論文 - 戸田　正博

Intraosseous venous structures adjacent to the jugular tubercle associated with an anterior condylar dural arteriovenous fistula

Mizutani K., Akiyama T., Minami Y., Toda M., Fujiwara H., Jinzaki M., Yoshida K.

Neuroradiology （Neuroradiology）  60 （ 5 ） 487 - 496 2018年05月

ISSN  00283940

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© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Although involvement of the osseous component with an anterior condylar dural arteriovenous fistula (AC-DAVF) has been frequently described, osseous venous structures in which AC-DAVFs develop have not been fully elucidated. We investigated osseous venous structures adjacent to the hypoglossal canal in normal controls and patients with AC-DAVFs. Methods: The study included 50 individuals with unruptured aneurysms as normal controls and seven patients with AC-DAVFs. Osseous venous structures adjacent to the hypoglossal canal in normal controls were analyzed using computed tomography (CT) digital subtraction venography. In patients with AC-DAVFs, the fistulous pouches, draining veins, and surrounding venous structures were examined using cone beam CT. Results: In 46.0% of laterals in normal controls, osseous venous structures were visualized within the jugular tubercle superomedially to the hypoglossal canal. We named these structures the jugular tubercle venous complex (JTVC). The JTVC was always continuous with the anterior condylar vein and was sometimes connected to surrounding venous channels. We detected nine fistulous pouches in the seven patients with AC-DAVFs. The fistulous pouches were in the JTVC (33.3%), anterior condylar vein (33.3%), and other venous channels within the exoccipital region (33.3%). Conclusion: Although the JTVC is a venous structure frequently found in normal people, it had not been investigated until now. The venous channel between the anterior condylar vein and JTVC is a common origin site for AC-DAVFs, and it was associated with 66.6% of the AC-DAVF cases in the current study.

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A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma

Shibao S., Ueda R., Saito K., Kikuchi R., Nagashima H., Kojima A., Kagami H., Pareira E., Sasaki H., Noji S., Kawakami Y., Yoshida K., Toda M.

Oncotarget （Oncotarget）  9 （ 30 ） 21569 - 21579 2018年04月

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© Shibao et al. Object: Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Methods: Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. Results: This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. Conclusion: These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.

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The analysis of the cerebral venous blood volume in cavernous sinus using 320 row multi-detector CT

Mizutani K., Toda M., Yajima Y., Akiyama T., Fujiwara H., Yoshida K., Jinzaki M.

Clinical Neurology and Neurosurgery （Clinical Neurology and Neurosurgery）  167   11 - 16 2018年04月

ISSN  03038467

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© 2018 Elsevier B.V. Objectives: : Functional venous anatomy in the brain has been mostly understood from the morphological and embryological points of view and no published study has directly evaluated the blood flow volume of cerebral small veins. We developed a method to directly evaluate the relative blood volume in small venous channels using multi-detector computed tomography (CT) and applied it to evaluate the blood volume in each tributary of the cavernous sinus, which plays an important role in cerebral venous drainage. Patients and Methods: : Ten patients with small brain tumors who had normal venous anatomy were included in the present study. All of them underwent preoperative 320-row multi-detector CT. After injecting the contrast bolus, we measured the Hounsfield units (HUs) at 10 time point over 60 s in each tributary of the cavernous sinus. The gamma distribution fitting to each HU enabled us to obtain a time-density curve and determine the relative venous volume in each venous channel. Results: : In terms of blood volume, the superficial middle cerebral vein and inferior petrosal sinus were the largest inflow and outflow channels of the cavernous sinus and accounted for 36.1% and 24.7% of its inflow and outflow on average, respectively. The superior orbital vein did not contribute to the blood volume passing through the cavernous sinus in the current study. Conclusions: : The present study allowed us to determine the relative blood volume in each tributary of the cavernous sinus, which was very useful to understand the physiological actual venous drainage pattern concerning the cavernous sinus in normal anatomy.

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An Analysis of Various Tracts of Mastoid Air Cells Related to Cerebrospinal Fluid Leak after the Anterior Transpetrosal Approach.

Tamura R,　Tomio　R,　Mohammad　F,　Toda　M, Yoshida　K

Journal of Neurosurgery 16   1 - 8 2018年03月

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Histopathological vascular investigation of the peritumoral brain zone of glioblastomas

Tamura R., Ohara K., Sasaki H., Morimoto Y., Yoshida K., Toda M.

