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The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.
Assuntos
Neoplasias Encefálicas , Metilação de DNA , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioma , Isocitrato Desidrogenase , Fator 4 Semelhante a Kruppel , Mutação , Humanos , Isocitrato Desidrogenase/genética , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Ilhas de CpG/genética , Feminino , Masculino , Astrocitoma/genética , Astrocitoma/patologia , Astrocitoma/metabolismo , Pessoa de Meia-Idade , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , AdultoRESUMO
Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.
Assuntos
Ependimoma , Neoplasias da Medula Espinal , Adulto , Criança , Humanos , Transcriptoma , Perfilação da Expressão Gênica , Mutação , Epigênese GenéticaRESUMO
PURPOSE: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. METHODS: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. RESULTS: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. CONCLUSIONS: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Glioblastoma/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Quimiorradioterapia , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/cirurgia , Tronco Encefálico/patologia , Neoplasias Encefálicas/patologiaRESUMO
PURPOSE: We aimed to evaluate the effect of deep learning-based reconstruction (DLR) on high-spatial-resolution three-dimensional T2-weighted fast asymmetric spin-echo (HR-3D T2-FASE) imaging in the preoperative evaluation of cerebellopontine angle (CPA) tumors. METHODS: This study included 13 consecutive patients who underwent preoperative HR-3D T2-FASE imaging using a 3 T MRI scanner. The reconstruction voxel size of HR-3D T2-FASE imaging was 0.23 × 0.23 × 0.5 mm. The contrast-to-noise ratios (CNRs) of the structures were compared between HR-3D T2-FASE images with and without DLR. The observers' preferences based on four categories on the tumor side on HR-3D T2-FASE images were evaluated. The facial nerve in relation to the tumor on HR-3D T2-FASE images was assessed with reference to intraoperative findings. RESULTS: The mean CNR between the tumor and trigeminal nerve and between the cerebrospinal fluid and trigeminal nerve was significantly higher for DLR images than non-DLR-based images (14.3 ± 8.9 vs. 12.0 ± 7.6, and 66.4 ± 12.0 vs. 53.9 ± 8.5, P < 0.001, respectively). The observer's preference for the depiction and delineation of the tumor, cranial nerves, vessels, and location relation on DLR HR-3D T2FASE images was superior to that on non-DLR HR-3D T2FASE images in 7 (54%), 6 (46%), 6 (46%), and 6 (46%) of 13 cases, respectively. The facial nerves around the tumor on HR-3D T2-FASE images were visualized accurately in five (38%) cases with DLR and in four (31%) without DLR. CONCLUSION: DLR HR-3D T2-FASE imaging is useful for the preoperative assessment of CPA tumors.
Assuntos
Aprendizado Profundo , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Cuidados Pré-Operatórios , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Cuidados Pré-Operatórios/métodos , Idoso , Ângulo Cerebelopontino/diagnóstico por imagem , Ângulo Cerebelopontino/cirurgia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/cirurgia , Interpretação de Imagem Assistida por Computador/métodos , Estudos Retrospectivos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgiaRESUMO
PURPOSE: The aim of this study is to assess the effect of super-resolution deep learning-based reconstruction (SR-DLR), which uses k-space properties, on image quality of intracranial time-of-flight (TOF) magnetic resonance angiography (MRA) at 3 T. METHODS: This retrospective study involved 35 patients who underwent intracranial TOF-MRA using a 3-T MRI system with SR-DLR based on k-space properties in October and November 2022. We reconstructed MRA with SR-DLR (matrix = 1008 × 1008) and MRA without SR-DLR (matrix = 336 × 336). We measured the signal-to-noise ratio (SNR), contrast, and contrast-to-noise ratio (CNR) in the basilar artery (BA) and the anterior cerebral artery (ACA) and the sharpness of the posterior cerebral artery (PCA) using the slope of the signal intensity profile curve at the half-peak points. Two radiologists evaluated image noise, artifacts, contrast, sharpness, and overall image quality of the two image types using a 4-point scale. We compared quantitative and qualitative scores between images with and without SR-DLR using the Wilcoxon signed-rank test. RESULTS: The SNRs, contrasts, and CNRs were all significantly higher in images with SR-DLR than those without SR-DLR (p < 0.001). The slope was significantly greater in images with SR-DLR than those without SR-DLR (p < 0.001). The qualitative scores in MRAs with SR-DLR were all significantly higher than MRAs without SR-DLR (p < 0.001). CONCLUSION: SR-DLR with k-space properties can offer the benefits of increased spatial resolution without the associated drawbacks of longer scan times and reduced SNR and CNR in intracranial MRA.
Assuntos
Aprendizado Profundo , Angiografia por Ressonância Magnética , Humanos , Angiografia por Ressonância Magnética/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Razão Sinal-Ruído , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.
