Language：English   Publisher：Journal of Medical Case Reports  

Background: Sinonasal ameloblastic tumors exhibit unique clinical, pathological, and genetic traits distinct from mandibular bone cases, accounting for the majority of ameloblastic tumors. Recent findings emphasize a notable genetic disparity, showing high BRAF mutation rates in mandibular cases versus very low rates in maxillary cases. Case presentation: We analyzed five sinonasal ameloblastic tumor cases treated at Kyushu University Hospital. All patients were Japanese, four male and one female, and their age ranged from 43 to 73 years. Three were diagnosed with ameloblastoma, with one experiencing recurrence that progressed to a life-threatening condition owing to the lack of effective treatment. One patient was histologically diagnosed as ameloblastic carcinoma, and another patient, although histologically diagnosed as ameloblastoma, presented with lymph node metastasis, confirming it as a metastasizing ameloblastoma with clinical malignancy. Local radical resection was performed in all five patients; however, three of them had positive resection margins, and two received postoperative (chemotherapy) radiation therapy. Recurrence was confirmed in two patients, with one patient undergoing chemoradiation therapy and achieving local control. BRAF mutations were detected in only one patient. Conclusion: Owing to anatomical challenges in achieving negative resection margins and the low BRAF mutation frequency, sinonasal ameloblastic tumors exhibit poor prognosis with high recurrence, malignancy, and metastasis rates. When factors predicting recurrence post-radical resection in these tumors are identified, chemoradiation therapy is recommended as an adjuvant postoperative treatment. However, it should be noted that this presentation of adjuvant therapy is based on the experience of only five cases.

DOI： 10.1186/s13256-025-05224-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Voice  

Objectives: Auditory-perceptual evaluation frameworks, such as the grade-roughness-breathiness-asthenia-strain (GRBAS) scale, are the gold standard for the quantitative evaluation of pathological voice quality. However, the evaluation is subjective; thus, the ratings lack reproducibility due to inter- and intra-rater variation. Prior researchers have proposed deep-learning-based automatic GRBAS score estimation to address this problem. However, these methods require large amounts of labeled voice data. Therefore, this study investigates the potential of automatic GRBAS estimation using deep learning with smaller amounts of data. Methods: A dataset consisting of 300 pathological sustained /a/ vowel samples was created and rated by eight experts (200 for training, 50 for validation, and 50 for testing). A neural network model that predicts the probability distribution of GRBAS scores from an onset-to-offset waveform was proposed. Random speed perturbation, random crop, and frequency masking were investigated as data augmentation techniques, and power, instantaneous frequency, and group delay were investigated as time-frequency representations. Results: Five-fold cross-validation was conducted, and the automatic scoring performance was evaluated using the quadratic weighted Cohen's kappa. The results showed that the kappa values of the automatic scoring performance were comparable to those of the inter-rater reliability of experts for all GRBAS items and the intra-rater reliability of experts for items G, B, A, and S. Random speed perturbation was the most effective data augmentation technique overall. When data augmentation was applied, power was the most effective for items G, R, A, and S; for Item B, combining group delay and power yielded additional performance gains. Conclusion: The automatic GRBAS scoring achieved by the proposed model using scant labeled data was comparable to that of experts. This suggests that the challenges resulting from insufficient data can be alleviated. The findings of this study can also contribute to performance improvements in other tasks such as automatic voice disorder detection.

DOI： 10.1016/j.jvoice.2022.10.020

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Language：Japanese   Publisher：耳鼻と臨床会  

方向別の文字起こし機能を持つデバイス(VUEVO、ピクシーダストテクノロジーズ社)の情報保障機器としての有用性を検証した。VUEVOは方向別に音声を文字起こしでき、音声が重なっても方向が重なっていなければそれぞれ文字起こしできるという特長があった。研究会や講演では、発表者、司会者、質問者それぞれの方向で文字起こしされ、従来の一つのスクリーンにすべての音声が文字起こしされる方法と比較して誰の発言か分かりやすい情報保障となった。特に、ステージ上の大きなスクリーンが使える時は、発言者の近くに文字が表示されるように配置することができた。このため、方向別に文字起こしする技術は今後の情報保障をより発展させる上で有用と考えられた。(著者抄録)

Language：Japanese   Publisher：Japan Audiological Society  

<p>　　We established age-dependent and side-dependent reference values for auditory processing test (APT) batteries. This study was conducted in 53 subjects aged 20-59 years with normal hearing. The results of the APT were used to establish reference values for each 10-year age group, using the 2SD method. Reference values for the tests performed on one ear at a time were established separately as the “superior” or “inferior” side, depending on the results for each test item.</p>
<p>　　Statistical differences among age groups were noted in the following test items: dichotic listening test, speech recognition under multi-talker noise (signal to noise ratio of +15dB, +10dB, and +5dB) of the Hatta-Ota version of APT, dichotic listening monosyllable test, fast speech recognition test (2x speed, mid-word), and speech recognition under speech noise of the Obuchi version of APT. The dominant test performance side was almost equally distributed between the right and left sides, even though most of the participants were right-handed. Based on these results, we propose different reference values for the APT for different age groups. We further propose setting up separate reference values for tests conducted on one ear at a time by the superior and inferior sides for each test item.</p>

DOI： 10.4295/audiology.68.65

CiNii Research

Language：English   Publisher：Discover Oncology  

Objectives: Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drug and suppresses T-cell proliferation and activity by inhibiting pyrimidine synthesis using dihydroorotase dehydrogenase (DHODH); however, several studies have demonstrated that LEF possesses anticancer and antiangiogenic effects in some malignant tumors. Therefore, we investigated the anticancer and antiangiogenic effects of LEF on oral squamous cell carcinoma (OSCC). Methods: To evaluate the inhibitory effect of LEF on OSCC, cell proliferation and wound-healing assays using human OSCC cell lines were performed. The DHODH inhibitory effect of LEF was evaluated by Western blot. To assess the suppression of pyrimidine biosynthesis induced by LEF on OSCC, cell proliferation assays with or without uridine supplementation were performed. The antiangiogenic effect of LEF was evaluated by in vitro tube formation assay using immortalized human umbilical vein endothelial cells, which were electroporatically transfected with hTERT. The tumor-suppressive effect of LEF in vivo was examined in both immunodeficient and syngeneic mice by implanting mouse OSCC cells. Tumor vascularization was evaluated by immunohistochemistry of the tumor extracted from syngeneic mice. Results: LEF dose-dependently inhibited OSCC proliferation and migration. LEF significantly inhibited DHODH expression, and uridine supplementation rescued the inhibitory effect of LEF. LEF dose-dependently suppressed endothelial tube formation. In the animal study, LEF significantly suppressed tumor growth in both immunodeficient and syngeneic mice. Histologically, LEF decreased DHODH expression and tumor vascularization. Conclusion: LEF is a potent anticancer agent with antiangiogenic effects on OSCC and might be clinically applicable to OSCC by drug repositioning.

