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Herein we discuss precision medicine for ependymoma. We reviewed the new molecular classifications of ependymoma, studies on the molecular mechanisms involved in carcinogenesis and proliferation, and the various studies exploring new therapeutic strategies. Of the nine molecular classifications of ependymoma, supratentorial ependymomas with ZFTA fusion, posterior fossa PFA group, and spinal ependymomas with MYCN amplification are treatment-resistant, and candidates for precision medicine. Precision medicine is considered to select a treatment method based on molecular biological information, but its application is thought to be difficult for ependymomas with few somatic mutations. Recent studies have shown that epigenetic mechanisms are involved in the development and growth of PFA ependymomas without recurrent somatic mutations. It has been found that ZFTA forms fusion genes with various genes other than the typical ZFTA-RELA fusion, and a common therapeutic target has been suggested for the genes downstream of it. Unfortunately, these findings have not yet been clinically applied to precision medicine for ependymoma, but newer discoveries are gradually accumulating. Further development of research is warranted.
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Ependimoma , Neoplasias Supratentoriais , Ependimoma/genética , Humanos , Medicina de PrecisãoRESUMO
In this article we explain in detail the Multidirectional Cranial Distraction Osteogenesis(MCDO)procedure for treating craniosynostosis, in which the multiple cranial bone flaps are pulled up in different directions by the external distractor with the helmet-type frame. MCDO has several advantages over conventional procedures such as unilateral cranial distraction osteogenesis(UCDO). First, the design of the osteotomy in MCDO is flexible depending on the deformities. Each bone flap can be moved to the desired direction in MCDO, while being moved only in one direction along the axis of the distractor in UCDO. This enables remodeling of the deformed cranium to the desired shape. Second, compared with UCDO, the distance between each bone flap after distraction is narrower in MCDO, allowing earlier bone formation and fusion, and thus a shorter consolidation period. Third, the expansion efficacy of MCDO is greater than that of UCDO. The maximum defects of MCDO were the large amount of osteotomy and the resulting heavy bleeding. Therefore, we have recently attempted to improve the design and procedure of osteotomy. The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis.
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Craniossinostoses , Osteogênese por Distração , Humanos , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Crânio/cirurgia , Retalhos Cirúrgicos , OsteogêneseRESUMO
BACKGROUND: Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning. We designed a professional identity formation-oriented reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical year curriculum. METHODS: A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire. RESULTS: Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. CONCLUSIONS: Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.
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Educação de Graduação em Medicina , Estudantes de Medicina , Adulto , Currículo , Feminino , Humanos , Japão , Aprendizagem , Aprendizagem Baseada em Problemas , Adulto JovemRESUMO
PURPOSE: Filar cysts (FCs) are detected incidentally on ultrasonography (US) of the neonatal spine. Their clinical significance has not been widely discussed in the literature because FCs are usually asymptomatic. This study aimed to investigate the clinical features of FCs and distinguish FCs that warrant attention. METHODS: We retrospectively analyzed 396 patients with lumbosacral skin stigmata. Patients who were younger than 1 month old at reference underwent US initially, and those older than 1 month of age underwent magnetic resonance imaging (MRI) at the age of 5-12 months. Patients with an FC in the US underwent subsequent MRI at the age of 5-12 months. Patients with an FC were followed clinically for at least 3 years. RESULTS: FCs were identified in 56 (14.1%) patients. Of the 195 children who underwent US initially, FCs were detected in 49 (25.1%) children. FCs were detected in seven children who underwent MRI initially. Of the 50 children with FCs who underwent MRI at the age of 5-12 months, FCs in 20 patients (40%) showed natural regression and FCs in 30 patients (60%) remained. Two of these 30 patients showed progression in size of the FC, and in both cases, the FCs were associated with a filar lipoma; however, the resected cysts were not neoplastic and did not have obvious clinical significance. CONCLUSIONS: Our study characterizes clinical features of filar cysts. Two-thirds of FCs remained in late infancy. The best sequence of MRI to follow-up FCs is heavily T2-weighted images.
