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Nakamaru Yuji

Hokkaido University Hospital Complex Clinical FacilitiesAssociate Professor

Researcher basic information

■ Degree
  • 博士(医学), 北海道大学
■ URL
researchmap URL■ Various IDs
Researcher number
  • 20344509
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 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 Field
  • Life Science, Otorhinolaryngology
■ Educational Organization

Career

■ Career
Career
  • 2008 - Jan. 2018
    Hokkaido University, 大学病院, 講師
  • 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 activity information

■ Papers
  • VEXAS syndrome with cochleovestibular involvement.
    Keishi Fujiwara; Shinya Morita; Kimiko Hoshino; Hideaki Takeda; Kento Komatsuda; Kaoru Kahata; Yuji Nakamaru; Akihiro Homma
    Auris, nasus, larynx, 53, 1, 70, 75, 18 Dec. 2025, [International Magazine]
    English, Scientific journal, We report a case of VEXAS syndrome in a 71-year-old man presenting with auricular chondritis, scleritis, hearing loss, and vestibular dysfunction. Although the clinical picture initially suggested relapsing polychondritis, hematologic findings and UBA1 variant confirmed VEXAS syndrome. Comprehensive audiovestibular testing revealed bilateral sensorineural hearing loss and global vestibular impairment. Steroid therapy led to partial improvement. This case highlights the potential for inner ear involvement in VEXAS syndrome, underscoring the importance of systematic audiovestibular evaluation and clinical awareness to differentiate it from similar conditions such as relapsing polychondritis.
  • Determinants of airway morphology in asthma: Inflammatory and noninflammatory factors.
    Kaoruko Shimizu; Naoya Tanabe; Hirokazu Kimura; Jun Miyata; Shotaro Chubachi; Yuji Nakamaru; Akira Oguma; Nobuyasu Wakazono; Kazufumi Okada; Houman Goudarzi; Ichizo Tsujino; Hironi Makira; Masaharu Nishimura; Satoshi Konno
    The journal of allergy and clinical immunology. Global, 4, 4, 100555, 100555, Nov. 2025, [International Magazine]
    English, Scientific journal, BACKGROUND: Patients with asthma may exhibit impaired airway tree morphology. The impact of difficult-to-treat traits on airway tree morphology remains unclear. OBJECTIVE: We sought to identify determinants of total airway branch count (TAC) detectable via computed tomography and explore associated blood and sputum biomarkers in nonsmokers and smokers with asthma. METHODS: Baseline computed tomography scans and pulmonary function tests (spirometry, diffusion capacity of carbon monoxide, and lung volume) were analyzed from the Hokkaido Severe Asthma Cohort (N = 190). TAC, segmental airway, visually evident mucus plugging and bronchiectasis, and parenchymal and extrapulmonary indices, such as the Lund-Mackay score, were evaluated. Relationships between TAC, difficult-to-treat traits, and blood/sputum biomarkers were analyzed using crude or multivariable regression models, adjusted for demographic factors. RESULTS: Blood or sputum eosinophilia, mucus plugs, high body mass index (BMI), asthma duration, and higher Lund-Mackay score correlated with low TAC. Low TAC was linked to airflow obstruction and heterogeneous ventilation (low alveolar volume/total lung capacity). BMI was inversely associated with TAC, independent of age, sex, smoking status, sputum eosinophil ratio, and asthma duration. The presence of bronchiectasis correlated with an increase in TAC. Sputum IL-5, IL-6, RANTES, and circulating YKL-40 (chitinase-3-like-1 protein) and leptin also inversely correlated with TAC. CONCLUSIONS: BMI, asthma duration, sinusitis, and the presence of bronchiectasis are significant determinants of airway tree morphology in asthma, alongside inflammation and mucus plugs. Both inflammatory and noninflammatory biomarkers were associated with low TAC.
  • Objective evaluation for Endoscopic Sinus Surgeries' proficiency by image analysis for postoperative 3D sinus models.
    Kaito Yamada; Masanobu Suzuki; Kou Miyaji; Kazuya Sase; Koki Ebina; Teppei Tsujita; Xiaoshuai Chen; Shunsuke Komizunai; Taku Senoo; Akira Nakazono; Ryosuke Watanabe; Shogo Kimura; Takayoshi Suzuki; Yuji Nakamaru; Kotaro Matoba; Dominik Hinder; Alexander Zhang; Alkis J Psaltis; Peter J Wormald; Atsushi Konno; Akihiro Homma
    Auris, nasus, larynx, 52, 5, 567, 574, 26 Aug. 2025, [International Magazine]
    English, Scientific journal, OBJECTIVE: Objective assessment for endoscopic sinus surgery skill proficiency is challenging, partly due to the great diversity of anatomies. Recently developed 3D-printed sinus models provide standardized anatomy with realistic tissue-feel. In this study, we developed a method to evaluate endoscopic sinus surgery skill proficiency through pre- and post-operative image analysis of CT images of dissected 3D sinus models and validated it by comparing to other surgical proficiency indices. METHODS: Forty-seven otolaryngologists performed endoscopic sinus surgery for 3D sinus models. CT images of each postoperative 3D model were taken. The region growing method, an image segmentation technique, was utilized to assess the surgical space expansion. The region of interest (ROI) was defined as the space within nasal cavity and paranasal sinuses and continuous from the anterior nostril with a width of >4.00 mm kept. The volume of ROI was estimated and compared with conventional assessment methods such as board-certification, the objective structured assessment of technical skills score, and the number of experienced surgery cases. Further, the 3D-CG images of ROI were created. The completion of surgical steps within the allocated time was evaluated based on the 3D-CG and compared with the recorded endoscopic video. RESULTS: The volume in postoperative models was 24.48±4.34 cm3 across all participants, respectively. The postoperative volume was significantly larger in board-certified participants (certified; 25.51±4.22 cm3 vs. uncertified; 22.87±4.14 cm3, p = 0.03). The volume is positively correlated to the objective structured assessment of technical skills score (r = 0.72, p < 0.01) and the number of experienced cases (r = 0.51, p = 0.01). The accuracy of the 3D-CG judgement for completion of a surgical middle meatal antrostomy, sphenoidotomy, and frontal sinusotomy were 91.3 %, 69.6 %, and 84.8 %, when compared to recorded endoscopic video, with high sensitivity and specificity. CONCLUSION: The combination of standardized 3D models and image analysis provides a simple and objective tool for the assessment of surgical skill proficiency.
  • Practical guideline for the management of allergic rhinitis in Japan 2024.
    Mitsuhiro Okano; Kimihiro Okubo; Minoru Gotoh; Mikiya Asako; Nobuo Ohta; Atsushi Kamijo; Kayoko Kawashima; Masafumi Sakashita; Daiju Sakurai; Tetsuya Terada; Yuji Nakamaru; Takechiyo Yamada; Shuji Yonekura; Aiko Oka; Marie Yamada; Tomokazu Yoshizaki
    Auris, nasus, larynx, 52, 4, 426, 441, Aug. 2025, [International Magazine]
    English, Scientific journal, The Practical Guideline for the Management of Allergic Rhinitis in Japan was first published in 1993. After the COVID-19 pandemic, the current 10th edition was published in 2024. The most recent collection of evidence from the literature, such as the sustained post-treatment effect of sublingual immunotherapy on Japanese cedar pollinosis, was added to the revised guideline, which incorporates evidence-based medicine. In this revised guideline, a diagram illustrating the pathogenesis of allergic rhinitis and the mechanisms of action of various pharmacological treatments has been added. Also included is a diagram that shows the mechanism of action of allergen immunotherapy and a more detailed description of the oral allergy syndrome. The clinical question and answer section was also revised along with the introduction of new questions, such as: Does anti-IgE antibody treatment effectively reduce the symptoms of severe seasonal allergic rhinitis? Also updated was the evidence-based step-by-step strategy for treatment.
  • The Therapeutic Effects of Systemic Corticosteroid and Immunosuppressants for New-Onset Cases and Mepolizumab for Recurrent Cases of Otitis Media Associated With Eosinophilic Granulomatosis with Polyangiitis.
    Shinya Morita; Atsushi Fukuda; Kimiko Hoshino; Yuji Nakamaru; Keishi Fujiwara; Masanobu Suzuki; Aya Honma; Akira Nakazono; Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 18 Jun. 2025, [International Magazine]
    English, Scientific journal, OBJECTIVE: The aims of this study were to evaluate the otologic features and outcomes of otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA) and validate the current treatment strategies, including systemic corticosteroid (CS) and immunosuppressants for new-onset cases and therapeutic targeting of interleukin (IL)-5 for recurrent cases. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Patients with otitis media associated with EGPA were eligible for inclusion. INTERVENTION: Systemic CS alone or a combination of systemic CS and intravenous cyclophosphamide (IVCY) was performed as induction therapy. Maintenance therapy with oral CS and immunosuppressant, such as rituximab, methotrexate, or azathioprine, was administered. Treatment with mepolizumab was performed at the time of relapse of major organ involvement in EGPA, exacerbation of asthma, and/or recurrence of ear, nose, and throat symptoms after remission induction. MAIN OUTCOME MEASURES: Air- and bone-conduction pure-tone thresholds, overall survival rate, EGPA relapse rate, and otitis media recurrence rate. RESULTS: Systemic CS-based induction therapy achieved remission in all patients with EGPA. In both the CS + IVCY and CS-alone groups, hearing thresholds in the remission and/or resolution phase were significantly better than those at initial presentation at all frequencies (p < 0.01). The 5-year estimated relapse rate of major organ involvement was 29.2%, and the 5-year estimated recurrence rate of otitis media was 43.6%. All cases of recurrent otitis media treated with mepolizumab achieved improvement in otologic symptoms and subsequent reduction in maintenance CS dose. However, half of ears with recurrent otitis media showed repeated secretion and cessation of middle ear discharge and required additional topical CS treatment during mepolizumab administration. CONCLUSIONS: Immunosuppressive treatment affords a good response to systemic manifestations as well as otitis media associated with EGPA. Meanwhile, a significant proportion of patients experienced exacerbation of otitis media during maintenance therapy. Mepolizumab might be the treatment of choice for recurrent cases.
  • Poly(I:C)刺激は鼻粘膜上皮細胞のHLA-G発現を亢進させる
    渡邉 良亮; 鈴木 正宣; 中薗 彬; 木村 将吾; 本間 あや; 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, 5回, 204, 204, 日本耳鼻咽喉科免疫アレルギー感染症学会, Apr. 2025
    Japanese
  • 発がん関連因子TRIM27の分子メカニズムに関する検討
    木村 将吾; 中丸 裕爾; 鈴木 正宣; 中薗 彬; 本間 あや; 渡邉 良亮; 本間 明宏; 畠山 鎮次
    日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 5回, 167, 167, 日本耳鼻咽喉科免疫アレルギー感染症学会, Apr. 2025
    Japanese
  • Intracellular glycogen accumulation in pyodermatitis-pyostomatitis vegetans.
