研究者詳細 - 小川　郁

論文 - 小川　郁

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Effects of tinnitus treatments on sleep disorders in patients with tinnitus

Wakabayashi Satoko, Saito Hideyuki, Oishi Naoki, Shinden Seiichi, Ogawa Kaoru

International Journal of Audiology 1 - 5 2017年09月

ISSN 1499-2027

Objective: To assess the effects of tinnitus treatments on sleep disorders in patients with tinnitus. Design: Subjects completed the Pittsburg Sleep Quality Index (PSQI), Tinnitus Handicap Inventory (THI), Self-rating Depression Scale (SDS), and State Trait Anxiety Inventory (STAI). The questionnaire results and the patients’ sex, age, time since the onset of tinnitus, and mean hearing level were examined, and differences between a sleep disorder group and a normal sleep group were examined. Patients completed the questionnaires again after initiating tinnitus treatments (counselling and use of sound generators), and the change in questionnaire scores at follow-up was evaluated. Study sample: Patients (N = 100) with tinnitus who visited Keio University Hospital and started treatment without medication between 2005 and 2008. Results: Sixty-six percent of the patients had sleep disorders. Compared with patients without sleep disorders, patients with sleep disorders had significantly higher SDS and STAI scores at the first visit. The mean PSQI scores showed significant improvement at follow-up. Conclusions: Sleep disorders in patients with tinnitus improved after tinnitus treatments. Complex interactions between depressive symptoms and anxiety may occur in these patients. The improvement in sleep disorders at follow-up was correlated with improvements in tinnitus severity and state anxiety.

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Clinical characteristics of patients with tinnitus evaluated with the Tinnitus Sample Case History Questionnaire in Japan

Kojima Takashi, Kanzaki Sho, Oishi Naoki, Ogawa Kaoru

PLoS ONE 12 （ 8 ） 2017年08月

ISSN 1932-6203

Background: The Tinnitus Sample Case History Questionnaire was determined as a standardized questionnaire for obtaining patient case histories and for characterizing patients into subgroups at the Tinnitus Research Initiative in 2006. In this study, we developed a Japanese version of this questionnaire for evaluating the clinical characteristics of patients with tinnitus. The Japanese version of the questionnaire will be available for evaluating treatments for tinnitus and for comparing data on tinnitus in research centers. Aims/Objectives: To evaluate the clinical characteristics of patients with tinnitus in Japan using a newly developed Japanese version of Tinnitus Sample Case History Questionnaire. Study design: This was a prospective study based on patient records. Setting: University hospitals, general hospitals, and clinics. Subjects and methods: We collected patient data using a Japanese translated version of the Tinnitus Sample Case History Questionnaire. In total, 584 patients who visited our institutions in Japan between August 2012 and March 2014 were included (280 males and 304 females; age 13–92 years; mean age, 60.8). We examined patients after dividing them into two groups according to the presence or absence of hyperacusis. The collected results were compared with those from the Tinnitus Research Initiative database. Results: Compared with the TRI database, there were significantly more elderly female patients and fewer patients with trauma-associated tinnitus. There was a statistically lower ratio of patients with hyperacusis. We found that patients with tinnitus in addition to hyperacusis had greater tinnitus severity and exhibited higher rates of various complications. Conclusion: The Japanese version of the Tinnitus Sample Case History Questionnaire developed in this study can be a useful tool for evaluating patients with tinnitus in Japan. The results of this multicenter study reflect the characteristics of patients with tinnitus who require medical care in Japan. Our data provides a preliminary basis for an international comparison of tinnitus epidemiology.

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Clinical outcomes of transoral videolaryngoscopic surgery for hypopharyngeal and supraglottic cancer

Imanishi Yorihisa, Ozawa Hiroyuki, Sakamoto Koji, Fujii Ryoichi, Shigetomi Seiji, Habu Noboru, Otsuka Kuninori, Sato Yoichiro, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Tomita Toshiki, Ogawa Kaoru

