記述言語：英語   掲載種別：研究論文（学術雑誌）  

© Copyright © 2020 Abe, Natsumeda, Okada, Watanabe, Tsukamoto, Kanemaru, Yoshimura, Oishi, Hashizume, Kakita and Fujii. Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with HIST1H3B K27M and ACVR1 G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with H3F3A gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze MGMT promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated MGMT promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with H3F3A gene mutation showed MGMT promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response to ALK2 inhibitor K02288 treatment in vitro. We confirmed in vitro that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.

DOI： 10.3389/fonc.2019.01568

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s13041-019-0510-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s40478-019-0774-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuronal growth cones are essential for nerve growth and regeneration, as well as for the formation and rearrangement of the neural network. To elucidate phosphorylation-dependent signaling pathways and establish useful molecular markers for axon growth and regeneration, we performed a phosphoproteomics study of mammalian growth cones, which identified >30,000 phosphopeptides of ∼1,200 proteins. The phosphorylation sites were highly proline directed and primarily MAPK dependent, owing to the activation of JNK, suggesting that proteins that undergo proline-directed phosphorylation mediate nerve growth in the mammalian brain. Bioinformatics analysis revealed that phosphoproteins were enriched in microtubules and the cortical cytoskeleton. The most frequently phosphorylated site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific protein involved in axon growth. This previously uncharacterized phosphorylation site was JNK dependent. S96 phosphorylation was specifically detected in growing and regenerating axons as the most frequent target of JNK signaling; thus it represents a promising new molecular marker for mammalian axonal growth and regeneration.

DOI： 10.1016/j.isci.2018.05.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

DOI： 10.1093/neuonc/noac243

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記述言語：英語  

Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.

DOI： 10.1111/neup.12822

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記述言語：英語  

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. The standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSLs. CASE PRESENTATION: A 54-year-old man with a history of gout presented with a change in character and cognitive dysfunction. MRI showed a large enhancing mass spanning the bilateral frontal lobes and the right temporal lobe. After endoscopic biopsy, an MTX, procarbazine, and vincristine (MPV) regimen was initiated for the treatment of the PCNSL. After the initiation of chemotherapy, the patient experienced a gout attack, and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute uric acid nephropathy. As the dramatic effect of MTX was observed, treatment was continued despite ARF, most probably due to acute hyperuricemia due to tumor lysis, which was treated in parallel. After an improvement in renal function, MTX was resumed, and rasburicase was initiated to control hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase, and renal function was preserved. CONCLUSIONS: Acute uric acid nephropathy should be considered when ARF occurs after the initiation of MTX in PCNSLs, especially in newly diagnosed PCNSL patients with large tumors or hyperuricemia.

DOI： 10.3390/jcm11195548

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記述言語：英語  

DOI： 10.1007/s11064-022-03639-4

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Human chorionic gonadotropin (hCG)-producing tumors cause peripheral precocious puberty (PP) in boys, but generally not in girls. Homology between LH and hCG activates the LH receptor in testicular Leydig cells, increases testosterone production, and causes virilization. However, since FSH action is required for follicle development, hCG action alone does not increase estradiol (E2) production and does not cause feminization. Only a few cases of peripheral PP with hCG tumors in girls have been reported. We describe the case of a 7-year-old Japanese girl with peripheral PP associated with an hCG-producing tumor. She had prolonged vomiting, loss of appetite, and Tanner stage III breast development. Although no apparent increase in growth rate, bone age was advanced at 9.8 years. Serum E2 was slightly elevated and LH and FSH were below the measurement sensitivity, and abdominal ultrasonography and computed tomography images showed no abnormal findings in the uterus or ovaries. Subsequently, she developed visual field disturbance and loss of consciousness, and brain magnetic resonance imaging revealed an intracranial tumor. Based on pathological findings and abnormally high serum hCG-β level (48,800 IU/L), intracranial choriocarcinoma was diagnosed. 2.5 months after the start of chemotherapy, the hCG-β level became almost negative and the breast development disappeared synchronously. Tissue immunostaining of the tumor showed strong positivity for aromatase and hCG, indicating that the choriocarcinoma cells themselves may have produced estrogen via aromatase. This unique case highlights the possibility that hCG-producing tumors can cause peripheral PP in girls as well as boys.

