Details of a Researcher - Toda, Masahiro

Papers - Toda, Masahiro

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Historic Overview of Genetic Engineering Technologies for Human Gene Therapy

Tamura R, Toda M

Neurol Med Chir(Tokyo) (Neurologia Medico-Chirurgica) 60 ( 10 ) 483 - 491 2020.10

Research paper (scientific journal), Joint Work, Accepted, ISSN 04708105

The concepts of gene therapy were initially introduced during the 1960s. Since the early 1990s, more than 1900 clinical trials have been conducted for the treatment of genetic diseases and cancers mainly using viral vectors. Although a variety of methods have also been performed for the treatment of malignant gliomas, it has been difficult to target invasive glioma cells. To overcome this problem, immortalized neural stem cell (NSC) and a nonlytic, amphotropic retroviral replicating vector (RRV) have attracted attention for gene delivery to invasive glioma. Recently, genome editing technology targeting insertions at site-specific locations has advanced; in particular, the clustered regularly interspaced palindromic repeats/CRISPR-associated-9 (CRISPR/ Cas9) has been developed. Since 2015, more than 30 clinical trials have been conducted using genome editing technologies, and the results have shown the potential to achieve positive patient outcomes. Gene therapy using CRISPR technologies for the treatment of a wide range of diseases is expected to continuously advance well into the future.

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Targeted Embolisation for Coexisting Conus Medullaris Arteriovenous Malfomation and Cauda Equina Arteriovenous Fistulas with a Varix on a Shared Drainer

Yoshida K, Niimi Y, Kamamoto D, Fukumura M, Imai R, Nagoshi N, Akiyama T

British Journal of Neurosurgery 2020.10

Research paper (scientific journal), Joint Work, Accepted

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Posture-induced changes in the vessels of the head and neck: evaluation using conventional supine CT and upright CT

Kosugi K, Yamada Y, Ymada M, Yokoyama Y, Fujiwara H, Yoshida Ke, Yoshida Ka, Toda M,　Jinzaki M

Scientific Reports (Scientific Reports) 10 ( 1 ) 2020.10

Research paper (scientific journal), Joint Work, Accepted

Since the venous system is affected by gravity, upright computed tomography (CT) in addition to conventional supine CT has great potential for evaluating postural changes in the venous system. We evaluated the morphological differences in the head and neck vessels by performing a contrast CT study in both the supine and the sitting positions. In this study, the 20 included participants (10 men and 10 women) were healthy adults aged 30 to 55 years. The cross-sectional area of the cervical vessels, craniocervical junction veins, and intracranial vessels were obtained quantitatively. Venous sinuses and venous plexuses that were difficult to measure were evaluated qualitatively. The average change in areas from a supine to an upright posture was − 77.87 ± 15.99% (P < 0.0001) in the right internal jugular vein (IJV), − 69.42 ± 23.15% (P < 0.0001) in the left IJV, − 61.52 ± 12.81% (P < 0.0001) in the right external jugular vein (EJV), and − 58.91 ± 17.37% (P < 0.0001) in the left EJV. In contrast, the change in the anterior condylar vein (ACV) from a supine to an upright posture was approximately + 144% (P < 0.005) on the right side and + 110% (P < 0.05) on the left side. In addition, according to the qualitative analysis, the posterior venous structures including the anterior condylar confluence (ACC) of the craniocervical junction became more prominent in an upright posture. Despite these changes, the intracranial vessels showed almost no change between postures. From a supine to an upright position, the IJVs and EJVs above the heart collapsed, and venous channels including the ACCs and ACVs opened, switching the main cerebral venous drainage from the IJVs to the vertebral venous system. Upright head CT angiography can be useful for investigating physiological and pathophysiological hemodynamics of the venous system accompanying postural changes.

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Pros and Cons of the Exoscope for Otologic Surgery

Kanzaki S, Takahashi S, Toda M, Yoshida K, Ogawa K.