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Cistos/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagem , Cistos/complicações , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Lipoma/complicações , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Doenças da Coluna Vertebral/complicações , UltrassonografiaRESUMO
BACKGROUND: Previously, the authors developed a new method of distraction osteogenesis for the treatment of craniosynostosis, multidirectional cranial distraction osteogenesis (MCDO). The purpose of this study is to review the authors' experience of MCDO for remodeling of the anterior cranium in the patients of craniosynostosis. METHODS: Forty-five patients with craniosynostosis underwent MCDO for anterior cranial remodeling from 2003 to 2017. The ages of the patients ranged from 8 to 72 months (mean: 23.9 months, median: 13 months). The involved sutures included the bicoronal suture in 14 patients, unicoronal suture in 4 patients, sagittal suture in 14 patients, metopic suture in 2 patient, and multiple sutures in 10 patients. RESULTS: An improvement of in cranial shape was achieved in 40 patients. In 1 patient, intraoperative massive bleeding forced us finishing the procedure before completing the planned osteotomy. Transient cerebrospinal fluid leakage occurred in 3 patients during the activation phase but recovered with conservative therapy. The mean blood transfusion was 25.5âmL/kg. The phase of activation ranged from 7 to 17 days (mean, 10.6 days) and the consolidation period ranged from 16 to 67 days (mean, 32.4 days). Loosening of traction pins occurred in 7 patients, resulting in undercorrection in 2 patients, and loosening of anchor pins occurred in 19 patients, resulting in acceleration of removal of the devices in 7 patients. CONCLUSIONS: Multidirectional cranial distraction osteogenesis was effective and has several advantages over the conventional procedures. Therefore, the authors conclude that MCDO will be a useful alternative for all phenotypes of craniosynostosis.
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Craniossinostoses/cirurgia , Osteogênese por Distração/métodos , Pinos Ortopédicos , Criança , Pré-Escolar , Suturas Cranianas/cirurgia , Feminino , Humanos , Lactente , Masculino , Osteotomia , Estudos Retrospectivos , Tração , Resultado do TratamentoRESUMO
Medulloepithelioma of the central nervous system (CNS) is a rare primitive neuroectodermal tumor characterized by highly malignant behavior occurring in early childhood. Few cases have been reported and optimal management remains unknown. Here, we report a case of CNS medulloepithelioma successfully treated with high-dose chemotherapy (HDCTX) followed by autologous stem cell transplantation (auto-SCT) without radiotherapy. At the last follow-up, 3.0 years after onset, the patient was alive with no sign of relapse and normal development. To the best of our knowledge, this is the first reported case of long-term survival of CNS medulloepithelioma treated by HDCTX/auto-PBSCT without radiotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumores Neuroectodérmicos Primitivos/terapia , Transplante de Células-Tronco de Sangue Periférico , Bussulfano/administração & dosagem , Pré-Escolar , Terapia Combinada , Relação Dose-Resposta a Droga , Humanos , Quimioterapia de Indução , Masculino , Melfalan/administração & dosagem , Tumores Neuroectodérmicos Primitivos/patologia , Prognóstico , Indução de Remissão , Transplante AutólogoRESUMO
Endoscopic third ventriculostomy (ETV) is a safe treatment option for chronic obstructive hydrocephalus. However, we encountered a case of chronic subdural hematoma (CSDH) with bilateral large hematoma volumes after ETV for chronic obstructive hydrocephalus. We herein report a rare complication of ETV. The patient was a 53-year-old woman who had been diagnosed with asymptomatic ventricular enlargement with aqueductal stenosis 5 years previously. However, over the course of 5 years, her gait and cognitive function gradually declined. ETV was administered to relieve symptoms. Head Magnetic resonance imaging performed 1 week after ETV indicated bilateral subdural hygroma. Three weeks after ETV, she presented with headache and left incomplete paralysis, and head Computed tomography (CT) demonstrated bilateral CSDH with a large volume hematoma. Burr-hole evacuation and drainage of the bilateral CSDH were performed, after which the symptoms resolved. However, 7 weeks after ETV, she again presented with headache and incomplete right paralysis, and CT revealed bilateral CSDH re-enlargement. After the second burr-hole evacuation and drainage of bilateral CSDH, her symptoms resolved. The bilateral CSDH continued to shrink following the second hematoma evacuation surgery and completely disappeared on CT scan performed 3 months after ETV. Ventricular enlargement due to chronic obstructive hydrocephalus stretches the brain mantle for several years. This long-term stretching may have diminished the brain compliance and led to the development, growth, and recurrence of CSDH. In ETV for chronic obstructive hydrocephalus, surgeons should consider the risk of postoperative CSDH with a high hematoma volume and tendency to recur.