BMC Cancer 17 （ 1 ） 2017年06月

ISSN 1471-2407

Background: Transoral videolaryngoscopic surgery (TOVS) was developed as a new distinct surgical procedure for hypopharyngeal cancer (HPC) and supraglottic cancer (SGC) staged at up to T3. However, long-term treatment outcomes of TOVS remain to be validated. Methods: Under a straight broad intraluminal view provided by combined use of a distending laryngoscope and a videolaryngoscope, we performed en bloc tumor resection via direct bimanual handling of the ready-made straight-form surgical instruments and devices. We retrospectively analyzed functional and oncologic outcomes of 72 patients with HPC (n = 58) or SGC (n = 14) whose minimum follow-up was 24 months or until death. Results: The cohort comprised nine patients of Tis, 23 of T1, 33 of T2, and 7 of T3. Among 36 patients (50%) who underwent neck dissection simultaneously, all but one were pathologically node-positive. Twelve patients underwent postoperative concurrent chemoradiation (CCRT) as adjuvant treatment, and another four patients underwent radiation or CCRT for second or later primary cancer. The endotracheal tube was removed in an operation room in all but two patients who underwent temporary tracheostomy. Pharyngeal fistula was formed transiently in two patients. The median time until patients resumed oral intake and could take a soft meal was 2 and 5 days, respectively. Eventually, 69 patients (96%) took normal meals. The 5-year cause-specific survival (CSS), overall survival (OS), larynx-preserved CSS, and loco-regional controlled CSS were 87.3%, 77.9%, 86.0%, and 88.0%, respectively. Multivariate analysis revealed N2-3 as an independent prognostic factor in both CSS (hazard ratio [HR] = 25.51, P = 0.008) and OS (HR = 4.90, P = 0.022), which indirectly reflected higher risk of delayed distant metastasis. Conclusions: Considering its sound functional and oncological outcomes with various practical advantages, TOVS can be a dependable, less invasive, and cost-effective surgical option of an organ-function preservation strategy for HPC and SGC.

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Characterization of slow-cycling cells in the mouse cochlear lateral wall

Li Yang, Watanabe Kotaro, Fujioka Masato, Ogawa Kaoru

PLoS ONE 12 （ 6 ） 2017年06月

ISSN 1932-6203

Cochlear spiral ligament fibrocytes (SLFs) play essential roles in the physiology of hearing including ion recycling and the generation of endocochlear potential. In adult animals, SLFs can repopulate after damages, yet little is known about the characteristics of proliferating cells that support SLFs’ self-renewal. Here we report in detail about the characteristics of cycling cells in the spiral ligament (SL). Fifteen P6 mice and six noise-exposed P28 mice were injected with 5-bromo-2′-deoxyuridine (BrdU) for 7 days and we chased BrdU retaining cells for as long as 60 days. Immunohistochemistry revealed that the BrdU positive IB4 (an endotherial marker) negative cells expressed an early SLF marker Pou3f4 but negative for cleaved-Caspase 3. Marker studies revealed that type 3 SLFs displayed significantly higher percentage of BrdU⁺ cells compared to other subtypes. Notably, the cells retained BrdU until P72, demonstrating they were dividing slowly. In the noise-damaged mice, in contrast to the loss of the other types, the number of type 3 SLFs did not altered and the BrdU incorporating- phosphorylated Histone H3 positive type 3 cells were increased from day 1 to 14 after noise exposure. Furthermore, the cells repopulating type 1 area, where the cells diminished profoundly after damage, were positive for the type 3 SLF markers. Collectively, in the latral wall of the cochlea, type 3 SLFs have the stem cell capacity and may contribute to the endogenous regeneration of lateral wall spiral ligament. Manipulating type 3 cells may be employed for potential regenerative therapies.

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Assessment of hyperacusis with a newly produced Japanese version of the Khalfa hyperacusis questionnaire

Oishi Naoki, Yamada Hiroyuki, Kanzaki Sho, Kurita Akihiro, Takiguchi Yoichiro, Yuge Isamu, Asama Yoji, Masuda Masatsugu, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 5 2017年04月