Surgical Innovation (Surgical Innovation) 2020.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 15533506

Introduction. There are a few discussions regarding usefulness of an exoscope in otologic surgery compared to a traditional microscope. Objective. The pros and cons of using a newly developed exoscope (ORBEYE™) during microotologic surgery were evaluated. Methods. The usefulness of the ORBEYE™ exoscope was retrospectively assessed in 6 otologic surgeries by 8 surgeons postoperatively. A questionnaire comprising 20 questions was designed and used for evaluation. Results. All the otologic surgeons agreed that the exoscope is useful as an educational tool; the exoscope had the highest score in the questionnaire (average: 4.75). The question “Will the ORBEYE exoscope replace the conventional tympanoplasty or stapes surgery?” had the lowest score (average: 3.13). Conclusions. The quality of the images and movies in the exoscope was considered to be high and improved; therefore, the exoscope was considered as a useful educational tool in otologic surgery. Similar to otologic endoscopic surgery, all the members such as the operator and assistants could head up and share 1 image. TM

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Endoscopic endonasal transinfraturbinate approach with nasoseptal window for removal of the pterygopalatine fossa tumor

Yamada H, Toda M, Abiko T, Ozawa H, Ogawa K, Yoshida K

J Craniofac Surg 2020.09

Research paper (scientific journal), Joint Work, Accepted

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A pilot study of the adverse events caused by the combined use of bevacizumab and vascular endothelial growth factor receptor-targeted vaccination for patients with a malignant glioma

Tamura R., Morimoto Y., Sato M., Hikichi T., Yoshida K., Toda M.

Vaccines (Vaccines) 8 ( 3 ) 1 - 10 2020.09

Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.

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Current understanding of lymphatic vessels in the central nervous system

Tamura R., Yoshida K., Toda M.

Neurosurgical Review (Neurosurgical Review) 43 ( 4 ) 1055 - 1064 2020.08

ISSN 03445607

Lymphangiogenesis is associated with some pathological conditions such as inflammation, tissue repair, and tumor growth. Recently, a paradigm shift occurred following the discovery of meningeal lymphatic structures in the human central nervous system (CNS); these structures may be a key drainage route for cerebrospinal fluid (CSF) into the peripheral blood and may also contribute to inflammatory reaction and immune surveillance of the CNS. Lymphatic vessels located along the dural sinuses absorb CSF from the adjacent subarachnoid space and brain interstitial fluid via the glymphatic system, which is composed of aquaporin-4 water channels expressed on perivascular astrocytic end-feet membranes. Magnetic resonance imaging (MRI) clearly visualized these lymphatic vessels in the human dura mater. The conception of some neurological disorders, such as multiple sclerosis and Alzheimer’s disease, has been changed by this paradigm shift. Meningeal lymphatic vessels could be a promising therapeutic target for the prevention of neurological disorders. However, the involvement of meningeal lymphatic vessels in the pathophysiology has not been fully elucidated and is the subject of future investigations. In this article, to understand the involvement of meningeal lymphatic vessels in neurological disorders, we review the differences between lymphangiogenesis in the CNS and in other tissues during both developmental and adulthood stages, and pathological conditions that may be associated with meningeal lymphatic vessels in the CNS.

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Sinking Skin Flap Syndrome Visualized by Upright Computed Tomography

Yoshida K, Toda M, Yamada Y, Yamada M, Yokoyama Y, Fujiwara H, Kosugi K, Fukumura M, Koike K, Takahashi S, Yoshida K, Jinzaki M

Acta Neurochir (Wien) (Acta Neurochirurgica) 162 ( 8 ) 1825 - 1828 2020.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 00016268

Sinking skin flap syndrome is a craniectomy complication characterized by new neurological dysfunction that typically worsens in the upright position and improves after cranioplasty. We present a 33-year-old man who experienced hemiparesis in the upright position after craniectomy. Upright computed tomography (CT) before cranioplasty showed a remarkable shift of the brain compared to supine CT. After cranioplasty, both symptoms and brain shift on CT resolved. Upright CT enables detection and objective evaluation of paradoxical herniation and midline shift that is not obvious on supine imaging modalities. Clinicians need to be aware of positional brain shift in postcraniectomy patients.

