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World Journal of Transplantation Jun 2022Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission organ transplant...
BACKGROUND
Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade. Previous surgeries, chemo-/radiotherapy, and ventriculo-peritoneal shunt placement can lead to a disruption of the blood-brain barrier, concurring to an increase in the transmission risk.
AIM
To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas.
METHODS
We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligodendrogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade, the elapsed time from the diagnosis to the onset of metastases, sites and number of metastases, prior surgeries, prior radiotherapy and/or chemotherapy, ventriculo-atrial or ventriculo-peritoneal shunt placement, and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion. Statistical analysis was performed using R software. Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed using and Fischer exact test. The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and: (1) Localization of metastases; (2) The occurrence of intracranial recurrences; and (3) The occurrence of multiple metastases.
RESULTS
Data on a total of 157 patients were retrieved. The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas. Respectively, 19% and 39% of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy. The most frequent metastatic sites were bone, bone marrow, and lymph nodes. The lungs and the liver were the most commonly involved visceral sites. There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy. Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra- central nervous system spread.
CONCLUSION
A long follow-up time does not exclude the presence of extraneural metastases. Therefore, targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.
PubMed: 35979537
DOI: 10.5500/wjt.v12.i6.131 -
Neurosurgical Review Oct 2022The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the... (Review)
Review
The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.
Topics: Astrocytoma; Brain; Brain Neoplasms; Colloid Cysts; Humans; Neuroendoscopy; Pituitary Neoplasms; Ultrasonics
PubMed: 35896917
DOI: 10.1007/s10143-022-01837-w -
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 -
CNS Neuroscience & Therapeutics Oct 2022Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.
METHODS
A quantitative meta-analysis was conducted using the random-effects model. Several potential factors were also reviewed qualitatively.
RESULTS
A total of 39 clinical trials were included after screening 1317 papers. Patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression-free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death-ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non-immunotherapy.
CONCLUSION
Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker-driven prospective studies are warranted.
Topics: Brain Neoplasms; DNA Methylation; DNA Modification Methylases; Glioblastoma; Humans; Immunotherapy; Neoplasm Recurrence, Local; Prognosis
PubMed: 35822692
DOI: 10.1111/cns.13915 -
Indian Journal of Surgical Oncology Jun 2022About half of the brain tumours are primary and the rest are metastatic. The impact of each of these treatments alone or together on the prognosis of patients with... (Review)
Review
About half of the brain tumours are primary and the rest are metastatic. The impact of each of these treatments alone or together on the prognosis of patients with astrocytoma tumours, especially low-grade astrocytoma, is unclear which may pose many challenges in the decision-making of surgeons and patients. Considering the importance of patient's outcomes with astrocytoma and lack of general statistics, this study aimed to determine the survival of patients with high-grade astrocytoma and low-grade astrocytoma after treatments. This study follows a systematic review and a meta-analysis approach. Following a systematic review and meta-analysis method, articles dated from 1982 to March 2020 were extracted from Embase, ScienceDirect, Scopus, PubMed and Web of Science (WoS) international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the index. Data were analysed using the Comprehensive Meta-Analysis software (version 2). According to a meta-analysis of studies, the mean overall survival in patients with high-grade astrocytoma was 31.9 ± 2.7 months, for 2-year survival, 38.1% (95% CI: 27.5-50.1%) and for 5-year survival was 28.6% (95% CI: 24.1-33.4%). Mean overall survival in patients with low-grade astrocytoma was 64.8 ± 7.4 months, for 2-year survival was 74.3% (95% CI: 32.6-94.5%) and for 5-year survival was 74.4% (95% CI: 57.9-86%). The highest mean for survival in patients with high-grade astrocytoma and in chemotherapy and radiation therapy treatments was 45.2 ± 5.2 months, and also the highest mean for survival in patients with low-grade astrocytoma in surgical treatment was 71.4 ± 8.8 months. The results of this study show that the average survival in patients with low-grade astrocytoma is high following the treatment, and in high-grade astrocytoma, there will be the highest survival rate, if the surgical treatment is combined with chemotherapy and radiation therapy. This study summarizes retrospective studies up to 2020 to evaluate the prognosis and survival of patients with brain astrocytoma tumours, and the results of this meta-analysis can be of interest to surgeons and specialists in this field.
