Language：English   Publisher：Pathology, research and practice  

Previously, we constructed a DNA-based next-generation sequencing (NGS) panel for an integrated diagnosis of gliomas according to the 2021 World Health Organization classification system. The aim of the current study was to evaluate the feasibility of a modified panel to include fusion gene detection via RNA-based analysis. Using this bimodal DNA/RNA panel, we analyzed 210 cases of gliomas and others to identify fusion genes in addition to gene alterations, including TERT promoter (TERTp) mutation and 1p/19q co-deletion, in formalin-fixed paraffin-embedded tissues. Of the 210 patients, fusion genes were detected in tumors of 35 patients. Eighteen of 112 glioblastomas (GBs) harbored fusion genes, including EGFR and FGFR3 fusions. In IDH-mutant astrocytoma, 6 of 30 cases showed fusion genes such as MET and NTRK2 fusions. Eleven molecular GBs and 20 not-elsewhere-classified cases harbored no gene fusions. Other 11 tumors including ependymoma, pilocytic astrocytoma, diffuse hemispheric glioma, infant-type hemispheric glioma, and solitary fibrous tumors exhibited diagnostic fusion genes. Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

DOI： 10.1016/j.prp.2024.155598

Scopus

PubMed

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：Neuropathology  

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.

DOI： 10.1111/neup.12970

Web of Science

Scopus

PubMed

Publisher：東京医学社  

DOI： 10.24479/ohns.0000001254

CiNii Research

Language：English   Publisher：Neuro-Oncology Advances  

Background. Homozygous deletion of the tumor suppression genes cyclin‑dependent kinase inhibitor 2A/B (CDKN2A/B) is a strong adverse prognostic factor in IDH‑mutant gliomas, particularly astrocytoma. However, the impact of hemizygous deletion of CDKN2A/B is unknown. Furthermore, the influence of CDKN2A/B status in IDH‑ mutant and 1p/19q‑codeleted oligodendroglioma remains controversial. We examined the impact of CDKN2A/B status classification, including hemizygous deletions, on the prognosis of IDH‑mutant gliomas. Methods. We enrolled 101 adults with IDH‑mutant glioma between December 2002 and November 2021. CDKN2A/B deletion was evaluated with multiplex ligation‑dependent probe amplification (MLPA). Immunohistochemical anal‑ ysis of p16/MTAP and promoter methylation analysis with methylation‑specific MLPA was performed for cases with CDKN2A/B deletion. Kaplan − Meier plots and Cox proportion hazards model analyses were performed to evaluate the impact on overall (OS) and progression‑free survival. Results. Of 101 cases, 12 and 4 were classified as hemizygous and homozygous deletion, respectively. Immunohistochemistry revealed p16‑negative and MTAP retention in cases with hemizygous deletion, whereas homozygous deletions had p16‑negative and MTAP loss. In astrocytoma, OS was shorter in the order of homozy‑ gous deletion, hemizygous deletion, and copy‑neutral groups (median OS: 38.5, 59.5, and 93.1 months, respec‑ tively). Multivariate analysis revealed hazard ratios of 9.30 (P = .0191) and 2.44 (P = .0943) for homozygous and hemizygous deletions, respectively. Conclusions. CDKN2A/B hemizygous deletions exerted a negative impact on OS in astrocytoma. Immunohistochemistry of p16/MTAP can be utilized to validate hemizygous or homozygous deletions in combina‑ tion with conventional molecular diagnosis.

DOI： 10.1093/noajnl/vdae069

Web of Science

Scopus

PubMed

Language：English   Publisher：Journal of Neurosurgery: Case Lessons  

GROUND The endoscopic endonasal approach to paramedian skull base lesions has garnered increasing attention in recent reports. However, ll a challenging approach. While the primary objective of the approach is the maximal removal of tumors through a minimally invasive procedure, sions of the approach rarely include information about the maximum preservation of nasal structures. This study aimed to retrospectively review nical outcomes of patients who had undergone an endoscopic endonasal approach to paramedian lesions, describe the technical and anatomical es related to this approach at the authors’ institution, and discuss the maximal preservation of nasal structures. RVATIONS The authors conducted a descriptive retrospective study of 17 surgical cases of paramedian endoscopic endonasal approaches med jointly by otolaryngologists and neurosurgeons from August 2018 to August 2022 at a tertiary hospital. ONS The approach to the paramedian region of the skull base was examined. Creating an appropriate corridor to maximize the surgical field is tial to allow a safe and accurate procedure. From an otolaryngologist’s perspective, the endoscopic modified medial maxillectomy is an essential dure that maximizes the surgical corridor and maximally preserves nasal morphology.

