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Yuji Nakamaru
Faculty of Medicine　Specialized Medicine　Sensory Organ Medicine
Associate Professor
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Last Updated :2024/05/18

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine　Specialized Medicine　Sensory Organ Medicine

Job Title

  • Associate Professor

Research funding number

  • 20344509

J-Global ID

Research Interests

  • サイトカイン   アレルギー性鼻炎   マクロファージ遊走阻止因子   好酸球   MIF   IL-4   アセチル化   免疫学   肥満細胞   TNF-α   鼻炎   アレルギー   ヒストン   SIRT1   アレルギー・ぜんそく   マイクロアレイ解析   ボツリヌス療法   Sunnybrook評価法   再活性化動態   ベル麻痺   水痘帯状疱疹ウイルス   Hunt症候群   顔面神経麻痺   単純ヘルペスウイルス   病的共同運動   

Research Areas

  • Life sciences / Otorhinolaryngology

Educational Organization

Academic & Professional Experience

  • 2008 - 2018/01 Hokkaido University
  • 2018 北海道大学大学院医学研究院 耳鼻咽喉科・頭頸部外科学教室 准教授

Research Activities

Published Papers

  • Kaoruko Shimizu, Hirokazu Kimura, Naoya Tanabe, Kazuya Tanimura, Shotaro Chubachi, Hiroaki Iijima, Susumu Sato, Nobuyasu Wakazono, Yuji Nakamaru, Kazufumi Okada, Hironi Makita, Houman Goudarzi, Masaru Suzuki, Masaharu Nishimura, Satoshi Konno
    Journal of Allergy and Clinical Immunology: Global 100277 - 100277 2772-8293 2024/05
  • Nayuta Tsushima, Satoshi Kano, Kanako C. Hatanaka, Takayoshi Suzuki, Seijiro Hamada, Hiroshi Idogawa, Yuji Nakamaru, Masanobu Suzuki, Yutaka Hatanaka, Akihiro Homma
    Auris Nasus Larynx 0385-8146 2023/11
  • Yuuki Fujiwara, Keishi Fujiwara, Hiroaki Motegi, Yukitomo Ishi, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 44 (8) 809 - 812 2023/09/01 
    OBJECTIVE: We report two cases of petrous apex cholesterol granuloma (PACG) treated with an endoscopic transsphenoidal approach. Vestibular functions of the two patients were evaluated quantitatively by video Head Impulse Test (vHIT) and/or vestibular evoked myogenic potentials (VEMPs). PATIENTS: Two patients with PACG who experienced episodes of dizziness are presented. INTERVENTION: An endoscopic transsphenoidal approach to PACG. MAIN OUTCOME MEASURE: The preoperative and postoperative vestibular functions as evaluated by vHIT and VEMP. RESULTS: Two cases of PACG were treated by a transsphenoidal approach. The internal auditory canal was compressed by the PACG in both cases. The patients both experienced episodes of dizziness before surgery and preoperative vestibular testing including vHIT and VEMP indicated dysfunction of vestibular nerves. After surgery, their symptoms were completely resolved, and the vestibular testing results were improved. CONCLUSIONS: This article is noteworthy for being the first to publish quantitative vestibular function testing for patients with PACG with vestibular dysfunction. PACG may show various symptoms, with dizziness being one of the most common symptoms. In cases in which the internal auditory canal is compressed by the PACG, vestibular functions should be evaluated by vHIT and VEMP. In the present cases, dizziness was found to be resolved by surgery to release the compression on internal auditory canal. Based on the present cases, the transsphenoidal approach is considered to be both safe and effective.
  • Nayuta Tsushima, Satoshi Kano, Koichi Yasuda, Takayoshi Suzuki, Seijiro Hamada, Yuji Nakamaru, Masanobu Suzuki, Yusuke Uchinami, Hidefumi Aoyama, Akihiro Homma
    International journal of clinical oncology 28 (9) 1218 - 1226 2023/06/17 
    BACKGROUND: The standard of care for sinonasal mucosal melanoma is surgery and postoperative radiotherapy (PORT). Our treatment strategy comprises endoscopic resection and PORT. We performed combined endoscopic and open resection or applied an external approach alone when sufficient resection was difficult to achieve endoscopically. The objective of this study was to evaluate the validity of our treatment strategy. METHODS: We assessed 30 patients with sinonasal mucosal melanoma who underwent definitive therapy between January 2002 and April 2021, and conducted a retrospective analysis. The median follow-up period was 2.2 years. The primary endpoint was overall survival. The Kaplan-Meier method was used for the calculation of survival rates, the cumulative incidence of distant metastasis, and local recurrence. RESULTS: Twenty-eight patients underwent surgery. The other two patients were treated by definitive proton beam therapy. Twenty-one of 28 (75%) patients underwent resection by endoscopic approach alone. Postoperative radiotherapy was performed for all 28 patients who underwent surgery. Twenty-one patients (70%) experienced recurrence during the observation period. Overall, distant metastasis was observed in 19 patients. Twelve patients died during the observation period, with 10 of the 12 patients (83%) dying of distant metastasis. The overall survival rate at 2 and 5 years was 70% and 46%, respectively. The cumulative incidence rate of distant metastasis at 2 years was 63%, while the 2-year cumulative incidence rate of local recurrence was 6.7%. CONCLUSION: The local disease was controlled by our treatment strategy. To improve treatment outcomes, control of the distant metastasis is needed.
  • S Kimura, M Suzuki, Y Nakamaru, S Kano, M Watanabe, A Honma, A Nakazono, N Tsushima, S Hatakeyama, A Homma
    Rhinology 2023/03/09 
    BACKGROUND: Tripartite motif-containing 27 (TRIM27) has been implicated in the progression of various cancers. However, the role of TRIM27 in sinonasal mucosal melanoma (SNMM) remains poorly understood. MATERIALS & METHODS: We retrospectively examined 28 patients with SNMM treated with between 2003 and 2021. We undertook immunohistochemical analysis of TRIM27, Ki-67, and p-Akt1 expression in SNMM tissues. We also investigated the relationship between TRIM27 expression and clinical characteristics, prognosis, Ki-67 as a tumor growth potential marker, and p-Akt1 as one of the prognostic factors in mucosal melanoma. RESULTS: TRIM27 expression was significantly higher in T4 disease than in T3 disease and was higher in stage IV than in stage III. Patients with high-TRIM27 SNMM had a significantly poorer prognosis in terms of overall survival (OS) and disease-free survival.There was also a significantly higher rate of distant metastasis. Univariate analysis for OS revealed that TRIM27 and T classification were significant poor prognostic factors. In addition, the Ki-67 positive score and the p-Akt1 total staining score were significantly higher in the high-TRIM27 group than in the low-TRIM27 group. CONCLUSIONS: High TRIM27 expression in SNMM was associated with advanced T classification, poor prognosis and distant metastasis. We suggest that TRIM27 has potential as a novel biomarker for prognosis in SNMM.
  • Hideaki Takeda, Masanobu Suzuki, Yuji Nakamaru, Shogo Kimura, Akira Nakazono, Aya Honma, Akihiro Homma
    JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY 32 (3) 299 - 303 1349-581X 2023
  • Masanobu Suzuki, Kou Miyaji, Kotaro Matoba, Takashige Abe, Yuji Nakamaru, Ryosuke Watanabe, Takayoshi Suzuki, Akira Nakazono, Atsushi Konno, Dominik Hinder, A J Psaltis, P J Wormald, Akihiro Homma
    Frontiers in medicine 10 1090743 - 1090743 2023 
    INTRODUCTION: Surgeons' mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient's anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models. MATERIALS AND METHODS: Forty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons' mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training. RESULTS: The total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons' mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = -2.3664, p = 0.0091, effort; z = -2.1704, p = 0.0346, and performance; z = -2.5992, p = 0.0017), the independent factors were increased (mental demand; z = -2.5992, p = 0.0023 and physical demand; z = -2.2509, p = 0.0213), and frustration did not change (p = 0.3625). CONCLUSION: Some of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars' mental burdens would be necessary during surgical training to sustain their mental health.
  • 佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 木村 孔一, 中丸 裕爾, 今野 哲
    アレルギー (一社)日本アレルギー学会 71 (8) 944 - 948 0021-4884 2022/09 
    現在,重症喘息に対する生物学的製剤の長期使用の報告がなされている.しかし,効果が認められる症例における必要治療継続期間,中止基準については明確な基準はない.今回,オマリズマブによる長期的なコントロール維持の後,投与間隔の延長に伴い,喘息病態が悪化を来たし,その後通常間隔投与に戻したものの,当初の効果を認めなかった重症喘息の1例を経験した.投与間隔を延長したことが,効果減弱に関与した可能性もあり,今後のオマリズマブの長期使用に関する診療の一助となると考え,報告する.(著者抄録)
  • Shinya Morita, Satoshi Kano, Kanako C Hatanaka, Yutaka Hatanaka, Takayoshi Suzuki, Atsushi Fukuda, Kimiko Hoshino, Keishi Fujiwara, Yuji Nakamaru, Akihiro Homma
    International journal of clinical oncology 27 (9) 1394 - 1403 2022/09 
    BACKGROUND: External auditory canal squamous cell carcinoma (EACSCC) is a rare form of malignant tumor. Due to the extremely limited understanding of the genomic landscape in EACSCC, the association between gene mutations and clinicopathologic features remains unclear. This study aimed to explore somatic gene mutations associated with the clinicopathological features in patients with EACSCC, and to identify the candidate gene mutations for predicting survival outcome in EACSCC. METHODS: Twenty-two tissue samples obtained from patients with EACSCC were analyzed for genetic mutations based on targeted next-generation sequencing and genetic expression based on IHC staining to investigate the driver of tumorigenesis and/or the candidates of genes for predicting clinical outcome in EACSCC. RESULTS: Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). TP53 mutations showed significant correlation with T classification (P = 0.027) and p53 expression phenotype (P < 0.001). The 5-year overall survival (OS) rates for EACSCC patients with TP53 mutations and wild-type TP53 were 45.0% and 75.0%, respectively. Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of OS rates for EACSCC patients (P = 0.007). CONCLUSION: This study has suggested that TP53 mutations have potential for use as a biomarker for identifying individuals at high risk of developing tumors and for predicting survival outcome in EACSCC. IHC staining for p53 might play a useful role as screening tool for detecting TP53 mutations in patients with EACSCC.
  • Masanobu Suzuki, Kou Miyaji, Ryosuke Watanabe, Takayoshi Suzuki, Kotaro Matoba, Akira Nakazono, Yuji Nakamaru, Atsushi Konno, Alkis James Psaltis, Takashige Abe, Akihiro Homma, Peter-John Wormald
    Laryngoscope investigative otolaryngology 7 (4) 943 - 954 2022/08 
    Background: The purpose of this study was to find a utility of a newly developed 3D-printed sinus model and to evaluate the educational benefit of simulation training with the models for functional endoscopic sinus surgery (FESS). Material and methods: Forty-seven otolaryngologists were categorized as experts (board-certified physicians with ≥200 experiences of FESS, n = 9), intermediates (board-certified physicians with <200 experiences of FESS, n = 19), and novices (registrars, n = 19). They performed FESS simulation training on 3D-printed models manufactured from DICOM images of computed tomography (CT) scan of real patients. Their surgical performance was assessed with the objective structured assessment of technical skills (OSATS) score and dissection quality evaluated radiologically with a postdissection CT scan. First we evaluated the face, content, and constructive values. Second we evaluated the educational benefit of the training. Ten novices underwent training (training group) and their outcomes were compared to the remaining novices without training (control group). The training group performed cadaveric FESS surgeries before and after the repetitive training. Results: The feedback from experts revealed high face and content value of the 3D-printed models. Experts, intermediates, and novices demonstrated statistical differences in their OSATS scores (74.7 ± 3.6, 58.3 ± 10.1, and 43.1 ± 11.1, respectively, p < .001), and dissection quality (81.1 ± 13.1, 93.7 ± 15.1, and 126.4 ± 25.2, respectively, p < .001). The training group improved their OSATS score (41.1 ± 8.0 to 61.1 ± 6.9, p < .001) and dissection quality (122.1 ± 22.2 to 90.9 ± 10.3, p = .013), while the control group not. After training, 80% of novices with no prior FESS experiences completed surgeries on cadaver sinuses. Conclusion: Repeated training using the models revealed an initial learning curve in novices, which was confirmed in cadaveric mock FESS surgeries. Level of evidence: N/A.
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 43 (5) 587 - 593 2022/06/01 
    OBJECTIVES: To evaluate semicircular canal function in patients with labyrinthine fistula (LF) due to cholesteatoma by the video Head Impulse Test (vHIT). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Ten patients with LF due to cholesteatoma and six without LF underwent vestibular examination. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for the semicircular canals in patients with LF. RESULTS: Seven of 10 cases (70.0%) in the fistula group were judged to have semicircular canal dysfunction based on preoperative evaluation. VOR gains in the patients with LF were significantly lower than those in the patients without LF. VOR gain decreased significantly in accordance with the severity of the LF. The postoperative VOR gain more than 6 months after surgery was significantly improved compared with the preoperative VOR gain. CONCLUSIONS: The vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with LF due to cholesteatoma as it is not influenced by middle ear pathology and can evaluate the function of the vertical canals. The vHIT could predict whether a LF is present or not before surgery, and the vHIT is essential for surgery for patients with LF.
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
    Auris, nasus, larynx 2022/04/22 
    Lateral semicircular canal (LSCC) malformations represent one of the most common types of inner ear malformation. As many cases of LSCC malformations are asymptomatic, detailed vestibular functions in such cases remain unclear. We present a case with bilateral LSCC malformations for whom the function of each vestibular organ was evaluated by caloric testing, video Head Impulse Test (vHIT) and vestibular evoked myogenic potentials (VEMP). Caloric testing showed canal paresis of the left side, whereas vHIT showed bilateral normal semicircular canal function. The results of VEMP indicated left saccular dysfunction. Discrepancies in caloric testing and vHIT results were observed and these discrepancies are thought to be due to endolymphatic hydrops rather than vestibular hypofunction, similar to that in Meniere disease.
  • 中薗 彬, 中丸 裕爾, 鈴木 正宣, 本間 あや, 木村 将吾, 本間 明宏
    日本耳鼻咽喉科頭頸部外科学会会報 (一社)日本耳鼻咽喉科頭頸部外科学会 125 (4) 702 - 702 2436-5793 2022/04
  • 佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 松本 宗大, 木村 孔一, 中丸 裕爾, 伊藤 陽一, 今野 哲
    日本呼吸器学会誌 (一社)日本呼吸器学会 11 (増刊) 143 - 143 2186-5876 2022/04
  • 難治性喘息 重症喘息における生物学的製剤の変更に影響する因子の検討
    佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 松本 宗大, 木村 孔一, 中丸 裕爾, 伊藤 陽一, 今野 哲
    日本呼吸器学会誌 (一社)日本呼吸器学会 11 (増刊) 143 - 143 2186-5876 2022/04
  • postコロナ・withコロナの耳鼻咽喉科診療 頭頸部の診療
    本間 明宏, 中丸 裕爾, 鈴木 正宣, 本間 あや
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集 日本耳鼻咽喉科免疫アレルギー感染症学会 2回 71 - 71 2022/03
  • 術前呼吸機能検査による鼻茸を伴う副鼻腔炎の予後推測
    中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 木村 将吾, 本間 明宏
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集 日本耳鼻咽喉科免疫アレルギー感染症学会 2回 77 - 77 2022/03
  • 鼻粘膜上皮細胞での細菌・ウィルス結合受容体発現に対する自然免疫シグナルの影響
    中薗 彬, 木村 将吾, 本間 あや, 鈴木 正宣, 中丸 裕爾, 本間 明宏
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集 日本耳鼻咽喉科免疫アレルギー感染症学会 2回 168 - 168 2022/03
  • 鼻粘膜上皮におけるMetallothionein-3発現解析
    鈴木 正宣, 中丸 裕爾, 中薗 彬, 本間 あや, 木村 将吾, 本間 明宏
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集 日本耳鼻咽喉科免疫アレルギー感染症学会 2回 185 - 185 2022/03
  • Shinya Morita, Yuji Nakamaru, Atsushi Fukuda, Keishi Fujiwara, Masanobu Suzuki, Kimiko Hoshino, Aya Honma, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 43 (3) e337-e343  2022/03/01 
    OBJECTIVE: This study aimed to quantify the cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex as extracellular trap cell death (ETosis)-derived products in the middle ear fluid, and to identify diagnostic biomarkers for the discrimination of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) from eosinophilic otitis media (EOM). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: OMAAV patients were eligible for inclusion in this analysis. Patients with EOM were examined as controls. INTERVENTION: All samples were obtained from the middle ear fluid in patients with OMAAV or EOM. The fluid samples were aspirated from the middle ear through the anterior-inferior portion of the tympanic membrane using a 1-ml tuberculin syringe with a 24- or 26-gauge needle under a microscope. MAIN OUTCOME MEASURES: The levels of cell-free DNA, cit-H3-DNA complex and MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay. RESULTS: Patients with OMAAV showed significantly higher levels of MPO-DNA complex compared to patients with EOM, regardless of the serum ANCA status at the time of sampling (p < 0.001 and p < 0.001, respectively). Meanwhile, there were no significant differences in the values of cell-free DNA or cit-H3-DNA complex between the OMAAV and EOM patients. CONCLUSION: The findings of this study suggest that the detection and quantification of MPO-DNA complex in the otitis media fluid can be utilized to discriminate OMAAV, especially in cases of eosinophilic granulomatosis with polyangiitis, from EOM regardless of the serum ANCA status. It should be noted that it is possible for cell-free DNA and cit-H3-DNA complex in fluid samples to be derived from dead cells other than neutrophils that undergo ETosis.
  • 山田 真司, 鈴木 正宣, 中丸 裕爾, 本間 あや, 中薗 彬, 木村 将吾, 安川 真一郎, 蠣崎 文彦, 本間 明宏
    耳鼻咽喉科・頭頸部外科 94 (2) 183 - 187 2022/02
  • Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Hirokazu Kimura, Yuji Nakamaru, Satoshi Konno
    Arerugi = [Allergy] 71 (8) 944 - 948 2022 
    At the time of writing of this manuscript, four biologics were clinically available for the treatment of severe asthma, and there were no established recommendations for the period of administration or timing of discontinuation of each biologic. We present a case of severe asthma that was well controlled with long-term omalizumab treatment; however, prolongation of the dosing intervals resulted in disease exacerbation that was refractory to omalizumab treatment despite the restoration of the recommended interval of administration. We suspect that the prolonged dosing intervals might have reduced the efficacy of omalizumab. We report this case because dosing intervals should be considered in clinical practice in cases of long-term omalizumab treatment.
  • Machiko Matsumoto-Sasaki, Kaoruko Simizu, Masanobu Suzuki, Masaru Suzuki, Hirokazu Kimura, Yuji Nakamaru, Yoichi M Ito, Akihiro Honma, Satoshi Konno
    Journal of asthma and allergy 15 187 - 195 2022 
    Purpose: Biologics have been used increasingly for the treatment of severe asthma. However, established guidelines for the selection, switching, or discontinuation of biologics do not exist. We aimed to identify the clinical characteristics of patients with asthma who required switching biologics and the factors associated with switching biologics. Patients and Methods: This was a retrospective study of 42 patients with severe asthma treated with biologics at the Hokkaido University Hospital between 23rd June 2016 and 30th April 2021, when two biologics were available in Japan. We compared the characteristics of subjects who continued and switched biologics. The time to switch the biologics was assessed by type 2 inflammatory biomarkers, pulmonary function indices, and the presence of comorbidities, including the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score and aspirin exacerbated respiratory diseases (AERD), using the Kaplan-Meier method and a multivariate Cox proportional hazards model. Results: Eight and five patients were treated by mepolizumab and benralizumab at baseline, respectively among the 31% (13/42) who switched the biologics. Subjects who required switching biologics were characterized by high blood eosinophil counts, younger age, JESREC scores of 11 points or higher, and AERD. The time taken to switch biologics was significantly shorter in the subgroups with high JESREC scores (≥11) or AERD, compared with their counterparts with low JESREC scores or without AERD (both, P < 0.05). JESREC scores of ≥11, but not the presence of AERD, were associated with time to switch biologics. Conclusion: The presence of eosinophilic chronic rhinosinusitis based on JESREC scores of ≥11 and younger age were factors associated with switching biologics in asthma.
  • Masanobu Suzuki, Erich Vyskocil, Kazuhiro Ogi, Kotaro Matoba, Yuji Nakamaru, Akihiro Homma, Peter J. Wormald, Alkis J. Psaltis
    Frontiers in Surgery 8 2021/10/01 
    Objective: Traditionally, cadaveric courses have been an important tool in surgical education for Functional Endoscopic Sinus Surgery (FESS). The recent COVID-19 pandemic, however, has had a significant global impact on such courses due to its travel restrictions, social distancing regulations, and infection risk. Here, we report the world-first remote (Functional Endoscopic Sinus Surgery) FESS training course between Japan and Australia, utilizing novel 3D-printed sinus models. We examined the feasibility and educational effect of the course conducted entirely remotely with encrypted telemedicine software. Methods: Three otolaryngologists in Hokkaido, Japan, were trained to perform frontal sinus dissections on novel 3D sinus models of increasing difficulty, by two rhinologists located in Adelaide, South Australia. The advanced manufactured sinus models were 3D printed from the Computed tomography (CT) scans of patients with chronic rhinosinusitis. Using Zoom and the Quintree telemedicine platform, the surgeons in Adelaide first lectured the Japanese surgeons on the Building Block Concept for a three Dimensional understanding of the frontal recess. They in real time directly supervised the surgeons as they planned and then performed the frontal sinus dissections. The Japanese surgeons were asked to complete a questionnaire pertaining to their experience and the time taken to perform the frontal dissection was recorded. The course was streamed to over 200 otolaryngologists worldwide. Results: All dissectors completed five frontal sinusotomies. The time to identify the frontal sinus drainage pathway (FSDP) significantly reduced from 1,292 ± 672 to 321 ± 267 s (p = 0.02), despite an increase in the difficulty of the frontal recess anatomy. Image analysis revealed the volume of FSDP was improved (2.36 ± 0.00 to 9.70 ± 1.49 ml, p = 0.014). Questionnaires showed the course's general benefit was 95.47 ± 5.13 in dissectors and 89.24 ± 15.75 in audiences. Conclusion: The combination of telemedicine software, web-conferencing technology, standardized 3D sinus models, and expert supervision, provides excellent training outcomes for surgeons in circumstances when classical surgical workshops cannot be realized.
  • Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Kazuhiro Ogi, Alkis J Psaltis, Yuji Nakamaru, Akihiro Homma, Peter-John Wormald, Sarah Vreugde
    Auris, nasus, larynx 48 (5) 890 - 897 2021/10 [Refereed][Not invited]
     
