Publications by authors named "Kimiko Hoshino"

21 Publications

  • Page 1 of 1

The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media.

Otol Neurotol 2021 Nov 19. Epub 2021 Nov 19.

Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objective: This study aimed to quantify the cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex as extracellular trap cell death (ETosis)-derived products in the middle ear fluid, and to identify diagnostic biomarkers for the discrimination of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) from eosinophilic otitis media (EOM).

Study Design: Prospective study.

Setting: Tertiary referral center.

Patients: OMAAV patients were eligible for inclusion in this analysis. Patients with EOM were examined as controls.

Intervention: All samples were obtained from the middle ear fluid in patients with OMAAV or EOM. The fluid samples were aspirated from the middle ear through the anterior-inferior portion of the tympanic membrane using a 1-ml tuberculin syringe with a 24- or 26-gauge needle under a microscope.

Main Outcome Measures: The levels of cell-free DNA, cit-H3-DNA complex and MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay.

Results: Patients with OMAAV showed significantly higher levels of MPO-DNA complex compared to patients with EOM, regardless of the serum ANCA status at the time of sampling (p < 0.001 and p < 0.001, respectively). Meanwhile, there were no significant differences in the values of cell-free DNA or cit-H3-DNA complex between the OMAAV and EOM patients.

Conclusion: The findings of this study suggest that the detection and quantification of MPO-DNA complex in the otitis media fluid can be utilized to discriminate OMAAV, especially in cases of eosinophilic granulomatosis with polyangiitis, from EOM regardless of the serum ANCA status. It should be noted that it is possible for cell-free DNA and cit-H3-DNA complex in fluid samples to be derived from dead cells other than neutrophils that undergo ETosis.
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http://dx.doi.org/10.1097/MAO.0000000000003431DOI Listing
November 2021

Characteristics of and Prognosis for Facial Palsy in Patients With Otitis Media With ANCA-Associated Vasculitis (OMAAV).

Otol Neurotol 2021 Dec;42(10):e1577-e1582

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

Objectives: The aim of the present study was to investigate the characteristics and prognosis of facial palsy in patients with otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV).

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Thirty-seven patients with OMAAV.

Main Outcome Measures: The patients were divided into the facial palsy group and non-palsy group. The severity of and prognosis for facial palsy were evaluated using the House-Brackmann facial grading system (HB). Characteristics were compared between the facial palsy group and non-palsy group.

Results: Facial palsy was observed in eight patients. The last HB grade for all patients was either grade I or II after treatment with a combination of corticosteroids and immunosuppressant therapy. There were no cases in which palsy relapsed. Facial palsy in OMAAV was significantly more common in female patients, and patients with facial palsy demonstrated significantly higher rates of hypertrophic pachymeningitis than did those without facial palsy.

Conclusions: Facial palsy in patients with OMAAV was detected in 21.6% and a good prognosis was obtained by use of the appropriate treatment. Facial palsy is one of the most important symptoms by which to diagnose OMAAV. When encountering the patients with intractable otitis media complicated with facial palsy, appropriate examination including ANCA titer should be performed.
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http://dx.doi.org/10.1097/MAO.0000000000003308DOI Listing
December 2021

Notch Signaling in Acquired Middle Ear Cholesteatoma.

Otol Neurotol 2021 10;42(9):e1389-e1395

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.

Hypothesis: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma.

Background: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated.

Methods: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler™ PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively.

Results: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 ± 32.4% and 44.9 ± 17.8%, respectively) were significantly lower than in the EAC skin (83.4 ± 17.5% and 55.7 ± 7.1%, respectively) (p < 0.001 and p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 ± 11.4%) was significantly higher than in the EAC skin (0.5 ± 0.7%) (p < 0.001).

Conclusion: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.
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http://dx.doi.org/10.1097/MAO.0000000000003245DOI Listing
October 2021

Psychological evaluation for patients with non-cured facial nerve palsy.

