (2021-2022) groups comprised low- and high-grade gliomas, with a maximal safe resection intention. Units of health gain were gross total resection and equal or increased Karnofsky performance status. Surgical and health costs were considered for analysis. The incremental cost-effectiveness ratio (ICER) was calculated for the two intervention alternatives. The cost-utility graphic and the evolution of surgical duration with the gained experience were also analyzed. Results 50 patients followed an iMR-assisted operation, while 17 underwent an iUS-guided surgery. Gross total resection was achieved in 70% with iMR and in 60% with iUS. Median postoperative Karnofsky was similar in both group (KPS 90). Health costs were € 3,220 higher with iMR, and so were surgical-related costs (€ 1,976 higher). The ICER was € 322 per complete resection obtained with iMR, and € 644 per KPS gained or maintained with iMR. When only surgical-related costs were analyzed, ICER was € 198 per complete resection with iMR and € 395 per KPS gained or maintained. Conclusion This is an unprecedented but preliminary cost-effectiveness analysis of the two most common intraoperative imaging devices in neurosurgical oncology. iMR, although being costlier and time-consuming, seems cost-effective in terms of complete resection rates and postoperative performance status. However, the differences between both techniques are small. Possibly, iMR and iUS are complementary aids during the resection: iUS real-time images assist while advancing towards the tumor limits, informing about the distance to relevant landmarks and correcting neuronavigation inaccuracy due to brain shift. Yet, at the end of resection, it is the iMR that reliably corroborates whether residual tumor remains.
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Affiliation(s)
- Alejandra Mosteiro
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
- Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain
- *Correspondence: Alejandra Mosteiro,
| | - Alberto Di Somma
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
- Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain
| | - Pedro Roldán Ramos
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
- Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain
| | - Abel Ferrés
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Andrea De Rosa
- Division of Neurosurgery, Università degli Studi di Napoli “Federico II”, Naples, Italy
| | - Sofía González-Ortiz
- Division of Neurosurgery, Università degli Studi di Napoli “Federico II”, Naples, Italy
| | - Joaquim Enseñat
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
- Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain
| | - Jose Juan González
- Department of Neurosurgery, Hospital Clínic de Barcelona, Barcelona, Spain
- Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain
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Yee PP, Wang J, Chih SY, Aregawi DG, Glantz MJ, Zacharia BE, Thamburaj K, Li W. Temporal radiographic and histological study of necrosis development in a mouse glioblastoma model. Front Oncol 2022; 12:993649. [PMID: 36313633 PMCID: PMC9614031 DOI: 10.3389/fonc.2022.993649] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
Tumor necrosis is a poor prognostic marker in glioblastoma (GBM) and a variety of other solid cancers. Accumulating evidence supports that necrosis could facilitate tumor progression and resistance to therapeutics. GBM necrosis is typically first detected by magnetic resonance imaging (MRI), after prominent necrosis has already formed. Therefore, radiological appearances of early necrosis formation and the temporal-spatial development of necrosis alongside tumor progression remain poorly understood. This knowledge gap leads to a lack of reliable radiographic diagnostic/prognostic markers in early GBM progression to detect necrosis. Recently, we reported an orthotopic xenograft GBM murine model driven by hyperactivation of the Hippo pathway transcriptional coactivator with PDZ-binding motif (TAZ) which recapitulates the extent of GBM necrosis seen among patients. In this study, we utilized this model to perform a temporal radiographic and histological study of necrosis development. We observed tumor tissue actively undergoing necrosis first appears more brightly enhancing in the early stages of progression in comparison to the rest of the tumor tissue. Later stages of tumor progression lead to loss of enhancement and unenhancing signals in the necrotic central portion of tumors on T1-weighted post-contrast MRI. This central unenhancing portion coincides with the radiographic and clinical definition of necrosis among GBM patients. Moreover, as necrosis evolves, two relatively more contrast-enhancing rims are observed in relationship to the solid enhancing tumor surrounding the central necrosis in the later stages. The outer more prominently enhancing rim at the tumor border probably represents the infiltrating tumor edge, and the inner enhancing rim at the peri-necrotic region may represent locally infiltrating immune cells. The associated inflammation at the peri-necrotic region was further confirmed by immunohistochemical study of the temporal development of tumor necrosis. Neutrophils appear to be the predominant immune cell population in this region as necrosis evolves. This study shows central, brightly enhancing areas associated with inflammation in the tumor microenvironment may represent an early indication of necrosis development in GBM.