    OBJECTIVE: Recently, depleted tissue zinc levels were found in nasal mucosa from patients with chronic rhinosinusitis (CRS) in correlation with tissue eosinophilia, however, no clinical biomarkers for tissue zinc levels have been identified. Metallothionein-3 (MT3) is an intracellular zinc chelator and previous data showed MT3 mRNA levels to be reduced in CRS patients with nasal polyps (CRSwNP). In this study, we examined the correlation between MT3 expression and zinc levels in nasal mucosa and primary human nasal epithelial cells (HNECs) to investigate whether MT3 could be a clinical biomarker for tissue zinc levels. METHOD: Tissue was harvested from 36 patients and mounted on tissue micro-array (TMA) slides. MT3 expression and tissue zinc fluorescence intensity were measured at different areas within the mucosa (surface epithelium and lamina propria) and compared between controls, CRSwNP and CRS without nasal polyps (CRSsNP) patients. MT3 mRNA and protein expression were examined in zinc-depleted HNECs by qPCR and immunofluorescence microscopy. RESULTS: MT3 expression in CRSwNP was significantly decreased in both surface epithelium (p<0.001 to controls) and lamina propria (p = 0.0491 to controls). There was a significant positive correlation between tissue zinc levels and MT3 expression in nasal mucosa (r = 0.45, p = 0.007). In zinc-deplete HNECs, MT3 expression was significantly decreased at mRNA (p = 0.02) and protein level (p<0.01). There was a significant positive correlation between tissue zinc levels and MT3 expression within individual HNECs (r = 0.59, p<0.001). CONCLUSIONS: MT3 expression reflects intramucosal zinc levels in both nasal mucosa and HNECs indicating MT3 could be used as a clinical biomarker for monitoring intracellular zinc levels in the nasal mucosa.
  • Atsushi Fukuda, Satoshi Kano, Yuji Nakamaru, Shinya Morita, Kimiko Hoshino, Keishi Fujiwara, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 42 (9) e1389-e1395  2021/10/01 [Refereed]
     
    HYPOTHESIS: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. BACKGROUND: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. METHODS: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler™ PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. RESULTS: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 ± 32.4% and 44.9 ± 17.8%, respectively) were significantly lower than in the EAC skin (83.4 ± 17.5% and 55.7 ± 7.1%, respectively) (p < 0.001 and p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 ± 11.4%) was significantly higher than in the EAC skin (0.5 ± 0.7%) (p < 0.001). CONCLUSION: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.
  • 鼻中隔前彎の客観的評価と適切な鼻中隔矯正術の術式選択
    木村 将吾, 中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 60 (3) 312 - 312 0910-9153 2021/09
  • 鼻粘膜上皮細胞におけるTLR3依存性自然免疫シグナル
    鈴木 正宣, 中丸 裕爾, 中薗 彬, 本間 あや, 木村 将吾, Sarah Vreugde, Wormald PJ, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 60 (3) 352 - 352 0910-9153 2021/09
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Yasushi Furuta, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 42 (10) e1577-e1582  2021/08/04 [Refereed]
     
    OBJECTIVES: The aim of the present study was to investigate the characteristics and prognosis of facial palsy in patients with otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with OMAAV. MAIN OUTCOME MEASURES: The patients were divided into the facial palsy group and non-palsy group. The severity of and prognosis for facial palsy were evaluated using the House-Brackmann facial grading system (HB). Characteristics were compared between the facial palsy group and non-palsy group. RESULTS: Facial palsy was observed in eight patients. The last HB grade for all patients was either grade I or II after treatment with a combination of corticosteroids and immunosuppressant therapy. There were no cases in which palsy relapsed. Facial palsy in OMAAV was significantly more common in female patients, and patients with facial palsy demonstrated significantly higher rates of hypertrophic pachymeningitis than did those without facial palsy. CONCLUSIONS: Facial palsy in patients with OMAAV was detected in 21.6% and a good prognosis was obtained by use of the appropriate treatment. Facial palsy is one of the most important symptoms by which to diagnose OMAAV. When encountering the patients with intractable otitis media complicated with facial palsy, appropriate examination including ANCA titer should be performed.
  • Yoshimasa Imoto, Masafumi Sakashita, Masaki Hayama, Yuji Nakamaru, Masanobu Suzuki, Yui Miyabe, Takechiyo Yamada, Hidekazu Saito, Syuji Yonekura, Kenji Kondo, Takaya Higaki, Kayoko Kawashima, Mitsuyoshi Urashima, Shigeharu Fujieda
    Allergology international : official journal of the Japanese Society of Allergology 70 (3) 373 - 375 2021/07 [Refereed]
  • 当科におけるアブミ骨手術症例の検討
    小林 諒, 福田 篤, 藤原 圭志, 中丸 裕爾, 本間 明宏
    耳鼻咽喉科臨床 補冊 耳鼻咽喉科臨床学会 (補冊157) 65 - 65 0912-1870 2021/06
  • 佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
    アレルギー (一社)日本アレルギー学会 70 (4) 315 - 320 0021-4884 2021/06 
    現在,重症喘息の治療には4種類の生物学的製剤が使用可能である.その薬剤選択においては,各種2型炎症関連バイオマーカーの測定値,及び好酸球性副鼻腔炎,アレルギー性鼻炎,アトピー性皮膚炎などの併存疾患の有無を考慮すべきと言われている.今回,好酸球性副鼻腔炎,好酸球性中耳炎を合併し,結果的に4種類の生物学的製剤を使用し,上・下気道それぞれの反応性の違いを観察しえた重症喘息の1症例を経験した.4剤の使い分けに関する明確なアルゴリズムは確立されていない現状を鑑み,生物学的製剤による総合的な治療戦略を考える上で意義が大きいと考え,報告する.(著者抄録)
  • 佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
    アレルギー (一社)日本アレルギー学会 70 (4) 315 - 320 0021-4884 2021/06
  • Shogo Kimura, Masanobu Suzuki, Aya Honma, Akira Nakazono, Masayuki Osawa, Yuji Nakamaru, Akihiro Homma
    Auris, nasus, larynx 49 (1) 67 - 76 2021/05/06 [Refereed]
     
    OBJECTIVE: Several methods have been reported to correct caudal deviation of the nasal septum, including open septorhinoplasty (OSR) and septoplasty with Killian incision (KI). In general, OSR is applied instead of KI for caudal deviation. However, there is little objective evidence own on the effects of OSR and KI for caudal deviation. In this study, we compared surgical outcomes between OSR and KI by quantifying nasal septum deviation using two simple and objective parameters on routine paranasal sinus CT scans. METHODS: We retrospectively analyzed 18 patients who underwent OSR and 11 patients who underwent septoplasty with KI between April 2006 and October 2019. Caudal deviation was defined on the basis of the "Anterior-posterior Position of the most deviated point of the nasal septum (AP)," which was measured on computerized tomography. The deformation rate (DR) of the nasal septum was also calculated. Nasal airway resistance and visual analogue scale (VAS) score for nasal obstruction were examined. RESULTS: The AP was significantly correlated with the VAS score (r=-0.58, p=0.017). The DR in patients with caudal septal deviation was significantly decreased by OSR (0.14±0.06 to 0.03±0.03, p=0.004), but not by KI (0.09±0.08 to 0.04±0.03, p=0.25). OSR also improved nasal airway resistance (1.10±0.44 to 0.42±0.15, p=0.02), and the VAS score (79.11±14.74 to 5.78±7.89, p=0.004). CONCLUSION: Nasal obstruction is more severe in patients with the caudal deviation. OSR corrects caudal deviation of the nasal septum more effectively than does KI. The AP could be useful for the evaluation of the deviation of the nasal septum and help in selecting the appropriate septoplastic technique.
  • Keishi Fujiwara, Atsushi Fukuda, Shinya Morita, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Yasushi Furuta, Akihiro Homma
    Auris, nasus, larynx 49 (1) 53 - 57 2021/05/04 [Refereed]
     
    OBJECTIVE: The aim of the present study was to evaluate the psychological condition of patients with non-cured facial nerve palsy and to investigate whether their psychological condition is correlated with the degree of facial nerve palsy, synkinesis or quality of life. METHODS: Thirty patients with non-cured facial nerve palsy were enrolled in this study. Psychological conditions were evaluated by questionnaires including State-Trait Anxiety Inventory and Self-rating Depression Scale. RESULTS: Of the thirty patients with non-cured facial nerve palsy, 17 (56.7%) and 15 patients (50.0%) felt anxiety and depression, respectively. Although there were no significant correlations between their psychological condition and the degree of facial nerve palsy or that of sequelae, significant correlations were observed between psychological condition and the degree of QOL, especially in terms of social function. CONCLUSIONS AND SIGNIFICANCE: Disabilities associated with facial nerve palsy may be overlooked when evaluation is performed by physician-graded instruments alone. To resolve this problem, patients with non-cured facial nerve palsy should be evaluated by not only physician-graded tools but also patient-based assessment tools.
  • 鼻腔粘膜上皮細胞における新型コロナウィルス細胞侵入因子の発現制御機構
    中薗 彬, 鈴木 正宣, 木村 将吾, 本間 あや, 中丸 裕爾, Ramezanpour Mahnaz, Vreugde Sarah, Wormald P.J., 本間 明宏
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集 日本耳鼻咽喉科免疫アレルギー感染症学会 1回 127 - 127 2021/05
  • Masanobu Suzuki, Takayoshi Suzuki, Masashi Watanabe, Shigetsugu Hatakeyama, Shogo Kimura, Akira Nakazono, Aya Honma, Yuji Nakamaru, Sarah Vreugde, Akihiro Homma
    Allergology international : official journal of the Japanese Society of Allergology 70 (2) 190 - 200 2021/04 [Refereed]
     
    Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems. In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions. In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 42 (4) e483-e488  2021/04/01 [Refereed]
     
    OBJECTIVES: To investigate usefulness of the video Head Impulse Test (vHIT) as a method for evaluating semicircular canal function in patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fourteen patients with OMAAV underwent vestibular examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for each semicircular canal. RESULTS: Seven (50.0%) of the 14 patients felt subjective symptoms of disequilibrium. Dysfunction in at least one semicircular canal was detected in all ears of the OMAAV patients evaluated by vHIT. Dysfunction in posterior semicircular canal was detected more frequently than that in the anterior or horizontal canal. There were no significant correlations between the gain in VOR and hearing loss. CONCLUSIONS: vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with OMAAV as vHIT is not influenced by middle ear pathology and was able to evaluate vertical canal function including the posterior canal.
  • Atsushi Fukuda, Keishi Fujiwara, Shinya Morita, Kimiko Hoshino, Hiroko Yanagi, Yuji Nakamaru, Akihiro Homma
    Acta oto-laryngologica 141 (3) 216 - 221 2021/03 [Refereed]
     
    BACKGROUND: Vertigo or dizziness after stapes surgery occurs sometimes, and it is generally temporary. However, while rare, it can be prolonged. AIMS/OBJECTIVES: To investigate the prognostic factors for duration of vertigo following stapedotomy using a time-to-event analysis. MATERIALS AND METHODS: The present study included a total of 35 primary ears (26 with otosclerosis and nine with congenital stapes fixation) from 31 patients. We assessed residual rates of nystagmus and complaints of subjective vestibular symptoms using Kaplan-Meier time-to-event methods. RESULTS: Postoperative spontaneous nystagmus was observed in 23 (65.7%) ears, and postoperative subjective vestibular symptoms were confirmed in 27 (77.1%) ears. The total mean duration of postoperative spontaneous nystagmus and subjective vestibular symptoms was 9.8 (range: 0-158) and 33.9 days (0-732), respectively. A history of stapes surgery in the opposite ear was a significant predictive factor for prolonged nystagmus and subjective vestibular symptoms (p = .0059 and p = .0146). CONCLUSIONS AND SIGNIFICANCE: For individuals with a history of stapes surgery in the opposite ear, spontaneous nystagmus and vertigo/dizziness sensations following stapedotomy may persist for a longer duration than in those without a history of stapes surgery in the opposite ear.
  • Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
    Auris, nasus, larynx 48 (1) 131 - 137 2021/02 [Refereed]
     
    OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.
  • Akihiro Homma, Yuji Nakamaru, Valerie J Lund, Ehab Y Hanna, Luiz Paulo Kowalski, Ronaldo Nunes Toledo, Antti A Mäkitie, Juan Pablo Rodrigo, Alessandra Rinaldo, Carl H Snyderman, Alfio Ferlito
    Auris, nasus, larynx 48 (1) 41 - 49 2021/02 [Refereed]
     
    Endonasal endoscopic surgery (EES) has been applied to the management of sinonasal (SN) tumors based on recent advances in endoscopic surgical techniques and technologies over the past three decades. EES has been mainly indicated for benign tumors and less aggressive malignant tumors. Notwithstanding this, EES has been gradually adopted for squamous cell carcinoma (SCC), which is the most common histology among SN malignancies. However, an analysis of the outcomes of EES for patients with SCC is difficult because most articles included SCC a wide range of different tumor histologies. Therefore, we herein review and clarify the current status of EES focusing on SCC from an oncological perspective. The oncologic outcomes and the ability to achieve a histologically complete resection are similar between endoscopic and open approaches in highly selected patients with SN-SCC. Surgical complications associated with EES are likely similar for SN-SCC compared to other sinonasal malignancies. The indications for a minimally invasive approach such as EES in the management of patients with SN-SCC should be stricter than those for less aggressive malignant tumors because of the aggressive nature of SCC. Also, it is important to achieve negative surgical margins with EES in patients with SCC. We believe that the indications for EES for SN-SCC are widening due to advances in diagnostic imaging, and endoscopic surgical techniques and technologies. However, while expanding the indications for EES for SN-SCC we must carefully confirm that the outcomes support this strategy.
  • Masanobu Suzuki, Clare Cooksley, Takayoshi Suzuki, Mahnaz Ramezanpour, Akira Nakazono, Yuji Nakamaru, Akihiro Homma, Sarah Vreugde
    Frontiers in allergy 2 780425 - 780425 2021 
    The respiratory tract is constantly at risk of invasion by microorganisms such as bacteria, viruses, and fungi. In particular, the mucosal epithelium of the nasal cavity and paranasal sinuses is at the very forefront of the battles between the host and the invading pathogens. Recent studies have revealed that the epithelium not only constitutes a physical barrier but also takes an essential role in the activation of the immune system. One of the mechanisms equipped in the epithelium to fight against microorganisms is the Toll-like receptor (TLR) response. TLRs recognize common structural components of microorganisms and activate the innate immune system, resulting in the production of a plethora of cytokines and chemokines in the response against microbes. As the epithelia-derived cytokines are deeply involved in the pathogenesis of inflammatory conditions in the nasal cavity and paranasal sinuses, such as chronic rhinosinusitis (CRS) and allergic rhinitis (AR), the molecules involved in the TLR response may be utilized as therapeutic targets for these diseases. There are several differences in the TLR response between nasal and bronchial epithelial cells, and knowledge of the TLR signals in the upper airway is sparse compared to that in the lower airway. In this review, we provide recent evidence on TLR signaling in the upper airway, focusing on the expression, regulation, and responsiveness of TLRs in human nasal epithelial cells (HNECs). We also discuss how TLRs in the epithelium are involved in the pathogenesis of, and possible therapeutic targeting, for CRS and AR.
  • Masanobu Suzuki, Akira Nakazono, Shinya Morita, Atsushi Fukuda, Aya Honma, Takayoshi Suzuki, Shogo Kimura, Yuji Nakamaru, Akihiro Homma
    Allergology international : official journal of the Japanese Society of Allergology 70 (1) 143 - 144 2021/01 [Refereed]
  • Akira Nakazono, Yuji Nakamaru, Mahnaz Ramezanpour, Takeshi Kondo, Masashi Watanabe, Shigetsugu Hatakeyama, Shogo Kimura, Aya Honma, P J Wormald, Sarah Vreugde, Masanobu Suzuki, Akihiro Homma
    Frontiers in cellular and infection microbiology 11 655666 - 655666 2021 [Refereed]
     
    Background: From the first detection in 2019, SARS-CoV-2 infections have spread rapidly worldwide and have been proven to cause an urgent and important health problem. SARS-CoV-2 cell entry depends on two proteins present on the surface of host cells, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). The nasal cavity is thought to be one of the initial sites of infection and a possible reservoir for dissemination within and between individuals. However, it is not known how the expression of these genes is regulated in the nasal mucosa. Objective: In this study, we examined whether the expression of ACE2 and TMPRSS2 is affected by innate immune signals in the nasal mucosa. We also investigated how fluticasone propionate (FP), a corticosteroid used as an intranasal steroid spray, affects the gene expression. Methods: Primary human nasal epithelial cells (HNECs) were collected from the nasal mucosa and incubated with Toll-like receptor (TLR) agonists and/or fluticasone propionate (FP), followed by quantitative PCR, immunofluorescence, and immunoblot analyses. Results: Among the TLR agonists, the TLR3 agonist Poly(I:C) significantly increased ACE2 and TMPRSS2 mRNA expression in HNECs (ACE2 36.212±11.600-fold change, p<0.0001; TMPRSS2 5.598±2.434-fold change, p=0.031). The ACE2 protein level was also increased with Poly(I:C) stimulation (2.884±0.505-fold change, p=0.003). The Poly(I:C)-induced ACE2 expression was suppressed by co-incubation with FP (0.405±0.312-fold change, p=0.044). Conclusion: The activation of innate immune signals via TLR3 promotes the expression of genes related to SARS-CoV2 cell entry in the nasal mucosa, although this expression is suppressed in the presence of FP. Further studies are required to evaluate whether FP suppresses SARS-CoV-2 viral cell entry.
  • Machiko Matsumoto Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Yuji Nakamaru, Satoshi Konno
    Arerugi = [Allergy] 70 (4) 315 - 320 2021 [Refereed]
     
    At the time of writing of this manuscript, four biologics were clinically available for treatment against severe asthma. The choice of four biologics has been taking into account of the results of several type 2 inflammationrelated biomarkers, and the comorbidities of asthma, such as eosinophilic chronic rhinosinusitis, allergic rhinitis, and atopic dermatitis.In this study, we have experienced a case of severe asthma complicated by eosinophilic chronic rhinosinusitis and eosinophilic otitis media, resulting in the use of four biologics, and we observed differential response of upper and lower airways. As a clear algorithm has not been established for the use of four biologics, our experience of this case would provide important lesson for considering the therapeutic strategies against severe asthma.
  • M Suzuki, M Ramezanpour, C Cooksley, T J Lee, B Jeong, S Kao, T Suzuki, A J Psaltis, Y Nakamaru, A Homma, P J Wormald, S Vreugde
    Rhinology 58 (5) 451 - 459 2020/10/01 [Refereed]
     
    BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro. METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts. RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion. CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.
  • 藤原 圭志, 柳 紘子, 森田 真也, 干野 季美子, 福田 篤, 中丸 裕爾, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科頭頸部外科学会 123 (4) 1142 - 1142 0030-6622 2020/09
  • 佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
    アレルギー (一社)日本アレルギー学会 69 (8) 678 - 682 0021-4884 2020/09 
    症例は66歳の好酸球性副鼻腔炎を合併した難治性喘息患者.ベンラリズマブ開始後,喘息症状は著明に改善し,末梢血好酸球数は0/μlとなり,月に数回程度使用していた頓用の経口ステロイドも不要となった.しかし,投与開始後7ヵ月目で喘息症状は再燃し,好酸球数は813/μlと増加したため,メポリズマブへ変更したところ,喘息症状に加え鼻症状も改善した.以上の経過からベンラリズマブに対する中和抗体が産生された可能性が考えられた.中和抗体は日常臨床において測定できないため,中和抗体産生に関する症例報告は認めない.本症例においても疑いにとどまるが,臨床経過からはその可能性は高い.また本症例の鼻症状はベンラリズマブへは反応が乏しく,メポリズマブで改善した.生物学的製剤の臓器における治療反応性の違いも重要な観点である.以上から,本症例は生物学的製剤の特色を多面的に反映した経過を示し,報告の価値は高い.(著者抄録)
  • 頭頸部粘膜悪性黒色腫に対する術後陽子線治療30GyE/5回の初期経験
    湊川 英樹, 安田 耕一, 出倉 康裕, 鈴木 正宣, 中丸 裕爾, 中薗 彬, 鈴木 崇祥, 対馬 那由多, 加納 里志, 鬼丸 力也, 清水 伸一, 本間 明宏, 青山 英史
    頭頸部癌 (一社)日本頭頸部癌学会 46 (2) 188 - 188 1349-5747 2020/07
  • Yuji Nakamaru, Masanobu Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Keishi Fujiwara, Shinya Morita, Satoshi Konno, Akihiro Homma
    ALLERGY & RHINOLOGY 11 2152-6567 2020/07 [Refereed]
     
    Background: Although the close relationship between the upper and lower airways has been highlighted previously, little is known about the association between lung function and the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the factors associated with pulmonary function that affect CRSwNP recurrence after surgery.Methods: We performed a series of routine pulmonary function tests for general anesthesia prior to CRSwNP surgery. The values for each parameter were compared in the presence or absence of recurrence.Results: Sixty-nine patients with CRSwNP were included. The percent predicted forced expiratory volume in one second (%FEV1) in the recurrent group was significantly lower than that in the non-recurrent group (P = .005). A multivariable logistic regression model revealed that %FEV1 was a positive predictor of recurrence (odds ratio: 0.96, 95% CI: 0.92-0.99, P = .023). There were no significant differences in the other pulmonary functions between the two groups.Conclusions: We found that %FEV1 may be a predictor of CRSwNP recurrence after surgery. As %FEV1 is a pulmonary function test that is routinely performed before surgery, this parameter is readily applicable. Moreover, as %FEV1 appears to have the potential to reveal concealed asthma, %FEV1 might be a particularly useful tool for the prediction of CRSwNP recurrence after surgery.
  • Keishi Fujiwara, Shinya Morita, Yasushi Furuta, Hiroko Yanagi, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 41 (5) e615-e622  2020/06 [Refereed]
     
    OBJECTIVES: The aim of the present study was to evaluate semicircular canal function by video Head Impulse Test (vHIT) in patients with facial nerve schwannoma (FNS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seven patients with FNS underwent vHIT examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex and the presence of catch-up saccade were examined for the semicircular canals including the vertical canals. RESULTS: Dysfunction of the semicircular canals was detected by vHIT in three of seven cases. Nystagmus beating toward the non-affected side was observed in all three cases with semicircular canal dysfunction. Dysfunction was observed in a case with no direct compression of the vestibular nerve or semicircular canals by FNS. CONCLUSIONS: Semicircular canal function in patients with FNS could be evaluated by vHIT. vHIT has two advantages for the evaluation of vestibular function in patients with FNS. First, vHIT could be used for the patients in whom a tumor exists in the external auditory canal or middle ear, unlike caloric testing. Second, as vHIT could evaluate all three canals, impaired vestibular nerves could be speculated from vHIT results when a tumor exists in internal auditory canal. vHIT should be performed in patients with FNS, especially before surgery, to evaluate vestibular function.
  • Kazumasa Sato, Hideyuki Ujiie, Shinichi Nakazato, Mika Watanabe, Erika Watanabe, Teruki Yanagi, Yuji Nakamaru, Dai Takagi, Ryuta Arai, Tomohiro Onodera, Takeshi Kondo, Takanori Teshima, Hiroshi Shimizu
    European journal of dermatology : EJD 30 (2) 182 - 183 2020/04/01 [Refereed]
  • Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroki Akamatsu, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Satoshi Kano, Akihiro Homma
    Journal of vestibular research : equilibrium & orientation 30 (2) 101 - 108 2020 [Refereed]
     
    OBJECTIVE: The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma. METHODS: Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated. RESULTS: The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed. CONCLUSIONS: From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.
  • Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Yuji Nakamaru, Satoshi Konno
    Arerugi = [Allergy] 69 (8) 678 - 682 2020 [Refereed]
     
    We report the case of a 66-year-old patient with severe asthma complicated by eosinophilic chronic rhinosinusitis (ECRS). The patient was initially treated with benralizumab, which resulted in marked improvement of asthma symptoms and reduced the peripheral blood eosinophil count to 0/μL. Additionally, oral steroids were discontinued. After 7 months of benralizumab administration, the asthma symptoms worsened and peripheral blood eosinophil count increased to 813/μL. The neutralizing antibodies to benralizumab may have resulted in the recurrence of symptoms due to eosinophilic inflammation. The nasal symptoms, on which benralizumab had an unremarkable effect, improved when treatment was switched to mepolizumab. However, the difference in effects of biologics on ECRS has not been elucidated and warrants further investigation. To the best of our knowledge, this is the first report of a case of severe asthma in which mepolizumab administration reversed the clinical deterioration of asthma, which was possibly caused by neutralizing antibodies to benralizumab.
  • 好酸球性中耳炎(EOM)と中耳炎を合併した好酸球性多発血管炎性肉芽腫症(EGPA)の比較
    福田 篤, 森田 真也, 藤原 圭志, 干野 季美子, 中丸 裕爾, 本間 明宏
    日本耳科学会総会・学術講演会抄録集 (一社)日本耳科学会 29回 508 - 508 2019/10
  • 加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 対馬 那由多, 鈴木 崇祥, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 (一社)日本頭頸部癌学会 45 (3) 300 - 304 1349-5747 2019/10 
    我々は、局所進行外耳道扁平上皮癌に対する治療成績、特にドセタキセル、シスプラチン、5-FUの併用(TPF)の化学療法同時併用放射線療法(CCRT)の治療成績と安全性、および腫瘍の進展範囲と予後との関係を検討した。対象は当科で根治治療を行った外耳道癌扁平上皮癌で、ピッツバーグ分類のT3-4の21症例とした。その結果、硬膜と顎関節への進展が頸部転移と相関を示し、顎関節への進展が局所再発と相関を示した。全症例の2年粗生存率(OS)は61.1%、2年局所制御率(LC)は52.1%であった。CCRT症例では、TPF併用の2年OSは85.7%、それ以外では25.0%、TPF併用の2年LCは57.1%、それ以外では25.0%であった。また、TPF併用CCRTにおけるG3以上の白血球減少は55%、好中球減少は45%であった。TPF併用のCCRTは局所進行外耳道扁平上皮癌に対して高い有効性と安全性を示した。(著者抄録)
  • 福田 篤, 森田 真也, 中丸 裕爾, 干野 季美子, 藤原 圭志, 赤澤 茂, 坂下 智博, 小原 修幸, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 122 (9) 1267 - 1268 0030-6622 2019/09
  • 当院における外鼻形成術および鼻中隔矯正術施行例の検討
    木村 将吾, 中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 58 (3) 632 - 632 0910-9153 2019/09
  • Atsushi Fukuda, Shinya Morita, Yuji Nakamaru, Kimiko Hoshino, Keishi Fujiwara, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 40 (8) e796-e802  2019/09 [Refereed]
     
    OBJECTIVE: To perform comparisons and clarify differences in clinical manifestations between eosinophilic otitis media (EOM) and otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Twenty-two ears of 11 patients exhibiting EOM (EOM group) and 20 ears of 12 patients exhibiting otitis media associated with EGPA (EGPA group). MAIN OUTCOME MEASURES: Otological manifestations, nasal and paranasal manifestations, incidence of asthma, positivity for serum antineutrophil cytoplasmic antibodies (ANCA), total serum immunoglobulin (Ig) E level, peripheral blood eosinophil fraction, and hearing outcomes. RESULTS: The incidence and age of onset of asthma and chronic rhinosinusitis were comparable between the EOM and EGPA groups. Moreover, otological findings and hearing outcomes at the initial visit were similar in both groups. Computed tomography images of the paranasal sinus showed predominant opacification of the ethmoid sinus in both groups. Although the total serum IgE level was not significantly different, the peripheral blood eosinophil fraction was significantly larger in the EGPA group than in the EOM group (p = 0.0035). Furthermore, the rate of myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA) positivity was significantly higher in the EGPA group than in the EOM group (p = 0.019). CONCLUSIONS: The findings of the present study suggest that the phenotypic characteristics of EOM closely resemble those of otitis media associated with EGPA in early stages before the appearance of vasculitis. Therefore, it is challenging to differentiate the two conditions purely on the basis of otorhinological examinations.
  • Keishi Fujiwara, Yasushi Furuta, Wakae Aoki, Yuji Nakamaru, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Akihiro Homma
    The Annals of otology, rhinology, and laryngology 128 (8) 721 - 727 2019/08 [Refereed]
     
    OBJECTIVES: To investigate the effectiveness of make-up therapy for patients with facial nerve palsy. METHODS: Seven female patients with facial nerve palsy who received specialist make-up therapy were enrolled. The objective of the make-up therapy was to obtain a symmetrical facial appearance. RESULTS: Overall score for the Facial Clinimetric Evaluation (FaCE) scale was significantly improved after make-up therapy. There was a tendency for symptoms of depression to be improved among patients after make-up therapy. CONCLUSION: Make-up therapy to improve the symmetry of facial appearance could afford a noninvasive and low-cost treatment for patients with facial nerve palsy, especially in terms of patient quality of life and psychological condition.
  • 森田 真也, 中丸 裕爾, 鈴木 正宣, 本間 明宏
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 37 (2) 77 - 78 0913-0691 2019/06
  • 福田 篤, 森田 真也, 藤原 圭志, 干野 季美子, 中丸 裕爾, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 122 (4) 627 - 627 0030-6622 2019/04
  • 藤原 圭志, 柳 紘子, 森田 真也, 干野 季美子, 福田 篤, 赤松 明樹, 中丸 裕爾, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 122 (4) 704 - 704 0030-6622 2019/04
  • Fukuda A, Morita S, Nakamaru Y, Hoshino K, Fujiwara K, Homma A
    The journal of international advanced otology 15 (1) 2 - 7 1308-7649 2019/04 [Refereed][Not invited]
     
    OBJECTIVES: The aim of the present study was to investigate the prognostic factors for short-term hearing outcomes of ossiculoplasty for primary pars flaccida cholesteatoma according to the European Academy of Otology and Neurotology/Japanese Otological Society (EAONO/JOS) and 2015 JOS staging systems. MATERIALS AND METHODS: A total of 34 patients with primary pars flaccida cholesteatoma who underwent one-stage tympanomastoidectomy with partial ossicular reconstruction using double cartilage block were included in the study. The postoperative pure-tone average air-bone gap (PTA-ABG) was calculated, and two criteria of successful hearing outcomes were defined as ≤10 and ≤20 dB. Patients were classified according to the EAONO/JOS and 2015 JOS staging systems. Cochran-Armitage test was used to statistically analyze staging, and Fisher's exact test was used to analyze other factors. RESULTS: Successful hearing outcome with postoperative PTA-ABG ≤10 and ≤20 dB occurred in 23.5% and 55.9% of cases, respectively. When postoperative PTA-ABG ≤20 dB was defined as successful, the success rate significantly decreased with increase in EAONO/JOS stage, and S0 pathological status of the stapes (no involvement) was a significantly favorable predictive factor. When postoperative PTA-ABG ≤10 dB was regarded as successful, the significantly favorable predictive factors were S0 pathological status of the stapes and development of mastoid cells with MC2-3 (better developed cells). CONCLUSION: Favorable prognostic factors for hearing outcomes of tympanomastoidectomy with partial ossicular reconstruction for primary pars flaccida cholesteatoma were low stage following the EAONO/JOS staging system and no stapes involvement and better development of mastoid cells following the 2015 JOS staging system.
  • Fujiwara K, Yanagi H, Morita S, Hoshino K, Fukuda A, Nakamaru Y, Homma A
    The Annals of otology, rhinology, and laryngology 128 (2) 113 - 120 0003-4894 2019/02 [Refereed][Not invited]
     
    OBJECTIVES:: The aim of this study was to investigate vertical semicircular canal function in patients with vestibular schwannoma (VS) by video head impulse test (vHIT). METHODS:: Fifteen patients with VS who had not received any treatment, including surgery or stereotactic radiotherapy, before vHIT examination were enrolled. Vestibulo-ocular reflex gain and catch-up saccade in vHIT were evaluated. RESULTS:: Dysfunction of anterior and posterior semicircular canals was detected by vHIT in 26.7% and 60.0%, respectively. Six patients (40.0%) demonstrated abnormalities referable to both vestibular nerve divisions. Abnormalities referable to the superior vestibular nerve were identified in 3 patients (20.0%), while 3 patients (20.0%) demonstrated a pattern indicative of inferior vestibular nerve involvement. Anterior semicircular canal vHIT produced fewer abnormalities than did either horizontal or posterior semicircular canal vHIT. CONCLUSIONS:: Dysfunction of the semicircular canals, including the vertical canals, in patients with VS was detected by vHIT. The anterior semicircular canal was less frequently involved than the horizontal or posterior semicircular canal. The examination of the vertical canals by vHIT is useful in the evaluation of vestibular function in patients with VS.
  • Shinya Morita, Yuji Nakamaru, Daigo Nakazawa, Masanobu Suzuki, Kimiko Hoshino, Atsushi Fukuda, Fumihiko Hattanda, Kanako Kusunoki, Utano Tomaru, Akihiro Ishizu, Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 40 (2) e99-e106 - e106 1531-7129 2019/02 [Refereed][Not invited]
     
    OBJECTIVE: This prospective study aimed to evaluate the diagnostic and clinical utility of the myeloperoxidase (MPO)-DNA complex as a NETosis-derived product in the middle ear fluid of patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Twenty-two patients diagnosed with OMAAV. INTERVENTION: Collection of the fluid samples from middle ear. MAIN OUTCOME MEASURE: The levels of the MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay. RESULTS: Patients with both systemic and localized forms of OMAAV showed significantly higher levels of the MPO-DNA complex compared to the controls (p < 0.001 and p = 0.002, respectively). In particular, they showed significantly higher levels of MPO-DNA complex compared to the controls, regardless of serum antineutrophil cytoplasmic antibody status (p < 0.001 and p < 0.001, respectively) or immunosuppressive therapy (p < 0.001 and p < 0.001, respectively) at the time of sampling. An optical density cutoff value of 0.16 at 405 nm according to the receiver operating characteristic curve showed a sensitivity of 86.4%, specificity of 95.5%, positive predictive value of 95.0% and negative predictive value of 87.5% for the diagnosis of OMAAV. Significant positive correlations were observed between the levels of MPO-DNA complex and the values for air conduction - (r = 0.49, p = 0.022) and bone conduction - pure tone average thresholds (r = 0.45, p = 0.035). CONCLUSIONS: The detection and quantification of the MPO-DNA complex in the otitis media fluid may aid in providing a definite diagnosis as well as predicting the activity and severity of OMAAV.
  • Masanobu Suzuki, Yuji Nakamaru, Dai Takagi, Aya Honma, Takayoshi Suzuki, Emi Takakuwa, Shinya Morita, Sarah Vreugde, Akihiro Homma
    Allergy & Rhinology 10 215265671881673 - 215265671881673 2152-6567 2019/01 
    Background IgG4-related disease is a new clinical entity frequently associated with swelling of the submandibular glands (SMGs). The long-term outcome of SMG swelling without steroid therapy remains unknown. Objective To examine whether swollen SMGs spontaneously regress without steroid therapy in the context of IgG4-related disease and to identify biomarkers that can predict the spontaneous regression of SMG swelling. Methods The SMG volume of 49 patients diagnosed with IgG4-related disease was calculated by measuring the axial and coronal planes of computed tomography scans. The change in SMG volume over time was measured and examined by treatment regimen, clinical data, and serum complement level. Results We found 28 of 49 (57%) IgG4-related disease patients to have swollen SMGs, with 15 of 20 (75%) of the swollen SMGs regressing without steroid therapy. The time required for the SMGs swelling to regress was significantly shorter in the steroid therapy group than in the no-steroid therapy group. Serum complement components at the initial visit were significantly lower in the regressed SMG group than in the nonregressed SMG group. Conclusion We observed 75% of swollen SMGs spontaneously regressed in patients with IgG4-related disease. The time required for the swollen SMGs to regress was longer in patients without steroid therapy than in those with steroid therapy. Serum complement level could be used as a predictor for the spontaneous regression of swollen SMGs in patients with IgG4-related disease.
  • Satoshi Kano, Shinya Morita, Yuji Nakamaru, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Akira Nakazono, Atsushi Fukuda, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Akihiro Homma
    Japanese Journal of Head and Neck Cancer 45 (3) 300 - 304 1349-5747 2019 [Refereed][Not invited]
     
    © 2019, Japan Society for Head and Neck Cancer. All rights reserved. We analyzed the treatment outcomes and safety of concomitant chemoradiotherapy (CCRT), especially with a combination of docetaxel, cisplatin and 5FU (TPF), for local advanced external auditory canal squamous cell carcinomas. In addition, we analyzed the correlation between tumor invasion site and prognosis. The study comprised 21 patients with the following criteria: (1) external auditory canal squamous cell carcinomas which were subject to radical treatment at Hokkaido University Hospital between 2007 and 2017, and (2) T3–4 classified according to the University of Pittsburg system. As a result, tumor invasion into the dura or temporomandibular joint was associated with neck lymph node metastasis, and tumor invasion into the temporomandibular joint was associated with local recurrence. The 2-year overall survival rate (OS) and 2-year local control rate (LC) were 61.1％ and 52.1％ in all patients, respectively. In patients treated with CCRT, the 2-year OS was 85.7％ in CCRT with TPF and 25.0％ in CCRT with others, and the 2-year LC was 57.1％ in CCRT with TPF and 25.0％ in CCRT with others. Grade 3︲4 leucopenia and neutropenia occurred in 55％ and 45％ of patients treated with CCRT with TPF, respectively. CCRT with TPF shows high efficacy and safety for local advanced external auditory canal squamous cell carcinomas.
  • Suzuki M, Ramezanpour M, Cooksley C, Li J, Nakamaru Y, Homma A, Psaltis A, Wormald PJ, Vreugde S
    American journal of respiratory cell and molecular biology 59 (4) 500 - 510 1044-1549 2018/10 [Refereed][Not invited]
     
    Matrix metalloproteinase (MMP)-9 is thought to be involved in the etiopathogenesis of chronic rhinosinusitis (CRS) with nasal polyps and cleaves collagen IV, causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP-9 expression is negatively affected by sirtuin (SIRT)-1 in human monocytotic cells, retinal endothelial cells, and epithelial carcinoma cells. However, it is unknown which factors affect MMP-9 expression and activity in human nasal epithelial cells (HNECs). To examine factors affecting MMP-9 expression and activity in HNECs, HNECs were stimulated with Toll-like receptor (TLR) agonists, followed by quantitative PCR, immunofluorescence, and zymography to examine MMP-9 expression and activity. MMP-9 expression was evaluated in sinonasal tissue of control subjects without CRS, and patients with CRS without nasal polyps and those with CRS with nasal polyps, in relation to the expression of SIRT1 using a tissue microarray. The effect of SIRT1 stimulation/inhibition on MMP-9 expression in HNECs was also tested. TLR3 agonists increased MMP-9 mRNA expression (473 fold, P = 0.0198) and activity (20.4-fold, P < 0.05). SIRT1 activation or inhibition reciprocally affected MMP-9 expression in the presence of TLR3 agonists. MMP-9 and SIRT1 expression within the epithelial layer of sinonasal tissue was inversely correlated only in patients with CRS but not in control subjects. TLR3 agonists increased MMP-9 expression and activity in HNECs, and the effect was abolished in the presence of SIRT1 activation. SIRT1 and MMP-9 expression was inversely correlated in CRS tissue, supporting SIRT1 as a possible therapeutic target for nasal polyp formation.
  • Atsushi Fukuda, Shinya Morita, Yuji Nakamaru, Kimiko Hoshino, Keishi Fujiwara, Shigeru Akazawa, Tomohiro Sakashita, Nobuyuki Obara, Akihiro Homma
    Auris Nasus Larynx 45 (5) 911 - 915 1879-1476 2018/10/01 [Refereed][Not invited]
     