Journal of Neuro-Oncology （Journal of Neuro-Oncology）  136 （ 2 ） 233 - 241 2018年01月

ISSN  0167594X

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© 2017, Springer Science+Business Media, LLC. To date, no histopathological vascular investigation focusing on peritumoral brain zone (PBZ) has been reported for glioblastoma. We analyzed 10 newly diagnosed cases of glioblastomas. For these PBZs, histopathological investigation was performed by hematoxylin–eosin (H&E) staining and immunohistochemistry was analyzed for CD31, CD34, Factor VIII, VEGF, VEGFR-1/2, Ki67, p53 and nestin. Although it was difficult to identify PBZ by H&E, Ki67 and p53 staining, there were apparent differences in nestin staining among PBZ, tumor core (TC), and normal zone (NZ). Therefore, in this study, we divided PBZ from TC and NZ by nestin staining. Differences in histological features, microvessel density, expression of VEGF and its receptors were assessed for PBZ, TC and NZ. The microvessel density, as determined by counting CD31, CD34 and VEGF receptors, and VEGF-A expression were lower in PBZ than TC. The expression patterns for CD31, CD34 and VEGF receptors in vessels show dissociation in PBZ. In addition, the vascular characteristics of the PBZ may correlate with findings of radiographic imaging. We provide the first clinicopathological evidence that PBZ exhibits unique angiogenic characteristics. These in situ observations will help to elucidate the mechanisms of tumor recurrence.

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Surgical Treatment of Cavernous Sinus Lesion in Patients with Nonfunctioning Pituitary Adenomas via the Endoscopic Endonasal Approach

Toda M., Kosugi K., Ozawa H., Ogawa K., Yoshida K.

Journal of Neurological Surgery, Part B: Skull Base （Journal of Neurological Surgery, Part B: Skull Base）  in press （ 5 ） S311 - S315 2018年

ISSN  2193634X

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© 2018 Georg Thieme Verlag KG Stuttgart . New York. Objective The main purpose of this article is to assess the effectiveness and safety of surgery via the endoscopic endonasal approach (EEA) for cavernous sinus (CS) lesion in patients with nonfunctioning pituitary adenomas (NFPA). Design Retrospective study. Setting Keio University Hospital. Participants Thirty patients who underwent CS surgery via the EEA between 2009 and 2017 for Knosp grade 4 NFPA with pre- and postoperative magnetic resonance imaging available for volumetric analysis. Main Outcome Measures Clinical presentation, extent of resection, and surgical complications. Results Gross total and near total resection of CS tumors was achieved in 12/30 (40%) cases of Knosp grade 4 NFPA. The average resection rate of CS lesions in these 30 patients was 73.5%; 77.3% in primary cases and 70.1% in recurrent cases that did not vary significantly. Preoperative visual disturbance and oculomotor nerve palsy improved in 12/19 (63.1%) and - (60%) cases, respectively. Complications associated with CS via the EEA were postoperative cerebrospinal leakage (1/30, 3.3%), meningitis (1/30, 3.3%), and transient cranial nerve palsy (2/30, 6.7%). These complications except a case of mild transient abducens nerve palsy occurred in recurrent cases with subdural lesions. Conclusions Although the optimal management of CS lesions in NFPA is controversial, debulking via the EEA is an effective and safe option that improves neurological symptoms and enables effective adjuvant radiotherapy. Recurrent cases with subdural invasion are technically challenging, even using the EEA, and special care is required to avoid complications.

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Preoperative Prediction of Solitary Fibrous Tumor/Hemangiopericytoma and Angiomatous Meningioma Using Magnetic Resonance Imaging Texture Analysis

Kanazawa T., Minami Y., Jinzaki M., Toda M., Yoshida K., Sasaki H.

