Faculty Profiles - Seiichiro Makihara

Papers - Seiichiro Makihara

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Endoscopic surgical strategy for highly vascular pediatric sinonasal and pterygopalatine fossa tumors. Reviewed International journal

Aiko Shimizu, Seiichiro Makihara, Minori Noda, Aya Murai, Mizuo Ando

Auris, nasus, larynx 52 ( 3 ) 243 - 247 2025.4

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Pediatric sinonasal tumors are rare, and minimally invasive approaches are preferred because of unknown long-term effects on development. We report three cases of highly vascular pediatric sinonasal and pterygopalatine fossa tumors that were successfully removed using an endonasal endoscopic approach with transcatheter arterial embolization (TAE). The patients (9-11 years old) had contrast-enhanced tumors in the left ethmoid sinus near the sphenopalatine foramen in case 1, in the right nasal cavity near the sphenopalatine foramen in case 2, and in the right pterygopalatine fossa in case 3, with diameters of 32, 50, and 61 mm, respectively. Computed tomography and magnetic resonance imaging demonstrated tumors with strong contrast enhancement and flow voids in all cases. TAE was performed in all cases on the day of surgery, followed by endoscopic sinus surgery with nasal septal modification. Pathology revealed pyogenic granuloma, nasal polyps, and juvenile angiofibroma. After TAE, tumor reduction improved visualization in case 1. Nasal septum manipulation enabled medial traction and tumor base identification in cases 2 and 3. The combination of preoperative TAE and septal modification proved effective for achieving complete endoscopic tumor removal. No complications occurred, and follow-up at 1-1.5 years showed no tumor recurrence or developmental abnormalities.

DOI： 10.1016/j.anl.2025.04.006

Identification of factors related to functional prognoses in craniopharyngiomas. Reviewed International journal

Tsuyoshi Umeda, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Naoya Kemmotsu, Ryoji Imoto, Yasuhito Kegoya, Ryo Mizuta, Yohei Inoue, Madoka Hokama, Seiichiro Makihara, Kosei Hasegawa, Kenichi Inagaki, Fumio Otsuka, Takao Yasuhara, Shota Tanaka

Journal of neuro-oncology 2025.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patients' social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center. METHODS: A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors. RESULTS: The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047). CONCLUSIONS: Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patients' social participation.

DOI： 10.1007/s11060-024-04925-7

Association Between Dinner-to-Bed Time and Gastroesophageal Reflux-Related Diseases in Children. Reviewed International journal

Kensuke Uraguchi, Naomi Matsumoto, Toshiharu Mitsuhashi, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

Cureus 17 ( 1 ) e77709 2025.1

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Gastroesophageal reflux disease (GERD) is characterized by esophageal mucosal injury due to the reflux of gastroduodenal contents. Typical symptoms include heartburn and acid regurgitation. In addition, gastroesophageal reflux (GER) can influence conditions such as otitis media, rhinitis, and asthma. This study aimed to examine the association between dinner-to-bed time and GER-related diseases, such as otitis media, allergic rhinitis, and asthma. METHODS: This was a longitudinal cohort study using secondary data. Data were collected from a large-scale birth cohort study conducted in Japan including babies born in 2001 and 2010. Dinner-to-bed time was categorized as "longer dinner-to-bed time" (>120 minutes), "shorter dinner-to-bed time" (≤120 minutes or less), and "irregular dinner-to-bed time." Modified Poisson regression with robust variance was used to estimate risk ratios (RRs). RESULTS: A total of 60,392 children were included in this study. Children with shorter dinner-to-bed time had a higher risk of asthma (adjusted RR (aRR) = 1.10; 95% confidence interval (CI), 1.03-1.18) than those with longer dinner-to-bed time. However, no significant association was observed between shorter dinner-to-bed time and otitis media or allergic rhinitis. Furthermore, supplementary analyses revealed that the risk of asthma was significantly higher in children born in 2001 (aRR = 1.13; 95% CI, 1.04-1.22). CONCLUSION: This study showed that dinner-to-bed time within 120 minutes after dinner increases the risk of developing asthma. This underscores the importance of considering lifestyle modifications, as certain pediatric asthma cases may be influenced by behaviors that promote GER.

DOI： 10.7759/cureus.77709

【指定難病 Up to Date】好酸球性副鼻腔炎

牧原靖一郎

岡山医学会雑誌 136 ( 3 ) 127 - 131 2024.12

【内視鏡下鼻副鼻腔手術-基本とコツで上手くなる】内視鏡下鼻副鼻腔手術の実際篩骨洞手術

清水藍子, 牧原靖一郎

耳鼻咽喉科・頭頸部外科 96 ( 13 ) 1121 - 1127 2024.12

【第一線のエキスパートが教える耳科・鼻科における術前プランニングと手術テクニック】TACMI(transseptal access with crossing multiple incisions)法

清水藍子, 牧原靖一郎

ENTONI ( 302 ) 123 - 129 2024.10

Language：Japanese Publisher：(株)全日本病院出版会

Transseptal access with crossing multiple incisions(TACMI)法は2017年に初めてOmuraらによって報告された手術手技である.両側の鼻中隔粘膜に切開を入れることにより,対側鼻孔からのアプローチと対側鼻腔の利用が可能となる.この手技により,より正確に腫瘍基部を確認でき,より少ない出血量で手術を行うことができる.2021年には健側の鼻中隔粘膜に切開をおかないMINI TACMIも報告された.TACMI法では両側の鼻中隔粘膜に切開を入れるため,鼻中隔穿孔のリスクがある.一方,MINI TACMIでは健側の鼻中隔粘膜が温存されるため,そのリスクは低減できる.TACMI法を成功させるには手順のみならず,通常の手術手技での意識も重要であると考えている.(著者抄録)

Endoscopic Transpterygoid Repair of Sphenoid Sinus Meningocele: A Comprehensive Case Report and Literature Review. Reviewed International journal

Aiko Shimizu, Seiichiro Makihara, Ryoji Imoto, Koji Hirashita, Mizuo Ando

Auris, nasus, larynx 51 ( 5 ) 875 - 879 2024.8

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

We report a challenging and uncommon case involving a 53-year-old Japanese man with cerebrospinal fluid (CSF) leakage caused by a meningocele in the lateral recess of the sphenoid sinus. Our innovative treatment approach involved a combination of transpterygoid and endoscopic modified medial maxillectomy techniques, with special emphasis on the preservation of the sphenopalatine artery. This strategic preservation was pivotal to the successful use of the ipsilateral nasoseptal flap for reconstruction, which played a crucial role in the prevention of postoperative CSF leakage. Otolaryngologists and neurosurgeons collaborated to perform the bath-plugging technique; effective collaboration was instrumental to the success of the procedure. This report highlights significant advancement from conventional frontal craniotomy to a more sophisticated endoscopic technique, shows the importance of meticulous surgical planning and execution, emphasizes careful preservation of critical anatomical structures during complex neurosurgical and otolaryngological procedures, and underscores the evolving landscape of surgical approaches for managing complex medical conditions.

DOI： 10.1016/j.anl.2024.08.003

Shifting paradigms in endoscopic sinus surgery: a comprehensive analysis from Japan's national database. Reviewed International journal

Seiichiro Makihara, Kensuke Uraguchi, Shohei Fujimoto, Aiko Shimizu, Shin Kariya, Mitsuhiro Okano, Takashi Yorifuji, Mizuo Ando

Acta oto-laryngologica 144 ( 9 ) 1 - 6 2024.8

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In 2013, Japan established a standardized classification system for categorizing endoscopic sinus surgery (ESS) into types I-V, yet no evaluation has been conducted thereof. OBJECTIVE: We assessed the ESS trends and status in Japan, focusing on outpatient and inpatient surgeries. MATERIAL AND METHODS: This descriptive retrospective cohort study used Japan's National Database of Health Insurance Claims and Specific Health Checkups between 2014 and 2021. The distribution of ESS types I-V and outpatient and inpatient surgeries was analysed, along with age groups and regional differences, focusing on ESS type III. RESULTS: Overall, 427,813 ESS procedures were performed, with types III and IV being most common. Outpatient ESS type III increased substantially compared to inpatient surgeries. Younger individuals favoured outpatient ESS type III over inpatient surgeries, with substantial regional variations across prefectures. CONCLUSIONS AND SIGNIFICANCE: The adoption of a standardized ESS classification in Japan has facilitated a detailed understanding of surgical trends. The shift toward outpatient surgeries, especially for type III ESS, aligns with global trends toward minimally invasive procedures and reflects changing patient preferences and healthcare delivery practices. Consequently, continuous monitoring and research are crucial for adapting surgical practices to the evolving healthcare needs and patient expectations.

DOI： 10.1080/00016489.2024.2389179

Pneumocephalus with Inverted Papilloma in the Frontoethmoidal Sinus: Case Report and Literature Review. Reviewed

Seiichiro Makihara, Yoshihiro Otani, Kensuke Uraguchi, Sawako Ono, Aiko Shimizu, Ryosuke Ikemachi, Yosuke Okazaki, Tomoyuki Ota, Hiroshi Matsumoto, Shotaro Miyamoto, Munechika Tsumura, Seiya Hayashi, Michiari Umakoshi, Koji Hirashita, Mizuo Ando

Acta medica Okayama 78 ( 4 ) 337 - 343 2024.8

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Here, we describe the unique case of a pneumocephalus originating from an inverted papilloma (IP) in the frontoethmoidal sinus. A 71-year-old man with diabetes presented with headaches and altered consciousness. Imaging revealed the pneumocephalus together with bone destruction in the left frontal sinus. He underwent simultaneous endoscopic endonasal and transcranial surgery using an ORBEYE exoscope. Pathological diagnosis of the tumor confirmed IP. Post-surgery, the pneumocephalus was significantly resolved and the squamous cell carcinoma antigen level, which had been elevated, decreased. This case underscores the importance of a multidisciplinary approach and innovative surgical methods in treating complex sinonasal pathologies.

DOI： 10.18926/AMO/67550

Neurectomy for allergic rhinitis in Japan: Increasing trends and surgeon preferences. Reviewed International journal

Seiichiro Makihara, Kei Hosoya, Kensuke Uraguchi, Yohei Maeda, Taro Komachi, Takashi Yorifuji, Mizuo Ando, Shoji Matsune, Kimihiro Okubo

Auris, nasus, larynx 51 ( 5 ) 834 - 839 2024.7

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: There is no consensus on the optimal surgical technique for allergic rhinitis (AR). Furthermore, the appropriateness of surgical intervention in children and older individuals remains debatable. This study aimed to analyze trends and patterns in the surgical management of AR in Japan, focusing on parasympathetic neurectomy. METHODS: Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we conducted a comprehensive review of procedures performed between April 2014 and March 2022. In addition, a cross-sectional survey targeting otolaryngologists across Japan was conducted to gather insights into surgical preferences and practices. RESULTS: The NDB data showed an increasing trend in neurectomies, with the most frequent age group being 25-29 years; the procedure was also performed in pediatric and older patients. The survey among otolaryngologists indicated that 58.2 % of surgeons preferred peripheral branch neurectomy of the posterior nasal nerve. The findings of this study also indicated a cautious approach toward conducting these procedures in children, with 51.2 % of surgeons considering patients less than 18 years of age unsuitable for the procedure. CONCLUSION: This study highlighted a shift toward simple and minimally invasive surgical methods, such as peripheral branch neurectomy, in Japan. However, further research is needed to understand the long-term outcomes and refine the surgical techniques. The findings of this study also emphasized the need for age-specific considerations when treating pediatric and older patients with AR.

DOI： 10.1016/j.anl.2024.07.005

Role of nasal polyp-derived innate lymphoid cells in staphylococcal enterotoxin-induced cellular responses. Reviewed International journal

Kengo Kanai, Aiko Oka, Shin Kariya, Tazuko Fujiwara, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Maki Akamatsu, Kazunori Nishizaki, Mizuo Ando, Mitsuhiro Okano

Allergology international : official journal of the Japanese Society of Allergology 73 ( 3 ) 477 - 480 2024.7

Pediatric otitis media in Japan: A nationwide longitudinal study of the pre- and post-pneumococcal conjugate vaccine eras born in 2001 and 2010. Reviewed International journal

Kensuke Uraguchi, Naomi Matsumoto, Toshiharu Mitsuhashi, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

Vaccine 42 ( 19 ) 4081 - 4087 2024.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Otitis media (OM) is a prevalent respiratory disease in children and poses significant public health challenges due to its impact on child health and economic burdens. However, there have no nationwide epidemiological studies conducted in Japan. This study investigates the epidemiological trends of OM in Japan, taking into account the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) introduction. METHOD: This study was retrospective cohort study using secondary data on the nationwide longitudinal birth cohort. This survey followed two cohorts born in 2001 (pre-PCV era) and 2010 (post-PCV era) until the age of 9. Every year, parents were surveyed about their children's health status, including occurrences of OM. The annual period prevalence and cumulative incidence of OM were assessed in this study, and the two cohorts were compared using a modified Poisson regression model adjusted environmental factors with the 2001 cohort as reference. RESULT: The study included 47,015 children from the 2001 cohort and 38,554 from the 2010 cohort. Peak annual period prevalence of OM varied by era. Cumulative incidence was 13.8 % for the 2001 cohort and 18.5 % for the 2010 cohort by 1.5 years of age and 28.9 % and 33.3 %, respectively, by 3.5 years of age. In particular, from the fourth survey onward, covering ages 2.5-3.5 years, a shift was observed from an increased risk to a decreased risk of OM. CONCLUSION: This nationwide longitudinal study emphasizes variations in OM epidemiology across Japan over time, with changes potentially influenced by the introduction of PCV7. In this study, due to the absence of individual PCV7 vaccination data, the effect of PCV7 was estimated based on the vaccination rate at the population level. The results suggest a notable decrease in the incidence of OM in later years, aligning with the increased uptake of PCV7.

DOI： 10.1016/j.vaccine.2024.05.020

Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base. Reviewed International journal

Seiichiro Makihara, Yoshihiro Otani, Kensuke Uraguchi, Aiko Shimizu, Aya Murai, Takaya Higaki, Naoki Akisada, Shohei Fujimoto, Takuma Makino, Joji Ishida, Kentaro Fujii, Takao Yasuhara, Tomoyuki Ota, Hiroshi Matsumoto, Mizuo Ando

Head & neck 46 ( 5 ) 1074 - 1082 2024.3

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

DOI： 10.1002/hed.27724

Various arrangements of pharyngeal flap in soft palate reconstruction after cancer treatment. Reviewed International journal

Hiroshi Matsumoto, Tomoyuki Ota, Motoi Kato, Takuma Makino, Seiichiro Makihara, Mizuo Ando, Yoshihiro Kimata

Head & neck 46 ( 7 ) 1573 - 1581 2024.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The pharyngeal flap (PF) is useful for reconstruction of soft palate defects, but effective arrangements of PF for various types of soft palate defects are controversial. Here, we classify three types of soft palate defects and discuss the arrangements of PF and their functional prognosis. METHODS: Reconstruction was performed based on the classification of the defects. Clinical details were collected, and postoperative function was analyzed. RESULTS: Eight patients were included in the study. The defect sizes ranged from 25 (width) × 40 (depth) to 40 × 60 mm. Six patients underwent pharyngeal flap reconstruction with free-flap reconstruction, and two underwent pharyngeal flap reconstruction. The pharyngeal flap was harvested at the maximum width of the posterior pharyngeal wall, ranging from 25 to 40 mm in length. Eating and speaking functions were maintained in all patients. CONCLUSIONS: Good postoperative function can be maintained by narrowing the velopharyngeal space with a pharyngeal flap.

DOI： 10.1002/hed.27712

高齢者に多い耳鼻咽喉科疾患鼻領域副鼻腔嚢胞

清水藍子, 牧原靖一郎

鼻アレルギーフロンティア 24 ( 1 ) 20 - 24 2024.2

Chronic rhinosinusitis possibly associated with decreased lung function in chronic cough patients. Reviewed International journal

Pengfei Zhao, Shin Kariya, Takaya Higaki, Seiichiro Makihara, Toru Rikimaru, Mitsuhiro Okano, Mizuo Ando

Brazilian journal of otorhinolaryngology 90 ( 4 ) 101424 - 101424 2024

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The purpose of this study is to investigate the lung function in Chronic Rhinosinusitis (CRS) patients with Chronic Cough (CC). METHODS: A total of 1413 CC patients were retrospectively screened and 109 CRS patients with CC were enrolled. Lung function, Lund-Mackay Computed Tomography (CT) score, smoking status, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples, and Sino-Nasal Outcome Test were examined. Normal control subjects are also recruited. RESULTS: The Forced Expiratory Volume in 1 second (FEV1.0), Percent Predicted FEV1.0, and FEV1.0/Forced Vital Capacity (FVC) ratio in the patients were significantly low as compared with the control subjects. The FEV1.0/FVC ratio was negatively correlated with the Lund-Mackay CT scores of the patients with a high CT score. CONCLUSIONS: The CRS patients with CC should be investigated with lung function. In addition, the multidisciplinary evaluation including a pulmonologist is needed to manage the CRS patients with CC. LEVEL OF EVIDENCE: Level 4.

DOI： 10.1016/j.bjorl.2024.101424

Association Between Clinical Remission of Infantile-Onset Allergic Rhinitis During the School-Age Period and the Type of Housing: A Longitudinal Population-Based Japanese Study. Reviewed International journal

Kensuke Uraguchi, Naomi Matsumoto, Toshiharu Mitsuhashi, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners 38 ( 4 ) 629 - 636 2023.12

Language：English Publishing type：Research paper (scientific journal)

This study investigated the association between housing type and clinical remission of infantile-onset allergic rhinitis (AR) in 53,575 children born in 2001 in Japan. Infantile-onset AR was defined as the presence of AR symptoms reported between ages 1.5 and 4.5 years, and remission was assessed between ages 10 and 12. The type of housing was categorized into detached houses and multi-unit residential buildings with 1-2, 3-5, or ≥6 floors. Among the 4,352 infantile-onset AR, 42.9% experienced remission. Notably, living in multi-unit residential buildings, particularly those with 1-2 and ≥6 floors, was positively associated with AR remission.

