研究者詳細 - 小川　郁

論文 - 小川　郁

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SOD1 gene polymorphisms in sudden sensorineural hearing loss

Kitoh Ryosuke, Nishio Shin Ya, Ogawa Kaoru, Okamoto Makito, Kitamura Ken, Gyo Kiyofumi, Sato Hiroaki, Nakashima Tsutomu, Fukuda Satoshi, Fukushima Kunihiro, Hara Akira, Yamasoba Tatsuya, Usami Shin ichi

Acta Oto-Laryngologica 1 - 5 2016年02月

ISSN 0001-6489

Conclusion The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population. Objectives To assess the gene association with sudden sensorineural hearing loss (SSNHL). Methods A two-stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL. Results Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus–positive group.

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Clinical Outcomes and Prognostic Factors for Salivary Duct Carcinoma

Otsuka Kuninori, Imanishi Yorihisa, Tada Yuichiro, Kawakita Daisuke, Kano Satoshi, Tsukahara Kiyoaki, Shimizu Akira, Ozawa Hiroyuki, Okami Kenji, Sakai Akihiro, Sato Yuichiro, Ueki Yushi, Sato Yukiko, Hanazawa Toyoyuki, Chazono Hideaki, Ogawa Kaoru, Nagao Toshitaka

Annals of Surgical Oncology 1 - 8 2016年01月

ISSN 1068-9265

Background: Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC. Methods: We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors. Results: The 3-year OS and DFS rates were 70.5 and 38.2 %, respectively. Multivariate analysis revealed that age ≥65 years (p <0.001) and N1 and N2 (p = 0.047 and

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Clinical review of globus patients with a focus on GERD cases

Uno Kosuke, Saito Koichiro, Yabe Haruna, Kono Takeyuki, Ogawa Kaoru

Journal of Otolaryngology of Japan 119 （ 11 ） 1388 - 1396 2016年

ISSN 0030-6622

Globus sensation is a common symptom seen daily in ear-nose-throat (ENT) clinics. Globus is affected by multiple factors, and of these, gastroesophageal reflux disease (GERD), has been recognized as a relatively more manageable cause of globus than the other causes. However, we still commonly encounter globus patients with unclear backgrounds who require multiple diagnostic and therapeutic modalities. To provide an appropriate treatment approach and create favorable situations for these patients, we developed and applied an intramural algorithm to manage globus considering GERD, laryngeal allergy, and psychological problems as major factors of this pathology. Twenty-six patients with globus sensation who visited our voice clinic from June 2012 to March 2015 were enrolled in this study. All these patients had undergone general ENT examinations, including naso-pharyngo-laryngeal endoscopies and cervicothoracic computed tomographic scans. Upper gastrointestinal endoscopy revealed 2 cancers. Further study classified 23 patients into the GERD group and 1 patient into the allergy group. Proton pump inhibitor (PPI) therapy was successful in 11 patients of the GERD group (response rate, 47.2%). Improvement in subjective symptoms of globus were measured by the scores of questionnaires, including the F scale and Reflux Symptom Index. Significant improvement in these scores were observed 1 month after PPI prescription in the PPI-responder group in this study. Further assessment of medical history as well as the scores of questionnaires to measure the severity levels of depression (Self-rating Depression Scale) and anxiety (State-Trait Anxiety Inventory-Form JYZ, STAI) proved that relatively longer lasting symptoms (≥4 months) or relatively higher anxiety scores (STAIS50 points) were predictive of PPI resistance. Our study results suggested that the pathology of globus is affected by multiple factors and that a multidisciplinary team approach is required for better management of this disease.

Modified endoscopic transnasal-transmaxillary-transpterygoid approach to parapharyngeal space tumor resection

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

Head and Neck 2016年

ISSN 1043-3074

Background: Conventional approaches for removing parapharyngeal space tumors require a cervical skin incision and resection of soft tissues between the skin and parapharyngeal space. The surgical visual field for this conventional approach is limited. Methods: To decrease invasiveness during removal of benign parapharyngeal space tumors and to enhance the visual field, we devised a new approach called the modified endoscopic transnasal-transmaxillary-transpterygoid approach (MENMAP). The "surgical corridor" to the parapharyngeal space consists of the maxillary sinus, submucous tunnel under the lateral nasal wall, and the space created by removing the pterygoid process. Results: We successfully performed en bloc removal of a parapharyngeal space tumor using the MENMAP approach. The only surgical complication was hypoesthesia of the right hard palate and maxillary gingiva, which gradually improved. Conclusion: The MENMAP approach is a viable alternative for removing parapharyngeal space tumors, as it is safe, feasible, and less invasive.