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Affiliation(s)
- Patricia P. Yee
- Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States
- Medical Scientist Training Program, Penn State College of Medicine, Hershey, PA, United States
| | - Jianli Wang
- Department of Radiology, Penn State College of Medicine, Hershey, PA, United States
| | - Stephen Y. Chih
- Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States
- Medical Scientist Training Program, Penn State College of Medicine, Hershey, PA, United States
| | - Dawit G. Aregawi
- Neuro-Oncology Program, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, United States
- Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, United States
- Department of Neurology, Penn State College of Medicine, Hershey, PA, United States
| | - Michael J. Glantz
- Neuro-Oncology Program, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, United States
- Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, United States
- Department of Medicine, Penn State College of Medicine, Hershey, PA, United States
| | - Brad E. Zacharia
- Neuro-Oncology Program, Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, United States
- Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, United States
| | | | - Wei Li
- Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States
- Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, United States
- Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA, United States
- *Correspondence: Wei Li,
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Al-Holou WN, Suki D, Hodges TR, Everson RG, Freeman J, Ferguson SD, McCutcheon IE, Prabhu SS, Weinberg JS, Sawaya R, Lang FF. Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas. J Neurosurg 2022; 137:1015-1025. [PMID: 34996044 DOI: 10.3171/2021.9.jns21718] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 09/20/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors' institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher's exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1-2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.
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Affiliation(s)
- Wajd N Al-Holou
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
- 3Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Dima Suki
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Tiffany R Hodges
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Richard G Everson
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Jacob Freeman
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Sherise D Ferguson
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Ian E McCutcheon
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Sujit S Prabhu
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Jeffrey S Weinberg
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Raymond Sawaya
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
| | - Frederick F Lang
- 1Department of Neurosurgery
- 2Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
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Norman S, Juthani RG, Magge R. Foundations of the Diagnosis and Management of Low-Grade Gliomas. World Neurosurg 2022; 166:306-312. [PMID: 36192862 DOI: 10.1016/j.wneu.2022.06.068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 12/15/2022]
Abstract
In the past, low-grade gliomas-World Health Organization (WHO) grade I and II tumors-were generally expected to have a much better prognosis than higher-grade (WHO grade III and IV) gliomas. However, diffuse gliomas (WHO grade II), unlike WHO grade I gliomas, are by definition infiltrative, limiting resection and potentially contributing to poor outcomes like those seen with malignant gliomas. Rapid progress in the understanding of the pathogenesis of these tumors indicates that specific molecular factors, especially isocitrate dehydrogenase mutation status and the presence or absence of the 1p/19q codeletion (deletion of the short arm of chromosome 1 and long arm of chromosome 19), are much more important than grade in determining prognosis and response to treatment. These molecular characteristics outweigh the histologic distinctions and have been quickly incorporated into the WHO classification of gliomas. Management of these tumors with surgery, radiation, and chemotherapy has similarly been transformed by these developments, highlighting the need for a customized approach for patients with low-grade gliomas.
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Affiliation(s)
- Sofya Norman
- Weill Cornell Medical College, New York, New York, USA
| | - Rupa Gopalan Juthani
- Department of Neurological Surgery, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York, USA.
