研究者詳細 - 小川　郁

論文 - 小川　郁

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Febrile neutropenia in patient with head and neck cancer treated with docetaxel, cisplatin and 5-fluorouracil (TPF protocol) - A comparison before and after the introduction of pegfilgrastim

Wasano Koichiro, Kawasaki Taiji, Hiraga Yoshihiko, Yamamoto Sayuri, Tomisato Shuta, Hashimoto Yosuke, Ogawa Kaoru

Practica Oto-Rhino-Laryngologica 110 （ 4 ） 287 - 293 2017年

ISSN 0032-6313

The TPF protocol composed of docetaxel, cisplatine and 5-fluorouracil, is the most commonly used chemotherapy regimen for the treatment of head and neck cancer. Recently, the importance of maintaining a relative dose-intensity (RDI) has been shown. Therefore, the treatment and prevention of febrile neutropenia, which can reduce the RDI of the TPF protocol, are important. Here, we compare patient outcomes before and after the introduction of pegfilgrastim for primary prophylaxis. The first group is consisted of 60 patients (88 chemotherapy courses) treated between January 2011 and October 2014 who did not receive prophylaxis. The second group consisted of 14 patients (20 chemotherapy courses) treated between November 2014 and July 2016 using pegfilgrastim. We examined the frequency of neutropenia (grade 3 and 4), febrile neutropenia (FN) and treatment-related death, the amount of granulocyte-colony stimulating factor (G-CSF) used, the cost for FN treatment and the hospitalization period. In the first group, there were 74 neutropenia events, 34 cases of FN and 2 treatment-related deaths; the average hospitalization period was 18.5 days. In the second group, there were 74 neutropenia events, 34 case of FN, and 0 treatment-related death; the average hospitalization period was 18.5 days. The frequency of adverse events, the amount of G-CSF used, the cost for FN and the hospitalization period were all significantly reduced by the introduction of pegfilgrastim. In conclusion, the administration of pegfilgrastim for the primary prophylaxis of FN was effective when included in the TPF protocol for the treatment of head and neck cancer.

Retrospective analysis of olfactory neuroblastoma cases treated with endoscopic endonasal approach

Ozawa Hiroyuki, Tomita Toshiki, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Ikari Yuichi, Saito Shin, Sato Yoichiro, Toda Masahiro, Ogawa Kaoru

Japanese Journal of Head and Neck Cancer 43 （ 1 ） 1 - 7 2017年

ISSN 1349-5747

We retrospectively reviewed nine cases of olfactory neuroblastoma in Keio University School of Medicine from 2010 to 2015. The surgical approach was the endoscopic endonasal approach, either alone or in combination with craniotomy, performed by a team of head and neck surgeons and a neurosurgeon. The distribution of patients according to the modified Kadish classification （A/B/C/D) and Dulguerov classification （T1/T2/ T3/T4) was 1/4/4/0 and 1/4/2/2. Tumors of six cases were removed by the endoscopic endonasal approach alone; three cases needed craniotomy to resect intra-dual tumors. Three-layered skull base reconstruction using fascia, pericranial flap and nasoseptal flap was used for five cases. None of the cases experienced cerebrospinal fluid leakage postoperatively. Seven patients received postoperative radiotherapy. Three cases experienced tumor recurrence, and underwent salvage surgery or radiotherapy. All cases remained alive, though the average observation time was less than 3 years. Recent reports have demonstrated that the endoscopic endonasal approach has a comparable control rate to the open approach for olfactory neuroblastoma. We believe that endoscopic endonasal skull base surgery should play a key role in the treatment of olfactory neuroblastoma in the years ahead.