DOI： 10.3171/CASE24218

Scopus

PubMed

DOI： 10.1093/neuonc/noae064.271

Web of Science

Language：English   Publisher：Clinical Anatomy  

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.

DOI： 10.1002/ca.24170

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Cancers  

Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood–brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

DOI： 10.3390/cancers16051009

Web of Science

Scopus

PubMed

Language：English   Publisher：Neuroradiology  

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.

DOI： 10.1007/s00234-024-03288-0

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Neuroradiology  

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.

DOI： 10.1007/s00234-023-03267-x

Web of Science

Scopus

PubMed

Web of Science

Language：English   Publisher：Neuroradiology  

The original article contains an error during online publication. There was an error in the previous version of Table 2. Specifically, the values of rrTBF for IDHm-noncodel and IDHm-codel were identical at 1.24 ± 1.23 [0.76–1.71]. The authors have provided a corrected version below. (Table presented.) Differences between IDHw, IDHm-noncodel and IDHm-codel in the ASL parameters IDHw (n = 21) IDHm-noncodel (n = 28) IDHm-codel (n = 22) P-value ASL Cortical high-flow sign 2/21(9.5%) 2/28(7.1%) 12/22(54.5%) <0.0001* rrTBF 1.31 ± 0.56 [1.05–1.56] 1.24 ± 1.23 [0.76–1.71] 1.31 ± 0.60 [1.05–1.58] 0.9473 *p < 0.05

DOI： 10.1007/s00234-023-03228-4

Web of Science

Scopus

PubMed

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Cancers  

Background: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. Methods: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Results: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Conclusions: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

DOI： 10.3390/cancers15174289

Web of Science

Scopus

PubMed

Language：English   Publisher：Neuroradiology  

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.

DOI： 10.1007/s00234-023-03186-x

Web of Science

Scopus

PubMed

Language：English   Publisher：The Japan Neurosurgical Society  

<p>We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts.</p>

DOI： 10.2176/jns-nmc.2022-0351

Web of Science

Scopus

PubMed

CiNii Research

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：(一社)日本脳神経外科学会  

膠芽腫患者を対象とした後ろ向き研究を実施し、FLAIR病変切除率を評価することで、supramaximal resection(SMR)の臨床効果について検討した。2006年12月～2018年8月に神経膠腫と診断された成人患者のうち、肉眼的全切除(GTR)が施行された成人33例(年齢中央値64歳、男性19例)を対象とした。評価項目は腫瘍切除率(手術前後のFLAIRおよびガドリニウム強調T1強調画像の腫瘍体積を3D画像体積分析装置により測定)、SMR率(0%から10%刻み)などとした。腫瘍を皮質灰白質との接触により、皮質群23例(SMR 8例、GTR 15例)、深在性群10例(SMR 4例、全切除6例)に分けて検討した。その結果、SMR閾値が30%以上の場合に全生存期間の改善が観察された。皮質群ではGTRと比較してSMRで全生存期間が延長する傾向が認められた(69.6ヵ月対22.1ヵ月)。一方、深在群ではGTRと比較してSMRで全生存期間が有意に短縮していた(10.2ヵ月対27.9ヵ月、p=0.0221)。以上から、FLAIR病変のsupramaximal resectionは神経膠腫患者の生存期間を延長可能であることが示された。

Language：English   Publisher：Neuroradiology  

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.

DOI： 10.1007/s00234-023-03177-y

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scientific Reports  

Glioblastoma, a malignant tumor, has no curative treatment. Recently, mitochondria have been considered a potential target for treating glioblastoma. Previously, we reported that agents initiating mitochondrial dysfunction were effective under glucose-starved conditions. Therefore, this study aimed to develop a mitochondria-targeted treatment to achieve normal glucose conditions. This study used U87MG (U87), U373, and patient-derived stem-like cells as well as chloramphenicol (CAP) and 2-deoxy-d-glucose (2-DG). We investigated whether CAP and 2-DG inhibited the growth of cells under normal and high glucose concentrations. In U87 cells, 2-DG and long-term CAP administration were more effective under normal glucose than high-glucose conditions. In addition, combined CAP and 2-DG treatment was significantly effective under normal glucose concentration in both normal oxygen and hypoxic conditions; this was validated in U373 and patient-derived stem-like cells. 2-DG and CAP acted by influencing iron dynamics; however, deferoxamine inhibited the efficacy of these agents. Thus, ferroptosis could be the underlying mechanism through which 2-DG and CAP act. In conclusion, combined treatment of CAP and 2-DG drastically inhibits cell growth of glioblastoma cell lines even under normal glucose conditions; therefore, this treatment could be effective for glioblastoma patients.