    Satsuki Naruse; Ken Natsuga; Sota Itamoto; Mika Watanabe; Teruki Yanagi; Yuji Nakamaru; Hideyuki Ujiie
    The Journal of dermatology, 52, 4, e313-e315, Apr. 2025, [International Magazine]
    English
  • Post-operative vestibular function outcomes evaluated by video Head Impulse Test in patients with non-vestibular schwannoma cerebellopontine angle tumors.
    Keishi Fujiwara; Shinya Morita; Hiroaki Motegi; Shigeru Yamaguchi; Yukitomo Ishi; Kimiko Hoshino; Atsushi Fukuda; Hideaki Takeda; Yuji Nakamaru; Miki Fujimura; Akihiro Homma
    Auris, nasus, larynx, 52, 1, 50, 58, Feb. 2025, [International Magazine]
    English, Scientific journal, OBJECTIVES: To evaluate post-operative semicircular canal function in patients with non-vestibular schwannoma (VS) cerebellopontine angle (CPA) tumors by video Head Impulse Test (vHIT). METHODS: Fourteen patients with non-VS CPA tumors who underwent surgery. The gain in vestibulo-ocular reflex (VOR) was examined pre- and post-operatively for the semicircular canals in patients with non-VS CPA tumors. RESULTS: Ten of 14 patients showed semicircular canal dysfunction in one or more of the semicircular canals pre-operatively and VOR gain was significantly correlated with hearing function. Two patients showed improvement in one or more semicircular canals at 1 month after surgery compared to the pre-operative results. Significant improvements in VOR gain were observed when comparing VOR gain at 1 month and 6 months after surgery. CONCLUSIONS: Detailed evaluation of semicircular canal function was achieved by using vHIT in patients with non-VS CPA tumors. The good prognosis for vestibular function as evaluated by vHIT post-operatively was confirmed in patients with non-VS CPA tumors when compared to those in patients with VS. As improvement may occur post-operatively, surgical approaches that preserve the vestibular nerves and semicircular canals should be chosen for patients with non-VS CPA tumors, regardless of preoperative vestibular function. Even if vestibular function deteriorates immediately after surgery, it may improve over time if the nerve is preserved.
  • Surgical skill analysis using explainable AI in endoscopic sinus surgery
    Kaito Yamada; Masanobu Suzuki; Kou Miyaji; Koki Ebina; Kazuya Sase; Teppei Tsujita; Xiaoshuai Chen; Takashige Abe; Shunsuke Komizunai; Yuji Nakamaru; Taku Senoo; Akihiro Homma; Atsushi Konno
    2025 IEEE/SICE International Symposium on System Integration (SII), 287, 291, IEEE, 21 Jan. 2025, [Peer-reviewed]
    International conference proceedings
  • Motion analysis for objective evaluation of psychomotor skills in Endoscopic Sinus Surgery
    K Miyaji; M Suzuki; R Watanabe; T Suzuki; K Matoba; A Nakazono; Y Nakamaru; K Ebina; T Abe; D Hinder; A J Psaltis; P J Wormald; A Homma; A Konno
    Rhinology Journal, Stichting Nase, 01 Dec. 2024
    Scientific journal, Background: This study aims to digitalize surgical maneuvers in ESS using a motion capture system under standardized conditionsprovided by 3D printed-sinus models. Methodology: Forty-seven otolaryngologists performed ESS on 3D printed modelsmanufactured from computed tomography (CT) images of actual patients. Participants were classified to 3 groups according tothe objective structured technical skills assessment score. All surgical maneuverers performed during ESS were captured by amotion capture system. The path length, velocity, acceleration, and jerk were calculated for each surgical instrument and comparedamong the groups. Principle Component Analysis (PCA) was utilized to identify which metrics reflected surgical skill level. Inaddition, ten registrars repeated the surgical dissection. Their motion metrics were also compared between first training and therepeated training and then subjected to the PCA. Results: Several metrics such as the angular acceleration and jerk of the cuttingforceps were identified by PCA as possible indicators distinguishing the different skill levels for the ESS maneuvers. PCA analysis inthe repetitive training also found the angular metrics of the upturned-cutting forceps correlating to their skill improvement.Conclusions: Combined with the validated 3D-printed sinus models, the motion capture system provided the objective evaluationof the surgical performances of ESS.
  • Nonspecific inflammatory pseudotumor of the maxillary and temporal fossa: a study of seven cases
    Wataru Kakuguchi; Yuichi Ashikaga; Yasuhito Moritani; Shintaro Nakano; Naohiro Ogawa; Rieko Yoshitatsu; Aya Yanagawa-Matsuda; Nako Maishi; Akihiko Kudo; Nanase Okazaki; Yuji Nakamaru; Ichiro Yabe; Yoshihiro Matsuno; Yoichi Ohiro
    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 138, 4, 494, 501, Elsevier BV, Oct. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVE: Inflammatory pseudotumor (IPT) is a rare, locally aggressive, benign neoplasm of unknown etiology. Because of its aggressive clinical behavior and locally destructive or infiltrative features, it may be mistaken for a malignant tumor. Approximately 5%-44% of extrapulmonary IPT occur in the head and neck, primarily affecting the orbit. STUDY DESIGN: Between 2008 and 2021, our hospital received referrals for seven patients (three men and four women, aged 42-73 years) with pain, swelling, mass, and trismus. Computed tomography, magnetic resonance imaging, and biopsy were performed on all patients to diagnose IPT. RESULTS: Of the seven patients, four received low-dose prednisolone (PSL), one underwent surgery, and two were left untreated. The IPT disappeared in one of the two untreated cases, whereas it improved and later deteriorated in the other. The surgical patient had no recurrence. Low-dose PSL was effective in two patients; however, high-dose PSL and immunosuppressants were required in the remaining two cases owing to infiltration into each orbit or brain region. CONCLUSIONS: Low-dose PSL treatment was applicable in IPT cases affecting the maxillary to temporal fossa region, wherein symptoms did not improve without treatment. However, when low-dose PSL was ineffective, high-dose PSL and immunosuppressants were required.
  • 鼻副鼻腔粘膜悪性黒色腫におけるTRIM27の検討
    木村 将吾; 中丸 裕爾; 鈴木 正宣; 中薗 彬; 本間 あや; 渡邉 良亮; 加納 里志; 対馬 那由多; 鈴木 崇祥; 井戸川 寛志; 本間 明宏; 渡部 昌; 近藤 豪; 畠山 鎮次
    日本鼻科学会会誌, 63, 3, 336, 336, (一社)日本鼻科学会, Sep. 2024
    Japanese
  • 鼻副鼻腔粘膜悪性黒色腫におけるTRIM27の検討
    木村 将吾; 中丸 裕爾; 鈴木 正宣; 中薗 彬; 本間 あや; 渡邉 良亮; 加納 里志; 対馬 那由多; 鈴木 崇祥; 井戸川 寛志; 本間 明宏; 渡部 昌; 近藤 豪; 畠山 鎮次
    日本鼻科学会会誌, 63, 3, 336, 336, (一社)日本鼻科学会, Sep. 2024
    Japanese
  • Evaluation of Semicircular Canal Function in Relapsing Polychondritis Patients with Dizziness and Sensorineural Hearing Loss Using Video Head Impulse Test.
    Kimiko Hoshino; Keishi Fujiwara; Shinya Morita; Atsushi Fukuda; Hideaki Takeda; Yuji Nakamaru; Akihiro Homma
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 26 Aug. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVE: To evaluate semicircular canal function using video head impulse test (vHIT) in relapsing polychondritis (RP) patients presenting with dizziness and sensorineural hearing loss. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Three patients with RP underwent vHIT and hearing tests. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined, and the correlation between semicircular canal dysfunction and hearing loss was investigated. RESULTS: Of the six ears, five exhibited semicircular canal dysfunction. Among these, one ear showed dysfunction in two semicircular canals, while the remaining four ears demonstrated dysfunction in all three semicircular canals. Sensorineural hearing loss, ranging from moderate to profound, was detected by pure-tone audiometry in all six ears. Furthermore, a significant correlation was observed between VOR gain in the horizontal semicircular canal (HSC) and hearing level. CONCLUSIONS: This study demonstrated semicircular canal dysfunction in RP patients presenting with dizziness and hearing loss using vHIT. Moreover, a significant correlation was found between HSC dysfunction and the severity of hearing loss. While inner ear involvement is a key clinical symptom included in the diagnostic criteria for RP, there have been few reports evaluating vestibular dysfunction, and this is the first report on the evaluation of several cases using vHIT. Accurate assessment of vestibular function by vHIT may facilitate early diagnosis and intervention in RP, potentially improving patient outcomes.
  • Evaluation of quality of life for patients with resolved facial nerve palsy.
    Keishi Fujiwara; Shinya Morita; Atsushi Fukuda; Kimiko Hoshino; Makoto Kobayashi; Yuji Nakamaru; Yasushi Furuta; Akihiro Homma
    Auris, nasus, larynx, 51, 3, 456, 459, Jun. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVES: The quality of life (QOL) for patients with resolved facial nerve palsy has not been evaluated adequately. The objective of this study is to investigate QOL for patients with resolved facial nerve palsy. METHODS: Forty-seven patients with resolved facial nerve palsy were included and the patients' QOL was evaluated using the Facial Clinimetric Evaluation Scale (FaCE Scale). RESULTS: Twenty-two of the 47 patients (46.8%) with resolved facial nerve palsy showed impaired QOL, especially in terms of facial comfort and eye comfort. In 10 cases followed-up after the condition was judged to be resolved, the median scores for the FaCE scale at the time the condition was judged to be resolved and at the last visit were 65.5 and 72, respectively. The mean durations from the onset of the palsy to diagnosis of cure and to the last visit were 2.4 ± 1.6 and 4.3 ± 2.2 months, respectively. There was a significant improvement in QOL after the condition was judged to be resolved. CONCLUSION: There were discrepancies between QOL and facial movement as evaluated by physicians in patients in whom facial nerve palsy was resolved as in patients with non-cured facial nerve palsy. Patients' QOL continued to improve even after physicians judged the condition to be resolved and this result indicated that there were cases where improvement in QOL was delayed in comparison to improvement in facial movement.
  • Evaluation of Semicircular Canal Function Using Video Head Impulse Test in Patients With Peripheral Vestibular Disorders Without Nystagmus.