DOI： 10.1016/j.pedhc.2023.11.011

Risk Factors for Anterior Skull Base Injury in Endoscopic Sinus Surgery Reviewed International journal

Seiichiro Makihara, Kensuke Uraguchi, Tomoyuki Naito, Aiko Shimizu, Aya Murai, Takaya Higaki, Yohei Noda, Shin Kariya, Mitsuhiro Okano, Mizuo Ando

Cureus 15 ( 11 ) e49273 2023.11

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Objectives This retrospective study aimed to investigate the relationships between the Keros classification, the Gera classification, the vertical height of the posterior ethmoid roof (ER), and anterior ethmoidal artery (AEA) types in Japanese patients. Methods We investigated the computed tomography (CT) slices of paranasal sinuses (120 sides) of 60 patients; measured the cribriform plate (CP) depth, lateral lamella CP angle (LLCPA), and vertical height of the lateral ER from the hard palate (LERHP) at the coronal plane of the posterior ethmoidal artery (PEA); and reviewed the AEA types, whether floating or non-floating. Results CP depth was positively correlated with LLCPA (r=0.63; p<0.01) and the height of LERHP (r=0.19; p<0.05). The height of the LERHP in females was significantly lower than that in males. With increased CP depth, floating AEAs became prevalent (p<0.001). Conclusion In females, low height of the posterior ethmoid sinus roof, where cerebrospinal fluid (CSF) leaks occurred while penetrating the basal lamella, often existed; the heights positively correlated with the Keros classification in Japanese patients. The Keros and Gera classifications, AEA type, and posterior ER height do not individually constitute a complete risk assessment but may correlate, preventing major complications, such as CSF leak and orbital hemorrhage.

DOI： 10.7759/cureus.49273

Nasopharyngeal low-grade papillary schneiderian carcinoma with cervical metastasis. Reviewed International journal

Kensuke Uraguchi, Kenji Nishida, Takuma Makino, Seiichiro Makihara, Masahiro Tabata, Shin Kariya, Mizuo Ando

Auris, nasus, larynx 50 ( 5 ) 821 - 826 2023.10

Language：English

Low-grade papillary Schneiderian carcinoma (LGPSC) is a rare and newly described type of cancer arising from the Schneiderian epithelium. Owing to cellular atypia, it is difficult to differentiate this type from other papillomas and malignancies. Although this condition remains unclear, it is associated with mortality and recurrence. Therefore, treating physicians should be aware of the possibility of LGPSC for prompt diagnosis and treatment. In this article, we present an additional case of nasopharyngeal LGPSC with cervical lymph node metastasis and reviewed the 14 cases reported thus far in the literature. A 76-year-old female was referred to our department for detailed examination of nasopharyngeal and cervical lymph node tumors detected by positron emission tomography-computed tomography. Based on the biopsy of the nasopharyngeal tumor, we suspected LGPSC. Considering the clinical course and pathological findings, the patient was diagnosed with cervical lymph node metastasis through neck dissection. We performed radiotherapy for the primary lesion of the nasopharynx, which led to the disappearance of the tumor. After 13 months following the radiotherapy, the patient died from a recurrence of retroperitoneal liposarcoma without the recurrence of LGPSC.

DOI： 10.1016/j.anl.2022.12.010

内視鏡下鼻副鼻腔手術後のナゾポアによる鼻内パッキングの有用性 Reviewed

岡愛子, 小池隆史, 北村寛志, 上斗米愛実, 金井健吾, 渡部佳弘, 今西順久, 野口佳裕, 赤松摩紀, 牧原靖一郎, 岡野光博

耳鼻咽喉科・頭頸部外科 95 ( 10 ) 849 - 853 2023.9

Language：Japanese Publisher：(株)医学書院

当院では慢性副鼻腔炎に対する内視鏡下鼻副鼻腔手術(ESS)後の出血予防を目的とした鼻内パッキングにナゾポア(日本ストライカー社)を用いている。今回、2020年12月～2021年12月にナゾポアを使用した46例の成績を報告した。ESSのクリニカルパス逸脱を伴う出血を認めたのは1例のみであり、再手術を要する大出血や重症感染症は認めなかった。ナゾポアに抗菌薬やステロイドを浸潤させることで創傷治癒促進も期待できることから、ナゾポアはESS後の鼻内パッキングに有用と考えられた。

Association between handwashing and gargling education for children and prevention of respiratory tract infections: a longitudinal Japanese children population-based study Reviewed International journal

Kensuke Uraguchi, Toshiharu Mitsuhashi, Naomi Matsumoto, Soshi Takao, Seiichiro Makihara, Mizuo Ando, Takashi Yorifuji

European Journal of Pediatrics 182 ( 9 ) 4037 - 4047 2023.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

PURPOSE: A longitudinal study was conducted to examine the effects of handwashing and gargling education for children on the prevention of respiratory tract infections (RTIs) in children in Japan. METHODS: The study included 38,554 children born in 2010 who were enrolled in a longitudinal study. Information on children's hygiene education regarding handwashing and gargling was collected in a survey at the age of 3.5 years. Based on parents' reports of doctors' diagnoses, airway infections and influenza events in the 12-month duration before the survey were evaluated for RTIs at the ages of 4.5 and 9 years. Poisson regression with robust variance was performed to examine the effects of hygiene education on RTIs prevention. The supplementary analysis was stratified by household income. RESULTS: Children were categorized into different groups: 38% in the handwashing and gargling group, 29% in the handwashing group, 0.1% in the gargling group, and 9.7% in the no-education group. Exclusions were made for non-respondent children (23%) and those in the gargling group. Hygiene education was associated with decreased influenza at the age of 4.5 years in the handwashing (adjusted RR [aRR] = 0.8; 95% CI, 0.8-0.9) and handwashing and gargling groups (aRR = 0.8; 95% CI, 0.8-0.9) compared with no education. However, no preventive effects on airway infections at the age of 4.5 and 9, influenza at the age of 9, or hospitalization between the ages of 3.5 and 9 years were detected. Handwashing and gargling could significantly prevent influenza in low-income households (aRR = 0.7; 95% CI, 0.6-0.8). Conclusions: Gargling education was widespread and mostly combined with handwashing education in Japan. Hygiene education significantly affected prevention of influenza infections at the age of 4.5 years, especially in low-income households. WHAT IS KNOWN: • Previous intervention studies showed handwashing and gargling are effective in preventing respiratory tract infections. WHAT IS NEW: • We conducted a longitudinal study on handwashing and gargling education in Japanese children and found that handwashing and gargling were widely practiced together. • Handwashing and gargling education were related to a reduction in influenza, particularly in low-income households.

DOI： 10.1007/s00431-023-05062-5

Other Link： https://link.springer.com/article/10.1007/s00431-023-05062-5/fulltext.html

Macroarray expression analysis of cytokines and prostaglandin metabolism-related genes in chronic rhinosinusitis Reviewed International journal

Aiko Oka, Kengo Kanai, Takaya Higaki, Seiichiro Makihara, Yohei Noda, Shin Kariya, Mizuo Ando, Wataru Nishimura, Mitsuhiro Okano

Journal of Allergy and Clinical Immunology: Global 2 ( 3 ) 100123 - 100123 2023.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

BACKGROUND: Chronic rhinosinusitis (CRS) can be divided into endotypes by functional or pathophysiologic findings. OBJECTIVE: The aim of this study was to analyze the expression of cytokines, prostaglandin (PG) synthases, and their receptors related to the pathogenesis of CRS, especially those contributing to nasal polyp (NP) formation. METHODS: NPs and uncinate tissue (UT) samples were collected from 90 patients who underwent endoscopic sinus surgery. They included 75 patients with CRS (including 45 with eosinophilic CRS [eCRS] and 30 with non-eCRS) and 15 patients without CRS. A total of 30 genes were selected for our original DNA array plate to analyze the levels of expression of 10 cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-13, IL-17A, IL-22, IL-25, IL-33, and TSLP), 4 prostaglandin synthases (prostaglandin D2 [PGD2] synthase, prostaglandin E2 synthase, COX-1, and COX-2), and their 16 receptors. Clustering analysis was performed according to the expression results, and clinical findings of patients from each cluster were investigated. RESULTS: The samples could be divided into 3 clusters. Cluster 1 showed elevated levels of expression of IL4, IL5, IL13, TSLP, IL1RL1 (ST2 [an IL-33 receptor]), HPGDS, and GPR44 (CRTH2, a PGD2 receptor); cluster 2 showed elevated levels of expression of IL17A and PTGES; and cluster 3 showed an elevated level of expression of IL25. Regarding clinical features, the main characteristics of each cluster were as follows: NPs from patients with eCRS for cluster 1, NPs and/or UT samples from patients with non-eCRS for cluster 2, and UTs from patients with non-CRS for cluster 3. CONCLUSION: The results suggest that there are associations between type 2 inflammation/PGD2 and eCRS and also between type 3 inflammation/prostaglandin E2 and non-eCRS.

DOI： 10.1016/j.jacig.2023.100123

Serum 1,25-dihydroxyvitamin D3 Levels in Patients with Eosinophilic Chronic Rhinosinusitis. Reviewed

Seiichiro Makihara, Shin Kariya, Shotaro Miyamoto, Kensuke Uraguchi, Aiko Oka, Munechika Tsumura, Yohei Noda, Mizuo Ando, Mitsuhiro Okano

Acta medica Okayama 76 ( 5 ) 527 - 533 2022.10

咽喉頭浮腫を合併したムンプス感染症の1例 Reviewed

内藤智之, 牧原靖一郎, 津村宗近, 松本淳也, 假谷伸, 安藤瑞生

耳鼻咽喉科・頭頸部外科 94 ( 11 ) 979 - 982 2022.10

Language：Japanese Publisher：(株)医学書院

＜文献概要＞はじめに流行性耳下腺炎はムンプスウイルスによる感染症であり,耳下腺の腫脹・疼痛や発熱を主症状とする。主に小児期に好発するが,成人発症も少なからず存在する。しばしば感音難聴や髄膜炎,睾丸炎などの合併症を生じるが,咽喉頭浮腫は比較的稀である。過去にも報告例があり1〜20),特に顎下部の腫脹を伴う場合では注意が必要とされている。今回,ムンプスウイルス感染に伴う喉頭浮腫と呼吸困難をきたした症例を経験したので,若干の文献的考察を含め報告する。

甲状腺悪性リンパ腫に対して輪状軟骨開窓術を施行した1例 Reviewed

松本淳也, 牧原靖一郎, 内藤智之, 土井彰, 小桜謙一, 假谷伸, 安藤瑞生

耳鼻咽喉科臨床 115 ( 7 ) 619 - 624 2022.7

Language：Japanese Publisher：耳鼻咽喉科臨床学会

症例は77歳男性で、2週間前頃から喉頭違和感を自覚しており、当科初診日深夜に呼吸困難が出現したため当院に救急搬送された。精査によりたこつぼ型心筋症と狭心症が明らかとなり、さらにCTで気管狭窄を伴う甲状腺腫瘍が認められた。急速に増大する甲状腺腫瘍であったため、未分化癌や悪性リンパ腫を疑い穿刺吸引細胞診を施行したが、検体不良との結果で診断を得られなかった。早期の確定診断に加え、気道管理の面から経皮的な気道確保への移行が必要と判断し、入院4日目に輪状軟骨開窓術と開放生検を同時に行う方針とした。術後2週目にび漫性大細胞性リンパ腫の確定診断に至り、たこつぼ型心筋症と狭心症は呼吸・循環管理により改善していたため、血液内科に転科のうえ術後21日目から化学療法が開始され、6コース完遂後に腫瘍は完全奏効となった。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00580&link_issn=&doc_id=20220705240012&doc_link_id=10.5631%2Fjibirin.115.619&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.115.619&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

ANL Secondary Publication 感染性副鼻腔嚢胞による鼻性眼窩内合併症の検討

牧原靖一郎, 假谷伸, 岡野光博, 内藤智之, 津村宗近, 西崎和則

日本耳鼻咽喉科頭頸部外科学会会報 125 ( 6 ) 1041 - 1042 2022.6

Subclinical obstructive lung function changes in patients with sinus fungus ball. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Ryotaro Omichi, Shotaro Miyamoto, Tomoyuki Naito, Kensuke Uraguchi, Aiko Oka, Munechika Tsumura, Mitsuhiro Okano, Mizuo Ando

Allergology international : official journal of the Japanese Society of Allergology 71 ( 4 ) 539 - 541 2022.4

Mapping naso-ocular symptom scores to EQ-5D-5L utility values in Japanese cedar pollinosis Reviewed International journal

Hiroshi Kumanomidou, Kengo Kanai, Aiko Oka, Takenori Haruna, Yuji Hirata, Sei ichiro Makihara, Takaya Higaki, Maki Akamatsu, Yoshitaka Okamoto, Shunya Ikeda, Mitsuhiro Okano

Allergology International 71 ( 2 ) 207 - 213 2022.4

Language：English Publishing type：Research paper (scientific journal)

Background: The total naso-ocular symptom score (TSS) is widely used as an endpoint to evaluate the severity of seasonal allergic rhinitis. However, it is not a generic preference-based measure. We sought to develop an algorithm for mapping between the TSS and health utility in Japanese cedar pollinosis (JCP). We also performed a cost-utility analysis of sublingual immunotherapy (SLIT) for JCP by using this algorithm. Methods: Patients with JCP filled out the TSS questionnaire and EQ-5D-5L simultaneously during the pollen season in 2019 and in 2020. We estimated a direct utility mapping model by regressing responses to individual TSS questions directly onto utility. The incremental cost-effectiveness ratio (ICER) of active SLIT to a placebo was determined by examining the drug expense and the estimated quality-adjusted life year (QALY) using a dataset from a double-blind placebo-controlled clinical trial. Results: A total of 238 records were included for analysis. The estimated utility decreased with increasing severity of rhinitis. Patients with comorbid asthma showed lower utility. A negative and significant correlation was seen between the TSS and utility in both 2019 and 2020. The estimated equations were: Y(utility) = −0.0161∗X(TSS) + 1.005 in non-asthmatic JCP patients. The ICER of active SLIT to the placebo was estimated to be 4,049,720 and 6,011,218 JPY/QALY in the first and second year, respectively. Conclusions: It is possible to reasonably predict utility from the total naso-ocular symptom score by using regression models. In the estimated algorithm, pre-seasonal SLIT for JCP is cost-effective.

DOI： 10.1016/j.alit.2021.11.002

【CT典型所見アトラス-まずはここを診る!】鼻副鼻腔領域鼻副鼻腔腫瘍/頭蓋底疾患乳頭腫/血瘤腫・血管腫・血管線維腫/鼻副鼻腔悪性腫瘍(上顎がん・嗅神経芽細胞腫)/髄膜脳瘤・髄膜瘤

牧原靖一郎, 假谷伸

耳鼻咽喉科・頭頸部外科 94 ( 4 ) 336 - 341 2022.4

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(株)医学書院

＜文献概要＞POINT ▼内反性乳頭腫の基部推定には,骨肥厚像,もしくは骨融解像が重要である。▼血管線維腫は蝶口蓋孔を中心に周囲に広がる腫瘤で,造影CTで強く濃染される。▼上顎がんは隣接する副鼻腔の骨破壊を生じ,壊死部位により内部不均一となる。▼頭蓋底に発生した髄膜脳瘤は,頭蓋底の骨欠損を介し,頭蓋内からの脳組織の脱出,脳溝の連続を認める。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02122&link_issn=&doc_id=20220405090009&doc_link_id=10.11477%2Fmf.1411202961&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1411202961&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Clinicopathologic Analysis of Sinonasal Inverted Papilloma, with Focus on Human Papillomavirus Infection Status. Reviewed International journal

Munechika Tsumura, Seiichiro Makihara, Asami Nishikori, Yuka Gion, Toshiaki Morito, Shotaro Miyamoto, Tomoyuki Naito, Kensuke Uraguchi, Aiko Oka, Tomoyasu Tachibana, Yorihisa Orita, Shin Kariya, Mitsuhiro Okano, Mizuo Ando, Yasuharu Sato

Diagnostics (Basel, Switzerland) 12 ( 2 ) 2022.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

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.

