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1.
Oncol Res ; 32(6): 1037-1045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827324

RESUMO

Background: The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. Methods: A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors. Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis. Inter-cohort statistical significance was evaluated. Results: Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. Out of the 22 IDH-mutant tumors, 10 (45.5%) tumors showed MGMT-promoter methylation and 12 (54.5%) tumors had unmethylated MGMT. All IDH-wildtype tumors had unmethylated MGMT. There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). Statistically significant differences in progression-free survival (PFS) were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide (TMZ) or TMZ plus other chemotherapies, regardless of their IDH or MGMT-methylation status (p-value=0.0014). Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS. Conclusions: The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. TMZ alone, compared to TMZ-plus, can increase PFS in upregulated PRMT5 tumors. Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.


Assuntos
Astrocitoma , Metilação de DNA , Metilases de Modificação do DNA , Enzimas Reparadoras do DNA , Progressão da Doença , Isocitrato Desidrogenase , Mutação , Regiões Promotoras Genéticas , Proteína-Arginina N-Metiltransferases , Proteínas Supressoras de Tumor , Humanos , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Isocitrato Desidrogenase/genética , Masculino , Feminino , Astrocitoma/genética , Astrocitoma/patologia , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Gradação de Tumores , Idoso , Temozolomida/uso terapêutico , Temozolomida/farmacologia , Regulação Neoplásica da Expressão Gênica
2.
Neurol Res ; : 1-11, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855923

RESUMO

OBJECTIVES: Central nervous system tuberculosis (TB) (CNS-TB) can occur in several forms, including intracranial tuberculoma, tuberculous brain abscess, TB meningitis (TBM), and spinal TB. Early treatment can save lives and prevent severe neurological complications. This study aimed to describe the characteristics and post-treatment outcomes of patients with CNS-TB and identify factors associated with poor outcomes. To the best of our knowledge, this is the largest CNS-TB study till date published in Saudi Arabia. METHODS: This retrospective cohort study included all patients diagnosed with CNS-TB in three tertiary centers in Saudi Arabia (King Abdulaziz Medical City in Jeddah, King Abdulaziz Medical City in Riyadh, and Al-Noor Specialist Hospital in Makkah) between 2009 and 2019. Data of patients' demographics, co-morbidities, presenting symptoms, type of CNS-TB, medical and surgical treatments, and outcome after completion of treatment were obtained from medical records. Treatment outcomes were categorized using the modified Rankin Scale for neurological disability. RESULTS: A total of 140 participants were included in this study from 2009 to 2019. Good outcomes were achieved in approximately 65% of cases, whereas 35% had poor outcomes based on the modified Rankin Scale. Glasgow Coma Scale score ≤10 at presentation and TBM/tuberculoma were significantly associated with poor outcomes. Moreover, the use of corticosteroids, more than three anti-TB medications, and surgical interventions were not significantly associated with good or poor outcomes. DISCUSSION: CNS-TB is associated with a high burden of long-term neurological morbidity. Early detection and treatment are crucial to prevent serious complications and decrease morbidity and mortality.

3.
Neurooncol Adv ; 6(1): vdad167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405204

RESUMO

Background: The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship. Methods: Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case-control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model. Results: Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66-0.91, P = .00; OCP: OR = 0.80, 95% CI 0.67-0.96, P = .02]. When stratified by duration of use, HRT use >1 year significantly reduced glioma risk (<1 year: OR = 0.82, 95% CI 0.63-1.07, P = 0.15; 1-5 years: OR = 0.79, 95% CI 0.67-0.92, P = .00; 5-10 years: OR = 0.80, 95% CI 0.66-0.97, P = .02; >10 years: OR = 0.69, 95% CI 0.54-0.88, P = .00). In contrast, only OCP use for >10 years significantly reduced glioma risk (<1 year: OR = 0.72, 95% CI 0.49-1.05, P = .09; 1-5 years: OR = 0.88, 95% CI 0.72-1.02, P = .09; 5-10 years: OR = 0.85, 95% CI 0.65-1.1, P = 0.21; >10 years: OR = 0.58, 95% CI 0.45-0.74, P = .00). Conclusions: Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.