DOI： 10.1507/endocrj.EJ21-0117

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Detection of BRAF V600E mutation in glioblastomas (GBMs) is important because of potential therapeutic implications. Still, the relative paucity of these mutations makes molecular detection in all GBMs controversial. In the present study, we analyzed clinical, radiographic and pathologic features of 12 BRAF V600E-mutant GBMs and 12 matched controls from 2 institutions. We found that a majority of BRAF V600E-mutant GBMs displayed a combination of well-circumscribed lesions, large cystic components with thin walls and solid cortical component on MRI, but with some overlap with matched BRAF wildtype controls (p = 0.069). BRAF V600E-mutant GBMs were also apt to gross total resection (83% vs 17%, p = 0.016) and morphologically displayed epithelioid features (83% vs 0%, p < 0.0001). Identification of these clinical, radiographic, and pathologic characteristics should prompt testing for BRAF V600E in IDH-wildtype GBM.

DOI： 10.1007/s10014-021-00407-0

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(一社)日本サイトメトリー学会  

筆者らは、神経の成長や再生に関わる因子を同定する目的で齧歯類のin vivoのサンプルからリン酸化GAP-43 T172を検出した。そのリン酸化蛋白質に対するリン酸化検出抗体を作製し、さらに責任キナーゼを同定した。次に齧歯類で検証したリン酸化配列がアミノ酸配列上、霊長類にも保存されていたことから、霊長類としてマーモセットの新生仔脳組織を用いたリン酸化プロテオミクスで局在性を検証した。これらのプロセスについて解説した。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02667&link_issn=&doc_id=20210715310002&doc_link_id=10.18947%2Fcytometryresearch.31.1_7&url=https%3A%2F%2Fdoi.org%2F10.18947%2Fcytometryresearch.31.1_7&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

There is growing interest in liquid biopsy, the less-invasive detection of circulating tumor DNA(ctDNA)or circulating tumor cells(CTCs)from cerebrospinal fluid(CSF)and/or serum of patients, for the diagnosis of brain tumors. We share our experience of detecting hot spot point mutations using droplet digital PCR(ddPCR)in ctDNA obtained from the CSF of patients with brain tumors. The detection of mutations such as IDH1 R132H, BRAF V600E, and TERT promoter mutations in gliomas can be diagnostic. For optimal detection of ctDNA, which is only seen at very low concentrations, proper handling and storage of CSF, high-yield extraction of ctDNA, and usage of sensitive PCR methods for detection are imperative. We discuss which mutations can be assessed when diagnosing brain tumors, with a specific focus on gliomas. Finally, we look at what the near future holds for liquid biopsy of brain tumor patients, including next-generation sequencing panel analysis and accurate assessment of fusion genes.

DOI： 10.11477/mf.1436204425

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for H3F3A K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of H3F3A K27M mutation was achieved in only one case (10%); H3F3A K27M mutation was suspected in three other cases (30%). H3F3A K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite H3F3A K27M or definite H3F3A wildtype) tended to be younger (median 7.5 years vs. 40.5 years; p = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; p = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.

DOI： 10.3390/diagnostics11040681

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記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

DOI： 10.1093/jnen/nlaa141

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Double functional pituitary adenomas are rare, and only a few cases of excessive clinical symptoms of both adrenocorticotropic hormone(ACTH)and growth hormone(GH)have been reported. We herein report a case of symptomatic ACTH-and GH-producing double pituitary adenomas, which were discretely located within the same pituitary gland. A 38-year-old woman presented with general malaise, facial and lower limb edema, unexplained weight gain, facial redness, acne, and nasal enlargement. Endocrinological findings matched with the diagnostic criteria for both acromegaly and Cushing's disease. Preoperative magnetic resonance imaging showed a 15-mm cyst-like lesion on the right side of the sellae surrounded by what was thought to be the normal contrast-enhancing pituitary gland. We assumed that the cyst-like lesion was an adenoma and performed endoscopic endonasal transsphenoidal surgery. However, the cyst-like lesion was a parenchymal tumor. Furthermore, the region we considered to be a normal pituitary gland was also found to be an adenoma. Both adenomas were completely resected. The postoperative blood analysis showed ACTH<1.0pg/dL, cortisol 1.8μg/dL, and insulin-like growth factor-1 60ng/mL, all of which were below reference levels. The histopathological examination confirmed the coexistence of two adenomas, a GH-producing adenoma and an ACTH-producing adenoma. We concluded that these adenomas were endocrinologically active within the pituitary gland. Thus, a diagnosis of double pituitary adenomas was made. When treating a patient with symptoms caused by hypersecretion of multiple anterior pituitary hormones, the possibility of coexisting multiple pituitary adenomas should be considered.