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Pineal parenchymal tumors (PPTs) are rare, accounting for less than 0.3% of all primary central nervous system (CNS) tumors. Pineal parenchymal tumors of intermediate differentiation (PPTID) (WHO grade 2 or 3) show an intermediate prognosis between pineocytoma and pineoblastoma. The clinical course is unknown, and the optimal treatment for PPTID, especially for recurrence, has not been determined. We report a case of PPTID with spinal dissemination over 10 years after treatment and survival for four years. A 56-year-old woman presented with headaches and diplopia. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a pineal mass, but leptomeningeal dissemination was not identified on whole-spine MRI. Microsurgical gross total tumor resection (GTR) was performed, and the pathological diagnosis was PPTID (grade 3). In addition, a later study found it to harbor a KBTBD4 mutation. She underwent whole-brain radiation therapy with a focal boost. The patient was unable to continue chemotherapy for severe myelosuppression after the first course of treatment. Eleven years after the surgery, she was unable to walk, and a whole-spine MRI revealed multiple masses at C3-4, T4, and cauda equina. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed accumulations of the same lesions. No recurrence was observed in the brain. A biopsy of the caudal portion was performed, and the histopathological findings were the same as those of the initial surgery. Spinal dissemination was refractory to chemotherapy but responded to whole spine radiotherapy with focal boost, and she remained tumor-free for four years. We considered good local control with a combination of GTR and subsequent radiation therapy to contribute to long-term survival. The timing of spinal radiation administration is controversial because of the tendency for late cerebrospinal dissemination. The importance of long-term follow-up of the spine and head is emphasized. In PPTID cases with good local control, withholding spinal radiation until spinal dissemination occurs may become a long-term treatment plan.
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Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.
Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Adulto , Humanos , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Estudos Retrospectivos , Qualidade de Vida , Seguimentos , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Resultado do Tratamento , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgiaRESUMO
Chordoma is a rare tumor that arises from chordal tissue during fetal life. Recently, the concept of poorly differentiated chordoma, a subtype of chordoma characterized by loss of SMARCB1/INI1 with a poorer prognosis than conventional chordomas, was established. It predominantly occurs in children and is rare in adults. Here, we report a rare adult case of poorly differentiated chordoma of the skull base with a unique course that rapidly systemically metastasized and had the shortest survival time of any adult chordoma reported to date. The patient was a 32-year-old male with a chief complaint of diplopia. MRI showed a widespread neoplastic lesion with the clivus as the main locus. Endoscopic extended transsphenoidal tumor resection was performed. Pathological findings showed that the tumor was malignant, and immunohistochemistry revealed a Ki-67 labeling index of 80%, diffusely positive brachyury, and loss of INI1 expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the residual tumor in the right cavernous sinus showed rapid growth. The patient was promptly treated with gamma knife three fractions. The residual tumor regressed, but the tumor developed systemic metastasis in a short period, and the patient died seven months after diagnosis. This report of a rapidly progressing and fatal adult poorly differentiated chordoma shows the highest Ki-67 labeling index reported to date. Prompt multidisciplinary treatment should be considered when the Ki-67 labeling index is high.
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BACKGROUND AND OBJECTIVES: The choice between inhalational and total intravenous anesthesia (TIVA) in revascularization surgery for Moyamoya disease (MMD) remains a topic of debate. Anesthesia methods have changed with the advent of new anesthetics. This study investigated whether modern anesthesia methods affected the development of neurological symptoms after revascularization surgery for MMD. METHODS: This single-center retrospective study included 63 adult patients (82 hemispheres) with MMD treated with direct and indirect bypass surgeries at our hospital between 2013 and 2022. Patients were divided into inhalational anesthesia (IA) and TIVA groups based on the anesthesia maintenance method. Baseline patient characteristics; postoperative neurological symptoms, including hyperperfusion syndrome, cerebral infarction, and transient neurological events (TNEs); and cortical hyperintensity belt (CHB) sign scores (5-point scale from 0 to 4) on postoperative magnetic resonance imaging were compared between the two groups. The operation methods, anesthetics, and intraoperative hemodynamic and ventilatory parameters were compared between patients with and without TNEs. RESULTS: The IA and TIVA groups comprised 39 and 43 hemispheres, respectively. The frequency of postoperative hyperperfusion syndrome and cerebral infarction did not differ between the groups, but the number of TNEs in the IA group (5/39; 13%) was significantly lower than that in the TIVA group (16/43; 37%). Multivariate logistic regression analysis revealed that TNEs were associated with TIVA (odds ratio, 3.91; 95% CI, 1.24-12.35; P = .02). The median [IQR] postoperative CHB sign score in the IA group (2 [1-3]) was significantly lower than that in the TIVA group (4 [3-4]). CONCLUSION: The IA group had fewer postoperative TNEs and lower CHB sign scores than the TIVA group. Although further studies are needed, this study provides insights into the prevention of TNEs with IA and reconsideration of the optimal anesthesia for MMD.