ISSN 0001-6489

Objectives: The purpose of this study was to determine the validity and reliability of a Japanese version of the Khalfa hyperacusis questionnaire (KHQ) and proposed a threshold KHQ score for classifying hyperacusis. Methods: In total, 112 patients with hyperacusis (group A) and 103 patients without hyperacusis (group B). The patients in group A were further classified into the following subgroups: subjects with hyperacusis as their chief complaint (n = 26, group A1) and subjects with hyperacusis accompanied by chief complaints of tinnitus and/or hearing loss (n = 86, group A2). Results: The average total questionnaire score for patients in group A was 11.8 ± 9.7, which was statistically significantly higher than that of patients in group B, 5.7 ± 4.8. Cronbach’s coefficients for internal consistency were high for the total score (0.92). The average total scores for groups A1 and A2 were 18.1 ± 11.1 and 9.9 ± 8.4, respectively, and the difference between the groups was statistically significant. Conclusions: We developed a Japanese version of the KHQ. It showed high reliability and validity; suggesting its usefulness in clinical practice. We propose that a total KHQ score of 16 is an appropriate cutoff for classifying hyperacusis

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A nationwide multicenter study of the Cochlin tomo-protein detection test

Matsuda Han, Sakamoto Kei, Matsumura Tomohiro, Saito Shiho, Shindo Susumu, Fukushima Kunihiro, Nishio Shin ya, Kitoh Ryosuke, Shibasaki Osamu, Ito Akinori, Araki Ryuichiro, Usami Shin ichi, Suzuki Mamoru, Ogawa Kaoru, Hasegawa Tomonori, Hagiwara Yoshiaki, Kase Yasuhiro, Ikezono Tetsuo

Acta Oto-Laryngologica 1 - 7 2017年03月

ISSN 0001-6489

Objective: To investigate the positive rate for the Cochlin tomo-protein (CTP: an inner ear-specific protein) detection test among patients with inner ear-related clinical manifestations and evaluate the clinical characteristics of definite perilymphatic fistula (PLF). Methods: We have performed an ELISA-based CTP detection test using middle ear lavage (MEL) samples from 497 cases of suspected PLF enrolled from 70 clinical centers nationwide between 2014 and 2015. In addition to the CTP-positive rate, audio-vestibular symptoms were compared between CTP-positive and -negative cases. Results: 8–50% of patients in category 1 (trauma, middle and inner ear disease cases), and about 20% of those in categories 2, 3 and 4 (external origin antecedent events, internal origin antecedent events, and without antecedent event, respectively) were positive for CTP. In category 1 cases, the earlier tested samples showed a higher CTP-positive rate, whereas no differences were observed in categories 2, 3 or 4. The characteristic clinical features in the earlier tested cases were nystagmus and fistula sign in CTP test-positive cases in category 1, and streaming water-like tinnitus in those in categories 2, 3 and 4. Conclusion: The present study clarified that CTP detection test-positive patients exist at considerable rates among patients with inner ear-related manifestations.

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Mitochondrial mutations in maternally inherited hearing loss

Mutai Hideki, Watabe Takahisa, Kosaki Kenjiro, Ogawa Kaoru, Matsunaga Tatsuo

BMC Medical Genetics 18 （ 1 ） 2017年03月

ISSN 1471-2350

Background: Although the mitochondrial DNA (mtDNA) mutations m.1555A > G and m.3243A > G are the primary causes of maternally inherited sensorineural hearing loss (SNHL), several other mtDNA mutations are also reported to be associated with SNHL. Methods: Screening of m.1555A > G and m.3243A > G mutations was performed for 145 probands. Nine probands fulfilled the following criteria: 1) bilateral and symmetric SNHL, 2) ≥ 4 family members with SNHL with a maternal trait of inheritance in ≥ 2 generations, 3) onset of SNHL before the age of 40 years, 4) high-frequency SNHL, and 5) no record of environmental factors related to SNHL. Sequencing of additional mtDNA regions was performed for five subjects meeting the clinical criteria, but the screening results were negative. Results: Among the nine cases meeting the five clinical criteria detailed above, three had the m.1555A > G mutation in MTRNR1, one had a m.3243A > G mutation in MTTL1, and one case had a m.7511T > C mutation in MTTS1. In the family with the m.7511T > C mutation, penetrance of SNHL among maternally related subjects was 9/17 (53%). The age at onset varied from birth (congenital) to adulthood. Hearing levels varied from normal to moderately impaired, unlike previously reported subjects with this mutation, where some maternal family members presented with profound SNHL. Family members with the m.7511T > C mutation and SNHL did not exhibit any specific clinical characteristics distinct from those of other individuals with SNHL and different mtDNA mutations. Among the 136 probands who did not meet the criteria detailed above, one case had the m.1555A > G mutation, and three cases had the m.3243A > G mutation. Conclusions: Since five of nine probands with the clinical criteria used in this study had mtDNA mutations, these criteria may be helpful for identification of candidate patients likely to have mtDNA mutations.