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Endoscopic endonasal removal of a pediatric paranasal ossifying fibroma using preoperative embolization

Saito S., Ozawa H., Ikari Y., Nakahara N., Ito F., Sekimizu M., Kameyama K., Akiyama T., Toda M., Ogawa K.

Otolaryngology Case Reports (Otolaryngology Case Reports) 14 2020.03

Background: Ossifying fibroma arising in the sinonasal tract is rare. Its treatment includes complete resection; however, this can be challenging to perform due to the well-vascularized nature of the fibroma. Some surgical techniques can control intraoperative hemorrhage; however, to date, no reports have assessed the use of preoperative embolization. Methods: We report a case of a child with ossifying fibroma arising from the ethmoid sinus, which was resected by endoscopic surgery using preoperative transarterial embolization. Conclusions: Embolization was effective in decreasing intraoperative hemorrhage. No complications related to the procedure or operation were encountered. Preoperative embolization should be considered for better control of the bleeding that occurs in ossifying fibromas, similar to that in other well-vascularized tumors.

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A case of moyamoya disease symptomatized early after nivolumab initiation - Possible association between immune checkpoint inhibitors and moyamoya disease

Ozawa H, Sekimizu M, Saito S, Nakamura S, Mikoshiba T, Toda M, Ogawa K

Clin Neurol Neurourg 2020.01

Research paper (scientific journal), Joint Work, Accepted

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Difference in the hypoxic immunosuppressive microenvironment of patients with neurofibromatosis type 2 schwannomas and sporadic schwannomas.

Tamura R, Morimoto Y, Sato M, Kuranari Y, Oishi Y, Kosugi K, Yoshida K, Toda M

J Neurooncol (Journal of Neuro-Oncology) 146 ( 2 ) 265 - 273 2020

Research paper (scientific journal), Joint Work, ISSN 0167594X

Background: Neurofibromatosis type 2 (NF2) patients uniformly develop multiple schwannomas. The tumor-microenvironment (TME) is associated with hypoxia and consists of immunosuppressive cells, including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). The hypoxic TME of NF2 schwannomas remains unclear. In addition, no comparative study has investigated immunosuppressive cells in NF2 and sporadic schwannomas. Methods: In 22 NF2 and 21 sporadic schwannomas, we analyzed the immunohistochemistry for Ki-67, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2, platelet derived growth factor receptor-beta (PDGFR-β), programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1), Foxp3, CD163, CD3, and CD8 to assess the immunosuppressive TME. Results: Most vessels in sporadic schwannomas exhibited slight or negative VEGFR1 and 2 expressions with pericytes coverage. In contrast, large vessels in NF2 schwannomas exhibited strong VEGFR1 and 2 expressions without pericytes. The number of CD3 , CD8 , and CD163 cells was significantly higher in NF2 schwannomas than in sporadic ones. The expression of PD-L1 and nestin positive cell ratio was higher in NF2 schwannomas than that in sporadic ones. The number of CD163 cells, nestin positive cell ratio, and HIF-1α expression were significantly associated with shorter progression-free survival in NF2 schwannomas. Conclusions: This study presents the clinicopathological features of the differences in immunosuppressive cells and the expression of immune checkpoint molecules between NF2 and sporadic schwannomas. Hypoxic TME was first detected in NF2-schwannomas, which was associated with the tumor progression. + + + +

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Prediction of postoperative recurrence of chronic subdural hematoma using quantitative volumetric analysis in conjunction with computed tomography texture analysis.