DOI： 10.1007/s12672-025-01763-5

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Language：Japanese   Publisher：耳鼻と臨床会  

悪性腫瘍に対する放射線化学療法(CRT)後のサルベージ手術は、創傷治癒の遅延が予想される。特に頭蓋底再建を伴う手術において創部感染、出血、髄液漏などの合併症が高頻度に起こる。そのため創部が上皮化するまで合併症に注意し、長期間、厳格なフォローアップが必要となる。今回、前頭蓋底再建を伴う鼻副鼻腔未分化癌のサルベージ手術後に創部の感染、出血、髄液漏を認め、それに対して創部のデブリードマンと髄液漏閉鎖術を行った症例を経験した。サルベージ手術後の髄液漏閉鎖術では、過去の手術やCRTの影響で頭蓋底再建に用いる材料が限られ、症例ごとによく吟味して再建材料と再建方法を選択する必要がある。本症例では、頭蓋底の欠損部が小さく、髄液漏の流量も比較的少なかったため、free graftを用いた頭蓋底再建法を選択し、髄液漏を停止させることができた。(著者抄録)

Language：English   Publisher：Clinical Anatomy  

Endoscopic endonasal skull base surgery is increasingly prevalent, with its scope expanding from pathogens in the midline region to those in the paramedian region. Maximizing anterior sphenoidectomy is important for the median approach, and lateralizing the pterygopalatine fossa is crucial for the paramedian approach. Maximizing the surgical corridor in the nasal cavity and minimizing damage to neurovascular structures are vital for establishing a surgical field with minimal bleeding, ensuring safe, precise, and gentle procedures. However, the relationship between the maxillofacial and skull base bones in endoscopic endonasal skull base surgery is difficult to understand because these bones are intricately articulated, making it challenging to visualize each bone's outline. Understanding important bones and their related neurovascular structures is essential for all skull base surgeons to maximize the surgical corridor and minimize iatrogenic injury to neurovascular structures. This study aimed to elucidate the role of the palatine bone from a microsurgical anatomical perspective. Three dry skulls were used to demonstrate the structure of the palatine bone and its relationship with surrounding bones. A formalin-perfused cadaveric head was dissected to show the related neurovascular structures. The arteries and veins of the cadaveric heads were injected with red- and blue-colored silicon. Dissection was performed using a surgical microscope and endoscope. In addition, the utilization of the palatine bone as a landmark to identify neurovascular structures, which aids in creating a wider surgical field with less bleeding, was shown in two representative cases. The palatine bone consists of unique complex structures, including the sphenoidal process, ethmoidal crest, pterygopalatine canal, and sphenopalatine notch, which are closely related to the sphenopalatine artery, maxillary nerve, and its branches. The ethmoidal crest of the palatine bone is a well-known structure that is useful for identifying the sphenopalatine foramen, controlling the sphenopalatine artery and nerve, and safely opening the pterygopalatine fossa. The sphenoidal process of the palatine bone is a valuable landmark for identifying the palatovaginal artery, which is a landmark used to safely and efficiently expose the vidian canal. The sphenoidal process is easily cracked with an osteotome and removed to expose the palatovaginal artery, which runs along the pharyngeal groove, just medial to the vidian canal. By opening the pterygopalatine canal (also known as the greater palatine canal), further lateralization of the periosteum-covered pterygopalatine fossa contents can be achieved. Overall, the sphenoidal process and ethmoidal crest can be used as important landmarks to maximize the surgical corridor and minimize unnecessary injury to neurovascular structures.

DOI： 10.1002/ca.24170

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Language：English   Publisher：Otology and Neurotology  

Objective: Squamous cell carcinoma (SCC) of the external auditory canal has a favorable prognosis when complete resection with negative margins is achieved. Early diagnosis and timely referral to specialized centers are crucial. However, definitive diagnosis is often delayed due to challenges in timely referral and the need for multiple biopsies. This study aims to examine the diagnostic trajectory of SCC of the external auditory canal, focusing on the number of biopsies required and the process leading to definitive diagnosis. Study Design: Retrospective case review and descriptive study. Setting: Tertiary referral center. Patients: We conducted a retrospective case review at a tertiary referral center, analyzing 56 cases of SCC of the external auditory canal treated between January 2015 and February 2024. Intervention(s): Medical records were retrospectively reviewed. Main Outcome measure(s): The course of events leading up to their visit of our hospital, the number of biopsies performed to be diagnosed, and the histopathological findings. Results: The time from initial presentation to referral ranged from 1 to 785 days (mean: 170.6 d; median: 130 d). A definitive diagnosis was achieved with the first biopsy in 35 cases (62.5%), whereas 21 cases (37.5%) required multiple biopsies. Only 21.4% of the cases were definitively diagnosed at the initial presenting facility, whereas 32.1% were diagnosed at our hospital. More than 90% of the tumors were well-differentiated or well-to moderately/poorly differentiated SCC. The number of biopsies required to confirm a definitive diagnosis was significantly associated with longer delays in hospital referral (correlation coefficient: 0.3122, p = 0.0192). Two cases of the hyperkeratotic SCC were presented as representative cases in which a definitive diagnosis was challenging. Conclusion: Early diagnosis of SCC of the external auditory canal relies on thorough biopsy evaluation. Given the tumor's tendency for high differentiation, obtaining biopsy samples with clear malignant features is critical for making an accurate and timely definitive diagnosis.

DOI： 10.1097/MAO.0000000000004559

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Language：English   Publisher：Journal of Craniofacial Surgery  

Two widely used en bloc resection techniques for external auditory canal malignancies are lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR). STBR is a surgical procedure that requires a skull base team, whereas LTBR is a widely practiced procedure worldwide that can be completed as an otological procedure. In LTBR, the external auditory canal is removed en bloc with basic otological techniques, including mastoidectomy and extended posterior tympanotomy. However, detailed descriptions of the osteotomy technique for the anterior deep portion of the external auditory canal are scarce. The authors examined the most challenging site for separation in LTBR using 11 cadaveric specimens. The average 3.8 mm length of bone just anteroinferior to the tympanic membrane tends to be left disconnected. Thus, it is necessary to appropriately separate this area according to its anatomic variations to achieve a complete en bloc resection with negative margins.

DOI： 10.1097/SCS.0000000000011446

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Voice  

Introduction: Vocal distortion, also known as a scream or growl, is used worldwide as an essential technique in singing, especially in rock and metal, and as an ethnic voice in Mongolian singing. However, the production mechanism of vocal distortion is not yet clearly understood owing to limited research on the behavior of the larynx, which is the source of the distorted voice. Objectives: This study used high-speed digital imaging (HSDI) to observe the larynx of professional singers with exceptional singing skills and determine the laryngeal dynamics in the voice production of various vocal distortions. In addition, this study aimed to classify vocal distortions based on laryngeal dynamics. Study Design: Cross-sectional study. Methods: The dynamic behavior of the larynx of six singers (four males and two females) was recorded using HSDI, with the majority of recordings captured at frame rates exceeding 8000 fps. The audio signals were recorded simultaneously. The data were analyzed as topography, glottal area waveforms, long-term average spectra, and spectrograms. Results: Our analysis revealed that, based on the laryngeal vibration pattern, vocal distortion could be categorized into two primary groups: “periodic” and “aperiodic.” In the “periodic” distorted vocalizations, it was suggested that the glottal sound source containing overtone components is generated by vocal fold vibrations, and subharmonic components in the voice are the result of amplitude modulation of the glottal jet by vibrations in the supraglottic region. However, “aperiodic” distorted vocalizations were found to be generated by the vocal folds, which are the main source of noise and generate strong noise due to aperiodic chaotic oscillations of the vocal folds. Conclusion: The diversity of distorted vocalizations is due to the physiologically and acoustically complex mechanism of voice production in the larynx.