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Utility of clinico-biological data for long-term prognosis of head and neck terminal cancer

Kawasaki Taiji, Wasano Koichiro, Yamamoto Sayuri, Tomisato Shuta, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 4 2017年03月

ISSN 0001-6489

Objective: The prognosis of terminal head and neck cancer is traditionally determined using indices such as the palliative prognosis index. We aimed to develop an alternative prognosis index using clinico-biological data. Methods: This retrospective case-series study included 33 head and neck cancer patients whose cancer recurred despite receiving radiation therapy between April 2010 and April 2014. Clinico-biological data were collected the day patients were diagnosed as terminal. Bivariate correlation analyses were performed on survival times and clinico-biological data. For multivariate regression analyses, patients were divided into two groups: (1) patients who survived >120 days, and (2) those who survived <120 days. Group clinico-biological data were used to determine survival-time cutoff points for the prognosis index. Results: Bivariate analyses revealed significant correlations between survival time and BMI, hemoglobin, albumin, C-reactive protein (CRP), Onodera’s Prognostic Nutritional Index (O-PNI), modified Glasgow Prognostic Score (mGPS), and Performance Status (PS). Multivariate analyses showed a strong correlation between survival time and BMI. The two groups differed significantly in BMI, albumin, CRP, O-PNI, and mGPS. In multivariate analyses BMI, CRP, and O-PNI differed significantly in the two groups. Conclusion: BMI ≤16.4, CRP ≥1.01, and O-PNI ≤33.4 are significant predictors of long-term survival in terminal cancer patients.

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Epidemiological survey of acute low-tone sensorineural hearing loss

Sato Hiroaki, Kuwashima Shigeru, Nishio Shin Ya, Kitoh Ryosuke, Fukuda Satoshi, Hara Akira, Hato Naohito, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Ogawa Kaoru, Sano Hajime, Sone Michihiko, Shojaku Hideo, Takahashi Haruo, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S34 - S37 2017年03月

ISSN 0001-6489

Objectives: A nationwide epidemiological survey involving 23 hospitals in Japan was conducted and the predictive values of demographic data were examined statistically. Methods: A total of 642 patients from 23 hospitals, including 20 university hospitals, in Japan were enrolled in the study. Age ranged from 8 to 87 years, and all were diagnosed with acute low-tone sensorineural hearing loss (ALHL) between 1994 and 2016. Demographic data for the patients, such as symptoms, gender, mean age, and distribution of ALHL grading, were collected and analyzed in relation to prognosis using Student’s t-test, χ ² test and logistic regression. Results: Female gender (p <.013), younger age (p <.001), low-grade hearing loss (p <.001), and shorter interval between onset and initial visit (p <.004) were significantly predictive of a good prognosis. The prognosis for definite ALHL was significantly better than that for probable ALHL (p <.007). Conclusions: The severity of initial hearing loss, interval between onset and initial visit and age were important prognostic indicators for ALHL, while female gender was an important prognostic indicator peculiar to ALHL.

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Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss

Yoshida Tadao, Sone Michihiko, Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Kanzaki Sho, Hato Naohito, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S38 - S43 2017年03月

ISSN 0001-6489

Objectives: The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis. Methods: Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis. Results: Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent. Conclusion: The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.

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Nationwide epidemiological survey of idiopathic sudden sensorineural hearing loss in Japan

Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Kanzaki Sho, Hato Naohito, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Testuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S8 - S16 2017年03月

ISSN 0001-6489

Objectives: Using a large-scale nationwide survey database, we investigated the epidemiological characteristics for idiopathic SSNHL in Japan. Methods: The subjects for this analysis were patients registered in a Japanese multicentre database between April 2014 and March 2016. A total of 3419 idiopathic SSNHL patients were registered in the database, and the clinical characteristics of the idiopathic SSNHL patients were obtained. Several factors associated with the severity of hearing impairment and prognosis were then investigated. Statistical analysis was performed to clarify the factors associated with the severity of hearing impairment and prognosis. Results: There were significant correlations between the severity of hearing loss and diabetes mellitus, kidney disease, past history of brain infarction, heart disease, age (under 16 years/elderly), and symptoms of vertigo/dizziness. We also analyzed the prognostic factors for idiopathic SSNHL, and found that the severity of hearing loss (Grade 3 or 4), heart disease, aged 65 years or over, time from onset to treatment (over 7 days), and symptoms of vertigo/dizziness were all significantly related to poor prognosis. Conclusion: The present large-scale clinical survey revealed current epidemiological trends for idiopathic sudden sensorineural hearing loss (SSNHL) and various factors associated with the severity of hearing impairment and prognosis.