DOI： 10.11477/mf.1436204171

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Biopsy is the gold standard for the diagnosis of primary CNS lymphoma (PCNSL). However, surgical biopsy has problems of morbidity related to hemorrhagic complications and false-negative findings, so safer and more reliable diagnostic methods are required. The aim of this study is to detect the MYD88 mutation, an important driver mutation, in the cerebrospinal fluid (CSF) of patients with CNS lymphoma. PATIENTS AND METHODS: Twenty-six patients with CNS lymphoma (20 primary CNS lymphoma and six CNS relapse from systemic lymphoma) were studied. We extracted cell-free DNA (cfDNA) from CSF by lumbar puncture. cfDNA was extracted from 1 mL of CSF, and Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) were performed. Furthermore, we performed DNA sequencing of MYD88 in 21 cases with available surgically obtained formalin-fixed paraffin-embedded (FFPE) tissue and compared the results. RESULTS: The median cfDNA amount extracted from 1 mL CSF was 219 ng/mL (25th to 75th percentile, 129 to 333 ng/mL). MYD88 mutations were detected from CSF in 76.9% (20 of 26 cases), and L265P in exon 5 was the most frequent mutation in 19 out of 20 (95.0%) cases. S219C in exon 3 was detected in one case. In four patients, MYD88 mutation was confirmed by ddPCR but not by Sanger sequencing. In all 21 cases with sufficient FFPE tissue for DNA analysis, the detection of MYD88 mutation from cfDNA was consistent with those of tumor-derived DNA from FFPE tissue. CONCLUSION: This pilot study provided evidence that the somatic driver mutation MYD88 can be reliably detected by combination of Sanger sequencing and ddPCR in the cfDNA taken from 1 mL of CSF in patients with CNS lymphomas.

DOI： 10.1200/PO.18.00308

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記述言語：英語  

DOI： 10.1080/10428194.2019.1639169

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.wneu.2019.05.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2176/nmc.oa.2018-0078

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2176/nmc.ra.2018-0044

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

DOI： 10.1007/s10143-017-0908-y

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DOI： 10.1016/j.jocn.2017.10.086

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

We present a pediatric case of a rapidly expanding third ventricle germ cell tumor (GCT). A 14-year-old boy suffered from gradual-onset central diabetes insipidus (DI) and received desmopressin treatment. Magnetic resonance imaging (MRI) showed nonspecific findings of the pituitary-hypothalamic axis. Nine months after the initial DI diagnosis, he developed progressively worsening headache. MRI demonstrated a third ventricle tumor causing noncommunicating hydrocephalus, although an MRI 16 weeks before admission did not show the lesion. We performed gross total resection (GTR) of the tumor in 2 stages: a translamina terminalis approach and an extended transsphenoidal approach. The lesion was histologically diagnosed as immature teratoma with some germinoma. His noncommunicating hydrocephalus resolved after surgery. Through postoperative radiochemotherapy (whole ventricle: 23.4 Gy/13 fractions, tumor bed: 27.0 Gy/15 fractions, and 3 courses of carboplatin-etoposide), he has was in complete remission at the 3-year follow-up and has continued his high school program. This case suggests the following: (1) a mixed GCT originating from the neurohypophysis/infundibulum can show rapidly expansive growth in a child with central DI
(2) GTR and adjuvant radiochemotherapy can result in a good therapeutic outcome in rapidly expanding GCT
and (3) the extended transsphenoidal approach is a complementary approach to transcranial resection of anterior third ventricle GCTs.