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Efficacy and objective evaluation of non-echo-planar diffusion-weighted MRI by the PROPELLER technique in the diagnosis of cholesteatoma

Yamada Hiroyuki, Oishi Naoki, Kanzaki Sho, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 120 （ 5 ） 714 - 721 2017年

ISSN 0030-6622

In the diagnosis of cholesteatoma, non-echo-planar diffusion-weighted MRI using the PROPELLER(periodically rotated overlapping parallel lines with enhanced reconstruction)technique has been reported to be useful. However, interpretation of positive findings is subjective and the decision criteria remain unclear. It is necessary to establish an objective standard for evaluation of the signal intensity. The aim of this study was to establish whether diffusion MRI using the PROPELLER technique is effective for the diagnosis of cholesteatoma. Furthermore, we investigated whether objective evaluation is possible by comparing the signal intensities and determining which region of brain is the most suitable for such comparison. We evaluated 35 ears with a postoperative diagnosis of cholesteatoma for which preoperative evaluation had been performed by MRI using the PROPRLLER technique. We determined a lesion as positive if it showed a higher intensity than the cerebellar white matter. Furthermore, for objective evaluation, we set regions of interest and compared the highest signal intensity of the target lesion with that of the following parts of the brain ; cerebellum, cerebellar white matter, temporal lobe, temporal lobe white matter. The sensitivity/positive-predictive value were 85.7%, and the specificity/negative-predictive value was 42.9%. The smallest lesion observed was 3.8 mm in diameter. In addition, in 4 of the 35 ears, no lesion could be detected. Objective evaluation by comparison of the highest signal intensities of the regions of interest matched with the diagnosis after surgery in 26 of the 31 ears. The findings suggested that the cerebellar white matter was the most suitable among the 4 regions evaluated for such comparison. This method is thought to be useful, especially in cases where macroscopic evaluation of the lesions is difficult.

A clinical study of pharyngeal small cell carcinoma

Ito Fumihiro, Ozawa Hiroyuki, Sekimizu Mariko, Watanabe Yoshihiro, Tomita Toshiki, Imanishi Yorihisa, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 120 （ 6 ） 825 - 832 2017年

ISSN 0030-6622

Extrapulmonary small cell carcinoma arising from the pharynx is rare. We have experienced 4 cases of pharyngeal small cell carcinoma. All the patients were male, and the mean age was 66 years old. The primary site was the oropharynx in 2 cases and the hypopharynx in 2 cases. All the patients initially underwent surgical resection, followed by chemotherapy or chemoradiotherapy. Three patients died because of distant metastasis. One patient is still alive without disease. Twentyfour cases of pharyngeal small cell carcinoma have been reported to date. An analysis of these 28 cases, including our 4 cases, revealed that 20 of the cases had died because of pharyngeal small cell carcinoma. Thus, pharyngeal small cell carcinoma appears to be associated with a relatively poor prognosis similar to that of pulmonary small cell carcinoma. Patients with T3/4 or metastatic diseases have an especially poor prognosis. When the primary site is resectable with minimum invasion, surgery followed by chemotherapy or chemoradiotherapy might offer a better chance of inhibiting local recurrence, compared with other strategies.

Endonasal endoscopic approach for a giant cavernous sinus meningioma that extended to the middle cranial fossa with preoperative embolization

Tamura Ryota, Toda Masahiro, Kohno Maya, Ozawa Hiroyuki, Tomita Toshiki, Akiyama Takenori, Ogawa Kaoru, Yoshida Kazunari

Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 6 20 - 22 2016年12月

ISSN 2214-7519

Background Transcranial surgery is considered more appropriate than an endonasal endoscopic approach (EEA) for a large cavernous sinus meningioma with lateral extension. Case presentation A 6-cm-diameter hypervascular meningioma around cavernous sinus invaded the orbital apex and infratemporal fossa. 80% of the tumor was removed without too much blood loss via endoscopic endonasal transpterygoidal-infratemporal approach. Preoperative embolization from some feeding arteries was done, and 80% of the tumor staining disappeared. Discussion Tumor removal rates for giant meningioma are worse with EEA than with the transcranial approach because of various anatomical limitations and blood control. Recently, EEA has become more widely used with approaches such as the transpterygoidal approach. The operation can be done safely with preoperative embolization because the operative view is clear without bleeding. Conclusion Preoperative embolization for a large hypervascular tumor makes EEA more effective. A giant meningioma can be removed by EEA if the anatomical limitations can be identified and approached safely and effectively.