    Objective: Although elevated anti-mumps IgM antibody levels were reported in 5.7%–7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit. Methods: This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated. Results: Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p = 0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively no significant difference was seen in these data (p = 0.4519). Conclusion: The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.
  • EAONO/JOS中耳真珠腫進展度分類を用いた術後聴力予後因子の検討
    福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 中丸 裕爾, 本間 明宏
    Otology Japan (一社)日本耳科学会 28 (4) 468 - 468 0917-2025 2018/09
  • vHITを用いた聴神経腫瘍症例の垂直半規管機能評価
    藤原 圭志, 森田 真也, 干野 季美子, 福田 篤, 中丸 裕爾, 本間 明宏
    Otology Japan (一社)日本耳科学会 28 (4) 637 - 637 0917-2025 2018/09
  • 当院における嗅神経芽細胞腫の治療方針と成績
    中薗 彬, 中丸 裕爾, 鈴木 正宣, 水町 貴諭, 高木 大, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 57 (3) 429 - 429 0910-9153 2018/09
  • 篩骨動脈を茎とする鼻中隔粘膜弁を用いた鼻中隔穿孔閉鎖術の1例
    勝俣 量平, 鈴木 正宣, 中薗 彬, 中丸 裕爾, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 57 (3) 504 - 504 0910-9153 2018/09
  • Morita S, Mizumachi T, Nakamaru Y, Sakashita T, Kano S, Hoshino K, Fukuda A, Fujiwara K, Homma A
    International journal of clinical oncology 23 (6) 1029 - 1037 1341-9625 2018/07 [Refereed][Not invited]
     
    BACKGROUND: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. METHODS: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. RESULTS: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. CONCLUSION: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.
  • 鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 36 (2) 118 - 119 0913-0691 2018/06
  • 鼻粘膜上皮細胞においてSIRT-1はPolyICに誘導されるMMP9を負に制御する
    鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 36 (2) 118 - 119 0913-0691 2018/06 [Not refereed][Not invited]
  • Shinichiro Yasukawa, Satoshi Kano, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Masanobu Suzuki, Takayoshi Suzuki, Akira Nakazono, Shinya Tanaka, Hiroshi Nishihara, Akihiro Homma
    International Journal of Clinical Oncology 23 (5) 1 - 9 1437-7772 2018/05/19 [Refereed][Not invited]
     
    Background: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. Methods: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. Results: The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. Conclusion: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.
  • 当科における局所進行外耳道扁平上皮癌の治療成績の検討
    加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 (一社)日本頭頸部癌学会 44 (2) 181 - 181 1349-5747 2018/05
  • Kimura H, Konno S, Makita H, Taniguchi N, Shimizu K, Suzuki M, Kimura H, Goudarzi H, Nakamaru Y, Ono J, Ohta S, Izuhara K, Ito YM, Wenzel SE, Nishimura M, Hi-CARAT investigators
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 0954-7894 2018/05 [Refereed][Not invited]
  • 当科における局所進行外耳道扁平上皮癌の治療成績の検討
    加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
    頭頸部癌 (一社)日本頭頸部癌学会 44 (2) 181 - 181 1349-5747 2018/05 [Not refereed][Not invited]
  • Shinya Morita, Yuji Nakamaru, Daigo Nakazawa, Fumihiko Hattanda, Haruki Shida, Yoshihiro Kusunoki, Kanako Watanabe, Sakiko Masuda, Dai Takagi, Masanobu Suzuki, Kimiko Hoshino, Atsushi Fukuda, Utano Tomaru, Akihiro Homma, Akihiro Ishizu
    Otology and Neurotology 39 (4) e257 - e262 1537-4505 2018/04/01 [Refereed][Not invited]
     
    Objective:The purpose was to explore the presence of myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil extracellular traps (NETs) in the middle ear fluid, and to clarify the correlation between its quantifiable level and hearing outcome in patients with otitis media associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Study Design:Prospective study.Setting:Tertiary referral center.Patients:Nine AAV patients presenting with otitis media.Intervention:Collection of the fluid samples from middle ear.Main Outcome Measure:The quantifiable levels of MPO-DNA complex using an enzyme-linked immunosorbent assay.Results:The quantifiable levels of MPO-DNA complex in patients with AAV were significantly higher than those in controls (p < 0.001). In particular, both ANCA-positive and-negative cases indicated higher levels of MPO-DNA complex compared with the controls (p = 0.004 and p = 0.006, respectively). The significant negative correlations were observed between the level of MPO-DNA complex and the functional hearing values for air (r =-0.82, p = 0.009) and bone conduction (r =-0.73, p = 0.028), respectively.Conclusion:This analysis is the first to reveal the presence of elevated levels of MPO-DNA complex in the middle ear fluid, suggesting the pathogenic role of NETs in otitis media associated with AAV. NETs may be a valuable biomarker for use in clinical decision-making and predicting hearing outcome, regardless of ANCA status.
  • 安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 539 - 539 0030-6622 2018/04
  • 中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 567 - 567 0030-6622 2018/04
  • 森田 真也, 中丸 裕爾, 干野 季美子, 福田 篤, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 557 - 557 0030-6622 2018/04 [Not refereed][Not invited]
  • 中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 567 - 567 0030-6622 2018/04 [Not refereed][Not invited]
  • 鼻副鼻腔内反性乳頭腫の悪性転化に関与する遺伝子変異の解析
    安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 539 - 539 0030-6622 2018/04 [Not refereed][Not invited]
  • Shinya Morita, Yuji Nakamaru, Atsushi Fukuda, Keishi Fujiwara, Kimiko Hoshino, Akihiro Homma
    Otology and Neurotology 39 (2) 189 - 195 1537-4505 2018/02/01 [Refereed][Not invited]
     
    Objective: We aimed to evaluate the clinical features and treatment outcomes for patients with idiopathic and secondary external auditory canal cholesteatoma (EACC), and to validate the treatment strategy from the perspective of hearing as well as etiology and staging. Study Design: Retrospective case series. Setting: Tertiary referral center and affiliated hospitals. Patients: Fifty-eight patients with idiopathic EACC and 14 patients with secondary EACC. Intervention: Conservative management and surgery. Main Outcome Measure: Air conduction (AC) pure-tone averages (PTAs) and mean air-bone gaps (ABGs). Results: There were no significant differences between hearing values before and after conservative management for idiopathic EACC patients with stages I-III, indicating that hearing abilities were preserved. For idiopathic EACC patients with stage IV disease treated with surgery, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 60.3 dB HL to a postoperative value of 32.4 dB HL (p = 0.013), and from 34.3 to 9.5 dB HL (p < 0.001), respectively. For secondary EACC, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 49.5 dB HL to a postoperative value of 23.2 dB HL (p < 0.001), and from 31.4 to 6.7 dB HL (p < 0.001), respectively. Conclusion: The treatment modalities should be selected based on the perspective of hearing as well as the extent of disease and etiology. The early lesions can be treated conservatively, whereas the advanced lesions or cases refractory to conservative management require complete surgical removal of EACC.
  • Satoshi Konno, for the HiCARAT Investigators, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, Masaharu Nishimura, Akira Isada, Takeshi Hattori, Kenichi Shimizu, Takayuki Yoshida, Kentaro Nagaoka, Shinji Nakane, Yoshiyuki Saito, Tsukasa Sasaki, Hideko Honda, Miho Deai, Ayako Muramoto, Natsumi Kudo, Nozomi Sato, Masanobu Suzuki, Hiroshi Saito, Tetsuya Kojima, Shiho Ichimura, Takashi Choji, Motoko Kobayashi, Akihiko Ishikuro, Yoshihiro Ohtsuka, Fumihiro Honmura, Yasushi Akiyama, Toshiyuki Harada, Akira Kamimura, Norio Tashiro, Hiroshi Mikami, Mistuhide Ohmichi, Yoshitaka Sugawara, Toshiki Takahashi, Makoto Yamamoto, Kei Takamura, Yoshio Tokuchi, Yuji Inoue, Katsunori Shigehara, Hideaki Ukita, Kouki Kikuchi, Hiroyuki Koba, Kyuichirou Sekine, Tsuyoshi Nakano, Yoshihiro Ohata, Noritomo Ohnuma, Fumihiko Sato, Hiroyuki Taguchi, Hiroyuki Sugawara, Osamu Honjo, Seiya Togashi, Hirotaka Nishikiori, Junya Kitada, Masaru Fujii, Eiji Shibuya, Hiroshi Tanaka, Yoshihiro Okamoto, Hiromitu Hiroumi, Kazuhiko Watanabe
    Annals of the American Thoracic Society 15 (1) 33 - 41 2325-6621 2018/01/01 [Refereed][Not invited]
     
    Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics.Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Results: Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. Conclusions: This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.
  • Kanako Nakayama, Sayaka Yamamoto, Kimiaki Uetake, Masafumi Yamada, Yusuke Tozawa, Masahiro Ueki, Shunichiro Takezaki, Hiroki Nishimura, Yuji Nakamaru, Tomoko Mitsuhashi, Noriko Oyama-Manabe, Keita Sakamoto, Ryuta Arai, Tadashi Ariga
    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 24 (1) 52 - 54 1076-1608 2018/01 [Refereed][Not invited]
  • Atsushi Fukuda, Shinya Morita, Taisuke Harada, Keishi Fujiwara, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
    Otology and Neurotology 38 (10) 1440 - 1444 1537-4505 2017/12/01 [Refereed][Not invited]
     
    Objective: To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma. Study Design: A retrospective case review. Setting: Tertiary referral center. Patients: Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6-82 yr of age). Intervention: Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging. Main Outcome Measures: Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal. Results: The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different ( p< 0.001). Conclusion: Our results suggest that T1W imaging may aid in the exclusion of false-positive cases on diagnostic non-EP DW MR imaging for cholesteatomas. A combination of non- EP DW and T1W imaging may improve the specificity and accuracy compared with non-EP DW imaging alone.
  • 福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 赤澤 茂, 中丸 裕爾, 本間 明宏
    Otology Japan (一社)日本耳科学会 27 (4) 568 - 568 0917-2025 2017/10 [Not refereed][Not invited]
  • 抗好中球細胞質抗体関連血管炎症候群に伴う難治性中耳炎における好中球細胞外トラップの発現
    森田 真也, 中丸 裕爾, 干野 季美子, 福田 篤, 本間 明宏
    Otology Japan (一社)日本耳科学会 27 (4) 429 - 429 0917-2025 2017/10 [Not refereed][Not invited]
  • 鼻粘膜上皮細胞での自然免疫シグナルによるMMP9の発現誘導
    鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 56 (3) 429 - 429 0910-9153 2017/09 [Not refereed][Not invited]
  • 鼻粘膜上皮細胞での自然免疫シグナルによるMMP9の発現誘導
    鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
    日本鼻科学会会誌 (一社)日本鼻科学会 56 (3) 429 - 429 0910-9153 2017/09 [Not refereed][Not invited]
  • 高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 35 (2) 238 - 239 0913-0691 2017/08 [Not refereed][Not invited]
  • Tomohiko Kakizaki, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
    ONCOLOGY LETTERS 14 (1) 987 - 992 1792-1074 2017/07 [Refereed][Not invited]
     
    Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a > 2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.
  • 福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 中丸 裕爾, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 120 (4) 535 - 535 0030-6622 2017/04 [Not refereed][Not invited]
  • 高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 120 (4) 557 - 557 0030-6622 2017/04 [Not refereed][Not invited]
  • 外耳道癌組織における免疫組織化学的手法に基づく発現分子解析
    森田 真也, 本間 明宏, 中丸 裕爾, 安川 真一郎, 福田 篤, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 120 (4) 566 - 566 0030-6622 2017/04 [Not refereed][Not invited]
  • Hirokazu Kimura, Satoshi Konno, Yuji Nakamaru, Hironi Makita, Natsuko Taniguchi, Kaoruko Shimizu, Masaru Suzuki, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Masaharu Nishimura
    Annals of the American Thoracic Society 14 (3) 332 - 341 2329-6933 2017/03 [Refereed][Not invited]
     
    RATIONALE: When they occur together, sinusitis and asthma are often thought to represent anatomically separate components of the same chronic inflammatory airway disease. Information about the effect of smoking on the interaction between sinusitis and asthma in patients who have both disorders is limited. OBJECTIVES: To evaluate the effect of cigarette smoking on the relationship between the presence and severity of sinusitis and selected asthma-related indices in adults who have asthma. METHODS: This study included 127 patients with severe asthma and 79 patients with mild to moderate asthma. Clinical data were obtained from all subjects during a 2-day stay at Hokkaido University Hospital (Sapporo, Japan). The Lund-Mackay scoring system was used to assess the anatomic extent and severity of sinusitis as revealed by sinus computed tomographic (CT) images obtained during hospitalization. We examined associations between Lund-Mackay scores and a variety of asthma-related indices and levels of biomarkers in blood and sputum. To clarify the effect of smoking on these associations, we conducted separate analyses for nonsmoking (<10 pack-years; n = 130) and smoking subjects (≥10 pack-years; n = 76). MEASUREMENTS AND MAIN RESULTS: In our cohort of adults with asthma, we found significant positive relationships between the presence and severity of sinusitis as assessed by Lund-Mackay score and the severity of asthma as measured by percent predicted FEV1 or FEV1/FVC for nonsmoking subjects (<10 pack-years) but not for cigarette smokers (>10 pack-years). Lund-Mackay scores correlated with blood and sputum eosinophil counts, serum IgE levels, and fractional exhaled nitric oxide, regardless of smoking status. Lund-Mackay scores also showed significant positive associations with serum periostin and chemokine C-C motif ligand 18 levels, regardless of smoking status, whereas a positive association with plasma osteopontin level was seen only for nonsmoking subjects. CONCLUSIONS: We found an association between the severity of sinusitis on CT imaging and the severity of concomitant asthma on spirometry for nonsmoking adults but not for smokers. In adults with asthma, CT imaging evidence of severe sinusitis indicates intense Th2-related inflammation, regardless of smoking status.
  • Shinya Morita, Yuji Nakamaru, Akihiro Homma, Shinichiro Yasukawa, Hiromitsu Hatakeyama, Tomohiro Sakashita, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 22 (1) 181 - 189 1341-9625 2017/02 [Refereed][Not invited]
     
    Background The aim of this study was to investigate the expression of p53, p16, cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and to evaluate the association between these biomarkers and clinicopathological features. Methods We performed a retrospective, single-institution review of 30 TBSCC patients treated with curative intent between April 2006 and March 2015. All tissue samples were obtained from pretreatment biopsy specimens or surgical specimens and using IHC staining. Results Ten patients were categorized as T1, seven as T2, five as T3 and eight as T4. Nine patients had clinically positive lymph node metastasis. The positive expression of p53 and EGFR was significantly associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was significantly more frequent in patients with positive lymph node metastasis compared with patients without node involvement (P = 0.017). In the analysis of the association between protein expression by IHC staining and prognosis, the positive expression of EGFR and Notch1 was significantly correlated with poor survival outcomes in TBSCC (P = 0.015 and P = 0.025) Conclusion Overexpression of p53 and EGFR may be valuable biomarkers for identifying individuals at high risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR was significantly associated with poor survival outcome. Anti-EGFR therapy has potential for use as the treatment modality of choice for advancedstage TBSCC as well as other head and neck squamous cell carcinomas.
  • Keishi Fujiwara, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
    AUDIOLOGY AND NEURO-OTOLOGY 22 (3) 190 - 195 1420-3030 2017 [Refereed][Not invited]
     
    Vogt-Koyanagi-Harada (VKH) disease is an idiopathic, multi-system autoimmune disorder characterized by bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological manifestations. The purpose of this study is to investigate vestibular functions in patients with VKH disease. A total of 43 patients with VKH disease in Hokkaido University Hospital were enrolled in this study. Subjective symptoms such as dizziness or vertigo and the results of various vestibular examinations including nystagmus testing, caloric testing, and vestibular-evoked myogenic potential (VEMP) testing were investigated. Eight of 42 patients (19.0%) complained of subjective vestibular symptoms. On the other hand, 12 of 28 patients (42.9%) showed nystagmus, and 7 of 15 patients (46.7%) showed unilateral or bilateral weakness in the caloric test. VEMP testing was performed for 16 patients. Seven (43.8%) and 8 (50.0%) patients were evaluated as abnormal in cervical VEMP and ocular VEMP testing, respectively. The rate of detection of nys-tagmus was significantly higher than that of subjective symptoms. As vestibular dysfunction in patients with VKH disease cannot be detected through history taking alone, nystagmus testing, caloric testing, and VEMP testing should be performed to evaluate vestibular functions associated with VKH disease. It is considered that abnormal VEMP findings are associated with otolith organ dysfunction. (C) 2017 S. Karger AG, Basel
  • A. Honma, D. Takagi, Y. Nakamaru, A. Homma, M. Suzuki, S. Fukuda
    JOURNAL OF LARYNGOLOGY AND OTOLOGY 130 (12) 1147 - 1152 0022-2151 2016/12 [Refereed][Not invited]
     
    Objective: This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery. Methods: Blood eosinophil numbers and serum interleukin- 5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed. Results: Blood eosinophil numbers and serum interleukin- 5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 +/- 26.1 vs 443.9 +/- 76.6 cells/mu l, p < 0.05), and decreased significantly after surgery (825.7 +/- 26.1 vs 76.7 +/- 25.8 cells/mu l, p < 0.05). Conclusion: Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.
  • アレルギー性鼻炎モデルマウスにおける鼻粘膜時計遺伝子発現リズム
    本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
    日本鼻科学会会誌 (一社)日本鼻科学会 55 (3) 468 - 468 0910-9153 2016/09 [Not refereed][Not invited]
  • Shinya Morita, Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
    OTOLOGY & NEUROTOLOGY 37 (8) 1174 - 1182 1531-7129 2016/09 [Refereed][Not invited]
     
    Objective: We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries. Study Design: Retrospective case series. Setting: Tertiary referral center. Patients: Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015. Intervention: Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT. Main Outcome Measure: The overall survival (OS) rate. Results: The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51-27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1-2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3-4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy. Conclusions: Patients with T1-2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3-4, especially in cases with unresectable tumors.
  • Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rinnosuke Kuramoto, Yuji Nakamaru, Rikiya Onimaru, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    PLOS ONE 11 (8) e0161734  1932-6203 2016/08 [Refereed][Not invited]
     
    Objective Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. Methods We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. Results At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). Conclusions The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT.
  • Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, Toshifumi Yamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase
    Nature microbiology 1 (6) 16054 - 16054 2016/04/25 [Refereed][Not invited]
     
    Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.
  • Shinya Morita, Yuji Nakamaru, Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Masayori Masuya, Satoshi Fukuda
    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 38 E1110 - E1116 1043-3074 2016/04 [Refereed][Not invited]
     
    Background. The purpose of this study was to compare the hearing outcomes after surgery with reconstruction of the external auditory canal in combination with tympanoplasty, radiotherapy (RT) alone, and surgery followed by postoperative RT for T1 to 2N0M0 external auditory canal cancer. Methods. We performed a retrospective, single-institution review of consecutive patients with early-stage external auditory canal cancer treated with surgery and/or RT between April 1997 and August 2013. Audiological data included the pretreatment hearing thresholds and those obtained at 12 months after the completion of therapy. Results. When we compared the functional gains for air-conduction pure-tone average thresholds and mean air-bone gaps, those in the surgery group (n = 10) were significantly higher than those in the RT (n = 13) and surgery 1 RT (n = 5) groups. Conclusion. Adequate techniques for reconstruction of the external auditory canal in combination with tympanoplasty after complete surgical resection is useful for hearing preservation in addition to good survival outcomes. (c) 2015 Wiley Periodicals, Inc.
  • Satomi Omotehara, Mutsumi Nishida, Megumi Satoh, Mamiko Inoue, Yusuke Kudoh, Tatsunori Horie, Akihiro Homma, Yuji Nakamaru, Kanako C. Hatanaka, Chikara Shimizu
    JOURNAL OF MEDICAL ULTRASONICS 43 (2) 257 - 262 1346-4523 2016/04 [Refereed][Not invited]
     