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Developmental disability and psychiatric conditions in 39 patients with stuttering

Tomisato Shuta, Oishi Naoki, Asano Kazumi, Watanabe Yoshihiro, Ogawa Kaoru

Japan Journal of Logopedics and Phoniatrics 57 （ 1 ） 7 - 11 2016年

ISSN 0030-2813

Stuttering may be related to developmental disability or mental diseases such as social anxiety disorder. However, there are few reports about these comorbid conditions in stuttering patients in Japan. In order to comprehend the relationship between stuttering and comorbid conditions, we conducted a chart review of 39 stuttering cases who sought consultation at Keio University Hospital in 2012 and 2013. Fifteen percent of the subjects had the following comorbid psychiatric conditions: mood disorder (depression and adjustment disorder), obsessive-compulsive disorder, epilepsy and tic disorder. Eighteen percent of the subjects had developmental disability, including definite or suspected developmental disability, and language development disorder. The age at which patients with developmental disability began stuttering was higher than that in patients without such disability. These findings suggest that clinical presentation of stuttering may be affected by comorbid developmental disability.

Comparative multidimensional assessment of laryngeal function and quality of life after radiotherapy and laser surgery for early glottic cancer

Kono Takeyuki, Saito Koichiro, Yabe Haruna, Uno Kosuke, Ogawa Kaoru

Head and Neck 2016年

ISSN 1043-3074

Background: This study was designed to comparatively assess laryngeal function and quality of life (QOL) of patients after laser surgery (LS) or radiotherapy (RT) for early glottic cancer. Methods: Sixty-four patients with T1 glottic cancer treated with RT or type II cordectomy underwent both subjective and objective vocal assessments. The LS group was divided into the following: (1) vaporization with defocused mode (laser surgery [LS]-Vap); and (2) excision with focused mode using lower power (LS-Ex). Results: Auditory-perceptual evaluation and videostroboscopic images in the LS-Ex group worsened shortly after treatment and time-dependent recovery was quicker than in the LS-Vap group. The LS-Ex group showed equivalent posttherapeutic vocal function with the RT group by acoustics, aerodynamics, and self-assessment questionnaire analysis, whereas the LS-Vap group showed statistically significant worse function. Conclusion: The multidimensional assessment showed that early glottic cancer could be successfully treated by either RT or LS-Ex with equivalent posttherapeutic laryngeal function and QOL.

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A case of middle ear implant VSB (Vibrant Soundbridge^®)

Inagaki Yozo, Kanzaki Sho, Yamada Hiroyuki, Watabe Takahisa, Oishi Naoki, Ogawa Kaoru, Iwasaki Satoshi

Practica Oto-Rhino-Laryngologica 109 （ 4 ） 239 - 246 2016年

ISSN 0032-6313

We participated in a clinical trial for a hearing aid system in Japan, "Verification of the efficacy and safety of the middle ear implant MVS (Medel Vibrant System) in conductive and mixed hearing loss". We present a report of a case that we encountered in our department. MVS is a Vibrant Soundbridge^® (VSB) middle ear implant device that is approved and is in wide use in Europe and the United States. It has been shown to have the potential to provide a high level of acoustic clarity and sound quality. Also, as compared to conventional hearing AIDS, there is no howling and the distortion frequency is lower. An additional advantage is the excellent transient response. The patient was a 33-year-old woman, with a history of bilateral hearing loss from birth, who was under observation whilst wearing a hearing aid. In an attempt to improve her hearing, we admitted her to our hospital. Based on the diagnosis of middle ear malformation and mixed hearing loss on both sides, we performed bilateral tympanoplasty. Since the hearing improvement following this procedure was poor on the right side, we prescribed a hearing aid. However, the patient did not adapt satisfactorily to this device. Four years after the initial diagnosis, we performed VSB middle ear implant surgery using the round window stimulation method, placing the transducer in the round window. The postoperative results were good. The speech inspection noise levels in both ears under a free-field, silent setting were 60 dBHL 85%, and 50 dBHL 100%. Thus, the postoperative course was good, the patient's satisfaction level improved and no adverse events occurred. VSB is likely to be a useful tool in rescue surgery for refractory middle ear cases. Also, it is useful as a standard rescue procedure in difficult hearing aid cases. In practice, otologic procedures are intended to improve the QOL and meet requirements in both diverse cases and individual patient conditions. Therefore, dissemination of VSB as one of the treatment choices for improving hearing loss is expected in the future.