World Neurosurgery （World Neurosurgery）  in press   e1208 - e1216 2018年

ISSN  18788750

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© 2018 Elsevier Inc. Background: Solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is radiologically difficult to distinguish from meningioma, especially angiomatous meningioma. This study aimed to detect texture parameters to distinguish SFT/HPC from angiomatous meningioma using magnetic resonance imaging texture analysis with commercially available software. Methods: We retrospectively investigated textural parameters in 43 newly diagnosed SFTs/HPCs, angiomatous meningiomas, and other World Health Organization (WHO) grade I meningiomas treated at Keio University Hospital. For T1 contrast-enhanced, T2, and apparent diffusion coefficient (ADC) images, texture analyses were performed. Regions of interest were drawn manually with reference to the greater signal on contrast-enhanced T1-weighted images. ADC values and texture parameters, including kurtosis, skewness, and entropy, were evaluated and compared between these 3 groups. Results: The mean ADC value was significantly high in angiomatous meningioma, compared with SFT/HPC and other WHO grade I meningioma. ADC entropy was highest in SFT/HPC, followed by angiomatous and other WHO grade I meningioma. T2 skewness was significantly high in SFT/HPC, compared with angiomatous and other WHO grade I meningioma. T1 contrast-enhanced skewness was significantly low in angiomatous meningioma, compared with other WHO grade I meningioma. Mean ADC value distinguished SFT/HPC from angiomatous meningioma with a positive predictive value (PPV) of 62.5% and specificity of 62.5%. ADC entropy distinguished SFT/HPC from angiomatous meningioma with a PPV of 100% and specificity of 100%. ADC skewness distinguished SFT/HPC from angiomatous meningioma with a PPV of 66.7% and specificity of 71.4%. Conclusions: This study demonstrated that magnetic resonance imaging texture analysis was useful for distinguishing SFT/HPC from meningioma, especially angiomatous meningioma.

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Treatment Strategy for Tuberculum Sellae Meningiomas Based on a Preoperative Radiological Assessment

Kuga D., Toda M., Yoshida K.

World Neurosurgery （World Neurosurgery）  in press   e1279 - e1288 2018年

研究論文（学術雑誌）,  ISSN  18788750

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© 2018 Elsevier Inc. Background: Although there are several surgical approaches for the treatment of tuberculum sellae (TS) meningiomas, clear indications for non–large TS meningiomas are still lacking. Methods: Our case series included 20 patients with TS meningiomas (<3 cm). We classified the tumors into 3 groups based on their radiologic relationship with the optic chiasm: type I, tumor with intact optic chiasm; type II, tumor with superiorly deviated optic chiasm; and type III, tumor with posteriorly deviated optic chiasm. Clinical outcomes, radiologic findings, and surgical approaches for the removal of each tumor type were retrospectively reviewed. Results: Resections using a pterional approach, interhemispheric approach, and an endoscopic endonasal approach were performed in three groups of 6, 7, and 7 patients. The rate of total tumor resection was equivalent across approaches, whereas postoperative visual dysfunction was observed in 1 patient (7.69%) undergoing a transcranial approach. Our evaluation of the sphenoid sinus shape across radiographs revealed that the patterns of bony wall elongation attached to these tumors significantly differed among tumor types, indicating that tumor origin and growth direction might affect the patterns of optic chiasm deviation. In addition, selective elongation of the TS provided a favorable surgical corridor for an endoscopic endonasal approach, especially in type II tumors. These results indicate that this tumor classification influenced surgical approach selection for non–large TS meningiomas. Conclusions: The aim of surgery is maximal tumor resection without causing visual dysfunction. The classification proposed here may predict surgical risk associated with meningioma resection and further inform the selection of a surgical approach.

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Skull Base Venous Anatomy Associated with Endoscopic Skull Base Neurosurgery: A Literature Review

Mizutani K., Akiyama T., Yoshida K., Toda M.