Auris Nasus Larynx 2021 May 4. Epub 2021 May 4.

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-Ku, N15W7, Sapporo 0608638, Hokkaido, Japan.

Objective: The aim of the present study was to evaluate the psychological condition of patients with non-cured facial nerve palsy and to investigate whether their psychological condition is correlated with the degree of facial nerve palsy, synkinesis or quality of life.

Methods: Thirty patients with non-cured facial nerve palsy were enrolled in this study. Psychological conditions were evaluated by questionnaires including State-Trait Anxiety Inventory and Self-rating Depression Scale.

Results: Of the thirty patients with non-cured facial nerve palsy, 17 (56.7%) and 15 patients (50.0%) felt anxiety and depression, respectively. Although there were no significant correlations between their psychological condition and the degree of facial nerve palsy or that of sequelae, significant correlations were observed between psychological condition and the degree of QOL, especially in terms of social function.

Conclusions And Significance: Disabilities associated with facial nerve palsy may be overlooked when evaluation is performed by physician-graded instruments alone. To resolve this problem, patients with non-cured facial nerve palsy should be evaluated by not only physician-graded tools but also patient-based assessment tools.
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http://dx.doi.org/10.1016/j.anl.2021.04.007DOI Listing
May 2021

Prognostic factors for duration of vertigo after stapes surgery via a time-to-event analysis.

Acta Otolaryngol 2021 Mar 29;141(3):216-221. Epub 2020 Dec 29.

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Background: Vertigo or dizziness after stapes surgery occurs sometimes, and it is generally temporary. However, while rare, it can be prolonged.

Aims/objectives: To investigate the prognostic factors for duration of vertigo following stapedotomy using a time-to-event analysis.

Materials And Methods: The present study included a total of 35 primary ears (26 with otosclerosis and nine with congenital stapes fixation) from 31 patients. We assessed residual rates of nystagmus and complaints of subjective vestibular symptoms using Kaplan-Meier time-to-event methods.

Results: Postoperative spontaneous nystagmus was observed in 23 (65.7%) ears, and postoperative subjective vestibular symptoms were confirmed in 27 (77.1%) ears. The total mean duration of postoperative spontaneous nystagmus and subjective vestibular symptoms was 9.8 (range: 0-158) and 33.9 days (0-732), respectively. A history of stapes surgery in the opposite ear was a significant predictive factor for prolonged nystagmus and subjective vestibular symptoms ( = .0059 and  = .0146).

Conclusions And Significance: For individuals with a history of stapes surgery in the opposite ear, spontaneous nystagmus and vertigo/dizziness sensations following stapedotomy may persist for a longer duration than in those without a history of stapes surgery in the opposite ear.
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http://dx.doi.org/10.1080/00016489.2020.1853808DOI Listing
March 2021

Usefulness of the Video Head Impulse Test for the Evaluation of Vestibular Function in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Otol Neurotol 2021 04;42(4):e483-e488

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objectives: To investigate usefulness of the video Head Impulse Test (vHIT) as a method for evaluating semicircular canal function in patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV).

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Fourteen patients with OMAAV underwent vestibular examination.

Main Outcome Measures: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for each semicircular canal.

Results: Seven (50.0%) of the 14 patients felt subjective symptoms of disequilibrium. Dysfunction in at least one semicircular canal was detected in all ears of the OMAAV patients evaluated by vHIT. Dysfunction in posterior semicircular canal was detected more frequently than that in the anterior or horizontal canal. There were no significant correlations between the gain in VOR and hearing loss.

Conclusions: vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with OMAAV as vHIT is not influenced by middle ear pathology and was able to evaluate vertical canal function including the posterior canal.
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http://dx.doi.org/10.1097/MAO.0000000000002975DOI Listing
April 2021

Analysis of semicircular canal function as evaluated by video Head Impulse Test in patients with vestibular schwannoma.