PubMed: 35782798
DOI: 10.1007/s13193-022-01533-7 -
Frontiers in Surgery 2022Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two... (Review)
Review
BACKGROUND
Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two infants presented with OPHG and a systematic review of the literature.
METHODS
We describe two cases of infants presenting with sudden decreased vision, poor feeding, and irritability due to OPHG. Both patients underwent urgent craniotomy and subtotal resection followed by chemotherapy. We systematically reviewed the literature using PubMed, Google Scholar, and Embase. In addition, we included all English published reports for all ages discussing the optic pathway (optic nerve and optic chiasm) or hypothalamic glioma associated with hemorrhage from the year of the first reported case (1970) to January 2022.
RESULTS
Of 17,949, 44 articles met the inclusion criteria of this review. A total of 56 cases were described with a mean of 21.35 years (0.5-70), with the male gender 52% and the female gender 45%. The hemorrhage location was sellar/suprasellar in 43% cases. Histopathology of included cases was pilocytic astrocytoma in 41%, followed by pilomyxoid astrocytoma in 16% cases. The outcome was unfavorable; 37.5% cases showed improvement, whereas 18% cases resulted in death.
CONCLUSION
Apoplexy of the OPHG can be fatal and associated with poor outcomes. A systematic review of the literature has shown that younger age, pilocytic or pilomexyoid astrocytoma histopathology, and chiasmal/hypothalamic locations are associated with a higher risk of intertumoral hemorrhage and poor prognosis. Further genetic studies for OPHG may provide information for high-risk patients.
PubMed: 35733436
DOI: 10.3389/fsurg.2022.891556 -
Frontiers in Immunology 2022Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade,... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade, but GBM therapy is still facing a dilemma due to the high recurrence rate. The inflammatory microenvironment is a general signature of tumors that accelerates epigenetic changes in GBM and helps tumors avoid immunological surveillance. GBM tumor cells and glioma-associated microglia/macrophages are the primary contributors to the inflammatory condition, meanwhile the modification of epigenetic events including DNA methylation, non-coding RNAs, and histone methylation and deacetylases involved in this pathological process of GBM, finally result in exacerbating the proliferation, invasion, and migration of GBM. On the other hand, histone deacetylase inhibitors, DNA methyltransferases inhibitors, and RNA interference could reverse the inflammatory landscapes and inhibit GBM growth and invasion. Here, we systematically review the inflammatory-associated epigenetic changes and regulations in the microenvironment of GBM, aiming to provide a comprehensive epigenetic profile underlying the recognition of inflammation in GBM.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioblastoma; Humans; Inflammation; Tumor Microenvironment
PubMed: 35572545
DOI: 10.3389/fimmu.2022.869307 -
World Journal of Surgical Oncology May 2022Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of...
BACKGROUND
Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.
METHODS
Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes.
RESULTS
The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression.
CONCLUSION
Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.
Topics: Brain Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Janus Kinases; NF-kappa B; Neoplastic Stem Cells; Neurogenesis; SOXC Transcription Factors; STAT Transcription Factors; Signal Transduction
PubMed: 35538578
DOI: 10.1186/s12957-022-02602-5 -
Global Spine Journal Jan 2023Systematic review: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome.
STUDY DESIGN
Systematic review: 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, = .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.
PubMed: 35486519
DOI: 10.1177/21925682221094766 -
International Journal of Molecular... Apr 2022Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular... (Review)
Review
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 35456984
DOI: 10.3390/ijms23084166