4.
Pathol Res Pract ; 254: 155118, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241776

RESUMO

BACKGROUND: Tumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. METHODS: A group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. RESULTS: The mean patients' age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. CONCLUSIONS: During cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Idoso , Pessoa de Meia-Idade , Glioblastoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Recidiva Local de Neoplasia , Neoplasias Encefálicas/patologia , Isocitrato Desidrogenase
5.
Surg Neurol Int ; 14: 331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810306

RESUMO

Background: Xanthogranuloma of the sellar region is an extremely rare benign entity with only case reports and series documented in the literature. We aim to describe in this report a case of a suprasellar xanthogranuloma that was diagnosed initially as a cystic craniopharyngioma. Case Description: A 28-year-old woman presented to the clinic with a 2-week history of headaches, blurred vision, nausea, and vomiting. She had no medical or surgical history, no signs of hormonal disturbances, and no family history of brain tumors or endocrine diseases. Her neurological examination was unremarkable except for bitemporal hemianopia on visual field testing. A magnetic resonance imaging of the brain showed a cystic mass in the sellar region that was compressing the optic chiasm with radiological features representing cystic craniopharyngioma. She underwent endoscopic transnasal transsphenoidal surgery to excise the mass, and only subtotal excision was achieved to preserve the pituitary function. The histopathology confirmed the diagnosis of a xanthogranuloma of the sellar region. The postoperative course was unremarkable, and she did not receive any adjuvant therapy. There was no recurrence of the clinical symptoms or the mass during the 18-month follow-up period. Conclusion: Although xanthogranuloma is uncommon, it should be included in the differential diagnosis of sellar/suprasellar lesions. Due to its wide range of radiological features that sometimes can mimic other lesions, a definitive diagnosis can only be made postoperatively. Surgical excision is the most accepted treatment with a favorable prognosis and low rates of recurrence.

6.
Surg Neurol Int ; 14: 323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810319

RESUMO

Background: Neuroglial cysts (NCs) are uncommon benign cysts covered by an epithelial layer, accounting for <1% of all intracranial cysts. The optimal management approach for these cysts remains a subject of debate. Given their rarity, management principles used for arachnoid cysts can be applied to NCs. Case Description: We present a case of a 35-year-old male without prior medical history, who presented to the neurosurgery clinic with complaints of absence seizures. A neurological examination revealed subtle weakness in the left upper limb. Brain magnetic resonance imaging demonstrated a large cystic lesion in the posterior frontal and anterior parietal lobes of the right hemisphere. The patient underwent an awake craniotomy, during which a cystoventricular fenestration was performed on the motor cortex cyst. Histopathological examination confirmed the diagnosis of NC. At the 4-month follow-up, the patient experienced complete recovery, with normal strength (5/5) in all limbs and absence of seizure remission. Conclusion: This case highlights the successful use of awake craniotomy for the fenestration of an NC in the motor cortex. Given the rarity of NCs, there is no consensus on the optimal treatment strategy. However, in this particular case, the patient achieved complete recovery without any new neurological deficits following the procedure.

7.
Neurosurg Rev ; 46(1): 168, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37414966

RESUMO

Hemangioblastoma is a rare benign tumor that can affect the central nervous system sporadically or in association with von Hippel-Lindau (VHL) syndrome. Despite the advances in the medical field, hemangioblastoma still has a significant morbidity and mortality burden. This review gathered and analyzed this entity's top one hundred cited articles. The Scopus database was screened using the following keywords ("Hemangioblastoma" OR "Haemangioblastoma" OR "Hemangioblastomata"). The results were sorted by citation count, highest to lowest. Articles discussing hemangioblastoma of the central nervous system were included. Two independent reviewers extracted the article-, author-, and Journal-based data. Articles were classified into four categories: clinical features/ natural history, treatment, histopathology, review, or radiology. The location, brain, spine, or both, and type, sporadic, VHL-associated, or both, were used to classify the articles. The search query resulted in 4023 articles, and the top 100 most cited articles were included. The number of citations totaled 8781, averaging 87.81 CC per article. The included papers were published in 41 different journals between 1952 and 2014 by more than 11 departments from 65 institutions and 16 countries. The number of citations ranged from 46 to 333. The peak publication activity was before the 2000s, contributing to 62% of all articles, and the most prolific decade was 1990-2000, with 37 publications. We conducted a comprehensive bibliometric analysis of data from the most influential publications on central nervous system hemangioblastoma. We identified publication dynamics and research gaps. More high-impact studies are warranted to enhance disease comprehension and management.


