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PURPOSE: The cortical high-flow sign with the non-enhancing area was reportedly found to be more frequent with oligodendroglioma, IDH-mutant and 1p/19q codeleted (ODG IDHm-codel) than with IDH-wildtype or astrocytoma, IDH-mutant on arterial spin labeling (ASL) in diffuse gliomas. This study aimed to compare the identification rate of the cortical high-flow sign on ASL in patients with ODG IDHm-codel to that on dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). METHODS: Participants consisted of 32 adult ODG IDHm-codel patients with pathologically confirmed. Subtraction images were generated from paired control and label images on ASL. For DSC, dynamic T2*-weighted perfusion weighted images were obtained after pre-bolus of gadolinium-based contrast agent. Regional cerebral blood flow/volume maps were generated based on the concentration-time curve and arterial input function. Tumor-affecting cortices without contrast enhancement on conventional MR imaging were targeted. The identification rate of the cortical high-flow sign was compared between ASL and DSC using the Pearson's Chi-Square test. RESULTS: Frequency of the cortical high-flow sign was significantly higher on ASL (18/32, 56.3%; p < 0.001) than on DSC (5/32, 15.6%). All cases with the positive cortical high-flow sign on DSC were identified on ASL. CONCLUSION: ASL effectively identifies the cortical high-flow sign in ODG IDHm-codel, surpassing DSC in identification rates.
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Neoplasias Encefálicas , Glioma , Oligodendroglioma , Adulto , Humanos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Marcadores de Spin , Imageamento por Ressonância Magnética/métodos , Mutação , Isocitrato Desidrogenase/genéticaRESUMO
PURPOSE: This study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method. METHODS: Thirty-three cases (men, 14; women, 19) comprising 19 astrocytomas and 14 oligodendrogliomas were evaluated. Four radiologists independently evaluated the presence of the T2-FLAIR mismatch sign. A 3D convolutional neural network (CNN) model was trained using 50 patients outside the test group (28 astrocytomas and 22 oligodendrogliomas) and transferred to evaluate the T2-FLAIR mismatch lesions in the test group. If the CNN labeled more than 50% of the T2-prolonged lesion area, the result was considered positive. The T1/T2-relaxation times and proton density (PD) derived from SyMRI were measured in both gliomas. Each quantitative parameter (T1, T2, and PD) was compared between gliomas using the Mann-Whitney U-test. Receiver-operating characteristic analysis was used to evaluate the diagnostic performance. RESULTS: The mean sensitivity, specificity, and area under the curve (AUC) of radiologists vs. AI were 76.3% vs. 94.7%; 100% vs. 92.9%; and 0.880 vs. 0.938, respectively. The two types of diffuse gliomas could be differentiated using a cutoff value of 2290/128 ms for a combined 90th percentile of T1 and 10th percentile of T2 relaxation times with 94.4/100% sensitivity/specificity with an AUC of 0.981. CONCLUSION: Compared to the radiologists' assessment using the T2-FLAIR mismatch sign, the AI and the SyMRI assessments increased both sensitivity and objectivity, resulting in improved diagnostic performance in differentiating gliomas.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Masculino , Humanos , Feminino , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Inteligência Artificial , Diagnóstico Diferencial , Estudos Retrospectivos , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Isocitrato Desidrogenase/genéticaRESUMO
Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as "Drug resistance gene testing for anticancer chemotherapy" and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.