    Purpose We evaluated the sonographic findings of immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS). Methods Nineteen patients with IgG4-SS and 12 healthy volunteers (controls) were enrolled. The following sonographic features were evaluated: (1) enlargement of the submandibular gland by measurement of the longitudinal diameter and thickness; (2) the contour texture of the submandibular gland (smooth or rough); (3) the internal echo texture, categorized into three sonographic patterns (homogeneous, multiple hypoechoic nodule, and diffuse hypoechoic); and (4) quantitative color Doppler signaling. Results The longitudinal diameter and the thickness (mean +/- A SD) of the submandibular gland were significantly greater in patients than in controls (p = 0.005 and p < 0.001, respectively). Contour roughness was seen in 62.9 and 8.3 % of patients and controls (p < 0.001), respectively. Homogeneous echo textures alone were seen in controls, whereas multiple hypoechoic nodule patterns were seen in 60 % of the patients, and diffuse hypoechoic patterns were seen in 40 %. Color Doppler signaling (mean +/- A SD) was significantly higher in patients as compared with controls (p < 0.001). Conclusion Patients could be distinguished from healthy volunteers using four distinctive sonographic findings, suggesting that ultrasonography would be a useful diagnostic tool for IgG4-SS.
  • Masanobu Suzuki, Masashi Watanabe, Yuji Nakamaru, Dai Takagi, Hidehisa Takahashi, Satoshi Fukuda, Shigetsugu Hatakeyama
    CELLULAR AND MOLECULAR LIFE SCIENCES 73 (5) 1085 - 1101 1420-682X 2016/03 [Refereed][Not invited]
     
    NF kappa B is one of the central regulators of cell survival, immunity, inflammation, carcinogenesis and organogenesis. The activation of NF kappa B is strictly regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. Several types of ubiquitination play important roles in multi-step regulations of the NF kappa B pathway. Some of the tripartite motif-containing (TRIM) proteins functioning as E3 ubiquitin ligases are known to regulate various biological processes such as inflammatory signaling pathways. One of the TRIM family proteins, TRIM39, for which the gene has single nucleotide polymorphisms, has been identified as one of the genetic factors in Behcet's disease. However, the role of TRIM39 in inflammatory signaling had not been fully elucidated. In this study, to elucidate the function of TRIM39 in inflammatory signaling, we performed yeast two-hybrid screening using TRIM39 as a bait and identified Cactin, which has been reported to inhibit NF kappa B- and TLR-mediated transcriptions. We show that TRIM39 stabilizes Cactin protein and that Cactin is upregulated after TNF alpha stimulation. TRIM39 knockdown also causes activation of the NF kappa B signal. These findings suggest that TRIM39 negatively regulates the NF kappa B signal in collaboration with Cactin induced by inflammatory stimulants such as TNF alpha.
  • Nakamaru Yuji, Takagi Dai, Suzuki Masanobu, Homma Aya, Fukuda Satoshi
    Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology) 日本鼻科学会 55 (1) 114 - 114 0910-9153 2016
  • Yuji Nakamaru, Dai Takagi, Masanobu Suzuki, Aya Homma, Shinya Morita, Akihiro Homma, Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY 21 (1) 45 - 53 1420-3030 2016 [Refereed][Not invited]
     
    Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease that manifests as asthma, recurrent sinusitis and peripheral eosinophilia. In this study, we investigated the clinical features of the ear and nasal manifestations of EGPA in comparison with those of granulomatosis with polyangiitis (GPA). Materials and Methods: Twenty-one patients diagnosed with EGPA were studied. The frequency of otologic manifestations, the degree of hearing loss and the frequency of nasal symptoms were assessed. The onset of ear symptoms, sinusitis and asthma in patients with EGPA were also examined. Results: Eleven patients (52.4%) with EGPA demonstrated otologic symptoms. The EGPA patients commonly presented mild-to-moderate mixed or sensorineural hearing loss. The pattern of hearing loss was mainly flat, and all but 1 patient achieved complete remission from their hearing impairments. Eighteen patients (85.7%) with EGPA demonstrated nasal symptoms. Patients with EGPA showed a significantly higher incidence of nasal polyps than did those with GPA. The median Lund and Mackey scoring system score was 13.7 for patients with EGPA, and ethmoid sinus shadows were more severe than those of the maxillary sinus. Most ear symptoms associated with EGPA were observed after definitive diagnosis, although sinusitis and asthma tended to manifest themselves before diagnosis. There were significant differences between the onset of ear symptoms and those of asthma and sinusitis. Conclusion: As over 80% of patients with EGPA had nasal symptoms and over half had ear symptoms, otolaryngologists should be aware of this disease. Recognition of the characteristic ear and nasal symptoms are thought to be particularly important to obtain an early diagnosis of EGPA. (C) 2016 S. Karger AG, Basel
  • Shinya Morita, Yuji Nakamaru, Keishi Fujiwara, Keiji Iizuka, Masayori Masuya, Akihiro Homma, Atsushi Fukuda, Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY 21 (3) 132 - 140 1420-3030 2016 [Refereed][Not invited]
     
    Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Meniere's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up. (C) 2016 S. Karger AG, Basel
  • Satoshi Konno, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, Masaharu Nishimura
    Annals of the American Thoracic Society 12 (12) 1771 - 1780 2325-6621 2015/12/01 [Refereed][Not invited]
     
    Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital staywere used for cluster analysis. After clustering using clinical variables, the sputum levels of 14moleculeswere measured to biologically characterize the clinical clusters. Measurements and Main Results: Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. Conclusions: This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation.
  • Konno S, Taniguchi N, Makita H, Nakamaru Y, Shimizu K, Shijubo N, Fuke S, Takeyabu K, Oguri M, Kimura H, Maeda Y, Suzuki M, Nagai K, Ito YM, Wenzel SE, Nishimura M, Hi-CARAT Investigators
    Annals of the American Thoracic Society 12 (12) 1771 - 1780 2329-6933 2015/12 [Refereed][Not invited]
  • Aya Honma, Yoshiko Yamada, Yuji Nakamaru, Satoshi Fukuda, Ken-ichi Honma, Sato Honma
    ENDOCRINOLOGY 156 (11) 4302 - 4311 0013-7227 2015/11 [Refereed][Not invited]
     
    The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans.
  • Akihiro Homma, Yuji Nakamaru, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Tomohiro Sakashita, Toshiaki Shichinohe, Yuma Ebihara, Satoshi Hirano, Hiroshi Furukawa, Toshihiko Hayashi, Yuhei Yamamoto, Satoshi Fukuda
    EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 272 (11) 3551 - 3556 0937-4477 2015/11 [Refereed][Not invited]
     
    Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.
  • Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Rikiya Onimaru, Shunsuke Terasaka, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiromitsu Hatakeyama, Jun Furusawa, Takatsugu Mizumachi, Satoshi Kano, Hiroki Shirato, Satoshi Fukuda
    AURIS NASUS LARYNX 42 (5) 377 - 381 0385-8146 2015/10 [Refereed][Not invited]
     
    Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes. Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis. Results: Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively. Conclusion: Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and nonsurgical approach remain to be solved through further research. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Keishi Fujiwara, Yasushi Furuta, Yuji Nakamaru, Satoshi Fukuda
    AURIS NASUS LARYNX 42 (4) 271 - 274 0385-8146 2015/08 [Refereed][Not invited]
     
    Objective: To investigate the time course of synkinesis as a sequela of facial nerve palsy so that we are able to determine an appropriate time for deciding the outcome of recovery in patients with facial nerve palsy. Methods: Nineteen consecutive patients with peripheral facial nerve palsy who developed synkinesis were enrolled. We compared the degree of synkinesis at 6 and 12 months after the onset of palsy. Our investigation consisted of (1) scoring using the Sunnybrook facial grading system and (2) computing the asymmetry (%) in eye opening width. We also judged whether all 19 cases were cured or not based on the treatment outcome criteria of the Japan Society of Facial Nerve Research at 6 and 12 months. Results: The synkinesis score based on Sunnybrook facial grading system and the degree of asymmetry in eye opening width during mouth movement deteriorated significantly between the 6th and 12th month after the onset of palsy. One of the cases regarded as "cured" at the 6th month was later judged to be "non-cured" due to deterioration in the synkinesis score at the 12th month. Conclusion: From our results, synkinesis deteriorated after the 6th month from the onset of palsy. Therefore, we should follow up the degree of synkinesis until at least the 12th month, and the outcome of recovery in patients with facial synkinesis should be evaluated at least 12 months after the onset. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Yuji Nakamaru, Dai Takagi, Akihiro Homma, Shigetsugu Hatakeyama, Satoshi Fukuda
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY 152 (1) 48 - 52 0194-5998 2015/01 [Refereed][Not invited]
     
    Objective Many proinflammatory cytokines are regulated by the acetylation and deacetylation of the core histone. Since dysregulation of T helper 2 cytokine production is a key in the pathogenesis of allergic diseases, we examined the role of histone deacetylase (HDAC) on interleukin (IL)-4 gene expression in mast cells. We also examined whether oxidative stress has any impact on HDAC activity. Study Design In vitro study. Setting Academic research laboratory. Methods An IgE-sensitized mast cell line (RBL-2H3 cells) was treated with varying concentrations of the HDAC inhibitors trichostatin A (TSA) and H2O2 and stimulated with antigens. The amount of IL-4 gene expression was quantified by real-time polymerase chain reaction. Quantitative measurement of IL-4 in the cell supernatant was performed using enzyme-linked immunosorbent assay. Moreover, HDAC activity was measured with the use of a nonisotopic assay that utilized an HDAC Fluorescent Activity Assay Kit. Results IL-4 mRNA expression was induced by antigens in IgE-sensitized RBL-2H3 cells. Pretreatment with TSA and H2O2 enhanced IL-4 mRNA expression up to 5-fold in a dose-dependent manner. Furthermore, HDAC activity in RBL-2H3 cells was reduced after treatment with H2O2. Conclusion Our results suggest that oxidative stress may up-regulate IL-4 gene expression in mast cells via a decrease in HDAC activity.
  • Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Yuji Nakamaru, Daisuke Yoshida, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    ACTA OTO-LARYNGOLOGICA 135 (9) 950 - 954 0001-6489 2015 [Refereed][Not invited]
     
    Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Patients and methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/ week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9; 7) (range = 4; 6-12; 5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.
  • Yuji Nakamaru, Noriyuki Fujima, Dai Takagi, Akiko Tsukahara, Daisuke Yoshida, Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 123 (7) 468 - 474 0003-4894 2014/07 [Refereed][Not invited]
     
    Objective: Accurate preoperative identification of the attachment site is the key to the successful surgical management of sinonasal inverted papillomas (IPs). This study investigated the value of preoperative imaging to identify the attachment sites of IPs. Methods: We analyzed 10 consecutive patients with pathologically proven IPs. Two radiologists predicted the attachment sites of IPs from computed tomography (CT), 3.0 Tesla magnetic resonance imaging (3.0T MRI), 1.5T MRI, and CT plus 3.0T MRI. The actual tumor attachment sites were confirmed via pathological examination of specimens and compared with the predicted sites. Results: Computed tomography showed the highest sensitivity (P < .0001), although both MRI formats showed greater specificity (P < .0001). The sensitivity of MRI plus CT was equal to that of CT and better than that of MRI (P <.0001), whereas its specificity was better than that of CT (P < .0001) and comparable to that of MRI. Prediction using 3.0T MRI appeared slightly superior to that using 1.5T MRI in terms of sensitivity and specificity, although the differences were not significant. Conclusion: Computed tomography and MRI had different features for prediction of sinonasal IP attachment sites. Preoperative CT plus MRI provided more useful information than CT or MRI alone.
  • Dai Takagi, Yuji Nakamaru, Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 123 (6) 420 - 424 0003-4894 2014/06 [Refereed][Not invited]
     
    Objective: Immunoglobulin (Ig) G4-related disease is systemic, and it has been reported that patients with IgG4-related disease complain of symptoms involving numerous organs. However, there are few reports concerning the otologic manifestations of IgG4-related disease. The purpose of this study is to investigate the clinical features of the otologic manifestations in IgG4-related disease. Methods: We recruited 39 consecutive patients diagnosed with IgG4-related disease. Otologic symptoms, laboratory data, and audiogram findings were retrospectively examined. Mucosal tissues from the inferior turbinate were obtained from subjects before treatment. The serum IgG4 and eosinophil levels together with clinical features were analyzed. Results: Five of the 39 cases had some otologic symptoms. Otitis media with effusion was present in 2 patients. Sensorineural hearing loss was also present in 1 patient. Eosinophilic otitis media was present in 2 patients with bilateral rhinosinusitis and bronchial asthma, and elevated serum eosinophil levels. Oral prednisolone was effective in the treatment of IgG4-related disease. Conclusion: We revealed a new clinical entity associated with the otologic manifestations of IgG4-related disease.
  • 森田 真也, 中丸 裕爾, 本間 明宏, 坂下 智博, 桝谷 将偉, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 117 (4) 565 - 565 0030-6622 2014/04 [Not refereed][Not invited]
  • Shinya Morita, Yuji Nakamaru, Nobuyuki Obara, Masayori Masuya, Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY 19 (1) 49 - 56 1420-3030 2014 [Refereed][Not invited]
     
    Objective: To clarify the characteristics and prognosis of hearing loss associated with Vogt-Koyanagi-Harada (VKH) disease. Methods: We retrospectively examined 85 patients diagnosed with VKH disease between January 1996 and December 2012. The control group included age-and gender-matched individuals without definitive ear disease. The patients with VKH disease were treated with high-dose systemic corticosteroids, which were tapered off gradually over a period of 6 months or more by the treating ophthalmologists according to the severity of the ocular inflammation. The features of hearing loss were analyzed based on pure tone audiometric data obtained at the initial presentation according to diagnostic criteria based on the ISO 7029 standard. The efficacy of corticosteroid therapy was evaluated by audiometry at the initial presentation and during therapy for 3-6 months. Results: In patients with VKH disease, the rate of hearing loss detected by audiometry was significantly higher than that of either subjective hearing loss (p < 0.001) or tinnitus (p < 0.001). Bilateral symmetrical hearing loss was the most common type of auditory disturbance associated with VKH disease. The degree of hearing loss was generally low, with no patients showing profound hearing loss. Hearing thresholds were significantly elevated at high frequencies compared with those at low-to-mid frequencies (p < 0.001). Hearing thresholds at all frequencies after high-dose corticosteroid therapy were significantly better than those at initial presentation (p < 0.001), and the rate of patients who returned to within normal-range pure tone thresholds at all frequencies was 74.8%. Conclusions: As auditory manifestations cannot be detected through history taking alone, audiometry should be performed to evaluate hearing loss associated with VKH disease. Early administration of high-dose systemic corticosteroids is effective for treating the auditory manifestations, which generally show a relatively good short-term prognosis. (C) 2013 S. Karger AG, Basel
  • Shinya Morita, Yuji Nakamaru, Akihiro Homma, Tomohiro Sakashita, Masayori Masuya, Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY 19 (6) 351 - 357 1420-3030 2014 [Refereed][Not invited]
     
    Objective: To evaluate postoperative hearing outcomes after lateral temporal bone resection (LTBR) with reconstruction of the external auditory canal (EAC) and conductive function for early-stage EAC carcinoma. Methods: We retrospectively examined patients diagnosed with early-stage EAC carcinoma treated with surgery alone between January 2006 and December 2012. Patients who had postoperative adjuvant chemotherapy and/or radiotherapy were excluded. Patients receiving LTBR in combination with tympanoplasty were divided into two groups based on the reconstruction of the EAC with and without (w/o) split-thickness skin grafts (STSGs). Audiological data included the preoperative hearing thresholds and the most recent postoperative hearing thresholds obtained at least 12 months after surgery. The hearing outcome was evaluated based on puretone audiograms using the Committee on Hearing and Equilibrium guidelines of the American Academy of Otolaryngology-Head and Neck Surgery for the evaluation of the results of treatment of conductive hearing loss. The postoperative quality of life (QOL) for patients was evaluated using the Glasgow Benefit Inventory (GBI). Results: All patients (n = 15) achieved disease-free survival without significant morbidity or mortality. When we compared the mean air-bone gaps after surgery, those in the STSG group (n = 8) were found to be significantly lower than those in the w/o STSG group (n = 7; p < 0.001). The success rate for postoperative hearing was 75.0% in the STSG group, which was significantly higher than that in the w/o STSG group (p = 0.014). All patients in the w/o STSG group showed stenosis and closure of the EAC at fewer than 10 months after surgery. In contrast, all patients in the STSG group showed preserved conformation of the new EAC for more than 12 months after surgery. When we compared the mean GBI score between the two groups of patients, the overall and general health scores in the STSG group were found to be significantly higher than those in the w/o STSG group (p = 0.021, p = 0.001). Conclusions: Reconstruction of the EAC using a rolled-up STSG technique in combination with tympanoplasty after LTBR is useful for hearing preservation and the observation of locoregional lesions after surgery, resulting in improved QOL for patients. (C) 2014 S. Karger AG, Basel
  • 耳鳴に対するエスシタロプラムの有効性に関する検討
    桝谷 将偉, 中丸 裕爾, 森田 真也, 福田 諭
    Otology Japan (一社)日本耳科学会 23 (4) 774 - 774 0917-2025 2013/10 [Not refereed][Not invited]
  • 外側側頭骨切除術に一期的鼓室形成術を施行した早期外耳道癌症例の検討
    中丸 裕爾, 森田 真也, 桝谷 将偉, 福田 諭
    Otology Japan (一社)日本耳科学会 23 (4) 669 - 669 0917-2025 2013/10 [Not refereed][Not invited]
  • Vogt-小柳-原田病における聴力像の特徴および聴力予後の検討
    森田 真也, 中丸 裕爾, 小原 修幸, 桝谷 将偉, 福田 諭
    Otology Japan (一社)日本耳科学会 23 (4) 513 - 513 0917-2025 2013/10 [Not refereed][Not invited]
  • 高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 31 (2) 73 - 74 0913-0691 2013/06 [Not refereed][Not invited]
  • Masanobu Suzuki, Yuji Nakamaru, Shigeru Akazawa, Takatsugu Mizumachi, Masanori Maeda, Dai Takagi, Kanako C. Hatanaka, Satoshi Fukuda
    LARYNGOSCOPE 123 (4) 829 - 834 0023-852X 2013/04 [Refereed][Not invited]
     
    Objectives/Hypothesis: Immunoglobulin (Ig)G4-related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4-related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4-related disease. Study Design: Retrospective review in a tertiary referral hospital. Methods: Twenty-three consecutive patients with IgG4-related disease, six allergic rhinitis (AR) patients, and eight healthy subjects (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and laboratory data were examined. Mucosal tissues from the inferior turbinate were obtained from all subjects before treatment. The level of IgG4-positive plasma cells and other infiltrating cells, and the number of nasal glands in the nasal subjects were compared among the three groups. Results: Ten (43.4%) of 23 cases had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the IgG4-related disease group than in the HS and AR groups, whereas the number of nasal glands in the IgG4-related disease group was significantly lower than in the HS and AR groups. Conclusions: The inflammatory lesions associated with IgG4-related disease exist on the nasal membrane. Thus, the nasal manifestations of IgG4-related disease were thought to be different from AR.
  • Dai Takagi, Yuji Nakamaru, Masanobu Suzuki, Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 121 (12) 816 - 820 0003-4894 2012/12 [Refereed][Not invited]
     
    Objectives: We investigated the function of the decreases in histone deacetylase (HDAC) and histone acetyltransferase (HAT) in Wegener's granulomatosis (WG) patients compared with healthy subjects. Methods: Seven patients with WG, diagnosed according to the American College of Rheumatology criteria, were examined. Fresh peripheral blood mononuclear cells were isolated from the WG patients and healthy subjects, and then whole-cell proteins were prepared. We measured the total HDAC and HAT activity in peripheral blood mononuclear cells from WG patients. The HDAC2 expression was analyzed by Western blot. Results: We found that total HDAC activity was significantly decreased in WG patients compared to that in healthy subjects (p < 0.05). Furthermore, we found a negative correlation between total HDAC activity and C-reactive protein titer. Total HAT activity was significantly increased in WG patients. Conclusions: These results demonstrated reduced HDAC activity and an increase in HAT activity in WG. These were associated with concomitant induction of WG-related inflammation. Thus, dysregulation of HDAC and HAT may contribute to the disease pathogenesis of WG.
  • 高木 大, 中丸 裕爾, 鈴木 正宣, 福田 諭
    耳鼻咽喉科・頭頸部外科 (株)医学書院 84 (13) 1021 - 1026 0914-3491 2012/12 [Not refereed][Not invited]
     