| | - Rajiv Magge
- Department of Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York, USA
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Fiore G, Abete-Fornara G, Forgione A, Tariciotti L, Pluderi M, Borsa S, Bana C, Cogiamanian F, Vergari M, Conte V, Caroli M, Locatelli M, Bertani GA. Indication and eligibility of glioma patients for awake surgery: A scoping review by a multidisciplinary perspective. Front Oncol 2022; 12:951246. [PMID: 36212495 PMCID: PMC9532968 DOI: 10.3389/fonc.2022.951246] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Background Awake surgery (AS) permits intraoperative mapping of cognitive and motor functions, allowing neurosurgeons to tailor the resection according to patient functional boundaries thus preserving long-term patient integrity and maximizing extent of resection. Given the increased risks of the awake scenario, the growing importance of AS in surgical practice favored the debate about patient selection concerning both indication and eligibility criteria. Nonetheless, a systematic investigation is lacking in the literature. Objective To provide a scoping review of the literature concerning indication and eligibility criteria for AS in patients with gliomas to answer the questions:1) "What are the functions mostly tested during AS protocols?" and 2) "When and why should a patient be excluded from AS?". Materials and methods Pertinent studies were retrieved from PubMed, PsycArticles and Cochrane Central Register of Controlled Trials (CENTRAL), published until April 2021 according to the PRISMA Statement Extension for Scoping Reviews. The retrieved abstracts were checked for the following features being clearly stated: 1) the population described as being composed of glioma(LGG or HGG) patients; 2) the paper had to declare which cognitive or sensorimotor function was tested, or 2bis)the decisional process of inclusion/exclusion for AS had to be described from at least one of the following perspectives: neurosurgical, neurophysiological, anesthesiologic and psychological/neuropsychological. Results One hundred and seventy-eight studies stated the functions being tested on 8004 patients. Language is the main indication for AS, even if tasks and stimulation techniques changed over the years. It is followed by monitoring of sensorimotor and visuospatial pathways. This review demonstrated an increasing interest in addressing other superior cognitive functions, such as executive functions and emotions. Forty-five studies on 2645 glioma patients stated the inclusion/exclusion criteria for AS eligibility. Inability to cooperate due to psychological disorder(i.e. anxiety),severe language deficits and other medical conditions(i.e.cardiovascular diseases, obesity, etc.)are widely reported as exclusion criteria for AS. However, a very few papers gave scale exact cut-off. Likewise, age and tumor histology are not standardized parameters for patient selection. Conclusion Given the broad spectrum of functions that might be safely and effectively monitored via AS, neurosurgeons and their teams should tailor intraoperative testing on patient needs and background as well as on tumor location and features. Whenever the aforementioned exclusion criteria are not fulfilled, AS should be strongly considered for glioma patients.
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Affiliation(s)
- Giorgio Fiore
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giorgia Abete-Fornara
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Arianna Forgione
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Leonardo Tariciotti
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Mauro Pluderi
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefano Borsa
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Cristina Bana
- Department of Neuropathophysiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Filippo Cogiamanian
- Department of Neuropathophysiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Maurizio Vergari
- Department of Neuropathophysiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Valeria Conte
- Neuro Intensive Care Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Manuela Caroli
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marco Locatelli
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giulio Andrea Bertani
- Department of Neurosurgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Axelson HW, Latini F, Jemstedt M, Ryttlefors M, Zetterling M. Continuous subcortical language mapping in awake glioma surgery. Front Oncol 2022; 12:947119. [PMID: 36033478 PMCID: PMC9416475 DOI: 10.3389/fonc.2022.947119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/20/2022] [Indexed: 11/29/2022] Open
Abstract
Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (≥7.5 and ≤5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a “gold standard” comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold ≥ 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold ≤ 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at ≥7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS ≤ 5 mA was not consistently confirmed by PS, which needs to be addressed.
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Affiliation(s)
- Hans W. Axelson
- Department of Medical Sciences, Section of Clinical Neurophysiology, Uppsala University, Uppsala, Sweden
- *Correspondence: Hans W. Axelson,
| | - Francesco Latini
- Department of Medical Sciences, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
| | - Malin Jemstedt
- Department of Medical Sciences, Speech-Language Pathology, Uppsala University, Uppsala, Sweden
| | - Mats Ryttlefors
- Department of Medical Sciences, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
| | - Maria Zetterling
- Department of Medical Sciences, Section of Neurosurgery, Uppsala University, Uppsala, Sweden
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Rincon-Torroella J, Rakovec M, Materi J, Raj D, Vivas-Buitrago T, Ferres A, Reyes Serpa W, Redmond KJ, Holdhoff M, Bettegowda C, González Sánchez JJ. Current and Future Frontiers of Molecularly Defined Oligodendrogliomas. Front Oncol 2022; 12:934426. [PMID: 35957904 PMCID: PMC9358027 DOI: 10.3389/fonc.2022.934426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 06/13/2022] [Indexed: 11/17/2022] Open
Abstract
Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.