Assuntos
Neoplasias do Sistema Nervoso Central , Hemangioblastoma , Doença de von Hippel-Lindau , Humanos , Bibliometria , Hemangioblastoma/cirurgia , Hemangioblastoma/patologia , Neoplasias do Sistema Nervoso Central/cirurgia , Encéfalo/patologia
8.
Cureus ; 15(2): e35213, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36968927

RESUMO

Background Cranioplasty (CP) is a common cranial reconstructive procedure. It is performed after craniectomy due to various causes such as relieving increased intracranial pressure, infection, and tumor infiltration. Although CP is an easy procedure, it is associated with a high rate of complications. We aimed to retrospectively investigate the outcomes of CP at the King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah (KAMC-J). Methods This is a retrospective observational study that included all patients who had CP (first time or redo) at KAMC-J from 1st January 2010 to 31st December 2020. Patients with congenital cranial malformation were excluded.  Result A total of 68 patients underwent CP. Of those, 23 (34%) had complications. The most common complication was infection (10.3%). Twelve of the 23 patients had major complications that necessitated reoperation. Of those 12, six underwent redo CP; three out of these six patients had further complications which were also managed surgically. On bivariate analysis, cranial defects over 50 cm² were associated with a higher rate of both infection and hydrocephalus (p=0.018) while the frontal site was associated with a higher rate of infection (p=0.014). Moreover, traumatic brain injury as an etiology was exclusively associated with post-cranioplasty hydrocephalus (p=0.03).  Conclusion Patients undergoing CP after craniectomy are prone to a considerably high rate of adverse outcomes. The overall rate of complications in this study was 34%, with an infection rate of 10.3% and a 1.5% mortality rate. Consistent with other studies, larger cranial defects as well as frontal sites have a higher rate of infection.

9.
Cureus ; 14(5): e25468, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35783878

RESUMO

Introduction Magnetic reasoning imaging (MRI) is the imaging modality of choice for detecting spinal pathologies. The study of the appropriateness of MRI utilization in Saudi Arabia is lacking. As a result, this research aims to assess the use and misuse of lumbar MRI in lower back pain (LBP) at the National Guard Hospital (NGH) in Jeddah city. Methods This is a retrospective cohort study that included all adult patients who had lumbar MRI for LBP at NGH in 2019. A total of 1,225 patients were included. Patients with extreme ages, trauma, recent lumbar spine surgery, spine or spinal canal tumors, and infection were excluded, leaving a number of 805 patients. Specific MRI findings were obtained and assessed in association with history and physical examination. Results LBP with radiculopathy was the most common complaint (82.9%) followed by LBP without radiculopathy (12.8%), with the lowest being limb pain alone (2.6%). Overall, 72% of patients had negative MRI findings, which did not explain their symptoms, and 28% had positive MRI findings that were not associated with their symptoms (p < 0.001). A complete physical examination was performed on 27.5% of patients, of which only 12% had positive findings. MRI was ordered for 72.5% of patients without a complete physical examination. Finally, 88.2% of patients who had MRI were managed conservatively, while only 6.7% were managed with surgery (p < 0.04). Conclusion The number of patients who had proper assessment prior to the ordering of MRI was significantly low. The decision to request MRI was not based on any scientific basis. This study has demonstrated that without proper and strict guidelines, MRIs will continue to be overutilized, which, in turn, will have negative consequences on the waiting time for an MRI and the cost of all the unnecessary MRIs. Furthermore, a good number of patients nowadays who do not have any indications for an MRI keep asking their physicians for it, and if the physician refuses, they transfer to another physician who will order the MRI.

10.
Surg Neurol Int ; 13: 120, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509546

RESUMO

Background: Hypertonic saline (HS) and mannitol are hyperosmolar agents that are usually used to reduce intracranial pressure (ICP) and provide a satisfactory brain relaxation. The aim of the study was to perform a systematic review and meta-analysis to compare the efficacy of HS and mannitol on brain relaxation intraoperatively in patient undergoing craniotomies for supra-tentorial brain tumors. Methods: A systematic review and meta-analysis of randomized control trials. We included randomized control trials that compared equiosmolar HS and mannitol in supratentorial tumors craniotomies and reported at least one of the following outcomes: degree of brain relaxation, ICP, central venous pressure, mean arterial pressure, perioperative fluid input, urine output, Na+ levels, and K+ levels. We searched Medline, Cochrane Central Register of Controlled Trials, and Embase using MESH terms and keywords. The bibliographic references of included studies and trial registries were also searched. Results: Seven articles were included. The degree brain of relaxation was comparable across the two groups with slight tendency toward HS (RR = 1.13, 95% CI 0.99-1.29; P = 0.08). Mannitol was associated with significantly higher urine output (standardized mean difference [SMD] = -1.33, 95% CI -1.56--1.10; P < 0.001). Na+ levels were higher in HS group (SMD = 1.47, 95% CI 0.86-2.09; P < 0.001). Mannitol was associated with non-significant decrease in CVP and increase fluid input (SMD = 0.42, 95% CI 0.00-0.85 and SMD = -0.18, 95% CI -0.37-0.02, respectively). Conclusion: Both HS and mannitol are associated with satisfactory brain relaxation with a non-statistically significant tendency for HS to achieve better relaxation scores with mannitol resulting in higher urine output while HS with higher Na+ levels.