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INTRODUCTION: Open-lip-type schizencephaly is characterized by trans-cerebral clefts filled with cerebrospinal fluid (CSF) between the subarachnoid space at the hemisphere surface and the lateral ventricles. Disorders related to CSF retention, including hydrocephalus and arachnoid cysts, have reportedly been associated with open-lip schizencephaly and have induced intracranial hypertension in some cases. However, detailed neuroimaging and surgical treatment findings have rarely been described. CASE PRESENTATION: We report 2 cases of open-lip schizencephaly with an expanding CSF-filled cavity overlying the ipsilateral cerebral hemisphere that manifested as signs of intracranial hypertension. Detailed three-dimensional heavily T2-weighted imaging revealed thin borders between the CSF-filled cavity and the subarachnoid space, but no separating structures between the cavity and the lateral ventricle, suggesting that the cavity was directly connected to the lateral ventricle through the schizencephalic cleft but not to the subarachnoid space. Neuroendoscopic observation in case 1 confirmed this finding. Endoscopic fenestration of the cavity to the prepontine cistern was ineffective in case 1. Shunting between the lateral ventricle (case 1) or CSF-filled cavity (case 2) and the peritoneal cavity slightly decreased the size of the CSF-filled cavity. DISCUSSION: We speculate that the thin borders along the margin of the CSF-filled cavity are membranes that previously covered the schizencephalic cleft and are now pushed peripherally. In addition, we believe that the cavity is a ventricular diverticulum protruding through the cleft and that shunting operation is effective against such expanding cavity. Detailed magnetic resonance imaging can be useful for evaluating patients with schizencephaly associated with CSF retention disorders.
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Esquizencefalia , Humanos , Masculino , Esquizencefalia/diagnóstico por imagem , Esquizencefalia/cirurgia , Esquizencefalia/complicações , Feminino , Divertículo/cirurgia , Divertículo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hidrocefalia/cirurgia , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Lactente , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/cirurgiaRESUMO
Endoscopic endonasal skull base surgery is increasingly prevalent, with its scope expanding from pathogens in the midline region to those in the paramedian region. Maximizing anterior sphenoidectomy is important for the median approach, and lateralizing the pterygopalatine fossa is crucial for the paramedian approach. Maximizing the surgical corridor in the nasal cavity and minimizing damage to neurovascular structures are vital for establishing a surgical field with minimal bleeding, ensuring safe, precise, and gentle procedures. However, the relationship between the maxillofacial and skull base bones in endoscopic endonasal skull base surgery is difficult to understand because these bones are intricately articulated, making it challenging to visualize each bone's outline. Understanding important bones and their related neurovascular structures is essential for all skull base surgeons to maximize the surgical corridor and minimize iatrogenic injury to neurovascular structures. This study aimed to elucidate the role of the palatine bone from a microsurgical anatomical perspective. Three dry skulls were used to demonstrate the structure of the palatine bone and its relationship with surrounding bones. A formalin-perfused cadaveric head was dissected to show the related neurovascular structures. The arteries and veins of the cadaveric heads were injected with red- and blue-colored silicon. Dissection was performed using a surgical microscope and endoscope. In addition, the utilization of the palatine bone as a landmark to identify neurovascular structures, which aids in creating a wider surgical field with less bleeding, was shown in two representative cases. The palatine bone consists of unique complex structures, including the sphenoidal process, ethmoidal crest, pterygopalatine canal, and sphenopalatine notch, which are closely related to the sphenopalatine artery, maxillary nerve, and its branches. The ethmoidal crest of the palatine bone is a well-known structure that is useful for identifying the sphenopalatine foramen, controlling the sphenopalatine artery and nerve, and safely opening the pterygopalatine fossa. The sphenoidal process of the palatine bone is a valuable landmark for identifying the palatovaginal artery, which is a landmark used to safely and efficiently expose the vidian canal. The sphenoidal process is easily cracked with an osteotome and removed to expose the palatovaginal artery, which runs along the pharyngeal groove, just medial to the vidian canal. By opening the pterygopalatine canal (also known as the greater palatine canal), further lateralization of the periosteum-covered pterygopalatine fossa contents can be achieved. Overall, the sphenoidal process and ethmoidal crest can be used as important landmarks to maximize the surgical corridor and minimize unnecessary injury to neurovascular structures.
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PURPOSE: Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. METHODS: At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. RESULTS: PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49 years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. CONCLUSIONS: Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.