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Affiliation(s)
- Jordina Rincon-Torroella
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Department of Neurosurgery, Hospital Clínic i Provincial, Barcelona, Spain
| | - Maureen Rakovec
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Josh Materi
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Divyaansh Raj
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | | | - Abel Ferres
- Department of Neurosurgery, Hospital Clínic i Provincial, Barcelona, Spain
| | | | - Kristin J. Redmond
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Matthias Holdhoff
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Chetan Bettegowda
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- *Correspondence: Chetan Bettegowda, ; José Juan González Sánchez,
| | - José Juan González Sánchez
- Department of Neurosurgery, Hospital Clínic i Provincial, Barcelona, Spain
- *Correspondence: Chetan Bettegowda, ; José Juan González Sánchez,
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Prokineticins as a Prognostic Biomarker for Low-Grade Gliomas: A Study Based on The Cancer Genome Atlas Data. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2309339. [PMID: 35845958 PMCID: PMC9283042 DOI: 10.1155/2022/2309339] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/23/2022] [Accepted: 05/31/2022] [Indexed: 11/17/2022]
Abstract
Lower-grade glioma (LGG) is a crucial pathological type of glioma. Prokineticins have not been reported in LGG. Prokineticins as a member of the multifunctional chemokine-like peptide family are divided into two ligands: PROK1 and PROK2. We evaluated the role of PROK1 and PROK2 in LGG using TCGA database. We downloaded the datasets of LGG from TCGA and evaluated the influence of prokineticins on LGG survival by survival module. Correlations between clinical information and prokineticins expression were analyzed using logistic regression. Univariable survival and multivariate Cox analysis was used to compare several clinical characteristics with survival. Correlation between prokineticins and cancer immune infiltrates was explored using CIBERSORT and correlation module of GEPIA. We analyzed genes of PROK1 and PROK2 affecting LGG, screened differentially expressed genes (DEGs), interacted protein-protein with DEGs through the STRING website, then imported the results into the Cytospace software, and calculated the hub genes. To analyze whether hub genes and prokineticins are related, the relationship between PROK1 and PROK2 and hub genes was assessed and shown by heat map. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. The univariate analysis using logistic regression and PROK1 and PROK2 showed opposite expression differences between tumor and normal tissues (
). PRO1 and PROK2 expressions showed significant differences in tumor grade, age, Iiscitrate DeHydrogenase (IDH) status, histological type, and 1P/19q codeletion. Multivariate analysis revealed that the up-regulated PROK1 and PROK2 expression is an independent prognostic factor for bad prognosis. Specifically, prokineticin expression level has significant correlations with infiltrating levels of Th1 cells, NK CD 56bright cells, and Mast cells in LGG. We screened 21 DEGs and obtained 5 hub genes (HOXC10, HOXD13, SOX4, GATA4, HOXA9). GSEA-identified FCMR activation, creation of C4 and C2 activators, and CD22-mediated BCR regulation in gene ontology (GO) were differentially enriched in high PROK1 and PROK2 expression phenotype pathway, cytoplasmic ribosomal proteins, and ribosome and were differentially enriched in the low PROK1 and PROK2 expression phenotype pathway. Prokineticins are a prognostic biomarker and the correlation between hub genes and LGG requires further attention.
