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1.
Fluorescein-guided resection of gliomas.
Save, AV, Gill, BJ, D'amico, RS, Canoll, P, Bruce, JN
Journal of neurosurgical sciences. 2019;(6):648-655
Abstract
Standard of care in the management of high-grade gliomas includes gross total resection (GTR) followed by treatment with radiation and temozolomide. GTR remains one of the few independent prognostic factors for improved survival in this disease. Sodium fluorescein is an organic fluorophore that has been studied as a surgical adjunct to improve the likelihood of achieving GTR in gliomas. Though sodium fluorescein does not selectively accumulate in glioma cells, it allows for real-time identification of regions of blood brain barrier breakdown, corresponding to the contrast-enhancing cores of high-grade gliomas. In addition to its high predictive value for identifying pathologic tissue, use of fluorescein has been shown to improve rates of GTR. In stereotactic needle biopsies, it helps reduce procedure time by rapidly confirming the presence of diagnostic tissue. Furthermore, in non-enhancing, low-grade gliomas, it labels focal regions of vascular dysregulation that have been correlated with high-grade features. Fluorescein has also been shown to be significantly less expensive than other contemporary surgical adjuncts such as intraoperative ultrasound, intraoperative MRI, and the recently FDA approved fluorophore, 5-aminolevulinic acid (5-ALA). Here, we review the current literature on the effectiveness of fluorescein as a surgical tool in the resection of gliomas.
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2.
Potassium channels and their role in glioma: A mini review.
Liu, J, Qu, C, Han, C, Chen, MM, An, LJ, Zou, W
Molecular membrane biology. 2019;(1):76-85
Abstract
K+ channels regulate a multitude of biological processes and play important roles in a variety of diseases by controlling potassium flow across cell membranes. They are widely expressed in the central and peripheral nervous system. As a malignant tumor derived from nerve epithelium, glioma has the characteristics of high incidence, high recurrence rate, high mortality rate, and low cure rate. Since glioma cells show invasive growth, current surgical methods cannot completely remove tumors. Adjuvant chemotherapy is still needed after surgery. Because the blood-brain barrier and other factors lead to a lower effective concentration of chemotherapeutic drugs in the tumor, the recurrence rate of residual lesions is extremely high. Therefore, new therapeutic methods are needed. Numerous studies have shown that different K+ channel subtypes are differentially expressed in glioma cells and are involved in the regulation of the cell cycle of glioma cells to arrest them at different stages of the cell cycle. Increasing evidence suggests that K+ channels express in glioma cells and regulate glioma cell behaviors such as cell cycle, proliferation and apoptosis. This review article aims to summarize the current knowledge on the function of K+ channels in glioma, suggests K+ channels participating in the development of glioma.
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Following the light in glioma surgery: a comparison of sodium fluorescein and 5-aminolevulinic acid as surgical adjuncts in glioma resection.
Navarro-Bonnet, J, Suarez-Meade, P, Brown, DA, Chaichana, KL, Quinones-Hinojosa, A
Journal of neurosurgical sciences. 2019;(6):633-647
Abstract
Gliomas are molecularly complex neoplasms and require a multidisciplinary approach to treatment. Maximal safe resection is often the initial goal of treatment and extent of resection (EOR) is an important prognostic factor correlating with both progression-free-survival (PFS) and overall survival (OS). Postoperative patient outcome is also a critical and independent prognosticator and high EOR must not be achieved at the expense of good functional outcome. Several intraoperative adjuvant techniques have been developed to help the surgeon push the boundaries of EOR while maintaining safety. Fluorescence-guided surgery for brain tumors is a contemporary adjuvant technique that allows for intraoperative delineation of diseased and normal brain thus improving maximal safe resection. The most extensively used fluorophores are 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SFL). These fluorophores have different spectrophotometric properties, mechanisms of action and considerations for use. Both have demonstrated utility in neurosurgical oncology. They are safe and both are FDA approved for use as surgical adjuncts during resection of primary CNS neoplasms although they have been used with varying success for other tumor types. When combined with other surgical adjuvant strategies such as neuronavigation, intraoperative ultrasound, intraoperative MRI, awake resection and/or electrophysiological mapping/monitoring, fluorescence-guided resection appears to further improve resection quality in regard to EOR and safety. In this article, we review the current knowledge related to both fluorophores for brain tumor resection, their benefits, and pitfalls, as well as the major advantages associated with their use. We also briefly review additional fluorophores in early clinical development. Fluorescence-guided surgery is a novel surgical adjuvant which allows for real-time delineation of neoplastic tissues. The most widely used fluorophores are 5-ALA and SFL. They are safe compounds and there is a large body of evidence suggesting improvement in EOR when these are employed. There are nuances to the use of each; the fluorescence intensity is dose-dependent in either case and the sensitivity and specificity for various tumors vary widely. Additional prospective studies will be necessary to parse the impact of this technique and these fluorophores on survival metrics.
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4.
Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature.
Sawlani, V, Davies, N, Patel, M, Flintham, R, Fong, C, Heyes, G, Cruickshank, G, Steven, N, Peet, A, Hartley, A, et al
Clinical oncology (Royal College of Radiologists (Great Britain)). 2019;(1):41-49
Abstract
AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. MATERIALS AND METHODS Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. RESULTS Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10-6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. CONCLUSION Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.
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Secondary parkinsonism due to drugs, vascular lesions, tumors, trauma, and other insults.