DOI： 10.3390/diagnostics12020454

Dermatomyositis With Carcinoma of Unknown Primary Disease in the Head and Neck Diagnosed by Muscle Biopsy During Neck Dissection. Reviewed International journal

Kensuke Uraguchi, Seiichiro Makihara, Makoto Tsugita, Toshiaki Morito, Shin Kariya, Mizuo Ando

JAMA otolaryngology-- head & neck surgery 148 ( 2 ) 195 - 196 2022.2

TACMI法とEndoscopic Denker's Approachの併用により摘出しえた鼻腔血管腫の1例 Reviewed

松本淳也, 牧原靖一郎, 大村和弘, 内藤智之, 土井彰, 假谷伸, 安藤瑞生

頭頸部外科 31 ( 3 ) 293 - 299 2022.2

Language：Japanese Publisher：(NPO)日本頭頸部外科学会

巨大な鼻腔血管腫の手術では良好な視野の確保が困難となることが多く,また術中に大量出血をきたすことがあるため,術式の選択が重要とされる。本症例は,78歳女性,左鼻腔を充満する血管腫症例である。術前塞栓術を試みたが施行できなかったため,手術の最初に栄養血管である蝶口蓋動脈の処理が必要であった。TACMI法とEndoscopic Denker's Approachを併用することで,蝶口蓋動脈凝固切断後の腫瘍の一塊切除が,内視鏡下に可能となった。これらの術式の併用は,巨大な鼻腔腫瘍,特に蝶口蓋動脈の処理も必要な場面において有用であると考えられた。(著者抄録)

Endoscopic tri-port approach法にて一塊切除した若年性血管線維腫例 Reviewed

牧原靖一郎, 大村和弘, 宮本翔太郎, 内藤智之, 浦口健介, 津村宗近, 假谷伸, 岡野光博, 安藤瑞生

日本鼻科学会会誌 60 ( 4 ) 546 - 552 2021.12

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(一社)日本鼻科学会

若年性血管線維腫は思春期男性に好発する易出血性の血管性腫瘍で,局所浸潤性が高く,鼻腔内から翼口蓋窩を中心に周囲組織を破壊進展する。手術療法は,様々な外切開が適応とされることが多かったが,近年では手術器具,技術,ナビゲーションシステムなどの進歩により経鼻内視鏡下に摘出される報告が増えている。Endoscopic tri-port approach法とは,Omuraらの提唱したTransseptal access with crossing multiple incisions(TACMI法),Direct approach to the anterior and lateral part of the maxillary sinus with an endoscope(DALMA法)と,Weberらの提唱した鼻涙管切断を伴う下鼻甲介処置を組み合わせることで,両外鼻孔からの経鼻中隔,経鼻腔,経上顎洞前壁の3つのポートを使用して,0度の内視鏡で翼口蓋窩や眼窩などへアプローチする方法である。今回我々は17歳の男性で,鼻腔,上咽頭から翼口蓋窩に一部進展の認める若年性血管線維腫,Radkowski分類Stage IIA期に対して,術前日に選択的血管塞栓術を施行した後に,Endoscopic tri-port approach法にて一塊切除した。Endoscopic tri-port approach法は顔面の外切開や歯齦部切開を施行することなく,可能な限り鼻中隔や下鼻甲介を温存しながら,広い術野で病変部への到達が可能であり,翼口蓋窩進展を認める若年性血管線維腫に対して有用なアプローチ法と考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01675&link_issn=&doc_id=20220111400012&doc_link_id=10.7248%2Fjjrhi.60.546&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.60.546&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Total en bloc resection for sinonasal squamous cell carcinoma by endoscopic endonasal surgery with Draf IIb procedure with video Reviewed

K. Uraguchi, S. Makihara, K. Kozakura

European Annals of Otorhinolaryngology, Head and Neck Diseases 138 119 - 121 2021.11

【手術道具・材料はこう使う!-プロに学ぶ基本とコツ】鼻科領域止血資材/創傷被覆材/フィブリン糊

牧原靖一郎

耳鼻咽喉科・頭頸部外科 93 ( 11 ) 915 - 919 2021.10

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(株)医学書院

＜文献概要＞Point ▼鼻副鼻腔内からの出血に対する止血方法の基本は,出血点を同定して凝固焼灼止血を行うことである。▼止血資材には,外来での鼻出血に対する処置などに使用される酸化セルロースやゼラチンスポンジ,主に頭蓋底手術に使用されるゼラチン・ヒトトロンビン合材など,状況に応じた選択肢がある。▼内視鏡下鼻内副鼻腔手術(ESS)終了後のパッキング資材として,圧迫による癒着予防効果をもち,吸引除去が可能なナゾポアが有用である。

Underwater posterior nasal neurectomy compared to resection of peripheral branches of posterior nerve in severe allergic rhinitis. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Syotaro Miyamoto, Kensuke Uraguchi, Munechika Tsumura, Shin Kariya, Mizuo Ando

Acta oto-laryngologica 141 ( 8 ) 780 - 785 2021.8

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

BACKGROUND: Several surgical procedures for posterior nasal neurectomy have been reported, but no conclusion has been reached about which procedure is best. OBJECTIVES: The aim is to evaluate the improvement in symptom medication scores for resection of the posterior nasal nerve trunk in an underwater environment, with submucous inferior turbinectomy, without injuring the sphenopalatine artery (SPA) in severe allergic rhinitis. MATERIAL AND METHODS: Improvements in symptom medication scores were retrospectively compared between 27 consecutive cases who underwent resection of the posterior nasal nerve trunk with turbinoplasty in an underwater environment without injuring the SPA (Underwater group) and, as a historical control, 16 consecutive cases who underwent resection of peripheral branches of the posterior nasal nerve with turbinoplasty (Control group). RESULTS: The improvements in symptom medication scores in the Underwater group were significantly better than in the Control group (3.07 vs. 1.96, p = 0.02). CONCLUSIONS AND SIGNIFICANCE: By using underwater posterior nasal neurectomy, we can easily and safely resect the posterior nasal nerve trunk under a clear surgical view without injuring the SPA. This technique with submucous inferior turbinectomy may, more than resection of peripheral branches of the posterior nasal nerve, be able to reduce the medication score and symptom medication score.

DOI： 10.1080/00016489.2021.1925151

Dysphagia in a Patient with Asymmetric Elevation of the Hyoid Bone. Reviewed International journal

Kensuke Uraguchi, Seiichiro Makihara, Shin Kariya

Dysphagia 36 ( 4 ) 761 - 763 2021.8

経鼻内視鏡手術で摘出したskip病変を伴う鼻腔粘膜悪性黒色腫症例 Reviewed

浦口健介, 小桜謙一, 牧原靖一郎, 土井彰, 假谷伸

日本鼻科学会会誌 60 ( 1 ) 1 - 5 2021.4

Language：Japanese Publisher：(一社)日本鼻科学会

鼻腔粘膜悪性黒色腫に関しては手術が可能な場合は手術が第一選択とされており,近年では内視鏡手術が選択される事が多くなってきている。今回,経鼻内視鏡手術で摘出したskip病変を伴う鼻腔粘膜悪性黒色腫の1例を経験したため報告する。症例は86歳男性。鼻腔腫瘍からの反復性鼻出血のため当科紹介された。腫瘍生検で鼻腔粘膜悪性黒色腫の診断となり全身麻酔下で経鼻内視鏡手術を行った。術後の鼻腔内視鏡検査で右上顎洞にskip病変を認めた。初回手術2ヵ月後に根治目的でendoscopic medial maxillectomy(EMM)を行ったところ,術前に指摘できなかったskip病変が右下鼻道にも認められた。現在,再手術後3年半経過しているが再発や転移を認めていない。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01675&link_issn=&doc_id=20210506380001&doc_link_id=10.7248%2Fjjrhi.60.1&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.60.1&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Effect of Prostaglandin D<inf>2</inf> on mRNA Expression of Three Isoforms of Hyaluronic Acid Synthase in Nasal Polyp Fibroblasts Reviewed International journal

Yuji Hirata, Shin Kariya, Kengo Kanai, Tazuko Fujiwara, Sei Ichiro Makihara, Ryotaro Omichi, Takaya Higaki, Takenori Haruna, Aiko Oka, Kazunori Nishizaki, Mitsuhiro Okano

American Journal of Rhinology and Allergy 35 ( 1 ) 44 - 51 2021.1

Language：English Publishing type：Research paper (scientific journal)

Background: Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D2 (PGD2) is also associated with the pathogenesis of CRS. However, little is known about whether PGD2 regulates hyaluronan production by human airway fibroblasts. Objective: We sought to determine the effect of PGD2 on the mRNA expression of three isoforms of membrane-bound hyaluronic acid synthase (HAS1, HAS2 and HAS3) in fibroblasts, the major source of hyaluronan production, derived from CRS patients. Methods: Nasal polyp-derived fibroblasts (NPDF) and uncinate tissue-derived fibroblasts (UTDF) were established from CRS patients with nasal polyps and those without, respectively. These fibroblasts were stimulated with PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. mRNA levels for HAS1, HAS2 and HAS3 were determined by real-time quantitative PCR. Results: PGD2 (1 µM) significantly enhanced HAS1 but not HAS2 or HAS3 mRNA expression by NPDF. Enhanced HAS1 mRNA expression was also obtained by stimulation with a DP receptor-selective agonist, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD2-induced HAS1 mRNA expression was seen in UTDF. Conclusion: PGD2 selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.

DOI： 10.1177/1945892420932781

A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery. Reviewed International journal

Kensuke Uraguchi, Kenichi Kozakura, Satoshi Oka, Takaya Higaki, Seiichiro Makihara, Toshi Imai, Akira Doi, Tsuyoshi Ohta, Shin Kariya, Kazunori Nishizaki

Medical mycology case reports 30 22 - 25 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

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.

DOI： 10.1016/j.mmcr.2020.09.004

Orbital complications of infected mucocele in the paranasal sinuses. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Mitsuhiro Okano, Tomoyuki Naito, Munechika Tsumura, Kazunori Nishizaki

Auris, nasus, larynx 47 ( 6 ) 990 - 995 2020.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

OBJECTIVE: Infected mucocele of the paranasal sinuses can induce orbital infection, including orbital subperiosteal abscess, which may lead to life-threatening intracranial complications. Effective diagnosis is important, and treatment should be aggressive. This paper presents our experiences in endoscopic surgical management of orbital complications secondary to infected paranasal sinus mucoceles. METHODS: From our retrospective review of the medical charts for 82 patients with 92 sides diagnosed with paranasal sinus mucoceles, we present 7 sides in 7 adult patients with orbital complications secondary to infected mucoceles. The collected data include the suggested etiology, side of sinus involvement, localization of abscess in the orbit, orbital wall bone defects caused by mucocele compression, ophthalmic symptoms, duration between symptom onset and initial visit, operation date, type of surgery performed, and follow-up. RESULTS: The mucocele was located in the ethmoid-frontal region in 9.8% of the sides (9/92), in the frontal sinus in 7.6% (7/92), in the ethmoidal sinus in 9.8% (9/92), in the maxillary sinus in 67.4% (62/92), in the maxillary-ethmoidal sinus in 3.3% (3/92), and in the sphenoid sinus in 2.2% (2/92). The patients with ethmoid-frontal mucoceles had a significantly higher incidence of orbital complications (6/9) as compared with the other sub-types of mucoceles (frontal, 0/7; ethmoidal, 0/9; maxillary, 1/62; maxillary-ethmoidal, 0/3; sphenoid, 0/2). Chandler's classification showed Type I in one, Type II in three, and Type III in three. Sinus involvement was observed at the ethmoid-frontal sinuses in six cases and the maxillary sinus in one case. All seven cases had a partial defect of the orbital wall bone (lamina papyracea, or inferior orbital wall bone) by mucocele compression, and the patients underwent endoscopic marsupialization. For the cases with subperiosteal abscess, the lamina papyracea was also removed partially for draining the abscess. In all cases, symptoms were resolved without any recurrence of the mucocele. CONCLUSIONS: Infected ethmoid-frontal mucoceles with a defect of the lamina papyracea tend to induce orbital infection, so prompt surgery for the infected mucoceles should be considered early even with Types I and II, before visual acuity is impaired, because surgery is the only curative treatment for the mucoceles.

DOI： 10.1016/j.anl.2020.05.012

都市部と郊外における昆虫アレルゲン感作の実態と、昆虫単独感作例の臨床免疫学的特徴 Reviewed

岡愛子, 小山田匠吾, 岡晋一朗, 古舘佐起子, 高橋優宏, 岩崎聡, 赤松摩紀, 野口佳裕, 假谷伸, 金井健吾, 牧原靖一郎, 西崎和則, 岡野光博

耳鼻咽喉科免疫アレルギー 38 ( 3 ) 57 - 63 2020.12

Language：Japanese Publisher：日本耳鼻咽喉科免疫アレルギー学会

【背景】わが国における昆虫アレルゲン感作の実態や,その特徴については未明な点が多い。【対象と方法】鼻症状を主訴に国際医療福祉大学三田病院(東京都)あるいは国際医療福祉大学病院(栃木県)を受診し,特異的IgE検査を施行した524症例(東京都316例,栃木県208例)を対象とした。2病院における昆虫(蛾,ユスリカ,ゴキブリ)感作率と,昆虫感作例,特に昆虫単独感作例の臨床免疫学的特徴を検討した。【結果】蛾,ユスリカ,ゴキブリの感作率は東京で30.7%,10.0%,10.6%,栃木で26.4%,10.6%,12.5%であり,東京と栃木で有意差を認めなかった。昆虫感作例の中,95.1%が蛾への感作を示した。昆虫非感作例と比較して昆虫感作例は,有意差をもって男性に多く血清総IgE値が高かった。昆虫単独感作例は他抗原との重複感作例と比較し,高齢者に有意に多く認めた。また有意な差を認めなかったものの,重複感作例と比較し昆虫単独感作例で通年性の症状を多く認めた。【まとめ】アレルギー性鼻炎の昆虫抗原として蛾の重要性が確認された。昆虫抗原への感作率は都市部と郊外で差を認めなかった。昆虫単独感作例は高齢男性が多い,総IgE値が高い,通年性症状という特徴を示した。特に高齢者では血管運動性鼻炎や老人性鼻漏の患者層と重なっており,総IgE値が高い症例では昆虫抗原を含めたIgE検査を行う必要が示唆された。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J01987&link_issn=&doc_id=20201228330001&doc_link_id=%2Fch6menek%2F2020%2F003803%2F001%2F0057-0063%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fch6menek%2F2020%2F003803%2F001%2F0057-0063%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

脳神経外科、耳鼻咽喉科が連携した下垂体、傍鞍部腫瘍に対する経鼻的内視鏡手術の取組み

井本良二, 平下浩司, 多々納幹貴, 川井伸彦, 柚木正敏, 吉野公博, 牧原靖一郎, 内藤智之, 津村宗近

香川労災病院雑誌 ( 26 ) 1 - 7 2020.12

Language：Japanese Publisher：香川労災病院

症例1は54歳男性で、数ヵ月前からの視力低下を自覚して近医眼科を受診、両耳側半盲を指摘され、精査加療目的に当科紹介受診となった。非機能性下垂体腺腫と術前診断し、経鼻的内視鏡手術における下垂体腺腫摘出術の方針とした。術後軽度の頭痛は認めたものの両側の視力および視野は改善を認め、尿崩症等の内分泌異常、髄液漏等もなく第15病日に退院となった。病理結果は下垂体腺腫であった。症例2は68歳男性で、1年前から嗅覚障害を自覚しており、近医耳鼻科を受診、嗅覚低下・嗅裂ポリープを認め当院耳鼻咽喉科に紹介受診となった。鼻腔内所見における嗅裂ポリープの生検にて嗅神経芽細胞腫と診断された。鼻腔経由での血管処理が困難と考え、左上眼瞼皮膚切開を併用し、前篩骨動脈、後篩骨動脈の凝固切断、経鼻内視鏡下に鼻副鼻腔腫瘍、頭蓋底骨、硬膜両嗅球、両嗅索を一塊切除した。術後経過は良好で第12病日に退院となった。

重症睡眠時無呼吸症候群を伴った成人ソトス症候群の1例 Reviewed

浦口健介, 牧原靖一郎, 内藤智之, 松本淳也, 津村宗近, 假谷伸

耳鼻咽喉科・頭頸部外科 92 ( 12 ) 1031 - 1036 2020.11

Language：Japanese Publisher：(株)医学書院

28歳男。出生時から顔貌異常があり、過成長を認めた。10代の頃にソトス症候群と臨床診断されていたが、全身状態が落ち着いていたため定期通院はしていなかった。今回、日中の眠気・頭痛があり、睡眠時無呼吸症候群の精査目的で当科を受診した。諸検査の結果から、下顎低形成による硬組織の異常から口腔・咽頭腔の狭小化をきたし、閉塞性睡眠時無呼吸症候群になっていると考えた。持続陽圧呼吸(CPAP)療法を行い、治療効果判定のためCPAP装着下にポリソムノグラフィ検査を行ったところ、AHI、AIとも改善していることが確認された。日中の眠気・頭痛も改善し、現在CPAPを継続しながらフォロー中である。

経眼窩アプローチを併用し、内視鏡下に一塊切除した嗅神経芽細胞腫例 Reviewed

津村宗近, 牧原靖一郎, 大村和弘, 内藤智之, 松本淳也, 假谷伸, 岡野光博, 西崎和則

頭頸部外科 30 ( 1 ) 119 - 125 2020.6

Language：Japanese Publisher：(NPO)日本頭頸部外科学会

嗅神経芽細胞腫は、近年経鼻内視鏡下摘出術が導入されているが、腫瘍切除方法については、頭蓋底骨、硬膜、嗅球、嗅索と鼻腔内腫瘍を一塊切除するか、multi-layer resectionを施行するかに関して議論がある。本症例は70歳男性、硬膜浸潤を認めるKadsish分類Stage Cで眼窩内側壁に接する嗅神経芽細胞腫症例である。腫瘍近接のため経鼻的に篩骨動脈の確保が困難と考え、上眼瞼皮膚切開による内視鏡下経眼窩アプローチでの前、後篩骨動脈の凝固切断を施行し、経鼻内視鏡下に腫瘍を一塊切除施行した。副鼻腔内が腫瘍で充満しており、経鼻的に篩骨動脈へのアプローチが困難な場合に、有用であると考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J04210&link_issn=&doc_id=20200720160020&doc_link_id=10.5106%2Fjjshns.30.119&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.30.119&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Unilateral mucosal advancement flapによる鼻中隔穿孔閉鎖例 Reviewed

牧原靖一郎, 内藤智之, 津村宗近, 假谷伸, 岡野光博, 西崎和則

頭頸部外科 30 ( 1 ) 113 - 118 2020.6

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(NPO)日本頭頸部外科学会

本症例は18歳の男性で、鼻ほじりが原因と考えられる13mm大の鼻中隔穿孔を認め、Unilateral mucosal advancement flap techniqueを使用して穿孔閉鎖施行した。術後は穿孔が閉鎖し、自覚症状が消失した。Unilateral mucosal advancement flap techniqueは片側鼻腔で穿孔の下方と上方に二つのflapを作成し、そのflap同士を縫合することで穿孔を閉鎖する方法である。Flapは双茎で血流もよく、Interposition graftと組み合わせることで、1cmを超える中等度の大きさの鼻中隔穿孔の閉鎖に有効な方法と考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J04210&link_issn=&doc_id=20200720160019&doc_link_id=10.5106%2Fjjshns.30.113&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.30.113&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media. Reviewed International journal

Shin Kariya, Mitsuhiro Okano, Pengfei Zhao, Yukihide Maeda, Yuko Kataoka, Takaya Higaki, Seiichiro Makihara, Jun Nishihira, Tomoyasu Tachibana, Kazunori Nishizaki

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 41 ( 3 ) 364 - 370 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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.