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Neoplasias Encefálicas , Glândula Pineal , Pinealoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Pinealoma/genética , Pinealoma/terapia , Pinealoma/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Estudos de Coortes , Intervalo Livre de Progressão , Glândula Pineal/patologia , Estudos RetrospectivosRESUMO
This study aimed to investigate whether arterial spin labeling (ASL) features allow differentiation of oligodendroglioma, IDH-mutant and 1p/19q-codeleted (IDHm-codel) from diffuse glioma with IDH-wildtype (IDHw) or astrocytoma, IDH-mutant (IDHm-noncodel). Participants comprised 71 adult patients with pathologically confirmed diffuse glioma, classified as IDHw, IDHm-noncodel, or IDHm-codel. Subtraction images were generated from paired-control/label images on ASL and used to assess the presence of a cortical high-flow sign. The cortical high-flow sign was defined as increased ASL signal intensity within the tumor-affecting cerebral cortex compared with normal-appearing cortex. Regions without contrast enhancement on conventional MR imaging were targeted. The frequency of the cortical high-flow sign on ASL was compared among IDHw, IDHm-noncodel, and IDHm-codel. As a result, the frequency of the cortical high-flow sign was significantly higher for IDHm-codel than for IDHw or IDHm-noncodel. In conclusion, the cortical high-flow sign could represent a hallmark of oligodendroglioma, IDH-mutant, and 1p/19q-codeleted without intense contrast enhancement.
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Neoplasias Encefálicas , Glioma , Oligodendroglioma , Adulto , Humanos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Mutação , Glioma/diagnóstico por imagem , Glioma/genética , Biomarcadores , Isocitrato Desidrogenase/genéticaRESUMO
PURPOSE: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated with tumor aggressiveness. The aim of this study was to identify features from MR spectroscopy (MRS) and multi-exponential models of DWI distinguishing wild-type TERT (TERTw) from TERT promoter mutation (TERTm) in IDH-wildtype diffuse astrocytic glioma. METHODS: Participants comprised 25 adult patients with IDH-wildtype diffuse astrocytic glioma. Participants were classified into TERTw and TERTm groups. Point-resolved spectroscopy sequences were used for MRS data acquisition. DWI was performed with 13 different b-factors. Peak height ratios of NAA/Cr and Cho/Cr were calculated from MRS data. Mean apparent diffusion coefficient (ADC), perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), distributed diffusion coefficient (DDC), and heterogeneity index (α) were obtained using multi-exponential models from DWI data. Each parameter was compared between TERTw and TERTm using the Mann-Whitney U test. Correlations between parameters derived from MRS and DWI were also evaluated. RESULTS: NAA/Cr and Cho/Cr were both higher for TERTw than for TERTm. The α of TERTw was smaller than that of TERTm, while the f of TERTw was higher than that of TERTm. NAA/Cr correlated negatively with α, but not with other DWI parameters. Cho/Cr did not show significant correlations with any DWI parameters. CONCLUSION: The combination of NAA/Cr and α may have merit in clinical situation to predict the TERT mutation status of IDH-wildtype diffuse astrocytic glioma without intense enhancement.
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Astrocitoma , Neoplasias Encefálicas , Telomerase , Adulto , Humanos , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Astrocitoma/patologia , Espectroscopia de Ressonância Magnética/métodos , Mutação , Telomerase/genéticaRESUMO
PURPOSE: Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. METHODS: Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134 mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. RESULTS: DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the two groups. CONCLUSION: The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.
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Acromegalia , Hormônio do Crescimento Humano , Hiponatremia , Neoplasias Hipofisárias , Humanos , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Estudos Retrospectivos , Incidência , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Sódio , Peso Corporal , Fator de Crescimento Insulin-Like I , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologiaRESUMO
Classification and molecular diagnosis of benign brain tumors, focusing on cranial and pasaspinal nerve tumors, meningioma, mesenchymal, and non-meningothelial tumors involving the central nervous system(CNS)has been reviewed based on the 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System. In sporadic schwannomas, the novel fusion gene SH3PXD2A-HTRA1, which activates the MAPK pathway, has been discovered. Meningioma shows frequent chromosomal alterations, including at the NF2 locus. Recent genomic studies have investigated mutations in TRAF7, KLF4, AKT1, and SMO in sporadic meningiomas. In the 5th edition, the meningioma should be graded regardless of the subtype. Thus, TERT promoter mutation and homozygous deletion of CDKN2A/B should be evaluated to define grade 2 and 3 meningiomas. In mesenchymal tumors, the term "hemangiopericytoma" has been deleted from solitary fibrous tumors.