Kanazawa T, Takahashi S, Minami Y, Jinzaki M, Toda M, Yoshida K

J Clin Neurosci (Journal of Clinical Neuroscience) 72 270 - 276 2020

Research paper (scientific journal), Joint Work, ISSN 09675868

Chronic subdural hematoma (CSDH) is a common disease in older individuals with a substantial rate of recurrence. The mechanism of CSDH recurrence remains unclear. This study aimed to detect imaging parameters that could indicate the risk for CSDH recurrence by using quantitative volumetric analysis and computed tomography (CT) texture analysis (CTTA). Clinical and imaging parameters were retrospectively investigated in 147 newly diagnosed CSDH lesions in 114 patients surgically treated at the Keio University Hospital during a 6-year period. For CT images, quantitative volumetric and texture analyses were performed. Hematoma volume, postoperative air volume, hematoma density, and texture parameters including kurtosis, skewness, and entropy were evaluated and compared with CSDH recurrence rate. Data were statistically evaluated, and a difference of p < 0.05 was considered significant. Reoperation for CSDH recurrence was required in 27 sides (18.4%) of 26 patients. Multivariate analysis showed that postoperative hematoma volume and postoperative hematoma density were independent risk factors for symptomatic CSDH recurrence that required reoperation. Postoperative hematoma volume, postoperative significant residual air, and postoperative hematoma density were also identified as independent risk factors for potential CSDH recurrence. Preoperative hematoma entropy was prone to be associated with both symptomatic and potential CSDH recurrence in univariate analysis, but not in multivariate analysis because of confounding factors. Quantitative volumetric analysis and CTTA could aid in distinguishing individuals at risk for CSDH recurrence.

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Efficacy of a topical gelatin-thrombin hemostatic matrix, FLOSEAL®, in intracranial tumor resection.

Kamamoto D, Kanazawa T, Ishihara E, Yanagisawa K, Tomita H, Ueda R, Jinzaki M, Yoshida K, Toda M

Surgical Neurology International (Surgical Neurology International) 72 ( 16 ) 270 - 276 2020

Research paper (scientific journal), Joint Work

Background: Hemostasis plays an important role in safe brain tumor resection and also reduces the risk for surgical complications. This study aimed to evaluate the efficacy of FLOSEAL®, a topical hemostatic agent that contains thrombin and gelatin granules, in brain tumor resections. Methods: We evaluated the hemostatic effect of FLOSEAL by scoring the intensity of bleeding from 1 (mild) to 4 (life threatening). We assessed the rate of success of hemostasis with 100 patients who underwent intracranial tumor resection. We also investigated the duration of the operation, the amount of intra- and postoperative bleeding, the number of hospital stays, and adverse events in patients who used FLOSEAL compared with those who did not use FLOSEAL. Results: FLOSEAL was applied to a total of 109 bleeding areas in 100 patients. A total of 95 bleeding areas had a score of 1 and 91 (96%) showed successful hemostasis. Thirteen bleeding areas scored 2 and 8 (62%) showed hemostasis with the first application of FLOSEAL. The second application was attempted with five bleeding areas and four showed hemostasis. About 94% (103/109 areas) of bleeding points successfully achieved hemostasis by FLOSEAL. Moreover, FLOSEAL significantly decreased the amount of intraoperative bleeding and postoperative bleeding as assessed with computed tomography on 1 day postoperatively compared with no use of FLOSEAL. There were no adverse events related to FLOSEAL use. Conclusion: Our results indicate that FLOSEAL is a reliable, convenient, and safe topical hemostatic agent for intracranial tumor resection.

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Surgical outcomes of anterior cerebellopontine angle meningiomas using the anterior transpetrosal approach compared with the lateral suboccipital approach.

Hassaan SA, Tamura R, Morimoto Y, Kosugi K, Mahmoud M, Abokerasha A, Moussa A, Toda M, Yoshida K