    Keishi Fujiwara; Shinya Morita; Kimiko Hoshino; Atsushi Fukuda; Hideaki Takeda; Yuji Nakamaru; Akihiro Homma
    Cureus, 16, 6, e62786, Jun. 2024, [International Magazine]
    English, Scientific journal, Objectives This study aims to evaluate semicircular canal function using video head impulse test (vHIT) in patients with peripheral vestibular disorders without nystagmus. Methods Patients who underwent vHIT were enrolled in this study, and the proportion of abnormal findings on vHIT in patients without nystagmus was investigated. In addition, the results of vestibular testing were investigated in cases in which both vHIT and caloric testing were performed in patients without nystagmus. Results Forty-six patients (23.4%) of 197 patients who had no abnormal findings on the nystagmus tests, including the gaze nystagmus test, positional nystagmus test, and positioning nystagmus test, showed dysfunction in at least one semicircular canal on vHIT. The most frequent diagnosis was vestibular schwannoma (14/46, 30.4%), and cases with bilateral vestibular dysfunction were also included (12/46, 26.1%). A disorganized pattern of catch-up saccade was observed more frequently in patients with subjective symptoms of dizziness/vertigo compared to those without subjective symptoms. Although the sensitivity of vHIT was low compared to caloric testing, vHIT could detect isolated vertical canal dysfunction not detected by caloric testing. Conclusions vHIT is considered to be a useful test for patients without nystagmus, as vHIT could detect abnormalities in approximately one-quarter of patients without nystagmus. vHIT is considered to be one of the first tests to be performed following nystagmus testing, including the gaze nystagmus test, the positional nystagmus test, and the positioning nystagmus test. On the other hand, there are some cases in which vHIT shows no abnormality while caloric testing shows canal paresis. It is necessary to perform vHIT, bearing in mind that there are abnormalities that cannot be detected by vHIT alone.
  • Pre- and post-operative semicircular canal function evaluated by video head impulse test in patients with vestibular schwannoma.
    Keishi Fujiwara; Shinya Morita; Hiroaki Motegi; Shigeru Yamaguchi; Yukitomo Ishi; Kimiko Hoshino; Atsushi Fukuda; Makoto Kobayashi; Yuji Nakamaru; Miki Fujimura; Akihiro Homma
    Auris, nasus, larynx, 51, 3, 542, 547, Jun. 2024, [International Magazine]
    English, Scientific journal, OBJECTIVES: To evaluate pre- and post-operative semicircular canal function in patients with vestibular schwannoma (VS) by the video Head Impulse Test (vHIT). METHODS: Nineteen patients with VS who underwent surgery were enrolled in this study. The gain in vestibulo-ocular reflex (VOR) and the degree of scatter in catch-up saccades were examined pre- and post-operatively for the semicircular canals in VS patients. RESULTS: Ten of 19 cases (52.6 %) with VS were defined as demonstrating both superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) impairment from the results of pre-operative vHIT. Hearing level and subjective vestibular symptoms showed significant correlations with pre-operative semicircular canal function. Compared to pre-operative vHIT results, VOR gains within 1 month after surgery were significantly reduced in all three canals; however, significant differences had disappeared in the anterior and posterior semicircular canals at 6 months after surgery. Cases of unknown origin had a significantly greater reduction in posterior semicircular canal function after surgery compared with those with disease of IVN origin. CONCLUSIONS: As vHIT could evaluate pre-operative vestibular nerve impairment, post-operative VOR gain reduction and the degree of vestibular compensation, semicircular canal function evaluated by vHIT provides a good deal of useful information regarding VS patients undergoing surgery compared to caloric testing, and vHIT should be performed pre- and post-operatively for patients with VS.
  • Validity of endoscopic ossiculoplasty immediately after its introduction for ossicular chain disruption.
    Atsushi Fukuda; Shinya Morita; Kimiko Hoshino; Keishi Fujiwara; Yuji Nakamaru; Akihiro Homma
    BMC surgery, 24, 1, 149, 149, 14 May 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Transcanal endoscopic ear surgery (TEES) reportedly requires a long learning curve and may be associated with more complications and longer operative times than microscopic ear surgery (MES). In this study, we aimed to examine the usefulness and validity of TEES for ossicular chain disruption in the early stages of its introduction in our institution. METHODS: TEES was performed on 11 ears (10 with congenital ossicular chain discontinuity and 1 with traumatic ossicular chain dislocation), and MES was performed with a retroauricular incision on 18 ears (6 with congenital ossicular chain discontinuity and 12 with traumatic ossicular chain dislocation) in a tertiary referral center. Postoperative hearing results, operative times, and postoperative hospital length of stay were retrospectively reviewed. The Mann-Whitney U test and Fisher's exact test was performed to compare variables between the TEES and MES groups. Pre- and postoperative air- and bone-conduction thresholds and the air-bone gap of each group were compared using the Wilcoxon signed-rank test. The Mann-Whitney U test and Wilcoxon signed-rank was performed to compare the pre- and postoperative air-bone gaps between the diagnoses. RESULTS: No significant differences in the postoperative air-conduction thresholds, bone-conduction thresholds, air-bone gaps, or incidence of air-bone gap ≤ 20 dB were observed between the TEES and MES groups. The air-conduction thresholds and air-bone gaps of the TEES group significantly improved postoperatively. The air-conduction thresholds and air-bone gaps of the MES group also significantly improved postoperatively. No significant difference was observed in the operative times between the groups (TEES group: median, 80 min; MES group: median, 85.5 min). The TEES group had a significantly shorter postoperative hospital stay (median, 2 days) than the MES group (median, 7.5 days). CONCLUSIONS: TEES was considered appropriate for the treatment of ossicular chain disruption, even immediately after its introduction at our institution. For expert microscopic ear surgeons, ossicular chain disruption may be considered a suitable indication for the introduction of TEES.
  • Increased adiposity to muscle ratio and severity of sinusitis affect quality of life in asthma—Computed tomographic analysis—
    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, 3, 3, 100277, 100277, Elsevier BV, May 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Deteriorated sinusitis and increased adiposity relative to muscle mass may affect quality of life in patients with asthma. However, whether these effects are observed regardless of intrapulmonary pathology is unknown. OBJECTIVES: We evaluated the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. METHODS: We recruited participants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups on the bases of the extrapulmonary indices. Multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio and LMS with AQLQ after adjusting for the airway fractal dimension for airway index and percentage of low attenuation volume to lung volume for parenchymal index. RESULTS: No significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (63 male and 100 female subjects). High VF/ESM (estimate [95% confidence interval] (-0.43 [-0.61, -0.25]) and high LMS scores (-0.22 [-0.41, -0.03]) were associated with low AQLQ scores when adjusted for age, body mass index, smoking status, blood eosinophil count, and intrapulmonary CT indices. CONCLUSIONS: Increased VF relative to ESM mass and high LMS may deteriorate asthma-related quality of life, regardless of presence of intrapulmonary disease.
  • Quantifying surgical skill using machine learning in Endoscopic Sinus Surgery
    YAMADA Kaito; SUZUKI Masanobu; MIYAJI Kou; EBINA Koki; SASE Kazuya; TSUJITA Teppei; CHEN Xiaoshuai; ABE Takashige; KOMIZUNAI Shunsuke; NAKAMARU Yuji; SENOO Taku; HOMMA Akihiro; KONNO Atsushi
    The Proceedings of JSME annual Conference on Robotics and Mechatronics (Robomec), 2024, 2P1-F01, The Japan Society of Mechanical Engineers, 2024
    Japanese, Endoscopic Sinus Surgery (ESS) is a widely performed but difficult procedure worldwide. Therefore, there is a need for quantitative feedback in ESS training. This paper describes the quantification of surgeons’ surgical skills using machine learning. A machine learning model was constructed using features calculated from the dynamic measurement data of surgical instruments in ESS. Five learning methods were applied: Support Vector Regression (SVR), Principal Component Analysis (PCA) SVR, Gradient Boosting Decision Tree (GBDT), Partial Least Squares (PLS), and Ridge. The mean absolute error (MAE) was calculated based on the score given by an experienced physician and was used as an accuracy index. Comparison of the methods showed that SVR and Ridge regression had the highest accuracy.
  • Long-term results of nasolacrimal duct and inferior turbinate swing technique for inverted papilloma of the maxillary sinus.
    Yuji Nakamaru; Masanobu Suzuki; Ken Shizuki; Aya Honma; Akira Nakazono; Shogo Kimura; Ryosuke Watanabe; Satoshi Kano; Nayuta Tsushima; Takayoshi Suzuki; Akihiro Homma
    SAGE open medicine, 12, 20503121241271877, 20503121241271877, 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: We developed a technique to preserve the entire nasolacrimal duct and inferior turbinate, by swinging the nasolacrimal duct upward and the inferior turbinate backward; that is, a nasolacrimal duct and inferior turbinate swing technique for sinonasal inverted papilloma of the maxillary sinus. In this study, we evaluated the long-term results of this technique. METHODS: A retrospective analysis was performed on the data for 53 consecutive pathologically confirmed inverted papilloma patients who were treated using nasolacrimal duct and inferior turbinate swing technique. The frequency of recurrence, the degree of nasolacrimal duct and inferior turbinate preservation, and the frequency of adverse events were assessed. RESULTS: The median follow-up period was 51 months (mean 62.5 months; range 10-187 months). No cases of recurrence within the maxillary sinus were observed among the cases treated using this technique, whereas three (5.7%) of the 53 cases experienced recurrence in areas other than the maxillary sinus. We could preserve the nasolacrimal duct in all cases. On the other hand, the inferior turbinate was resected during surgery in one case. No epiphora, dacryocystiits, numbness of the cheek, or collapse of the ala of the nose was observed. CONCLUSION: This nasolacrimal duct and inferior turbinate swing technique method is a safe and effective method for the excision of primary or recurrent inverted papilloma and demonstrates low rates of recurrence and complications.
  • Can high-fidelity 3D models be a good alternative for cadaveric materials in skill assessment for endoscopic sinus surgery? A comparison study in assessment for surgical performance in 3D models and cadavers.
    Masanobu Suzuki; Ryosuke Watanabe; Akira Nakazono; Yuji Nakamaru; Takayoshi Suzuki; Shogo Kimura; Kotaro Matoba; Manabu Murakami; Dominik Hinder; A J Psaltis; Akihiro Homma; P J Wormald
    Frontiers in medicine, 11, 1301511, 1301511, 2024, [International Magazine]
    English, Scientific journal, INTRODUCTION: Traditionally formal assessment of surgical skills has not been part of a surgeon's accreditation process. The widely adopted apprentice model of "on-the-job training" does create additional risk for the patients. In the past surgical training has used cadavers, but these are expensive, require dedicated wet-lab facilities and are in increasingly short supply. In many countries religious and cultural practices also preclude cadaveric use. Recent 3D-printed technology allows mass reproduction of high-fidelity 3D models. In this study, we examined the utility of 3D sinus models compared to cadaver dissection for surgical skill assessment for endoscopic sinus surgery (ESS). MATERIALS AND METHODS: A total of 17 otolaryngologists performed Endoscopic Sinus Surgery (ESS) on 3D printed sinus models and then repeated these procedures on cadavers. Their surgical performance was assessed with the Objective Structured Assessment of Technical Skills (OSATS) score for ESS and time was taken to complete an ESS procedure. Their performance on the 3D models and cadavers was compared. RESULTS: There were no significant differences in the OSATS score between 3D models and cadavers (50.41 ± 13.31 vs. 48.29 ± 16.01, p = 0.36). There was a strong positive correlation between the score in 3D models and those in cadavers (r = 0.84, p < 0.001). No significant differences were found in time for a mini-ESS (21:29 ± 0:10 vs. 20:33 ± 0:07, p = 0.53). There were positive correlations between 3D models and cadavers in time taken for a mini-ESS (r = 0.55, p = 0.04). CONCLUSION: The surgical performance on the 3D models was comparable to that on cadavers. This supports the utility of the 3D models as an inexhaustible alternative for cadavers in ESS surgical skill assessment.