DOI： 10.1097/MAO.0000000000002537

ポリグリコール酸フェルト(デュラウェーブ)を用いて頭蓋底硬膜再建した2症例 Reviewed

浦口健介, 小桜謙一, 牧原靖一郎, 福田真紀, 土井彰, 太田剛史

日本耳鼻咽喉科学会会報 123 ( 3 ) 257 - 263 2020.3

Language：Japanese Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会

内視鏡経鼻頭蓋底手術は広く行われるようになったが、手術侵襲の程度によっては時に硬膜再建が必要になることがある。今回、硬膜補綴材であるポリグリコール酸(PGA)フェルトを使用し硬膜再建を行った2症例を報告する。症例1は78歳男性。嗅神経芽細胞腫(Kadish分類Stage B)の腫瘍切除後に硬膜欠損に対してPGAフェルト・鼻中隔粘膜弁を用いて硬膜再建した。症例2は68歳女性。外反性乳頭腫に合併した扁平上皮癌であり、術中に篩板からの髄液漏を認めPGAフェルト・有茎粘膜弁を用いて硬膜再建した。術後に感染や髄液漏はなく、PGAフェルトを用いることで簡便かつ短時間で低侵襲に硬膜再建を行うことができた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J01099&link_issn=&doc_id=20200409390011&doc_link_id=%2Fdz0jibik%2F2020%2F012303%2F011%2F0257-0263%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2020%2F012303%2F011%2F0257-0263%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Corrigendum to “Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts” (Allergology International (2016) 65(4) (414–419), (S1323893016300259), (10.1016/j.alit.2016.03.003)) International journal

Kengo Kanai, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Ryotaro Omichi, Sei ichiro Makihara, Yuji Hirata, Kazunori Nishizaki

Allergology International 69 ( 1 ) 163 - 163 2020.1

Language：English Publishing type：Research paper (scientific journal)

The authors regret that the following two corrections are needed. The authors would like to apologize for any inconvenience caused. 1. The current text for the Authors' Contributions: “MO and KN designed the study and wrote the manuscript. TF, SK, KK, SM and YH contributed to data collection. TH and RO performed the statistical analysis and interpretation of the results”. The correct text should be “KK, MO and KN designed the study and wrote the manuscript. TF, SK, KK, SM and YH contributed to data collection. TH and RO performed the statistical analysis and interpretation of the results”. The underlined initial has been added. 2. The affiliation number of the last author “Kazunori Nishizaki” was mentioned incorrectly as “b”. The correct affiliation should be “a”.

DOI： 10.1016/j.alit.2019.11.001

Long-term treatment with clarithromycin and carbocisteine improves lung function in chronic cough patients with chronic rhinosinusitis Reviewed International journal

Shin Kariya, Mitsuhiro Okano, Takaya Higaki, Seiichiro Makihara, Tomoyasu Tachibana, Kazunori Nishizaki

AMERICAN JOURNAL OF OTOLARYNGOLOGY 41 ( 1 ) 102315 - 102315 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO-ELSEVIER INC

Purpose: Chronic cough is a common complaint. Because the pathophysiology of chronic cough is complicated, the management of chronic cough is challenging. To the best of our knowledge, no previous study has examined the effect of macrolide antibiotics in chronic cough patients with chronic rhinosinusitis. The purpose of this study is to determine the changes in lung function for chronic cough patients with chronic rhinosinusitis who are treated by clarithromycin and carbocisteine.Materials and methods: Thirty-two chronic cough patients with chronic rhinosinusitis were recruited. Patients using inhaled corticosteroids and/or a bronchodilator, asthmatic patients, and patients with abnormal findings on auscultation and/or chest X-ray examination were excluded from this study. The patients received low-dose clarithromycin treatment for 3 months. Both before and after the treatment, a computed tomography (CT) scan of the paranasal sinuses, lung function test, peripheral blood test, and sino-nasal outcome test (SNOT-20) were applied.Results: Both the lung function and Lund-MacKay CT scores were improved by the long-duration therapy with macrolide antibiotics. The change in obstructive pulmonary function and the improvement of the CT score in each subject were significantly correlated. SNOT scores also improved after the treatment.Conclusions: The macrolide antibiotics treatment has beneficial effects on lung function in non-asthmatic chronic cough patients with normal chest X-ray findings. The improvement of chronic rhinosinusitis may have some role in the lung condition. Upper respiratory tract examination and treatment may be useful for the management of chronic cough.

DOI： 10.1016/j.amjoto.2019.102315

False vocal cord perforation with abscess treated by negative pressure wound therapy. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Tomoyuki Naito, Kensuke Uraguchi, Junya Matsumoto, Yohei Noda, Mitsuhiro Okano, Kazunori Nishizaki

SAGE open medical case reports 8 2050313X20915415 2020

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS INC

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.

DOI： 10.1177/2050313X20915415

Methotrexate-associated lymphoproliferative disorder with multiple pulmonary nodules and bilateral cervical lymphadenopathy. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Mai Noujima-Harada, Nobuya Ohara, Tomoyuki Naito, Junya Matsumoto, Yohei Noda, Mitsuhiro Okano, Tadashi Yoshino, Kazunori Nishizaki

Auris, nasus, larynx 46 ( 6 ) 927 - 933 2019.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

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.

DOI： 10.1016/j.anl.2019.01.010

Attachment-oriented endoscopic surgical management for inverted papillomas in the nasal cavity and paranasal sinuses. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Tomoyuki Naito, Kensuke Uraguchi, Junya Matsumoto, Yohei Noda, Mitsuhiro Okano, Kazunori Nishizaki

Auris, nasus, larynx 46 ( 5 ) 748 - 753 2019.10

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

OBJECTIVE: The treatment of all forms of sinonasal inverted papilloma (IP) is a complete, wide, local resection. The main surgical purpose is to remove all diseased mucosa and mucoperiosteum, together with a cuff of normal-looking mucosa at the attachment site, followed by drilling and/or coagulation. Our aim is to present our experiences in endoscopic surgical management of IP by using attachment-oriented excision. METHODS: We present 20 cases of sinonasal IP. The data collected includes the histopathological diagnosis, staging, extension of the tumor, tumor attachment site, approach to surgery, serum squamous cell carcinoma antigen (SCCA) level, and recurrences. RESULTS: All patients underwent endoscopic surgery. A Caldwell-Luc operation was required in addition to the endoscopic surgery in one case. There was one case of recurrence (5%). After the additional operation, there was no recurrence. The tumor attachment sites vary, and the case of recurrence had a wide attachment site at the primary surgery. No major intra- or post-operative complications were observed. CONCLUSION: The present study shows that attachment-oriented excision for IP is useful for complete resection of IP. Surgeons should choose the surgical approach according to the location of the tumor attachment site rather than the Krouse staging system.

DOI： 10.1016/j.anl.2019.02.007

非定型悪性外耳道炎の2例 Reviewed

牧原靖一郎, 假谷伸, 内藤智之, 松本淳也, 石原久司, 岡野光博, 西崎和則

耳鼻咽喉科・頭頸部外科 91 ( 7 ) 594 - 599 2019.6

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(株)医学書院

症例1は70歳男性で、右顔面神経麻痺と右耳痛を主訴とした。外耳道内に肉芽形成を認め、CTで右鼓室と乳突洞の軟部組織陰影、外耳道骨部から鼓室、乳突洞にかけての骨破壊像を認めた。細菌検査で右耳漏からアスペルギルスが検出された。顔面神経麻痺を伴った右悪性外耳道炎と診断し、シタフロキサシンの内服と高気圧酸素療法を行った。また、外耳道内にビホナゾールの塗布とブロー液による処置を行った。症例2は71歳男性で、両耳漏と両耳痛を主訴とした。外耳道内に肉芽形成を認め、CTで両側外耳道骨部から鼓室、乳突洞、両側下顎頭にかけて骨破壊像を認めた。細菌検査で耳漏からニューキノロン耐性緑膿菌を検出した。両側悪性外耳道炎と診断し、タゾバクタム/ピペラシリンの点滴と高気圧酸素療法を行った。2例とも経過は良好であったが、症例2は治療開始後25ヵ月に既往の悪性リンパ腫が再発し死亡した。

鼻副鼻腔血瘤腫の3例 Reviewed

牧原靖一郎, 内藤智之, 浦口健介, 松本淳也, 假谷伸, 岡野光博, 西崎和則

耳鼻咽喉科・頭頸部外科 91 ( 7 ) 588 - 593 2019.6

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(株)医学書院

症例1は40歳男性で、反復性の左鼻出血と鼻の痛みを主訴とした。CTで左上顎洞から一部の前篩骨洞にかけて内部不均一で造影効果の乏しい腫瘤性病変を認めた。上顎洞血瘤腫を疑い、endoscopic modified medial maxillectomy(EMMM)を施行した。症例2は80歳女性で、反復性の左鼻出血を主訴とした。CTで左上顎洞に充満する陰影を認め、脳血管造影で明らかな栄養血管や腫瘍濃染を認めなかった。上顎洞血瘤腫を疑い、EMMMを施行した。症例3は73歳男性で、頭痛を主訴とした。CTで左蝶形骨洞に充満する陰影を認め、脳血管造影で明らかな栄養血管や腫瘍濃染を認めなかった。蝶形骨洞血瘤腫を疑い、拡大蝶形骨洞手術を施行した。手術は正円孔、翼突管を同定し、広く蝶形骨洞前壁を開放した術野で行った。3例とも病理診断は血瘤腫で、症例1は術後約5年、症例2は術後約8ヵ月、症例3は術後2年5ヵ月の現在まで再発を認めていない。

Dangerous noodle: A case of swallowing syncope and a review of 122 cases from the literature. Reviewed

Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Aiko Oka, Hiroo Ueeda, Yohei Noda, Kazunori Nishizaki

Journal of arrhythmia 35 ( 1 ) 145 - 148 2019.2

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

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.

DOI： 10.1002/joa3.12130

Determining an Appropriate Time to Start Prophylactic Treatment with Intranasal Corticosteroids in Japanese Cedar Pollinosis Reviewed International journal

Takenori Haruna, Shin Kariya, Takaya Higaki, Sei-ichiro Makihara, Kengo Kanai, Yasutoshi Komatsubara, Aiko Oka, Kazunori Nishizaki, Mitsuhiro Okano

Medical Sciences 7 ( 1 ) 2019.1

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

: Prophylactic treatment with intranasal corticosteroids is effective for pollen-induced seasonal allergic rhinitis. However, the appropriate time to start this treatment remains unclear. We performed a double-blinded, randomized, placebo-controlled trial. Starting on February 1, 2014, patients with Japanese cedar pollinosis received either fluticasone furoate nasal spray (FFNS) for 8 weeks (Group A: n = 24), placebo nasal spray for 2 weeks followed by FFNS for 6 weeks (Group B: n = 23), or placebo for 4 weeks followed by FFNS for 4 weeks (Group C: n = 23). The primary endpoint was comparison of the total naso-ocular symptom score (TSS). Secondary endpoints including the increment cost effective ratio (ICER) were also determined. Continuous pollen dispersion began on the 24th of February. Therefore, Group A and Group B received 3-weeks and 1-week of prophylactic treatment, respectively, whereas Group C received post-onset treatment. During the peak pollen-dispersal period, significant differences in TSS were seen between the groups, particularly between Group A and C. The ICER of Group B vs. Group C was lower than that of Group A vs. Group C. These results suggest that long-term prophylactic treatment with FFNS is clinically the most potent treatment, whereas short-term prophylactic treatment is cost effective for pollen-induced allergic rhinitis.

DOI： 10.3390/medsci7010011

Utility of the axillary flap approach to the frontal recess in patients with chronic rhinosinusitis Reviewed

Seiichiro Makihara, Shin Kariya, Mitsuhiro Okano, Tomoyuki Naito, Kensuke Uraguchi, Junya Matsumoto, Kazunori Nishizaki

Otorinolaringologia 69 ( 3 ) 135 - 140 2019

Authorship：Lead author Publishing type：Research paper (scientific journal)

BACKGROUND: The frontal recess and sinus are the most likely areas for sinus surgery failure. A significant difference between races in the anatomical structure of paranasal sinuses has been reported. The axillary flap approach is one of the surgical techniques of endoscopic sinus surgery (ESS) that can improve access to the frontal recess. In this study, we examined the usefulness of the axillary flap approach to accessing the frontal recess and sinus by identifying the frontal ostium during ESS in Japanese patients. METHODS: We performed ESS with the axillary flap approach on 38 patients (59 sides). Demographic data, identification of the frontal ostium, surgical findings, preoperative and postoperative symptoms, incidence of revision surgery, and postoperative complications were collected. RESULTS: The frontal sinus ostium was identified in 96.6% (57 of 59) of the sides. All of the frontal sinus cells detected in a preoperative CT scan were identified during ESS with the axillary flap approach without using a 70-degree endoscope. The symptoms significantly improved after ESS. Three sides had middle meatal adhesions after ESS that required surgical repair under local anesthesia. There was no major postoperative complication such as cerebrospinal fluid leak, orbital injury, or hemorrhage requiring blood transfusion. No patient required revision ESS. CONCLUSIONS: The axillary flap technique is a safe and simple surgical procedure that provides excellent access to the frontal recess without using a 70-degree endoscope, even in Japanese patients. It allows clearance of cells in the recess with identification of the frontal ostium, leading to successful ESS.

DOI： 10.23736/S0392-6621.19.02224-0

The Relationship Between the Width of the Frontal Recess and the Frontal Recess Cells in Japanese Patients. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Mitsuhiro Okano, Tomoyuki Naito, Kensuke Uraguchi, Junya Matsumoto, Yohei Noda, Kazunori Nishizaki

Clinical medicine insights. Ear, nose and throat 12 1179550619884946 - 1179550619884946 2019

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The agger nasi cell (ANC) is an easily identifiable landmark when approaching the frontal sinus. The success of endoscopic frontal sinus surgery may be influenced by the width of the frontal recess (FR). The aim of this study is to examine the relationship between the FR width and the ANC size in Japanese patients. In addition, the effect of various frontal recess cells (FRCs) on the development of frontal sinusitis has been examined. MATERIALS AND METHODS: Multiplanar computed tomography (CT) scans of the nasal cavities and paranasal sinuses in 95 patients (190 sides) before endoscopic sinus surgery were reviewed. The presence of FRCs, the thickness of the frontal beak (FB), the ANC size, and the anterior-to-posterior (A-P) length of the frontal isthmus (FI) and FR were evaluated in patients with and without frontal sinusitis. RESULTS: The prevalence of the ANC, frontal cell types 1, 2, 3, and 4, frontal bullar cell (FBC), suprabullar cell, supraorbital ethmoid cell, and interfrontal sinus septal cell was 85.3%, 11.6%, 0%, 7.9%, 0%, 25.3%, 45.8%, 16.8%, and 15.3%, respectively. The ANC volume showed a significant positive correlation with the A-P length of the FI and FR. The incidence of frontal sinusitis in the patients with FBCs was significantly higher than that without FBCs. CONCLUSION: A large ANC offers a greater potential to facilitating the approach to the frontal sinus because of the extensiveness of the FR in Japanese patients. The presence of FBCs may be related to a higher incidence of frontal sinusitis.

DOI： 10.1177/1179550619884946

Low Incidence of Allergic Fungal Rhinosinusitis in Japanese Patients. Reviewed International journal

Seiichiro Makihara, Shin Kariya, Tomoyuki Naito, Junya Matsumoto, Mitsuhiro Okano, Kazunori Nishizaki

Clinical medicine insights. Ear, nose and throat 12 1179550619870758 - 1179550619870758 2019

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a noninvasive fungal disease of the sinuses with a very high recurrence rate. A very small number of Japanese cases have been reported. MATERIAL AND METHODS: The subjects were 6 patients with AFRS out of 429 patients who underwent endoscopic sinus surgery at Kagawa Rosai Hospital between December 2011 and November 2017. We retrospectively examined the clinical features and outcomes of these 6 patients. RESULTS: The incidence of AFRS was 1.4% (6/429). Allergic fungal rhinosinusitis was unilateral in 5 cases and bilateral in 1. Computed tomography revealed hyperdense areas representing allergic mucin, but no patient exhibited bone erosion. Magnetic resonance imaging showed hypointense or no signal regions at the locations of allergic mucin. Postoperatively, 1 patient developed recurrence. Because the recurrent patient had no significant symptoms, he refused further surgery and received drug therapy. Preoperative eosinophil counts and total IgE levels were elevated in all patients; postoperatively, both remained high in the patient who developed recurrence. Postoperative treatments included steroid therapy and nasal irrigation. CONCLUSIONS: Allergic fungal rhinosinusitis is less prevalent in Japan than in Western nations. Peripheral blood eosinophil and serum IgE values may be used as the biomarkers. SIGNIFICANCE: Allergic fungal rhinosinusitis is prone to recurrence. Postoperative treatment including steroid therapy is important in the management of AFRS.

DOI： 10.1177/1179550619870758

Impact of Preoperative Systemic Corticosteroids on the Histology and Diagnosis of Eosinophilic Chronic Rhinosinusitis. Reviewed International journal

Kosuke Akiyama, Seiichiro Makihara, Kensuke Uraguchi, Yasushi Samukawa, Aiko Oka, Hiroshi Hoshikawa

International archives of allergy and immunology 179 ( 2 ) 81 - 88 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

BACKGROUND: The histological changes corticosteroids induce in nasal polyps, and whether these changes have an impact on the diagnosis of eosinophilic chronic rhinosinusitis (ECRS), currently remain unclear. OBJECTIVES: A prospective controlled multicenter trial was conducted to evaluate the efficacy of the low-dose and short-term oral prednisolone (oPSL) treatment for tissue eosinophil infiltrations in ECRS. METHODS: Subjects with ECRS diagnosed by previous biopsies received a low dose of oPSL for 3 days (PSL 3) or 7 days (PSL 7) before surgery. Changes in the tissue eosinophil count after these treatments were evaluated. Furthermore, the percent change of tissue eosinophil count from baseline and its impact on the diagnosis defined by the JESREC study were examined. RESULTS: There were 23 and 21 subjects in the PSL 3 and PSL 7 groups, respectively. Polyp scores, clinical symptom scores, and the proportion of blood eosinophils significantly decreased after the treatment, and no significant differences were observed between the groups. The entire tissue eosinophil count tended to be slightly decreased in both groups without reaching a statistically significant value. The median percent change of tissue eo-sinophil count from baseline was 83.6%, and only the posttreatment proportion of blood eosinophil showed a mild correlation with it. Seven out of 44 nasal polyp specimens collected from the superficial part of the middle meatus showed < 70 eosinophils/high-power field; therefore, the false negative rate was 15.9%, but decreased to 11.4% when other parts were included in the histological evaluation. CONCLUSIONS: Low-dose and short-term oPSL did not appear to markedly affect the tissue eosinophil count in ECRS patients; however, the potential for misdiagnoses due to the effects of oPSL cannot be rejected. The diagnosis of ECRS prior to the administration of corticosteroids or tissue evaluations using multiple tissue parts is desirable.