DOI： 10.1159/000480021

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

Background Since the origin and growth pattern of third ventricle ectopic pituitary adenoma (ectPA) remain unclear, its optimal surgical approach is debatable. Clinical presentation We present a rare case of null cell pituitary adenoma arising from the pituitary infundibulum with long-term preoperative follow-up images. The tumor was resected gross-totally via an extended transsphenoidal approach. Conclusion To our best knowledge, this is the first case with long-term preoperative follow-up images, which can bridge the knowledge gap in operations of third ventricle ectPA as following: (1) Truly third ventricle ectPA can exist, (2) the third ventricle ectPA extended into the sella turcica along the pituitary stalk, (3) this ectPA can arise from the suprasellar peri-infundibular ectopic pituitary cells or the pars tuberalis of the adenohypophysis, and therefore adhere to the optic chiasm, (4) thus neurosurgeons should take great care in resection of ectPA arising from the infundibulum, and (5) it can be resected through an endoscopic extended transsphenoidal approach.

DOI： 10.1016/j.inat.2017.08.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

We present a pediatric case of neurohypophyseal germinoma with a perifocal inflammatory reaction (PIR) with volume fluctuation caused by diagnostic radiation-induced regression (DRIR). On-target biopsy failed to confirm the histology because PIR hardly contained any germinoma cells. DRIR-related fluctuation of the tumor volume disguised germinoma as inflammation. We analyzed the cerebrospinal fluid (CSF) and detected a high level of placental alkaline phosphatase (PLAP), which demonstrated the neurohypophyseal lesion to be germinoma and brought the patient from successful radiochemotherapy up to complete remission. PIR adjacent to the germinoma (PIRAG) disappeared completely following radiochemotherapy, although it contained almost no germinoma cells. Examination of the CSF-PLAP level can complement the diagnosis of germinoma and will decrease the risk of misdiagnosis. Neurosurgeons should keep in mind PIRAG, DRIR, and the diagnostic value of CSF-PLAP when germinoma is suspected. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000450583

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MANEY PUBLISHING  

Objectives: The study objectives are (1) to identify factors predicting the excellent visual recovery after transsphenoidal removal of pituitary tumors and (2) to describe the association of excellent visual recovery and early restoration of symmetry of the decompressed optic chiasm.
Methods: Thirty-five patients with visual symptoms due to pituitary tumors underwent endoscopic endonasal surgery. All patients received perioperative diagnostic magnetic resonance (MR) imaging and ophthalmological assessments within 2 weeks before surgery, within 2 weeks after surgery, and 3 months or later after surgery. Preoperative best-corrected visual acuity (BCVA &gt;= 20/20), degree of visual field deficit (VFD, less than half of VF), thickness of retinal nerve fiber layer (RNFL) measured by optical coherence tomography (OCT), and thickness of ganglion cell complex (GCC) measured by OCT were considered for statistical analysis as predictive factors of VF outcome. Multivariate logistic regression models were used in statistical evaluation of data.
Results: In the multivariate analysis, RNFL (odds ratio = 62.137, P &lt; 0.001) and preoperative VFD (odds ratio = 8.244, P &lt; 0.02) proved to be effective as factors predicting sufficient VF recovery. Postoperative restoration of symmetry of the optic chiasm was related to sufficient VF recovery (P &lt; 0.0001, Fisher's exact test) and RNFL (P &lt; 0.0001, Fisher's exact test).
Discussion: Early decompression is crucial for sufficient VF recovery, in particular, while RNFL preserves normal or borderline thickness and while VFD keeps within hemianopia. Morphological reversibility is associated with functional reversibility in the optic chiasm compressed by a pituitary tumor. In particular, early morphological recovery suggests functional recovery, which indicates neurocyte reserve in the compressed optic pathway with functional recovery.