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The Preventive Effect of the Traditional Japanese Herbal Medicine, Hochuekkito, against Influenza A Virus via Autophagy in vitro

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

Pharmacology 99 - 105 2016年10月

ISSN 0031-7012

Background: Hochuekkito (HKT), a traditional Japanese herbal medicine, enhances the immunity of elderly or weak individuals. It is also known to have preventive effects against influenza clinically. However, the detailed mechanisms of the preventive effects have not been clarified. We examined the relationship between the preventive effects of HKT and autophagy, a known stress response and quality control mechanism, using Madin-Darby canine kidney cells and influenza A/PR/8/34 (H1N1) virus. Methods: The effect of HKT on autophagy in influenza A virus (IAV)-infected cells was assessed by Western blotting and fluorescence microscopy using an RFP-GFP-LC3B sensor kit. Results: In Western blotting, treatment with HKT before IAV infection (pre-HKT) tended to induce autophagy in IAV-infected cells at an early stage of infection, eventually suppressing IAV-induced autophagy. Moreover, several autolysosomes, indicative of normal autophagosome-lysosome fusion, were observed in Pre-HKT cells transduced with RFP-GFP-LC3B but not in untreated IAV-infected cells. Conclusions: These findings indicated that IAV-mediated inhibition of the fusion of autophagosomes with lysosomes was prevented by HKT treatment before infection. According to these results, we propose that this phenomenon is one of the preventive effects of HKT against IAV.

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Pretreatment Hematologic Findings as Novel Predictive Markers for Facial Palsy Prognosis

Wasano Koichiro, Kawasaki Taiji, Yamamoto Sayuri, Tomisato Shuta, Shinden Seiichi, Ishikawa Toru, Minami Shujiro, Wakabayashi Takeshi, Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (United States) 155 （ 4 ） 581 - 587 2016年10月

ISSN 0194-5998

Objective To examine the relationship between prognosis of 2 different facial palsies and pretreatment hematologic laboratory values. Study Design Multicenter case series with chart review. Setting Three tertiary care hospitals. Subjects and Methods We examined the clinical records of 468 facial palsy patients who were treated with an antiviral drug in combination with either oral or intravenous corticosteroids in participating hospitals between 2010 and 2014. Patients were divided into a Bell's palsy group or a Hunt's palsy group. We used the Yanagihara facial nerve grading system to grade the severity of facial palsy. "Recovery" from facial palsy was defined as achieving a Yanagihara score ≥36 points within 6 months of onset and having no accompanying facial contracture or synkinesis. We collected information about pretreatment hematologic findings, demographic data, and electrophysiologic test results of the Bell and Hunt group patients who recovered and those who did not. We then compared these data across the 2 palsy groups. Results In the Bell's palsy group, recovered and unrecovered patients differed significantly in age, sex, electroneuronography score, stapedial muscle reflex, neutrophil rate, lymphocyte rate, neutrophil-to-lymphocyte ratio, and initial Yanagihara score. In the Hunt's palsy group, recovered and unrecovered patients differed in age, electroneuronography score, stapedial muscle reflex, monocyte rate, platelet count, mean corpuscular volume, and initial Yanagihara score. Conclusions Pretreatment hematologic findings, which reflect the severity of inflammation and bone marrow dysfunction caused by a virus infection, are useful for predicting the prognosis of facial palsy.