J Vestib Res 2020 ;30(2):101-108

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objective: The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma.

Methods: Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated.

Results: The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed.

Conclusions: From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.
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http://dx.doi.org/10.3233/VES-200695DOI Listing
June 2021

Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Facial Nerve Schwannoma.

Otol Neurotol 2020 06;41(5):e615-e622

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

Objectives: The aim of the present study was to evaluate semicircular canal function by video Head Impulse Test (vHIT) in patients with facial nerve schwannoma (FNS).

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Seven patients with FNS underwent vHIT examination.

Main Outcome Measures: The gain in vestibulo-ocular reflex and the presence of catch-up saccade were examined for the semicircular canals including the vertical canals.

Results: Dysfunction of the semicircular canals was detected by vHIT in three of seven cases. Nystagmus beating toward the non-affected side was observed in all three cases with semicircular canal dysfunction. Dysfunction was observed in a case with no direct compression of the vestibular nerve or semicircular canals by FNS.

Conclusions: Semicircular canal function in patients with FNS could be evaluated by vHIT. vHIT has two advantages for the evaluation of vestibular function in patients with FNS. First, vHIT could be used for the patients in whom a tumor exists in the external auditory canal or middle ear, unlike caloric testing. Second, as vHIT could evaluate all three canals, impaired vestibular nerves could be speculated from vHIT results when a tumor exists in internal auditory canal. vHIT should be performed in patients with FNS, especially before surgery, to evaluate vestibular function.
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http://dx.doi.org/10.1097/MAO.0000000000002591DOI Listing
June 2020

Make-Up Therapy for Patients With Facial Nerve Palsy.

Ann Otol Rhinol Laryngol 2019 Aug;128(8):721-727

1 Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Objectives: To investigate the effectiveness of make-up therapy for patients with facial nerve palsy.

Methods: Seven female patients with facial nerve palsy who received specialist make-up therapy were enrolled. The objective of the make-up therapy was to obtain a symmetrical facial appearance.

Results: Overall score for the Facial Clinimetric Evaluation (FaCE) scale was significantly improved after make-up therapy. There was a tendency for symptoms of depression to be improved among patients after make-up therapy.

Conclusion: Make-up therapy to improve the symmetry of facial appearance could afford a noninvasive and low-cost treatment for patients with facial nerve palsy, especially in terms of patient quality of life and psychological condition.
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http://dx.doi.org/10.1177/0003489419841396DOI Listing
August 2019

Differentiation Between Eosinophilic Otitis Media and Otitis Media Associated With Eosinophilic Granulomatosis With Polyangiitis.

Otol Neurotol 2019 09;40(8):e796-e802

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.

Objective: To perform comparisons and clarify differences in clinical manifestations between eosinophilic otitis media (EOM) and otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA).

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Twenty-two ears of 11 patients exhibiting EOM (EOM group) and 20 ears of 12 patients exhibiting otitis media associated with EGPA (EGPA group).

Main Outcome Measures: Otological manifestations, nasal and paranasal manifestations, incidence of asthma, positivity for serum antineutrophil cytoplasmic antibodies (ANCA), total serum immunoglobulin (Ig) E level, peripheral blood eosinophil fraction, and hearing outcomes.

Results: The incidence and age of onset of asthma and chronic rhinosinusitis were comparable between the EOM and EGPA groups. Moreover, otological findings and hearing outcomes at the initial visit were similar in both groups. Computed tomography images of the paranasal sinus showed predominant opacification of the ethmoid sinus in both groups. Although the total serum IgE level was not significantly different, the peripheral blood eosinophil fraction was significantly larger in the EGPA group than in the EOM group (p = 0.0035). Furthermore, the rate of myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA) positivity was significantly higher in the EGPA group than in the EOM group (p = 0.019).

