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Neurosurgical Review Nov 2023Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to... (Review)
Review
Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.
Topics: Female; Humans; Pregnancy; Brain Neoplasms; Wakefulness; Craniotomy; Glioma; Anesthesia, General
PubMed: 37910275
DOI: 10.1007/s10143-023-02187-x -
Nutrients Jul 2022Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches.... (Review)
Review
Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches. Lipid-soluble vitamins have gained attention in malignant brain tumors owing to their pleiotropic properties and their anti-cancer potential have been reported in a number of human GBM cell lines. The aim of this paper is to systematically review and describe the roles of various biomarkers regulated by lipid-soluble vitamins, such as vitamins A, D, E, and K, in the pathophysiology of GBM. Briefly, research articles published between 2005 and 2021 were systematically searched and selected from five databases (Scopus, PubMed, Ovid MEDLINE, EMBASE via Ovid, and Web of Science) based on the study's inclusion and exclusion criteria. In addition, a number of hand-searched research articles identified from Google Scholar were also included for the analysis. A total of 40 differentially expressed biomarkers were identified from the 19 eligible studies. The results from the analysis suggest that retinoids activate cell differentiation and suppress the biomarkers responsible for stemness in human GBM cells. Vitamin D appears to preferentially modulate several cell cycle biomarkers, while vitamin E derivatives seem to predominantly modulate biomarkers related to apoptosis. However, vitamin K1 did not appear to induce any significant changes to the Raf/MEK/ERK signaling or apoptotic pathways in human GBM cell lines. From the systematic analysis, 12 biomarkers were identified that may be of interest for further studies, as these were modulated by one or two of these lipid-soluble vitamins.
Topics: Adult; Biomarkers; Brain Neoplasms; Glioblastoma; Humans; Lipids; Vitamins
PubMed: 35889829
DOI: 10.3390/nu14142873 -
Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
British Journal of Cancer Jun 2023Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS.
METHODS
We conducted a systematic review to identify CS cases to create a retrospective cohort. We tested genotype-phenotype correlations and calculated cumulative incidence and hazard rates (HR) for cancer and cancer-free death, standardised incidence rates (SIR) and survival after cancer.
RESULTS
This study includes 234 publications reporting 621 patients from 35 countries. Over nine percent had cancer, including rhabdomyosarcoma, bladder, and neuroblastoma. The rate of cancer and death associated with p.Gly12Ser were lower when compared to all other variants (P < 0.05). Higher mortality for p.Gly12Cys, p.Gly12Asp, p.Gly12Val and p.Gly60Val and higher malignancy rate for p.Gly12Ala were confirmed (P < 0.05). Cumulative incidence by age 20 was 13% (cancer) and 11% (cancer-free death). HR (death) was 3-4% until age 3. Statistically significant SIRs were found for rhabdomyosarcoma (SIR = 1240), bladder (SIR = 1971), and neuroblastoma (SIR = 60). Survival after cancer appeared reduced.
CONCLUSIONS
This is the largest investigation of cancer in CS to date. The high incidence and SIR values found to highlight the need for rigorous surveillance and evidence-based guidelines for this high-risk population.
Topics: Humans; Costello Syndrome; Retrospective Studies; Genotype; Rhabdomyosarcoma; Neuroblastoma
PubMed: 36966234
DOI: 10.1038/s41416-023-02229-7 -
Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696 -
World Neurosurgery Jun 2022Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the... (Review)
Review
BACKGROUND
Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the oncometabolite 2-hydroxyglutarate. Therefore, therapies targeting reversal of epigenetic dysregulation in gliomas have been suggested. However, the utility of epigenetic treatments in gliomas remains unclear. Here, we present the first clinical systematic review of epigenetic therapies in treatment of IDH-mutant gliomas and highlight their safety and efficacy.
METHODS
We conducted a systematic search of electronic databases from 2000 to January 2021 following PRISMA guidelines. Articles were screened to include clinical usage of epigenetic therapies in case reports, prospective case series, or clinical trials. Primary and secondary outcomes included safety/tolerability of epigenetic therapies and progression-free survival/overall survival, respectively.
RESULTS
A total of 133 patients across 8 clinical studies were included in our analysis. IDH inhibitors appear to have the best safety profile, with an overall grade 3/grade 4 adverse event rate of 9%. Response rates to IDH-mutant inhibitors were highest in nonenhancing gliomas (stable disease achieved in 55% of patients). In contrast, histone deacetylase inhibitors demonstrate a lower safety profile with single-study adverse events as high as 28%.