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PURPOSE: This study aims to ascertain which specific types of sacrococcygeal dimples are associated with underlying spinal cord malformations. METHODS: From 2008 to 2011, we prospectively examined children less than 2 years old with sacrococcygeal dimples. Each patient underwent clinical assessment of dimples and magnetic resonance imaging. We devised the following new classification of dimples according to their location: type 1, dimples located within the gluteal crease, including coccygeal pits; type 2, dimples located at the upper edge of the gluteal crease with associated curving or deformity of that crease; and type 3, dimples located well above the gluteal crease. RESULTS: We evaluated 142 patients with sacrococcygeal dimples. Although we identified spinal malformations such as spinal lipomas, filum cysts, and thickened fila terminalia in only 17 % of infants with type 1 dimples, we observed them in 45 % with type 2 and 55 % with type 3. Thus, in terms of the rate of spinal malformations, there are significant differences between types 1 and 2 and between types 1 and 3. CONCLUSIONS: We propose a new classification of sacrococcygeal dimples. Although type 2 dimples have previously been classified as simple dimples that require no further investigation, we have identified that they are strongly associated with spinal deformities, comparable to atypical type 3 dimples. Thus, both types 2 and 3 dimples warrant radiological investigation.
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Defeitos do Tubo Neural/classificação , Defeitos do Tubo Neural/patologia , Região Sacrococcígea/anormalidades , Anormalidades da Pele/complicações , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Camurati-Engelmann disease (CED) causes bone pain, muscle weakness, and cranial nerve symptoms due to abnormal thickening of the long bones of the limbs and the cortex of the skull. The pathophysiology of CED is a gain-of-function variant of transforming growth factor beta 1 (TGFB1). The ophthalmological symptoms of CED are usually caused by increased intracranial pressure and optic canal stenosis. Here, we report the case of a patient in whom prednisolone was effective against papilledema caused by CED. In this case, when papilledema was observed in both fundi, the patient showed increased bone pain, fever, and elevated CRP and ALP levels. Brain magnetic resonance imaging (MRI) revealed a high short tau inversion recovery (STIR) signal in both optic nerves, suggesting edematous changes. Prednisolone ameliorated bone pain, fever, and papilledema, resulting in a slight improvement of the visual function of the right eye. Our results suggest that prednisolone may be effective in treating ophthalmologic symptoms in addition to bone pain in patients with CED.
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Germinoma is a rare CNS germ cell tumor preferentially affecting children and young adults. Intracranial germinomas arise typically in the neurohypophysis and pineal region and occasionally in the basal ganglia and thalamus. Germinomas in the basal ganglia and thalamus are characterized by the ipsilateral cerebral and brainstem hemiatrophy with slowly progressive neurological deficits, which is due to tumor infiltration into the thalamocortical and corticospinal tract and induction of anterograde and retrograde Wallerian degeneration. We report an 11-year-old boy with a mass located in the fornix incidentally discovered on the first work-up of his minor head injury. Imaging findings revealed the ipsilateral atrophy of the mammillary body and the fornix. Stereotactic brain biopsy was performed and the final diagnosis was germinoma. The ipsilateral atrophy of the mammillary body and the fornix implied the transsynaptic degeneration via the Papez circuit. We discuss the unique nature of germinomas and underlying pathological mechanisms.