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Relationships among drinking and smoking habits, history of diseases, body mass index and idiopathic sudden sensorineural hearing loss in Japanese patients

Umesawa Mitsumasa, Kobashi Gen, Kitoh Ryoshuke, Nishio Shin Ya, Ogawa Kaoru, Hato Naohito, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S17 - S23 2017年03月

ISSN 0001-6489

Objectives: To present the cardiovascular risk factors in idiopathic sudden sensorineural hearing loss (SSNHL) patients enrolled in a nationwide epidemiological survey of hearing disorders in Japan. Materials and methods: We compiled the cardiovascular risk factors in 3073 idiopathic SSNHL subjects (1621 men and 1452 women) and compared their proportions with controls as part of the National Health and Nutrition Survey in Japan, 2014. The cardiovascular risk factors consisted of drinking and smoking habits, a history of five conditions related to cardiovascular disease and body mass index. Results: The proportion of current smokers was significantly higher among men aged 50–59, 60–69 and 70+ and among women aged 30–39, 40–49 and 60–69. The proportion of patients with a history of diabetes mellitus was significantly higher among men aged 50–59, 60–69 and 70+, but not in women. In addition, male and female SSNHL subjects aged 60–69 showed lower proportions of current drinking; and female SSNHL subjects aged 60–69 showed higher proportions of overweight (BMI ≥25 kg/m²). Conclusions: The present cross-sectional study revealed showed significantly higher proportions of current smokers among both men and women as well as those with a history of diabetes mellitus among men across many age groups in patients with idiopathic SSNHL compared with the controls.

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The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss

Okada Masahiro, Hato Naohito, Nishio Shin Ya, Kitoh Ryosuke, Ogawa Kaoru, Kanzaki Sho, Sone Michihiko, Fukuda Satoshi, Hara Akira, Ikezono Tetsuo, Ishikawa Kotaro, Iwasaki Satoshi, Kaga Kimitaka, Kakehata Seiji, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nakagawa Takashi, Nishizaki Kazunori, Noguchi Yoshihiro, Sano Hajime, Sato Hiroaki, Suzuki Mikio, Shojaku Hideo, Takahashi Haruo, Takeda Hidehiko, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin Ichi

Acta Oto-Laryngologica 137 S30 - S33 2017年03月

ISSN 0001-6489

Objective: To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies. Methods: Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups. Results: In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids. Conclusion: A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.

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The clinical features and prognosis of mumps-associated hearing loss

Morita Shinya, Fujiwara Keishi, Fukuda Atsushi, Fukuda Satoshi, Nishio Shin ya, Kitoh Ryosuke, Hato Naohito, Ikezono Tetsuo, Ishikawa Kotaro, Kaga Kimitaka, Matsubara Atsushi, Matsunaga Tatsuo, Murata Takaaki, Naito Yasushi, Nishizaki Kazunori, Ogawa Kaoru, Sano Hajime, Sato Hiroaki, Sone Michihiko, Suzuki Mikio, Takahashi Haruo, Tono Tetsuya, Yamashita Hiroshi, Yamasoba Tatsuya, Usami Shin ichi

Acta Oto-Laryngologica 1 - 4 2017年02月

ISSN 0001-6489

Conclusions: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss. Objective: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes. Subjects and methods: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016. Results: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

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Hochuekkito, a Japanese Herbal Medicine, Restores Metabolic Homeostasis between Mitochondrial and Glycolytic Pathways Impaired by Influenza A Virus Infection

Takanashi Keita, Dan Katsuaki, Kanzaki Sho, Hasegawa Hideki, Watanabe Kenji, Ogawa Kaoru