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

Journal of Otolaryngology of Japan 119 （ 5 ） 721 - 726 2016年

ISSN 0030-6622

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.

Distinct expression pattern of a deafness gene, KIAA1199, in a primate Cochlea

Hosoya Makoto, Fujioka Masato, Okano Hideyuki, Ogawa Kaoru

BioMed Research International 2016 2016年

ISSN 2314-6133

Deafness is one of the most common types of congenital impairments, and at least half of the cases are caused by hereditary mutations. Mutations of the gene KIAA1199 are associated with progressive hearing loss. Its expression is abundant in human cochlea, but interestingly the spatial expression patterns are different between mouse and rat cochleae; the pattern in humans has not been fully investigated. We performed immunohistochemical analysis of a nonhuman primate, common marmoset (Callithrix jacchus), cochlea with a KIAA1199-specific antibody. In the common marmoset cochlea, KIAA1199 protein expression was more widespread than in rodents, with all epithelial cells, including hair cells, expressing KIAA1199. Our results suggest that the primate pattern of KIAA1199 expression is wider in comparison with rodents and may play an essential role in the maintenance of cochlear epithelial cells.

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Frequency and specific characteristics of the incomplete partition type III anomaly in children

Kanno Ayako, Mutai Hideki, Namba Kazunori, Morita Noriko, Nakano Atsuko, Ogahara Noboru, Sugiuchi Tomoko, Ogawa Kaoru, Matsunaga Tatsuo

Laryngoscope 2016年

ISSN 0023-852X

Objectives/Hypothesis: To determine the frequency of the incomplete partition type III anomaly and the genetic and clinical features associated with POU3F4 mutations in children with hearing loss. Study Design: Retrospective case series from 2000 to 2014 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals. Methods: A total of 1,004 patients (from 938 families) who had hearing loss by 10 years of age and had undergone computed tomography scanning of their temporal bones were enrolled in this genetic, clinical, and radiological study. Results: The incomplete partition type III anomaly was identified in six patients (0.6%), each of whom had an enlargement of the vestibular aqueduct at the end close to the vestibule. The six patients also had POU3F4 variants, and a genetic analysis revealed frameshift deletions in three patients, a missense variant in two patients of the same family, and a large deletion in one patient. Three of the six patients with POU3F4 variants were sporadic cases, and in one patient the genetic mutation occurred de novo. Conclusions: It was indicated that POU3F4 mutations can be predicted by incomplete partition type III anomaly by radiological examination of the inner ear. All six of the patients showed mixed hearing loss, but none showed fluctuations in hearing, which may be related to the lack of vestibular aqueduct enlargement at the operculum.

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Multidimensional vocal assessment after laser treatment for recurrent respiratory papillomatosis