DOI： 10.1016/j.jvoice.2024.11.041

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

進行中下咽頭癌症例ではしばしば外側咽頭後リンパ節(ルビエールリンパ節,以下RLN;Rouviere lymph node)に転移を来すが,RLN転移病変に対する治療に関する報告は少なく,未だ統一した見解はない。今回,初回治療時にRLN転移を有した中下咽頭原発扁平上皮癌症例22例について検討した。原発巣を含む病変への初回治療内容は,手術11例/(化学)放射線療法11例であり手術例のうち3例でRLN転移病変を合併切除し,残る8例ではRLN転移病変は切除せず術後に放射線治療を行った。全体のRLN再発率は18.2%であり,RLN病変に対して(化学)放射線療法のみを行った症例でも比較的良好に制御されていた。一方,RLNの制御状況に関わらず,特に下咽頭癌症例では治療後の遠隔転移発生率が66.7%と高く予後不良であった。下咽頭癌症例ではより厳重な治療後の経過観察が必要である。(著者抄録)

Language：English   Publisher：Knowledge Enterprise Journals  

Background: Stuttering is a speech fluency disorder that can significantly affect quality of life. Among adults who seek consultations for stuttering, 40–60% have comorbid social anxiety disorder (SAD). The Liebowitz Social Anxiety Scale (LSAS) has been developed to assess the severity of SAD, while the overall assessment of the speaker’s experience of stuttering for adults (OASES-A) questionnaire can measure the broader impact of stuttering. However, some medical professionals lack knowledge of such questionnaires. / Aims: Here, we aimed to investigate the correlation between the severity of stuttering and the OASES-A, and between the OASES-A and the LSAS. / Methods: Overall, 51 adults who stutter were included in this study. Stuttering frequency was assessed using a Japanese test, whereas the OASES-A questionnaire captured the comprehensive impact of stuttering on the participants’ lives. The LSAS was used to measure the severity of social anxiety. Pearson’s correlation analysis was used to determine the relationship between the variables. / Results: The average stuttering frequency was 10%, and the mean OASES-A total score was 2.86. The mean total LSAS score was 51.5. While no significant correlation was found between stuttering frequency and OASES-A total scores, a significant correlation was noted between LSAS and OASES-A total scores. / Conclusion: This study found that stuttering frequency did not correlate with the OASES-A. Notably, a novel moderate correlation was identified between OASES-A and LSAS total scores. The LSAS may help to evaluate the challenges faced by people who stutter when the OASES-A is unavailable.

CiNii Research

Language：English   Publisher：Pathology Research and Practice  

Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA in situ hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.

DOI： 10.1016/j.prp.2024.155642

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Language：Japanese   Publisher：耳鼻と臨床会  

われわれ中耳真珠腫新鮮例に対し、原則として一期的に外耳道後壁保存鼓室形成術を行っており、乳突蜂巣の発育が不良な症例には外耳道後壁削除・乳突開放型の手術を選択している。真珠腫の分類や術式ごとの治療成績の検討のため、2013年1月から2020年12月までに初回手術を行った131例について聴力改善率と再発率について後方視的に検討を行った。聴力改善率については既報と遜色がなかったが、IV型症例では不良であった。再発率について、内視鏡による補助的な観察と、上鼓室の前方換気ルート開放の有用性に関して検討を行った。遺残再発率は、内視鏡導入後は有意差を認めないものの低下した。再形成再発は前方ルート開放を行った症例では少なかった。(著者抄録)

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

BACKGROUND/AIM: The benefit of neoadjuvant chemotherapy (NAC) in the treatment of head and neck squamous cell carcinoma (HNSCC) remains unclear. PATIENTS AND METHODS: We retrospectively collected 30 patients with HNSCC who had undergone radical resection after NAC. We pathologically evaluated the therapeutic response to NAC, and classified the residual tumor patterns. In addition, we compared the maximum horizontal diameter on pathology with imaging. RESULTS: The residual patterns were categorized as follows: 10 cases of shrunken type, 11 cases of mixed type, and seven cases of fragmented type. The majority of underestimation cases - those cases in which the maximum horizontal diameter measured on post-NAC imaging was less than the pathological size after resection - were multifocal residual lesions, with a tendency for more frequent "positive" or "close" surgical margins. CONCLUSION: The strategy of performing NAC to reduce resection volume is not appropriate, and resection margins should be based on the assessment before NAC.

DOI： 10.21873/anticanres.17289

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

症例は53歳男性で、左側舌の疼痛を主訴とした。左側口腔癌cT3N1M0の診断で左側舌可動部半側切除、左側頸部郭清、前外側大腿皮弁再建、気管切開術を施行し、術後はシスプラチン併用化学放射線療法を施行した。術後8ヵ月目に遠隔転移を認めたため緩和照射を開始し、終了翌日からニボルマブを導入した。ニボルマブ初回投与後11日目に口腔全体および咽頭から喉頭にかけて白色粘膜びらんが出現し、免疫チェックポイント阻害剤(ICI)による有害事象と同様の対応としてプレドニゾロン(PSL)とプロトンポンプインヒビター投与を開始した。ニボルマブ2回目投与後4日目に粘膜炎が急激に再増悪し、ICI関連口腔咽頭粘膜炎と確定診断した。オピオイドによる疼痛コントロールを行いつつ経口流動食と補助食品で栄養確保し、ニボルマブ2回目投与後2ヵ月目に粘膜びらんはほぼ消退したが、反復する嚥下性肺炎により呼吸不全が進行し、ニボルマブ初回投与後3ヵ月半目に死亡した。

Language：English   Publisher：Auris Nasus Larynx  

Objective: The “Summary of Japanese clinical practice guidelines for Bell's palsy (idiopathic facial palsy) - 2023 update edited by the Japan Society of Facial Nerve Research” aims to review the latest evidence regarding the treatment of Bell's palsy and to provide appropriate recommendations. Method: Regarding the treatment of Bell's palsy, a guideline panel identified key clinical questions using an analytic PICO framework. The panel produced recommendations following the standards for trustworthy guidelines and the GRADE approach. The panel considered the balance of benefits, harm, and preferences when making recommendations. Results: The panel identified nine key clinical questions: systemic (high/standard dose) corticosteroids, intratympanic corticosteroids, systemic antivirals, decompression surgery, acupuncture, physical therapy, botulinum toxin, and reanimation surgery. Conclusion: These guidelines strongly recommend systemic standard-dose corticosteroids for the clinical management of Bell's palsy. Other treatments are weakly recommended due to insufficient evidence. The absolute risk reduction of each treatment differed according to the disease severity. Therefore, physicians and patients should decide on treatment based on the disease severity.

DOI： 10.1016/j.anl.2024.07.003

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Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.67.409

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.67.395

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.67.492

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.67.440

CiNii Research

Language：English   Publisher：Communications Medicine  

Background: Speech discrimination (SpD) is exacerbated by hearing loss, but the relationship between pure-tone audiometry (PTA) and SpD is poorly described and understood in the aging process. It is also unclear whether severity of left-right (L-R) differences in PTA threshold disproportionately affects SpD. Methods: We conducted a retrospective cross-sectional study of a broad age range (10–99 years) of patients in Japan. Demographic data, SpD, and PTA threshold data were collected for each patient and side (L-R). We evaluated the association between chronological age and overall SpD, and SpD according to severity of PTA-threshold difference for ear pairs. Asymmetries in L-R PTA thresholds were stratified into four equally spaced categories: <10dB L-R difference to ≥40 dB L-R difference. Results: Among the 2760 eligible participants, data from 5508 ears are analyzed. Overall SpD gradually decreases with age, with SpD scores in the oldest groups being significantly worse (Kruskal-Wallis followed by Dunn’s test; p < 0.0001) than those of the youngest group. Comparison of worse-hearing ears to better-hearing ears within the same severity of hearing impairment reveals significant differences on SpD in ears that have moderate or severe hearing impairment (p < 0.0001). Post-hoc analysis identifies significant differences in SpD between the worse-hearing ears and the better-hearing ears that have hearing differences of 20 dB or more. Conclusions: SpD is dramatically affected by age and asymmetrical hearing. Therefore, appropriate audiological interventions should be proactively considered according to an individual’s hearing level, age, and difference in L-R hearing levels.