DOI： 10.1159/000496437

The examination of ige and peripheral blood mononuclear cells responses to flour extracts in a baker's rhinitis patient Reviewed

Takenori Haruna, Mitsuhiro Okano, Tazuko Fujiwara, Takaya Higaki, Shin Kariya, Seiichiro Makihara, Kengo Kanai, Tomoyasu Tachibana, Yuko Matsuyama, Yasutoshi Komatsubara, Yuto Naoi, Kazunori Nishizaki

Japanese Journal of Allergology 68 ( 1 ) 35 - 42 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Allergology

Background: Baker's rhinitis is a kind of occupational allergic rhinitis mainly caused by intranasal exposure to wheat and/or rye flour in bakery workers. Continuous exposure to flour may induce the onset of asthma in these patients. Method: We experienced a case of 34-year-old male with baker's rhinitis without asthma, and investigated responses of IgE and peripheral blood mononuclear cells (PBMCs) to flour extracts used in the bakery in practice. Result: In the immunoblotting, the patient's IgE reacted with 18 and 30kDa molecules in the extracts of 6 flours used in the bakery. The patient's PBMC produced a substantial amount of IL-5 and IL-13 in response to these flour extracts. Conclusion: It is suggested that water/salt soluble components of wheat flour selectively induce type 2 cytokines production in baker's rhinitis.

DOI： 10.15036/arerugi.68.35

Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J00009&link_issn=&doc_id=20190208340007&doc_link_id=1390845713054037760&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390845713054037760&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

NLRP3 inflammasome expression in lipopolysaccharide-induced otitis media. Reviewed International journal

Shin Kariya, Mitsuhiro Okano, Pengfei Zhao, Yukihide Maeda, Yuko Kataoka, Takaya Higaki, Yohei Noda, Seiichiro Makihara, Kazunori Nishizaki

Acta oto-laryngologica 138 ( 12 ) 1061 - 1065 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

BACKGROUND: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a critical molecule mediating interleukin-1β (IL-1β) responses. However, the role of the NLRP3 inflammasome in otitis media has not been fully examined. AIMS/OBJECTIVES: The purpose of this study is to assess the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in lipopolysaccharide-induced otitis media. MATERIALS AND METHODS: BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 h after injection. Concentrations of IL-1β, NLRP3, ASC, 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: The transtympanic injection of lipopolysaccharide significantly upregulated levels of IL-1β, NLRP3, ASC, and caspase-1 in the middle ear as compared with the control mice. The proteins of NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear cavity. CONCLUSIONS AND SIGNIFICANCE: Lipopolysaccharide induces NLRP3 inflammasome components in the middle ear. The NLRP3 inflammasome may play an important role in the pathogenesis of otitis media. Modulation of inflammasome-mediated inflammation may be a novel therapeutic strategy for otitis media.

DOI： 10.1080/00016489.2018.1515499

【私はこうしている-鼻科手術編】鼻科手術全般鼻科手術のための局所解剖鼻副鼻腔

岡野光博, 牧原靖一郎

JOHNS 34 ( 9 ) 1083 - 1085 2018.9

【私はこうしている-鼻科手術編】各種疾患に対する手術副鼻腔真菌症

牧原靖一郎, 岡野光博

JOHNS 34 ( 9 ) 1269 - 1272 2018.9

Glottic cancer in patients without complaints of hoarseness. International journal

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Seiichiro Makihara, Misato Hirai, Kentaro Miki, Yuya Ogawara, Hisashi Ishihara, Yuko Matsuyama, Iku Abe-Fujisawa, Aiko Shimizu, Yasuharu Sato, Kazunori Nishizaki

Head & neck 40 ( 7 ) 1608 - 1608 2018.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The authors have brought to our attention that an incorrect affiliation was supplied for Yorihisa Orita, Kentaro Miki, Iku Abe–Fujisawa, and Kazunori Nishizaki. All authors and their corrected affiliations appear below. Tomoyasu Tachibana, MD, 1 Yorihisa Orita, MD, PhD, 2 Hidenori Marunaka, MD, 3 Seiichiro Makihara, MD, PhD, 4 Misato Hirai, MD, PhD, 5 Kentaro Miki, MD, 2 Yuya Ogawara, MD, 1 Hisashi Ishihara, MD, 4 Yuko Matsuyama, MD, 1 Iku Abe–Fujisawa, MD, 2 Aiko Shimizu, MD, 1 Yasuharu Sato, MD, PhD, 6 Kazunori Nishizaki, MD, PhD 21 Department of Otolaryngology, Himeji Red Cross Hospital, Hyogo, Japan, 2 Department of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, 3 Department of Otolaryngology, Okayama Medical Center, Okayama, Japan, 4 Department of Otolaryngology, Kagawa Rosai Hospital, Kagawa, Japan, 5 Department of Otolaryngology, Okayama Saiseikai General Hospital, Okayama, Japan, 6 Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

DOI： 10.1002/hed.25196

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis. Reviewed International journal

Takenori Haruna, Shin Kariya, Tazuko Fujiwara, Takaya Higaki, Seiichiro Makihara, Kengo Kanai, Rumi Fujiwara, Satoshi Iwasaki, Yoshihiro Noguchi, Kazunori Nishizaki, Mitsuhiro Okano

Allergology international : official journal of the Japanese Society of Allergology 67 ( 3 ) 392 - 398 2018.7

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY ALLERGOLOGY

BACKGROUND: IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). METHODS: Dispersed nasal polyp (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS with and without NP, respectively. Cells were incubated with SEB, and then the levels of IL-10 in the cell supernatants were determined. The effect of neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-γ, and IL-17A production was examined. Expression of IL-10 in NPs was also determined. RESULTS: IL-10 was expressed in infiltrating inflammatory cells in NPs. NP cells, especially non-adherent NP cells, produced substantial amounts of IL-10 in response to SEB. Although baseline production of IL-10 was significantly higher in NP cells than UT cells, the degree of IL-10 response to SEB was not significantly different between the cell types. The degree of IL-10 production was negatively correlated with the degree of eosinophilia both in tissues and peripheral blood whereas positively correlated with the 1-s forced expiratory volume/forced vital capacity ratio. Patients with severe ECRS displayed a significant decrease in IL-10 production compared with those with non-ECRS. IL-10 neutralization significantly augmented SEB-induced IL-13 and IFN-γ production by NP cells. CONCLUSIONS: Impaired IL-10 production in response to SEB in NP may exacerbate the pathophysiology of ECRS including eosinophilia and lower airway obstruction.

DOI： 10.1016/j.alit.2018.02.001

内視鏡手術で摘出した蝶形骨洞線維性骨異形成症例 Reviewed

浦口健介, 牧原靖一郎, 内藤智之, 假谷伸, 中川隆之, 岡野光博, 西崎和則

日本鼻科学会会誌 57 ( 2 ) 138 - 144 2018.7

Language：Japanese Publisher：(一社)日本鼻科学会

線維性骨異形成症は非腫瘍性の線維性骨病変であり、頭蓋顔面領域に発生することが多い。今回、蝶形骨洞線維性骨異形成症に対して内視鏡手術で摘出した症例を経験したので報告する。症例は26歳男性。前医で頭痛の精査のためCTを撮影したところ蝶形骨洞に陰影が認められ当科紹介となった。初回の内視鏡下生検手術時の病理組織検査は化骨性線維腫の疑いという診断であった。その後、経鼻内視鏡下に腫瘤摘出術を行い、最終的には線維性骨異形成症の診断となった。術後1年半経過しているが再発はなく無症状で経過観察中である。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01675&link_issn=&doc_id=20180724360004&doc_link_id=10.7248%2Fjjrhi.57.138&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.57.138&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Neck metastasis in patients with T1-2 supraglottic cancer Reviewed

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Sei ichiro Makihara, Misato Hirai, Yuka Gion, Kana Ikegami, Kentaro Miki, Takuma Makino, Yasuyuki Noyama, Yasutoshi Komatsubara, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Auris Nasus Larynx 45 ( 3 ) 540 - 545 2018.6

Publishing type：Research paper (scientific journal)

Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer. Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015. Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p = 0.004). In multivariate analysis, age <70 years (p = 0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p = 0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer. Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis.

DOI： 10.1016/j.anl.2017.06.002

Pulmonary function in patients with eosinophilic chronic rhinosinusitis. Reviewed International journal

Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki

Auris, nasus, larynx 45 ( 3 ) 476 - 481 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

OBJECTIVE: There is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients. METHODS: Pulmonary function was measured in 53 patients with eosinophilic chronic rhinosinusitis with asthma, 58 patients with eosinophilic chronic rhinosinusitis without asthma, and 30 patients with non-eosinophilic chronic rhinosinusitis. The diagnosis of chronic rhinosinusitis was based on the definition in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012. Eosinophilic chronic rhinosinusitis was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system. The relationship between pulmonary function and clinical parameters was assessed. These parameters included radiographic severity of chronic rhinosinusitis, peripheral blood eosinophil percentage, serum total immunoglobulin E level, and eosinophilic infiltration in nasal polyps. RESULTS: The pulmonary function of the patients with eosinophilic chronic rhinosinusitis was significantly affected. The eosinophilic chronic rhinosinusitis patients had more peripheral airway obstruction as compared to the patients with non-eosinophilic chronic rhinosinusitis. CONCLUSION: Our findings indicated latent obstructive lung function changes in the eosinophilic chronic rhinosinusitis patients. The patients with eosinophilic chronic rhinosinusitis should be carefully monitored in order to detect lung diseases.

DOI： 10.1016/j.anl.2017.07.020

Laryngeal squamous cell papilloma is highly associated with human papillomavirus. Reviewed International journal

Yorihisa Orita, Yuka Gion, Tomoyasu Tachibana, Kana Ikegami, Hidenori Marunaka, Seiichiro Makihara, Yasuhiko Yamashita, Kentaro Miki, Takuma Makino, Naoki Akisada, Yusuke Akagi, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

Japanese journal of clinical oncology 48 ( 4 ) 350 - 355 2018.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

OBJECTIVE: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. METHODS: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody. RESULTS: In 21 cases (61.8%) with laryngeal squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%) were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11 (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients (<60 years) showed a higher rate of HPV infection than older patients. Among the 34 cases with laryngeal papilloma, no malignant transformation was observed during the study period. With IHC staining, positive expression of p16 was observed in 20 cases (58.8%). HPV infection and p16-expression were associated with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV-positivity in the oral cavity, and none of the 15 oropharyngeal cases were positive for HPV, and none of the oral cavity and oropharyngeal cases showed koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly correlated each other. CONCLUSIONS: HPV infection is frequently associated with laryngeal squamous cell papilloma, and koilocytosis is a characteristic pathological finding. To the best of our knowledge, this is the first report which have described infections with multiple HPV types in laryngeal papilloma.

DOI： 10.1093/jjco/hyy009

前頭洞・蝶形骨洞に同時に発見された副鼻腔真菌症例 Reviewed

浦口健介, 牧原靖一郎, 内藤智之, 岡愛子, 假谷伸, 岡野光博, 西崎和則

日本鼻科学会会誌 56 ( 4 ) 625 - 631 2017.12

Language：Japanese Publisher：(一社)日本鼻科学会

副鼻腔真菌症は一般には上顎洞へ片側に発症するとされており、前頭洞や両側に副鼻腔真菌症が発症することは極めて稀である。今回、前頭洞真菌症と対側の蝶形骨洞へ同時に発見された副鼻腔真菌症の1例を経験したため、文献的考察を加えて報告する。症例は71歳女性。頭痛により他院で頭部CTを撮影したところ前頭洞陰影を認めたため当科紹介された。CT上は左の前頭洞真菌症であり全身麻酔下にEndoscopic modified Lothrop procedureで真菌塊を摘出した。術後、CTで再評価したところ対側の右蝶形骨洞側窩のみに限局する陰影を認めた。初回CTを見直したところ蝶形骨洞には以前から陰影あり、蝶形骨洞真菌症に対して全身麻酔下で右蝶形骨洞開窓しハイドロデブリッダーシステムR(日本メドトロニック、東京)を用いて洗浄した。術後1年間経過したが真菌の再発を認めず、外来で経過観察中である。副鼻腔真菌症は複数洞や両側罹患の可能性もあるため、術前のCT読影を厳密にするべきと考えた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01675&link_issn=&doc_id=20180122310012&doc_link_id=10.7248%2Fjjrhi.56.625&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.56.625&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

意識障害を契機に発見された前頭洞型髄膜脳瘤例 Reviewed

假谷伸, 岡野光博, 檜垣貴哉, 春名威範, 牧原靖一郎, 大道亮太郎, 西崎和則

日本鼻科学会会誌 56 ( 4 ) 564 - 569 2017.12

Language：Japanese Publisher：(一社)日本鼻科学会

髄膜脳瘤は頭蓋骨の欠損孔から頭蓋内容が頭蓋外に脱出する疾患である。先天性の骨欠損による髄膜脳瘤は後頭部に多く発生し、頭蓋底に発生することは稀である。今回、前頭洞後壁の骨欠損部から鼻腔へと脱出した前頭洞型頭蓋底髄膜脳瘤症例に対して、前頭開頭術と経鼻内視鏡下鼻副鼻腔手術を併用した切除術を施行し、良好な経過を得たので報告する。症例は40歳、男性。感冒薬を内服後に意識障害を認め、近医総合病院へ救急搬送された。横紋筋融解症を認め、透析などの加療が施行された。また、頭部MRIで左篩骨洞・前頭洞陰影と脳室拡大を認めた。髄液鼻漏所見を認めたため同院耳鼻咽喉科へ紹介され、左鼻腔内腫瘤の生検を行ったところ脳組織とのことであった。横紋筋融解症が改善したのちも意識障害が遷延するため、精査加療目的で当院脳神経外科へ転院となった。意識障害はフェノバルビタールナトリウムなどの点滴静注治療により軽快した。髄膜脳瘤に対して前頭開頭術と内視鏡下鼻副鼻腔手術を併用した切除手術と前頭蓋底再建術を施行した。術後2年を経過して髄膜脳瘤の再発は認められない。近年、頭蓋底髄膜脳瘤に対しては内視鏡による経鼻的アプローチのみで切除術を行う報告が増加している。本症例は前頭洞後壁に骨欠損部があり、内視鏡下操作のみでは硬膜再建が困難と判断した。髄膜脳瘤は比較的まれな疾患であり、症例によって適切なアプローチ法を検討することが必要と思われた。(著者抄録)

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扁桃周囲膿瘍のCT所見と臨床経過 Reviewed

岡愛子, 牧原靖一郎

日本気管食道科学会会報 68 ( 3 ) 217 - 221 2017.6

Language：Japanese Publisher：(NPO)日本気管食道科学会

扁桃周囲膿瘍の治療として抗菌薬などによる保存的治療、穿刺もしくは切開排膿、全身麻酔下での即時膿瘍扁桃摘出術(膿瘍扁摘)がある。治療が有効でない場合には深頸部膿瘍や縦隔炎などで致死的となることがあり注意が必要である。今回、造影CT所見と治療法の選択、臨床経過について検討を行った。対象は2013年1月から2016年4月に当院を受診し、造影CTで扁桃周囲膿瘍を認めた100例とした。CT軸位断で膿瘍腔の最大径を計測し、計測部位が口蓋垂末端よりも頭側にあるものを上極型、尾側にあるものを下極型とし、膿瘍径、喉頭浮腫の有無、治療法、治療期間を検討した。上極型の方が膿瘍径は大きかったが、喉頭浮腫は下極型で多かった。保存的治療とした症例は全例膿瘍径16mm以下であり、膿瘍扁摘や穿刺・切開の症例と比較して小さかった。上極型では穿刺・切開で十分排膿可能であり、膿瘍扁摘により治療した症例と比較して治療期間が短く、最も多く選択された治療法であった。下極型では膿瘍扁摘と穿刺・切開で入院期間に差がなく、膿瘍径の大きな症例では確実な排膿が可能で再発防止になる膿瘍扁摘を選択した症例が多かった。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01054&link_issn=&doc_id=20170622400001&doc_link_id=%2Fea4broes%2F2017%2F006803%2F001%2F0217-0221%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2017%2F006803%2F001%2F0217-0221%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Delayed esophageal perforation 17 years after anterior cervical fusion surgery with plating. Reviewed

Hisanori Ikuma, Katsuhiko Ishibashi, Kazuta Yamashita, Ryoji Joko, Seiichiro Makihara, Masahiko Kobayashi, Yoshiki Yokoyama

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 22 ( 3 ) 566 - 570 2017.5

【花粉症研究の進歩】鼻噴霧ステロイドの効果的な使い方の研究

春名威範, 岡野光博, 檜垣貴哉, 牧原靖一郎

アレルギー・免疫 24 ( 3 ) 328 - 333 2017.2

Language：Japanese Publisher：(株)医薬ジャーナル社

鼻噴霧用ステロイド薬はアレルギー性鼻炎に対して強力な抗炎症作用を示す。花粉症の本格発症前の最小持続炎症の制御という観点から,これまで,鼻噴霧用ステロイド薬は花粉症初期治療薬としての有用性が議論されていたが,最新版の鼻アレルギー診療ガイドライン(2016年版)からは,鼻噴霧用ステロイド薬は初期療法の1つとして記載されるようになった。自験例も含めいくつかのプラセボ対照二重盲検比較試験において,鼻噴霧用ステロイド薬によるスギ・ヒノキ花粉症に対する初期治療は,プラセボと比較して症状およびQOLの増悪を有意に抑制した。一方,安全性に関しては実薬とプラセボとの間に有意な差を認めなかった。さらに発症後治療と比較しても花粉の本格飛散後の鼻眼症状の増悪を有意に抑制した。以上の結果からは鼻噴霧用ステロイド薬による初期治療は有効かつ安全な治療法であることが明らかとなった。しかし,初期治療の適切な開始時期や飛散花粉数による効果の変化など今後の検討も必要である。(著者抄録)

IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression Reviewed

Yasuyuki Noyama, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takaya Higaki, Takenori Haruna, Sei ichiro Makihara, Kengo Kanai, Takahisa Koyama, Masami Taniguchi, Jun ichi Ishitoya, Akira Kanda, Yoshiki Kobayashi, Mikiya Asako, Koichi Tomoda, Kazunori Nishizaki

Allergology International 66 ( 1 ) 42 - 51 2017.1

Publishing type：Research paper (scientific journal)

Background IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined. Results IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. Conclusions These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.