DOI： 10.1038/s41598-023-37483-5

Web of Science

Scopus

PubMed

Language：English  

DOI： 10.1177/20584601231184565

Web of Science

PubMed

Web of Science

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：一般社団法人 日本内分泌学会  

DOI： 10.1507/endocrine.99.s.update_14

CiNii Research

Language：Japanese   Publisher：(一社)日本内分泌学会  

症例は68歳男性で、左眼瞼下垂、視力低下を主訴に、前医の頭部MRIにて下垂体部の腫瘍を指摘され、手術目的に当院紹介となった。下垂体腫瘍に対し外科的腫瘍摘出術を施行し、病理組織学的にトルコ鞍内脊索腫と診断された。術前後の内分泌学的所見を評価すると、術前に認めた下垂体前葉ホルモン基礎値の広範な低下は、術後にはPRLを除いて改善し、術後はホルモン補充療法を行わず経過観察する方針とした。また、眼瞼下垂と視力低下は術後改善し、術後7ヵ月の時点で再発は認めなかった。

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>An 18-year-old male patient had developed epileptic seizures with loss of consciousness 3 years earlier, and despite subsequent drug treatment, he still had recurrent epileptic seizures. Imaging studies revealed a meningoencephalocele with protrusion of the temporal lobe from the middle cranial fossa to the lateral fossa of the sphenoid sinus. Since this was thought to be the focus of the temporal lobe epilepsy, he was admitted to our hospital for resection of the meningoencephalocele. The patient underwent transnasal endoscopic resection of the meningoencephalocele in the lateral fossa of the sphenoid bone, followed by multilayer skull base reconstruction using a pedicled middle turbinate mucosal (MT) flap. Postoperatively, the epileptic seizures disappeared, and the patient has recovered without cerebrospinal fluid leakage or wound complications. If the area is localized near the sphenopalatine foramen, such as the lateral fossa of the sphenoid sinus, an MT flap can be used instead of a nasal septal mucosal flap. Furthermore, by using a minimal transpterygoid approach and preserving the sphenopalatine artery and its branch, the middle turbinate artery, it was possible to use the MT flap during skull base reconstruction.</p>

DOI： 10.11334/jibi.69.2_116

CiNii Research

Language：Japanese   Publisher：耳鼻と臨床会  

症例は18歳、男性。3年前に意識消失を伴うてんかん発作を発症、その後薬物治療を行うもてんかん発作を繰り返す状態であった。画像検査で中頭蓋窩から蝶形骨洞側窩に陥入する側頭葉の髄膜脳瘤を指摘され、側頭葉てんかんの焦点と考えられたため髄膜脳瘤切除目的に当院入院となった。経鼻内視鏡下に蝶形骨側窩の髄膜脳瘤を切除し、その後、有茎中鼻甲介粘膜弁を用いて多層での頭蓋底再建を行った。術後、てんかん発作は消失、髄液漏や創部の合併症なく経過している。蝶形骨洞側窩のように蝶口蓋孔近傍で限局した箇所であれば鼻中隔粘膜弁でなくても中鼻甲介粘膜弁での代用が可能で、minimal transpterygoid approachを用い、さらに蝶口蓋動脈とその分枝である中鼻甲介動脈を温存することで頭蓋底再建時に中鼻甲介粘膜弁の利用が可能となった。(著者抄録)