DOI： 10.1038/s43856-024-00587-8

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Language：English   Publisher：Journal of Neurosurgery Case Lessons  

GROUND The endoscopic endonasal approach to paramedian skull base lesions has garnered increasing attention in recent reports. However, ll a challenging approach. While the primary objective of the approach is the maximal removal of tumors through a minimally invasive procedure, sions of the approach rarely include information about the maximum preservation of nasal structures. This study aimed to retrospectively review nical outcomes of patients who had undergone an endoscopic endonasal approach to paramedian lesions, describe the technical and anatomical es related to this approach at the authors’ institution, and discuss the maximal preservation of nasal structures. RVATIONS The authors conducted a descriptive retrospective study of 17 surgical cases of paramedian endoscopic endonasal approaches med jointly by otolaryngologists and neurosurgeons from August 2018 to August 2022 at a tertiary hospital. ONS The approach to the paramedian region of the skull base was examined. Creating an appropriate corridor to maximize the surgical field is tial to allow a safe and accurate procedure. From an otolaryngologist’s perspective, the endoscopic modified medial maxillectomy is an essential dure that maximizes the surgical corridor and maximally preserves nasal morphology.

DOI： 10.3171/CASE24218

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Language：English   Publisher：Knowledge Enterprise Journals  

Stuttering (childhood-onset fluency disorder) is characterized by disruptions in speech fluency. In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the diagnosis of social anxiety disorder in people who stutter is prohibited. However, the introduction of the DSM-5 enabled the diagnosis of social anxiety disorder concurrently with stuttering, making the concerns of people who stutter more visible. Understanding the performance-only subtype of social anxiety disorder introduced in DSM-5 can prevent underestimating the concerns of people who stutter and lead to appropriate support. While cognitive-behavioral therapy is effective in treating stuttering, accumulating evidence for pharmacotherapy is also necessary.

CiNii Research

Language：English   Publisher：Cancers  

The optimal timing for actively discontinuing immune checkpoint inhibitor therapy in long-term responders with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains unresolved. We conducted a retrospective study of 246 patients with R/M HNSCC treated with nivolumab to determine the optimal timing to actively discontinue nivolumab therapy. We examined the point at which progression-free survival (PFS) plateaued in all cases. We compared the prognosis of 19 (7.7%) ongoing cases and 227 (92.3%) discontinued cases and analyzed treatment duration and treatment-free interval (TFI). The 6-year overall survival was 11.8% (median, 12.1), and the 6-year PFS was 15.3% (median, 3.0). The PFS curve remained stable for 3 years. The median duration of nivolumab treatment was 2.9 months (range 0.03–81.9): Ongoing group, 41.8 (5.6–81.9); Decision group, 36.8 (4.0–70.1); Toxicity group, 30.6 (2.8–64.8); and progressive disease group, 2.0 (0.03–42.9). TFI in the Decision group was 15.1 months (0.6–61.6) and 30.6 months (2.8–64.8) in the Toxicity group. Long-term responses in R/M HNSCC patients treated with nivolumab are rare but gradually increasing. For this patient group, our best estimate of the optimal time to end treatment is 3 years, as the PFS in this study reached a plateau at that timepoint.

DOI： 10.3390/cancers16142527

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PubMed

Language：English   Publisher：Nature Communications  

The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.

DOI： 10.1038/s41467-024-49375-x

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PubMed

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

Spontaneous cerebrospinal fluid (sCSF) leaks are rare, and their diagnosis and treatment often present significant challenges. This paper discusses and reports cases experienced at our facility. We retrospectively reviewed three of five cases of sCSF leaks experienced at the Department of Otolaryngology and Head and Neck Surgery, Kyushu University, from December 2020 to December 2022, excluding CSF otorrhea. All three patients were female; their mean age was 56 years (44-71 years). Two of the three patients were obese (first degree), and one was average weight (according to the criteria of the Japan Society for the Study of Obesity). Two patients had hypertension, and one had sleep apnea syndrome as an underlying disease. In all cases, leakage sites, which were all the cribriform plate, can be endoscopically identified, and all could be closed by an endoscopic intranasal approach. We reviewed cases of sCSF leaks. Although some patients had difficulty identifying the leakage site in a narrow and complex nasal cavity, an endoscopic survey was useful in identifying the leakage site. All cases were closed and there were no signs of recurrence. Identifying the site of leakage and selecting the appropriate closure method depending on the extent of the leakage is essential in treating such cases.

DOI： 10.7759/cureus.62042

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PubMed

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder caused by APC mutations. It is characterized by the presence of more than 100 adenomatous polyps in the large intestine. In addition to colorectal adenomas, FAP is associated with various neoplastic lesions, including thyroid cancer. We experienced two cases of papillary thyroid carcinoma associated with FAP in a young woman who had been diagnosed with FAP and colorectal cancer when her papillary thyroid carcinoma was first diagnosed. The second patient had multiple lesions in both lobes, and cervical lymph node metastasis was suspected; therefore, total thyroidectomy and bilateral cervical dissection were performed. The multifocal and multicentric nature of papillary carcinoma of the thyroid gland associated with FAP suggests that total thyroidectomy is advisable.</p>

DOI： 10.11334/jibi.70.3_150

CiNii Research

Language：English   Publisher：Journal of Immunotherapy  

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.

DOI： 10.1097/CJI.0000000000000503

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PubMed

Language：English   Publisher：Molecular Genetics and Genomic Medicine  

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, β-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

DOI： 10.1002/mgg3.2427

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PubMed

Language：English   Publisher：Pnas Nexus  

The activation and differentiation of B cells into plasma cells (PCs) play critical roles in the immune response to infections and autoimmune diseases. Toll-like receptor 9 (TLR9) responds to bacterial and viral DNA containing unmethylated CpG motifs and triggers immune responses in B cells; however, abnormal recognition of self-DNA by TLR9 can cause autoimmune diseases. When stimulated with TLR9 agonists, follicular (FO) B cells, a subset of B cells residing in the FO regions of secondary lymphoid organs, exhibit a propensity for activation but fail to give rise to PCs. The factors that enable the transition of TLR9-activated FO B cells from activation to differentiation into PCs remain unclear. In this study, we show that type I interferon-alpha (IFNα) signaling causes FO B cells activated by CpG stimulation to differentiate into PCs. Although CpG stimulation alone only temporarily increased interferon regulatory factor 4 (IRF4) expression in FO B cells, co-stimulation with both CpG and IFNα enhanced and maintained high IRF4 expression levels, ultimately enabling the cells to differentiate into PCs. Overexpression of IRF4 in FO B cells results in CpG-induced PC transition without IFN signaling. Furthermore, co-stimulation of TLR9 and IFNα receptors significantly enhanced mammalian target of rapamycin (mTOR) signaling, which regulates IRF4 expression and PC generation. These findings suggest that IFNα may play a key role in promoting the fate of PC differentiation in FO B cells activated by TLR9 stimulation.