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Rosette-forming glioneuronal tumors (RGNTs) are benign WHO grade 1 tumors that occur in the ventricular system, particularly the fourth ventricle. RGNTs and dysembryoplastic neuroepithelial tumors (DNTs) are both categorized as neuronal and mixed neuronal-glial tumors and may be difficult to distinguish. Coexistence of the two tumor types has been reported. Here, we report a pediatric case of RGNT with DNT-like features showing intraventricular dissemination. The tumor occurred in the medial temporal lobe and presented with specific pathological glioneuronal elements including floating neurons, which are typical in DNTs, but was diagnosed as RGNT because of the presence of neurocytic rosettes. Genetic analysis detected fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain, which was previously reported to be specific for DNT. RGNTs with FGFR1-ITD may show atypical clinical presentation and pathological features.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Sequências de Repetição em Tandem/genética , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
Frontometaphyseal dysplasia (FMD), also known as Gorlin-Cohen syndrome, is a rare genetic syndrome. This syndrome affects the skeletal system and connective tissue, and causes a wide spectrum of manifestations of the skull, tubular bones, cardiovascular system, urinary system, and/or gastrointestinal system. Craniofacial findings of FMD are characterized by protruding supraorbital ridge, broad nasal bridge, hypertelorism, down-slanting palpebral fissures, and/or micrognathia. We describe a case of a 2-year-old girl diagnosed with sagittal synostosis accompanied with FMD. She presents anterior sagittal synostosis cranial form, compressed cerebrospinal fluid space (which suggested increased intracranial pressure), and the supraorbital hyperostosis. She underwent multi-directional cranial distraction osteogenesis in the calvaria and shaving of the supraorbital ridges. Despite concerns about bone fragility associated with FMD, the surgery was accomplished as usual. The patient had no intra- and postoperative complications. After 6 months of follow-up, the cranial shape has improved and the cerebrospinal fluid space has widened, but the supraorbital ridge has protruded again. Re-protrusion of the supraorbital ridge appears to be due to age-appropriate vigorous osteogenesis. The multi-directional cranial distraction osteogenesis procedure has been useful for treating sagittal synostosis even concomitant with FMD.
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Fronto-orbital advancement by distraction osteogenesis is a useful means of surgically correcting bicoronal synostosis. However, the scope for morphological revision is limited. To address this issue, we developed a multidirectional cranial distraction osteogenesis (MCDO) technique that we quantitatively assessed in patients with bicoronal synostosis. In this case series, five patients with bicoronal synostosis were treated with MCDO at a mean age of 13.4 months (range 9-22 months). Distraction started 5 days after surgery and the activation period was 11.2 days (range 10-14 days). The distraction devices were removed 47.2 days (range 33-67 days) after completing distraction. Improved cranial shape was confirmed by CT data. Mean preoperative CI, APL, and ICV readings of 102.1%, 13.5 cm, and 1179.4 ml, respectively, had reached 94.0%, 14.9 cm, and 1323.9 ml, respectively, upon device removal. These values were well preserved at 1 year (90.4%, 15.8 cm, and 1461.3 ml, respectively). In conclusion, MCDO successfully enables both cranial expansion and correction of a flat forehead, constituting a valid treatment alternative for patients with bicoronal synostosis.
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Craniossinostoses , Osteogênese por Distração , Humanos , Lactente , Crânio , Resultado do TratamentoRESUMO
Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II-IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1R132H. In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in ß-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.
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Neoplasias Encefálicas/metabolismo , Carnitina/análogos & derivados , Glioblastoma/metabolismo , Isocitrato Desidrogenase/genética , Metabolômica/métodos , Adulto , Idoso , Biomarcadores Tumorais/deficiência , Neoplasias Encefálicas/patologia , Carnitina/deficiência , Divisão Celular/genética , Linhagem Celular Tumoral , Feminino , Glioblastoma/patologia , Glutaratos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oxirredução , Prognóstico , Transdução de Sinais/genética , TransfecçãoRESUMO
INTRODUCTION: Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution. Therefore, by changing the concentration, it is easy to make gels of various hardness. METHODS: In this study, a mass of gel that looked like a tumor was placed into another gel that looked like the brain. A part of the "brain" was regarded as the eloquent area. Three types of "tumor" were prepared: hard, moderately hard, and soft tumors. Residents tried to remove the tumor entirely with minimal brain invasion. The training was repeated with 3 types of gel. After resection, the weight of the residual tumor, resected normal brain, and resected eloquent area were measured, and the time taken for removal was recorded. RESULTS: These data were compared between residents and neurosurgeons. We also analyzed how these data improved with repeated practice. In most cases, residual tumor, resected normal brain, resected eloquent area, and time taken for removal were less in neurosurgeons than in residents. Repeated training made residents more skillful. The responses of the trainees were almost all favorable. CONCLUSIONS: Our devices with "tumors" of various hardness appear to be suitable for resident training in each surgical skill. For the next step of this study, we will attempt to fabricate more practical 3-dimensional gel models for presurgical simulation.