Language：English   Publisher：Neuro-Oncology Advances  

Background: Copy number alterations (CNAs) are common in diffuse gliomas and have been shown to have diagnostic significance. While liquid biopsy for diffuse glioma has been widely investigated, techniques for detecting CNAs are currently limited to methods such as next-generation sequencing. Multiplex ligation-dependent probe amplification (MLPA) is an established method for copy number analysis in pre-specified loci. In this study, we investigated whether CNAs could be detected by MLPA using patients' cerebrospinal fluid (CSF). Methods: Twenty-five cases of adult diffuse glioma with CNAs were selected. Cell-free DNA (cfDNA) was extracted from the CSF, and DNA sizes and concentrations were recorded. Twelve samples, which had appropriate DNA sizes and concentrations, were subsequently used for analysis. Results: MLPA could be successfully performed in all 12 cases, and the detected CNAs were concordant with those detected using tumor tissues. Cases with epidermal growth factor receptor (EGFR) amplification, combination of gain of chromosome 7 and loss of chromosome 10, platelet-derived growth factor receptor alpha amplification, cyclin-dependent kinase 4 amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion were clearly distinguished from those with normal copy numbers. Moreover, EGFR variant III was accurately detected based on CNA. Conclusions: Thus, our results demonstrate that copy number analysis can be successfully performed by MLPA of cfDNA extracted from the CSF of patients with diffuse glioma.

DOI： 10.1093/noajnl/vdac178

Web of Science

Scopus

PubMed

Language：English   Publisher：Neuro-Oncology Advances  

Background: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. Methods: Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. Results: TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. Conclusions: Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas.

DOI： 10.1093/noajnl/vdad078

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：(公財)日本眼科学会  

背景:炎症性筋線維芽細胞性腫瘍(IMT)は筋線維芽細胞の増殖と炎症細胞浸潤を特徴とする中間悪性腫瘍であり,肺,腹腔骨盤内,後腹膜に好発し,眼窩に発生することはまれである.今回,眼窩に発生したIMTの1例を経験したので報告する.症例:46歳,女性.複視を主訴に近医眼科を受診し,眼窩に腫瘍を指摘され九州大学病院眼科を紹介受診した.初診時に右眼球結膜下の赤色調腫瘤および画像診断で右眼窩内下方に35×20×15mmの紡錘形腫瘤を認め,眼球運動障害を来していた.結膜下の腫瘤を生検したところ,炎症細胞浸潤を伴った紡錘形細胞の増殖を認めた.免疫染色の結果,増殖細胞はanaplastic lymphoma kinase(ALK),α-平滑筋アクチン(α-SMA),desmin陽性であり,IMTと診断した.結膜切開および鼻内視鏡下にアプローチして全摘出し,術後24ヵ月の現在,再発は認めていない.結論:眼窩腫瘍で非上皮性腫瘍を疑う際はIMTの可能性も検討する必要がある.(著者抄録)

Language：English   Publisher：Scientific Reports  

This study aimed to determine whether quantitative relaxometry using synthetic magnetic resonance imaging (SyMRI) could differentiate between two diffuse glioma groups with isocitrate dehydrogenase (IDH)-mutant tumors, achieving an increased sensitivity compared to the qualitative T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign. Between May 2019 and May 2020, thirteen patients with IDH-mutant diffuse gliomas, including seven with astrocytomas and six with oligodendrogliomas, were evaluated. Five neuroradiologists independently evaluated the presence of the qualitative T2-FLAIR mismatch sign. Interrater agreement on the presence of the T2-FLAIR mismatch sign was calculated using the Fleiss kappa coefficient. SyMRI parameters (T1 and T2 relaxation times and proton density) were measured in the gliomas and compared by the Mann–Whitney U test. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. The sensitivity, specificity, and kappa coefficient were 57.1%, 100%, and 0.60, respectively, for the qualitative T2-FLAIR mismatch sign. The two types of diffuse gliomas could be differentiated using a cutoff value of 178 ms for the T2 relaxation time parameter with 100% sensitivity, specificity, accuracy, and positive and negative predictive values, with an area under the curve (AUC) of 1.00. Quantitative relaxometry using SyMRI could differentiate astrocytomas from oligodendrogliomas, achieving an increased sensitivity and objectivity compared to the qualitative T2-FLAIR mismatch sign.

DOI： 10.1038/s41598-022-13036-0

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

高齢患者の内側側頭葉に発症した、BRAF変異を伴わずH3 K27M変異を伴った、グレード3神経節膠腫の稀少例を報告した。症例は56歳男性で、一過性の視野欠損を主訴に、他院に来院した。MRI所見では左側頭葉に腫瘍を認め、生検により、びまん性星細胞腫と病理診断されたが、18ヵ月の経過観察の間に病変が徐々に増大し、生検から36ヵ月後に施行したT1強調画像でガドリウム増強が認められたため、九州大学病院脳神経外科に紹介された。治療では腫瘍切除術が行われ、切除試料の組織学的検査から、グレード3の神経節膠腫と診断され、テモゾロミドによる同時化学放射線治療が施行された。治療サイクル2サイクル後に病状進行による悪化はみられたが、腫瘍切除術後23ヵ月以上の生存転帰が得られた。なお、Sanger法によるシーケンス解析と高感度融解曲線解析をIDH1遺伝子、IDH2遺伝子、BRAF遺伝子、H3F3A遺伝子の各遺伝子について行ったところ、IDH1/2やBRAF V600E遺伝子変異は検出されなかったが、H3 K27M遺伝子変異が検出された。