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Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Tumores Fibrosos Solitários , Humanos , Meningioma/diagnóstico , Meningioma/genética , Homozigoto , Deleção de Sequência , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genéticaRESUMO
The mutation p.K27M in H3F3A (H3 K27M mutation) is mainly detected in diffuse midline glioma. However, recent studies have demonstrated that H3 K27M mutation could also be observed in a subset of gangliogliomas. Importantly, most H3 K27-mutated ganglioglioma cases also harbor BRAF V600E mutation. Herein, we report a rare case of H3 K27M-mutated ganglioglioma grade 3 without BRAF mutation arising in the medial temporal lobe in an elderly man. A small biopsy specimen was sampled. The pathological diagnosis was diffuse astrocytoma. The tumor progressed gradually during an 18-month follow-up period. Gadolinium enhancement on magnetic resonance imaging was noted 36 months after the biopsy. The patient was referred to a hospital for tumor resection. Histological analysis of resected specimens led to a diagnosis of ganglioglioma grade 3 with H3 K27M mutation. The patient underwent concurrent temozolomide chemotherapy with radiotherapy. Although the patient's condition deteriorated after chemotherapy due to disease progression, he survived for more than 23 months after tumor resection. We present this rare case and discuss the involvement of H3 K27M mutation in ganglioglioma grade 3.
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Neoplasias Encefálicas , Ganglioglioma , Glioma , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Meios de Contraste , Gadolínio , Ganglioglioma/genética , Glioma/genética , Histonas/genética , Humanos , Masculino , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Lobo Temporal/patologiaRESUMO
It is often difficult to distinguish infectious disease of the central nervous system from a wide variety of non-infectious diseases, as neurosurgeons have few opportunities to treat them. Differentiation of infectious diseases from neoplastic diseases is often challenging. Since it often takes time to eliminate infectious diseases, it is necessary to utilize all the obtained medical information to make a proper diagnosis to avoid missing the appropriate chance of surgical treatment. In this paper, we describe tips for and pitfalls of accurately distinguishing such diseases, including brain abscess versus glioblastoma, meningitis versus dural lesions, and infection versus lymphoproliferative disorders in immunocompromised patients. In these cases, it is difficult to make a decision based only on the examination and imaging findings on admission, and it is important to make a diagnosis based on medical history and patient background.
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Abscesso Encefálico , Doenças do Sistema Nervoso Central , Glioblastoma , Meningite , Abscesso Encefálico/diagnóstico , Doenças do Sistema Nervoso Central/diagnóstico , Humanos , Meningite/diagnósticoRESUMO
PURPOSE: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. METHODS: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis. RESULTS: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist's interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20-50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). CONCLUSIONS: Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.
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Neoplasias Encefálicas , Glioblastoma , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Gadolínio , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Temozolomida/uso terapêutico , Resultado do TratamentoRESUMO
High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.
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Neoplasias Encefálicas/genética , Diferenciação Celular/genética , Glioblastoma/genética , Neovascularização Patológica/genética , Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Cocultura , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Dispositivos Lab-On-A-Chip , Proteínas Luminescentes/metabolismo , Células-Tronco Mesenquimais/metabolismo , Mesoderma/crescimento & desenvolvimento , Mesoderma/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Proteína Vermelha FluorescenteRESUMO
BACKGROUND: In the treatment for glioblastoma (GBM), treatment modalities, such as bevacizumab (BEV) and carmustine wafers implants have been approved in Japan since 2013. However, it is unclear whether such a trend in treatment complexity can accelerate treatment centralization. The aim of this study was to reveal the current trend in the treatment of GBM in Japan. METHODS: We used diagnostic procedure combination (DPC) database to analyze the data of 1,774 patients from 305 institutions between April 2016 and March 2019. To analyze the situations associated with first-line BEV use during concurrent TMZ (temozolomide)-radiotherapy, we compared TMZ alone and TMZ-BEV groups. RESULTS: Of the 1,774 patients with GBM, tumor removal by craniotomy was performed in 1,572 (88.6%) patients, and stereotactic biopsy was performed in 156 (8.8%) patients. A total of 1,229 (69.3%) patients underwent radiotherapy, and 1,287 (72.5%) patients underwent chemotherapy. TMZ alone was administered to 878 (68.2%) and TMZ combined with BEV in 381 (29.6%) patients. In the TMZ-BEV group, as compared to the TMZ-alone group, the rate of discharge to home was significantly lower (P = 0.0044), and the rate of stereotactic biopsy was significantly higher (P < 0.0001). No significant difference was observed in the distribution of patients between the TMZ alone and TMZ-BEV groups depending on the scale of institution (P = 0.1240). CONCLUSION: First-line BEV administration seems to be selected properly regardless of the institutional scale. This Japan-wide study of GBM treatment revealed that high level and newly introduced treatments have been steadily generalized in Japanese institutions.
