-
Cancers Aug 2023Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade... (Review)
Review
BACKGROUND
Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas.
METHODS
A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores.
RESULTS
16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved.
CONCLUSIONS
The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale.
PubMed: 37627158
DOI: 10.3390/cancers15164130 -
Frontiers in Surgery 2024Recently, non-technical skills (NTS) and teamwork in particular have been demonstrated to be essential in many jobs, in business as well as in medical specialties,...
BACKGROUND
Recently, non-technical skills (NTS) and teamwork in particular have been demonstrated to be essential in many jobs, in business as well as in medical specialties, including plastic, orthopedic, and general surgery. However, NTS and teamwork in neurosurgery have not yet been fully studied. We reviewed the relevant literature and designed a mock surgery to be used as a team-building activity specifically designed for scrub nurses and neurosurgeons.
METHODS
We conducted a systematic review by searching PubMed (Medline) and CINAHL, including relevant articles in English published until 15 July 2023. Then, we proposed a pilot study consisting of a single-session, hands-on, and cadaver-free activity, based on role play. Scrub nurses were administered the SPLINTS (Scrub Practitioners' List of Intraoperative Non-Technical Skills) rating form as a self-evaluation at baseline and 20-30 days after the simulation. During the experiment, surgeons and scrub nurses role-played as each other, doing exercises including a simulated glioma resection surgery performed on an advanced model of a cerebral tumor (Tumor Box, UpSurgeOn®) under an exoscope. At the end, every participant completed an evaluation questionnaire.
RESULTS
A limited number of articles are available on the topic. This study reports one of the first neurosurgical team-building activities in the literature. All the participating scrub nurses and neurosurgeons positively evaluated the simulation developed on a roleplay. The use of a physical simulator seems an added value, as the tactile feedback given by the model further helps to understand the actual surgical job, more than only observing and assisting. The SPLINTS showed a statistically significant improvement not only in "Communication and Teamwork" ( = 0.048) but also in "Situation Awareness" ( = 0.031).
CONCLUSION
Our study suggests that team-building activities may play a role in improving interprofessional teamwork and other NTS in neurosurgery.
PubMed: 38558881
DOI: 10.3389/fsurg.2024.1386887 -
Acta Neurochirurgica May 2024Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A... (Review)
Review
PURPOSE
Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions.
METHODS
We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy.
RESULTS
Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions.
CONCLUSIONS
Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery.
Topics: Humans; Craniotomy; Wakefulness; Cognition; Neuropsychological Tests; Monitoring, Intraoperative; Intraoperative Neurophysiological Monitoring
PubMed: 38713405
DOI: 10.1007/s00701-024-06062-6 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
Cancers Jul 2023Diffuse midline glioma (DMG), -altered are highly aggressive, incurable central nervous system (CNS) tumors. The current standard palliative treatment is radiotherapy,... (Review)
Review
Molecular Characterization and Treatment Approaches for Pediatric -Altered Diffuse Midline Glioma: Integrated Systematic Review of Individual Clinical Trial Participant Data.
Diffuse midline glioma (DMG), -altered are highly aggressive, incurable central nervous system (CNS) tumors. The current standard palliative treatment is radiotherapy, with most children succumbing to the disease in less than one year from the time of diagnosis. Over the past decade, there have been significant advancements in our understanding of these heterogeneous tumors at the molecular level. As a result, most of the newer clinical trials offered utilize more targeted approaches with information derived from the tumor biopsy. In this systematic review, we used individual participant data from seven recent clinical trials published over the past five years that met our inclusion and exclusion criteria to analyze factors that influence overall survival (OS). We found that the most prominent genetic alterations H3.3 () and were associated with worse OS and that ACVR had a protective effect. In addition, re-irradiation was the only statistically significant treatment modality that showed any survival benefit. Our findings highlight some important characteristics of DMG, -altered and their effects on OS along with the importance of continuing to review clinical trial data to improve our therapies for these fatal tumors.
PubMed: 37444588
DOI: 10.3390/cancers15133478 -
European Radiology Feb 2024To evaluate the methodological quality and diagnostic accuracy of MRI-based radiomic studies predicting O6-methylguanine-DNA methyltransferase (MGMT) promoter...
OBJECTIVES
To evaluate the methodological quality and diagnostic accuracy of MRI-based radiomic studies predicting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in gliomas.