Pharmacology 240 - 249 2017年02月

ISSN 0031-7012

Background: Hochuekkito (HKT), a traditional Japanese herbal medicine (Kampo), has been used to treat symptoms of several diseases. In a recent clinical study, HKT was shown to be protective against the influenza virus infection. However, the underlying mechanism of the prophylactic effect is not clear. Mitochondrial and glycolytic pathways play important roles in cellular energy metabolism to maintain biological functions. These metabolic pathways are affected by the influenza virus infection. In this study, we examined the relationship between the preventive effects of HKT against the influenza virus infection and cellular energy metabolism in mitochondria and glycolysis using Madin-Darby canine kidney cells and influenza A/PR/8/34 (H1N1) virus (IAV). Methods: Mitochondrial and glycolytic metabolic pathways were evaluated on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), respectively, using the XF24 Extracellular Analyzer. Results: The OCR/ECAR ratio in IAV-infected cells was lower than that in control cells. Cells that were treated with HKT before IAV infection showed a metabolic pattern similar to that in the control cells (increase in both OCR and ECAR). Conclusions: Our results suggest that HKT not only activates both mitochondrial and glycolytic energy metabolism in IAV-infected cells but also helps maintain metabolic homeostasis similar to that in noninfected cells.

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Cochlear Cell Modeling Using Disease-Specific iPSCs Unveils a Degenerative Phenotype and Suggests Treatments for Congenital Progressive Hearing Loss

Hosoya Makoto, Fujioka Masato, Sone Takefumi, Okamoto Satoshi, Akamatsu Wado, Ukai Hideki, Ueda Hiroki R., Ogawa Kaoru, Matsunaga Tatsuo, Okano Hideyuki

Cell Reports 18 （ 1 ） 68 - 81 2017年01月

ISSN 2211-1247

Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, the most frequent syndromic form of hereditary hearing loss, is associated with mutations in the anion exchanger pendrin. Loss of pendrin function as an anion exchanger is thought to be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant pendrin aggregates and increased susceptibility to cellular stresses in cochlear epithelial cells induced from patient-derived induced pluripotent stem cells (iPSCs). These degenerative phenotypes were rescued by site-specific gene corrections. Moreover, low-dose rapamycin and metformin reduced aggregation and cell death. Our results provide an unexpected, comprehensive understanding of deafness due to “degenerative cochlear disease” and may contribute to rational therapeutic development. This iPSC-based disease model provides an approach to the study of pathogenesis and therapeutic development for hereditary hearing loss.

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Phonosurgical resection using submucosal infusion technique for precancerous laryngeal leukoplakia

Kono Takeyuki, Saito Koichiro, Yabe Haruna, Ogawa Kaoru

Laryngoscope 127 （ 1 ） 153 - 158 2017年01月

ISSN 0023-852X

Objectives/Hypothesis: This study was designed to assess the feasibility of the submucosal infusion technique combined with microflap dissection as a radical therapeutic and diagnostic option for precancerous laryngeal leukoplakia. Study Design: Retrospective study. Methods: Severe dysplasia or carcinoma in situ was diagnosed after phonomicrosurgical dissections in 25 patients with unilateral laryngeal leukoplakia. Of these, 15 patients preferred no additional surgery (observation group), whereas 10 patients underwent further laser subligamental cordectomy (additional surgery group). The relationship between the initial surgical margin and histopathological characteristics of additionally excised tissues was assessed to evaluate diagnostic reliability. Disease control was assessed to determine the oncologic efficacy of the therapeutic procedure. Comparative multidimensional vocal assessments were performed in both groups to evaluate functional advantages of one-stage excision. Results: After the initial phonomicrosurgical resection, three patients had residual dysplastic lesions near the vocal process and anterior commissure, whereas three other patients had lesions suspicious for recurrence. No postoperative malignant transformation was observed in any patient. Although well-preserved vocal function was observed in the observation group, vocal quality deteriorated shortly after laser surgery in the additional surgery group. Regarding acoustics, aerodynamics, and quality-of-life evaluations, statistically equivalent scores were observed between the observation and control groups, whereas scores were inferior in the additional surgery group than in the control group. Conclusions: Phonomicrosurgical resection may be a therapeutic option with oncologic efficacy against precancerous laryngeal leukoplakia. This radical management might achieve more satisfactory postoperative vocal function. Level of Evidence: NA Laryngoscope, 127:153–158, 2017.