DOI： 10.1093/pnasnexus/pgae152

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Language：Japanese   Publisher：日本口腔・咽頭科学会  

口腔領域の転移性悪性腫瘍は,全口腔悪性腫瘍の約1%で,中でも膵癌の舌転移は極めて稀とされる.今回,膵癌舌転移の1例を経験したので報告する.症例は56歳男性,主訴は舌痛,舌腫瘤.X年膵癌cT3N1aM0,StageIIBの診断で膵全摘術を施行.X+2年縦隔リンパ節再発を来し,緩和化学療法を開始した.PDによるレジメン変更及び縦隔病変への放射線治療により,病勢はコントロールできていた.X+4年,舌に疼痛を伴う腫瘤性病変が出現した.各種検査で膵癌舌転移と診断した.舌腫瘍は増大傾向で疼痛悪化に伴う経口摂取困難が生じていたため,緩和治療として舌部分切除術を施行した.舌痛は改善,経口摂取も良好となった.今回の外科治療は,がん終末期のQOL改善に寄与できた.(著者抄録)

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PubMed

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>Cysts of different embryological etiologies may occur in the head and neck region, including congenital cysts, such as thyroglossal duct cysts, branchial cleft cysts, and lymphangiomas; and acquired cysts, such as plunging ranulas. The treatment of these cysts can be divided into two main categories: excision and sclerotherapy, such as OK-432. We herein report two cases in which OK-432 was effective in treating cysts in the pharynx that were refractory to repeated surgical removal and multiple puncture drainage. Case 1 was a woman in her 30s who had a cyst at the root of the tongue that had been resected twice but had recured within a few months. Case 2 was a woman in her 60s who had undergone repeated surgical procedures for a cyst on the root of the tongue over 30 years ago both cases were treated with OK-432, which allowed the cyst to shrink and remain in a reduced size. Some cysts in the head and neck region are rare, but they recur repeatedly and are refractory, making them difficult to treat. Sclerotherapy with OK-432 may be an effective outpatient treatment option for these cases that are difficult to treat surgically.</p>

DOI： 10.11334/jibi.70.1_20

CiNii Research

Language：Japanese   Publisher：日本顔面神経学会  

顔面神経麻痺患者の苦痛を評価するツールとして、言語聴覚士としての経験に基づき、従来のFaCE Scaleに5項目を追加したFaCE"ちどり版"を使用している。5項目の内訳は「顔が動きにくいためイライラする」「顔の動きにくさを気にせずにはいられない」「まぶたがかぶさって見えにくい」「洗顔剤やシャンプーが目にしみる」「顔が動きにくいため気分が落ち込みがちになる」である。今回、当院で2017～2022年に顔面神経減荷術を受けた患者のうち術後6ヵ月以上経過を確認できた7例を対象とし、ちどり版のスコアと、柳原法、Sunnybrook法のスコアとの相関性について検討した。結果、柳原法スコア、Sunnybrook法の運動スコアとの間に有意な正の相関が認められ、Sunnybrook法の安静時スコアとの間に有意な負の相関が認められた。

Language：Japanese   Publisher：日本顔面神経学会  

顔面神経麻痺は症状が明確であるため患者は発症早期に医療機関を受診することが多いが、種々の理由から受診が遅れたり、適切な時期に必要な治療を受けられなかったりするケースも見受けられる。今回、脳梗塞に伴う末梢性顔面神経麻痺の発症から1ヵ月以上経過して当院に転院となった後、適切な評価およびリハビリテーションを行ったことで良好な結果が得られた症例を提示し、専門医療機関の存在意義と病診連携の重要性について述べた。

Language：Japanese   Publisher：耳鼻と臨床会  

頭頸部領域には発生学的に病因の異なる嚢胞が生じることがあり、正中頸嚢胞、側頸嚢胞、リンパ管腫/奇形などの先天性嚢胞や、ガマ腫などの後天性嚢胞が挙げられる。これら嚢胞の治療法としては、手術摘出とOK-432(ピシバニール)に代表される硬化療法の2つに大別される。手術摘出や複数回の穿刺排液を繰り返すも難治性であった、咽頭に発生した嚢胞に対し、OK-432(ピシバニール)を投与し、効果を認めた2例を経験したので報告する。症例1は30代の女性で、舌根の嚢胞を2回切除するも数ヵ月で再増大した症例である。症例2は60代の女性で、30年以上にわたり舌根の嚢胞に手術処置を繰り返した症例である。2例ともOK-432(ピシバニール)投与で、縮小した状態が維持できるようになった。頭頸部領域に発生する嚢胞の中には、まれではあるが複数回再発し難治性のものもあり、この場合治療に難渋することとなる。外科的治療法で対応が困難な症例において、OK-432(ピシバニール)による硬化療法は、外来で対応可能な、かつ効果的な治療選択肢の一つとなり得ると思われた。(著者抄録)

Language：Japanese   Publisher：日本顔面神経学会  

人工内耳(CI)の添付文書では、植込装置付近での神経刺激装置や電気メスの使用はインプラントの障害や損傷の可能性があり禁忌とされている。今回、高度難聴でCI植込み術を受けている患者がBell麻痺を発症し精査目的で当科に紹介された。前医では柳原法6/40点、当科初診時には14/40点と改善を認めたものの、客観的評価との整合性を確認すべくENoG検査を実施することとした。実施にあたり、同検査の可否についてCIのメーカーに問い合わせたところ、回答は「神経刺激とインプラント間の電流経路の特定が困難なため安全な距離は不明」「バイポーラー型電気メスを参考にインプラントの電極から3cm離せば可能であるが、医療機関の判断で行う」とのことであった。これらを踏まえ、ENoG検査は可能であると判断し、実施した。そのさい以下の注意・工夫を行い、検査を無事に施行できた。1)顔面神経刺激時にはCI体外機器を外す。2)体外機器を外すと意思疎通困難になることから、文字による情報補償のためのタブレット端末を配置する。3)検査前後にCIのプログラミングソフトでインピーダンス値を測定し、変化がないことを確認する。

Language：Japanese   Publisher：日本顔面神経学会  

顔面神経麻痺患者の苦痛を評価するツールとして、言語聴覚士としての経験に基づき、従来のFaCE Scaleに5項目を追加したFaCE Scale"ちどり版"を使用している。5項目の内訳は「顔が動きにくいためイライラする」「顔の動きにくさを気にせずにはいられない」「まぶたがかぶさって見えにくい」「洗顔剤やシャンプーが目にしみる」「顔が動きにくいため気分が落ち込みがちになる」である。今回、当院で2018～2022年に加療されたHunt症候群患者のうち、発症直後と1年以上経過時に"ちどり版"とFaCE Scale原版による評価が行えた14例を対象として"ちどり版"の有用性を検討した。方法は、FaCE Scaleの6分野ごとに、発症直後と1年以上経過時での"ちどり版"による評価の変化と原版による評価の変化を比較した。その結果、6分野のうち「顔の動き」と「社会活動」は"ちどり版"のほうが鋭敏に改善度を評価できると考えられた。

Language：Japanese   Publisher：Japan Otological Society  

<p>Malignant tumors of the temporal bone such as squamous cell carcinoma of the external auditory canal are extremely rare. Reportedly, en bloc resection with negative margins is the most reliable treatment strategy for these lesions. Lateral temporal bone resection (LTBR) and subtotal temporal bone resection (STBR) represent en bloc resection methods for malignant tumors of the external auditory canal. Retrospective single-center observational studies have reported that treatment results tend to be better at facilities that perform en bloc resection. However, owing to technical difficulties associated with the surgical techniques, studies recommend piecemeal tumor resection in patients who require treatment beyond classical/conventional LTBR (cLTBR). En bloc resection facilitates objective evaluation of histologically negative margins, whereas the surgeon’s subjective judgment is highly likely to affect margin evaluation in cases of piecemeal resection, and definitive histopathological evaluation of postoperative resection margins becomes difficult. Several studies have reported that tumor control using postoperative adjuvant therapy is challenging in patients with positive resection margins. However, appropriate additional postoperative adjuvant therapy is essential to prevent recurrence in patients with positive resection margins. Histopathological evaluation of resection margins is important for prompt treatment decision-making regarding additional postoperative chemo(radio)therapy. From this perspective, en bloc resection without exposure of the malignant tumor is a preferred therapeutic option.</p><p>Various osteotomy lines are used based on tumor extension; therefore, methods of en bloc resection of the temporal bone are not merely categorized into LTBR and STBR but can be classified as follows: (a) cLTBR, (b) extended LTBR, (c) modified STBR, and (d) cSTBR. En bloc resection of the temporomandibular joint is a challenging surgical procedure; therefore, cSTBR and concomitant en bloc resection of the temporomandibular joint represents one of the most technically demanding procedures in temporal bone surgery. Although some information on cSTBR is available in textbooks and articles, it is unclear whether all surgical techniques for STBR are clearly described. In this report, we outline cSTBR performed at our hospital.</p>