METHODS
PubMed Medline, EMBASE, and Web of Science were searched to identify MRI-based radiomic studies on MGMT methylation in gliomas published until December 31, 2022. Three raters evaluated the study methodological quality with Radiomics Quality Score (RQS, 16 components) and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis Or Diagnosis (TRIPOD, 22 items) scales. Risk of bias and applicability concerns were assessed with QUADAS-2 tool. A meta-analysis was performed to estimate the pooled area under the curve (AUC) and to assess inter-study heterogeneity.
RESULTS
We included 26 studies, published from 2016. The median RQS total score was 8 out of 36 (22%, range 8-44%). Thirteen studies performed external validation. All studies reported AUC or accuracy, but only 4 (15%) performed calibration and decision curve analysis. No studies performed phantom analysis, cost-effectiveness analysis, and prospective validation. The overall TRIPOD adherence score was between 50% and 70% in 16 studies and below 50% in 10 studies. The pooled AUC was 0.78 (95% CI, 0.73-0.83, I = 94.1%) with a high inter-study heterogeneity. Studies with external validation and including only WHO-grade IV gliomas had significantly lower AUC values (0.65; 95% CI, 0.57-0.73, p < 0.01).
CONCLUSIONS
Study RQS and adherence to TRIPOD guidelines was generally low. Radiomic prediction of MGMT methylation status showed great heterogeneity of results and lower performances in grade IV gliomas, which hinders its current implementation in clinical practice.
CLINICAL RELEVANCE STATEMENT
MGMT promoter methylation status appears to be variably correlated with MRI radiomic features; radiomic models are not sufficiently robust to be integrated into clinical practice to accurately predict MGMT promoter methylation status in patients with glioma before surgery.
KEY POINTS
• Adherence to the indications of TRIPOD guidelines was generally low, as was RQS total score. • MGMT promoter methylation status prediction with MRI radiomic features provided heterogeneous diagnostic accuracy results across studies. • Studies that included grade IV glioma only and performed external validation had significantly lower diagnostic accuracy than others.
PubMed: 38308012
DOI: 10.1007/s00330-024-10594-x -
Diagnostics (Basel, Switzerland) Dec 2023F-Fluciclovine ([F]FACBC) has been recently proposed as a synthetic radiolabeled amino acid for positron emission tomography (PET) imaging in patients with brain... (Review)
Review
BACKGROUND
F-Fluciclovine ([F]FACBC) has been recently proposed as a synthetic radiolabeled amino acid for positron emission tomography (PET) imaging in patients with brain neoplasms. Our aim is to evaluate the diagnostic performance of [F]FACBC PET in high-grade glioma (HGG) patients, taking into account the literature data.
METHODS
A comprehensive literature search was performed. We included original articles evaluating [F]FACBC PET in the detection of HGG before therapy and for the suspicion of tumor recurrence. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratios (DOR), including 95% confidence intervals (95% CI), were measured. Statistical heterogeneity and publication bias were also assessed.
RESULTS
ten studies were included in the review and eight in the meta-analysis (113 patients). Regarding the identification of HGG, the sensitivity of [F]FACBC PET ranged between 85.7% and 100%, with a pooled estimate of 92.9% (95% CI: 84.4-96.9%), while the specificity ranged from 50% to 100%, with a pooled estimate of 70.7% (95% CI: 47.5-86.5%). The pooled LR+, LR-, and DOR of [F]FACBC PET were 2.5, 0.14, and 37, respectively. No significant statistical heterogeneity or publication bias were found.
CONCLUSIONS
evidence-based data demonstrate the good diagnostic accuracy of [F]FACBC PET for HGG detection. Due to the still limited data, further studies are warranted to confirm the promising role of [F]FACBC PET in this context.
PubMed: 38132194
DOI: 10.3390/diagnostics13243610 -
Journal of Neurological Surgery Reports Oct 2023Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an...