  • Neutrophil Extracellular Trap Formation and Deoxyribonuclease I Activity in Patients with Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
    Shinya Morita; Yuji Nakamaru; Atsushi Fukuda; Keishi Fujiwara; Masanobu Suzuki; Kimiko Hoshino; Aya Honma; Akira Nakazono; Akihiro Homma
    International archives of allergy and immunology, 185, 8, 810, 819, 2024, [International Magazine]
    English, Scientific journal, INTRODUCTION: No previous studies have evaluated the levels of neutrophil extracellular trap (NET) remnants or the importance of deoxyribonuclease (DNase) I activity based on the disease activity of otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). The aim of this study was to explore the formation of NETs in the middle ear of patients with OMAAV during the onset and remission phases of the disease, with a particular focus on the relationships between the quantifiable levels of NET remnants and DNase I activity. METHODS: OMAAV patients were eligible for inclusion. Patients with otitis media with effusion (OME) were examined as controls. The levels of cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex were quantified using an enzyme-linked immunosorbent assay. DNase I activity was measured using a fluorometric method. RESULTS: The quantifiable levels of cell-free DNA, cit-H3-DNA complex, and MPO-DNA complex in the middle ear lavage of patients with OMAAV at onset were significantly higher than those in patients with OMAAV at remission and in patients with OME. DNase I activity in the patients with OMAAV at onset was significantly lower than those in patients with OMAAV at remission and OME and was negatively correlated with the level of MPO-DNA complex. CONCLUSIONS: This study suggests that NET remnants and DNase I activity may be potentially useful biomarkers for the diagnosis and disease activity of OMAAV.
  • Clinical outcomes for olfactory neuroblastoma.
    Akira Nakazono; Hiroaki Motegi; Masanobu Suzuki; Yuji Nakamaru; Shigeru Yamaguchi; Yukitomo Ishi; Satoshi Kano; Nayuta Tsushima; Aya Honma; Takayoshi Suzuki; Shogo Kimura; Seijiro Hamada; Jun Taguchi; Yasushi Shimizu; Takashi Mori; Koichi Yasuda; Hidefumi Aoyama; Ichiro Kinoshita; Miki Fujimura; Akihiro Homma
    Frontiers in oncology, 14, 1329572, 1329572, 2024, [International Magazine]
    English, Scientific journal, BACKGROUND: Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB. METHODS: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data. RESULTS: Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS. CONCLUSION: Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.
  • 鼓室型グロムス腫瘍の3例
    小林 諒; 森田 真也; 福田 篤; 干野 季美子; 藤原 圭志; 中丸 裕爾; 本間 明宏
    日本耳科学会総会・学術講演会抄録集, 33回, 296, 296, (一社)日本耳科学会, Nov. 2023
    Japanese
  • 当科における耳小骨離断に対する経外耳道的内視鏡下耳科手術の成績
    福田 篤; 森田 真也; 干野 季美子; 小林 諒; 藤原 圭志; 中丸 裕爾; 本間 明宏
    日本耳科学会総会・学術講演会抄録集, 33回, 390, 390, (一社)日本耳科学会, Nov. 2023
    Japanese
  • Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations
    Nayuta Tsushima; Satoshi Kano; Kanako C. Hatanaka; Takayoshi Suzuki; Seijiro Hamada; Hiroshi Idogawa; Yuji Nakamaru; Masanobu Suzuki; Yutaka Hatanaka; Akihiro Homma
    Auris Nasus Larynx, Elsevier BV, Nov. 2023
    Scientific journal
  • Quantitative Evaluations of Vestibular Function in Patients With Petrous Apex Cholesterol Granulomas Treated With an Endoscopic Transsphenoidal Approach: A Report of Two Cases.
    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, 01 Sep. 2023, [International Magazine]
    English, Scientific journal, 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.
  • Treatment outcomes of the patient with sinonasal mucosal melanoma: the role of endoscopic resection and postoperative radiotherapy.
    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, 17 Jun. 2023, [Domestic magazines]
    English, Scientific journal, 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.
  • 疼痛を伴わなかった悪性外耳道炎例
    佐藤 禄; 福田 篤; 森田 真也; 藤原 圭志; 中丸 裕爾; 本間 明宏
    耳鼻咽喉科臨床, 116, 6, 567, 572, 耳鼻咽喉科臨床学会, Jun. 2023
    Japanese, 症例は76歳男性で、左耳漏、左顔面神経麻痺、嚥下困難の精査加療目的に当科入院となった。入院時、耳痛は認めなかったが、側頭骨CTで左外耳道前壁から鼓室前壁にかけて強い骨融解像を伴う軟部陰影が充満し、頭蓋底の一部にも骨融解像がみられた。第2病日に生検および左後壁保存型鼓室形成術IIIc型を施行し、病理組織所見・画像所見より悪性外耳道炎に合併した頭蓋底骨髄炎の診断に至った。術後は6週間にわたり抗菌薬の静注を続け、頭蓋底病変は改善傾向にあったため、内服に切り替え第52病日に軽快退院した。抗菌薬は内服開始2年後に終了し、顔面神経麻痺は回復し、抗菌薬中止後1年4ヵ月間にわたり明らかな再燃は認めなかった。
  • TRIM27の鼻副鼻腔粘膜悪性黒色腫におけるバイオマーカーとしての検討
    木村 将吾; 中丸 裕爾; 鈴木 正宣; 本間 あや; 中薗 彬; 加納 里志; 対馬 那由多; 鈴木 崇祥; 浜田 誠二郎; 本間 明宏
    日本耳鼻咽喉科頭頸部外科学会会報, 126, 4, 562, 562, (一社)日本耳鼻咽喉科頭頸部外科学会, Apr. 2023
    Japanese
  • TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma.
    S Kimura; M Suzuki; Y Nakamaru; S Kano; M Watanabe; A Honma; A Nakazono; N Tsushima; S Hatakeyama; A Homma
    Rhinology, 09 Mar. 2023, [International Magazine]
    English, Scientific journal, 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.
  • Nasal irrigation improving nasal obstruction and QoL of patients: two cases of HHT after nasal dermoplasty
    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, Japan Society for Head and Neck Surgery, 2023
    Scientific journal
  • Mental workload during endoscopic sinus surgery is associated with surgeons' skill levels.
    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, [International Magazine]
    English, Scientific journal, 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.
  • アブミ骨手術の術後成績の検討 とくにピストントリミングの有無との関連について
    小林 諒; 福田 篤; 森田 真也; 藤原 圭志; 中丸 裕爾; 本間 明宏
    耳鼻咽喉科臨床, 115, 9, 747, 752, 耳鼻咽喉科臨床学会, Sep. 2022
    Japanese, 対象は2014年1月~2021年3月の39例44耳(男性10例、女性29例、平均年齢41.8歳)。診断は耳硬化症が30耳、耳小骨奇形が14耳であり、全例で顕微鏡下にstapedotomyを施行しCO2レーザーを用いてアブミ骨底板を開窓した。平均気導聴力は術前58.3dBから術後36.2dBと有意な改善を認めたが、平均骨導聴力は術後有意な変化を認めなかった。平均気骨導差は術前30.5dBから術後8.4dBと有意な改善を認めた。日本耳科学会基準に基づく術後成功例は36耳(81.8%)であった。術後聴力成績に影響を及ぼす因子として、テフロンピストンのリングをトリミングした場合に成功率が有意に低かった。ピストンリングのトリミングを行い成功に至らなかった症例のなかにはキヌタ骨長脚からピストンが脱落している症例もあり、テフロンピストンリングはできる限りトリミングせずに使用することが望ましい。
  • オマリズマブの長期投与後、投与間隔延長による不応を呈した重症喘息の1例
    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, 71, 8, 944, 948, (一社)日本アレルギー学会, Sep. 2022
    Japanese
  • Association of gene mutations with clinicopathologic features in patients with external auditory canal squamous cell carcinoma.
    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, Sep. 2022, [Domestic magazines]
    English, Scientific journal, 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.
  • Repetitive simulation training with novel 3D-printed sinus models for functional endoscopic sinus surgeries.
    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, Aug. 2022, [International Magazine]
    English, Scientific journal, 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.
  • Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Labyrinthine Fistula Due to Cholesteatoma.
    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, 01 Jun. 2022, [International Magazine]
    English, Scientific journal, 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.
  • Discrepancies in the caloric testing and video Head Impulse Test results in a case with bilateral lateral semicircular canal malformations.
    Keishi Fujiwara; Shinya Morita; Atsushi Fukuda; Kimiko Hoshino; Yuji Nakamaru; Akihiro Homma
    Auris, nasus, larynx, 22 Apr. 2022, [International Magazine]
    English, 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.
  • 内視鏡下頭蓋底手術を考慮した嗅神経芽細胞腫に対する新規病期分類の検討
    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, 125, 4, 702, 702, (一社)日本耳鼻咽喉科頭頸部外科学会, Apr. 2022
    Japanese
  • 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, 11, 増刊, 143, 143, (一社)日本呼吸器学会, Apr. 2022
    Japanese
  • 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, 11, 増刊, 143, 143, (一社)日本呼吸器学会, Apr. 2022
    Japanese
  • 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, 2回, 71, 71, 日本耳鼻咽喉科免疫アレルギー感染症学会, Mar. 2022
    Japanese
  • 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, 2回, 77, 77, 日本耳鼻咽喉科免疫アレルギー感染症学会, Mar. 2022
    Japanese
  • 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, 2回, 168, 168, 日本耳鼻咽喉科免疫アレルギー感染症学会, Mar. 2022
    Japanese
  • 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, 2回, 185, 185, 日本耳鼻咽喉科免疫アレルギー感染症学会, Mar. 2022
    Japanese
  • The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media.
    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, 01 Mar. 2022, [International Magazine]
    English, Scientific journal, 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.
  • 前頭開頭術後に生じた前頭蓋底粘液嚢胞の2例
    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, Feb. 2022
  • [A CASE OF SEVERE ASTHMA RESULTING IN DISEASE EXACERBATION AFTER PROLONGATION OF THE DOSING INTERVAL AFTER LONG-TERM OMALIZUMAB ADMINISTRATION].