DOI： 10.1179/1743132814Y.0000000407

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration-an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

DOI： 10.1038/ncomms3740

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER WIEN  

High-definition imaging in endoscopic transsphenoidal pituitary surgery accounts for significantly better identification of anatomic structures. This report presents the clinical images of the adenohypophysis and neurohypophysis under high-definition endoscopic observation, and provides some clues for pituitary-sparing surgery.
Ten demonstrative cases of pituitary lesions, including three cases of gonadotropin-producing pituitary adenoma, two cases of somatotropin-secreting pituitary adenoma, and five cases of Rathke's cleft cysts, were entered in this study. From these cases, we extracted helpful intraoperative findings that affected the surgeon's decision about surgical procedures and led to favorable results.
The extracted findings contain the following lessons: (1) to find a boundary plane that separate a lesion from the pituitary; (2) to mark the difference of color between the adenohypophysis and the neurohypophysis; (3) to identify the location of the pituitary stalk connecting to the neurohypophysis; (4) to observe the color change of the pituitary induced by decompression; (5) to know pathological findings of the pituitary surface; (6) to distinguish the parenchyma of the neurohypophysis from pathological tissues; and (7) to recognize the intrasellar findings at the completion of removal. Recognition of these findings led to an excellent result in each case.
Despite being shown in a limited number of cases, on the basis of HD endoscopic images, accurate identification of the neurohypophysis and the pituitary stalk as well as adenohypophysis during surgery contributes to pituitary-conserving operations.

DOI： 10.1007/s00701-013-1687-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The efficacy and toxicity of high-dose methotrexate (HD-MTX)-based chemotherapy were retrospectively reviewed in patients with primary central nervous system lymphoma (PCNSL). All immunocompetent patients with histologically or radiographically diagnosed PCNSL treated between 2006 and 2012 at Niigata University Hospital were enrolled. Thirty-eight patients with a diagnosis of PCNSL were treated with one of two regimens during different time periods. During the first period, from 2006 to 2009, three 3-week cycles of MPV (MTX + procarbazine + vincristine) were administered (MPV3 group). In the second period, from 2010 to 2012, five 2-week cycles of MTX were administered (MTX5 group). High-dose cytarabine was used in both groups following HD-MTX-based chemotherapy. Whole-brain radiotherapy was used for patients who did not attain a complete response (CR) based on magnetic resonance images. In the MPV3 group, 20 out of 23 patients (87%) completed the planned treatment. The CR rate after chemotherapy was 30%, and 57% after radiation therapy. Thirteen out of 15 patients (87%) in the MTX5 group completed the planned treatment. The CR rates after chemotherapy and radiation therapy were 53% and 93%, respectively. Renal dysfunction was assessed by measuring creatinine clearance rates, which were very similar in both groups. In terms of hematologic toxicity and other adverse reactions, there was no significant difference between the two groups. In conclusion, dose-dense MTX chemotherapy improved outcome with acceptable toxicity compared with the treatment schedule for three cycles of MPV treatment.

DOI： 10.2176/nmc.oa2013-0195

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(一社)日本医用マススペクトル学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：日本脳腫瘍病理学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2017051753

記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2017051754

記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2016392694

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

2006〜2014年に初回手術を受けたGH産生下垂体腺腫連続73例を対象に、手術年代により分類し、2006〜2008年の26例をA群、2009〜2011年の19例をB群、2012〜2014年の28例をC群とし、初診時の症状、GH基礎値、合併症および予後を比較した。その結果、C群はA、B群に比べ初診時の軟部組織の肥大が軽度で、GH基礎値が低く、microadenomaが少なからずみられた。また、C群は術前に耐糖能異常を示す患者が少なく、術後さらに減少した。更にC群は術後に照射・投薬などの追加治療を要する症例が少なかった。近年の早期発見傾向は治療成績の向上に寄与し、患者に恩恵をもたらしていると考えられた。

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2016135737

記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2016135687

記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2016135688

記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟県医師会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：山形県病医誌編集委員会  