Acta Neurochir (Wien) (Acta Neurochirurgica) 162 ( 6 ) 1243 - 1248 2020

Research paper (scientific journal), Joint Work, ISSN 00016268

Background: Anterior transpetrosal approach (ATPA) and lateral suboccipital approach (LSO) are the major surgical approaches for cerebellopontine angle (CPA) meningiomas. Particularly, anterior CPA meningiomas are challenging lesions to be treated surgically. To date, only a few studies have directly compared the outcomes of both approaches focusing on the anterior CPA meningiomas. Methods: For the comparative analysis, anterior CPA meningiomas that were eligible for both APTA and LSO were collected in our hospital from April 2005 to March 2017. Anterior CPA meningiomas targeted for this study were defined as follows: (1) without cavernous sinus, clivus, and middle cranial fossa extension, (2) the posterior edge is 1 cm behind the posterior wall of the internal auditory canal, and (3) the inferior edge is above the jugular tuberculum. Based on these criteria, the operative outcomes of 17 patients and 13 patients who were operated via ATPA and LSO were evaluated. Results: The complication rate of the LSO group was significantly higher than that of the ATPA group (30.7% vs. 0%, p = 0.033). The removal rate did not differ between the ATPA and LSO groups (97.35% vs. 99.23%, p = 0.12). The operative time was significantly shorter in the LSO group than in the ATPA group (304.3 min vs. 405.8 min, p = 0.036). Conclusions: Although the LSO is more widely used for CPA meningiomas, ATPA is also considered for these anterior CPA meningiomas.

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Quantitative assessment and clinical relevance of VEGFRs-positive tumor cells in refractory brain tumors.

Tamura R, Sato M, Morimoto Y, Ohara K, Kosugi K, Oishi Y, Kuranari Y, Murase M, Yoshida K, Toda M

Exp Mol Pathol (Experimental and Molecular Pathology) 114 2020

Research paper (scientific journal), Joint Work, ISSN 00144800

Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)1 and 2 signaling is a potent activator of tumor angiogenesis. Although the expressions of VEGFR1 and VEGFR2 were initially thought to be limited to the endothelial cells, it is now known that both the receptors are expressed in tumor cells. This is the first study wherein VEGFRs-positive tumor cells are quantitatively evaluated for brain tumors with upregulated VEGF/VEGFR signaling. The percentage of VEGFRs-positive tumor cells was quantitatively evaluated in various brain tumors (10 glioblastomas, 22 neurofibromatosis type 2 [NF2]-related schwannomas, 21 sporadic schwannomas, 27 chordomas, 36 meningiomas, 29 hemangioblastomas, 11 hemangiopericytoma, and 13 ependymomas) using immunohistochemistry. VEGF-A expression was also analyzed using quantitative real-time polymerase chain reaction. Double immunofluorescence staining using anti-PDGFR-β and anti-CD34 antibody, microvessel density, and vessel diameter were analyzed to evaluate the vascular characteristics. Chordomas demonstrated an extremely higher percentage of VEGFR1 and VEGFR2-positive tumor cells than other tumors. In contrast, meningiomas and hemangiopericytomas showed few VEGFRs-positive tumor cells. The percentage of positive tumor cells in chordomas, hemangioblastomas, and NF2 schwannomas was associated with clinical courses, such as shorter progression free survival, and growth speed. Glioblastomas and NF2 schwannomas showed larger tumor vessels without pericyte coverage. The present study is the first to quantitatively analyze VEGFR1- and VEGFR2- positive tumor cells in various types of refractory brain tumors. This novel parameter significantly correlated with the progressive clinical courses.

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Gene Therapy Using Neural Stem/Progenitor Cells Derived from Human Induced Pluripotent Stem Cells: Visualization of Migration and Bystander Killing Effect.

Tamura R, Miyoshi H, Morimoto Y, Oishi Y, Sampetrean O, Iwasawa C, Mine Y, Saya H, Yoshida K, Okano H, Toda M