Conclusions: The findings of the present study suggest that the phenotypic characteristics of EOM closely resemble those of otitis media associated with EGPA in early stages before the appearance of vasculitis. Therefore, it is challenging to differentiate the two conditions purely on the basis of otorhinological examinations.
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http://dx.doi.org/10.1097/MAO.0000000000002295DOI Listing
September 2019

Short-Term Hearing Prognosis of Ossiculoplasty in Pars Flaccida Cholesteatoma Using the EAONO/JOS Staging System.

J Int Adv Otol 2019 Apr;15(1):2-7

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University, School of Medicine and Graduate School of Medicine, Hokkaido, Japan.

Objectives: The aim of the present study was to investigate the prognostic factors for short-term hearing outcomes of ossiculoplasty for primary pars flaccida cholesteatoma according to the European Academy of Otology and Neurotology/Japanese Otological Society (EAONO/JOS) and 2015 JOS staging systems.

Materials And Methods: A total of 34 patients with primary pars flaccida cholesteatoma who underwent one-stage tympanomastoidectomy with partial ossicular reconstruction using double cartilage block were included in the study. The postoperative pure-tone average air-bone gap (PTA-ABG) was calculated, and two criteria of successful hearing outcomes were defined as ≤10 and ≤20 dB. Patients were classified according to the EAONO/JOS and 2015 JOS staging systems. Cochran-Armitage test was used to statistically analyze staging, and Fisher's exact test was used to analyze other factors.

Results: Successful hearing outcome with postoperative PTA-ABG ≤10 and ≤20 dB occurred in 23.5% and 55.9% of cases, respectively. When postoperative PTA-ABG ≤20 dB was defined as successful, the success rate significantly decreased with increase in EAONO/JOS stage, and S0 pathological status of the stapes (no involvement) was a significantly favorable predictive factor. When postoperative PTA-ABG ≤10 dB was regarded as successful, the significantly favorable predictive factors were S0 pathological status of the stapes and development of mastoid cells with MC2-3 (better developed cells).

Conclusion: Favorable prognostic factors for hearing outcomes of tympanomastoidectomy with partial ossicular reconstruction for primary pars flaccida cholesteatoma were low stage following the EAONO/JOS staging system and no stapes involvement and better development of mastoid cells following the 2015 JOS staging system.
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http://dx.doi.org/10.5152/iao.2019.5983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483445PMC
April 2019

The Diagnostic and Clinical Utility of the Myeloperoxidase-DNA Complex as a Biomarker in Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Otol Neurotol 2019 02;40(2):e99-e106

Department of Otolaryngology - Head and Neck Surgery.

Objective: This prospective study aimed to evaluate the diagnostic and clinical utility of the myeloperoxidase (MPO)-DNA complex as a NETosis-derived product in the middle ear fluid of patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV).

Study Design: Prospective study.

Setting: Tertiary referral center.

Patients: Twenty-two patients diagnosed with OMAAV.

Intervention: Collection of the fluid samples from middle ear.

Main Outcome Measure: The levels of the MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay.

Results: Patients with both systemic and localized forms of OMAAV showed significantly higher levels of the MPO-DNA complex compared to the controls (p < 0.001 and p = 0.002, respectively). In particular, they showed significantly higher levels of MPO-DNA complex compared to the controls, regardless of serum antineutrophil cytoplasmic antibody status (p < 0.001 and p < 0.001, respectively) or immunosuppressive therapy (p < 0.001 and p < 0.001, respectively) at the time of sampling. An optical density cutoff value of 0.16 at 405 nm according to the receiver operating characteristic curve showed a sensitivity of 86.4%, specificity of 95.5%, positive predictive value of 95.0% and negative predictive value of 87.5% for the diagnosis of OMAAV. Significant positive correlations were observed between the levels of MPO-DNA complex and the values for air conduction - (r = 0.49, p = 0.022) and bone conduction - pure tone average thresholds (r = 0.45, p = 0.035).

Conclusions: The detection and quantification of the MPO-DNA complex in the otitis media fluid may aid in providing a definite diagnosis as well as predicting the activity and severity of OMAAV.
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http://dx.doi.org/10.1097/MAO.0000000000002081DOI Listing
February 2019

Evaluation of Vertical Semicircular Canal Function in Patients With Vestibular Schwannoma.

Ann Otol Rhinol Laryngol 2019 Feb 26;128(2):113-120. Epub 2018 Oct 26.

1 Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objectives:: The aim of this study was to investigate vertical semicircular canal function in patients with vestibular schwannoma (VS) by video head impulse test (vHIT).

Methods:: Fifteen patients with VS who had not received any treatment, including surgery or stereotactic radiotherapy, before vHIT examination were enrolled. Vestibulo-ocular reflex gain and catch-up saccade in vHIT were evaluated.

Results:: Dysfunction of anterior and posterior semicircular canals was detected by vHIT in 26.7% and 60.0%, respectively. Six patients (40.0%) demonstrated abnormalities referable to both vestibular nerve divisions. Abnormalities referable to the superior vestibular nerve were identified in 3 patients (20.0%), while 3 patients (20.0%) demonstrated a pattern indicative of inferior vestibular nerve involvement. Anterior semicircular canal vHIT produced fewer abnormalities than did either horizontal or posterior semicircular canal vHIT.

Conclusions:: Dysfunction of the semicircular canals, including the vertical canals, in patients with VS was detected by vHIT. The anterior semicircular canal was less frequently involved than the horizontal or posterior semicircular canal. The examination of the vertical canals by vHIT is useful in the evaluation of vestibular function in patients with VS.
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http://dx.doi.org/10.1177/0003489418808545DOI Listing
February 2019

Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer.

Int J Clin Oncol 2018 Dec 5;23(6):1029-1037. Epub 2018 Jul 5.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Background: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck.

Methods: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems.

Results: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers.

Conclusion: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.
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http://dx.doi.org/10.1007/s10147-018-1314-3DOI Listing
December 2018

Elevated Level of Myeloperoxidase-Deoxyribonucleic Acid Complex in the Middle Ear Fluid Obtained From Patients With Otitis Media Associated With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Otol Neurotol 2018 04;39(4):e257-e262

Faculty of Health Sciences.

Objective: The purpose was to explore the presence of myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil extracellular traps (NETs) in the middle ear fluid, and to clarify the correlation between its quantifiable level and hearing outcome in patients with otitis media associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Study Design: Prospective study.

Setting: Tertiary referral center.

Patients: Nine AAV patients presenting with otitis media.

Intervention: Collection of the fluid samples from middle ear.

Main Outcome Measure: The quantifiable levels of MPO-DNA complex using an enzyme-linked immunosorbent assay.

Results: The quantifiable levels of MPO-DNA complex in patients with AAV were significantly higher than those in controls (p < 0.001). In particular, both ANCA-positive and -negative cases indicated higher levels of MPO-DNA complex compared with the controls (p = 0.004 and p = 0.006, respectively). The significant negative correlations were observed between the level of MPO-DNA complex and the functional hearing values for air (r = -0.82, p = 0.009) and bone conduction (r = -0.73, p = 0.028), respectively.

Conclusion: This analysis is the first to reveal the presence of elevated levels of MPO-DNA complex in the middle ear fluid, suggesting the pathogenic role of NETs in otitis media associated with AAV. NETs may be a valuable biomarker for use in clinical decision-making and predicting hearing outcome, regardless of ANCA status.
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http://dx.doi.org/10.1097/MAO.0000000000001708DOI Listing
April 2018

Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss using second-generation enzyme immunoassay: A retrospective, multi-institutional investigation in Hokkaido, Japan.

Auris Nasus Larynx 2018 Oct 8;45(5):911-915. Epub 2017 Dec 8.

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.

Objective: Although elevated anti-mumps IgM antibody levels were reported in 5.7%-7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit.

Methods: This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated.

Results: Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p=0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively; no significant difference was seen in these data (p=0.4519).

Conclusion: The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.
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http://dx.doi.org/10.1016/j.anl.2017.11.016DOI Listing
October 2018

Clinical Characteristics and Treatment Outcomes for Patients With External Auditory Canal Cholesteatoma.

Otol Neurotol 2018 02;39(2):189-195

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objective: We aimed to evaluate the clinical features and treatment outcomes for patients with idiopathic and secondary external auditory canal cholesteatoma (EACC), and to validate the treatment strategy from the perspective of hearing as well as etiology and staging.

Study Design: Retrospective case series.

Setting: Tertiary referral center and affiliated hospitals.

Patients: Fifty-eight patients with idiopathic EACC and 14 patients with secondary EACC.

Intervention: Conservative management and surgery.

Main Outcome Measure: Air conduction (AC) pure-tone averages (PTAs) and mean air-bone gaps (ABGs).

Results: There were no significant differences between hearing values before and after conservative management for idiopathic EACC patients with stages I-III, indicating that hearing abilities were preserved. For idiopathic EACC patients with stage IV disease treated with surgery, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 60.3 dB HL to a postoperative value of 32.4 dB HL (p = 0.013), and from 34.3 to 9.5 dB HL (p < 0.001), respectively. For secondary EACC, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 49.5 dB HL to a postoperative value of 23.2 dB HL (p < 0.001), and from 31.4 to 6.7 dB HL (p < 0.001), respectively.

Conclusion: The treatment modalities should be selected based on the perspective of hearing as well as the extent of disease and etiology. The early lesions can be treated conservatively, whereas the advanced lesions or cases refractory to conservative management require complete surgical removal of EACC.
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http://dx.doi.org/10.1097/MAO.0000000000001659DOI Listing
February 2018

Value of T1-weighted Magnetic Resonance Imaging in Cholesteatoma Detection.

Otol Neurotol 2017 12;38(10):1440-1444

*Department of Otolaryngology-Head and Neck Surgery †Department of Radiation Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Objective: To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma.

Study Design: A retrospective case review.

Setting: Tertiary referral center.

Patients: Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6-82 yr of age).

Intervention: Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging.

Main Outcome Measures: Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal.

Results: The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different (p < 0.001).

Conclusion: Our results suggest that T1W imaging may aid in the exclusion of false-positive cases on diagnostic non-EP DW MR imaging for cholesteatomas. A combination of non-EP DW and T1W imaging may improve the specificity and accuracy compared with non-EP DW imaging alone.
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http://dx.doi.org/10.1097/MAO.0000000000001558DOI Listing
December 2017

Evaluation of Vestibular Functions in Patients with Vogt-Koyanagi-Harada Disease.

Audiol Neurootol 2017 28;22(3):190-195. Epub 2017 Oct 28.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Vogt-Koyanagi-Harada (VKH) disease is an idiopathic, multisystem autoimmune disorder characterized by bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological manifestations. The purpose of this study is to investigate vestibular functions in patients with VKH disease. A total of 43 patients with VKH disease in Hokkaido University Hospital were enrolled in this study. Subjective symptoms such as dizziness or vertigo and the results of various vestibular examinations including nystagmus testing, caloric testing, and vestibular-evoked myogenic potential (VEMP) testing were investigated. Eight of 42 patients (19.0%) complained of subjective vestibular symptoms. On the other hand, 12 of 28 patients (42.9%) showed nystagmus, and 7 of 15 patients (46.7%) showed unilateral or bilateral weakness in the caloric test. VEMP testing was performed for 16 patients. Seven (43.8%) and 8 (50.0%) patients were evaluated as abnormal in cervical VEMP and ocular VEMP testing, respectively. The rate of detection of nystagmus was significantly higher than that of subjective symptoms. As vestibular dysfunction in patients with VKH disease cannot be detected through history taking alone, nystagmus testing, caloric testing, and VEMP testing should be performed to evaluate vestibular functions associated with VKH disease. It is considered that abnormal VEMP findings are associated with otolith organ dysfunction.
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http://dx.doi.org/10.1159/000481426DOI Listing
July 2018

Atypical adenoma of the thyroid diagnosed as anaplastic cancer by cytopathology.