    急性副鼻腔炎に対するLevofloxacin 500mg1日1回投与の早期治療効果と安全性を検討した。解析対象は26症例で、急性炎症を起こしてから10日以内であり、投与期間は全て7日間であった。重症度は中等症6例、重症20例であった。投与開始3日後、自覚症状、他覚所見ともに有意なスコアの改善を認め、投与終了時の有効率は84.6%であり、特に重症例での有効率は90.0%であった。やや有効にとどまった症例を4例認めたが、自覚症状、他覚所見どちらも改善を示さない無効例はなかった。やや有効の4例中2例は、鼻中隔彎曲等による中鼻道の狭小化があり、その後内視鏡的副鼻腔手術を施行して改善した。24例には細菌学的検査を施行し、10例から12種の原因菌が同定された。Haemophilus influenzaeが5株と最多で、Streptococcus pneumoniaeの4株が続いた。副作用は1例に軽度の全身そう痒感が発現したが、内服は継続可能であった。
  • Hiroko Yanagi, Yuji Nakamaru, Dai Takagi, Kanako Kubota, Satoshi Fukuda
    RHINOLOGY 50 (3) 325 - 331 0300-0729 2012/09 [Refereed][Not invited]
     
    Background: The diagnosis of extranodal natural killer (NK)/T-cell lymphoma (NK/T-cell lymphoma) is often difficult and any delay in its diagnosis leads to a worsened prognosis. We analysed the factors that make the diagnosis of this type of tumour difficult. Methodology/Principal: We retrospectively reviewed the medical records of 20 patients with NK/T-cell lymphoma treated in our department, and assessed the clinical features and laboratory findings of the cases. Moreover, we classified factors related to delays in diagnosing NK/T cell lymphoma as follows: (1) insufficient specimen size, (2) massive necrosis, (3) large number of inflammatory cells, and (4) poor atypia. We selected cases requiring two or more biopsies for correct diagnosis and checked which factors were the main cause of misdiagnosis. Results: The average period required for a correct diagnosis was 12.8 months. The most frequent factor leading to diagnostic delay was inflammatory cell infiltration. Massive necrosis and poor atypia were also important factors in diagnostic delay. Conclusions: In cases with necrotic lesions of the nose or pharynx, the possibility of NK/T cell lymphoma should be explored and samples, of as large a size as possible, should be obtained together with EBER-ISH for pathological examination. Repeat biopsies should also be performed for diagnosis.
  • 早期外耳道癌に対して外側側頭骨切除術に一期的鼓室形成術を施行した4症例
    森田 真也, 中丸 裕爾, 福田 諭
    Otology Japan (一社)日本耳科学会 22 (4) 579 - 579 0917-2025 2012/09 [Not refereed][Not invited]
  • 中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 215 - 216 0913-0691 2012/06 [Not refereed][Not invited]
  • 高木 大, 中丸 裕爾, 鈴木 正宣, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 76 - 77 0913-0691 2012/06 [Not refereed][Not invited]
  • 鈴木 正宣, 中丸 裕爾, 赤澤 茂, 水町 貴諭, 前田 昌紀, 高木 大, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 70 - 71 0913-0691 2012/06 [Not refereed][Not invited]
  • 鈴木 正宣, 中丸 裕爾, 赤澤 茂, 水町 貴諭, 前田 昌紀, 高木 大, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 115 (4) 413 - 413 0030-6622 2012/04 [Not refereed][Not invited]
  • Yuji Nakamaru, Dai Takagi, Nobuhiko Oridate, Akihiro Homma, Satoshi Fukuda
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY 146 (1) 119 - 121 0194-5998 2012/01 [Refereed][Not invited]
     
    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P=.001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P=.007). Crust formation (P=.001), saddle nose (P=.024), and sinusitis (P=.001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.
  • Yuuta Kamoshima, Shunsuke Terasaka, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda, Kiyohiro Houkin
    Case Reports in Neurology 4 (1) 34 - 37 1662-680X 2012/01 [Refereed][Not invited]
     
    Giant mucoceles of the frontal sinus are rare but their recognition is important in the differential diagnosis of proptosis and fronto-orbital lesions. The authors describe a patient with frontal giant mucocele with intracranial as well as orbit and ethmoid sinus involvement. Thirty-two years after a frontal sinus fracture, a 51-year-old female presented with headache, and left exophthalmos and ophthalmoplegia. Computed tomography and magnetic resonance imaging demonstrated a giant frontal sinus mucocele with extension into the left anterior cranial fossa. The mucocele was treated with a transcranial and endoscopic transnasal approach. The frontal sinus was then cranialized with reconstruction of the posterior wall, and finally a wide nasal drainage was performed. The clinical symptoms disappeared immediately after surgery. Copyright © 2012 S. Karger AG, Basel.
  • Modified Lothrop Procedureにより内視鏡的に切除した前頭洞内に茎を持つ内反性乳頭腫症例
    中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
    日本鼻科学会会誌 (一社)日本鼻科学会 50 (3) 379 - 379 0910-9153 2011/11 [Not refereed][Not invited]
  • IgG4関連疾患における鼻腔病変の検討
    赤澤 茂, 中丸 裕爾, 高木 大, 水町 貴諭, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 29 (2) 77 - 78 0913-0691 2011/06 [Not refereed][Not invited]
  • Yuji Nakamaru, Yasushi Furuta, Dai Takagi, Nobuhiko Oridate, Satoshi Fukuda
    RHINOLOGY 48 (4) 452 - 456 0300-0729 2010/12 [Refereed][Not invited]
     
    Background: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP). Methodologies: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumours arising from the anterior part of the maxilla, sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer's test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery. Results: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumours. No patient suffered tumour recurrence. There was no difference in lacrimal duct function between the diseased and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100. Conclusions: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.
  • Yuji Nakamaru, Yasushi Furuta, Dai Takagi, Nobuhiko Oridate, Satoshi Fukuda
    RHINOLOGY 48 (4) 452 - 456 0300-0729 2010/12 [Refereed][Not invited]
     
    Background: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP). Methodologies: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumours arising from the anterior part of the maxilla, sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer's test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery. Results: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumours. No patient suffered tumour recurrence. There was no difference in lacrimal duct function between the diseased and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100. Conclusions: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.
  • 古田 康, 松村 道哉, 鈴木 正宣, 中丸 裕爾
    日本鼻科学会会誌 (一社)日本鼻科学会 49 (3) 415 - 415 0910-9153 2010/07 [Not refereed][Not invited]
  • Syuji Yonekura, Yoshitaka Okamoto, Daiju Sakurai, Shigetoshi Horiguchi, Toyoyuki Hanazawa, Atsuko Nakano, Fumiyo Kudou, Yuji Nakamaru, Kohei Honda, Akira Hoshioka, Naoki Shimojo, Yoichi Kohno
    Allergology International 59 (4) 381 - 388 1440-1592 2010 [Refereed][Not invited]
     
    Background: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis. Methods: The study population comprised 31 subjects (21 males and 10 females) aged from 7 to 15 years old. Twenty patients (the active group) received house dust extract and 11 received placebo via sublingual administration. Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks. During the study period, the subjects recorded their daily nasal symptoms and use (dose and frequency) of other medications in a nasal allergy diary. Results: The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks. The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group. The only local adverse effect was a bitter taste reported by one patient. There were no other local or systemic adverse effects associated with SLIT. Conclusions: Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children.© Japanese Society of Allergology.
  • 鈴木 正宣, 大谷 文雄, 松村 道哉, 蠣崎 文彦, 森田 真也, 佐藤 宏紀, 中丸 裕爾, 古田 康
    耳鼻咽喉科・頭頸部外科 (株)医学書院 82 (1) 67 - 72 0914-3491 2010/01 [Not refereed][Not invited]
     
    反復性鼻出血に対し内視鏡下蝶口蓋動脈結紮術を施行した14例15側(男11例・女3例・42〜76歳)について報告した。適応は、保存的療法で止血できず、蝶口蓋動脈の支配領域からの出血が疑われる症例とした。鼻出血の危険因子として、高血圧合併8例、5例に抗凝固薬使用を認めた。術前全例にガーゼタンポンがなされ、うち9例はバルーンタンポンも施行した。術前の輸血は2例に要した。手術時間は平均80分で、粘膜下下甲介切除術を7例に、鼻中隔矯正術を4例に併施した。出血量はほとんどが少量であったが、4例では100〜400mlと多かった。術後のガーゼ留置期間は平均1.6日間で、ガーゼ抜去時の出血が3例でみられたが、動脈性ではなくガーゼで止血できた。血小板機能異常を合併した1例のみ術後も出血が続き、バイポーラー焼灼術、アルゴンプラズマレーザーによる鼻腔粘膜焼灼術を要した。手術から退院までの平均日数は4.9日で、重篤な合併症はなかった。
  • Yuji Nakamaru, Chaitanya Vuppusetty, Hiroo Wada, Jill C. Milne, Misako Ito, Christos Rossios, Mark Elliot, James Hogg, Sergei Kharitonov, Hajime Goto, Jean E. Bemis, Peter Elliott, Peter J. Barnes, Kazuhiro Ito
    FASEB JOURNAL 23 (9) 2810 - 2819 0892-6638 2009/09 [Refereed][Not invited]
     
    Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The object of this study was to identify the molecular mechanism underlying this increase of MMP9 expression, and here we show that oxidative stress-dependent reduction of a protein deacetylase, SIRT1, known as a putative antiaging enzyme, causes elevation of MMP9 expression. A sirtuin inhibitor, splitomycin, and SIRT1 knockdown by RNA interference led an increase in MMP9 expression in human monocytic U937 cells and in primary sputum macrophages, which was detected by RT-PCR, Western blot, activity assay, and zymography. In fact, the SIRT1 level was significantly decreased in peripheral lungs of patients with COPD, and this increase was inversely correlated with MMP9 expression and MMP9 promoter activation detected by a chromatin immunoprecipitation assay. H(2)O(2) reduced SIRT1 expression and activity in U937 cells; furthermore, cigarette smoke exposure also caused reduction of SIRT1 expression in lung tissue of A/J mice, with concomitant elevation of MMP9. Intranasal treatment of a selective and novel SIRT1 small molecule activator, SRT2172, blocked the increase of MMP9 expression in the lung as well as pulmonary neutrophilia and the reduction in exercise tolerance. Thus, SIRT1 is a negative regulator of MMP9 expression, and SIRT1 activation is implicated as a novel therapeutic approach to treating chronic inflammatory diseases, in which MMP9 is abundant.-Nakamaru, Y., Vuppusetty, C., Wada, H., Milne, J. C., Ito, M., Rossios, C., Elliot, M., Hogg, J., Kharitonov, S., Goto, H., Bemis, J. E., Elliott, P., Barnes, P. J., Ito, K. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J. 23, 2810-2819 (2009). www.fasebj.org
  • 術中に内反性乳頭腫と判明した一側性上顎洞病変症例
    水町 貴諭, 中丸 裕爾, 高木 大, 福田 諭
    日本鼻科学会会誌 (一社)日本鼻科学会 48 (3) 276 - 276 0910-9153 2009/08 [Not refereed][Not invited]
  • 鼻腔病変を有したIgG4関連疾患2症例
    水町 貴諭, 中丸 裕爾, 前田 昌紀, 高木 大, 久保田 佳奈子, 河上 洋, 福田 諭
    アレルギーの臨床 (株)北隆館 29 (8) 712 - 716 0285-6379 2009/08 [Not refereed][Not invited]
     
    鼻腔に病変を呈したIgG4関連疾患の2症例を経験した。症例はいずれも50歳代の男性で、鼻腔に痂皮の付着を認めた。血清IgG4値は高値で、下鼻甲介からの生検では腺組織に異型はなく、間質にIgG4陽性の形質細胞の浸潤を認めた。IgG4関連の病変は1例は自己免疫性膵炎をはじめ全身の臓器にみられたが、他の1例は頭頸部領域に限局していた。病変が全身にみられた症例に対してはステロイドの全身治療を、頭頸部に限局していた症例に対してはステロイド点鼻療法を行ったが、いずれも病変は軽快し、現在のところ再燃はなく経過観察中である。(著者抄録)
  • Nobuhiko Oridate, Akihiro Homma, Seigo Suzuki, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Tomohiro Sakashita, Noriko Nishizawa, Yasushi Furuta, Satoshi Fukuda
    ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY 135 (4) 363 - 368 0886-4470 2009/04 [Refereed][Not invited]
     
    Objective: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. Design: The VRQOL and VHI-10 questionnaires. Setting: University hospital. Patients: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. Main Outcome Measure: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. Results: The mean VRQOL scores for patients who had undergone radiotherapy (n=63), chemoradiotherapy (n=29), laser surgery (n=14), or total laryngectomy (n=27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. Conclusion: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.
  • Tomohiro Sakashita, Nobuhiko Oridate, Akihiro Homma, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Yutaka Sawamura, Yuhei Yamamoto, Yasushi Furuta, Satoshi Fukuda
    SKULL BASE-AN INTERDISCIPLINARY APPROACH 19 (2) 127 - 132 1531-5010 2009/03 [Refereed][Not invited]
     
    Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors. Design: Retrospective analysis. Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases). Main outcome measures: Perioperative complications and risk factor associated with their incidence. Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported. Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.
  • Tomohiro Sakashita, Nobuhiko Oridate, Akihiro Homma, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Yutaka Sawamura, Yuhei Yamamoto, Yasushi Furuta, Satoshi Fukuda
    SKULL BASE-AN INTERDISCIPLINARY APPROACH 19 (2) 127 - 132 1531-5010 2009/03 [Refereed][Not invited]
     
    Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors. Design: Retrospective analysis. Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases). Main outcome measures: Perioperative complications and risk factor associated with their incidence. Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported. Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.
  • 鈴木 正宣, 折舘 伸彦, 本間 明宏, 中丸 裕爾, 畠山 博充, 目須田 康, 古田 康, 福田 諭
    耳鼻咽喉科・頭頸部外科 (株)医学書院 81 (3) 219 - 221 0914-3491 2009/03 [Not refereed][Not invited]
     
    42歳男。4ヵ月前に嗄声が出現し、保存的治療でいったん改善したが、再増悪を来たした。間接喉頭鏡で左披裂部内側壁、左声帯に3ヶ所、右声帯に2ヶ所の喉頭腫瘍を認め、喉頭ファイバースコピーで腫瘍は乳頭状増殖を示した。喉頭乳頭腫の診断で喉頭直達鏡による腫瘍切除術を施行し、一部採取した腫瘍の迅速病理では悪性所見なしの結果であった。喉頭用スキマーブレード(2.9mm)を装着したマイクロデブリッダーを用いて腫瘍切除を行い、腫瘍自体は軟らかく、ブレード内に吸引された腫瘍のみを切除可能であった。回転数はブレードの熱による瘢痕化を防ぐため、毎分60回転の超低速とした。ごく少量の出血を認めたが、マイクロデブリッダーによる吸引と20万倍エピネフリン塗布で対処できた。切除組織の病理組織像は核異型、分裂像に乏しく、乳頭腫と診断された。術後は沈黙療法を行い、4日目に退院した。嗄声は改善し、術後5ヵ月で再増悪、腫瘍再発はない。
  • 内視鏡下鼻副鼻腔内反性乳頭腫手術における上顎洞前壁の処理 対側鼻腔からのアプローチ法
    中丸 裕爾, 古田 康, 原 敏浩, 水町 貴諭, 福田 諭
    日本鼻科学会会誌 (一社)日本鼻科学会 47 (3) 290 - 290 0910-9153 2008/08 [Not refereed][Not invited]
  • IgG4関連疾患としての鼻腔病変について
    水町 貴諭, 前田 昌紀, 中丸 裕爾, 福田 諭
    日本鼻科学会会誌 (一社)日本鼻科学会 47 (3) 276 - 276 0910-9153 2008/08 [Not refereed][Not invited]
  • Keita Oikawa, Yasushi Furuta, Yuji Nakamaru, Nobuhiko Oridate, Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 116 (9) 674 - 680 0003-4894 2007/09 [Refereed][Not invited]
     
    Objectives: We sought to determine the value of preoperative staging by magnetic resonance imaging (MRI) assessment in the surgical management of sinonasal inverted papillomas (IPs). Methods: Preoperative MRI staging was used to assess 22 patients with IPs. In addition to the Krouse staging system, T3 cases were categorized as subgroup T3-B if tumors extended into the frontal sinus or the supraorbital recess; otherwise, they were categorized as T3-A. Standard endoscopic sinus surgery (ESS) was the first choice for T1 and T2 cases. Endoscopic approaches, including ESS combined with endoscope-assisted transantral approach and endoscopic medial maxillectomy, were considered in T3-A cases, and external approaches were considered in T3-B cases. Patients were followed for a minimum of 1 year after surgery. Results: Preoperative MRI staging and postoperative staging were coincident in 21 of the 22 patients (95%). All 8 T2 cases were treated by an endoscopic approach. Of 10 T3-A cases, 9 (90%) were treated by an endoscopic approach and 1 (residual case) was treated by an external approach. All 3 of the T3-B cases underwent an external approach. One T4 case with malignant transformation underwent an external approach followed by radiotherapy. After a median follow-up period of 22 months, none of the 22 patients had had a recurrence. No major complications were observed after endoscopic approaches, but epiphora or hemorrhage requiring transfusion occurred in 3 of the 5 patients (60%) who underwent external approaches. Conclusions: Preoperative staging of IP by MRI is useful for selecting cases that can be managed by endoscopic approaches, resulting in lower rates of tumor recurrence and morbidity.
  • 喉頭癌治療後の音声に関するQOLの検討
    折舘 伸彦, 古田 康, 本間 明宏, 鈴木 清護, 中丸 裕爾, 鈴木 章之, 畠山 博充, 瀧 重成, 坂下 智博, 西澤 典子, 目須田 康, 福田 諭
    頭頸部癌 (一社)日本頭頸部癌学会 33 (2) 178 - 178 1349-5747 2007/05 [Not refereed][Not invited]
  • Masanori Maeda, Yoshiki Yanagawa, Kazuya Iwabuchi, Keita Minami, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda, Kazunori Onoe
    IMMUNOBIOLOGY 212 (7) 537 - 547 0171-2985 2007 [Refereed][Not invited]
     
    Interleukin (IL)-21 shows pleiotropic effects on the proliferation, differentiation, and effector functions of leukocytes. However, the influence of IL-21 on dendritic cell (DC) activation of natural killer T (NKT) cells has not yet been elucidated. In the present study, we examined the effect of IL-21 on murine myeloid DC ability to induce NKT cell production of interferon-gamma (IFN-gamma) and IL-4. Pretreatment of DCs with IL-21 and a-galactosylceramide (alpha-GalCer), an NKT cell-specific ligand, resulted in the enhanced ability of the DCs to induce NKT cell production of IFN-gamma but not IL-4 in vitro compared to DCs pretreated with alpha-GalCer alone. A similar effect of IL-21 was observed when DCs pretreated with IL-21 and alpha-GalCer in vitro were transferred into naive mice. Direct administration of IL-21 to the mice also enhanced IFN-gamma production after injection of a-GalCer. Thus, IL-21 can modify DC ability to selectively enhance NKT cell production of IFN-gamma upon stimulation with alpha-GalCer. (c) 2007 Elsevier GmbH. All rights reserved.
  • Dai Takagi, Kazuya Iwabuchi, Masanori Maeda, Yuji Nakamaru, Yasushi Furuta, Satoshi Fukuda, Luc Van Kaer, Jun Nishihira, Kazunori Onoe
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18 (5) 829 - 836 1107-3756 2006/11 [Refereed][Not invited]
     
    Macrophage migration inhibitory factor (MIF) plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-HC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We found that MIFTg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIFTg mice and significantly increased numbers of CD69(+) T cells were detected in the spleens of these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with alpha-galactosylceramide (alpha-GalCer). Further, repeated administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play :an ameliorating role upon stimulation with alpha-GalCer in the inflammatory process in MIFTg mice.
  • 前田 昌紀, 柳川 芳毅, 岩淵 和也, 中丸 裕爾, 高木 大, 福田 諭, 小野江 和則
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 24 (2) 207 - 208 0913-0691 2006/09
  • 折舘 伸彦, 目須田 康, 西澤 典子, 森 美果, 中丸 裕爾, 本間 明宏, 古田 康, 福田 諭
    日本気管食道科学会会報 (NPO)日本気管食道科学会 57 (3) 262 - 267 0029-0645 2006/06 [Not refereed][Not invited]
     