Hum Gene Ther (Human Gene Therapy) 31 ( 5-6 ) 352 - 366 2020

Research paper (scientific journal), Joint Work, ISSN 10430342

Glioblastoma is the most aggressive brain tumor characterized by diffuse infiltration into the normal brain parenchyma. Neural stem cells are known to possess the tumor-tropic migratory capacity and thus can be used as cellular vehicles for targeted delivery of therapeutic agents. In the present study, we evaluated the efficacy of herpes simplex virus thymidine kinase (HSV-TK) suicide gene therapy for glioblastoma using neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs). Although transduction of hiPSCs is preferable for a safe and stable supply in the clinical setting, high-level and/or constitutive HSV-TK expression was highly cytotoxic to hiPSCs. To overcome this problem, we used the tetracycline-inducible system to control the expression of HSV-TK. hiPSC-derived NS/PCs expressing HSV-TK were transplanted in an orthotopic xenograft mouse model of human glioblastoma. Glioblastoma cell growth in mice was dramatically inhibited following ganciclovir (GCV) administration. Survival of the mice was significantly prolonged with administration of GCV compared with control groups. Time-lapse imaging of organotypic brain slice cultures first demonstrated the directional migration of NS/PCs toward glioblastoma cells and the bystander killing effect upon GCV treatment. hiPSC-derived NS/PCs with HSV-TK/GCV suicide gene system may have considerable therapeutic potential for the treatment of glioblastoma. Color images are available online.

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Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.

Tamura R, Morimoto Y, Kosugi K, Sato M, Oishi Y, Ueda R, Kikuchi R, Nagashima H, Hikichi T, Noji S, Kawakami Y, Sasaki H, Yoshida K, Toda M

BMC Cancer (BMC Cancer) 20 ( 1 ) 196 2020

Research paper (scientific journal), Joint Work

Background: The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated. Methods: We performed the first clinical trial to assess VEGFR1 and 2 vaccination along with temozolomide (TMZ) -based chemoradiotherapy for the patients with primary glioblastomas. Furthermore, histopathological changes after the vaccination were evaluated using paired pre- and post- vaccination specimens. Results: The disappearance of radiographically enhanced lesion was observed in 2 patients after the vaccination, including one in which the methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not observed. The histopathological findings of pre- and post-vaccination specimens demonstrated that tumor vessels showed negative or slight VEGFRs expressions after the vaccination and most endothelial cells were covered with PDGFR-β-positive pericytes. Notably, CTLs induced by VEGFRs peptide vaccination attacked not only tumor vessels but also tumor cells and regulatory T cells expressing VEGFRs even in recurrent tumors. Conclusions: VEGFR1 and 2 vaccination may have a preliminary synergistic effect when administered with TMZ. The limitation of the present study was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study. Trial registration: This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.

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Analysis of the superficial middle cerebral vein in sphenoid ridge meningioma using contrast-enhanced dynamic computed tomography angiography.

Murase M, Mizutani K, Kawata K, Fujiwara H, Jinzaki M, Toda M, Yoshida K

Clin Neurol Neurosurg 191:105683, 2020 (Clinical Neurology and Neurosurgery) 191 ( 105683 ) 2020

Research paper (scientific journal), Joint Work, ISSN 03038467

Objective: The superficial middle cerebral vein (SMCV) is of clinical importance because of its contribution to the venous drainage of the superficial part of the cerebrum. Sphenoid ridge meningioma (SRM) grows adjacent to the SMCV and its drainage routes, and is thought to occasionally influence the hemodynamics of the SMCV, although this has seldom been suggested in the literature. We investigated the effect of SRM on the SMCV via blood flow analysis using multi-detector computed tomography. Patients and Methods: Overall, 22 patients with SRM who preoperatively underwent contrast-enhanced dynamic computed tomography at our institution were included in this study. We serially measured the Hounsfield units at each point of the SMCV and its adjacent veins on the side on which the tumor was located. We then obtained a time-density curve for each point via gamma distribution fitting. We determined the time-to-peak at each point by calculating the derivative of the time-density curve function and deduced the direction of blood passing through each vein by comparing the time-to-peak values between several points. Results: In total, 26 SMCVs were measured in 19 out of 22 cases. Of the 26 SMCVs, 16 were patent in the medial portion and contributed to normal venous drainage: 4 of them emptied into the cavernous sinus (CS), and 12 of them into the para-cavernous sinus (ParaCS). Out of the 10 that had their medial portions occluded because of the effects of the tumor, 6 SMCVs mainly drained into the vein of Labbé and/or the vein of Trolard retrogradely. However, in 2 of these, the small medial portions of the SMCVs near the occluded portion were maintained anterogradely by the collateral venous structures. In 4 SMCVs, the blood flow through the collateral veins remained anterograde; this was considered to contribute to normal venous drainage. Conclusion: The SRM is likely to cause occlusion or stenosis in the SMCV and influence its hemodynamics. In cases in which the connection between the SMCV and the CS or the ParaCS has been lost, the SMCV may still be involved in normal venous drainage via the collateral veins in some of those cases. Thus, the contribution of these veins to normal venous drainage in the brain should be analyzed preoperatively in careful detail.