Language：English   Publisher：Journal of Neurological Surgery, Part B: Skull Base  

Objective: En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the outcomes of surgical cases of advanced TB-SCC (T3-T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule. Design: This is a case series study with chart review. Setting: The study was conducted at two academic tertiary care medical centers. Participants: Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan-Meier method. Main Outcome Measure: This study shows disease-specific 5-year DSS rate. Results: The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%). Conclusion: En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension.

DOI： 10.1055/s-0041-1722930

Web of Science

Scopus

PubMed

Language：English   Publisher：Neuropathology  

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.

DOI： 10.1111/neup.12793

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：World Neurosurgery  

Background: Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course and relapse pattern in patients with glioblastoma. Methods: We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n = 51) and post-bevacizumab (n = 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated. Results: Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P = 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P = 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 [0.26–2.62], P = 0.7377). The rate of early focal recurrence was significantly lower (P = 0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P = 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P = 0.0021, univariate analysis; P = 0.0144, multivariate analysis). Conclusions: Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.

DOI： 10.1016/j.wneu.2021.12.075

Web of Science

Scopus

PubMed

Language：English   Publisher：Surgical Neurology International  

Background: Glioependymal cysts (GECs) are rare, benign congenital intracranial cysts that account for 1% of all intracranial cysts. Surgical interventions are required for patients with symptomatic GECs. However, the optimal treatment remains controversial, especially in infants. Here, we report a male infant case of GECs that successfully underwent minimally invasive combined neuroendoscopic cyst wall fenestration and cyst-peritoneal (CP) shunt. Case Description: The boy was delivered transvaginally at 38 weeks and 6 days of gestation with no neurological deficits. Magnetic resonance imaging (MRI) at birth revealed multiple cysts with smooth and rounded borders and a non-enhancing wall in the right parieto-occipital region. The size of the cyst had increased rapidly compared to that of the prenatal MRI, which was performed at 37 weeks and 2 days. On the day of birth, Ommaya cerebrospinal fluid (CSF) reservoir was placed into the largest outer cyst. The patient underwent intermittent CSF drainage; however, he experienced occasional vomiting. At 2 months, he underwent combined neuroendoscopic cyst wall fenestration and CP shunt through a small hole. The patient's postoperative course was uneventful and there was no recurrence of the cyst. The pathological diagnosis was GEC. Conclusion: Combined neuroendoscopic cyst wall fenestration and CP shunt are a minimally invasive and effective treatment for infants with GECs.

DOI： 10.25259/SNI_133_2022

Scopus

PubMed

Language：English   Publisher：British Journal of Radiology  

Objective: To determine whether the γ distribution (GD) model of diffusion MRI is useful in the evaluation of the isocitrate dehydrogenase (IDH) mutation status of glioblastomas. Methods: 12 patients with IDH-mutant glioblastomas and 54 patients with IDH-wildtype glioblastomas were imaged with diffusion-weighted imaging using 13 b-values from 0 to 1000 s/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) < 1.0×10−3 mm2/s; f2, D > 1.0×10−3 and <3.0×10−3 mm2/s; f3, D > 3.0 × 10−3 mm2/s. The GD model-derived parameters measured in gadolinium-enhancing lesions were compared between the IDH-mutant and IDH-wildtype groups. Receiver operating curve analyses were performed to assess the parameters' diagnostic performances. Results: The IDH-mutant group’s f1 (0.474 ± 0.143) was significantly larger than the IDH-wildtype group’s (0.347 ± 0.122, p = 0.0024). The IDH-mutant group’s f2 (0.417 ± 0.131) was significantly smaller than the IDH-wildtype group’s (0.504 ± 0.126, p = 0.036). The IDH-mutant group’s f3 (0.109 ± 0.060) was significantly smaller than the IDH-wildtype group’s (0.149 ± 0.063, p = 0.0466). The f1 showed the best diagnostic performance among the GD model-derived parameters with the area under the curve value of 0.753. Conclusion: The GD model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and was useful in the differentiation of these tumors. Advances in knowledge: Diffusion MRI based on the γ distribution model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and its use enabled the significant differentiation of these tumors. The γ distribution model may contribute to the non-invasive identification of the IDH mutation status based on histological viewpoint.