Despite advances in multimodal oncologic therapies and molecular genetics, overall survival (OS) in patients with high-grade astrocytomas remains poor. We present an illustrative case and systematic review of rare, predominantly extra-axial World Health Organization (WHO) grade 4 astrocytomas located within the cerebellopontine angle (CPA) and explore the impact of anatomic location on diagnosis, management, and outcomes. A systematic review of adult patients with predominantly extra-axial WHO grade 4 CPA astrocytomas was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through December 2022. Eighteen articles were included comprising 21 astrocytomas: 13 exophytic tumors arising from the cerebellopontine parenchyma and 8 tumors originating from a cranial nerve root entry zone. The median OS was 15 months with one-third of cases demonstrating delayed diagnosis. Gross total resection, molecular genetic profiling, and use of ancillary treatment were low. We report the only patient with an integrated isocitrate dehydrogenase 1 (IDH-1) mutant diagnosis, who, after subtotal resection and chemoradiation, remains alive at 40 months without progression. The deep conical-shaped corridor and abundance of eloquent tissue of the CPA significantly limits both surgical resection and utility of device-based therapies in this region. Prompt diagnosis, molecular characterization, and systemic therapeutic advances serve as the predominant means to optimize survival for patients with rare skull base astrocytomas.
PubMed: 37854309
DOI: 10.1055/a-2172-7770 -
Frontiers in Oncology 2023This study aims to depict the scientific advancements in immunotherapy for glioma by analyzing the top 100 most frequently cited articles over the past 20 years.
PURPOSE
This study aims to depict the scientific advancements in immunotherapy for glioma by analyzing the top 100 most frequently cited articles over the past 20 years.
METHODS
The top 100 most influential papers in immunotherapy for glioma were identified from the Web of Science Core Collection. Citations, countries/regions, institutions, journals, authorships, keywords, and references were extracted and analyzed by CiteSpace, VOSviewer, R software, and an online bibliometric platform.
RESULTS
The United States possessed a robust global presence, leading in terms of publications and maintaining strong collaborative ties with numerous countries. The institution that made the greatest contributions was Duke University, with 16 papers. Heimberger AB, Sampson JH, and Reardon DA secured the top three positions with 15, 12, and 11 papers, respectively. "Macrophage ontogeny," "microglia," "polarization," "mass cytometry," "tumor mutation burden," "sensitivity," "msh6," "pd-1 blockade," and "dna repair" were the recent hot keywords. "Microglia" and "polarization" as the emerging research directions should be given more consideration.
CONCLUSIONS
This is the first bibliometric analysis to identify the top 100 papers on immunotherapy for glioma. "Microglia" and "polarization" will be hot spots for future research. The clinical efficacy of glioma immunotherapy is not yet satisfactory, and there is an urgent need to search for more tumor specific antigens and targets that can assist in early diagnosis, precise treatment, prognosis, and recurrence prediction of glioma.
PubMed: 38293697
DOI: 10.3389/fonc.2023.1307924 -
The Indian Journal of Radiology &... Oct 2023High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact... (Review)
Review
High-grade gliomas (HGGs) are the most prevalent primary malignancy of the central nervous system. The tumor results in vasogenic and infiltrative edema . Exact anatomical differentiation of these edemas is so important for surgical planning. Multimodal imaging could be used to differentiate the edema type. The aim of this study was to investigate the role of multimodal imaging in the differentiation of vasogenic edema from infiltrative edema in patients with HGG (grade III and grade IV). A search on PubMed, EMBASE, Scopus, and ISI Web of Science Core Collection up to June 2022 using terms related to (a) multimodal imaging AND (b) HGG AND (c) edema. (PROSPERO registration number: CRD42022336131) Two reviewers screened the articles and independently extracted the data. We included original articles assessing the role of multimodal imaging in differentiating vasogenic from infiltrative edema in patients with HGG. Six high-quality articles remained for the narrative synthesis. Dynamic susceptibility contrast imaging showed that relative cerebral blood volume and relative cerebral blood flow were higher in the infiltrative edema component than in the vasogenic edema component. Diffusion tensor imaging revealed a dispute on fractional anisotropy. The apparent diffusion coefficient was comparable between the two edematous components. Magnetic resonance spectroscopy exhibited an increment in choline/creatinine ratio and choline/N-acetyl aspartate ratio in the infiltrative edema component. Strict study selection, low sample size of relevant published studies, and heterogeneity in endpoint variables were the major drawbacks. Multimodal imaging, including dynamic susceptibility contrast and magnetic resonance spectroscopy, might help differentiate between vasogenic and infiltrative edema.
PubMed: 37811185
DOI: 10.1055/s-0043-1772466