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A Comparative Study Between Traditional Microscopic Surgeries and Endoscopic Endonasal Surgery for Skull Base Chordomas

Oishi Y, Tamura R, Takahashi S, Morimoto Y, Sato M, Horikoshi T, Hassaan S, Yoshida K, Toda M

World Neurosurg (World Neurosurgery) 134 e1099 - e1107 2020

Research paper (scientific journal), Joint Work, ISSN 18788750

Background: Skull base chordomas (SBCs) are rare clinically aggressive neoplasms, developing local recurrences after surgical resection. Although SBCs have traditionally been resected by craniotomy or microscopic transsphenoidal surgery (TSS), the recent development of the endoscopic endonasal approach (EEA) has revolutionized treatment strategies through minimally invasive techniques. This study aimed to evaluate clinical outcomes after traditional microsurgeries or EEAs for SBCs. Methods: The present retrospective study investigated 66 patients with primary SBCs who underwent surgery between 1977 and 2019. Resection was performed via EEA in 17 cases, craniotomy in 23, transoral approach in 8, TSS in 12, staged surgery in 4, and others in 2. The median follow-up period for progression-free survival (PFS) was 19.5 months. Results: There were no significant differences in preoperative tumor volume or resection rate among these approaches. The incidence of postoperative cranial nerve palsy was significantly lower in EEA than that in craniotomy (P < 0.05). Although total resection was observed in 4 cases of EEA expanding into the superior and inferior part of the clivus, no cases of transoral approach or TSS achieved total resection for both parts. No significant difference in PFS was found among these approaches. Multivariate analysis showed that being female and the absence of radiotherapy were significantly associated with shorter PFS (P < 0.05 and P < 0.001, respectively). The resection rate was not associated with PFS. Conclusions: EEA is a less invasive surgical approach for SBCs. The development of surgical instruments and postoperative radiotherapy will further improve patients' outcomes.

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Cerebrospinal fluid leakage due to nasoseptal flap partial necrosis: a pitfall for skull base reconstruction of endoscopic endonasal surgery

Yamada H, Toda M, Fukumura M, Ozawa H, Ogawa K, Yoshida K

Surg Neurol Int (Surgical Neurology International) 11 ( 121 ) 2020

Research paper (scientific journal), Joint Work

Background: Vascularized nasoseptal flaps allow for the reconstruction of large dural defects and have remarkably reduced the incidence of postoperative complications during endoscopic endonasal skull base surgery. Nevertheless, some complications related to nasoseptal flap have been reported. Flap necrosis is a rare, but serious issue is associated with meningitis and cerebrospinal fluid (CSF) leak. Case Description: We performed endoscopic endonasal removal of the tuberculum sella meningioma in a 39-year-old woman with a history of Turner syndrome using abdominal fat, fascia, and a vascularized nasoseptal flap for dural and skull base defect reconstruction. After surgery, she developed CSF leak, and reoperation revealed partial necrosis of the septal flap that caused leakage. At this time, with a concern that removal of the necrotic part may lead to the insufficient size of the flap, we filled the gap tightly with fat pieces. However, the CSF leak recurred, and thus, we performed debridement of the necrotic region and reformed the multilayered reconstruction, following which she no longer experienced CSF leakage. Conclusion: Our case suggested that partial rather than total flap necrosis could occur, possibly due to variances of vascular anatomy, leading to focal ischemia. Debridement of the necrotic region may be an important solution for recurrent cerebrospinal leakage secondary to partial necrosis of a nasoseptal flap.

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