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Pre-therapeutic nutritional assessment for predicting severe adverse events in patients with head and neck cancer treated by radiotherapy

Kono Takeyuki, Sakamoto Koji, Shinden Seiichi, Ogawa Kaoru

Clinical Nutrition 2016年08月

ISSN 0261-5614

Background & aims: Malnutrition is common in patients with head and neck cancer (HNSCC). It may be related to severe adverse toxicity as a result of radiotherapy. The aim was to investigate nutritional screening factors for severe adverse events. Methods: A retrospective chart review of 101 patients who underwent radiotherapy from 2009 to 2013 was performed. The relationships among severe adverse events and pretreatment nutritional parameters, including static variables (serum albumin, total protein, total lymphocyte counts, body mass index), dynamic variables (retinol-binding protein, transferrin, pre-albumin), and nutritional screening tools (Onodera's Prognostic Nutrition Index [O-PNI]; Nutrition Risk Index; Controlling Nutritional Status [CONUT] score; Nutritional Risk Screening 2002) were evaluated in addition to patient and treatment factors. Results: According to the static parameters, approximately 30% of patients were malnourished before treatment. Twenty-four patients exhibited severe adverse events. On univariate analysis, combined chemotherapy, advanced staging, O-PNI <40, and CONUT score ≥5 were significant predictors of severe adverse events. Multivariate analysis revealed that O-PNI <40 and combined chemotherapy independently predict severe adverse events. Conclusions: O-PNI is considered a useful nutritional factor for predicting severe adverse events in HNSCC patients undergoing chemoradiotherapy and facilitates the planning of aggressive nutritional interventions prior to treatment.

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Expression pattern of wolframin, the WFS1 (Wolfram syndrome-1 gene) product, in common marmoset (Callithrix jacchus) cochlea

Suzuki Noriomi, Hosoya Makoto, Oishi Naoki, Okano Hideyuki, Fujioka Masato, Ogawa Kaoru

NeuroReport 27 （ 11 ） 833 - 836 2016年08月

ISSN 0959-4965

Wolfram syndrome is an autosomal recessive disorder of the neuroendocrine system, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness) syndrome, and considered an endoplasmic reticulum disease. Patients show mutations in WFS1, which encodes the 890 amino acid protein wolframin. Although Wfs1 knockout mice develop diabetes, their hearing level is completely normal. In this study, we examined the expression of wolframin in the cochlea of a nonhuman primate common marmoset (Callithrix jacchus) to elucidate the discrepancy in the phenotype between species and the pathophysiology of Wolfram syndrome-associated deafness. The marmoset cochlea showed wolframin immunoreactivity not only in the spiral ligament type I fibrocytes, spiral ganglion neurons, outer hair cells, and supporting cells, but in the stria vascularis basal cells, where wolframin expression was not observed in the previous mouse study. Considering the absence of the deafness phenotype in Wfs1 knockout mice, the expression of wolframin in the basal cells of primates may play an essential role in the maintenance of hearing. Elucidating the function of wolframin protein in the basal cells of primates would be essential for understanding the pathogenesis of hearing loss in patients with Wolfram syndrome, which may lead to the discovery of new therapeutics.

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Successful continual intratympanic steroid injection therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis

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

Auris Nasus Larynx 2016年05月

ISSN 0385-8146

Objective: To report the treatment efficacy of continual intratympanic steroid injection (ITSI) therapy in a patient with refractory sensorineural hearing loss accompanied by relapsing polychondritis. Patient: A 49-year-old female diagnosed with relapsing polychondritis at the age of 45 years and who had been treated with corticosteroids and immunosuppressants developed sensorineural hearing loss in the left ear. Intervention: Her unilateral hearing loss did not recover despite receiving one cyclophosphamide pulse treatment, one methylprednisolone pulse treatment, and weekly leukapheresis. Thus, we decided to initiate weekly ITSI therapy. Main outcome measure: Pure tone audiometry. Results: A week after the first ITSI treatment, the patient's hearing improved. We continued ITSI therapy and attempted to extend the interval between treatments, but her hearing worsened when ITSI therapy was delivered at 2- to 3-week intervals. Thus, we returned ITSI therapy to once per week for 21 months (total of 71 treatments). She experienced no adverse events, like tympanic perforation, and 1 year after terminating the therapy, her hearing remained stable and did not worsen. Conclusions: Continual, weekly ITSI therapy was effective in treating sensorineural hearing loss accompanied by relapsing polychondritis. ITSI therapy may be a promising treatment option for sensorineural hearing loss caused by autoimmune disease.