Kono Takeyuki, Yabe Haruna, Uno Kosuke, Saito Koichiro, Ogawa Kaoru

Laryngoscope 2016年

ISSN 0023-852X

Objectives/Hypothesis: Recurrent respiratory papillomatosis (RRP) is a benign epithelial tumor that exhibits a high frequency of recurrence. This study assesses the vocal function after laser treatment for RRP, particularly in relation to the frequency of surgery. Study Design: Retrospective study. Methods: Thirty RRP patients who underwent laser surgery that controlled the tumor were included. Preoperative and postoperative Grade, Roughness, Breathiness, Asthenia, and Strain Scale, videostroboscopic findings, aerodynamic and acoustic parameters, and self-assessment questionnaires were measured and compared with an age- and sex-matched control group. Subsequently, to evaluate the association between postoperative voice quality and the number of surgeries, the patients were divided into three groups (group 1: single surgery, group 2: 2-5 surgeries, group3: >6 surgeries), and comparative multidimensional vocal assessments were performed. Results: The mean number of surgeries was 3.4 (range, 1-8). Although all patients exhibited poorer vocal function than the control group preoperatively, they showed improvement in postoperative subjective and objective parameters. However, four patients who underwent one surgery with relatively aggressive ablation exhibited vocal cord scarring and deteriorated objective parameters. All remaining patients showed voice quality that was on par with the control group. Subgroup analysis proved no association between post-therapeutic voice quality and the patient characteristics, including preoperative staging and the number of surgical treatments performed. Conclusions: RRP patients can achieve a close to normal voice with high satisfaction even after recurrent surgical treatment when ablation of a subepithelial lesion using sufficient laser energy is adequate.

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Auditory resting-state functional connectivity in tinnitus and modulation with transcranial direct current stimulation

Minami Shujiro B., Oishi Naoki, Watabe Takahisa, Uno Kimiichi, Kaga Kimitaka, Ogawa Kaoru

Acta Oto-Laryngologica 135 （ 12 ） 1286 - 1292 2015年12月

ISSN 0001-6489

Conclusions: The functional connectivity (FC) between the right and left auditory cortex is weak in tinnitus patients. Transcranial direct current stimulation (tDCS) over the auditory cortex has potential as a tool to modulate auditory-based FC. Objective: This study investigated the effects of applying tDCS in tinnitus patients, and searched for modulation of brain networks in resting-state functional magnetic resonance imaging (rs-fMRI) through an analysis of FC with the stimulated brain region. Subjects and methods: Nine male patients with chronic tinnitus and 10 male volunteers with normal hearing were enrolled. The subjects were evaluated with rs-fMRI immediately before and after tDCS. The tinnitus patients filled out the self-evaluation questionnaires designed to measure tinnitus conditions before tDCS treatment and 1 week afterwards. Results: The FC between the right and left auditory cortex was significantly weaker in tinnitus patients than in controls. After tDCS treatment, in the tinnitus group, the primary auditory cortex showed a reduction in the amount of statistically significant connectivity with the somatosensory area and motor area, but maintained strong significant connectivity (p < 0.005) with the auditory area and insular cortex. In contrast, in the control group, there remained strong significant connectivity between the primary auditory cortex and the somatosensory area, motor area, insular cortex, and auditory area.

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Application of Kampo medicine on tinnitus and hearing loss

Ogawa Kaoru

Otolaryngology - Head and Neck Surgery (Japan) 87 （ 13 ） 1080 - 1084 2015年12月

ISSN 0914-3491

Novel in vivo imaging analysis of an inner ear drug delivery system

Kanzaki Sho, Watanabe Kotaro, Fujioka Masato, Shibata Shinsuke, Nakamura Masaya, Okano Hirotaka James, Okano Hideyuki, Ogawa Kaoru

Hearing Research 330 142 - 146 2015年12月

ISSN 0378-5955

Systemic application of drugs is commonly used in clinical situations. Some of these drugs are ototoxic. Since there are few studies on in vivo monitoring of drug delivery dynamics, the time course or bioavailability of drugs in the inner ear of live animals following systemic drug application remains unknown. For instance, it is unknown whether the volume of a drug delivered systemically correlates with its inner ear pharmacokinetics. We previously established a new in vivo imaging system to monitor drug delivery in live mice. In the present study, we used this system to compare drug concentration in the inner ear over time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP promoter and human beta-globin intron 2. Luciferin delivered into the inner ear of these mice reacts with luciferase, and the resulting signals are detected in GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear the intensity and duration of luciferin/luciferase signals after systemic injections of different volumes of luciferin. An IVIS^® imaging system was used to observe signals, and these signals were compared to the drug dynamics of luciferin delivered through subcutaneous (sc) injections. The volume of sc-injected drug correlated significantly with photon counts measured in the inner ear. Photons were detected almost immediately after injection, peaking 20 min after injection. Drug concentration did not affect inner ear signals. Luciferin injected systemically appeared in the inner ear between highest and lowest concentration. Drug volume is an important parameter to know if the inner ear requires a higher level of the drug. We observed that it is the volume of a drug-not its concentration-that is the important factor. Indeed, the more volume of a drug injected systemically increased the concentration of that drug in the inner ear. This study provides a better understanding of in vivo drug delivery dynamics measured in the inner ear. Further studies will show whether a high dosage of drug is effective or not. This article is part of a Special Issue entitled .