DOI： 10.11289/otoljpn.34.143

CiNii Research

Language：Japanese   Publisher：Japan Society for Head and Neck Cancer  

Patients with advanced pharyngeal carcinoma often develop metastasis to the lateral retropharyngeal lymph node （RLN; Rouvière lymph node）, but there are few reports on the treatment of RLN metastatic lesions, and no unified opinion has been reached. In this study, we reviewed 22 cases of squamous cell carcinoma of the oropharyngeal and hypopharynx that had RLN metastasis at the time of initial treatment at our hospital. Initial treatment included 11 cases of surgery and 11 cases of chemoradiotherapy. Of the patients who underwent surgery, 3 patients had RLN metastatic lesions resected and in the remaining 8 patients, RLN metastatic lesions were not resected and postoperative radiation therapy was administered. The recurrence rate of RLN was 18.2％ of all cases, and the control of RLN lesions was relatively good even in cases treated with chemoradiotherapy alone. Regardless of whether the RLN was controlled after treatment, the distant metastasis rate was especially high for hypopharyngeal cancer at 66.7％, indicating a poor prognosis. Therefore, more rigorous metastatic follow-up is required after treatment in cases of hypopharyngeal cancer.

DOI： 10.5981/jjhnc.50.298

CiNii Research

Language：English   Publisher：Cancer Diagnosis and Prognosis  

Background/Aim: Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, with most recurrences occurring within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment is associated with prognosis in patients with HNSCC, further investigation is needed. Patients and Methods: Patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n=500). Early recurrence (ER) was defined as disease recurrence within six months of radical treatment, whereas late recurrence (LR) was defined as recurrence after more than six months. Continuous variables were assessed using the Mann–Whitney U-test and categorical variables were assessed using Fisher’s exact test. Results: A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing ER (recurrence within two to six months) and LR (recurrence after six months), respectively. Multivariate analyses identified two independent risk factors for poor prognosis: ER [hazard ratio (HR)=3.200, 95% confidence interval (CI)=1.570-6.521, p=0.001] and absence of radiotherapy (HR=0.374, 95%CI=0.191-0.733, p=0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in these patients. Conclusion: The selection of treatment for patients with recurrent head and neck squamous cell carcinoma should consider the timing of recurrence, the initial treatment regimen, and the strategy for changing salvage therapy depending on the recurrence status.

DOI： 10.21873/cdp.10378

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Diagnosis and Prognosis  

BACKGROUND/AIM: There is limited evidence about the significance of head and neck surgical observation at the time of diagnosis and follow-up of oral cancer after treatment. The aim of this study was to elucidate the prognosis and prognostic factors of oral squamous cell carcinoma (OSCC), analyze cases of double cancers, and highlight the importance of examinations during both diagnosis and post-treatment for OSCC. PATIENTS AND METHODS: We performed a retrospective analysis of 272 OSCC cases treated for the first time during a 10-year period from April 2013 to March 2023 at Kyushu University Hospital. Information obtained in the clinical setting, such as age, stage, prognosis, and presence of double cancers, was used in the analysis. RESULTS: The mean age of 272 patients was 69 years; 203 patients were males and 69 were females. The most common oral cancer sites were the tongue (54.4%). The 5-year overall survival rate was 63.8%. Double cancer was found in 93 patients (34.2%). Synchronous double cancers were found in 38 patients (14.0%), 50% of whose cancer types were head and neck cancers. CONCLUSION: We analyzed 272 OSCC patients treated at the Kyushu University Hospital, and the results were comparable to those reported by other institutions. Tumor site, age, and stage were identified as prognostic factors. Half of the patients with synchronous double cancers had head and neck cancer, and 3-10% of patients with double cancers after treatment for OSCC also had head and neck cancer, suggesting the importance of otorhinolaryngological observation at the time of the diagnosis and after treatment.

DOI： 10.21873/cdp.10294

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Language：English  

[This corrects the article DOI: 10.1371/journal.pone.0271907.].

DOI： 10.1371/journal.pone.0303720

PubMed

Publisher：Science Advances  

Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common group of cancers in the world, and patients have a poor prognosis. Here, we present data indicating that YAP1 may be a strong driver of the onset and progression of oral SCC (OSCC), a major subtype of HNSCC. Mice with tongue-specific deletion of Mob1a/b and thus endogenous YAP1 hyperactivation underwent surprisingly rapid and highly reproducible tumorigenesis, developing tongue carcinoma in situ within 2 weeks and invasive SCC within 4 weeks. In humans, precancerous tongue dysplasia displays YAP1 activation correlating with reduced patient survival. Combinations of molecules mutated in OSCC may increase and sustain YAP1 activation to the point of oncogenicity. Strikingly, siRNA or pharmacological inhibition of YAP1 blocks murine OSCC onset in vitro and in vivo. Our work justifies targeting YAP1 as therapy for OSCC and perhaps HNSCC, and our mouse model represents a powerful tool for evaluating these agents.

DOI： 10.1126/sciadv.adn0844

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

Squamous cell carcinoma of the external auditory canal (EACSCC) is an extraordinarily rare and aggressive malignant disease. Establishment of EACSCC cell line with robust molecular characteristics is essential for the basic and translational research of EACSCC. Here, we show the newly established EACSCC cell line SCEACono2, derived from a patient with well-to-moderately differentiated EACSCC. We analyzed histologic and genetic features of SCEACono2 hiring multiple experiments, including next-generation sequencing (NGS). Immunocytochemical staining of SCEACono2 showed positivity of p53 and SCC1/2. Furthermore, SCEACono2 exhibited a unique characteristic that cytokeratin, vimentin as well as cancer stem cell markers (CD44, CD133, ALP and Oct3/4) were positive. SCEACono2 had an ability to form tumors at the temporal lesion xenograft nude mice model. NGS revealed that SCEACono2 harbored the somatic mutations of TP53 (p.G245S) and NOTCH1 (p.A465T). RNA-seq and downstream bioinformatics analysis revealed significant enrichment of genes involved in inflammation and cell adhesion in SCEACono2 compared to SCC-9 and HSC-4. STR profiling indicated no evidence of cross-contamination. In conclusion, SCEACono2 could serves as a promising and robust research resource of EACSCC in vitro and in vivo.

DOI： 10.1038/s41598-023-46926-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Surgery Case Reports  

INTRODUCTION: Cholesterol granulomas, which frequently present in the temporal bone of the skull, are recognized as benign lesions occurring due to chronic inflammation or hemorrhage. However, cholesterol granuloma of the mediastinum is extremely rare. PRESENTATION OF CASE: An asymptomatic 43-year-old man with an incidental finding of anterior mediastinal mass by positron emission tomography scan was referred to our hospital. Preoperative computed tomography showed a well-circumscribed nodule 2 cm in size in the anterior mediastinum. A total tumor resection through a suprasternal approach was performed. Microscopically, numerous cholesterol clefts with an alveolar-like growth pattern and foreign body reaction were observed, indicating a pathological diagnosis of cholesterol granuloma. DISCUSSION: Cholesterol granuloma is generally thought to be initiated by cell degeneration and hemorrhage resulting from trauma or inflammation. The patient's long-term rugby experience may have played a role in the development of cholesterol granuloma. It is difficult to diagnose a cholesterol granuloma based on preoperative imaging alone, and anatomy often makes preoperative biopsy or cytology difficult. CONCLUSION: Complete resection and pathological examination may be unavoidable for diagnosis and treatment.