    Machiko Matsumoto-Sasaki; Kaoruko Shimizu; Masanobu Suzuki; Masaru Suzuki; Hirokazu Kimura; Yuji Nakamaru; Satoshi Konno
    Arerugi = [Allergy], 71, 8, 944, 948, 2022, [Domestic magazines]
    Japanese, Scientific journal, 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.
  • Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma.
    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, [International Magazine]
    English, Scientific journal, 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.
  • 後天性中耳真珠腫におけるNotchシグナル関連分子発現についての検討
    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, 31回, 422, 422, (一社)日本耳科学会, Oct. 2021
    Japanese
  • Remote Training of Functional Endoscopic Sinus Surgery With Advanced Manufactured 3D Sinus Models and a Telemedicine System
    Masanobu Suzuki; Erich Vyskocil; Kazuhiro Ogi; Kotaro Matoba; Yuji Nakamaru; Akihiro Homma; Peter J. Wormald; Alkis J. Psaltis
    Frontiers in Surgery, 8, Frontiers Media SA, 01 Oct. 2021
    Scientific journal, 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.
  • Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa.
    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, Oct. 2021, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • Notch Signaling in Acquired Middle Ear Cholesteatoma.
    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, 01 Oct. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 60, 3, 312, 312, (一社)日本鼻科学会, Sep. 2021
    Japanese
  • 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, 60, 3, 352, 352, (一社)日本鼻科学会, Sep. 2021
    Japanese
  • Characteristics of and Prognosis for Facial Palsy in Patients With Otitis Media With ANCA-Associated Vasculitis (OMAAV).
    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, 04 Aug. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • The clinical features of intractable allergic rhinitis based on a questionnaire administered to clinicians.
    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, Jul. 2021, [Peer-reviewed], [International Magazine]
    English
  • 甲状腺穿刺吸引細胞診後に急速びまん性甲状腺腫大をきたした2例
    本間 あや; 加納 里志; 中丸 裕爾; 本間 明宏
    耳鼻咽喉科臨床 補冊, 補冊157, 113, 113, 耳鼻咽喉科臨床学会, Jun. 2021
    Japanese
  • 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, 補冊157, 65, 65, 耳鼻咽喉科臨床学会, Jun. 2021
    Japanese
  • 4剤の生物学的製剤を使用し上下気道の反応性の違いを観察し得た重症喘息の1例
    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, 70, 4, 315, 320, (一社)日本アレルギー学会, Jun. 2021
    Japanese
  • 4剤の生物学的製剤を使用し上下気道の反応性の違いを観察し得た重症喘息の1例
    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, 70, 4, 315, 320, (一社)日本アレルギー学会, Jun. 2021
    Japanese
  • Objective evaluation of caudal deviation of the nasal septum and selection of the appropriate septoplasty technique.
    Shogo Kimura; Masanobu Suzuki; Aya Honma; Akira Nakazono; Masayuki Osawa; Yuji Nakamaru; Akihiro Homma
    Auris, nasus, larynx, 49, 1, 67, 76, 06 May 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, 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.
  • Psychological evaluation for patients with non-cured facial nerve palsy.
    Keishi Fujiwara; Atsushi Fukuda; Shinya Morita; Hiroko Yanagi; Kimiko Hoshino; Yuji Nakamaru; Yasushi Furuta; Akihiro Homma
    Auris, nasus, larynx, 49, 1, 53, 57, 04 May 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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, 1回, 127, 127, 日本耳鼻咽喉科免疫アレルギー感染症学会, May 2021
    Japanese
  • Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases.
    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, Apr. 2021, [Peer-reviewed], [Corresponding author], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • Usefulness of the Video Head Impulse Test for the Evaluation of Vestibular Function in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
    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, 01 Apr. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • Prognostic factors for duration of vertigo after stapes surgery via a time-to-event analysis.
    Atsushi Fukuda; Keishi Fujiwara; Shinya Morita; Kimiko Hoshino; Hiroko Yanagi; Yuji Nakamaru; Akihiro Homma
    Acta oto-laryngologica, 141, 3, 216, 221, Mar. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.
    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, Feb. 2021, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, 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.
  • Endonasal endoscopic surgery for sinonasal squamous cell carcinoma from an oncological perspective.
    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, Feb. 2021, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • TLR Signals in Epithelial Cells in the Nasal Cavity and Paranasal Sinuses.
    Masanobu Suzuki; Clare Cooksley; Takayoshi Suzuki; Mahnaz Ramezanpour; Akira Nakazono; Yuji Nakamaru; Akihiro Homma; Sarah Vreugde
    Frontiers in allergy, 2, 780425, 780425, 2021, [International Magazine]
    English, Scientific journal, 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.
  • Comparison of clinical characteristics of the nasal manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) and eosinophilic chronic rhinosinusitis (ECRS).
    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, Jan. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
    English
  • Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells.
    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, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • [A CASE OF SEVERE ASTHMA WHO REQUIRED A SWITCH OF FOUR BIOLOGICS: DIFFERENTIAL RESPONSES ON UPPER AND LOWER AIRWAYS].
    Machiko Matsumoto Sasaki; Kaoruko Shimizu; Masanobu Suzuki; Masaru Suzuki; Yuji Nakamaru; Satoshi Konno
    Arerugi = [Allergy], 70, 4, 315, 320, 2021, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, 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.
  • Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis.
    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, 01 Oct. 2020, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • video Head Impulse Testを用いたOMAAV症例の半規管機能評価
    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, 123, 4, 1142, 1142, (一社)日本耳鼻咽喉科頭頸部外科学会, Sep. 2020
    Japanese
  • ベンラリズマブ不応後にメポリズマブへ変更した難治性喘息の1例
    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, 69, 8, 678, 682, (一社)日本アレルギー学会, Sep. 2020
    Japanese
  • 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, 46, 2, 188, 188, (一社)日本頭頸部癌学会, Jul. 2020
    Japanese
  • Preoperative Pulmonary Function Testing to Predict Recurrence of Chronic Rhinosinusitis With Nasal Polyps
    Yuji Nakamaru; Masanobu Suzuki; Aya Honma; Akira Nakazono; Shogo Kimura; Keishi Fujiwara; Shinya Morita; Satoshi Konno; Akihiro Homma
    ALLERGY & RHINOLOGY, 11, Jul. 2020, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Facial Nerve Schwannoma.
    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, Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • Rosai-Dorfman disease: earlier spontaneous regression of skin lesions relative to nasal, pharyngeal, and bone lesions.
    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, 01 Apr. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Analysis of semicircular canal function as evaluated by video Head Impulse Test in patients with vestibular schwannoma.
    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, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • [A CASE OF SEVERE ASTHMA SWITCHED TO MEPOLIZUMAB DUE TO LATE-OCCURRING UNRESPONSIVENESS TO BENRALIZUMAB].
    Machiko Matsumoto-Sasaki; Kaoruko Shimizu; Masanobu Suzuki; Masaru Suzuki; Yuji Nakamaru; Satoshi Konno
    Arerugi = [Allergy], 69, 8, 678, 682, 2020, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, 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, 29回, 508, 508, (一社)日本耳科学会, Oct. 2019
    Japanese
  • 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; 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, 45, 3, 300, 304, (一社)日本頭頸部癌学会, Oct. 2019
    Japanese
  • 【二次出版】ANL Secondary Publication 急性感音難聴患者における抗ムンプスIgM抗体陽性率 北海道における後向き多施設共同研究
    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, 122, 9, 1267, 1268, (一社)日本耳鼻咽喉科学会, Sep. 2019
    Japanese
  • 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, 58, 3, 632, 632, (一社)日本鼻科学会, Sep. 2019
    Japanese
  • Differentiation Between Eosinophilic Otitis Media and Otitis Media Associated With Eosinophilic Granulomatosis With Polyangiitis.
    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, Sep. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • Make-Up Therapy for Patients With Facial Nerve Palsy.
    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, Aug. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • ANCA関連血管炎性中耳炎における好中球細胞外トラップの測定と臨床応用
    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, 37, 2, 77, 78, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2019
    Japanese
  • 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
    日本耳鼻咽喉科学会会報, 122, 4, 627, 627, (一社)日本耳鼻咽喉科学会, Apr. 2019
    Japanese
  • video Head Impulse Testを用いた聴神経腫瘍患者の半規管機能評価
    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, 122, 4, 704, 704, (一社)日本耳鼻咽喉科学会, Apr. 2019
    Japanese
  • Short-Term Hearing Prognosis of Ossiculoplasty in Pars Flaccida Cholesteatoma Using the EAONO/JOS Staging System.
    Fukuda A; Morita S; Nakamaru Y; Hoshino K; Fujiwara K; Homma A
    The journal of international advanced otology, 15, 1, 2, 7, Apr. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • Evaluation of Vertical Semicircular Canal Function in Patients With Vestibular Schwannoma.
    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, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • The Diagnostic and Clinical Utility of the Myeloperoxidase-DNA Complex as a Biomarker in Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.
    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, Feb. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, 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.
  • Spontaneous Regression of Swollen Submandibular Glands in IgG4-Related Disease
    Masanobu Suzuki; Yuji Nakamaru; Dai Takagi; Aya Honma; Takayoshi Suzuki; Emi Takakuwa; Shinya Morita; Sarah Vreugde; Akihiro Homma
    Allergy & Rhinology, 10, 215265671881673, 215265671881673, SAGE Publications, Jan. 2019
    Scientific journal, 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.

  • Treatment outcomes of local advanced external auditory canal squamous cell carcinomas
    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, 2019, [Peer-reviewed]
    Scientific journal
  • Sirtuin-1 Controls Poly (I:C)-Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells.
    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, Oct. 2018, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal, 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.
  • Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss using second-generation enzyme immunoassay: A retrospective, multi-institutional investigation in Hokkaido, Japan
    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, Elsevier Ireland Ltd, 01 Oct. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 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, 28, 4, 468, 468, (一社)日本耳科学会, Sep. 2018
    Japanese
  • 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, 28, 4, 637, 637, (一社)日本耳科学会, Sep. 2018
    Japanese
  • 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, 57, 3, 429, 429, (一社)日本鼻科学会, Sep. 2018
    Japanese
  • 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, 57, 3, 504, 504, (一社)日本鼻科学会, Sep. 2018
    Japanese
  • Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer.
    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, Jul. 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, 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.
  • 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, 36, 2, 118, 119, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2018
    Japanese
  • 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, 36, 2, 118, 119, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2018
    Japanese
  • Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing
    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, Springer Tokyo, 19 May 2018, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • 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, 44, 2, 181, 181, (一社)日本頭頸部癌学会, May 2018
    Japanese
  • Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up.