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Tympanoplasty for chondrodysplasia punctata

Hosoya Makoto, Kanzaki Sho, Wakabayashi Satoko, Ogawa Kaoru

Auris Nasus Larynx 2016年05月

ISSN 0385-8146

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Usefulness and Limitation of Thyroglobulin Measurement in Fine Needle Aspirates (FNA-Tg) for Diagnosis of Neck Lymph Node Metastasis from Thyroid Carcinoma

Sakamoto Koji, Imanishi Yorihisa, Tomita Toshiki, Ozawa Hiroyuki, Sato Yoichiro, Inagaki Yozo, Yamada Hiroyuki, Ito Fumihiro, Suzuki Noriomi, Kono Takeyuki, Saito Shin, Noguchi Masaru, Nishiyama Takanori, Nakamura Shintaro, Fujita Hiroko, Watabe Takahisa, Shinden Seiichi, Ogawa Kaoru

Nihon Jibiinkoka Gakkai kaiho 119 （ 5 ） 721 - 726 2016年05月

ISSN 0030-6622

BACKGROUND: Preoperative diagnosis of lymph node metastasis from thyroid carcinoma is usually confirmed by using fine needle aspiration cytology (FNAC) when thyroid carcinoma is suspected based on the clinical findings. However, the result of FNAC sometimes leads to a false negative, especially in cases of hypocellular lesions such as metastases with cystic change. Thyroglobulin measurement in fine needle aspirates (FNA-Tg) has been shown to be a useful technique to detect the protein specifically secreted by thyroid follicular cells. Elevated FNA-Tg levels in an extra-thyroidal lesion means that the lesion comprises thyroid-originated tissue, most of which suggests the metastasis from thyroid carcinoma. Thus, FNA-Tg is expected to improve the sensitivity of FNAC for the aforementioned purpose.PATIENTS AND METHODS: From 2008 to 2012, 49 extra-thyroidal lesions from 43 patients with thyroid carcinoma were examined using both FNAC and FNA-Tg, followed by surgical resection with a histopathological diagnosis. The results were retrospectively reviewed and analyzed.RESULTS: Among 49 lesions, 47 were metastatic lymph nodes from thyroid carcinoma (46 papillary carcinoma and one follicular carcinoma), one was a metastatic lymph node from submandibular gland adenocarcinoma, and one was an ectopic thyroid gland. In the 47 cases of thyroid carcinoma, the sensitivity of FNAC was 57.4% (27/47), whereas that of FNA-Tg was 76.6% (36/47). When both methods were combined, the sensitivity increased to 93.6% (44/47). Metastasis from submandibular gland adenocarcinoma was considered to be an example of a false positive from FNAC, whereas an ectopic thyroid gland was an FNA-Tg false positive. Three lesions were negative for both FNAC and FNA-Tg, although metastases were suspected by imaging studies and confirmed by histopathological diagnosis, which were consistent with examples of a false negative from both FNAC and FNA-Tg findings.CONCLUSIONS: FNAC reflects whether the lesion has malignant cells, whereas FNA-Tg reflects whether the lesion has thyroid-originated tissue that specifically secrets thyroglobulin. Therefore, FNAC and FNA-Tg are considered to be complementary to each other for the preoperative diagnosis of lymph node metastasis from thyroid carcinoma. FNA-Tg was validated to improve the preoperative diagnostic sensitivity especially when combined with FNAC, however, it is attended with the possibility of a false positive or negative finding, which requires caution in interpretation of the findings.