CONCLUSION
IDH inhibitors appear promising given their benign toxicity profile and ease of monitoring. Histone deacetylase inhibitors appear to have a narrow therapeutic index, as lower concentrations do not appear effective, while increased doses can produce severe immunosuppressive effects. Preliminary data suggest that epigenetic therapies are generally well tolerated and may control disease in certain patient groups, such as those with nonenhancing lesions.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioma; Histone Deacetylase Inhibitors; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 35314408
DOI: 10.1016/j.wneu.2022.03.051 -
Clinical Endocrinology Jul 2021To describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs).
OBJECTIVE
To describe the presentation and outcomes of patients with adrenal ganglioneuromas (AGNs).
DESIGN
Single-centre retrospective cohort study (1 January 1995 to 31 December 2019) and systematic review of literature (1 January 1980 to 19 November 2019).
PATIENTS
Diagnosed with histologically confirmed AGN.
MEASUREMENTS
Baseline clinical, imaging and biochemical characteristics, recurrence rates and mortality. Subgroup analysis was performed on tumours with histologic elements of ganglioneuroma and pheochromocytoma (ie composite tumours).
RESULTS
The cohort study included 45 patients with AGN, 20 (44%) of which had composite tumours. Compared to pure AGN, patients with composite tumour were older (median age, 62.5 vs. 35 years, p < .001), had smaller tumours (median size, 3.9 vs. 5.7 cm, p = .016) and were discovered incidentally less frequently (65% vs. 84%, p = .009). No recurrences or ganglioneuroma-specific mortality occurred during follow-up (range, 0-266 months). The systematic review included 14 additional studies and 421 patients. The mean age of diagnosis was 39 years, and 47% were women. AGNs were discovered incidentally in 72% of patients, were predominantly unilateral (99%) and had a mean diameter of 5.8 cm and an unenhanced computed tomography (CT) attenuation of -118 to 49 Hounsfield units (HU). On imaging, 69% of AGNs were homogenous, 41% demonstrated calcifications, and 40% were lobulated.
CONCLUSIONS
AGNs are rare benign tumours that present with variable imaging features including large size, unenhanced CT attenuation >20 HU, calcifications and lobulated shape. Imaging characteristics can assist in establishing a diagnosis and avoiding an unnecessary adrenalectomy. The association of pheochromocytomas with AGNs is frequent. Diagnosis should include biochemical testing.
Topics: Adrenal Gland Neoplasms; Adult; Cohort Studies; Female; Ganglioneuroma; Humans; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 33721367
DOI: 10.1111/cen.14460 -
Nutrients Feb 2022People consume nitrates, nitrites, nitrosamines, and NOCs compounds primarily through processed food. Many studies have yielded inconclusive results regarding the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People consume nitrates, nitrites, nitrosamines, and NOCs compounds primarily through processed food. Many studies have yielded inconclusive results regarding the association between cancer and dietary intakes of nitrates and nitrites. This study aimed to quantify these associations across the reported literature thus far.
METHODS
We performed a systematic review following PRISMA and MOOSE guidelines. A literature search was performed using Web of Science, Embase, PubMed, the Cochrane library, and google scholar up to January 2020. STATA version 12.0 was used to conduct meta-regression and a two-stage meta-analysis.
RESULTS
A total of 41 articles with 13 different cancer sites were used for analysis. Of these 13 cancer types/sites, meta-regression analysis showed that bladder and stomach cancer risk was greater, and that pancreatic cancer risk was lower with increasing nitrite intakes. Kidney and bladder cancer risk were both lower with increasing nitrate intakes. When comparing highest to lowest (reference) categories of intake, meta-analysis of studies showed that high nitrate intake was associated with an increased risk of thyroid cancer (OR = 1.40, 95% CI: 1.02, 1.77). When pooling all intake categories and comparing against the lowest (reference) category, higher nitrite intake was associated with an increased risk of glioma (OR = 1.12, 95% CI: 1.03, 1.22). No other associations between cancer risk and dietary intakes of nitrates or nitrites were observed.
CONCLUSION
This study showed varied associations between site-specific cancer risks and dietary intakes of nitrate and nitrite. Glioma, bladder, and stomach cancer risks were higher and pancreatic cancer risk was lower with higher nitrite intakes, and thyroid cancer risk was higher and kidney cancer risk lower with higher nitrate intakes. These data suggest type- and site-specific effects of cancer risk, including protective effects, from dietary intakes of nitrate and nitrite.
Topics: Diet; Glioma; Humans; Nitrates; Nitrites; Risk
PubMed: 35277025
DOI: 10.3390/nu14030666 -
Scientific Reports Aug 2022High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However,... (Meta-Analysis)
Meta-Analysis
High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91-0.95]) and DSC-MRI (AUC = 0.93 [0.90-0.95]), compared to DCE-MRI (AUC = 0.90 [0.87-0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Sensitivity and Specificity; Treatment Outcome
PubMed: 35918373
DOI: 10.1038/s41598-022-16726-x