DOI： 10.1016/j.alit.2016.04.017

Evaluation of a New and Simple Classification for Endoscopic Sinus Surgery Reviewed

Kengo Kanai, Mitsuhiro Okano, Takenori Haruna, Takaya Higaki, Ryotaro Omichi, Sei Ichiro Makihara, Munechika Tsumura, Shin Kariya, Yuji Hirata, Kazunori Nishizaki

Allergy and Rhinology 8 ( 3 ) 2017

Publishing type：Research paper (scientific journal)

Objective: In 2013, the Japanese Rhinologic Society proposed a simple classification for endoscopic sinus surgery (ESS). This classification consists of five procedures (type I, fenestration of the ostiomeatal complex, with uncinectomy and widening of the natural ostium; type II, single-sinus procedure, with manipulating the inside of the sinus; type III, polysinus procedure; type IV, pansinus procedure; type V, extended procedure beyond the sinus wall). The clinical relevance of this classification in chronic rhinosinusitis (CRS) and paranasal sinus cyst was evaluated. Study Design: A retrospective validation study. Methods: A total of 122 patients (195 sinuses) who underwent ESS in Okayama University Hospital in 2012 were enrolled. The relationships between the ESS classification and the clinical course, including the operation time, bleeding amounts during surgery and postoperative changes of olfaction, the computed tomography (CT) score, and nasal airway resistance were analyzed. Results: A total of 195 ESS procedures were classified into type I (n = 3), type II (n = 17), type III (n = 91), type IV (n = 82), and type V (n = 2). The major phenotypes of type II, III, and IV ESS were paranasal sinus cyst (68%), CRS without nasal polyps (77%), and CRS with nasal polyps (55%), respectively, and the difference was significant. The degree of ESS based on this classification was positively and significantly correlated with the operation time and bleeding amounts. As a whole, olfaction, CT score, and nasal airway resistance were significantly improved after surgery. The degree of improvement was similar between type III and type IV ESS. Conclusion: This simple classification for ESS reflected the perioperative burden of the disease.

DOI： 10.2500/ar.2017.8.0208

眼窩骨膜下膿瘍を合併したビスフォスフォネート関連顎骨壊死症例 Reviewed

牧原靖一郎, 岡野光博, 浦口健介, 岡愛子, 假谷伸, 西崎和則

日本鼻科学会会誌 55 ( 4 ) 515 - 523 2016.12

Authorship：Lead author Language：Japanese Publisher：(一社)日本鼻科学会

ビスフォスフォネート(Bisphosphonate:BP)製剤は癌の骨転移の治療や,骨粗鬆症の予防に対して広く使用されている。一方,2003年に米国で初めて報告されたビスフォスフォネート関連顎骨壊死(Bisphosphonate-Related Osteonecrosis of the Jaw:BRONJ)はわが国においても少なからぬ発生を認め,その予防法や対処法の確立は急務である。今回我々は,副鼻腔炎から眼窩骨膜下膿瘍を続発したBRONJ症例を経験したので報告する。症例は86歳,女性。1ヵ月前から続く右側上歯肉部からの膿汁排出を主訴に近医歯科を受診し,当院歯科口腔外科へ紹介となった。約10年前より骨粗鬆症に対してBP製剤であるアレンドロネートを,慢性関節リウマチに対してメチルプレドニゾロンやメトトレキサートを内服していた。CTにて右側副鼻腔陰影を認め,当科を紹介され慢性副鼻腔炎と診断した。歯科にてBRONJと診断され,アレンドロネート休薬から3ヵ月後に腐骨除去と右内視鏡下副鼻腔手術(以下ESS)を予定し,抗生剤での保存的加療を開始した。休薬から2.5ヵ月後に右眼瞼発赤が生じ,造影CTにて右眼窩骨膜下膿瘍の所見を認めた。同日,眼窩紙様板除去を含むESSと腐骨除去,周囲骨削除の緊急手術を施行した。術後,骨膜下膿瘍,骨壊死の再増悪もなく,経過良好である。BRONJ症例への腐骨除去など外科治療の際にはBP製剤の休薬が望まれるが,BRONJを伴う慢性副鼻腔炎に対しては,全身状態が許せば通常上顎骨に対して侵襲は少ないと考えられるESSを腐骨除去より先行させることも選択肢となりうる可能性が示唆された。(著者抄録)

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Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts Reviewed

Kengo Kanai, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Ryotaro Omichi, Sei ichiro Makihara, Yuji Hirata, Kazunori Nishizaki

Allergology International 65 ( 4 ) 414 - 419 2016.10

Publishing type：Research paper (scientific journal)

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) E2 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 PGD2 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 PGD2 regulates VEGF release by nasal polyp fibroblasts. Methods Nasal polyp fibroblasts were established from nasal polyps. These fibroblasts were stimulated with serial dilutions of PGD2 or PGD2 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 μM of PGD2 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, PGD2-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 PGD2-induced VEGF release. Conclusions PGD2 stimulates VEGF production via DP but not CRTH2 receptors in nasal polyp fibroblasts.

DOI： 10.1016/j.alit.2016.03.003

A Study of Cases of Brainstem/cerebellar Infarction Detected as False Negatives by Initial MRI. Reviewed

Kensuke Uraguchi, Shin Kariya, Aiko Oka, Munetika Tsumura, Hisashi Ishihara, Tomomi Miyatake, Yuji Hirata, Seiichiro Makihara, Kazunori Nishizaki

Nihon Jibiinkoka Gakkai kaiho 119 ( 10 ) 1290 - 9 2016.10

Language：Japanese

Brainstem/cerebellar infarction is known to cause various cranial nerve symptoms that may require otorhinolaryngological evaluation. Acute-phase cerebellar infarction is evaluated by MRI with diffusion-weighted imaging (MRI-DWI). However, in the acute phase, MRI-DWI may show false-negative results, because of which patients are referred to the department of otolaryngology for further evaluation of the cranial nerve symptoms. We investigated 250 cases of brainstem/cerebellar infarction in 245 patients who were admitted to our hospital between 2010 and 2015. Of the 250 cases, eight cases were diagnosed at the department of otolaryngology after detailed evaluators for dizziness or dysphagia, and three of them were false negative on initial MRI-DWI. In total, we examined 16 cases detected as false negatives upon initial MRI-DWI. Of the 16 cases, 12 were brainstem infarctions, three were cerebellar infarctions, and one was infarction of the brainstem and cerebellum. All 16 cases were evaluated by initial MRI-DWI within 12 h of onset. Careful observation of the neurological findings and follow-up MRI-DWI are useful for the detailed evaluation of patients suspected to have a cerebellar infarction.

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頸部放射線治療後に喉頭壊死を起こした2症例 Reviewed

岡愛子, 森照茂, 牧原靖一郎

日本気管食道科学会会報 67 ( 4 ) 283 - 288 2016.8

Language：Japanese Publisher：(NPO)日本気管食道科学会

頭頸部癌において放射線治療の適応は広がってきているが、重大な合併症の一つに喉頭壊死がある。今回、放射線治療後の喉頭壊死2症例を経験した。【症例1】67歳男性。喉頭癌T3N0M0に対してcetuximab併用放射線療法(70Gy)を施行。治療終了5ヵ月後に気道狭窄症状を認め緊急気管切開を行った。画像検査で再発、喉頭壊死の鑑別不能であり喉頭摘出を行った。病理検査では悪性所見を認めなかった。【症例2】79歳男性。盲腸癌、左頸部リンパ節転移に対して化学放射線治療(66Gy)を施行。3年8ヵ月後に左頸部リンパ節が再増大し、気道狭窄症状を認め緊急気管切開を行った。再発頸部リンパ節転移に対して追加照射(54Gy)を行い、治療終了1ヵ月後に嚥下困難、悪臭が出現した。喉頭壊死と診断し、総頸動脈浸潤が疑われたため手術は行わず、高圧酸素治療を行った。悪臭などの症状は一旦消失したものの、1ヵ月後に原病死した。喉頭の壊死、炎症と癌の残存、再発との鑑別は難しく、治療をかねて喉頭摘出術となるケースが多い。保存的治療として抗生剤、ステロイド、高圧酸素などがあり、全身状態や患者の喉頭温存希望が強い症例では治療選択肢となる。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01054&link_issn=&doc_id=20160829410006&doc_link_id=%2Fea4broes%2F2016%2F006704%2F006%2F0283-0288%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2016%2F006704%2F006%2F0283-0288%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis Reviewed

Yasuyuki Noyama, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Sei ichiro Makihara, Takenori Haruna, Kengo Kanai, Takaya Higaki, Kazunori Nishizaki

Allergology International 65 ( 3 ) 259 - 265 2016.7

Publishing type：Research paper (scientific journal)

Background Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. Methods We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. Results In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. Conclusions These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

DOI： 10.1016/j.alit.2015.12.007

内視鏡下鼻内手術を施行した巨大な鼻口蓋管嚢胞例 Reviewed

牧原靖一郎, 浦口健介, 岡愛子, 石原久司, 宮武智実, 假谷伸, 岡野光博, 西崎和則

耳鼻咽喉科・頭頸部外科 88 ( 7 ) 525 - 530 2016.6

Authorship：Lead author Language：Japanese Publisher：(株)医学書院

鼻口蓋管嚢胞の根治的治療法として一般に嚢胞全摘出術が行われるが、嚢胞が巨大な場合には摘出後の死腔の処理が問題となる。今回著者等は、巨大な嚢胞に対して内視鏡下鼻内手術を行い、嚢胞を両側鼻腔に開窓し、良好な結果が得られたので報告した。症例は38歳男で、嚢胞の大きさは画像検査上57×56×48mmで、鼻腔底部と口蓋部に骨欠損があり、摘出術を施行した場合には鼻腔と口蓋の間に瘻孔を形成する可能性があった。また、手術で口腔内に開窓すると創が汚染され、鼻腔と口蓋の間に瘻孔を形成する可能性もあった。さらに、鼻腔底に嚢胞壁が大きく進展していたため、手術では、鼻腔粘膜よりも強固な口蓋粘膜を温存して嚢胞を鼻腔に開窓した。

内視鏡下副鼻腔手術を施行した好酸球性副鼻腔炎症例の検討 Reviewed

牧原靖一郎, 浦口健介, 岡愛子, 石原久司, 宮武智実, 假谷伸, 岡野光博, 西崎和則

耳鼻咽喉科・頭頸部外科 88 ( 6 ) 429 - 433 2016.5

Authorship：Lead author Language：Japanese Publisher：(株)医学書院

2012年1月から2015年6月までに保存的治療で十分な治療効果が得られず、内視鏡下副鼻腔手術(ESS)を行った好酸球性副鼻腔炎(ECRS)45症例を対象として、術前後の自覚症状、quality of life(QOL)の変化と内視鏡所見の変化について検討した。術前、術後3ヵ月前後、6ヵ月前後の時点での鼻症状アンケートで自覚症状、QOLに関する質問を評価するとともに、鼻内ポリープスコアを用いて内視鏡評価を比較した結果、自覚症状スコア、QOLスコアの両方において、術後3ヵ月、6ヵ月ともに嗅覚低下、鼻閉やTotal Nasal Symptom Scoreなど多くの項目で有意な改善を認め、概ね良好な術後経過をたどった。

Glottic cancer in patients without complaints of hoarseness. Reviewed International journal

Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Seiichiro Makihara, Misato Hirai, Kentaro Miki, Yuya Ogawara, Hisashi Ishihara, Yuko Matsuyama, Iku Abe-Fujisawa, Aiko Shimizu, Yasuharu Sato, Kazunori Nishizaki

Head & neck 38 Suppl 1 E316-20 - E320 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

BACKGROUND: Few studies have investigated the clinical characteristics of patients with glottic cancer without hoarseness. METHODS: This retrospective clinical study investigated 371 patients with glottic cancer. RESULTS: Thirty-two of the 371 patients (8.6%) with glottic cancer first presented to hospitals with complaints other than hoarseness. Although proportions of stage I and T1 disease were significantly higher among patients without hoarseness than among those with hoarseness (p = .0036 and p = .0004, respectively), survival curves showed no significant differences between groups (p = .1334). CONCLUSION: Patients with glottic cancer without complaints of hoarseness were diagnosed at an earlier stage than those with hoarseness. Accumulation of more cases may lead to better survival of patients with glottic cancer without hoarseness compared to those with hoarseness. Checking the larynx of patients without hoarseness or encouraging internists to check the larynx when performing gastroscopic or respiratory examinations may lead to improvement of glottic cancer prognosis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E316-E320, 2016.

DOI： 10.1002/hed.23992

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 Reviewed

Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takaya Higaki, Sei Ichiro Makihara, Takenori Haruna, Yasuyuki Noyama, Takahisa Koyama, Ryotaro Omichi, Yorihisa Orita, Kentaro Miki, Kengo Kanai, Kazunori Nishizaki

Allergology International 65 ( 1 ) 96 - 102 2016.1

Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.alit.2015.08.005

Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps Reviewed

Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Takaya Higaki, Yasuyuki Noyama, Sei Ichiro Makihara, Kengo Kanai, Kazunori Nishizaki

Journal of Allergy and Clinical Immunology 136 ( 2 ) 343 - 350.e8 2015.8

Publishing type：Research paper (scientific journal)

Background Recent studies have revealed that Staphylococcus aureus and its components participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyps. Objective We sought to determine whether staphylococcal protein A (SpA) from S aureus regulated cellular responses in nasal polyps, especially when coupled to immunoglobulins in immune complexes (ICs). Methods Dispersed nasal polyp cells (DNPCs) or peripheral blood monocytes were cultured in vitro with SpA in the presence or absence of IgG, and IL-5, IL-13, IFN-γ, IL-17A, and IL-10 levels were measured in the supernatants. The effect of SpA exposure on staphylococcal enterotoxin B-induced cytokine production by DNPCs in the presence and absence of IgG, IgA, and autologous serum was also examined. Results Exposure to SpA induced DNPCs to produce significantly higher IL-10, IL-13, and IL-17A levels than DNPCs without SpA, although the magnitude of the IL-17A increase was less than that of IL-10 and IL-13. SpA induced IL-10 production mainly from adherent DNPCs, and this was significantly enhanced in the presence of IgG; similar results were observed in peripheral blood monocytes. IC formation between SpA and IgG (SpA-IgG ICs) was confirmed by using native polyacrylamide gel electrophoresis. SpA-IgG ICs, but not SpA alone, almost completely suppressed staphylococcal enterotoxin B-induced IL-5, IL-13, IFN-γ, and IL-17A production by DNPCs; similar inhibition was observed in DNPCs treated with SpA in the presence of either IgA or autologous serum. Conclusions Our results suggest that SpA can regulate the pathogenesis of enterotoxin-induced inflammation in patients with chronic rhinosinusitis with nasal polyps through coupling to immunoglobulins.

DOI： 10.1016/j.jaci.2014.10.058

【これからのアレルギー性鼻炎対策】新しい全噴霧用ステロイド薬の使い方

春名威範, 岡野光博, 檜垣貴哉, 牧原靖一郎, 野山和廉

ENTONI ( 180 ) 37 - 42 2015.5

Language：Japanese Publisher：(株)全日本病院出版会

鼻噴霧用ステロイド薬はアレルギー性鼻炎に対して強力な抗炎症作用を示すことが知られている。鼻アレルギー診療ガイドラインでは、花粉症に対して、鼻噴霧用ステロイド薬は主に症状の増悪時や重症例に対して用いることが推奨されている。一方、本格発症前の最小持続炎症を制御するという観点から、初期治療における鼻噴霧用ステロイド薬の可能性が議論されている。自験例も含めて、いくつかのプラセボ対照二重盲検比較試験において、鼻噴霧用ステロイド薬を用いたスギ・ヒノキ花粉症に対する初期治療は、プラセボと比べて症状増悪およびQOL増悪を有意に抑制するという報告がある。一方、安全性については実薬とプラセボとの間に有意な差を認めなかった。さらには、発症後治療と比較しても本格飛散後の鼻症状および眼症状の増悪を有意に抑制した。以上の結果より、鼻噴霧用ステロイド薬を用いた花粉症初期治療は有効かつ安全な治療法である可能性が示唆された。今後は、初期治療の至適開始時期や飛散する花粉数による効果の変化などの検討も望まれる。(著者抄録)

急性リンパ性白血病の寛解導入療法中に発症した鼻脳型ムーコル症例 Reviewed

牧原靖一郎, 石原久司, 宮武智実, 津村宗近, 野田洋平, 檜垣貴哉, 假谷伸, 岡野光博, 西崎和則

日本鼻科学会会誌 54 ( 1 ) 31 - 37 2015.5

Authorship：Lead author Language：Japanese Publisher：(一社)日本鼻科学会

急性浸潤型副鼻腔真菌症は眼窩や脳内に進展し極めて難治性で予後不良な疾患である。今回,急性リンパ性白血病の寛解導入療法中に発症し,不幸な転機となった鼻脳型ムーコル症の一例を経験したため,文献的考察を加えて報告する。症例は74歳,女性。当院血液内科で急性リンパ性白血病と診断され,入院2日目より寛解導入療法を開始した。治療開始後から徐々に左視力低下,軽い左眼周囲の痛みを感じ,入院21日目より左眼瞼腫脹,複視を認めるようになり,25日目に眼科受診。左眼球運動の全方向への障害,左眼圧の上昇,左視力低下を認め,CTで副鼻腔炎からの左眼窩蜂窩織炎の疑いにて同日当科紹介受診した。両側鼻内,特に左鼻副鼻腔粘膜は大部分が黒色で壊死性変化をきたしており,病理検査でムーコル症の診断となった。診断後からリポソーマルアムホテリシンBの全身投与を開始した。左眼球摘出も含めたデブリードマンを勧めるも,患者とその家族が拒否したため,入院32日目に鼻副鼻腔内の病変部位を内視鏡下鼻副鼻腔手術にて可及的に除去した。左眼窩内への操作は行わなかった。術後からアムホテリシンBによる鼻腔内洗浄を開始した。入院33日目には左眼光覚消失,37日目より口蓋の穿孔,鞍鼻が生じた。入院96日目に急性細菌性肺炎生じ,98日目に永眠された。拡大手術を行い,薬物治療を併用したとしても根治する保証はない非常に予後の悪い疾患のため,できるだけの早期診断と治療開始が必要と考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J01675&link_issn=&doc_id=20150827370006&doc_link_id=10.7248%2Fjjrhi.54.31&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.54.31&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