    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, May 2018, [Peer-reviewed], [Internationally co-authored]
  • 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, 44, 2, 181, 181, (一社)日本頭頸部癌学会, May 2018
    Japanese
  • Elevated Level of Myeloperoxidase-Deoxyribonucleic Acid Complex in the Middle Ear Fluid Obtained from Patients with Otitis Media Associated with Antineutrophil Cytoplasmic Antibody-associated Vasculitis
    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, Lippincott Williams and Wilkins, 01 Apr. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 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, 121, 4, 539, 539, (一社)日本耳鼻咽喉科学会, Apr. 2018
    Japanese
  • 当院における嗅神経芽細胞腫の治療方針と成績
    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, 121, 4, 567, 567, (一社)日本耳鼻咽喉科学会, Apr. 2018
    Japanese
  • ANCA関連血管炎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
    日本耳鼻咽喉科学会会報, 121, 4, 557, 557, (一社)日本耳鼻咽喉科学会, Apr. 2018
    Japanese
  • 当院における嗅神経芽細胞腫の治療方針と成績
    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, 121, 4, 567, 567, (一社)日本耳鼻咽喉科学会, Apr. 2018
    Japanese
  • 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, 121, 4, 539, 539, (一社)日本耳鼻咽喉科学会, Apr. 2018
    Japanese
  • Clinical Characteristics and Treatment Outcomes for Patients with External Auditory Canal Cholesteatoma
    Shinya Morita; Yuji Nakamaru; Atsushi Fukuda; Keishi Fujiwara; Kimiko Hoshino; Akihiro Homma
    Otology and Neurotology, 39, 2, 189, 195, Lippincott Williams and Wilkins, 01 Feb. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Distinct phenotypes of smokers with fixed airflow limitation identified by cluster analysis of severe asthma
    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, American Thoracic Society, 01 Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Relapsing Polychondritis With Increased Bone Marrow Signal on Magnetic Resonance Imaging in a 13-Year-Old Girl.
    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, Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Value of T1-weighted magnetic resonance imaging in cholesteatoma detection
    Atsushi Fukuda; Shinya Morita; Taisuke Harada; Keishi Fujiwara; Kimiko Hoshino; Yuji Nakamaru; Akihiro Homma
    Otology and Neurotology, 38, 10, 1440, 1444, Lippincott Williams and Wilkins, 01 Dec. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 急性感音難聴患者におけるムンプスIgM抗体陽性率の検討(第2報)
    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, 27, 4, 568, 568, (一社)日本耳科学会, Oct. 2017
    Japanese
  • 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, 27, 4, 429, 429, (一社)日本耳科学会, Oct. 2017
    Japanese
  • 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, 56, 3, 429, 429, (一社)日本鼻科学会, Sep. 2017
    Japanese
  • 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, 56, 3, 429, 429, (一社)日本鼻科学会, Sep. 2017
    Japanese
  • IgG4関連疾患における鼻副鼻腔病変の検討
    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, 35, 2, 238, 239, 日本耳鼻咽喉科免疫アレルギー学会, Aug. 2017
    Japanese
  • Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma
    Tomohiko Kakizaki; Hiromitsu Hatakeyama; Yuji Nakamaru; Dai Takagi; Takatsugu Mizumachi; Tomohiro Sakashita; Satoshi Kano; Akihiro Homma; Satoshi Fukuda
    ONCOLOGY LETTERS, 14, 1, 987, 992, Jul. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • 当科の弛緩部型中耳真珠腫の臨床的検討
    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, 120, 4, 535, 535, (一社)日本耳鼻咽喉科学会, Apr. 2017
    Japanese
  • IgG4関連疾患における鼻副鼻腔病変の検討
    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, 120, 4, 557, 557, (一社)日本耳鼻咽喉科学会, Apr. 2017
    Japanese
  • 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, 120, 4, 566, 566, (一社)日本耳鼻咽喉科学会, Apr. 2017
    Japanese
  • Sinus Computed Tomographic Findings in Adult Smokers and Nonsmokers with Asthma. Analysis of Clinical Indices and Biomarkers.
    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, Mar. 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal, 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.
  • Expression of p53, p16, cyclin D1, epidermal growth factor receptor and Notch1 in patients with temporal bone squamous cell carcinoma
    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, Feb. 2017, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal
  • Evaluation of Vestibular Functions in Patients with Vogt-Koyanagi-Harada Disease
    Keishi Fujiwara; Shinya Morita; Kimiko Hoshino; Atsushi Fukuda; Yuji Nakamaru; Akihiro Homma
    AUDIOLOGY AND NEURO-OTOLOGY, 22, 3, 190, 195, 2017, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery
    A. Honma; D. Takagi; Y. Nakamaru; A. Homma; M. Suzuki; S. Fukuda
    JOURNAL OF LARYNGOLOGY AND OTOLOGY, 130, 12, 1147, 1152, Dec. 2016, [Peer-reviewed]
    English, Scientific journal
  • 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, 55, 3, 468, 468, (一社)日本鼻科学会, Sep. 2016
    Japanese
  • The Outcomes of Surgery and Chemoradiotherapy for Temporal Bone Cancer
    Shinya Morita; Akihiro Homma; Yuji Nakamaru; Tomohiro Sakashita; Hiromitsu Hatakeyama; Satoshi Kano; Atsushi Fukuda; Satoshi Fukuda
    OTOLOGY & NEUROTOLOGY, 37, 8, 1174, 1182, Sep. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer
    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, Aug. 2016, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.
    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, 25 Apr. 2016, [Peer-reviewed], [International Magazine]
    English, 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.
  • Comparison of hearing outcomes after treatment for early-stage external auditory canal cancer
    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, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis
    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, Apr. 2016, [Peer-reviewed]
    English, Scientific journal
  • TRIM39 negatively regulates the NF kappa B-mediated signaling pathway through stabilization of Cactin
    Masanobu Suzuki; Masashi Watanabe; Yuji Nakamaru; Dai Takagi; Hidehisa Takahashi; Satoshi Fukuda; Shigetsugu Hatakeyama
    CELLULAR AND MOLECULAR LIFE SCIENCES, 73, 5, 1085, 1101, Mar. 2016, [Peer-reviewed]
    English, Scientific journal
  • Preoperative Assessments for Sinonasal Inverted Papilloma
    Nakamaru Yuji; Takagi Dai; Suzuki Masanobu; Homma Aya; Fukuda Satoshi
    Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology), 55, 1, 114, 114, Japan Rhinologic Society, 2016
    Japanese
  • Otologic and Rhinologic Manifestations of Eosinophilic Granulomatosis with Polyangiitis
    Yuji Nakamaru; Dai Takagi; Masanobu Suzuki; Aya Homma; Shinya Morita; Akihiro Homma; Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY, 21, 1, 45, 53, 2016, [Peer-reviewed]
    English, Scientific journal
  • The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo
    Shinya Morita; Yuji Nakamaru; Keishi Fujiwara; Keiji Iizuka; Masayori Masuya; Akihiro Homma; Atsushi Fukuda; Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY, 21, 3, 132, 140, 2016, [Peer-reviewed]
    English, Scientific journal
  • Distinct phenotypes of cigarette smokers identified by cluster analysis of patients with severe asthma
    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, American Thoracic Society, 01 Dec. 2015, [Peer-reviewed]
    English, Scientific journal
  • Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.
    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, Dec. 2015, [Peer-reviewed]
  • Glucocorticoids Reset the Nasal Circadian Clock in Mice
    Aya Honma; Yoshiko Yamada; Yuji Nakamaru; Satoshi Fukuda; Ken-ichi Honma; Sato Honma
    ENDOCRINOLOGY, 156, 11, 4302, 4311, Nov. 2015, [Peer-reviewed]
    English, Scientific journal
  • Early and long-term morbidity after minimally invasive total laryngo-pharyngo-esophagectomy with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision
    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, Nov. 2015, [Peer-reviewed]
    English, Scientific journal
  • Management for squamous cell carcinoma of the nasal cavity and ethmoid sinus: A single institution experience
    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, Oct. 2015, [Peer-reviewed]
    English, Scientific journal
  • Comparison of facial synkinesis at 6 and 12 months after the onset of peripheral facial nerve palsy
    Keishi Fujiwara; Yasushi Furuta; Yuji Nakamaru; Satoshi Fukuda
    AURIS NASUS LARYNX, 42, 4, 271, 274, Aug. 2015, [Peer-reviewed]
    English, Scientific journal
  • Oxidative Stress Regulates IL-4 Gene Expression in Mast Cells through the Reduction of Histone Deacetylase
    Yuji Nakamaru; Dai Takagi; Akihiro Homma; Shigetsugu Hatakeyama; Satoshi Fukuda
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 152, 1, 48, 52, Jan. 2015, [Peer-reviewed]
    English, Scientific journal
  • The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck
    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, 2015, [Peer-reviewed]
    English, Scientific journal
  • The effectiveness of escitalopram to tinnitus patients
    Masayori Masuya; Yuji Nakamaru; Sinya Morita; Satoshi Fukuda
    Otolaryngology - Head and Neck Surgery (Japan), 86, 12, 1047, 1050, Igaku-Shoin Ltd, 01 Nov. 2014
    Japanese, Scientific journal
  • Prediction of the Attachment Site of Sinonasal Inverted Papillomas by Preoperative Imaging
    Yuji Nakamaru; Noriyuki Fujima; Dai Takagi; Akiko Tsukahara; Daisuke Yoshida; Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 123, 7, 468, 474, Jul. 2014, [Peer-reviewed]
    English, Scientific journal
  • Otologic Manifestations of Immunoglobulin G4-Related Disease
    Dai Takagi; Yuji Nakamaru; Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 123, 6, 420, 424, Jun. 2014, [Peer-reviewed]
    English, Scientific journal
  • 早期外耳道癌症例に対する治療前後の聴力に関する検討
    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, 117, 4, 565, 565, (一社)日本耳鼻咽喉科学会, Apr. 2014
    Japanese
  • Characteristics and Prognosis of Hearing Loss Associated with Vogt-Koyanagi-Harada Disease
    Shinya Morita; Yuji Nakamaru; Nobuyuki Obara; Masayori Masuya; Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY, 19, 1, 49, 56, 2014, [Peer-reviewed]