DOI： 10.1259/bjr.20210392

Web of Science

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2021.02.138

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00234-020-02456-2

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.clineuro.2019.105556

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.inat.2019.100498

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.inat.2018.10.007

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.diii.2019.02.010

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2018.10.047

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2018.09.054

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.wneu.2018.03.069

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-018-0313-4

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.12408

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-017-0287-7

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.12362

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.12347

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00330-016-4328-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2147/OTT.S125587

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.7887/jcns.26.750

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.7887/jcns.26.404

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.inat.2016.08.001

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jmri.25261

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2147/OTT.S115911

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0160489

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2176/nmc.oa.2016-0172

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11060-015-1886-y

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/neuonc/nos145

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-011-0046-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-011-0049-x

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10014-011-0038-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1158/1078-0432.CCR-10-0207

Event date： 2019.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

【背景】近年、経鼻内視鏡下手術の適応は様々な頭蓋底疾患に拡大しつつある。当院では2018年8月よりほぼ全ての経鼻内視鏡下手術に耳鼻科医合同でのbinostril four hands approachを導入した。その経験から耳鼻咽喉科医合同手術の有用性について報告する。【対象】2018年8月から2019年5月までに耳鼻科合同経鼻内視鏡下手術を行った連続29症例についての解析を行った。また、2016年3月から2017年12月までに脳外科単独で手術を行った下垂体腺腫連続20症例を比較対象とした。【結果】全29症例の内訳は、下垂体腺腫17例、頭蓋咽頭腫3例、ラトケ嚢胞1例、鞍結節部髄膜腫３例、軟骨肉腫３例、眼科内腫瘍1例、コレステリン肉芽腫１例であった。耳鼻科合同手術群では脳外科単独群と比較して、手術時間は有意に長かったが、初発症例においては摘出率が向上していた。両者ともに術後合併症は見られなかった。その他の頭蓋底疾患についても１例において術後髄液漏を認めた以外は術後合併症は認めず、良好な腫瘍摘出が得られた。【考察・結語】surgical corridorの作成から、内視鏡保持、術後の鼻腔ケアまで耳鼻科医が関与することは、経鼻内視鏡手術を行ううえで非常に有用であり、特に眼窩内腫瘍や錐体骨病変などの外側展開が必要な症例についてはそのメリットが大きかった。更には解剖学的知識や手術手技を共有することでお互いの技術向上や新たなアプローチの開発にも繋がり、合同手術の意義は非常に大きいと思われる。

Event date： 2019.9

Language：Japanese  

Country：Japan  

Event date： 2018.12

Language：Japanese  

Venue：ヒルトン小田原   Country：Japan  

【背景】
WHO2016以降、グリオーマ診断には病理診断に遺伝子診断が統合されたが、これらの遺伝子解析が全て行える施設は限られている。当院では2015年より病理部でATRX、IDH1、TP53の免疫染色をルーチンとして開始した。そこで今回我々はこれらの免疫染色の結果とWHO2016診断に必要な遺伝子解析結果とを比較し、より簡便な方法である免疫染色でグリオーマの層別化が可能かどうかを検討した。
【対象／方法】
2015年2月以降に九州大学病院で手術が行われたグリオーマ症例92例を対象とした。これらの症例において、免疫染色の結果とIDH1/2,TERTプロモーター変異および1p/19qLOHの解析結果とを比較検討した。
【結果／結語】
IDHについては免疫染色とシークエンスの結果は良好に一致した（95.5%）。IDH mutant, 1p/19q codel症例においては全症例でATRXの発現は保持されており、TERTプロモーター変異を認めた。一方IDH mutant, 1p/19q non-codel症例では全例でATRXの染色は陰性であり、TERTプロモーター変異も認めなかった。IDH wild 症例においては、ATRXの染色陽性例、陰性例が混在していた。全症例を通じてATRXの発現欠失およびTERTプロモーター変異を同時に有する症例は存在しなかった。これらの結果から、IDH mutant症例では免疫染色のみでoligodendroglioma系、astrocytoma系の鑑別が可能であった。一方でIDH wild typeの腫瘍ではATRX欠失がなく、TERTプロモーター変異も認めない症例が少なからず存在し、さらなる分子生物学的意義の検討が必要であると思われた。