11.
Turk Patoloji Derg ; 38(1): 34-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34514580

RESUMO

OBJECTIVE: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections. MATERIAL AND METHOD: The authors reviewed the histopathological results of 383 brain tumors, including IOFS and permanent histological diagnosis. The cases were classified into three diagnostic compatibilities (i) Perfect fit; the diagnosis of IOFS was identical to the permanent diagnosis, (ii) Partial compatibility; IOFS diagnosis was not incorrect but was too broad to be considered full compatibility, (iii) Conflict; IOFS diagnosis is completely different from the permanent diagnosis. The permanent diagnosis was used as a primary criterion and was compared to IOFS diagnosis and recurrence rate using different statistical methods. RESULTS: 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy. Approximately, 53.8 % of the cases revealed perfect matching in the diagnosis between IOFSs and permanent sections, while 16.2% of the cases revealed complete mismatching in the diagnosis between the sections. The remaining 30% of the cases showed partial compatibility in the diagnosis between the two diagnostic methods. There was no significant difference in recurrence rate among all cases of different diagnostic compatibility (p=0.54). CONCLUSION: There is a diagnostic discrepancy between IOFSs and permanent sections. However, cases that revealed no consensus in the diagnoses showed no negative effect on the patient outcome. Further studies should be conducted to explore the reasons of this conflict in the two diagnostic methods.


Assuntos
Neoplasias Encefálicas , Secções Congeladas , Biópsia , Neoplasias Encefálicas/diagnóstico , Humanos , Estudos Retrospectivos
12.
Cureus ; 13(12): e20246, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34912650

RESUMO

Objectives The objectives of this study are to explore the most common causes, patterns, and severities of head traumas, to evaluate the outcomes of traumatic head injury (TBI) patients followed in the clinic, and to calculate the prevalence of admitted cases. Methods In our retrospective cohort study, we included all the cases of adults above 18 years old diagnosed with head traumas (171 patients). The inclusion criteria were patients who presented to the emergency department at National Guard Health Affairs (NGHA), Jeddah, Saudi Arabia from 2016 to 2020. Patients were categorized according to their Glasgow Coma Scale (GCS) score upon admission. Results Of the 171 patients in this study, 151 (88.3%) were males and 20 (11.7%) were females. The median age of our patients was 31 years. Most of the cases had no medical illnesses 124 (72.5%). The most common mechanism of injury was motor vehicle accidents (MVAs) in the majority of our cases (105, 61.4%), followed by falls from heights (34, 19.9%). The commonest computed tomography (CT) finding was subdural hematoma (47, 27.4%). The majority of the associated injuries were thoracic cases (43, 25.1%), followed by spinal (40, 23.4%). Most of the patients were admitted to NGHA (120, 70.2%), while the rest (51, 29.8%) were transferred from other hospitals. Of the total of 171 patients, 134 (78.4%) were treated conservatively. There were no associations between mortality nor length of stay and patients' demographics, except for GCS on admission showed a significant p-value (<0.005). Conclusion In this study, it was found that the most common causes of TBI are MVAs followed by falls from heights. Therefore, preventive measures such as traffic safety rules need to be addressed.