    English, Scientific journal
  • Hearing Preservation after Lateral Temporal Bone Resection for Early-Stage External Auditory Canal Carcinoma
    Shinya Morita; Yuji Nakamaru; Akihiro Homma; Tomohiro Sakashita; Masayori Masuya; Satoshi Fukuda
    AUDIOLOGY AND NEURO-OTOLOGY, 19, 6, 351, 357, 2014, [Peer-reviewed]
    English, Scientific journal
  • 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, 23, 4, 774, 774, (一社)日本耳科学会, Oct. 2013
    Japanese
  • 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, 23, 4, 669, 669, (一社)日本耳科学会, Oct. 2013
    Japanese
  • 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, 23, 4, 513, 513, (一社)日本耳科学会, Oct. 2013
    Japanese
  • IgG4関連硬化性疾患に併発した副鼻腔炎
    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, 31, 2, 73, 74, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2013
    Japanese
  • Nasal manifestations of immunoglobulin G4-related disease
    Masanobu Suzuki; Yuji Nakamaru; Shigeru Akazawa; Takatsugu Mizumachi; Masanori Maeda; Dai Takagi; Kanako C. Hatanaka; Satoshi Fukuda
    LARYNGOSCOPE, 123, 4, 829, 834, Apr. 2013, [Peer-reviewed]
    English, Scientific journal
  • Dysregulation of Histone Deacetylase and Histone Acetyltransferase in Development of Wegener's Granulomatosis
    Dai Takagi; Yuji Nakamaru; Masanobu Suzuki; Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 121, 12, 816, 820, Dec. 2012, [Peer-reviewed]
    English, Scientific journal
  • 急性副鼻腔炎に対するLevofloxacin 1日1回500mg投与の治療効果
    高木 大; 中丸 裕爾; 鈴木 正宣; 福田 諭
    耳鼻咽喉科・頭頸部外科, 84, 13, 1021, 1026, (株)医学書院, Dec. 2012
    Japanese, 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。
  • Extranodal natural killer/T-cell lymphoma: a diagnostic dilemma
    Hiroko Yanagi; Yuji Nakamaru; Dai Takagi; Kanako Kubota; Satoshi Fukuda
    RHINOLOGY, 50, 3, 325, 331, Sep. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, 22, 4, 579, 579, (一社)日本耳科学会, Sep. 2012
    Japanese
  • ヒストン脱アセチル化作用を有するSIRT1によるMMP-9の発現調節
    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, 30, 2, 215, 216, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2012
    Japanese
  • ヒストンアセチル化がWegener肉芽腫症におよぼす影響について
    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, 30, 2, 76, 77, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2012
    Japanese
  • IgG4関連疾患の鼻腔病変における組織学的検討
    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, 30, 2, 70, 71, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2012
    Japanese
  • IgG4関連疾患の鼻腔病変における組織学的検討
    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, 115, 4, 413, 413, (一社)日本耳鼻咽喉科学会, Apr. 2012
    Japanese
  • Otolaryngologic Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
    Yuji Nakamaru; Dai Takagi; Nobuhiko Oridate; Akihiro Homma; Satoshi Fukuda
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 146, 1, 119, 121, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • Giant frontal mucocele occurring 32 years after frontal bone fracture: A case report
    Yuuta Kamoshima; Shunsuke Terasaka; Yuji Nakamaru; Dai Takagi; Satoshi Fukuda; Kiyohiro Houkin
    Case Reports in Neurology, 4, 1, 34, 37, 1, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • 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, 50, 3, 379, 379, (一社)日本鼻科学会, Nov. 2011
    Japanese
  • Transoral surgery of the larynx and pharynx using Weerda-type videolaryngoscope
    Nobuhiko Oridate; Akihiro Homma; Yuji Nakamaru; Seigo Suzuki; Satoshi Fukuda
    Oto-Rhino-Laryngology Tokyo, 54, 5, 355, 359, 15 Oct. 2011
    Japanese, Scientific journal
  • 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, 29, 2, 77, 78, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2011
    Japanese
  • Preservation of the nasolacrimal duct during endoscopic medial maxillectomy for sinonasal inverted papilloma
    Yuji Nakamaru; Yasushi Furuta; Dai Takagi; Nobuhiko Oridate; Satoshi Fukuda
    RHINOLOGY, 48, 4, 452, 456, Dec. 2010, [Peer-reviewed]
    English, Scientific journal
  • Frontal trephination for frontal sinus mucocele
    Yuji Nakamaru; Satoshi Iizuka; Dai Takagi; Satoshi Fukuda
    Oto-Rhino-Laryngology Tokyo, 53, 5, 49, 50, Oct. 2010
    Japanese, Scientific journal
  • Two cases of aspergillosis of the sphenoid sinus
    干野 季美子; 中丸 裕爾; 高木 大; 福田 諭
    耳鼻咽喉科・頭頸部外科, 82, 9, 623, 628, 株式会社医学書院, 20 Aug. 2010
  • 反復性鼻出血に対する内視鏡下蝶口蓋動脈結紮術施行例の検討
    古田 康; 松村 道哉; 鈴木 正宣; 中丸 裕爾
    日本鼻科学会会誌, 49, 3, 415, 415, (一社)日本鼻科学会, Jul. 2010
    Japanese
  • Sublingual immunotherapy with house dust extract for house dust-mite allergic rhinitis in children
    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, Japanese Society of Allergology, 2010, [Peer-reviewed]
    English, Scientific journal
  • 反復性鼻出血に対する内視鏡下蝶口蓋動脈結紮術施行例の検討
    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, 82, 1, 67, 72, (株)医学書院, Jan. 2010
    Japanese, 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。
  • Endoscopic transseptal approach for sinonasal inverted papilloma attached to the anterior maxillary siuns
    Yuji Nakamaru; Tosihiro Hara; Takatsugu Mizumachi; Fukuda Satosi; Furuta Yasushi
    Oto-Rhino-Laryngology Tokyo, 52, 5, 386, 388, Oct. 2009
    Japanese, Scientific journal
  • A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9
    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, Sep. 2009, [Peer-reviewed]
    English, Scientific journal
  • 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, 48, 3, 276, 276, (一社)日本鼻科学会, Aug. 2009
    Japanese
  • 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, 29, 8, 712, 716, (株)北隆館, Aug. 2009
    Japanese
  • Voice-Related Quality of Life After Treatment of Laryngeal Cancer
    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, Apr. 2009, [Peer-reviewed]
    English, Scientific journal
  • Complications of Skull Base Surgery: An Analysis of 30 Cases
    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, Mar. 2009, [Peer-reviewed]
    English, Scientific journal
  • マイクロデブリッダーが有用であった成人型多発性喉頭乳頭腫の1症例
    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, 81, 3, 219, 221, (株)医学書院, Mar. 2009
    Japanese, 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, 47, 3, 290, 290, (一社)日本鼻科学会, Aug. 2008
    Japanese
  • 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, 47, 3, 276, 276, (一社)日本鼻科学会, Aug. 2008
    Japanese
  • Surgical equipments for endoscopic medial maxillectomy
    Yasushi Furuta; Masahiko Saheki; Yuji Nakamaru; Jun Furusawa; Satoshi Fukuda
    Oto-Rhino-Laryngology Tokyo, 50, 5, 379, 381, Oct. 2007
    Japanese, Scientific journal
  • Preoperative staging and surgical approaches for sinonasal inverted papilloma
    Keita Oikawa; Yasushi Furuta; Yuji Nakamaru; Nobuhiko Oridate; Satoshi Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 116, 9, 674, 680, Sep. 2007, [Peer-reviewed]
    English, Scientific journal
  • 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, 33, 2, 178, 178, (一社)日本頭頸部癌学会, May 2007
    Japanese
  • IL-21 enhances dendritic cell ability to induce interferon-gamma production by natural killer T cells
    Masanori Maeda; Yoshiki Yanagawa; Kazuya Iwabuchi; Keita Minami; Yuji Nakamaru; Dai Takagi; Satoshi Fukuda; Kazunori Onoe
    IMMUNOBIOLOGY, 212, 7, 537, 547, 2007, [Peer-reviewed]
    English, Scientific journal
  • Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice
    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, Nov. 2006, [Peer-reviewed]
    English, Scientific journal
  • IL-21による樹状細胞の機能制御
    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, 24, 2, 207, 208, 日本耳鼻咽喉科免疫アレルギー学会, Sep. 2006
    Japanese
  • 咽喉頭酸逆流症状に対する酸抑制治療の効果とHelicobacter pylori感染との関連
    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, 57, 3, 262, 267, (NPO)日本気管食道科学会, Jun. 2006
    Japanese
  • 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, 109, 4, 410, 410, (一社)日本耳鼻咽喉科学会, Apr. 2006
    Japanese
  • 鼻副鼻腔内反性乳頭腫の術式選択におけるstaging systemの問題点
    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, 15, 3, 195, 201, (NPO)日本頭頸部外科学会, Feb. 2006
    Japanese, 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
  • A prospective study of pollen dispersal prediction and identifying the usefulness of different parameters
    Masanori Maeda; Shiro Maguchi; Yuji Nakamaru; Dai Takagi; Satoshi Fukuda
    Journal of Otolaryngology of Japan, 109, 5, 455, 460, Oto-Rhino-Laryngological Society of Japan Inc., 2006, [Peer-reviewed]
    Japanese, Scientific journal
  • S100A2 expression as a predictive marker for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral cavity
    F Suzuki; N Oridate; A Homma; Y Nakamaru; T Nagahashi; K Yagi; S Yamaguchi; Y Furuta; S Fukuda
    ONCOLOGY REPORTS, 14, 6, 1493, 1498, Dec. 2005, [Peer-reviewed]
    English, Scientific journal
  • Laryngeal zoster mimicking a laryngeal cancer
    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, Oct. 2005, [Peer-reviewed]
    English, Scientific journal
  • Plantago lanceolata (English plantain) pollinosis in Japan
    Y Nakamaru; S Maguchi; N Oridate; D Takagi; Y Furuta; S Fukuda
    AURIS NASUS LARYNX, 32, 3, 251, 256, Sep. 2005, [Peer-reviewed]
    English, Scientific journal
  • Macrophage migration inhibitory factor (MIF) contributes to the development of allergic rhinitis
    Y Nakamaru; N Oridate; J Nishihira; D Takagi; Y Furuta; S Fukuda
    CYTOKINE, 31, 2, 103, 108, Jul. 2005, [Peer-reviewed]
    English, Scientific journal
  • 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, 108, 4, 457, 457, (一社)日本耳鼻咽喉科学会, Apr. 2005
    Japanese
  • Mucocele of the frontal sinus treated with skull base surgery : A case report
    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, 14, 3, 247, 251, (NPO)日本頭頸部外科学会, 05 Feb. 2005
    Japanese, 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
  • Prognostic significance of cytoplasmic macrophage migration inhibitory factor expression in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy
    F Suzuki; Y Nakamaru; N Oridate; A Homma; T Nagahashi; S Yamaguchi; J Nishihira; Y Furuta; S Fukuda
    ONCOLOGY REPORTS, 13, 1, 59, 64, Jan. 2005, [Peer-reviewed]