DOI： 10.1016/j.ijscr.2023.108852

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PubMed

Language：Japanese   Publisher：(一社)日本耳科学会  

細径の蝸牛軸巻き付き型の人工内耳電極は挿入時に蝸牛内で屈曲(tip fold-over)することがある.この問題は電極が曲がる向きと蝸牛が曲がる向きが一致しないミスアライメントという状態のときに起こりやすい.このため,執刀医は電極のカイル平面をなるべく蝸牛のコイル平面に一致させて電極を挿入する必要がある.われわれは,手術中に視認できるキヌタ骨を利用して蝸牛コイル平面を想定する方法を検討した.2017年から2021年の期間に,一人の執刀医が施行した人工内耳植込み術症例のうち内耳奇形症例を除外した65耳(右29耳,左36耳)について検討した.キヌタ骨平面と蝸牛コイル平面が為す角度をキヌタ-蝸牛角と定義し集計した.キヌタ-蝸牛角は平均では34.6°であった.左右および手術時年齢による統計的な有意差は見られなかった.本研究により,手術中に確認できるキヌタ骨平面を利用して蝸牛コイル平面を正確に想定することが可能とわかった.(著者抄録)

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.66.409

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.66.442

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.66.407

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.66.401

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.66.405

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Journal of Surgical Pathology  

The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis ( P =0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis ( P =0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.

DOI： 10.1097/PAS.0000000000002086

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PubMed

Language：English   Publisher：In Vivo  

Background/Aim: In recent years, individual patient cancer genomic profiling (CGP) has become more accessible, allowing determination of therapeutic strategies using driver gene mutations in cancer therapy. However, this precision oncology approach, tailored to specific patients, remains experimental. In this study, we verified the feasibility and benefit of using CGP to guide treatment of malignant head and neck tumors. We aimed to evaluate the profiling and clinical courses of patients with head and neck malignancies who underwent CGP and determine the extent to which CGP for head and neck malignancies has resulted in beneficial drug administration. Patients and Methods: We analyzed CGP results, prognosis, and drug administration status in 27 patients. These patients had completed (or were expected to complete) standard therapy or had rare cancers without standard therapy. Results: At least one somatic actionable gene alteration was seen in 25 (92.6%) patients, with a median number of actionable alterations per patient of 4 (range=0-11). Drugs in clinical trials were recommended to 22 (81.5%) patients, but none could participate. However, 3 patients (11.1%) could use approved drugs off-label based on CGP results. The most common genetic abnormality was TP53 (66.7%), with TP53 mutations leading to poor prognosis. Conclusion: CGP is clinically useful and serves as a bridge to increase the number of therapeutic options. However, candidate drugs confirmed using CGP may be ineffective when administered. Therefore, oncologists should not blindly accept CGP therapeutic recommendations but should make recommendations that lead to optimal therapies after proper verification.

DOI： 10.21873/invivo.13312

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PubMed

Language：English   Publisher：In Vivo  

Background/Aim: Pembrolizumab monotherapy and pembrolizumab with chemotherapy (combination therapy) are standard treatments for recurrent and metastatic head and neck squamous cell carcinoma (R/M-HNSCC). This study aimed to explore which of the two, pembrolizumab monotherapy or combination therapy is superior for long-term use. Patients and Methods: Participants of the study were 139 patients with histologically confirmed squamous cell carcinoma who had been treated with pembrolizumab monotherapy or combination therapy at the Kyushu University and related facilities. We analysed differences regarding long-term survival rate and adverse events (AEs) between the pembrolizumab monotherapy and combination therapy groups. Results: The overall 2-year progression-free survival and 2-year overall survival were 28.6% and 41.8%, respectively; these results were not significantly different between the two groups. Patients in the monotherapy group with AEs had a significantly better prognosis than those without AEs (in both the monotherapy and combination

DOI： 10.21873/invivo.13318

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PubMed

Language：English   Publisher：Cancers  

Background: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. Methods: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Results: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Conclusions: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

DOI： 10.3390/cancers15174289

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PubMed

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>Granulomatosis with polyangiitis (GPA) is a rare multi-system disease characterized by necrotic and granulomatous changes of the respiratory tract, kidneys, and other organs. The most common initial symptom of this disease is necrotizing granuloma in the nasal and paranasal cavity, and oral lesions are rare. Strawberry gums is an oral lesion and a characteristic sign of GPA. While this feature is rare, it is characteristic and can serve as a clinical indicator of disease occurrence. We herein report a case of strawberry gums as the first presenting sign of GPA. The patient was a 24-year-old woman who was referred to our hospital because of gingival pain. The gingival surface appeared granular, resembling an over-ripe strawberry. Based on the clinical, laboratory, imaging, and histopathological findings, a diagnosis of GPA was made. The patient responded very well to treatment with steroids and immunosuppressants, and the strawberry gums disappeared. The diagnosis was established based on the finding of strawberry gums.</p>

DOI： 10.11334/jibi.69.4_325

CiNii Research

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

Background: Stuttering is a childhood-onset fluency disorder. Part of the counseling for middle and high school students with persistent stuttering is related to school refusal. Anxiety disorders are known to contribute to school refusal. However, it is not known whether social anxiety disorder (SAD) is a factor in school refusal among adolescents who stutter. Methods: In our first study, we examined the relationship between school refusal and SAD in 84 middle and high school students who stutter; 26% of the 84 students were in the school refusal group and the remaining 74% were in the school attendance group. The second study examined whether SAD was associated with 10 factors related to speech and stuttering frequency using the Japanese version of the Liebowitz Social Anxiety Scale for Children and Adolescents to determine the presence of SAD. Of the 84 students in the first study, 40 participated in the second study. Results: The school refusal group of adolescents who stutter had significantly higher rates of SAD than the school attendance group. Fifty percent of adolescents who stutter met the criteria for SAD. Moreover, adolescents who stutter with SAD had significantly higher scores on the items “When speaking in public, do you experience tremors in your limbs?” and “After you stutter, do you have negative thoughts about yourself?” than the adolescents who stutter without SAD. Conclusions: When examining adolescents who stutter, checking for comorbid SAD may lead to better support. Moreover, noticing their repetitive negative thinking, nervousness, and trembling during speech may help to resolve SAD.

DOI： 10.1111/ped.15622

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PubMed

Language：English   Publisher：Ear Nose and Throat Journal  

Objective: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs. Methods: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed. Results: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively. Conclusions: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended.

DOI： 10.1177/01455613211013084

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Scopus

PubMed

Language：Japanese   Publisher：耳鼻と臨床会  

多発血管炎性肉芽腫症(granulomatosis with polyangiitis;GPA)は上気道や肺の壊死性肉芽腫性血管炎、糸球体腎炎、中・小血管の血管炎を臨床病理的特徴とする疾患である。本疾患の初発症状が上気道に高頻度で認められることから、耳鼻咽喉科医がその診断や治療に重要な役割を担う。口腔内症状が出現することはまれとされているが、歯肉にはstrawberry gumと称される本疾患に特徴的な病変を生じることが知られている。今回われわれはstrawberry gumが初発症状となりGPAの早期診断に至った症例を経験したため報告する。症例は24歳、女性。2週間続く歯肉の腫脹を主訴に、近医歯科より当院を紹介受診された。歯肉に特徴的な点状出血を伴う腫脹を認め、strawberry gumの所見と考えた。さらに鼻前庭に粘膜炎症、CTで肺結節陰影を認め、歯肉生検の結果、GPAの診断に至り、ステロイドと免疫抑制剤の併用療法で改善に至った。特徴的な歯肉病変であるstrawberry gumがGPAの早期診断に重要な手掛かりとなった。日常診療において着目すべき所見であると考える。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Clinical Medicine  

BACKGROUND: Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. METHODS: We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. RESULTS: We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. CONCLUSIONS: Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant.