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Expression of Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma

Habu Noboru, Imanishi Yorihisa, Kameyama Kaori, Shimoda Masayuki, Tokumaru Yutaka, Sakamoto Koji, Fujii Ryoichi, Shigetomi Seiji, Otsuka Kuninori, Sato Yoichiro, Watanabe Yoshihiro, Ozawa Hiroyuki, Tomita Toshiki, Fujii Masato, Ogawa Kaoru

BMC Cancer 15 （ 1 ） 2015年10月

Background: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed neck metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. Methods: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells. The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC. Results: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular and muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and NPV of 82.0%, 61.5%, and 86.8%, respectively, while vascular invasion showed the highest specificity and PPV of 94.6% and 71.4%, respectively. Conclusion: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 can be considered a potential predictor for selecting patients at high risk of developing DNM.

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Closure of tracheoesophageal puncture with pedicled fascia flap of the sternocleidomastoid muscle

Wasano Koichiro, Suzuki Noriomi, Kawasaki Taiji, Yamamoto Sayuri, Minami Shujiro, Yamashita Taku, Ogawa Kaoru

Auris Nasus Larynx 42 （ 4 ） 318 - 321 2015年08月

ISSN 0385-8146

Objective: Closure of a tracheoesophageal puncture (TEP) formed during voice prosthesis implantation may sometimes be required. We report a new method of closure that we have termed the RESET method. Methods: We used the RESET method for four patients. An initial incision was made at the mucocutaneous junction of the tracheostoma, and the trachea and esophagus were separated. The TEP was sectioned, and the tracheal and esophageal sides were sutured into separate layers. A pedicled fascia flap lifted from the sternocleidomastoid muscle was sandwiched between the trachea and the esophagus, and subsequently secured. Results: The TEP was closed in all patients, and no complications were observed. Conclusion: The RESET method, using a pedicled fascia flap with stable perfusion, is a simple, reliable method of TEP closure.

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Magnetic resonance monitoring of superparamagnetic iron oxide (SPIO)-labeled stem cells transplanted into the inner ear

Watada Yukiko, Yamashita Daisuke, Toyoda Masashi, Tsuchiya Kohei, Hida Naoko, Tanimoto Akihiro, Ogawa Kaoru, Kanzaki Sho, Umezawa Akihiro

Neuroscience Research 95 21 - 26 2015年06月

ISSN 0168-0102

In the field of regenerative medicine, cell transplantation or cell-based therapies for inner ear defects are considered to be promising candidates for a therapeutic strategy. In this paper, we report on a study that examined the use of magnetic resonance imaging (MRI) to monitor stem cells transplanted into the cochlea labeled with superparamagnetic iron oxide (SPIO), a contrast agent commonly used with MRI. First, we demonstrated in vitro that stem cells efficiently took up SPIO particles. This was confirmed by Prussian blue staining and TEM. In MRI studies, T2 relaxation times of SPIO-labeled cells decreased in a dose-dependent manner. Next, we transplanted SPIO-labeled cells directly into the cochlea in vivo and then performed MRI 1. h, 2 weeks, and 4 weeks after transplantation. The images were evaluated objectively by measuring signal intensity (SI). SI within the ears receiving transplants was significantly lower (P < 0.05) than that of control sides at the 1-h assessment. This novel method will be helpful for evaluating stem cell therapies, which represents a new strategy for inner ear regeneration. To the best of our knowledge, this study is the first to demonstrate that local transplantation of labeled stem cells into the inner ear can be visualized in vivo via MRI.

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Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss

Yamashita Daisuke, Sun Guang wei, Cui Yong, Mita Shiro, Otsuki Naoki, Kanzaki Sho, Nibu Ken Ichi, Ogawa Kaoru, Matsunaga Tatsuo

Journal of Neuroscience Research 93 （ 5 ） 788 - 795 2015年05月

ISSN 0360-4012

The sigma-1 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma-1 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise-induced or aging-associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging-associated hearing loss. These results suggest that cutamesine reduces noise-induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise.