Vascularized middle turbinate flap for the endoscopic endonasal reconstruction of the anterior olfactory groove

Tamura Ryota, Toda Masahiro, Kohno Maya, Watanabe Yoshihiro, Ozawa Hiroyuki, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurosurgical Review 39 （ 2 ） 297 - 302 2016年04月

ISSN 0344-5607

A vascularized middle turbinate flap (MTF) might be useful in the repair of lesions in the anterior olfactory groove. The sizes of the MTF and inferior turbinate flap (ITF) and these distances up to the frontal base were analyzed by computed tomography (CT) using a picture archiving and communication system (PACS) in 20 patients. The minimum flap measurement to reconstruct the skull base was defined as the distance from the basal plate to the medial slope or lateral slope edge of the MTF and the ITF on the coronal view. Next, we reviewed clinical data from three patients with dural deficits who underwent endoscopic vascularized MTF reconstruction. The distance to the frontal base from the ITF was significantly longer than that from the MTF. The minimum length of the MTF measured by coronal CT was similar to the distance to the frontal base. In contrast, the minimum length of the ITF was shorter than the distance to the frontal base. These results suggest that the MTF might be superior to the ITF for coverage of the anterior frontal base. Three patients who underwent MTF reconstruction for a defect in the anterior olfactory groove had good outcomes and no complications. The MTF is a good option for reconstruction of defects in the anterior part of the olfactory groove.

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Sustained effect of hyaluronic acid in subcutaneous administration to the cochlear spiral ganglion

Inagaki Yozo, Fujioka Masato, Kanzaki Sho, Watanabe Kotaro, Oishi Naoki, Itakura Go, Yasuda Akimasa, Shibata Shinsuke, Nakamura Masaya, James Okano Hirotaka, Okano Hideyuki, Ogawa Kaoru

PLoS One 11 （ 4 ） 2016年04月

The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sctreated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea.

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A nationwide study on enlargement of the vestibular aqueduct in Japan

Noguchi Yoshihiro, Fukuda Satoshi, Fukushima Kunihiro, Gyo Kiyofumi, Hara Akira, Nakashima Tsutomu, Ogawa Kaoru, Okamoto Makito, Sato Hiroaki, Usami Shin ichi, Yamasoba Tatsuya, Yokoyama Tetsuji, Kitamura Ken

Auris Nasus Larynx 2016年03月

ISSN 0385-8146

Objective: To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients. Methods: In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000. Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness. Results: In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6-24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91. dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10. dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7. dB (median, 91.3. dB; interquartile range, 71.3-103.8. dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0-9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness. Conclusion: The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.

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Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder

Wasano Koichiro, Matsunaga Tatsuo, Ogawa Kaoru, Kunishima Shinji

European Archives of Oto-Rhino-Laryngology 1 - 6 2016年03月

ISSN 0937-4477

MYH9 disorder is a rare autosomal-dominant disorder. We previously reported that it is caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9 disorder causes congenital macrothrombocytopenia accompanied by progressive sensorineural hearing loss, nephropathy, and cataract. However, there are few reports that describe the audiological features of MYH9 disorder. The objective of this study was to characterize auditory and other phenotypes of patients with MYH9 disorder. We examined nine subjects from one Japanese family. Audiological, ophthalmological, hematological, and imaging examinations were used to assess clinical features. We carried out genetic analysis of the causative gene, MYH9. Five subjects exhibited macrothrombocytopenia and neutrophil cytoplasmic inclusion bodies. Immunofluorescence analysis of neutrophil NMMHC-IIA revealed abnormal type II localization. Two subjects had high-frequency dominant hearing loss, which was adult onset and progressive. Only one subject had cataract. MYH9 sequencing analysis of all thrombocytopenic subjects revealed a heterozygous c.4270G>A mutation in exon 30 (p.D1424N). We identified five patients with MYH9 disorder from the family. The hearing impairment associated with MYH9 disorder in this family was characterized as adult onset, progressive, and high-frequency dominant. Hematological manifestations of MYH9 disorder show complete penetrance, whereas extra-hematological manifestations show incomplete penetrance and variable expressivity in this family.

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Distinct Expression Patterns of Causative Genes Responsible for Hereditary Progressive Hearing Loss in Non-Human Primate Cochlea

Hosoya Makoto, Fujioka Masato, Ogawa Kaoru, Okano Hideyuki

Scientific Reports 6 2016年02月

Hearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5, and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset.