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Luo C, Wang S, Shan W, Liao W, Zhang S, Wang Y, Xin Q, Yang T, Hu S, Xie W, Xu N, Zhang Y. A Whole Exon Screening-Based Score Model Predicts Prognosis and Immune Checkpoint Inhibitor Therapy Effects in Low-Grade Glioma. Front Immunol 2022; 13:909189. [PMID: 35769464 PMCID: PMC9234137 DOI: 10.3389/fimmu.2022.909189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/16/2022] [Indexed: 11/23/2022] Open
Abstract
Objective This study aims to identify prognostic factors for low-grade glioma (LGG) via different machine learning methods in the whole genome and to predict patient prognoses based on these factors. We verified the results through in vitro experiments to further screen new potential therapeutic targets. Method A total of 940 glioma patients from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) were included in this study. Two different feature extraction algorithms – LASSO and Random Forest (RF) – were used to jointly screen genes significantly related to the prognosis of patients. The risk signature was constructed based on these screening genes, and the K-M curve and ROC curve evaluated it. Furthermore, we discussed the differences between the high- and low-risk groups distinguished by the signature in detail, including differential gene expression (DEG), single-nucleotide polymorphism (SNP), copy number variation (CNV), immune infiltration, and immune checkpoint. Finally, we identified the function of a novel molecule, METTL7B, which was highly correlated with PD-L1 expression on tumor cell, as verified by in vitro experiments. Results We constructed an accurate prediction model based on seven genes (AUC at 1, 3, 5 years= 0.91, 0.85, 0.74). Further analysis showed that extracellular matrix remodeling and cytokine and chemokine release were activated in the high-risk group. The proportion of multiple immune cell infiltration was upregulated, especially macrophages, accompanied by the high expression of most immune checkpoints. According to the in vitro experiment, we preliminarily speculate that METTL7B affects the stability of PD-L1 mRNA by participating in the modification of m6A. Conclusion The seven gene signatures we constructed can predict the prognosis of patients and identify the potential benefits of immune checkpoint inhibitors (ICI) therapy for LGG. More importantly, METTL7B, one of the risk genes, is a crucial molecule that regulates PD-L1 and could be used as a new potential therapeutic target.
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Affiliation(s)
- Cheng Luo
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Department of Biomedical Engineering, Tsinghua University, Beijing, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
| | - Songmao Wang
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Wenjie Shan
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Open Faculty for Innovation, Education, Science, Technology and Art, Tsinghua Shenzhen International Graduate School, Shenzhen, China
| | - Weijie Liao
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
| | - Shikuan Zhang
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Yanzhi Wang
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- School of Life Sciences, Tsinghua University, Beijing, China
| | - Qilei Xin
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Department of Chemical Engineering, Tsinghua University, Beijing, China
| | - Tingpeng Yang
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Department of Chemical Engineering, Tsinghua University, Beijing, China
| | - Shaoliang Hu
- Research and Development Department, Shenzhen Combined Biotech Co., Ltd, Shenzhen, China
| | - Weidong Xie
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Open Faculty for Innovation, Education, Science, Technology and Art, Tsinghua Shenzhen International Graduate School, Shenzhen, China
| | - Naihan Xu
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Open Faculty for Innovation, Education, Science, Technology and Art, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- *Correspondence: Naihan Xu, ; Yaou Zhang,
| | - Yaou Zhang
- China State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- Open Faculty for Innovation, Education, Science, Technology and Art, Tsinghua Shenzhen International Graduate School, Shenzhen, China
- *Correspondence: Naihan Xu, ; Yaou Zhang,
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Teng C, Zhu Y, Li Y, Dai L, Pan Z, Wanggou S, Li X. Recurrence- and Malignant Progression-Associated Biomarkers in Low-Grade Gliomas and Their Roles in Immunotherapy. Front Immunol 2022; 13:899710. [PMID: 35677036 PMCID: PMC9168984 DOI: 10.3389/fimmu.2022.899710] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 04/12/2022] [Indexed: 12/15/2022] Open
Abstract
Despite a generally better prognosis than high-grade glioma (HGG), recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of low-grade glioma (LGG). It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and recurrent LGG (rLGG), normal brain tissue and secondary glioblastoma (sGBM), primary LGG (pLGG) and rLGG, and pLGG and sGBM, were compared using Chinese Glioma Genome Atlas (CGGA) and Genotype-Tissue Expression Project (GTEx) databases. In this study, 296 downregulated and 396 upregulated differentially expressed genes (DEGs) with high consensus were screened out. Univariate Cox regression analysis of data from The Cancer Genome Atlas (TCGA) yielded 86 prognostically relevant DEGs; a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) was established using the least absolute shrinkage and selection operator (LASSO) regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model. Gene Set Enrichment Analysis (GSEA) revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups was analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutational burden and tumor methylation burden in the high- and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for the five key genes was analyzed, and findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.
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Affiliation(s)
- Chubei Teng
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China.,Department of Neurosurgery, The First Affiliated Hospital, University of South China, Hengyang, China
| | - Yongwei Zhu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Yueshuo Li
- Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Luohuan Dai
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Zhouyang Pan
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Siyi Wanggou
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
| | - Xuejun Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.,Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China
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