Event date： 2018.8

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2017.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2016.10

Language：Japanese  

Country：Japan  

Event date： 2016.6

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

【目的】
小児頭蓋内胚細胞腫瘍は、適切な初期治療を完遂することで治癒が可能となりつつある一方、長期生存例においては放射線照射や化学療法による機能予後の低下についてもフォーカスが当たるようになってきた。今回我々は当院における小児頭蓋内胚細胞腫瘍患者の長期治療成績と機能予後についての検討を行ったので報告する。
【対象】
症例は1987年から2012年の25年間に当院で初期治療を行い、３年以上の追跡が可能であった初回治療時年齢18歳以下の頭蓋内胚細胞腫瘍患者39例を対象とした。低悪性度群（G群）が29例、中間悪性度群（I群）が4例、高悪性度群（P群）が6例であった。年齢は2歳から18歳（中央値13歳）であり、観察期間は37カ月から310カ月（中央値120カ月）であった。
【結果】
死亡した症例は4例(G群1例、I群1例、P群2例)であった。死亡原因として腫瘍死した症例は初期治療が完遂できなかったP群の1例のみであり、その他の原因として、間脳下垂体機能不全が2例、放射線誘発性膠芽腫が1例であった。また、検査が可能であった症例のうち、間脳下垂体機能不全によるホルモン補充療法を要する症例が20例/39例（54.7％）、抑うつ傾向にある症例が6例/24例（35％）で認められた。また多くの症例で、進学や就職が可能であったが、精神発達遅滞を来した症例を4例認めた。死亡した4例を除いてKPSが70以下の症例は7例/39であり、原因は前述の高次脳機能障害に加え、腫瘍そのものによる視力視野障害と不全片麻痺であった。
【考察】
頭蓋内胚細胞腫瘍は、高悪性度群であっても初期治療を完遂することで良好な生命予後が期待できると思われた。また腫瘍関連死の回避や長期生存者のQOLを考慮すると、厳格なホルモン補充療法や精神神経疾患の早期発見、早期治療が非常に重要であると考えられた。

Event date： 2016.5

Language：Japanese  

Country：Japan  

Event date： 2024.5

Language：Japanese  

Country：Japan  

Event date： 2024.5

Language：Japanese  

Country：Japan  

Event date： 2023.7

Language：Others  

Venue：東京   Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.6

Language：Japanese  

Country：Japan  

Event date： 2023.2

Language：Japanese  

Venue：那覇   Country：Japan  

Event date： 2022.11

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Country：Japan  

Event date： 2022.5

Language：Japanese  

Country：Japan  

Event date： 2022.5

Language：Japanese  

Country：Japan  

【背景】経鼻内視鏡手術の適応はトルコ鞍近傍疾患から様々な頭蓋底疾患へと拡がりつつある が、眼窩内病変、特に筋円錐内の腫瘍に対する経鼻内視鏡アプローチはいまだチャレンジング である。本発表では我々の経験をもとに、眼窩内筋円錐内腫瘍に対する本アプローチの有用性 や可能性について報告する。 【対象】2019年1月から2021年4月までの間に経鼻内視鏡アプローチで手術を行なった眼窩内腫 瘍10例を対象とした。 【結果】眼窩内腫瘍全10例のうち、筋円錐内腫瘍は4例あり、それぞれの組織型はCavernous hemangioma2例、Schwannoma1例、MALT lymphoma1例であった。全例で両側鼻孔アプローチ を用い、病側上顎洞を開放した後に眼窩下内側壁を広く露出した。Periorbitaを切開後、内直 筋、下直筋の間より腫瘍の摘出操作を行った。摘出後はperiorbitaは可能な限り縫合した。当 初より生検術を予定していたMalt lymphoma以外の全ての症例で腫瘍は全摘出が可能であっ た。術前に視力低下を認めていた2例については、術後視力が改善したが、1例で術後軽度の 視野欠損が新たに生じた。また、1例では術後の眼球陥凹にて術半年後に眼窩底再建を行なっ た。 【考察・結語】眼窩内側下方に存在する腫瘍は、開頭や外側からのアプローチは困難であり、 経鼻内視鏡アプローチの良い適応である。一方で、内視鏡下での手術器具の操作性を考える と、腫瘍が筋円錐内に存在する場合は、Cavernous hemangiomaやSchwannomaなどの癒着の少な い良性腫瘍が適している。侵襲性や整容面など、経鼻内視鏡手術は開頭手術よりも優れている 点も多く、本アプローチは症例に応じて積極的に考慮されるべきである。ただし、本アプロー チを遂行するには、眼窩内だけでなく、鼻腔、副鼻腔の解剖についても熟知していることが重 要である。