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Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation

Hosoya Makoto, Fujioka Masato, Kobayashi Reona, Okano Hideyuki, Ogawa Kaoru

Neuroscience Research 2016年02月

ISSN 0168-0102

Ion homeostasis in the inner ear is essential for proper hearing. Anion exchangers are one of the transporters responsible for the maintenance of homeostasis, but their expression profile in the primate cochlea has not been fully characterized. However, species-specific overlapping expression patterns and functional compensation in other organs, such as the kidney, pancreas and small intestine, have been reported. Here, we determined the expression patterns of the anion exchangers SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A11, SLC4A2 and SLC4A3 in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). Although the pattern of expression of SLC26A4 and SLC26A5 was similar to that in rodents, SLC26A7, SLC4A2, SLC4A3 exhibited different distributions. Notably, five transporters, SLC26A4, SLC26A6, SLC26A11 SLC4A2 and SLC4A3, were expressed in the cells of the outer sulcus. Our results reveal a species-specific distribution pattern of anion exchangers in the cochlea, particularly in the outer sulcus cells, suggesting functional compensation among these exchangers. This "primate-specific" pattern may be related to the human-specific hearing loss phenotypes of channelopathy disorders, including the SLC26A4-related diseases Pendred syndrome/DFNB4.

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Sigmoid incision rescue nasoseptal flap technique for endoscopic endonasal skull base surgery

Ozawa Hiroyuki, Tomita Toshiki, Watanabe Yoshihiro, Sekimizu Mariko, Ito Fumihiro, Ikari Yuichi, Saito Shin, Toda Masahiro, Ogawa Kaoru

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion The sigmoid-incision (S-I) rescue flap technique has the advantage of both reduced-invasiveness and providing a sufficient surgical corridor for endoscopic endonasal skull base surgery (EESBS). Objective Skull base reconstruction with nasoseptal flap (NSF) is critically important in managing post-operative cerebrospinal fluid (CSF) leakage after tumor removal by EESBS. The NSF needs to be elevated before sphenoidotomy and posterior septectomy to preserve the pedicle. However, most extradural surgery without CSF leakage does not require NSF and, therefore, NSF preparation is often futile. As a result, a rescue flap technique to overcome this problem has been developed, whereby a new S-I rescue flap method is used that enables wide exposure of the sphenoidal rostrum and smooth manipulation of surgical instruments to preserve the NSF pedicle. Materials and methods Starting in April 2014, 19 cases underwent EESBS with S-I rescue flap. Results All patients underwent tumor resection under an adequate operative field with smooth manipulation of surgical instruments. Two complications were experienced. One patient had CSF leak after removal of the nasal packing, but the leakage was successfully closed by conventional NSF. Another patient had epistaxis from the septal wall, but this was controlled by electrocautery.

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The effects of cochlear implantation in Japanese single-sided deafness patients

Kitoh Ryosuke, Moteki Hideaki, Nishio Shinya, Shinden Seiichi, Kanzaki Sho, Iwasaki Satoshi, Ogawa Kaoru, Usami Shin ichi

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion Cochlear implantation (CI) for Japanese single-sided deafness patients resulted in improved speech perception, increased sound localization accuracy, and reduced tinnitus handicap. Objectives This study reports results for five adult SSD cases with CI, focusing on the benefits they obtained in terms of speech recognition, sound localization, and tinnitus handicap. Methods Five Japanese patients meeting the eligibility criteria were included in this study. All patients were implanted with a fully inserted MED-EL Concerto FLEX28® implant (MED-EL, Innsbruck, Austria). Speech perception outcomes in noise, as well as sound localization and tinnitus disturbance, were assessed pre-surgically and at 1, 3, 6, and 12 months after CI activation. Results The Japanese monosyllable test score in noise improved gradually after implantation. In some cases, speech perception ability appeared unstable, particularly in the first 1–6 months after implantation. The sound localization ability showed marked improvement in all cases, with the disturbance to daily life caused by tinnitus also decreasing in all cases from the early post-operative period.

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小川 郁

論文 - 小川 郁

小川　郁

論文 - 小川　郁