    本邦では逆流性食道炎罹患率とHelicobactor pylori感染率について逆相関を示唆する報告が多いが,咽喉頭異常感,慢性咳嗽,嗄声などの咽喉頭酸逆流症状を訴える患者におけるH.pylori感染率についての報告はまだない.われわれは咽喉頭酸逆流症状にて北海道大学病院耳鼻咽喉科を受診した患者のうち血清H.pylori抗体を測定し得た67例を対象としてH.pylori抗体陽性率,咽喉頭酸逆流症状,酸抑制治療への反応性との関連を検討した.対象患者群の血清抗H.pylori抗体の陽性率は61.2%であり,H.pylori抗体陽性群と陰性群の間には,患者背景,治療前の自覚症状の各項目において有意差を認めなかった.Kaplan-Meier解析により咽喉頭症状改善率についてはH.pylori抗体陽性群は陰性群に比べ酸抑制治療に対する反応が良好であるが,食道症状については両群間に有意差を認めないことが示された(著者抄録)
  • 鼻副鼻腔乳頭腫T3症例に対する内視鏡下手術の検討
    及川 敬太, 古田 康, 中丸 裕爾, 本間 明宏, 折舘 伸彦, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 109 (4) 410 - 410 0030-6622 2006/04 [Not refereed][Not invited]
  • 古田 康, 及川 敬太, 中丸 裕爾, 本間 明宏, 折舘 伸彦, 福田 諭
    頭頸部外科 (NPO)日本頭頸部外科学会 15 (3) 195 - 201 1349-581X 2006/02 [Not refereed][Not invited]
     
    著者らは術前MRIにより伸展範囲を評価して術式を選択している.そこで,この方法により治療を行った20例の術式選択についてまとめた.またKrouseのstaging systemの問題点について考察した.男性13例,女性7例を対象にした結果,T1は再発例の1例,T2と診断された8例中6例で,内視鏡下副鼻腔手術(ESS)を施行した.T3と診断された10例中5例は,lateral rhinotomyアプローチによるmedial maxillectomyを選択した.T4と診断されたのは,22年前に初回手術を行った後の再発例の1例だけであった.術後5ヵ月から40ヵ月の経過観察をし,T1からT3症例においては再発は認められていない.T4症例は,放射線照射により縮小したが,照射後7ヵ月が経過し腫瘍が増大しつつある
  • Masanori Maeda, Shiro Maguchi, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda
    Journal of Otolaryngology of Japan 109 (5) 455 - 460 0030-6622 2006 [Refereed][Not invited]
     
    BACKGROUND: Birch pollen is the major pollen allergen in Hokkaido, Northern Japan. We reported a Betula masting model based on the resource budget model hypothesis. In addition to weather conditions, cumulative hours of sunlight and mean temperature from May to July of the previous year, this model used the amount of annual pollen dispersed in previous and penultimate years as a parameter based on data from 1990 to 2000. OBJECTIVE: We compared the predicted and observed amount of pollen dispersed for 3 years from 2001 to 2003 and evaluated the usefulness of each parameter in this model. METHODS: Birch pollen was measured using the Durham sampler at the Hokkaido University Graduate School of Medicine Research Institute in Sapporo. RESULTS: The difference between predicted and observed amounts of pollen dispersal was about 200-500 grains cm-2. The annual pollen dispersed in the previous year was found to be the most useful parameter. CONCLUSION: This model is useful in predicting whether the amount of birch pollen will be less than average, about average, more than average, or much more than average.
  • F Suzuki, N Oridate, A Homma, Y Nakamaru, T Nagahashi, K Yagi, S Yamaguchi, Y Furuta, S Fukuda
    ONCOLOGY REPORTS 14 (6) 1493 - 1498 1021-335X 2005/12 [Refereed][Not invited]
     
    The purpose of this study was to discover whether S100A2 expression is associated with late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral cavity. We retrospectively investigated the clinicopathological parameters and S100A2 expression in surgical specimens taken from 52 patients with T1-2N0M0 invasive squamous cell carcinoma of the oral cavity (OSCC) who had not undergone elective neck dissection or irradiation to the neck. All of the clinic opathological factors and S100A2 expression were compared in terms of late cervical metastasis. In univariate analysis, late cervical metastasis correlated with poor overall survival. A higher rate of late cervical metastasis was observed in patients with S100A2-negative tumors than those with S100A2-positive tumors. Multivariate analysis on late cervical metastasis revealed that S100A2 expression was demonstrated to be the only independent factor for late cervical metastasis. Our results indicate that patients with stage I or 11 invasive OSCC without SIOOA2 expression should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is being considered.
  • E Higuchi, Y Nakamaru, R Ohwatari, T Sakashita, Y Mesuda, A Homma, Y Furuta, S Fukuda
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY 133 (4) 647 - 647 0194-5998 2005/10 [Refereed][Not invited]
  • Y Nakamaru, S Maguchi, N Oridate, D Takagi, Y Furuta, S Fukuda
    AURIS NASUS LARYNX 32 (3) 251 - 256 0385-8146 2005/09 [Refereed][Not invited]
     
    Objective: The objective was to ascertain the prevalence of Plantago lanceolata (English plantain) pollinosis in Japan. Methods: A total of 160 patients with allergic rhinitis were examined at the Hokkaido University Hospital Otolaryngology Clinic between January 2002 and December 2003. We investigated the frequency of P. lanceolata antigen-specific immunoglobulin E (IgE) antibody-positive serum using the radioallergosorbent test (RAST), the P. lanceolata pollen counts in the Sapporo area and the clinical symptoms of patients with allergic rhinitis caused by this pollen. Results: P. lanceolata pollen was dispersed throughout the Sapporo area from mid-May to early September, peaking in the latter half of May. The airborne pollen count showed little variation between years. The P lanceolata RAST-positive rate was 12.8%, which was close to those for ragweed and sagebrush. All subjects showed overlapping antigen sensitization, that is, none displayed sensitization (by RAST) exclusively to P. lanceolata. The onset of subjective symptoms peaked in June and the symptoms worsened from April to October. Conclusion: P. lanceolata was dispersed over a long period, from mid-May to early September. The P. lanceolata RAST-positive rate (12.8%) was similar to those for sagebrush and ragweed, which are dispersed during the fall. These results suggest that P lanceolata is an important causative agent of pollinosis in Japan. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
  • Y Nakamaru, N Oridate, J Nishihira, D Takagi, Y Furuta, S Fukuda
    CYTOKINE 31 (2) 103 - 108 1043-4666 2005/07 [Refereed][Not invited]
     
    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine whose expression has been found to be critical to the generation of antigen-specific immune responses. Recent studies suggested that MIF played a role in the initiation and maintenance of allergic diseases. To elucidate MIF's role in the pathogenesis of allergic rhinitis (AR), we sensitized MIF-deficient gene knockout (KO) mice and wild-type (WT) mice intraperitoneally with ovalbumin (OVA) and compared their clinical symptoms and allergic responses after intranasal challenge. Antigen-induced nasal symptoms were significantly reduced in MIF KO mice compared to WT mice. Histological examination of nasal mucosa showed that the number of infiltrating eosinophils in MIF KO mice was significantly lower than that in WT mice (P < 0.05). The concentration of TNF-alpha. in nasal mucosa was also significantly lower in MIF KO mice than in WT mice (P < 0.05). We have demonstrated that the absence of MIF affects several aspects of experimental AR. One mechanism by which these effects might be mediated is by down regulating TNF-alpha. The block of allergic inflammation in MIF KO mice suggests that MIF may play a role in the allergic response. (c) 2005 Elsevier Ltd. All rights reserved.
  • 鼻副鼻腔内反性乳頭腫におけるstage別治療成績の検討
    及川 敬太, 古田 康, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 108 (4) 457 - 457 0030-6622 2005/04 [Not refereed][Not invited]
  • FUJIWARA Keishi, FURUTA Yasushi, NAKAMARU Yuji, AIZAWA Hiroshi, SAWAMURA Yutaka, FUKUDA Satoshi
    頭頸部外科 = Journal of Japan Society for Head and Neck Surgery (NPO)日本頭頸部外科学会 14 (3) 247 - 251 1349-581X 2005/02/05 [Not refereed][Not invited]
     
    63歳男.左内眼角部の腫脹を指摘された.頭部CTで前頭洞内に充満する軟部組織陰影と前頭洞後壁の骨の菲薄化を認め,MRI所見と併せて前頭洞嚢胞と診断した.内視鏡下両鼻内前頭洞開放術および鼻中隔矯正術を施行し術後経過良好であったが,退院後より頭痛,膿性鼻漏が出現した.前頭洞後壁に肉芽の存在を確認し,画像所見より硬膜炎を合併した急性前頭洞炎と診断した.鼻漏の細菌培養でMRSAを認め,抗生剤投与や鼻洗浄などの保存的治療で頭痛は改善したが,鼻漏は持続した.肉芽除去が必要であったが,鼻内からは困難と考え,開頭による除去術を選択し,前頭開頭による肉芽のデブリードメンおよびgaleo-pericranial flap(GF)による前頭蓋底再建術を施行した.術後経過は良好で,細菌培養でMRSAは認められず,6ヵ月後に施行した頭部MRIガドリニウム造影ではGFで前頭洞内が充填され,硬膜炎が消退している像を認めた.1年9ヵ月経過し,炎症の再燃はない
  • F Suzuki, Y Nakamaru, N Oridate, A Homma, T Nagahashi, S Yamaguchi, J Nishihira, Y Furuta, S Fukuda
    ONCOLOGY REPORTS 13 (1) 59 - 64 1021-335X 2005/01 [Refereed][Not invited]
     
    The macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine as well as a tumor growth regulator. Although the positive and negative effects of the MIF on tumor cell growth have been reported, the exact role of the MIF in tumorigenesis remains ambiguous. We examined the expression of the MIF protein in tumor specimens obtained from 50 head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m(2)), 4-7 times every week; a total radiation therapy dose of 65-75 Gy over 6.5-7.5 weeks, and determined whether the MIF level is related to clinical outcomes of these patients. Immunostaining with an MIF specific antibody was performed in formalin-fixed, paraffin-embedded specimens. The MIF protein was expressed to various extent in the tumor tissue specimens from the HNSCC patients. Prognostic analysis using the Kaplan-Meier method with regard to the MIF expression revealed that the patients with the MIF-negative tumors had a worse prognosis when compared to those with the MIF expression. The results of this study suggest that the intratumoral MIF expression has a prognostic value in HNSCC patients administered concurrent chemoradiotherapy.
  • 中丸 裕爾, 福田 諭, 伊藤 一洋, バーンズピーター
    アレルギー 一般社団法人 日本アレルギー学会 54 (8) 1098 - 1098 2005
  • 本間 明宏, 中丸 裕爾, 佐伯 昌彦, 福田 諭
    頭頸部外科 (NPO)日本頭頸部外科学会 14 (2) 109 - 113 1349-581X 2004/10 [Not refereed][Not invited]
     
    25歳男.右鼻閉が出現し,時々鼻出血があった.ファイバースコープで上咽頭右側に表面平滑,毛細血管の豊富な拍動する腫瘤を認めた.CTでも上咽頭右側から鼻腔後方に造影CTで強く増強される陰影を認めた.MRIではT1強調画像で筋肉と同等の信号,T2強調画像で脳実質と同等の信号を呈していた.診断は上咽頭血管線維腫で,腫瘤が小さいため鼻内内視鏡下に摘出し,術前には塞栓術を行った.手術時にはナビゲーションを用い,出血量が少なく解剖学的位置を正確に確認し摘出できた
  • D Takagi, K Iwabuchi, C Iwabuchi, Y Nakamaru, S Maguchi, R Ohwatari, Y Furuta, S Fukuda, S Joyce, K Onoe
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 136 (3) 591 - 600 0009-9104 2004/06 [Refereed][Not invited]
     
    The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) Valpha24(+)Vbeta11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) Valpha24(+)Vbeta11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.
  • D Takagi, Y Nakamaru, S Maguchi, Y Furuta, S Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 113 (5) 388 - 393 0003-4894 2004/05 [Refereed][Not invited]
     
    In this study, we analyzed the clinical features, diagnostic criteria, treatment, and outcome of atypical bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). The evaluation was made by audiogram and laboratory data in 6 cases treated at Hokkaido University Hospital. We measured MPO-ANCA by enzyme-linked immunosorbent assay; the result was positive in all cases. The hearing loss developed bilaterally and progressed to total deafness within several weeks. The onset of hearing loss was not simultaneous in the 2 ears. Methylprednisolone pulse therapy was effective in 9 ears. Three ears showed no improvement; 2 of the 3 ears had already exhibited total deafness at the first visit. After the treatment, the titer of MPO-ANCA decreased in all patients. The level of MPO-ANCA should be tested in patients with bilateral progressive hearing loss of unknown origin and can be used as a marker of the disease's activity.
  • 鼻副鼻腔乳頭腫の術式選択におけるstaging systemの検討
    及川 敬太, 古田 康, 永橋 立望, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 107 (4) 399 - 399 0030-6622 2004/04 [Not refereed][Not invited]
  • Y Nakamaru, D Takagi, N Oridate, Y Furuta, J Nishihira, S Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY 113 (3) 205 - 209 0003-4894 2004/03 [Refereed][Not invited]
     
    The aim of this study was to assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of allergic rhinitis (AR). Serum MIF concentrations were measured by a specific enzyme-linked inummosorbent assay. In order to elucidate the cellular source of MIF, we performed double immunostaining of biopsy specimens of the nasal mucous membrane with markers for MIF and for inflammatory cells. The mean MIF level in sera from patients with AR was significantly higher than that in sera from healthy controls. Moreover, the levels were significantly correlated with the severity of the clinical symptoms. The majority of the MIF-positive cells at the site of allergic inflammation were eosinophils. These data suggest that MIF plays a role in the initiation and maintenance of AR. Eosinophils formed the largest population of MIF-producing cells; this finding suggests that they may be a major source of MIF at inflammatory sites in atopic disease.
  • M Kashiwamura, E Chida, M Matsumura, Y Nakamaru, N Suda, Y Terayama, S Fukuda
    OTOLOGY & NEUROTOLOGY 25 (1) 9 - 13 1531-7129 2004/01 [Refereed][Not invited]
     
    Objective: To determine the efficacy of Burow's solution as an otologic preparation for the treatment of chronic ear infection. Study Design: Two studies were included: 1) a prospective clinical study and 2) a laboratory study on antibacterial and antifungal effects. Setting: A private otology practice and a laboratory study. Patients: Fifty-eight patients with refractory otorrhea. Intervention: Diagnosis by otoscopy, audiometry, and bacteriology. Methods: Burow's solution was mixed in solutions with four organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, Candida albicans, and Aspergillus. Soon after Burow's solution was mixed in the solutions with organisms. and 5, 10, and 20 minutes thereafter, the mixtures were cultured on agars. The numbers of the bacterial or fungal colonies were counted to evaluate the effect of Burow's solution. Main Outcome Measures: Changes in the clinical findings of the ears, the symptom of otorrhea, and side effects were assessed. Results: Thirty-five (70%) of the 50 ears assessed were "cured" and 10 (20%) ears assessed were "improved." No significant side effect was observed. Regarding the laboratory study, the four organisms disappeared within 20 minutes after Burow's solution was mixed. Conclusion: Burow's solution was considered to be an effective otologic preparation.
  • 喉頭全摘に至った喉頭帯状疱疹の一例
    樋口 榮作, 中丸 裕爾, 大渡 隆一郎, 坂下 智博, 目須田 康, 本間 明宏, 古田 康, 福田 諭
    耳鼻咽喉科免疫アレルギー 日本耳鼻咽喉科免疫アレルギー学会 21 (2) 80 - 82 0913-0691 2003/06 [Not refereed][Not invited]
     
    73歳男.咽頭痛が出現した.炎症所見と腎機能障害も認めた.造影CT所見では,左披裂部の腫脹と両頸部リンパ節の腫脹が認められた.病理組織所見では,一部の扁平上皮に中等度から高度の異型が認められた.咽頭痛が強く,喉頭もしくは下咽頭の悪性腫瘍を疑った.喉頭浮腫によると,思われる呼吸困難が出現したため,緊急気管切開術を行った.喘息発作,誤嚥を発症し,全身状態が悪化した.喉頭直達鏡下生検術を行った.臨床所見と経過,検査結果から,一側性第IX,X,XI脳神経麻痺を伴う喉頭帯状疱疹と確定診断した.気管食道分離による誤嚥の防止を目的とした喉頭全摘術を行った.術後経過は良好で退院した.その後現在まで経過良好である
  • 頭頸部扁平上皮癌の放射線化学療法施行例におけるマクロファージ遊走阻止因子の発現の検討
    鈴木 章之, 中丸 裕爾, 本間 明宏, 永橋 立望, 折館 伸彦, 古田 康, 福田 諭
    頭頸部腫瘍 (一社)日本頭頸部癌学会 29 (2) 363 - 363 0911-4335 2003/05 [Not refereed][Not invited]
  • 鼻副鼻腔inverted papilloma再発例の検討
    及川 敬太, 古田 康, 永橋 立望, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 106 (4) 393 - 393 0030-6622 2003/04 [Not refereed][Not invited]
  • Yuji Nakamaru, Dai Takagi, Masanori Maeda, Yasushi Furuta, Satoshi Fukuda, Shiroh Maguchi
    Journal of Otolaryngology of Japan 106 (3) 185 - 191 0030-6622 2003 [Refereed][Not invited]
     
    Introduction: Relapsing polychondritis (RP) manifests as an inflammation of cartilaginous structures throughout the body. Since RP affects cartilage tissues and proteoglycan-rich structures, symptoms appear in the ear, nose, eye, joints, and respiratory system. Otolaryngologists are frequently involved in RP's initial diagnosis, since it is likely to affect the head and neck regions. The etiology of RP remains unknown and it is relatively uncommon, so appropriate treatment remains to be determined. We studied the clinical course and treatment response. Methods: We studied clinical courses in 12 cases of RP treated at our hospital in the 11 years from 1991 to 2001. Results: In 11 of the 12 cases, conventional steroid therapy was implemented. Five required steroid pulse therapy, and 7 immunosuppressive drugs to control the disease. Strong initial therapy such as steroid pulse therapy plus immunosuppressive drugs suppressed inflammation and decreased its relapse in severe RP patients. One patient could be controlled only with nonsteroidal antiinflammatory drugs. Side effects such as cataracts and diabetes from steroid therapy or pancytopenia from Dapson were found in some patients. All 12 are alive at present. Six were subsequently released from steroid therapy. Anti-type II collagen antibody was not useful as an indicator for treatment but helpful as one of a complementary factors for diagnosis. Conclusion: Manifestations of RP are sometimes self-limited, but in most cases, inflammation is recurrent, gradually worsening and finally becoming life-threatening. It is difficult to determine the severity of RP and choose appropriate treatment in its initial stage. Because severe RP cannot be controlled with conventional steroid therapy, strong therapy is indicated in initial treatment if patients have serious symptoms.
  • D Takagi, Y Nakamaru, S Maguchi, Y Furuta, S Fukuda
    LARYNGOSCOPE 112 (9) 1684 - 1690 0023-852X 2002/09 [Refereed][Not invited]
     
    Objective/Hypothesis: To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegener's granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan. Study Design: We retrospectively reviewed 15 cases of WG with ear involvement. Methods: Twenty-five patients with WG were treated at Hokkaido University Graduate School of Medicine between 1992 and 2001. Fifteen of these patients had otologic symptoms. We evaluated the clinical course, method of therapy, and outcomes in all cases. Diagnosis of WG was made when the patients had clinical findings and a positive titer of cytoplasmic pattern antineutrophil cytoplasmic antibodies (c-ANCA), or when there were clear histologic findings. We also present three case reports. Results: In 15 cases, the most frequent finding was chronic otitis media. Sensorineural hearing loss was present in 2 patients. In 7 patients whose otologic manifestations were the primary involvement of WG, all were confirmed positive for c-ANCA and were treated with glucocorticoids and immunosuppressive drugs. Three patients who could be treated within 1 month of symptom onset showed marked improvement. Conclusions: In localized cases, biopsy specimens are often small, and it is frequently difficult to make a histologic diagnosis. The prognosis for hearing was poor when appropriate treatment was not given in the early stages of the disease. Therefore, WG should be included in the differential diagnosis in cases of atypical inflammatory states of the ear. Early diagnosis and appropriate treatment are important to prevent irreversible changes in the middle ear and inner ear.
  • T Sugaya, A Ishizu, H Ikeda, Y Nakamaru, K Fugo, M Higuchi, H Yamazaki, K Imai, T Yoshiki
    EXPERIMENTAL AND MOLECULAR PATHOLOGY 72 (1) 56 - 61 0014-4800 2002/02 [Refereed][Not invited]
     