13.
Childs Nerv Syst ; 37(12): 3847-3860, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34345934

RESUMO

PURPOSE: To systematically review reported cases of Seckel syndrome (SS) and point out cases associated with central nervous system (CNS) vasculopathy and provide a summary of their clinical presentation, management, and outcomes including our illustrative case. METHODS: We conducted a search on the MEDLINE, PubMed, Google Scholar, and Cochrane databases using the keywords "Seckel + syndrome." We identified 127 related articles reporting 252 cases of SS apart from our case. Moreover, we searched for SS cases with CNS vasculopathies from the same databases. We identified 7 related articles reporting 7 cases of CNS vasculopathies in SS patients. RESULTS: The overall rate of CNS vasculopathy in SS patients is 3.16% (n = 8/253), where moyamoya disease (MMD) accounted for 1.97%. The mean age is 13.5 years (6-19 years), with equal gender distribution (M:F, 1:1). The most common presenting symptoms were headache and seizure followed by weakness or coma. Aneurysms were mostly located in the basilar artery, middle cerebral artery, and internal carotid artery, respectively. Regardless of the management approach, 50% of the cases sustained mild-moderate neurological deficit, 37.5% have died, and 12.5% sustained no deficit. CONCLUSION: A high index of suspicion should be maintained in (SS) patients, and MMD should be part of the differential diagnosis. Prevalence of CNS vasculopathy in SS is 3.16% with a much higher prevalence of MMD compared to the general population. Screening for cerebral vasculopathy in SS is justifiable especially in centers that have good resources. Further data are still needed to identify the most appropriate management plan in these cases.


Assuntos
Transtornos Cerebrovasculares , Nanismo , Microcefalia , Doença de Moyamoya , Adolescente , Sistema Nervoso Central , Transtornos Cerebrovasculares/epidemiologia , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/epidemiologia
14.
Biologics ; 15: 289-297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335021

RESUMO

PURPOSE: Wilms tumor 1 (WT1) gene has recently shown a role in gliomagenesis, making it a potential immunotherapy target in glioblastomas. We aimed to investigate the most sensitive method to detect WT1 expression in glioblastoma and explore the relationship between WT1 expression, IDH1 mutation and recurrence interval. PATIENTS AND METHODS: Clinical data were collected from 44 patients with glioblastomas, treated with adjuvant therapies. WT1 expression was assessed in all cases using immunohistochemistry (IHC), while its gene expression was assessed in 13 clustered samples using polymerase chain reaction (qPCR). IDH1 mutation was assessed using IHC. The sensitivity between IHC and RT-qPCR was examined. Kaplan-Meier curves were used to compare the recurrence-free interval (RFI) between IDH1 and WT1 expression groups. RESULTS: IDH1wildtype was found in 26 cases (59.1%) and the remaining 18 cases (40.9%) were IDH1mutant. Through IHC, WT1 was overexpressed in 32 cases (72.7%), partially expressed in 9 cases (20.5%) and not expressed in only 3 cases. For the 13 cases tested by qPCR, 6 cases showed WT1 upregulation and 7 cases showed WT1 downregulation. There was no significant difference in WT1 expression among cases with different RNA concentrations regardless the testing method (p-value >0.05). However, the difference between IHC and qPCR was significant. IDH1mutant cases with WT1 overexpression showed significant difference in RFI (p-value =0.048). CONCLUSION: Parallel testing for WT1 expression using IHC and qPCR is not reliable. However, IHC provides more accurate results. Moreover, IDH1mutant glioblastomas with WT1 overexpression are associated with late RFI particularly if temozolomide with additional chemotherapies are used.

15.
Pathol Oncol Res ; 27: 1609778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257620

RESUMO

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.


Assuntos
Biomarcadores Tumorais/genética , Quimiorradioterapia/mortalidade , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/patologia , Isocitrato Desidrogenase/genética , Recidiva Local de Neoplasia/patologia , Proteínas Supressoras de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida
16.
World Neurosurg ; 154: e547-e554, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34325024

RESUMO

INTRODUCTION: After the official announcement of the coronavirus disease-19 pandemic on March 11, 2020, the disease impacted most aspects of health care delivery, especially postgraduate education and training. METHOD: A cross-sectional, online questionnaire-based assessment was performed. The study participants involved neurosurgery residents and program directors (PDs) across the country between May 16 and May 27, 2020. RESULTS: Approximately 74 of 95 (77.9%) of the residents experienced an impact on their training calendar. Before the pandemic, 51 residents (53.3%) were involved in 2-3 surgeries per week, but during the pandemic, 66 (69.5%) were attending 0-1 case per week. Fifty-three residents (55.8%) agreed that academic sessions were affected despite the helpful effort of online teaching sessions. Thirty-four (35.8%) residents graded their anxiety during coronavirus disease-19 times as high. Ten PDs (58.8%) confirmed spending 3-5 hours per week on educational activities normally, whereas during the pandemic, 15 PDs (88.2%) reduced their educational hours to 0-2 hours per week. CONCLUSION: Our study showed that educational activities significantly decreased and shifted toward virtual teaching methods. Operative volume showed a substantial reduction for both junior and senior residents. Academic and clinical teaching was the main concern for PDs, and they faced challenges interviewing newly matched residents.