ガイドライン耳鼻科シリーズ鼻アレルギー診療ガイドライン通年性鼻炎と花粉症

牧原靖一郎, 岡野光博

岡山医学会雑誌 127 ( 1 ) 55 - 57 2015.4

NSAIDsにシメチジン追加後早期に疼痛が改善した石灰沈着性頸長筋腱炎例 Reviewed

石原久司, 牧原靖一郎, 宮武智実, 津村宗近, 假谷伸

耳鼻咽喉科臨床 108 ( 3 ) 243 - 247 2015.3

Language：Japanese Publisher：耳鼻咽喉科臨床学会

45歳男。3日前に急激な頸部痛、嚥下痛および頸部可動域制限が出現し、前医でロキソプロフェンナトリウムを処方されるも改善しなかった。血液検査で白血球数とCRP値の軽度高値を認め、CTで咽後部に低吸収領域を認めたが、膿瘍を疑う周囲の造影効果は認めなかった。また、頸長筋腱が停止する環軸椎前面に石灰沈着を認めた。なお、前医でのMRIではT2強調像で椎前部に高信号領域を認めていた。以上より石灰沈着性頸長筋腱炎と診断し、前医からのロキソプロフェンナトリウムは継続とし、シメチジン1回量200mgを朝夕食後で追加した。シメチジン開始翌日には、初診時の疼痛を10として6まで疼痛が改善し、3日後には2まで改善して頸部回旋が可能になった。初診後4日後には疼痛は1まで改善し、白血球数とCRP値も正常化した。初診後11日に疼痛は消失し、CTで環軸椎前面の石灰化が縮小し吸収傾向にあることを確認し、26日後にシメチジンを中止した。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J00580&link_issn=&doc_id=20150306220012&doc_link_id=10.5631%2Fjibirin.108.243&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.108.243&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

How long should we continue S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck? Reviewed International journal

Misato Hirai, Yorihisa Orita, Soshi Takao, Tomoyasu Tachibana, Hidenori Marunaka, Seiichiro Makihara, Kentaro Miki, Yasuyuki Noyama, Sayaka Fuji, Akiko Torigoe, Yasuharu Sato, Kazunori Nishizaki

Acta oto-laryngologica 135 ( 10 ) 1079 - 85 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

CONCLUSION: It appears that patients with SCCHN should be recommended to take S-1 for more than 1 year and, if possible, more than 2 years, as adjuvant chemotherapy for SCCHN. OBJECTIVES: There is no established consensus on the duration of administration of S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Since it might be difficult to undergo prospective randomized study to identify the optimal duration of the administration period of S-1 without a standard, the authors have undergone a retrospective clinical study to decide the tentative standard of therapeutic duration of S-1 as adjuvant chemotherapy for SCCHN. METHODS: The clinical records of 89 patients with SCCHN who underwent adjuvant chemotherapy with S-1 were investigated. RESULTS: The median duration of S-1 administration as adjuvant chemotherapy for SCCHN was 7 months (range = 0.1-58 months). Disease-free survivals (DFSs) were generally longer when S-1 administration periods were longer. After adjusting for prognostic factors, S-1 administration periods of 24 months or longer showed significantly lower hazard ratios (HRs) than 0-12 months.

DOI： 10.3109/00016489.2015.1049664

Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takaya Higaki, Takenori Haruna, Osamu Matsushita, Yohei Noda, Seiichiro Makihara, Kengo Kanai, Yasuyuki Noyama, Masami Taniguchi, Kazunori Nishizaki

Allergology international : official journal of the Japanese Society of Allergology 63 ( 4 ) 563 - 73 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY ALLERGOLOGY

BACKGROUND: In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of non-superantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume/forced vital capacity ratio (FEV1/FVC). RESULTS: Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxin-induced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmatics CONCLUSIONS: S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.

DOI： 10.2332/allergolint.14-OA-0703

Endoscopic modified Lothrop procedureが有用であった前頭陥凹骨腫例 Reviewed

牧原靖一郎, 石原久司, 宮武智実, 小林正佳, 假谷伸, 岡野光博, 西崎和則

日本鼻科学会会誌 53 ( 4 ) 542 - 546 2014.12

Authorship：Lead author Language：Japanese Publisher：(一社)日本鼻科学会

Endoscopic modified Lothrop procedure(EMLP)は内視鏡下で両側前頭洞を単洞化する術式で,Frontal ethmoidal cells type 4などの通常の内視鏡下鼻副鼻腔手術(ESS)で前頭洞開放が困難な症例,前頭陥凹の癒着や骨増生を認める症例,眼窩壁や前頭洞後壁の骨欠損を認める症例,鼻外前頭洞手術の不成功症例,前頭洞嚢胞や前頭洞内腫瘍症例などに有用である。今回,EMLPが有用であった前頭陥凹骨腫例を経験したので,文献的考察を加えて報告する。症例は49歳女性。右眉上部に疼痛を自覚し,当院を紹介受診した。CT上,右前頭陥凹に径22mm大の骨腫像を認め,右前頭洞に充満する軟部陰影像も認めた。以上から前頭陥凹骨腫により鼻前頭管が閉塞して生じた前頭洞炎と診断した。抗菌薬等による保存的治療で改善しなかったので鼻内手術の適応とした。骨腫は前頭蓋底,右眼窩紙様板,篩板側壁,frontal beak,前頭洞中隔,右中鼻甲介と癒合していた。EMLPを施行し,それらの癒合部を安全に処理した上で骨腫を摘出し,前頭洞を広く開放した。術後経過は良好である。今回の結果から,前頭陥凹骨腫に対してEMLPの適用は有用であると考えられる。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J01675&link_issn=&doc_id=20150601320007&doc_link_id=10.7248%2Fjjrhi.53.542&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.53.542&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

眼窩骨膜内に膿瘍形成を認めた例 Reviewed

牧原靖一郎, 石原久司, 宮武智実, 唐木將行, 津村宗近, 假谷伸, 岡野光博, 西崎和則

日本鼻科学会会誌 53 ( 4 ) 506 - 512 2014.12

Authorship：Lead author Language：Japanese Publisher：(一社)日本鼻科学会

骨膜は2層構造を認めるといわれている。今回,眼窩骨膜内に膿瘍形成をきたし,内視鏡下鼻副鼻腔手術(ESS)を行うことで改善を認めた一例を経験したので,文献的考察を加えて報告する。症例は35歳,男性。2012年X月昼より,鼻から額の左側に痛みがあり,近医耳鼻科受診。レボフロキサシン処方された。翌日,同部位の疼痛が激しくなり,当科紹介受診。副鼻腔CTでは左上顎洞,左篩骨洞,左前頭洞に陰影を認めるも,眼窩内に異常所見認めなかった。入院にてセフトリアキソン開始。2日後,左眼痛の悪化と左眼瞼腫脹を認め,造影CTにて眼窩骨膜下膿瘍が考えられる所見があり,同日,ESSを施行した。術中出血が多く,左上顎洞,左篩骨洞,左前頭洞から膿汁排出がみられ,術前の眼窩内陰影が軽度であったことから,紙様板への操作は行わなかった。術後,一旦左眼痛の改善認めるも,6日後,左眼瞼腫脹の明らかな増悪あり,同日再手術を施行した。左眼窩骨膜下膿瘍を考え,眼窩骨膜下を剥離するも膿汁排出を認めなかったが,骨膜を2層に剥離すると膿汁排出が認められた。術後経過良好にて14日後に退院となった。抗生剤による保存的治療に対して抵抗性である眼窩内感染症に対しては速やかに手術加療が必要であると感じた。本症例ではESSが非常に有効で,Chandlerの分類でgroup III以上の眼窩内感染症を認める場合は眼窩紙様板の除去と膿瘍開放術も必要と考えられた。画像上,眼窩骨膜下膿瘍と考えられる場合,眼窩紙様板を除去しても排膿されない時は,眼窩骨膜内に膿瘍形成を生じていることもあり注意が必要と思われた。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J01675&link_issn=&doc_id=20150601320002&doc_link_id=10.7248%2Fjjrhi.53.506&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.53.506&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

当院での下垂体部腫瘍に対する内視鏡下経鼻下垂体手術

平下浩司, 畝田篤仁, 松本淳志, 大久保修一, 柚木正敏, 吉野公博, 牧原靖一郎

香川労災病院雑誌 ( 20 ) 15 - 18 2014.11

Language：Japanese Publisher：香川労災病院

当院では下垂体部腫瘍に対する手術のアプローチ方法として、以前は手術用顕微鏡を用いたSublabial approach(以下Hardy法)を施行していたが、21012年10月から内視鏡下経鼻手術(以下;経鼻)を導入した。今回、Hardy法を施行した群(10例)と経鼻施行群(15例)とで「手術時間」「入院日数」「合併症」などを比較検討した。結果、手術時間はHardy法群が平均290分、経鼻群が249分、入院日数はそれぞれ平均19.5日、15.3日であった。合併症はHardy法群で副腎機能低下を1例(10%)、鼻出血を1例(10%)、尿崩症を2例(20%)に認め、経鼻群で副腎機能低下を1例(7%)、尿崩症を6例(40%)に認めた。Hardy法と経鼻の両方を経験した症例が6例あり、その感想は総じて「経鼻のほうが術後に楽だった」とのことであった。代表例として経鼻群の1例を提示した。

当院における外来化学療法室の現状と課題

滝本秀隆, 坂本路代, 山崎美佐, 土佐直子, 亀井美紀, 横山智美, 能願美由紀, 中尾三千代, 乃一真由美, 永田拓也, 井上秀幸, 木村圭吾, 村岡篤, 平下浩司, 牧原靖一郎, 水野全裕, 川田昭徳, 香川労災病院化学療法委員会

香川労災病院雑誌 ( 20 ) 1 - 4 2014.11

Language：Japanese Publisher：香川労災病院

当院における2013年度の外来化学療法件数は5709件で、統計をとり始めた2006年度から7年連続で増加しており、2006年度の2倍以上に増加した。曜日別の件数をみると、2012年度には、最も多い曜日と少ない曜日で1.7倍の開きがあったが、2013年度は医師の外来日を変更したことで曜日によるバラツキが減少した。2009～2013年度における件数の推移を原疾患別にみると、血液疾患のみが増加し続けており、乳癌は2011年まで減少傾向にあったが、その後増加し、血液疾患に次いで2番目の数となっている。2006～2013年度における件数の推移を診療科別にみると、2010年までは外科の件数が圧倒的に多かったが、内科が急激に増加しており、2013年には外科を上回った。このほか、婦人科と泌尿器科の件数も緩やかに増加し続けている。当院の外来化学療法は今後も増加すると予想されることから、安全で効率的な外来化学療法室の運用を行えるよう、人員の確保や職員の教育システム構築が必要と考えられる。

浸潤型蝶形骨洞アスペルギルス症に対して蝶形骨洞単洞化手術を施行した1例 Reviewed

牧原靖一郎, 岡野光博, 石原久司, 宮武智実, 津村宗近, 假谷伸, 西崎和則

耳鼻咽喉科・頭頸部外科 86 ( 9 ) 765 - 770 2014.8

Authorship：Lead author Language：Japanese Publisher：(株)医学書院

症例は68歳男性で、右眼痛、頭痛で近医CTにて浸潤性副鼻腔真菌症、副鼻腔腫瘍を疑い紹介受診した。両側内視鏡下副鼻腔手術を行い、両側上顎洞、右篩骨洞、右蝶形骨洞にアスペルギルス様真菌塊を認め、抜去後洗浄して終了した。術翌日よりボリコナゾール(VRCZ)内服を開始した。初診4ヵ月後のCTで右蝶形骨洞内の再燃を認め、右蝶形骨洞単洞化手術を行った。術後も生食洗浄を続けたが、早期に粘膜が肥厚し、術後1ヵ月で右蝶形洞内は肉芽に覆われた。初診8ヵ月後に右蝶形骨洞内の肉芽除去、真菌除去を行った。術前のβ-D-グルカン値の異常高値を認め、問診で無症状のためVRCZ内服を自己中断していたことが判明し、手術後にVRCZ内服のコンプライアンスは改善し、術後1ヵ月半で蝶形骨洞の肉芽は消失した。β-D-グルカン値も正常に回復し、服薬履行確認にtherapeutic drug monitoringを開始した。現在約1年経過で蝶形骨洞の所見も良好な状態を維持している。

Local expression of interleukin-17a is correlated with nasal eosinophilia and clinical severity in allergic rhinitis. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Yohei Noda, Takaya Higaki, Tomomi Miyateke, Kengo Kanai, Takenori Haruna, Shin Kariya, Kazunori Nishizaki

Allergy & rhinology (Providence, R.I.) 5 ( 1 ) 22 - 7 2014.4

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：OCEAN SIDE PUBLICATIONS INC

Interleukin (IL)-17A is a major cytokine produced by Th17 cells, which are associated with chronic inflammations. The local expression of IL-17A in allergic rhinitis (AR) remains to be characterized. We sought to determine the role of IL-17A expression in human inferior turbinate mucosa in the pathophysiology of AR. Inferior turbinate mucosa was sampled from medical treatment-resistant, surgery-required patients with perennial AR (PAR, n = 21), nonallergic rhinitis with eosinophilia syndrome (NARES, n = 7), and nonallergic hypertrophic rhinitis (HR, n = 13). IL-17A expression was determined with immunohistochemical staining. The mean number of IL-17A(+) cells and eosinophils per field were counted. Total serum immunoglobulin E (IgE) levels, blood eosinophil count, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio were also examined in each patient. IL-17A was primarily expressed in infiltrating inflammatory cells. The number of IL-17A(+) cells in nasal mucosa was significantly higher in the PAR group compared with HR (p = 0.002) and NARES (p = 0.021) groups. There was a significant and positive correlation between the number of IL-17A(+) cells and total nasal symptom score (rho = 0.403; p = 0.011), especially sneezing score (rho = 0.471; p = 0.003). The number of IL-17A(+) cells was significantly and positively correlated with the degree of eosinophil infiltration (rho = 0.623; p < 0.001), but not with total serum IgE levels (rho = 0.284; p = 0.098), blood eosinophil counts (rho = 0.302; p = 0.056), or FEV1/FVC ratio (rho = 0.092; p = 0.569). The present study provides evidence that IL-17A expression in the nasal mucosa is associated with the pathophysiology of AR, including disease severity and nasal eosinophilia.

DOI： 10.2500/ar.2014.5.0078

Pulmonary function in patients with chronic rhinosinusitis and allergic rhinitis Reviewed

S. Kariya, M. Okano, T. Oto, T. Higaki, S. Makihara, T. Haruna, K. Nishizaki

Journal of Laryngology and Otology 128 ( 3 ) 255 - 262 2014.3

Publishing type：Research paper (scientific journal)

Background: A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases. Methods: Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels. Results: The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis. Conclusion: The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis.

DOI： 10.1017/S0022215114000450

【スギ花粉症の発症と初期治療】鼻噴霧ステロイド薬を用いた初期治療の有効性

小山貴久, 岡野光博, 春名威範, 野山和廉, 假谷伸, 檜垣貴哉, 牧原靖一郎, 西崎和則

臨床免疫・アレルギー科 60 ( 6 ) 664 - 667 2013.12

当院における外来化学療法室の現状と課題

滝本秀隆, 坂本路代, 藤浦美佐, 土佐直子, 亀井美紀, 能願美由紀, 中尾三千代, 乃一真由美, 香川秀子, 永田拓也, 井上秀幸, 木村圭吾, 村岡篤, 平下浩司, 牧原靖一郎, 水野全裕, 川田昭徳, 香川労災病院化学療法委員会

香川労災病院雑誌 ( 19 ) 1 - 5 2013.10

鼻出血を契機に発見された鼻腔原発のglomangiopericytomaの1例 Reviewed

大道亮太郎, 假谷伸, 岡野光博, 牧原靖一郎, 小野田友男, 江口元治, 西崎和則

頭頸部外科 23 ( 2 ) 141 - 144 2013.10

Language：Japanese Publisher：(NPO)日本頭頸部外科学会

glomangiopericytomaは鼻副鼻腔原発の血管周囲筋様細胞の表現型を伴う境界から低悪性度の新生物である。その発生頻度は全鼻副鼻腔腫瘍のうち1%以下とされており、非常にまれな腫瘍である。この腫瘍は従来hemangiopericytomaの一亜型とされてきたが、一般的な軟部組織に発生するhemangiopericytomaとは発生部位、生物学的挙動、組織学的特徴の観点から区別され、2005年のWHO基準にて正式に疾患分類として登録された。比較的新しい疾患概念であることなどから、hemangiopericytomaとの鑑別が十分なされていないことがあり、注意を要する疾患とされている。われわれは今回鼻出血を主訴に来院した右鼻腔原発のglomangiopericytomaに対し、内視鏡下に切除手術を施行し、良好な経過を得た1例を経験したので報告する。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J04210&link_issn=&doc_id=20131127350004&doc_link_id=10.5106%2Fjjshns.23.141&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.23.141&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media. Reviewed International journal

Shin Kariya, Mitsuhiro Okano, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Motoharu Eguchi, Kazunori Nishizaki

The Laryngoscope 123 ( 6 ) 1514 - 8 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

OBJECTIVES/HYPOTHESIS: Granulocyte/macrophage colony-stimulating factor is important in the pathogenesis of acute and chronic inflammatory disease. We hypothesized that granulocyte/macrophage colony-stimulating factor plays a pivotal role in middle ear inflammation and that neutralization of granulocyte/macrophage colony-stimulating factor would inhibit neutrophil migration into the middle ear and production of inflammatory mediators. STUDY DESIGN: Animal experiment. METHODS: We used transtympanic administration of lipopolysaccharide, a major component of gram-negative bacteria, into mice to induce an experimental otitis media. Control mice received injection of phosphate-buffered saline into the middle ear cavity. Mice were systemically treated with granulocyte/macrophage colony-stimulating factor neutralizing antibody or control immunoglobulin G via intraperitoneal injection 2 hours before transtympanic injection of lipopolysaccharide or phosphate-buffered saline. Middle ear effusions were collected. Concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in middle ear effusions were measured by enzyme-linked immunosorbent assay. Histologic examination of the middle ear was also performed. RESULTS: Transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony-stimulating factor, IL-1β, TNF-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle ear. Concentrations of cytokines and chemokines were significantly decreased in mice injected with granulocyte/macrophage colony-stimulating factor neutralizing antibody. Infiltration of inflammatory cells into the middle ear cavity induced by lipopolysaccharide was also significantly reduced by neutralization of granulocyte/macrophage colony-stimulating factor. CONCLUSIONS: Systemic injection of granulocyte/macrophage colony-stimulating factor neutralizing antibody inhibits the middle ear inflammation induced by lipopolysaccharide in mice. Our findings suggest that granulocyte/macrophage colony-stimulating factor may offer a novel therapeutic target for the management of intractable otitis media.