World Neurosurgery （World Neurosurgery）  in press   405 - 414 2018年

ISSN  18788750

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© 2018 Elsevier Inc. An understanding of the anatomy and function of the skull base venous channels is fundamentally important for safe performance of endoscopic surgery for skull base lesions. This review focuses on 4 skull base venous channels—namely, the intercavernous sinuses, basilar plexus, osseous veins, and inferior petroclival vein—because these have been less recognized by neurosurgeons than other major venous channels such as the inferior petrosal sinus. We reviewed the literature concerning these 4 venous channels and discussed their anatomy and function. The literature review was mainly based on an electronic search in PubMed using the following terms: “intercavernous sinus,” “basilar plexus,” “emissary veins,” “diploic vein,” “basilar plexus,” “intraosseous vein,” “inferior petroclival/petro-occipital vein,” and “transclival.” A total of 50 articles were included in this review. Detailed anatomic features of the 4 structures have been elucidated in the literature. All of these venous channels run along the skull base and have multiple connections with surrounding venous structures. Because of their location, they occasionally obstruct the surgical view and are sometimes implicated in intraoperative hemorrhage, air embolism during endoscopic skull base surgery, and postoperative hematoma. They usually function as a venous reservoir of cranial venous drainage; however, they are less often directly involved in normal brain perfusion. Knowledge about the functional and morphologic anatomy of the skull base venous channels is important for neurosurgeons to avoid unexpected complications during endoscopic skull base surgery.

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Endoscopic Endonasal Approach Combined with a Simultaneous Transcranial Approach for Giant Pituitary Tumors

戸田 正博

World Neurosurgery （World Neurosurgery）  in press   173 - 179 2018年

研究論文（学術雑誌）,  ISSN  18788750

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© 2018 Elsevier Inc. Background: The endoscopic endonasal approach is widely used for treating giant pituitary adenomas. However, a small subset of tumors is still challenging to treat, and the risk of complications increases when an endoscopic endonasal approach alone is used. The simultaneous combined endoscopic endonasal and transcranial approach is a surgical option for such difficult adenomas; however, very few studies have described the technical nuances and benefits of this approach. Methods: We treated 3 patients with giant pituitary adenoma and 1 patient with pituicytoma. Radiologic findings and clinical outcomes were retrospectively reviewed. Results: All patients had preoperative visual disturbances. A pterional approach was combined with an endoscopic endonasal approach to treat all the patients. Near-total and subtotal tumor removal was accomplished in 3 patients; however, only partial tumor removal was possible in 1 patient. Postoperative visual function improved in 3 patients, but there were no changes in 1 patient. There were no major complications; however, each patient developed either adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone deficiency or ACTH deficiency and persistent diabetes. Importantly, no cerebrospinal fluid leakage was observed in the patients. Conclusions: Our simultaneous combined endoscopic and transcranial approach offers safe tumor resection and a low rate of complications. In this procedure, it is important that tumor debulking be performed by the main surgeon via a single surgical route and not by 2 surgeons using the simultaneous endonasal and transcranial approach, to avoid interference in the surgical field. This approach may be considered as a surgical option for carefully selected tumors in the sellar region.

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Combined Endoscopic Endonasal and Video-microscopic Transcranial Approach with Preoperative Embolization for a Posterior Pituitary Tumor

Yoshida K., Toda M., Akiyama T., Takahashi S., Nishimoto M., Ozawa H., Ikari Y., Yoshida K.

World Neurosurgery （World Neurosurgery）  119   201 - 208 2018年

ISSN  18788750

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© 2018 Elsevier Inc. Background: Posterior pituitary tumor is rare, and its optimal surgical strategy is undetermined. Surgical removal of posterior pituitary tumors is often complicated by their hypervascularity. Prevention and preparation for excessive hemorrhage is crucial for safe resection. Case Description: A 69-year-old woman presented with bitemporal hemianopsia and was found to have a sellar tumor with suprasellar extension, resembling a pituitary adenoma. Microscopic transsphenoidal resection was attempted but was interrupted by a massive intraoperative hemorrhage. Pathologic diagnosis was a spindle cell oncocytoma, and she was referred to our institution. She underwent preoperative embolization to decrease tumor vascularity, and resection was performed using a combined endoscopic endonasal and video-microscopic transcranial approach, using a 4K three-dimensional (3D) video microscope. The final diagnosis was a posterior pituitary tumor with immunopositivity for thyroid transcription factor-1, with preferred interpretation as a pituicytoma. Conclusions: A combined endonasal and transcranial approach with preoperative embolization is a useful strategy for hypervascular posterior pituitary tumors. A 4K 3D video microscope is compact, and it provides high-resolution images, contributing larger surgical space and facilitating a multi-team surgery.

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Severe headache in a patient with meningioma showing extensive dural tail correlates with IgG4-positive plasma cells and eosinophils: A case report and review of literature

Kuranari Y., Tamura R., Mikami S., Ohara K., Toda M., Yoshida K.