Assuntos
COVID-19 , Internato e Residência/estatística & dados numéricos , Neurocirurgia/educação , Pandemias , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Arábia Saudita , Inquéritos e Questionários , Adulto Jovem
17.
Epidemiol Health ; 43: e2021037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34030435

RESUMO

OBJECTIVES: Central nervous system (CNS) tumors are a major and growing global healthcare challenge. Western Saudi Arabia has an inconsistent data registry; therefore, the epidemiology of CNS tumors is unclear across the country. This study is aimed to assemble the epidemiological matrix of CNS tumors in the Western Province of Saudi Arabia. METHODS: A retrospective analysis was performed using clinical data obtained from 3 neuroscience centers in Western Saudi Arabia in the period 2014-2019. The sample size included 663 adult and pediatric cases from the local and expatriate populations diagnosed with CNS tumors. The distributions of age, sex, clinical presentation, tumor location, type of surgery, histological subtype, genetic characteristics, and recurrence rate were explored. RESULTS: The analysis included 500 adult cases and 163 pediatric cases up to 18 years of age with a male-to-female ratio of 1.16. The mean age at diagnosis was 38.0±22.6 years. The supratentorium was the most common location (n=515, 77.7%). Most patients presented with headache (n=298, 44.9%), followed by a focal neurological deficit (19.9%). The most common primary CNS tumor was glioblastoma (n=234, 35.3%), followed by meningioma (n=100, 15.1%). The recurrence rate after surgery was estimated to be 40.9% among all CNS tumors. CONCLUSIONS: This is the first tumor registry of Western Province of Saudi Arabia that describes the distribution of primary CNS tumors and highlights their epidemiological matrix. Several incidence trends in terms of histological type, age group, sex, location, and recurrence were determined, and some genetic characteristics were recognized.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Adulto Jovem
18.
J Neurooncol ; 152(3): 541-549, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33661424

RESUMO

OBJECTIVE: To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. METHOD: We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. RESULTS: No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. CONCLUSION: Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA , Enzimas Reparadoras do DNA/genética , Dacarbazina/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , O(6)-Metilguanina-DNA Metiltransferase/genética , Prognóstico , Temozolomida/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor
19.
Surg Neurol Int ; 11: 257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33024595

RESUMO

BACKGROUND: Synovial sarcoma (SS) of the spine is a rare malignant soft-tissue tumor, and there are few reported cases. The aim of this paper is to report a rare case of spinal SS involving the paraspinal muscles, and to review all such cases reported in the literature. CASE DESCRIPTION: In this paper, we report a rare case of spinal SS involving the paraspinal muscles in a 12-year-old girl. The patient underwent surgical excision of the mass with adjuvant radiation and chemotherapy. At the 1-year follow-up, there was no evidence of local tumor recurrence, and the patient's symptoms had improved. In addition, we identified and reviewed 33 reported cases of SS involving the spine. CONCLUSION: Due to the limited number of reported cases in the literature, it is difficult to predict the outcomes of spinal SS. Further, different treatment modalities have been used to treat spinal SS. However, most of the reported cases had poor outcomes. Therefore, prospective multi-center studies are needed to further investigate the treatment strategies and outcomes for patients with spinal SS.

20.
Int J Health Sci (Qassim) ; 11(3): 54-62, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28936153

RESUMO

The treatment recommendations provided in this manuscript are intended to serve as a knowledge base for clinicians and health personals involved in treating patients with high-grade malignant glioma. In newly diagnosed patients, complete resection or biopsy is required for histological characterization of the tumor, which in turn is essential to decide the treatment strategy. In patients with good or borderline performance score, radiotherapy (RT), and chemotherapy are the preferred management. In patients with poor performance score, RT with best possible supportive care is the mainstay of the management. All patients have to undergo brain magnetic resonance imaging procedure quarterly or half-yearly for 5 years and then on an annual basis. In patients with recurrent malignant glioma, wherever possible re-resection or re-irradiation or chemotherapy can be considered along with supportive and palliative care. High-grade malignant glioma should be managed in a multidisciplinary center with the best of the possible care that is available based on the evidence as discussed in this manuscript.

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