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Novel pre-therapeutic scoring system using patient and haematological data to predict facial palsy prognosis

Wasano K., Ishikawa T., Kawasaki T., Yamamoto S., Tomisato S., Shinden S., Minami S., Wakabayashi T., Ogawa K.

Clinical Otolaryngology 2017年

ISSN 1749-4478

Objectives: We describe a novel scoring system, the facial Palsy Prognosis Prediction score (PPP score), which we test for reliability in predicting pre-therapeutic prognosis of facial palsy. We aimed to use readily available patient data that all clinicians have access to before starting treatment. Design: Multicenter case series with chart review. Setting: Three tertiary care hospitals. Participants: We obtained haematological and demographic data from 468 facial palsy patients who were treated between 2010 and 2014 in three tertiary care hospitals. Patients were categorised as having Bell's palsy or Ramsey Hunt's palsy. Main outcome measures: We compared the data of recovered and unrecovered patients. PPP scores consisted of combinatorial threshold values of continuous patient data (eg platelet count) and categorical variables (eg gender) that best predicted recovery. We created separate PPP scores for Bell's palsy patients (PPP-B) and for Ramsey Hunt's palsy patients (PPP-H). Results: The PPP-B score included age (≥65 years), gender (male) and neutrophil-to-lymphocyte ratio (≥2.9). The PPP-H score included age (≥50 years), monocyte rate (≥6.0%), mean corpuscular volume (≥95 fl) and platelet count (≤200 000 /μL). Patient recovery rate significantly decreased with increasing PPP scores (both PPP-B and PPP-H) in a step-wise manner. PPP scores (ie PPP-B score and PPP-H score) ≥2 were associated with worse than average prognosis. Conclusions: Palsy Prognosis Prediction scores are useful for predicting prognosis of facial palsy before beginning treatment.

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Current status and problems associated with tinnitus treatment at municipal hospitals

Inagaki Yozo, Mashino Kenji, Oishi Naoki, Kanzaki Sho, Ogawa Kaoru, Shinden Seiichi

Practica Oto-Rhino-Laryngologica 110 （ 3 ） 163 - 169 2017年

ISSN 0032-6313

Based on a series of studies including brain function tests, we reinforced and improved treatment for tinnitus by developing a tinnitus retraining therapy (TRT) that incorporates the "tinnitus pain model"; our laboratory subsequently introduced this therapy in 2013. This model provides a clinical explanation that tinnitus manifests and worsens through nerve synchronization of the auditory path and the non-auditory path with the pain network. Therefore, the target of tinnitus therapy based on this model is the auditory path generating the tinnitus and the pain network that worsens the tinnitus. The therapy mainly uses "acoustic therapy" and "directive counseling", which are the same as the original TRT. What characterizes this method is the central use of a hearing aid in the "acoustic therapy" targeting tinnitus patients with hearing loss. TRT incorporating the "tinnitus pain model" would be ideal for the establishment of an outpatient department dedicated to hearing loss and tinnitus. In actual practices, however, many hospitals avoid offering "directive counseling", as it is often difficult to provide sufficient counseling in a general outpatient setting. This report examined the tinnitus treatment practice of a municipal hospital with two otolaryngologists. The hospital administered TRT incorporating the "tinnitus pain model" to 62 cases (average age: 68.7 years, prevalence period: 16 months [median]). All the cases were treated with "directive counseling", while 32 cases used hearing aids as a part of "acoustic therapy". The tinnitus handicap inventory (THI) score showed a statistically significant reduction after treatment from 49.3±23.0 to 24.8±21.1. The improvement rate, based on an "improvement of 20 THI points or above" and "16 or lower final THI points" as the statistical criteria, was 62.9%. The proactive involvement of municipal hospitals in tinnitus treatment may reduce the frequency of doctor shopping by tinnitus patients and could help to break the "vicious circle" of tinnitus treatment practices.

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

Kikuchi Ryogo, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Turkish neurosurgery 27 （ 1 ） 1 - 7 2017年

ISSN 1019-5149

AIM: This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists.MATERIAL AND METHODS: We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS.RESULTS: Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed.CONCLUSION: T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

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