著者らの施設におけるガンマナイフ治療の経験を報告した。対象は2001年5月〜2009年4月までにガンマナイフ治療を行った聴神経腫瘍15例(男性7例、女性8例、平均年齢66歳)であった。腫瘍容積は平均3.1cm3、治療辺縁線量は平均54%等線量曲線で12Gy、追跡期間は平均2.6年であった。この治療後、臨床症状をはじめ合併症、腫瘍容積の変化について調べた結果、1)治療前に有効聴力のあった2例で治療後の悪化は認めず、全例で治療後に外科的治療を要した例はなかった。2)治療後の合併症は1例に一過性の顔面神経麻痺がみられたが、保存的治療で回復した。3)腫瘍容積の変化は縮小10例(67%)、不変1例(7%)、増大4例(26%、うち2例は縮小傾向)であった。4)縮小ないし縮小傾向のパターンは、治療後増大なしに縮小が3例(20%)、治療後1.2〜1.5倍に増大後1年以内に縮小が6例(40%)、治療後1〜2年で1.5〜2.5倍に増大後徐々に縮小が3例(20%)であった。以上、これらのことからも本治療は安全で有効な治療法と考えられた。

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その他リンク： http://search.jamas.or.jp/link/ui/2010097877

記述言語：日本語   出版者・発行元：(一社)日本小児神経外科学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

症例は56歳,男性.検診時に白血球および血小板減少を指摘された.精査にて脾腫とインターロイキン2レセプター(IL-2R)の高値を認めたため,脾原発性悪性リンパ腫あるいは慢性リンパ性白血病(hairy cell leukemia)を疑われた.診断目的にハンドアシスト法腹腔鏡補助下脾臓摘出術を施行した.病理組織診断では非定型的B細胞慢性リンパ性白血病と診断された.術後合併症なく,第14病日に退院となった.脾臓摘出後より骨髄抑制は軽快し,現在再発の徴候無く経過観察中である.自験例および文献的考察から,ハンドアシスト法腹腔鏡補助下脾臓摘出術は脾臓を損傷することなく体外に摘出可能であり,血液悪性疾患に対して診断目的に脾臓摘出術を行う際には,考慮すべき術式選択の1つである.

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記述言語：日本語   出版者・発行元：新潟医学会  

症例は56歳、男性。検診時に白血球および血小板減少を指摘された。精査にて脾腫とインターロイキン2レセプター(IL-2R)の高値を認めたため、脾原発性悪性リンパ腫あるいは慢性リンパ性白血病(hairy cell leukemia)を疑われた。診断目的にハンドアシスト法腹腔鏡補助下脾臓摘出術を施行した。病理組織診断では非定型的B細胞慢性リンパ性白血病と診断された。術後合併症なく、第14病日に退院となった。脾臓摘出後より骨髄抑制は軽快し、現在再発の徴候無く経過観察中である。自験例および文献的考察から、ハンドアシスト法腹腔鏡補助下脾臓摘出術は脾臓を損傷することなく体外に摘出可能であり、血液悪性疾患に対して診断目的に脾臓摘出術を行う際には、考慮すべき術式選択の1つである。(著者抄録)

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その他リンク： http://hdl.handle.net/10191/32619

記述言語：日本語   出版者・発行元：新潟医学会  

今回,著者らは慢性腎不全患者における術後methicillin-resistant Staphylococcus aureus (MRSA)腹腔内膿瘍に対してlinezohd (ZYVOX^[〇!R])が著効した1例を経験した.慢性腎不全患者における術後感染症に対する抗菌薬の選択を考える上で示唆に富む症例と考えられたので報告する.症例は53歳,男性.慢性腎不全のため透析療法施行中であり,十二指腸乳頭部癌の診断で,幽門輪温存膵頭十二指腸切除術が施行された.術後10病日に胆管空腸吻合部の縫合不全による胆汁漏を認めた.19病日に38.7℃の発熱と腹痛があり,腹部CT検査では挙上空腸前面に腹腔内膿瘍を認めたため,経皮的膿瘍ドレナージを施行した.細菌培養検査でMRSA (3+)が検出されたため,linezolid投与(600mg×2回/日)を開始した.投与後,臨床症状は改善し,腹部CT検査で膿瘍は消失した.腹腔内留置ドレーンからの培養検査でもMRSAは陰性化した.Linezolidは透析療法施行中の患者に対しても通常量投与が可能であり,腎不全患者におけるMRSA感染症に対し考慮されるべき抗菌薬の1つである.

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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