Höllerhage, M
International review of neurobiology. 2019;:377-418
Abstract
In addition to neurodegenerative disorders, there are many secondary forms of parkinsonism. The most common cause for secondary parkinsonism is the intake of distinct drugs. Neuroleptics and calcium channel blockers have been mainly described to induce parkinsonism, but also other drugs were suspected to cause or worsen parkinsonism. Another common cause for secondary parkinsonism are vascular lesions (i.e. vascular parkinsonism). Furthermore, also brain tumors have been described as rare causes for parkinsonism. Moreover, parkinsonism can be caused by chronic traumatic encephalopathy, which is a special case, since secondary insults to the brain leads to the occurrence of a neuropathologically defined disease. Other rare causes for secondary parkinsonism are lesions caused by infectious or immunological diseases as well as toxins or street drugs.
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6.
State of the art of fluorescence guided techniques in neurosurgery.
La Rocca, G, Della Pepa, GM, Menna, G, Altieri, R, Ius, T, Rapisarda, A, Olivi, A, Sabatino, G
Journal of neurosurgical sciences. 2019;(6):619-624
Abstract
Achieving a safe and extensive neoplasm resection can be considered the main goal of brain tumor surgery. This paper is first aimed at providing an overview of the evolution of those tools serving the purpose. From the dawn of neurosurgery to the present days, major innovations have followed one another. However, those techniques may frequently lack of an instant biological feedback on the true extension and the infiltration of the tumor. Intraoperative fluorescence modalities could indeed fill this gap. Fluorescence guided surgery will be therefore introduced and discussed in this context. Our focus will be on the most common fluorescence techniques used in neurosurgery, namely 5-aminolevulinic acid, sodium fluorescein and in indocyanine green. Mode of action, strengths and weaknesses and level of evidence of each modality will be discussed.
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7.
Brain Tumors of Glial Origin.
Waker, CA, Lober, RM
Advances in experimental medicine and biology. 2019;:281-297
Abstract
Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.
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Surgical Adjuncts to Increase the Extent of Resection: Intraoperative MRI, Fluorescence, and Raman Histology.
Hollon, T, Stummer, W, Orringer, D, Suero Molina, E
Neurosurgery clinics of North America. 2019;(1):65-74
Abstract
In low-grade glioma surgery, depicting tumor margins is challenging. 7 - Bowden 2018 - Sodium Fluorescein Facilitates Guided Sampling of Diagnostic Tumor Tissue.pdf Several tools have emerged to assist surgical decision-making. Intraoperative MRI, albeit expensive and time-consuming, can provide useful information during surgery. Fluorescence-guidance with 5-aminolevulinic acid (5-ALA) helps provide real-time information during surgery regardless of brain-shift, assists in finding anaplastic foci in low-grade tumors, and enables diagnosis of malignant tissue. Raman histology has potential for detecting viable tumor in biopsied tissue and for identifying tumor infiltration in vivo. This article analyzes and discusses these surgical adjuncts.
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Controversial roles for dexamethasone in glioblastoma - Opportunities for novel vascular targeting therapies.
Dubinski, D, Hattingen, E, Senft, C, Seifert, V, Peters, KG, Reiss, Y, Devraj, K, Plate, KH
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2019;(8):1460-1468
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Abstract
Glioblastoma is a highly aggressive and treatment resistant primary brain tumor. Features of glioblastoma include peritumoral cerebral edema, the major contributor to neurological impairment. Although the current clinical approach to edema management is administration of the synthetic corticoid dexamethasone, increasing evidence indicates numerous adverse effects of dexamethasone on glioblastoma burden at the molecular, cellular and clinical level. The contradictions of dexamethasone for glioblastoma and brain metastasis therapy are discussed in this article. Finally, alternative strategies for cerebrovascular edema therapy with vascular stabilizing, anti-permeability agents that are either approved or in clinical trials for diabetic retinopathy and macula edema, are addressed.
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The social trajectory of brain tumor: a qualitative metasynthesis.
Cubis, L, Ownsworth, T, Pinkham, MB, Chambers, S
Disability and rehabilitation. 2018;(16):1857-1869
Abstract
PURPOSE Research indicates that strong social ties can buffer the adverse effects of chronic illness on psychological well-being. Brain tumor typically leads to serious functional impairments that affect relationships and reduce social participation. This metasynthesis aimed to identify, appraise and integrate the findings of qualitative studies that reveal the impact of brain tumor on social networks. METHODS Four major databases (PubMed, CINAHL, Cochrane Library and PsycINFO) were systematically searched from inception to September 2016 for qualitative studies that reported findings on the impact of primary brain tumor on social networks during adulthood. Twenty-one eligible studies were identified and appraised according to the Consolidated Criteria for Reporting Qualitative Research. Key findings of these studies were integrated to form superordinate themes. RESULTS The metasynthesis revealed the core themes of: 1) Life disrupted; 2) Navigating the new reality of life; and 3) Social survivorship versus separation. CONCLUSIONS Multiple changes typically occur across the social trajectory of brain tumor, including a loss of pre-illness networks and the emergence of new ones. Understanding the barriers and facilitators for maintaining social connection may guide interventions for strengthening social networks and enhancing well-being in the context of brain tumor. Implications for rehabilitation Social networks and roles are disrupted throughout the entire trajectory of living with brain tumor Physical, cognitive and psychological factors represent barriers to social integration Barriers to social integration may be addressed by supportive care interventions Compensatory strategies, adjusting goals and expectations, educating friends and family and accepting support from others facilitate social reintegration throughout the trajectory of living with brain tumor.