Surgical Neurology International （Surgical Neurology International）  9 （ 1 ） 202 2018年

研究論文（学術雑誌）

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© 2018 Surgical Neurology International | Published by Wolters Kluwer - Medknow. Background: Meningiomas originate from meningothelial cells of the arachnoid membrane. Few cases of meningioma with infiltration of inflammatory cells, such as lymphocytes and plasma cells, have been reported, and the mechanisms underlying meningioma-induced inflammatory reactions have not been fully elucidated. Case Description: In this study, we report an extremely rare case of meningioma with infiltration of both IgG4-positive plasma cells and eosinophils showing extensive dural tail and reactive inflammation of the surrounding arachnoid tissue. The main clinical manifestation was a severe headache, which was improved by surgical excision of the tumor. Conclusion: Only 8 cases of meningioma with IgG4-positive plasma cells have been reported, and only one case exhibited eosinophil infiltration. IgG4-related inflammatory response might mediate inflammation in surrounding tissue, resulting in thickening of the dura adjacent to a meningioma and severe headache. The mechanisms underlying inflammation by meningiomas require further investigation.

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Subtemporal approach: Intra- and extradural approach, anterior petrosal approach, and endonasal approach

Toda M., Yoshida K.

Japanese Journal of Neurosurgery （Japanese Journal of Neurosurgery）  27 （ 11 ） 818 - 827 2018年

ISSN  0917950X

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The subtemporal approach is applied to the middle cranial fossa and infratemporal fossa in addition to the tentorial incisura, petroclivus, and brain stem lesions. To minimize compression damage to the temporal lobe, it is essential to perform the craniotomy along the middle cranial fossa, to remove the zygomatic arch for supratentorial lesions, and to remove the petrous pyramid for infratentorial lesions. To avoid venous damage, the drainage pathways of the superficial sylvian vein and bridging veins, including Labbé’s vein, should be preoperatively evaluated. Furthermore, with the recent advances in endoscopic surgery, it has become possible to approach the middle cranial fossa and infratemporal fossa endonasally. In the endonasal approach, surgical simulation is important because of the variations in the nasal cavity and paranasal sinus structures. In this article, we outline the surgical anatomy of the middle cranial fossa required for the subtemporal approach, including the endonasal approach, and variations in the venous drainage of the superficial sylvian vein and petrosal vein. Moreover, we describe the treatment of pontine lesions by the subdural subtemporal approach, Meckel cave lesions by the epidural subtemporal approach, petroclival lesions by the anterior transpetrosal approach, and infratemporal lesions by the endonasal approach.

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Clinical and molecular prognostic factors for long-term survival of the patients with glioblastomas in a single institutional consecutive cohort.

Nakagawa Y, Sasaki H, Ohara K, Ezaki T, Toda M, Ohira T, Kawase T, Yoshida K.

World Neurosurg. 106   165 - 173 2017年10月

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The impact of several craniotomies on transcranial motor evoked potential monitoring during neurosurgery.

Tomio R, Akiyama T, Toda M, Ohira T, Yoshida K

J Neurosurg.  127 （ 3 ） 543 - 552 2017年09月

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Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells.

Kikuchi R, Sampetrean O, Saya H, Yoshida K, Toda M

J Neurooncol. 133 （ 2 ） 297 - 307 2017年06月

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Analysis of the venous channel within the clivus using multidetector computed tomography digital subtraction venography.

Mizutani K, Toda M, Kurasawa J, Akiyama T, Fujiwara H, Jinzaki M, Yoshida K

Neuroradiology 59 （ 3 ） 213 - 219 2017年03月

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Functional analysis of KIF20A, a potential immunotherapeutic target for glioma

Saito K, Ohta S, Kawakami Y, Yoshida K, Toda M

J Neurooncol 132 （ 1 ） 63 - 74 2017年03月

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Delayed and isolated oculomotor nerve palsy following minor head trauma.

Nakagawa Y, Toda M, Shibao S, Yoshida K.

Surg Neurol Int. 8 （ 20 ）  2017年02月

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Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

Kikuchi R, Toda M, Tomita T, Ogawa K, Yoshida K

Turkish Neurosurg 27 （ 1 ） 1 - 7 2017年01月

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