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Pico<inf>2</inf> monitoring of transferred jejunum perfusion using an air tonometry technique after hypopharyngeal cancer surgery

Ozawa Hiroyuki, Imanishi Yorihisa, Ito Fumihiro, Watanabe Yoshihiro, Kato Takashi, Nameki Hideo, Isobe Kiyoshi, Ogawa Kaoru

Medicine (United States) 94 （ 11 ） e632 2015年03月

ISSN 0025-7974

This study aimed to investigate the usefulness of intraluminal Pco 2 (Pico 2) monitoring by air tonometry for the assessment of the vascular condition of the transferred jejunum after surgery for hypopharyngeal cancer. Pico 2 in the transplanted jejunum of 24 patients was monitored using air tonometry after radical surgery for hypopharyngeal cancer from 2003 to 2010. All but 1 patient, who removed the catheter before monitoring began, were monitored safely. Pico 2 in the transferred jejunum correlated with arterial Pco 2 (Paco 2) that was measured concurrently, and dissociation of Pico 2 from Paco 2 was observed in cases with vascular complication. In those cases without postoperative vascular complication, the Pico 2 value gradually increased for 3 hours but then decreased by 12 hours after surgery. Three patients experienced major vascular complication. All 3 patients had continuous elevation of Pico 2 >100mm Hg, although vascular flow in 1 patient recovered by removal of a venous thrombosis and reanastomosis of the vein 7.5 hours after surgery. Four other patients who experienced elevation of Pico 2 had their skin suture released for decompression of their neck wound, resulting in a decrease in Pico 2 after treatment. The current results demonstrated that continuous monitoring of Pico 2 by air tonometry accurately reflects the vascular condition of the transferred jejunum, and this method is one of the best options for postoperative monitoring of jejunum blood perfusion.

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Usefulness of Clinicobiological Data Obtained Prior to Cervical Lymph Node Biopsy

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

Nihon Jibiinkoka Gakkai kaiho 118 （ 3 ） 206 - 212 2015年03月

ISSN 0030-6622

INTRODUCTION: We commonly use data obtained prior to cervical lymph node biopsy for the diagnosis of malignant lymphoma. Based on such data, we can confirm whether a biopsy should be performed in some cases. Currently, the parameters used to indicate a presurgery examination prior to biopsy have been very few. So, we retrospectively analyzed cases of cervical lymph node biopsy. Moreover, we examined the usefulness of clinicobiological data obtained prior to cervical lymph node biopsy to evaluate various factors related to the diagnosis of malignant lymphoma.METHODS: This study included 77 patients for whom the initial diagnostic impression was malignant lymphoma before surgery. Of the 77 cases, 40 were diagnosed as having malignant lymphoma and 37 were diagnosed as having non-malignant lymphoma. We performed a case-controlled study to evaluate the differences in clinicobiological data between malignant and non-malignant lymphoma in terms of the following parameters: (1) age, (2) sex, (3) number of white blood cells, (4) white blood cell lymphocyte count, (5) percentage of white blood cell lymphocytes, (6) percentage of eosinophils (%), (7) percentage of monocytes (%), (8) atypical lymphocytes (%), (9) hemoglobin level, (10) lactate dehydrogenase level, (11) C-reactive protein level, (12) soluble interleukin-2 receptor (IL-2R) level, and (13) cytological findings. We used multivariate and univariate analyses to study the data statistically.RESULTS: The following 5 factors were found to be significant in a Wilcoxon t-test for malignant lymphoma: percentage of white blood cell lymphocytes, sIL-2R level, age, white blood cell lymphocyte count, and cytological findings; these factors were also significant when examined using a Pearson χ2 test. The other factors did not differ significantly between the malignant and non-malignant lymphomas. The percentage of white blood cell lymphocytes and the cytological findings were identified as significant independent factors for the diagnosis of malignant lymphoma in a multivariate analysis, whereas the other factors were not found to be significant.CONCLUSION: Based on the results of the univariate and multivariate analyses performed in the present study, the decline in the percentage of white blood cell lymphocytes and the cytological findings obtained prior to cervical lymph node biopsy are significant indicators of malignant lymphoma.

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