    English, Scientific journal
  • 366 SIRT1によるMMP-9発現の調節(サイトカイン, ケモカインとその受容体(2), 第55回日本アレルギー学会秋季学術大会)
    中丸 裕爾; 福田 諭; 伊藤 一洋; バーンズピーター
    アレルギー, 54, 8, 1098, 1098, 一般社団法人 日本アレルギー学会, 2005
    Japanese
  • 鼻咽腔血管線維腫に対するナビゲーションガイド下鼻内内視鏡による摘出の経験
    本間 明宏; 中丸 裕爾; 佐伯 昌彦; 福田 諭
    頭頸部外科, 14, 2, 109, 113, (NPO)日本頭頸部外科学会, Oct. 2004
    Japanese, 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
  • Immunoregulatory defects of V alpha 24(+)V beta 11(+) NKT cells in development of Wegener's granulomatosis and relapsing polychondritis
    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, Jun. 2004, [Peer-reviewed]
    English, Scientific journal
  • Clinical features of bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody
    D Takagi; Y Nakamaru; S Maguchi; Y Furuta; S Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 113, 5, 388, 393, May 2004, [Peer-reviewed]
    English, Scientific journal
  • 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, 107, 4, 399, 399, (一社)日本耳鼻咽喉科学会, Apr. 2004
    Japanese
  • Macrophage migration inhibitory factor in allergic rhinitis: Its identification in eosinophils at the site of inflammation
    Y Nakamaru; D Takagi; N Oridate; Y Furuta; J Nishihira; S Fukuda
    ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 113, 3, 205, 209, Mar. 2004, [Peer-reviewed]
    English, Scientific journal
  • The efficacy of Burow's solution as an ear preparation for the treatment of chronic ear infections
    M Kashiwamura; E Chida; M Matsumura; Y Nakamaru; N Suda; Y Terayama; S Fukuda
    OTOLOGY & NEUROTOLOGY, 25, 1, 9, 13, Jan. 2004, [Peer-reviewed]
    English, Scientific journal
  • 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, 21, 2, 80, 82, 日本耳鼻咽喉科免疫アレルギー学会, Jun. 2003
    Japanese, 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, 29, 2, 363, 363, (一社)日本頭頸部癌学会, May 2003
    Japanese
  • 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, 106, 4, 393, 393, (一社)日本耳鼻咽喉科学会, Apr. 2003
    Japanese
  • Treatment of relapsing polychondritis
    Yuji Nakamaru; Dai Takagi; Masanori Maeda; Yasushi Furuta; Satoshi Fukuda; Shiroh Maguchi
    Journal of Otolaryngology of Japan, 106, 3, 185, 191, Oto-Rhino-Laryngological Society of Japan Inc., 2003, [Peer-reviewed]
    Japanese, Scientific journal
  • Otologic manifestations of Wegener's granulomatosis
    D Takagi; Y Nakamaru; S Maguchi; Y Furuta; S Fukuda
    LARYNGOSCOPE, 112, 9, 1684, 1690, Sep. 2002, [Peer-reviewed]
    English, Scientific journal
  • Clonotypic analysis of T cells accumulating at arthritic lesions in HTLV-I env-pX transgenic rats
    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, Feb. 2002, [Peer-reviewed]
    English, Scientific journal
  • A case of invasive aspergillosis of the paranasal sinuses with a feature of allergic Aspergillus sinusitis
    Y Nakamaru; S Fukuda; S Maguchi; D Takagi; Y Inuyama
    OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 126, 2, 204, 205, Feb. 2002, [Peer-reviewed]
    English, Scientific journal
  • Diagnosis of the elongated styloid process by three-dimensional computed tomography
    Y Nakamaru; S Fukuda; S Miyashita; M Ohashi
    AURIS NASUS LARYNX, 29, 1, 55, 57, Jan. 2002, [Peer-reviewed]
    English, Scientific journal
  • Correlation between the levels of circulating adhesion molecules and PR3-ANCA in Wegener's granulomatosis
    M Takizawa; S Maguchi; Y Nakamaru; Y Miyatake; S Fukuda; Y Inuyama
    AURIS NASUS LARYNX, 28, S59, S62, May 2001, [Peer-reviewed]
    English, Scientific journal
  • 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, 104, 1増刊, 77, 77, (一社)日本耳鼻咽喉科学会, Jan. 2001
    Japanese
  • Immunological hyperresponsiveness in HTLV-1 LTR-env-pX transgenic rats: A prototype animal model for collagen vascular and HTLV-I-related inflammatory diseases
    Y Nakamaru; A Ishizu; H Ikeda; T Sugaya; K Fugo; M Higuchi; H Yamazaki; T Yoshiki
    PATHOBIOLOGY, 69, 1, 11, 18, 2001, [Peer-reviewed]
    English, Scientific journal
  • Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.
    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, Apr. 1997, [International Magazine]
    English, Scientific journal, 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.
  • A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I.
    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, Feb. 1997, [Peer-reviewed]
    English, Scientific journal
  • The association between human leukocyte antigens (HLA) and cytoplasmic-antineutrophil cytoplasmic antibody (cANCA)-positive Wegener's granulomatosis in a Japanese population
    Y. Nakamaru; S. Maguchi; M. Takizawa; S. Fukuda; Y. Inuyama
    Rhinology, 34, 3, 163, 165, Sep. 1996, [Peer-reviewed]
    English, Scientific journal
  • ANTINEUTROPHIL CYTOPLASMIC ANTIBODY (C-ANCA) LEVELS IN RELATION TO THE TREATMENT OF WEGENER'S GRANULOMATOSIS
    MAGUCHI Shiroh; TAKIZAWA Masahiko; MIYATAKE Yukiko; NAKAMARU Yuuji; FUKUDA Satoshi; INUYAMA Yukio
    Nippon Jibiinkoka Gakkai Kaiho, 98, 6, 974, 983, The Oto-Rhino-Laryngological Society of Japan, Inc., 20 Jun. 1995
    Japanese, 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.
  • Laryngeal Carcinoma with Mediastinal Lesions; A Report of 3 Cases
    KASHIWAMURA Masaaki; YAMADA Kazuyuki; HIYAMA Shigeki; FUKUDA Satoshi; MAGUCHI Shirou; YORITA Akiharu; NAKAMARU Yuuji; INUYAMA Yukio
    Pract.Otol. (Kyoto), 88, 2, 219, 224, The Society of Practical Otolaryngology, 01 Feb. 1995
    Japanese, 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.
  • 当科における鼻骨骨折症例の検討
    中丸 裕爾; 本間 明宏; 飯塚 桂司
    耳鼻咽喉科・頭頸部外科, 65, 9, 745, 748, (株)医学書院, Sep. 1993
    Japanese, 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
  • Intravascular Papillary Endothelial Hyperplasia in the Left Submandibular Area; A Case Report
    Yuji Nakamaru; Keiji Iizuka; Akihiro Honma; Yutaka Yoshida
    Practica Oto-Rhino-Laryngologica, 86, 12, 1747, 1751, 耳鼻咽喉科臨床学会, 1993
    English, Scientific journal
■ Other Activities and Achievements
■ Syllabus
  • 医学総論, 2024年, 博士後期課程, 医学研究科
  • 基本医学研究, 2024年, 修士課程, 医学院
  • 基本医学総論, 2024年, 修士課程, 医学院
  • 医学総論, 2024年, 博士後期課程, 医学院
  • 基盤医学研究, 2024年, 博士後期課程, 医学院
  • 臨床医学研究, 2024年, 博士後期課程, 医学院
  • 耳鼻咽喉科学, 2024年, 学士課程, 医学部
■ Research Themes
  • 顆粒球細胞外トラップによる難治性副鼻腔炎の病態解明と新規バイオマーカー作成
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    中丸 裕爾
    抗好中球細胞質抗体(anti-neutrophil cytoplasmic antibody: ANCA)関連血管炎(AAV)に伴う副鼻腔炎や好酸球性副鼻腔炎は、保存的治療が効果の乏しい難治性副鼻腔炎である。近年、顆粒球細胞外トラップ(extracellular traps: ETs)という、病原微生物を捕捉するために好中球や好酸球から放出される網状の物質が、過剰に産生されることで自己免疫性疾患やアレルギー疾患などを引き起こすことがわかってきた。AAVにおいては腎臓や中耳において好中球ETsが、喘息や好酸球性副鼻腔炎においては好酸球ETsが炎症局所に存在することが報告されているが、鼻副鼻腔における各ETsを定量した報告はない。
    今回の研究では、難治性副鼻腔炎(AAV、好酸球性副鼻腔炎)症例の検体を用いて、好酸球、好中球両方のETsの存在および発現レベル値を測定することで好酸球性副鼻腔炎やAAVによる副鼻腔炎の診断・疾患活動性に関するバイオマーカーとしての有用性を評価することを目的とする。
    本年は1. 難治性副鼻腔炎(AAV、好酸球性副鼻腔炎)患者を疾患群、一般的な副鼻腔炎(急性副鼻腔炎、非好酸球性副鼻腔炎)患者を対照群として、血液、鼻汁、鼻腔粘膜組織を採取した。また、2. ETsを構成するcell-free DNA、Cit-H3-DNA複合体、MPO-DNA複合体などをELISA法で測定した。
    現在、好酸球性副鼻腔炎と通常の慢性副鼻腔炎の鼻汁検体が好酸球性副鼻腔炎16例、通常の副鼻腔炎が7例集まっている。現在までの検討の結果、好酸球性副鼻腔炎と一般的な副鼻腔炎において、ETsの有意差が認められる項目も出てきている。
    今後症例を増やし検討を続ける。
    日本学術振興会, 基盤研究(C), 北海道大学, 23K08928
  • Basic research of SIRT1 activator to treat eosinophilic sinusitis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2020 - 31 Mar. 2023
    Nakamaru Yuji
    To investigate the role of SIRT1 in the pathology of eosinophilic sinusitis, we evaluated 1. SIRT1 expression in the inflamed area of eosinophilic sinusitis, and 2. SIRT1-induced changes in nasal mucosal epithelial barrier function. First, the expression of SIRT1 in the inflamed area of eosinophilic sinusitis was confirmed by immunohistochemical staining. SIRT1 expression in the inferior turbinate mucosa was found to be abundant in epithelial cells. Next, to examine epithelial barrier function, we investigated the role of SIRT1 in the transepithelial barrier function of the nasal mucosal epithelium. No change in barrier function was observed with the use of inhibitors and promoter drug alone.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 20K09703
  • Role of NKT cells on eosinochilic chronic rhinosinusitis
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2014 - 31 Mar. 2017
    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, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26462575
  • basic research of SIRT1 activator for curative treatment of allergic rhinitis
    Grants-in-Aid for Scientific Research
    2015 - 2017
    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, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 15K10775
  • Basic research of SIRT1 for treatment of allergic rhinitis
    Grants-in-Aid for Scientific Research
    2012 - 2014
    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, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 24592574
  • The investigation of SIRT1 for permanent cure of allergic rhinitis
    Grants-in-Aid for Scientific Research
    2009 - 2011
    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.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 21592173
  • Basic study for permanent cure of allergic rhinitis with use of the activator of a histone deacetylase
    Grants-in-Aid for Scientific Research(基盤研究(C))
    2007 - 2008
    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, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 19591950
  • basic research of macrophage inhibitory factor for allergic rhinitis treatment
    Grants-in-Aid for Scientific Research(基盤研究(C))
    2005 - 2006
    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, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 17591772
  • Investigation on the pathogenesis of herpetic facial nerve paralysis
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2004 - 2006
    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...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 16390482
  • 抗マクロファージ遊走阻止因子を用いたアレルギー性鼻炎治療のための基礎的研究
    科学研究費補助金(若手研究(B))
    2003 - 2004
    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...
    文部科学省, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 15790918