Event date： 2021.9

Language：Japanese  

Country：Japan  

【背景】近年、内視鏡の技術や手技の向上とともに、経鼻内視鏡手術の適応はトルコ鞍近傍疾患から様々な頭蓋底疾患へと拡がりつつあるが、翼口蓋窩や中頭蓋窩などの外側に存在する病変に対しては経鼻単独ではアプローチ困難な場合も多い。今回、我々は両側鼻孔に加えて口唇下より上顎洞前壁にもエントリーホールを作成し、3ポート下での手術操作を可能とすることで、同部位の病変に対応した。本発表では、本アプローチの有用性や可能性について当院での経験を元に報告する。
【方法】2019年4月から2021年5月までの間に本アプローチを用いて手術を行なった4症例について後方視的に解析した。
【結果】症例は若年性血管繊維腫２例、神経鞘腫１例、軟骨肉腫１例であった。口唇下に開けたエントリーホールと同側病変へのアプローチを行なった症例が３例（血管繊維腫、神経鞘腫）、対側病変へのアプローチが１例（軟骨肉腫）であった。本アプローチの使用により、同側病変では翼口蓋窩や眼窩下〜外側の操作が可能となり、対側病変では、vidian nerveを温存しながら、対側の錐体尖部の操作が可能であった。全症例で、腫瘍は全摘出が可能であった。術後経度の上口唇の感覚鈍麻が出現したが、その他は特に大きな合併症は認めなかった。
【考察・結語】
翼口蓋窩腫瘍や錐体尖部などの病変は、経鼻腔アプローチでは観察は行えても、実際の手術操作が困難な場合がある。新たなポートを作成することで、このような症例でも器具の干渉を減らし、視野や操作範囲の拡大することが可能となる。複数のアプローチを柔軟に組み合わせることで、今後の内視鏡手術の適応がさらに拡大していくことが期待される。

Event date： 2020.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

【背景】近年、内視鏡技術や手技の向上とともに、経鼻内視鏡手術の適応はトルコ鞍近傍疾患から様々な頭蓋底疾患へと拡がりつつあるが、それに伴い、アプローチの選択や術後の再建において、脳神経外科単独での対応が困難な例もしばしば経験するようになった。当院では2018年8月より耳鼻咽喉科と合同で頭蓋底チームを結成し、ほぼ全ての経鼻内視鏡下手術に耳鼻科合同手術を導入している。今回はその中で特に眼窩内腫瘍や中頭蓋窩腫瘍など外側病変に対するアプローチの工夫やバリエーションについて、当院での経験を元に報告する。
【方法】2018年8月から2020年3月までの間に耳鼻咽喉科との合同手術を行なった連続71症例（開頭、内視鏡）を後方視的に解析した。
【結果】眼窩内腫瘍は5例、中頭蓋窩腫瘍は３例であった。これらのうち、経鼻内視鏡単独で治療が完遂したものは眼窩内腫瘍で２例、中頭蓋窩腫瘍で２例であった。腫瘍が眼窩内内側上方へ進展している３症例については、経鼻内視鏡下手術に、形成外科医による経眼瞼アプローチを加えたcombined surgeryを行った。また、外側に進展が見られた眼窩内腫瘍１例と中頭蓋窩腫瘍１例では、犬歯窩より上顎洞前壁にもコントロールホールを作製し、multiport surgeryを行なった。術後眼球陥凹にて眼窩底再建を1例で行なった他は特に大きな合併症は認めなかった。
【考察・結語】
眼窩内腫瘍や中頭蓋窩腫瘍などの外側に存在する腫瘍は経鼻腔のみのアプローチでは手術操作困難な場合もある。複数の診療科での合同手術を行うことで通常の経鼻アプローチに加えて犬歯窩アプローチや眼瞼アプローチなどを柔軟に組み合わせることが可能となり、内視鏡手術の適応がさらに拡大していくことが期待される。

Event date： 2017.2

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Country：Japan  

Event date： 2016.12

Language：Japanese  

Country：Japan  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese