MDPI Acta Medica Okayama 2075-4418 12 2 2022 Clinicopathologic Analysis of Sinonasal Inverted Papilloma, with Focus on Human Papillomavirus Infection Status 454 EN Munechika Tsumura Department of Otolaryngology Head and Neck Surgery, Kagawa Rosai Hospital Seiichiro Makihara Department of Otolaryngology Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Asami Nishikori Division of Pathophysiology, Graduate School of Health Sciences, Okayama University Yuka Gion Division of Pathophysiology, Graduate School of Health Sciences, Okayama University Toshiaki Morito Shotaro Miyamoto Department of Otolaryngology Head and Neck Surgery, Kagawa Rosai Hospital Tomoyuki Naito Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital Kensuke Uraguchi Department of Otolaryngology Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Aiko Oka Department of Otorhinolaryngology, School of Medicine, International University of Health and Welfare Tomoyasu Tachibana Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital Yorihisa Orita Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kumamoto University Shin Kariya Department of Otolaryngology Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Mitsuhiro Okano Department of Otorhinolaryngology, School of Medicine, International University of Health and Welfare Mizuo Ando Department of Otolaryngology Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Yasuharu Sato Department of Pathology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 10 2021 Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss e0258977 EN Kensuke Uraguchi Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihide Maeda Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Takahara Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mizuo Ando Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-kappa B subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-kappa B would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-kappa B-interacting inflammatory molecules, TNF alpha and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2211-7539 30 2020 A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery 22 25 EN Kensuke Uraguchi Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Kozakura Department of Otorhinolaryngology, Kochi Health Sciences Center Satoshi Oka Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Takaya Higaki Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Makihara Department of Otorhinolaryngology, Head and Neck Surgery, Kagawa Rosai Hospital Toshi Imai Department of Hematology and Blood Transfusion, Kochi Health Sciences Center Akira Doi Department of Otorhinolaryngology, Kochi Health Sciences Center Tsuyoshi Ohta Department of Neurosurgery, Kochi Health Sciences Center Shin Kariya Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 01680102 2020 Immediate changes in transcription factors and synaptic transmission in the cochlea following acoustic trauma: A gene transcriptome study EN Yukihide Maeda Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kensuke Uraguchi Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junko Takahara Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Fujimoto Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sugaya Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology- Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss. No potential conflict of interest relevant to this article was reported.

Lippincott, Williams & Wilkins Acta Medica Okayama 15317129 41 3 2020 Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media 364 370 EN Shin Kariya Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pengfei Zhao Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihide Maeda Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Kataoka Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Makihara Department of Otolaryngology―Head and Neck Surgery, Kagawa Rosai Hospital Jun Nishihira Department of Medical Bioinformatics, Hokkaido Information University Tomoyasu Tachibana Departments of Otolaryngology, Japanese Red Cross Society Himeji Hospital Kazunori Nishizaki Department of Otolaryngology―Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. Background: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. Methods: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF－/－) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. Results: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF－/－ mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF－/－ mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. Conclusion: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2050-313X 8 2020 False vocal cord perforation with abscess treated by negative pressure wound therapy 2050313X20915415 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomoyuki Naito Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Kensuke Uraguchi Department of Otolaryngology, Kochi Health Sciences Center Junya Matsumoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Yohei Noda Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Perforation of the larynx is very rare but may result in severe airway complications that include pneumothorax, pneumonia, mediastinitis, and retropharyngeal abscess. If conservative treatment fails, aggressive treatments including reconstructive surgery with pedicle flap are considered. Negative pressure wound therapy has been used for large skin defects, necrotizing fasciitis, pharyngocutaneous fistula, stoma dehiscence, osteoradionecrosis of the mandible, chyle fistula, flap failure, and lymphangioma in the field of head and neck surgery. We report a case of false vocal cord perforation with abscess successfully treated by negative pressure wound therapy after abscess treatment. The result suggests that negative pressure wound therapy can be an alternative or adjunctive approach for larynx perforation when the perforation is difficult to close after conservative therapy. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1323-8930 65 4 2016 Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts 414 419 EN Kengo Kanai Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Fujiwara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Haruna Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sei-ichiro Makihara Department Otorhinolaryngology, Kagawa Rosai Hospital Yuji Hirata Department Otorhinolaryngology, Kagawa Prefectural Central Hospital Kazunori Nishizaki Department Otorhinolaryngology, Kagawa Prefectural Central Hospital Background: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E-2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD(2) metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production. In the present study, we sought to determine whether PGD(2) regulates VEGF release by nasal polyp fibroblasts. Methods: Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD(2) or PGD(2) receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. The concentration of VEGF in the culture supernatants was determined using ELISA. Results: 5 mM of PGD(2) significantly induced VEGF release by nasal polyp fibroblasts. VEGF release was also obtained by stimulation with a DP receptor-selective, but not with a CRTH2 receptor-selective agonist. In addition, PGD(2)-induced VEGF release was significantly inhibited by pre-treatment with DP receptor-selective antagonists. In contrast, pre-treatment with a CRTH2 receptor-selective antagonist significantly enhanced PGD(2)-induced VEGF release. Conclusions: PGD(2) stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 13238930 2020 Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis EN Aiko Oka Department of Otorhinolaryngology, International University of Health and Welfare Graduate School of Medicine Takahiro Ninomiya Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Tazuko Fujiwara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuka Gion Division of Pathophysiology, Okayama University Graduate School of Health Sciences Akira Minoura Department of Hygiene, Public Health and Preventive Medicine, Showa University School of Medicine Shin-ichi Haruna Department of Otorhinolaryngology, Head & Neck Surgery, Dokkyo Medical University Naohiro Yoshida Department of Otolaryngology, Jichi Medical University Saitama Medical Center Yasunori Sakuma Department of Otorhinolaryngology, Yokohama City Medical Center Kenji Izuhara Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School Junya Ono Shino-Test Co., Ltd. Masami Taniguchi Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Takenori Haruna Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahisa Koyama Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuji Takabayashi Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Yoshimasa Imoto Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Masafumi Sakashita Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Masanori Kidoguchi Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shigeharu Fujieda Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 35 1 2018 Dangerous noodle: A case of swallowing syncope and a review of 122 cases from the literature. 145 148 EN Kensuke Uraguchi Department of Otolaryngology Kochi Health Sciences Center Shin Kariya Department of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiichiro Makihara Department of Otolaryngology-Head and Neck Surgery Kagawa Rosai Hospital Aiko Oka Department of Otolaryngology-Head and Neck Surgery Kagawa Rosai Hospital Hiroo Ueeda Department of Cardiovascular Medicine Kagawa Rosai Hospital Yohei Noda Department of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology-Head and Neck Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Swallowing syncope is a rare medical condition. Even though it has been known as a neurally mediated syncope, the definitive mechanism of this condition remains unclear. We show in this study an additional case of swallowing syncope and review the 122 reported cases from the literature. A 47-year-old Japanese man had been suffering from recurrent syncopal attacks, when he fainted immediately after swallowing. Holter electrocardiogram monitoring demonstrated a sinus pause (maximum R-R interval of 3.8 seconds) after he swallowed a noodle quickly. A permanent pacemaker was implanted because the frequency of syncope increased. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1748-717X 14 1 2019 Dose distribution of intensity-modulated proton therapy with and without a multi-leaf collimator for the treatment of maxillary sinus cancer: a comparative effectiveness study. 209 EN Soichi Sugiyama Departments of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Kuniaki Katsui Departments of Proton Beam Therapy, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Yuki Tominaga Department of Radiation Technology, Tsuyama Chuo Hospital Takahiro Waki Department of Radiology, Tsuyama Chuo Hospital, Tusyama Norihisa Katayama Departments of Radiology, Okayama University Hospital Hidenobu Matsuzaki Departments of Oral Diagnosis and Dentomaxillofacial Radiology, Okayama University Hospital Shin Kariya Departments of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine Masahiro Kuroda Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kazunori Nishizaki Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Departments of Radiology, Dentistry and Pharmaceutical Science, Okayama University Graduate School of Medicine BACKGROUND: Severe complications, such as eye damage and dysfunciton of salivary glands, have been reported after radiotherapy among patients with head and neck cancer. Complications such as visual impairment have also been reported after proton therapy with pencil beam scanning (PBS). In the case of PBS, collimation can sharpen the penumbra towards surrounding normal tissue in the low energy region of the proton beam. In the current study, we examined how much the dose to the normal tissue was reduced by when intensity-modulated proton therapy (IMPT) was performed using a multi-leaf collimator (MLC) for patients with maxillary sinus cancer. METHODS: Computed tomography findings of 26 consecutive patients who received photon therapy at Okayama University Hospital were used in this study. We compared D2% of the region of interest (ROI; ROI-D2%) and the mean dose of ROI (ROI-mean) with and without the use of an MLC. The organs at risk (OARs) were the posterior retina, lacrimal gland, eyeball, and parotid gland. IMPT was performed for all patients. The spot size was approximately 5-6 mm at the isocenter. The collimator margin was calculated by enlarging the maximum outline of the target from the beam's eye view and setting the margin to 6 mm. All plans were optimized with the same parameters. RESULTS: The mean of ROI-D2% for the ipsilateral optic nerve was significantly reduced by 0.48 Gy, and the mean of ROI-mean for the ipsilateral optic nerve was significantly reduced by 1.04 Gy. The mean of ROI-mean to the optic chiasm was significantly reduced by 0.70 Gy. The dose to most OARs and the planning at risk volumes were also reduced. CONCLUSIONS: Compared with the plan involving IMPT without an MLC, in the dose plan involving IMPT using an MLC for maxillary sinus cancer, the dose to the optic nerve and optic chiasm were significantly reduced, as measured by the ROI-D2% and the ROI-mean. These findings demonstrate that the use of an MLC during IMPT for maxillary sinus cancer may be useful for preserving vision and preventing complications. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 03858146 46 6 2019 Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy 927 933 EN Seiichiro Makihara Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mai Noujima-Harada Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Nobuya Ohara Department of Pathology, Kagawa Rosai Hospital Tomoyuki Naito Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Junya Matsumoto Department of Otolaryngology-Head & Neck Surgery, Kagawa Rosai Hospital Yohei Noda Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology, International University of Health and Welfare School of Medicine Tadashi Yoshino Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences As has been well recognized, methotrexate (MTX) leads to a state of immunosuppression and can provide a basis for the development of lymphoproliferative disorders (LPDs). MTX-associated LPDs can affect nodal sites as well as extranodal sites, though the manifestation of an LPD in the form of multiple pulmonary nodules is rare. Here, we report two cases of MTX-associated LPD with multiple bilateral pulmonary nodules, which was a finding suggestive of lung cancer, and bilateral cervical lymphadenopathy. After withdrawal of MTX, the multiple bilateral pulmonary nodules and bilateral cervical lymphadenopathy disappeared without chemotherapy in both cases. From these results, patients with pulmonary nodules and cervical lymphadenopathy should be examined for head and neck malignant tumors. Also, physicians should carefully check the administration of MTX. In patients with an MTX-associated LPD, we need to make an early diagnosis and consider discontinuing the administration of MTX as soon as possible. No potential conflict of interest relevant to this article was reported.

The International Institute of Anticancer Research Acta Medica Okayama 0258-851X 33 1 2019 Relationship Between Renal Dysfunction and Oral Mucositis in Patients Undergoing Concurrent Chemoradiotherapy for Pharyngeal Cancer: A Retrospective Cohort Study. 183 189 EN HIROFUMI MIZUNO Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HISATAKA MIYAI Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences AYA YOKOI Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences TERUMASA KOBAYASHI Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences CHIAKI INABU Junpukai Daiku Dental Clinic TAKAYUKI MARUYAMA Center for Innovative Clinical Medicine, Okayama University Hospital DAISUKE EKUNI Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences NOBUYOSHI MIZUKAWA Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Hospital SHIN KARIYA Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KAZUNORI NISHIZAKI Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences YOSHIHIRO KIMATA Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MANABU MORITA Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND/AIM: The aim of this retrospective cohort study was to investigate the association between renal dysfunction (RD) and the development of oral mucositis (OM) in patients undergoing concurrent chemoradiotherapy (CCRT) for pharyngeal cancer including radiation to the oral cavity. PATIENTS AND METHODS: Of 130 patients diagnosed as having pharyngeal cancer who received CCRT at the Okayama University Hospital Head and Neck Cancer Center, 44 were finally selected. RESULTS: During the observation period, 24 (54.5%) patients experienced severe OM (grade 3). The Cox proportional hazards regression model demonstrated that RD (hazard ratio(HR)=2.45, 95% confidence interval(CI)=1.067-6.116, p=0.035) and nasopharynx/oropharynx as center of the irradiated area (HR=2.56, 95% CI=1.072-5.604, p=0.034) were significantly associated with the incidence of severe OM (grade 3). CONCLUSION: In patients with pharyngeal cancer treated with CCRT including radiation to the oral cavity, RD at baseline can be a risk factor for developing severe OM. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 13238930 68 2 2019 Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis 216 224 EN Takahisa Koyama Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuharu Sato Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuka Gion Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Haruna Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Fujiwara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akira Minoura Department of Public Health, Showa University School of Medicine Soshi Takao Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yorihisa Orita Department of Otolaryngology-Head and Neck Surgery, Kumamoto University Kengo Kanai Department of Otorhinolaryngology-Head & Neck Surgery, Kagawa Prefectural Central Hospital Masami Taniguchi Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course. No potential conflict of interest relevant to this article was reported.

Taylor & Francis Acta Medica Okayama 0001-6489 137 5 2017 The impact of chronic rhinosinusitis on long-term survival in lung transplantation recipients 529 533 EN Shin Kariya Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuhiro Okano Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Oto Department of Thoracic Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takenori Haruna Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yohei Noda Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazunori Nishizaki Department of Otolaryngology-Head and Neck Surgery , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences CONCLUSIONS: Chronic rhinosinusitis diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012, not by computed tomography alone, is one of the prognostic factors affecting long-term survival in patients with lung transplantation. Endoscopic sinus surgery might play a beneficial role in the management of lung transplantation recipients with chronic rhinosinusitis. OBJECTIVE: To show the effect of paranasal sinus infection on post-lung transplantation survival. METHOD: Lung transplantation recipients were included in this study. Computed tomography was performed before and after lung transplantation. The severity of chronic rhinosinusitis was evaluated by Lund-Mackay scoring system. The survival rate was calculated by the Kaplan-Meier method. RESULTS: One hundred and forty-eight patients received lung transplantation for various indications. Chronic rhinosinusitis was found in 18.9% (28/148) of the lung transplantation recipients. Of 28 patients with chronic rhinosinusitis, seven patients underwent endoscopic sinus surgery due to persistent post-nasal drip. The recipients with chronic rhinosinusitis who did not receive endoscopic sinus surgery (n = 21) showed a significantly lower survival rate as compared to the patients without chronic rhinosinusitis. There was no statistically significant difference in the survival rate between the recipients with (n = 50) and without (n = 98) paranasal sinus abnormality on computed tomography. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1323-8930 65 1 2016 Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-γ production in chronic rhinosinusitis with nasal polyps 96 102 EN Mitsuhiro Okano Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tazuko Fujiwara Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Kariya Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takaya Higaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sei-ichiro Makihara Department of Otorhinolaryngology, Kagawa Rosai Hospital Takenori Haruna Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Noyama Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahisa Koyama Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryotaro Omichi Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yorihisa Orita Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Miki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kengo Kanai Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital Kazunori Nishizaki Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND: Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs). METHODS: DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-γ in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined. RESULTS: Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-γ by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN-γ production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs. CONCLUSIONS: These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0954-7894 42 8 2012 COX/PGE(2) axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps 1217 1226 EN T Higaki M Okano T Fujiwara S Makihara S Kariya Y Noda T Haruna K Nishizaki Background Lipopolysaccharide (LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway. Objective We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells (DNPCs). Methods Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B (SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-gamma within the supernatant were measured. The effects of PGE(2) on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE(2) production and mRNA expression of COX-1, COX-2 and microsomal PGE(2) synthase-1 (m-PGES-1) were measured. Results Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-gamma production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE(2) production and expression of COX-2 and m-PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE(2) inhibited IL-5, IL-13 and IFN-gamma production. LPS alone induced IL-5, IL-13 and IFN-gamma production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE(2) itself, inhibited IL-5 and IL-13 production. Conclusions and Clinical Relevance These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/PGE(2) axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 64 6 2010 Comparing the cochlear spiral modiolar artery in type-1 and type-2 diabetes mellitus:a human temporal bone study 375 383 EN Shin Kariya Sebahattin Cureoglu Hisaki Fukushima Norimasa Morita Muzeyyen Y. Baylan Yukihide Maeda Kazunori Nishizaki Michael M. Paparella Original Article 10.18926/AMO/41323 This study examined whether pathological findings were present in cochlear vessels for patients with diabetes mellitus. Twenty-six temporal bones from 13 patients with type 1 diabetes mellitus and 40 temporal bones from 20 patients with type 2 diabetes mellitus were examined. Type 2 diabetic temporal bones were divided into 2 groups according to diabetic management (22 temporal bones with insulin therapy, and 18 with oral hypoglycemic drugs). Age-matched normal control temporal bones were also selected. The vessel wall thickness in the cochlear spiral modiolar artery was measured under a light microscope, and the vessel wall ratio (vessel wall thickness/outer diameter of the vessel×100) was calculated. The vessel wall thickness and vessel wall ratio in type 1 diabetes mellitus were significantly greater than in normal controls. Type 2 diabetic patients with insulin therapy showed significantly greater vessel wall thickness and vessel wall ratios than controls. In type 2 diabetes mellitus, the vessel wall thickness and vessel wall ratio were greater in patients treated with insulin therapy than in those treated with oral hypoglycemic agents. Type 2 diabetic patients with insulin therapy showed an increased vessel wall thickness and vessel wall ratio compared to patients with type 1 diabetes mellitus. In conclusion, the cochlea in patients with diabetes mellitus shows circulatory disturbance compared to age-matched normal controls. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 118 11 2004 Abnormal direction of internal auditory canal and vestibulocochlear nerve 902 905 EN Shin Kariya kazunori Nishizaki Hirofumi Akagi Michael M. Paparella Several internal auditory canal (IAC) anomalies have been reported.To our knowledge, only one case with anabnormal direction of the IAC has been reported in an infant with Pierre Robin syndrome. In this paper, wepresent the first report of two non-syndromic cases with abnormal IAC direction. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2005 Role of Macrophage Migration Inhibitory Factor in Otitis Media with Effusion in Adults EN Shin Kariya No potential conflict of interest relevant to this article was reported.