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BACKGROUND: Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. METHODS: Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. RESULTS: The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931). CONCLUSIONS: Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.
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Hipotensão Intracraniana , Vazamento de Líquido Cefalorraquidiano , Espaço Epidural/diagnóstico por imagem , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Hipotensão Intracraniana/terapia , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
ABSTRACT: This study aimed to evaluate the treatment outcomes and the efficiency of techniques of fronto-orbital advancement (FOA) and posterior cranial vault expansion (PCVE) using distraction osteogenesis in patients with multiple craniosynostosis. We assessed the treatment results and outcomes of 8 patients with multiple craniosynostosis at the Kagoshima University Hospital between 2005 and 2019. Each 4 patients underwent FOA and PCVE, respectively, using distraction osteogenesis. The cranial volume and developmental quotient (DQ) were measured at the preoperative period and 1 year after surgery. The mean patient age at surgery was 22 months. The mean preoperative cranial volume was 1027 and 1071âcm3 in the FOA and PCVE groups, respectively. The mean preoperative DQ scores were 74 and 67, respectively. After 1-year of follow-up, the corresponding mean cranial volume became 1108 and 1243âcm3, respectively. The corresponding mean DQ scores also improved to 74 and 81, respectively. The postoperative follow-ups in all cases were uneventful, except for persistent epilepsy in 1 patient. Fronto-orbital advancement and PCVE using distraction osteogenesis might contribute to good outcomes in expanding cranial volume, cosmetic osteogenesis, and infantile development in patients with multiple craniosynostosis. Regarding the cranial volume expansion, especially, PCVE using distraction osteogenesis is more effective than FOA.
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Craniossinostoses , Osteogênese por Distração , Craniossinostoses/cirurgia , Humanos , Lactente , Período Pós-Operatório , Crânio , Resultado do TratamentoRESUMO
BACKGROUND: Narrowness of the spinal canal is associated with the development of cervical myelopathy. While studies have addressed the sagittal diameter of the cervical spinal canal, few evaluated the correlation between the size of the spinal canal and the vertebral level. We addressed this issue. METHODS: Our retrospective study included 102 patients with cranial or spinal disorders. We examined the correlation between the cervical spinal canal diameter (SCD) at C1 to C7 and the inner anteroposterior diameter (IAPD) of the atlas on CT images. RESULTS: At C1, the SCD was largest, at C4 it was smallest. While there was a strong correlation between the IAPD and the SCD at C1 (r = 0.8), the correlation between the size of the atlas and the SCD at C4 to C7 was weak (r = 0.2-0.3). We divided our patients into a normal group (n = 34, SCD ≥ 12 mm at any levels) and a stenosis group (n = 68, SCD < 12 mm at all levels). The mean SCD at C2 to C7 was significantly larger in the normal group. There was no significant difference between the two groups with respect to the IAPD and the SCD at C1. CONCLUSIONS: The size of the subaxial spine does not necessarily affect the size of the atlas. The pathophysiology of spinal canal stenosis should be considered separately at the C1- and the subaxial level.
Assuntos
Canal Medular , Estenose Espinal , Vértebras Cervicais/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Canal Medular/diagnóstico por imagem , Estenose Espinal/diagnóstico por imagem , Coluna Vertebral , Tomografia Computadorizada por Raios XRESUMO
Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson's disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.
Assuntos
Frutose/análogos & derivados , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Biogênese de Organelas , Rotenona/toxicidade , Adenilato Quinase/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Frutose/química , Frutose/farmacologia , Inativação Gênica/efeitos dos fármacos , Metformina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Células PC12 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacos , RatosRESUMO
Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade â £ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.