DOI： 10.1002/lary.23795

鼻中隔膿瘍を伴った浸潤型蝶形骨洞アスペルギルス症例 Reviewed

牧原靖一郎, 竹内彩子, 山本美紀, 妹尾一範, 赤木成子, 福本晶, 津村宗近, 石原久司, 假谷伸, 岡野光博, 西崎和則

耳鼻咽喉科臨床 106 ( 3 ) 213 - 220 2013.3

Authorship：Lead author Language：Japanese Publisher：耳鼻咽喉科臨床学会

86歳男。鼻中隔膿瘍は切開排膿によって改善した。蝶形骨洞アスペルギルス症に対しては内視鏡下鼻内副鼻腔手術による真菌塊除去後にボリコナゾール(VRCZ)投与を開始したが、症状は増悪した。その後、鼻中隔膿瘍の菌培養検査での真菌MIC値を参考にして抗真菌剤をミカファンギンナトリウムとイトラコナゾールに変更したところ、症状は改善した。本例はVRCZに抵抗性のアスペルギルス症であり、真菌MIC値は薬剤選択に非常に有用であった。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00580&link_issn=&doc_id=20130227280005&doc_link_id=10.5631%2Fjibirin.106.213&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.106.213&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Characterization of IL-18 expression and release in the pathogenesis of chronic rhinosinusitis. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Seiichiro Makihara, Rumi Fujiwara, Takaya Higaki, Shin Kariya, Yohei Noda, Takenori Haruna, Kazunori Nishizaki

International archives of allergy and immunology 160 ( 3 ) 275 - 86 2013

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

BACKGROUND: Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS). METHODS: The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined. RESULTS: Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18(+) cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production. CONCLUSIONS: These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.

DOI： 10.1159/000341668

Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis. Reviewed International journal

Takaya Higaki, Mitsuhiro Okano, Seiichiro Makihara, Tazuko Fujiwara, Takenori Haruna, Yohei Noda, Shin Kariya, Kazunori Nishizaki

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 109 ( 6 ) 458 - 64 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

BACKGROUND: The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. OBJECTIVES: To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. METHODS: We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. RESULTS: The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P < .01) and POT (3.9; P = .03) groups. All patients in the placebo and POT groups were classified as having persistent rhinitis, whereas 80% of the EIT group met the ARIA classification criteria (P = .03). The quality-of-life score and nasal eosinophil cationic protein levels were lower in the EIT and POT groups compared with the placebo group. Daytime sleepiness, smell disturbance, and the mean dose of loratadine taken as the rescue medication were similar. Treatment with mometasone was well tolerated. CONCLUSION: EIT with INSs is superior to POT in controlling pollinosis.

DOI： 10.1016/j.anai.2012.08.016

Roles of IL-17, Th1, and Tc1 cells in patients with IgG4-related sclerosing sialadenitis. Reviewed International journal

Nobuo Ohta, Seiichiro Makihara, Mitsuhiro Okano, Kazuya Kurakami, Akihiro Ishida, Takatoshi Furukawa, Yusuke Suzuki, Tomoo Watanabe, Seiji Kakehata, Masaru Aoyagi

The Laryngoscope 122 ( 10 ) 2169 - 74 2012.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

OBJECTIVES/HYPOTHESIS: Immunoglobulin G4 (IgG4)-related sclerosing sialadenitis is a recently recognized disease entity characterized by high serum IgG4 concentration and IgG4-producing plasma cell expansion in affected organs, which show fibrotic or sclerotic changes. However, little is known about the roles of CD4+ and CD8+ T cells or interleukin (IL)-17 in this disease. The purpose of this study was to evaluate the characteristics of CD4+ and CD8+ T cells and IL-17 in patients with IgG4-related sclerosing sialadenitis. STUDY DESIGN: A retrospective clinical study at the Yamagata University School of Medicine. METHODS: The patient group consisted of six males and four females with an average age of 57.9 years (range, 38 to 73 years). Subsets of T helper (Th)1, Th2, T cytotoxic type (Tc)1, and Tc2 cells from patients with IgG4-related sclerosing sialadenitis were examined by using intracellular cytokine flow cytometry. Expression of IL-17 in the patients' lesions was also investigated immunohistochemically. RESULTS: Six patients with IgG4-related sclerosing sialadenitis with high ratios of IgG4/IgG and prominent infiltration of IgG4-positive plasmacytes in the involved salivary glands had systemic complications, including pancreatitis, retroperitoneal fibrosis, and/or inflammatory pseudotumor of the lung after the initial swelling of the salivary glands. Populations of Th1 and Tc1 cells were significantly greater in IgG4-related sclerosing sialadenitis than in the controls (P < .05), but Th2 and Tc2 cell populations were not significantly increased. Expression of IL-17 was observed in the lesions of affected patients. CONCLUSIONS: Increases in Th1 and Tc1 cell populations and IL-17 expression might be involved in the mechanism of pathogenesis of IgG4-related sclerosing sialadenitis.

DOI： 10.1002/lary.23429

COX/PGE<inf>2</inf> axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps Reviewed

T. Higaki, M. Okano, T. Fujiwara, S. Makihara, S. Kariya, Y. Noda, T. Haruna, K. Nishizaki

Clinical and Experimental Allergy 42 ( 8 ) 1217 - 1226 2012.8

Publishing type：Research paper (scientific journal)

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-γ within the supernatant were measured. The effects of PGE2 on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE2 production and mRNA expression of COX-1, COX-2 and microsomal PGE2 synthase-1 (m-PGES-1) were measured. Results: Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-γ production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE2 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 PGE2 inhibited IL-5, IL-13 and IFN-γ production. LPS alone induced IL-5, IL-13 and IFN- γ production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE2 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/PGE2 axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps. © 2012 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2222.2012.04015.x

滲出性中耳炎を合併した翼口蓋窩嚢胞例 Reviewed

牧原靖一郎, 岡野光博, 折田頼尚, 小野田友男, 假谷伸, 津村宗近, 西崎和則

耳鼻咽喉科臨床 105 ( 7 ) 631 - 636 2012.7

Authorship：Lead author Language：Japanese Publisher：耳鼻咽喉科臨床学会

67歳女性。咬合時の左顔面違和感を主訴に近医を受診、CT検査にて左翼口蓋窩腫瘍を疑われ、著者らの施設へ紹介となった。所見では副鼻腔CTで左上顎洞後方、翼口蓋窩に長径14mmと短径6mmのニ房性の嚢胞状腫瘤が認められた。また、MRIでは同部位にT1にて低信号、T2にて低信号と高信号が混在する腫瘤が確認された。以上、これらの画像所見を踏まえ、本症例は嚢胞性病変を考え、しばらく経過観察としていたが、左滲出性中耳炎を合併し、MRIで腫瘤サイズの増大とともに左乳突蜂巣に液体貯留が認められた。そこで、診断確定目的で内視鏡下鼻内副鼻腔手術を行なったところ、病理組織学的に翼口蓋窩に発生した類表皮嚢胞と診断された。経過は術後より咬合時の左顔面違和感が改善し、左滲出性中耳炎も治癒が得られた。目下、術後1年経過で開放部の閉塞や滲出性中耳炎の再燃はみられていない。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J00580&link_issn=&doc_id=20120705310005&doc_link_id=10.5631%2Fjibirin.105.631&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.105.631&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Early interventional treatment with intranasal mometasone furoate in Japanese cedar/cypress pollinosis: a randomized placebo-controlled trial. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Masayo Kimura, Takaya Higaki, Takenori Haruna, Yohei Noda, Kengo Kanai, Shin Kariya, Kazunori Nishizaki

Allergology international : official journal of the Japanese Society of Allergology 61 ( 2 ) 295 - 304 2012.6

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY ALLERGOLOGY

BACKGROUND: Little is known about the safety and effectiveness of early interventional treatment (EIT) with intranasal corticosteroids for seasonal allergic rhinitis. We designed a double-blinded, randomized, placebo-controlled 12-week trial of EIT with mometasone furoate nasal spray (MFNS) for Japanese cedar/cypress pollinosis (JCCP). METHODS: A total of 50 JCCP patients received MFNS (200μg once daily: n = 25) or placebo (n = 25) starting on February 1, 2010. Treatments continued until the end of April. The primary endpoint was the comparison of the total nasal symptom score (TNSS) between the MFNS and placebo groups. The secondary endpoints included comparisons of QOL, daytime sleepiness, nasal ECP levels, and safety. RESULTS: Continuous dispersion of Japanese cedar pollen began on February 22. Although the placebo group showed a significant worsening of symptoms after the start of the continuous dispersion, no worsening occurred in the MFNS group. A significant difference in the TNSS between the two groups was seen starting at 4 weeks after the treatment. Similar results were seen for QOL and sleepiness. Nasal ECP levels in March were significantly lower in the MFNS group. A total of 56% of the MFNS group progressed to a persistent allergic rhinitis state in accordance with the ARIA classification, as opposed to 84% of the placebo group. MFNS was well tolerated, and the plasma cortisol concentrations were similar between the two groups. CONCLUSIONS: EIT with MFNS for JCCP is both safe and effective. This treatment can potentially lessen symptoms and help pollinosis patients remain in the intermittent state.

DOI： 10.2332/allergolint.11-OA-0382

Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D<inf>2</inf> receptor (DP)-dependent pathway Reviewed

M. Eguchi, S. Kariya, M. Okano, T. Higaki, S. Makihara, T. Fujiwara, K. Nagata, H. Hirai, S. Narumiya, M. Nakamura, K. Nishizaki

Clinical and Experimental Immunology 163 ( 2 ) 260 - 269 2011.2

Publishing type：Research paper (scientific journal)

Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

DOI： 10.1111/j.1365-2249.2010.04292.x

Role of fungal antigens in eosinophilia-associated cellular responses in nasal polyps: A comparison with enterotoxin Reviewed

M. Okano, T. Fujiwara, T. Haruna, S. Kariya, S. Makihara, T. Higaki, K. Nishizaki

Clinical and Experimental Allergy 41 ( 2 ) 171 - 178 2011.2

Publishing type：Research paper (scientific journal)

Summary: Background Fungi and/or Staphylococcus aureus enterotoxins (SEs) may participate in the pathogenesis of eosinophilic inflammation in cases of chronic rhinosinusitis with nasal polyps (CRSwNP).Objective We sought to determine the effects of fungal antigens on eosinophilia-associated cellular responses in nasal polyps.Methods Dispersed nasal polyp cells (DNPCs) were prepared from 13 patients with CRSwNP. DNPCs were cultured with fungal extracts (Aspergillus, Alternaria and Candida) or SEB for 72 h, after which the levels of IL-5, IL-13 and RANTES were measured within the supernatant. Responses to β-d-glucan, mannan and chitin were also examined.Results 38.5%, 69.2% and 30.8% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Aspergillus. 53.8%, 53.8% and 7.7% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Alternaria. 53.8%, 38.5% and 15.4% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Candida. All DNPCs produced these cytokines in response to 0.1 μg/mL of SEB. SEB induced significantly greater cytokine levels than the fungal extracts. No correlation between cytokine production following exposure to each of the fungal extracts or SEB and various clinical features, including nasal polyp eosinophilia and radiological severity of sinusitis was observed. Neither sensitization to fungus nor comorbidity with bronchial asthma was correlated with the fungal extract-induced cytokine production by DNPCs. β-d-glucan, mannan and chitin did not induce significant cytokine production.Conclusions These results suggest that, although DNPCs produce IL-5, IL-13 and RANTES in response to fungal extracts, fungal antigens including major carbohydrates are less capable of inducing eosinophilia-associated cellular responses in nasal polyps than SEB. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2222.2010.03584.x

Characterization of pollen antigen-induced IL-31 production by PBMCs in patients with allergic rhinitis. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Yohei Noda, Kengo Kanai, Shin Kariya, Hiroshi Yasueda, Kazunori Nishizaki

The Journal of allergy and clinical immunology 127 ( 1 ) 277 - 9 2011.1

慢性上気道炎症におけるIL-17A発現の臨床的意義とその制御機構

牧原靖一郎, 岡野光博, 藤原田鶴子, 檜垣貴哉, 野田洋平, 假谷伸, 西崎和則

耳鼻咽喉科免疫アレルギー 28 ( 3 ) 217 - 222 2010.9

Regulation and characterization of IL-17A expression in patients with chronic rhinosinusitis and its relationship with eosinophilic inflammation. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Yohei Noda, Takaya Higaki, Kazunori Nishizaki

The Journal of allergy and clinical immunology 126 ( 2 ) 397 - 400 2010.8

【ステロイドによる局所療法のアップデート】新規鼻噴霧用ステロイド薬の急性鼻副鼻腔炎に対する欧米での評価

牧原靖一郎, 岡野光博

アレルギー・免疫 17 ( 4 ) 591 - 598 2010.3

Authorship：Lead author Language：Japanese Publisher：(株)医薬ジャーナル社

本邦では、リン酸デキサメタゾンなどの全身性ステロイド薬はネブライザーなどの投与に限り副鼻腔炎に対する適応を有するが、鼻噴霧用ステロイド薬は副鼻腔炎に対する適応を有さない。一方、海外ではmometasone furoate(MFNS)やfluticasone propionate(FP)のようなバイオアベイラビリティが低く、局所への効果の強い鼻噴霧用ステロイド薬(intranasal corticosteroids;INCS)は急性副鼻腔炎に対して、抗生剤に上乗せすることで抗生剤単独よりも症状改善をきたすことが示されている。INCSが高用量の場合はさらに効果が増すことも示唆されている。INCS単剤投与の場合は、中等症以下の急性副鼻腔炎に対し、アモキシシリン単剤投与よりも効果が認められた報告もみられる。一方、INCS使用はプラセボと比較し目立った副作用は認められず、高い安全性が示されている。(著者抄録)

Prostaglandin E(2) suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Takenori Haruna, Shin Kariya, Seiichiro Makihara, Takaya Higaki, Kazunori Nishizaki

The Journal of allergy and clinical immunology 123 ( 4 ) 868 - 74 2009.4

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

BACKGROUND: Recent investigations have revealed that staphylococcal enterotoxins (SEs), COX metabolism, or both might participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyposis. OBJECTIVE: We sought to determine whether COX metabolism, especially prostaglandin (PG) E(2), plays a significant role in SE-induced cellular responses in nasal polyps. METHODS: Dispersed nasal polyp cells (DNPCs) were prepared from nasal polyps by means of enzymatic digestion. DNPCs were cultured with SEB in the presence or absence of COX inhibitors (diclofenac and indomethacin) for 72 hours; then the levels of IL-5, IL-13, RANTES, and eotaxin in the supernatants were measured. The effect of PGE(2) on SEB-induced responses by diclofenac-treated DNPCs was examined, especially in terms of receptor specificity. RESULTS: DNPCs produced significant amounts of IL-5, IL-13, and RANTES in response to SEB. COX inhibitors significantly increased the production of these cytokines. The degree of local eosinophilia was significantly and positively correlated with the changes in IL-5 production induced by diclofenac treatment. PGE(2) significantly and dose-dependently inhibited SEB-induced IL-5, IL-13, and RANTES production by diclofenac-treated DNPCs. E-prostanoid (EP) 2 receptor-selective agonist strongly inhibited the production of all 3 cytokines. EP3 and EP4 receptor-selective agonists partially suppressed these responses, whereas EP1 receptor-selective agonist did not. Interestingly, all of the combined treatments with 2 of the 4 EP receptor-selective agonists significantly inhibited the SEB-induced responses by diclofenac-treated DNPCs. CONCLUSIONS: These results suggest that PGE(2) inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.

DOI： 10.1016/j.jaci.2009.01.047

A case of renal metastasis originating from primary hypopharyngeal and esophageal cancer Reviewed

NOMIYA Shigenobu, MAKIHARA Seiichirou, MATSUMOTO Rie, ORITA Yorihisa, KARIYA Shin, ONODA Tomoo, TOMINAGA Susumu, NISHIZAKI Kazunori

Stomato-pharyngology 20 ( 3 ) 293 - 298 2008

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society of Stomato-pharyngology

Renal metastasis originating from metachronous development of hypopharyngeal and esophageal cancer is reported. A 60-year-old man had received pharyngolaryngectomy for hypopharyngeal cancer in 2003. He had stomachache in 2005 and a right renal tumor was found with CT and MRI. Percutaneous needle biopsy was performed and histological results showed squamous cell carcinoma. At the same time, squamous cell carcinoma was detected in the esophagus. He had chemotherapy but it was ineffective. This case was thought to be a rare case of metastatic renal cancer arising from multiple primary cancers.

DOI： 10.14821/stomatopharyngology1989.20.293

Other Link： http://search.jamas.or.jp/link/ui/2008358660

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