    Human T cell leukemia virus type I (HTLV-I) env-pX transgenic rat, (env-pX rats) develop chronic destructive arthritis resembling rheumatoid arthritis in humans. Immunological characteristics were compared with those of collagen-induced arthritis (CIA). Rheumatoid factor was present in some env-pX rats regardless of the development of arthritis, but not in nontransgenic rats with CIA. All rats with CIA produced anti-type It collagen (IIC) antibody, but never so in env-pX rats with naturally occurring arthritis. Although expansions of oligoclonal T cells were evident in the affected joints, no particular clone was shown to infiltrate into the arthritic lesions in env-pX rats. In contrast to CIA. in which clonal expansions of IIC-specific T cells are implicated, locally expanded T cell clones against various antigens of the joints may play pathogenetic roles in the arthritis seen in env-pX rats. However, complementarity-determining region 3 of the TCR Vbeta gene of T cells accumulating at the affected joints in env-pX rats contained the GGA amino acid sequence, which was reported to be a conserved motif in HTLV-I env-pX transgenic mice with arthritis. These findings suggest that common antigens) might be recognized by T cells accumulating at sites of arthritis in both transgenic rats and mice. (C) Elsevier Science.
  • Y Nakamaru, S Fukuda, S Maguchi, D Takagi, Y Inuyama
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY 126 (2) 204 - 205 0194-5998 2002/02 [Refereed][Not invited]
  • Y Nakamaru, S Fukuda, S Miyashita, M Ohashi
    AURIS NASUS LARYNX 29 (1) 55 - 57 0385-8146 2002/01 [Refereed][Not invited]
     
    Objective: To examine whether the styloid process can be imaged by three-dimensional Computer tomography reconstruction (3-DCT) distinctly enough to be used for diagnosis, and whether the image findings are explanatory of the symptoms. Methods: We performed 3-DCT in four patients suspected to have elongated styloid process in Our hospital. The apparatus we used was X-vigor (Toshiba), and the processing software was X-tension; the slicing thickness was 1.0 min and the shifting speed of CT table was 1.0 mm per rotation. One hundred and twenty images were reconstructed for a view. Results: In all cases. the 3-DCT showed the exact full length or the styloid process. Two cases were diagnosed as elongation of the styloid process by 3-DCT and their image findings were explanatory of the symptoms. In other two cases, the 3-DCT showed no difference between the right and the left styloid processes, and thus the diagnosis of elongation of the styloid process had to be excluded. Conclusion: We suggest that 3-DCT is useful for the diagnosis, explanation to patients and selection of treatment in some cases of elongated styloid process, but further study in more cases is required before we can fully confirm the utility. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • M Takizawa, S Maguchi, Y Nakamaru, Y Miyatake, S Fukuda, Y Inuyama
    AURIS NASUS LARYNX 28 S59 - S62 0385-8146 2001/05 [Refereed][Not invited]
     
    Objective: The adhesion of neutrophils to the vascular endothelial cells appears to be important for the pathogenesis of vasculitis in Wegener's granulomatosis (WG). To determine the pathological significance of the neutrophil adhesion, we have examined and evaluated the relationships between the levels of adhesion molecules and proteinase-3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA), and between the levels of TNF-a and disease activities in WG. Methods: sELAM-1 and sICAM-1 in sera from WG and healthy donors were detected by ELISA. SLe(x) and LFA-1 on neutrophils were detected by flow cytometry. Results: The level of sICAM-1 was significantly higher in active WG than in inactive WG, tending to reflect individual disease activities. There was no difference in the level of sELAM-1 between WG patients and healthy donors. Conclusion: Our study suggests that the adhesion of neutrophils to the vascular endothelium is significant for the pathogenesis of the vasculitis in WG. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
  • 両側性ムンプス難聴の1例
    水町 貴諭, 福田 諭, 千田 英二, 中丸 裕爾, 黒田 努, 犬山 征夫, 間口 四郎
    日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 104 (1増刊) 77 - 77 0030-6622 2001/01 [Not refereed][Not invited]
  • Y Nakamaru, A Ishizu, H Ikeda, T Sugaya, K Fugo, M Higuchi, H Yamazaki, T Yoshiki
    PATHOBIOLOGY 69 (1) 11 - 18 1015-2008 2001 [Refereed][Not invited]
     
    We have earlier reported that diverse collagen vascular diseases, including arthritis, arteritis, thrombosis, myocarditis, myositis, sialo-/dacryoadenitis and dermatitis develop with the advent of autoantibodies in transgenic rats carrying the LTR-env-pX gene of human T lymphocyte virus type I (LTR-env-pX rats). To clarify the pathogenesis of these collagen vascular diseases, immunological features of LTR-env-pX rats were examined. In LTR-env-pX rats affected with these diseases, expression of CD80/86 on both tissue-infiltrating and peripheral T cells increased, compared with findings in non-transgenic rats with experimental inflammatory diseases. CD80/86 was also upregulated on peripheral T cells in LTR-env-pX rats prior to the development of diseases. Lymphocytes from LTR-env-pX rats showed an increase in autologous proliferation and were hyperreactive against several mitogens, including concanavalin A, immobilized anti-CD3 antibodies, and superantigens in vitro. Anti gen-specific immune response was also enhanced in LTR-env-pX rats. The collective evidence indicates that lymphocytes of LTR-env-pX rats constitutively express surface molecules related to T cell activation and are immunologically hyperresponsive. Bone marrow cell transfer from LTR-env-pX rats to lethally irradiated non-transgenic rats revealed that these immunologically pre-activated and hyperresponsive lymphocytes play a critical role in the pathogenesis of several collagen vascular diseases, especially of dermatitis in LTR-env-pX rats. Copyright (C) 2001 S. Karger AG, Basel.
  • T Yoshiki, H Ikeda, U Tomaru, O Ohya, T Kasai, I Yamashita, K Morita, H Yamazaki, A Ishizu, Y Nakamaru, K Kikuchi, S Tanaka, A Wakisaka
    Leukemia 11 Suppl 3 245 - 6 0887-6924 1997/04 
    To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.
  • Yamazaki H, Ikeda H, Ishizu A, Nakamaru Y, Sugaya T, Kikuchi K, Yamada S, Wakisaka A, Kasai N, Koike T, Hatanaka M, Yoshiki T
    Int Immunol 9 (2) 339 - 346 0953-8178 1997/02 [Refereed][Not invited]
  • Y. Nakamaru, S. Maguchi, M. Takizawa, S. Fukuda, Y. Inuyama
    Rhinology 34 (3) 163 - 165 0300-0729 1996/09 [Refereed][Not invited]
     
    The present study examined the association between various human leukocyte antigens (HLA) and cytoplasmic-antineutrophil cytoplasmic antibody (cANCA)-positive Wegener's granulomatosis (WG) in Japanese subjects to determine whether HLA antigens are involved in the pathogenesis of this disease. The study involved 16 subjects with cANCA-positive WG treated in our department. HLA-typing of the lymphocytes was performed using a lymphocyte microcytotoxicity assay. Of the subjects with cANCA-positive WG, 62.5% (10/16) were positive for HLA-DR9, as compared to 26% of the healthy control subjects. This HLA-DR9 elevation was statistically significant (p < 0.01, Pc < 0.05) were also noted a weaker association between HLA-B55 and cANCA-positive WG (p < 0.05). The results indicate that an association may exist between certain HLA-class allotypes and WG.
  • MAGUCHI Shiroh, TAKIZAWA Masahiko, MIYATAKE Yukiko, NAKAMARU Yuuji, FUKUDA Satoshi, INUYAMA Yukio
    Nippon Jibiinkoka Gakkai Kaiho The Oto-Rhino-Laryngological Society of Japan, Inc. 98 (6) 974 - 983 0030-6622 1995/06/20 
    We assessed the clinical significance of cANCA in relation to the diagnosis and follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the ELISA kit for the detection of cANCA.
    The NephroScholor C-ANC test for cANCA was revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly less sensitive than the indirect immunofluorescence assay using human neutrophils, which has been in widespread use for the detection of ANCAs.
    With NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed quantitatively. When conventional immunosuppressive therapy with prednisolone and cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer decreased, and thus it also seemed useful for the follow-up of Wegener's granulomatosis patients. However, a rising ANCA titer during the course of the disease was not always correlated with the occurrence of a relapse as previously reported. Based on these findings, it is not recommended that treatment be changed immediately because of elevation of the ANCA titer alone, and it never seemed too late to increase immunosuppressive therapy, even after a clinical exacerbation was observed.
    Several treatments other than the conventional immunosuppressive therapy have often been applied for our patients, especially in the limited type of this disease, and these treatments, including sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and cyclophosphamide alone, have often been useful. We conclude that the choice of therapy must depend on the severity or the condition of the individual patient, and this therapeutic policy should reduce unnecessary side effects of potentially toxic drugs.
  • KASHIWAMURA Masaaki, YAMADA Kazuyuki, HIYAMA Shigeki, FUKUDA Satoshi, MAGUCHI Shirou, YORITA Akiharu, NAKAMARU Yuuji, INUYAMA Yukio
    Pract.Otol. (Kyoto) The Society of Practical Otolaryngology 88 (2) 219 - 224 0032-6313 1995/02/01 
    Mediastinal metastasis of or invasion by laryngeal carcinoma is not common. If it is not found in the early stage and treated, it causes miserable symptoms such as tracheal stenosis or intratrachal hemorrhage. We treated three patients with laryngeal carcinoma with mediastinal metastasis or invasion. The primary lesion was subglottic in two and glottic in one. The clinical course and some examination results suggested that two patients had metastases and one had direct invasion.
    We concluded that patients with laryngeal cancer, especially subglottic, should be examined for mediastinal, as well as cervical lymphnode metastasis, as soon as possible. We otolaryngologists should be able to find mediastinal lesions early using examinations such as CT scans.
  • 中丸 裕爾, 本間 明宏, 飯塚 桂司
    耳鼻咽喉科・頭頸部外科 (株)医学書院 65 (9) 745 - 748 0914-3491 1993/09 [Not refereed][Not invited]
     
    6年間に受診した鼻骨骨折症例について,成因と治療内容に対する満足度等につきアンケート調査を行った。鼻骨骨折の成因では,暴行,交通事故,スポーツの順に多く,それぞれの項目につき更に詳しく成因を検討した。治療に対するアンケートでは,整復後の外観に関しては,83%の患者が満足しているが,約1/3の患者が鼻閉感を訴えた。固定に関しては,内固定に関する不満が多く,固定期間は4日,外固定は7日程度が苦痛を与えないという面ではよい
  • Yuji Nakamaru, Keiji Iizuka, Akihiro Honma, Yutaka Yoshida
    Practica Oto-Rhino-Laryngologica 耳鼻咽喉科臨床学会 86 (12) 1747 - 1751 0032-6313 1993 [Not refereed][Not invited]
     
    A 72-year-old woman had noted left submandibular swelling for 7 years. On examination a 5 × 5 cm smooth, hard, fixed, painless mass was palpable in the left submandibular area. CT scan showed a circumscribed, isodense mass near the bifurcation of the carotid artery. Extirpation of the tumor was performed. The pathological diagnosis was intravascular papillary endothelial hyperplasia. The postoperative course was good, and the patient remains free of disease more than 5 months after surgery. Intravascular papillary endothelial hyperplasia is characterized by intravascular endothelial proliferation that resembles angiosarcoma. This disease seems to be the result of a peculiar process of thrombus undergoing organization. The prognosis is good, and the treatment is usually total extirpation of the tumor. © 1993, The Society of Practical Otolaryngology. All rights reserved.

MISC

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 中丸 裕爾
     
    好酸球性副鼻腔炎は難治の副鼻腔炎で中高年において発症する。鼻腔粘膜上皮の脆弱化が発症の一因とされているが、詳細は不明である。申請者らは老化の保護因子であるSIRT1蛋白を研究し、COPDなどの加齢に伴い発症する炎症性疾患においてSIRT１蛋白の減少が、疾患の病態を形成することを明らかにしてきた。鼻腔粘膜組織において上皮にSIRT1が強発現していることを見出したため本研究の着想にいたった。 本年度までに、①好酸球性副鼻腔炎炎症局所におけるSIRT1発現、②SIRT1による鼻粘膜上皮バリア機能の変化を評価した。 まず好酸球性副鼻腔炎炎症局所のSIRT1の発現を免疫組織化学染色で確認した。1. 手術時に摘出した好酸球性副鼻腔炎患者鈎状突起粘膜および鼻茸組織および対照として肥厚性鼻炎にて手術した下鼻甲介粘膜より凍結切片を作成。2. 抗SIRT1抗体を用い、切片を染色。ABC法にて発色して観察。3. 好酸球性副鼻腔炎炎症局所におけるSIRT1の局在を検討した。結果、下鼻甲介粘膜におけるSIRT1の発現は、上皮細胞に多く認められた。特に上皮の基底層に強い発現を認めた。 次に上皮バリア機能を検討するために、鼻腔粘膜上皮の経上皮バリア機能におけるSIRT1の役割を検討した。手術時に摘出した下甲介粘膜より鼻腔上皮細胞を単離し、Transwell上層に散布し、Air Liquid Interface（ALI）法で培養した。21日培養後、SIRT1の抑制剤(resveratrol)あるいは促進剤(splitomicin)を添加し経上皮電気抵抗を測定した。Covid19パンデミックのため手術が減少しており患者数が集まらず現在検討中である。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2017/03 
    Author : Takagi Dai
     
    To analize the role of NKT cells and HDAC activity on eosinophilic chronic rhinosinusitis, we collected PBMC form patients. We investigated HDAC activity using HDAC activity kit, and found that HDAC activity was significantly decreased in patients of eosinophilic chronic rhinosinusitis. Furthermore, we investigated eosinophilic chronic rhinosinusitis patients before and after surgery, and found that Blood eosinophil count was significantly reduced after surgery in the eosinophilic chronic rhinosinusitis group. We also found that serum IL-5 tended to be reduced after surgery in eosinophilic chronic rhinosinusitis patients.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2015 -2017 
    Author : Nakamaru Yuji
     
    To elucidate histone deacetylase for production of TSLP in patients with allergic rhinitis we used Beas-2B cells. After those cells were confluent, the inhibitor of histone deacetylase was added. Thirty minutes after the inhibitor was added, we stimulated the cells with ODN2006. Twenty four hours later, those cells were collected and the amout of TSLP mRNA was evaluated. We found that the inhibitor of histone deacetylase increased the amount of TSLP with dose-dependent manner. On the other hand,the activator of histone deacetylase decleased the amount of TSLP with dose-dependent manner.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012 -2014 
    Author : NAKAMARU Yuji
     
    In this study, we compared IL-33 expression at the inferior turbinate of the control and patients with allergic rhinisitis. IL-33 expression of the allergic rhinitis patients were up-regulated than those of the control. We next compared SIRT1 expressions of the inferior tubinates between the control and allergic rhinitis patients. The SIRT1 expressions of the allergic patients significantly lower than those of the controls.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2011 
    Author : NAKAMARU Yuji
     
    To investigate the role of SIRT1 for the production of IL-4 in human mast cell, we used activator and inhibitor of SIRT1. Cells treated with SIRT1 activator decreased IL-4 production. On the other hand, the SITR1 inhibitor increased IL-4 production in human mast cells. The SIRT1 protein thought to be negatively modulate IL-4 production in human mast cell.
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2007 -2008 
    Author : Yuji NAKAMARU
     
    ラット肥満細胞(RBL-2H3細胞)をDNP特異的IgEと培養し、ヒストン脱アセチル化酵素阻害剤(Tricostatin A : TSA)を加え、NP-KLH(抗原)を反応させ培養後、細胞を回収した。RNAを採取し、逆転写後real time PCRにてTh2型サイトカイン(IL-4, IL-5)mRNA量を測定した。結果であるが、TSAを添加した細胞ではTSAの濃度依存性にIL-4, IL-5ともにmRNAの産生量が増加した。また、抗原刺激後の培養上清中の蛋白をELISA法にて測定すると、TSAによる肥満細胞からのIL-4の産生亢進は蛋白レベルでも確認できた。以上より、ヒストン脱アセチル化酵素はTh2型サイトカイン産生を抑制している可能性が示唆された。次に、ヒト肥満細胞株にてSIRT1の肥満細胞のTh2型サイトカイン産生に関する実験をした。TSAの代わりにSIRT1の抑制剤であるsuraminを添加した。するとsuraminの濃度依存性にIL-4の産生増加が認められた。一方SIRT1の活性化剤であるresveratorolを添加すると抗原刺激にて誘導されたIL-4の産生は抑制された。またSIRT1のsiRNAを肥満細胞に導入して遺伝子をknock downするとIL-4の産生は増加した。以上のことから、SIRT1は肥満細胞にたいしてTh2型サイトカイン産生を抑制する働きをし...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2005 -2006 
    Author : Yuji NAKAMARU
     
    To elucidate Macrophage migration inhibitory factor (MIF)'s role in the pathogenesis of allergic rhinitis (AR), we sensitized MIF-deficient gene knockout (KO) mice and wild type (WT) mice intraperitoneally with ovalbumin (OVA) and compared their clinical symptoms and allergic responses after intranasal challenge. Antigen-induced nasal symptoms were significantly reduced in MIF KO mice compared to WT mice. Histological examination of nasal mucosa showed that the number of infiltrating eosinophils in MIF KO mice was significantly lower than that in WT mice (P< 0.05). The concentration of TNF-...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2004 -2006 
    Author : Yasushi FURUTA, Hirofumi SAWA, Yuji NAKAMARU
     
    1,Patterns of herpes virus reactivation in facial nerve paralysisWe analyzed the relationship between HSV-1NZV load and onset of facial paralysis in patients with facial paralysis. The results indicate that facial paralysis can occur at various times between the early and the regression phase of HSV-1NZV reactivation, suggesting that there are variable patterns of development of facial nerve dysfunction caused by herpes virus reactivation and the progression of neuritis.2,Gene expression analysis in patients with Bell's palsyGene expression profile was analyzed in patients with Bell's palsy...
  • 文部科学省：科学研究費補助金(若手研究(B))
    Date (from‐to) : 2003 -2004 
    Author : 中丸 裕爾
     
    自然免疫と獲得免疫の橋渡しをするサイトカインであるマクロファージ遊走阻止因子(MIF)に着目し、アレルギー性鼻炎における役割について検討を行なった。この研究課題採択以前に、研究代表者はMIFがアレルギー性鼻炎患者の末梢血中で増加し、その血中濃度は患者の臨床症状と同期することを報告していた。この研究課題では次のステップとして、以下2点について明らかにすることを目的とした。1.鼻粘膜浸潤する炎症細胞のなかで、MIFを産生する細胞を同定する。2.MIFの遺伝子ノックアウトマウス(MIF KOマウス)を用いてアレルギー性鼻炎モデルマウスを作成し正常モデルマウスとアレルギー症状、好酸球浸潤、鼻粘膜中のサイトカイン濃度を比較する。1.MIF産生細胞の同定アレルギー性鼻炎患者下甲介粘膜を抗MIF抗体と炎症細胞の表面マーカー(好酸球;EPO,マクロファージ;CD68,T細胞;CD3)の2重染色にて検討した。結果MIF陽性細胞の大部分はEPOも陽性であった。以上よりアレルギー性炎症局所でのMIF産生細胞は好酸球であることが判明した。2.MIF KOマウスにおけるアレルギー性鼻炎モデルの検討MIF KOマウスにおいては野生型マウスに比べアレルギー鼻症状(くしゃみ、鼻を掻く動作)が有意に減少していた。同様に鼻粘膜に浸潤する好酸球数も有意に減少していた。鼻粘膜中のサイトカインの検討ではTNF-αの濃...

Educational Activities

Teaching Experience

  • Master's Thesis Research in Medical Sciences
    開講年度 : 2021
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • Basic Principles of Medicine
    開講年度 : 2021
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • Principles of Medicine
    開講年度 : 2021
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学 Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology
  • Dissertation Research in Medical Sciences
    開講年度 : 2021
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • Dissertation Research in Clinical Medicine
    開講年度 : 2021
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学 [Otolaryngology, Diagnosis, Treatment, Head and Neck Surgery, Otology, Equilibrium research, Rhinology, Stomato-pharyngology, Laryngology, Logopedics and Phoniatrics, Tracheoesophagology]
  • Otolaryngology
    開講年度 : 2021
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 耳鼻咽喉科、診断、治療，頭頸部外科学，耳科学、平衡科学，鼻科学，口腔咽頭科学，喉頭科学，音声言語学，気道食道科学

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