Diagn Cytopathol 2017 Oct 22;45(10):928-933. Epub 2017 May 22.

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.

Atypical adenoma of the thyroid is a rare form of tumor, and its accurate diagnosis prior to surgical resection is difficult as the histological and pathological morphologies are very similar to those of anaplastic thyroid carcinoma (ATC), and its anaplastic transformation remains to be elucidated. We reported a case of a 75-year-old female with a thyroid isthmus nodule diagnosed repeatedly by FNAC as anaplastic carcinoma. Both the first and second FNAC specimen slides showed a large number of scattered or aggregated atypical cells consisting of large, pleomorphic nuclei with irregular membranes, chromatin clumps and prominent nucleoli. The morphology of the surgical specimen was similar to that of an anaplastic carcinoma and although it showed signs of transition from a normal follicular epithelium, there was no invasive growth or mitosis. This lesion was diagnosed as an atypical adenoma, and a papillary carcinoma was also present in the right lobe of the thyroid. Here we evaluate the molecular features of atypical adenomas in comparison with 9 ATC samples, and discuss whether or not atypical adenomas represent a form of premalignant lesion. Ki-67 expression was found to be very low in atypical adenomas whereas all ATC samples showed high levels of Ki-67 expression. Epithelial-mesenchymal transition (EMT) marker expression suggested that atypical adenomas maintain their epithelial phenotype to a higher degree than do ATCs. Differential diagnosis between ATC and atypical adenoma is difficult by cytological and histological methods alone, and Ki-67 and EMT marker expression may support the diagnosis.
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http://dx.doi.org/10.1002/dc.23751DOI Listing
October 2017

The potential diagnostic role of the number of ultrasonographic characteristics for patients with thyroid nodules evaluated as bethesda I-v.

Front Oncol 2014 23;4:261. Epub 2014 Sep 23.

Otolaryngology - Head and Neck Surgery, Hokkaido University Graduate School of Medicine , Sapporo , Japan.

Objective: Fine-needle aspiration cytology (FNAC) is considered to be the most reliable method of examination for thyroid nodules. However, when thyroid nodules are evaluated as Bethesda I-V, the role of ultrasonography is considered to be enhanced. We investigated the association between a number of ultrasonographic (US) characteristics and the risk of thyroid malignancy, and assessed the optimal compromise on the number of US characteristics for predicting thyroid malignancy.

Methods: Seventy-three patients, whose thyroid nodules were evaluated as Bethesda I-V by FNAC prior to surgery, were treated surgically. A number of US characteristics, such as microcalcification, irregular margins, hypoechogenicity, a taller-than-wide shape, and the absence of halo sign, were assessed before surgery. The optimal compromise on the number of US characteristics was analyzed using a receiver operating characteristics (ROC) curve. The area under the ROC curve (AUC) represents the overall discriminatory ability of a test.

Results: The risk of malignancy was 11.8% in patients without any US characteristics, 44.4% in those with one characteristic, 61.5% in those with two characteristics, 75% in those with three characteristics, 90% in those with four characteristics, and 100% in those with five characteristics. The AUC was favorable (0.81599). At least two US characteristics were revealed to be the optimal compromise on the number of US characteristics based on the ROC curve.

Conclusion: We proved the role of the number of US characteristics in predicting thyroid malignancy. It was thought that a surgical approach should be considered for patients with at least two US characteristics.
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http://dx.doi.org/10.3389/fonc.2014.00261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172018PMC
October 2014
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