DOI： 10.3390/jcm12134290

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PubMed

Language：English   Publisher：ORL  

Introduction: Type I thyroplasty is one of the most useful surgeries for unilateral vocal fold paralysis. The study objective was to determine whether type I thyroplasty is safe and perioperative antithrombotic management is acceptable in patients undergoing antithrombotic therapy. Methods: This is a single-hospital retrospective cohort study. The records of 204 patients who underwent type I thyroplasty at a Japanese university hospital, between 2008 and July 2018 were reviewed. We compared the prothrombin time international normalized ratio, prothrombin time, operative time, intraoperative blood loss, and intra- and postoperative complications between patients who did and did not receive antithrombotic therapy. Results: Of 204 patients, 51 (25%) received antithrombotic therapy (antithrombotic group). The remaining 153 patients were assigned to the control group. There were no significant differences in operative time, intraoperative blood loss, or intraoperative complications between the two groups. Sixteen (31%) patients in the antithrombotic group had a hemorrhage or hematoma in the vocal fold mucosa postoperatively, no patient had airway obstruction necessitating tracheostomy, and all patients recovered with follow-up observation only. There were no cases of intraoperative or postoperative complications, such as ischemic heart disease, ischemic stroke, or deep vein thrombosis. Conclusion: Type I thyroplasty with careful pre- and postoperative management is safe in patients undergoing antithrombotic therapy.

DOI： 10.1159/000529905

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PubMed

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

炎症性筋線維芽細胞性腫瘍(Inflammatory myofibroblastic tumor:IMT)は,炎症細胞浸潤と紡錘形細胞の増生を特徴とする稀な中間悪性腫瘍である。3例の喉頭IMTを報告する。1例目は60歳男性で,声帯腫瘍に対し直達喉頭鏡下腫瘍摘出術を施行。2例目は53歳男性で,同様に摘出術を施行した。3例目は40歳男性で,声門下腫瘤の生検のみ施行した。全例FISH法にてALK融合遺伝子を確認しIMTと診断した。治療は外科的切除が第一選択だが,緩徐な増大であることが多く,経過観察に留めることもある。しかし喉頭IMTは,急速増大し窒息に至ることもあり,適切な治療時期の選択が重要である。(著者抄録)

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>We herein report a case series of 18 cochlear implant users who underwent magnet resonance imaging (MRI). The loci of imaging were head/neck (9 cases), thoracic vertebrae (2 cases), shoulder (1 case), liver (1 case), lower vertebrae (2 cases), whole vertebrae (1 case), and pelvis (2 cases). Nine cases had MRI images that contains artifacts caused by the implanted device. Four cases experienced device-related, MRI-derived complications, and one of them underwent magnet replacement surgery. Among the different MRI sequences, diffusion-weighted images and apparent diffusion coefficient (ADC) maps were more negatively influenced by the magnet than T1- or T2-weighted or MR angiography images. Understanding the artifact size and affected structures when MRI is performed on cochlear implant users is useful for determining the indications of MRI and magnet removal surgery, not merely for otolaryngologists but for any healthcare professionals.</p>

DOI： 10.11334/jibi.69.3_153

CiNii Research

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

The jugular foramen harbors anatomically complex bony, venous and neural structures. It is closely associated with small canals including the mastoid, tympanic, and cochlear canaliculi, and the stylomastoid foramen. The minute intraosseous branches of Arnold's and Jacobson's nerves (<1 mm in length) remain difficult to study with current imaging techniques, and cadaveric dissection is the most reliable approach. Our aim was to examine the variations of Jacobson's and Arnold's canaliculi and nerves and to provide detailed cadaveric graphics. To reveal the anatomical structures of small canals around the jugular foramen, 25 sides of dry skulls and 14 sides of cadaveric heads were examined. Intraosseous branches varied more in Arnold's nerve than Jacobson's nerve. In our cadaveric dissection, all specimens formed a single canal for Jacobson's nerve connecting the jugular foramen to the tympanic cavity. The intraosseous course of Arnold's nerve varied in its communication with the facial nerve. A descending branch crossing the facial nerve was identified in five of 14 sides, an ascending branch in 13. In two specimens, an ascending branch clearly reached the base of the stapedius muscle. Classical anatomical studies of cadavers remain a supplementary tool for analyzing these tiny structures. The present study confirms Gray's findings of 1913. Variations of these nerves could be even more complex than previously reported. Our study provides additional information regarding the anatomy of Jacobson's and Arnold's nerves.

DOI： 10.1002/ca.23998

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PubMed

Language：Japanese   Publisher：耳鼻と臨床会  

MRIを撮影した人工内耳装用症例を2021年までに18例経験した。MRIの撮影範囲の内訳は頭頸部9例、胸髄2例、肩関節1例、肝臓1例、腰仙髄2例、脊椎1例、骨盤2例であった。このうち頭頸部MRIを撮影した8例は撮影範囲に人工内耳のアーチファクトを認めた。MRI撮影後の人工内耳トラブルが4例に生じ、うち1例で体内器の磁石を入れ替える手術を要した。MRIの強調像のうち、拡散強調像は磁石を入れた状態では評価困難であった。MRI画像の欠損範囲や検査後のトラブルを把握しておくことで、他科の医師とのMRI検査計画を立てやすくなり、また患者の検査への理解を深めることに役立てることが可能と考えられた。(著者抄録)

Publisher：Journal of Gynecologic Oncology  

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2-PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

DOI： 10.3802/jgo.2023.34.e24

Scopus

Language：English   Publisher：In Vivo  

Background/Aim: Lacrimal sac tumors are rare tumor types, with a long time interval from disease onset to diagnosis. We aimed to investigate the characteristics and outcomes of patients with lacrimal sac tumors. Patients and Methods: The medical records of 25 patients with lacrimal sac tumors initially treated at the Kyushu university hospital from January 1996 to July 2020 were reviewed. Results: Our analysis included 3 epithelial benign tumors (12.0%) and 22 malignant (88.0%) tumors (squamous cell carcinoma, n=6; adenoid cystic carcinoma, n=2; sebaceous adenocarcinoma, n=2; mucoepidermoid carcinoma, n=1; malignant lymphoma, n=10). The average time from symptom onset to diagnosis was 14.7 months (median=8 months; range=1-96 months). The analysis of patients revealed that lacrimal sac mass (22/25, 88.0%) was the most frequent symptom and a possible tumor marker. Most epithelial benign (n=3) and malignant epithelial (n=12) tumors were treated surgically (14/15, 93.3%). One malignant case was treated with heavy ion beam therapy. Eight patients were treated with postoperative (chemo)radiation therapy because of positive surgical margins (including one unanalyzed case). Local control was ultimately achieved in all but one case. The patient survived for 24 months with immune checkpoint inhibitors and subsequent chemotherapy for local and metastatic recurrence. Conclusion: We report our experience in the diagnosis and treatment of lacrimal sac tumors and analyze the clinical trends in cases involving these tumors. Postoperative radiotherapy and pharmacotherapy, including immune checkpoint inhibitors, may be useful for recurrent cases.

DOI： 10.21873/invivo.13198

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PubMed

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>An 18-year-old male patient had developed epileptic seizures with loss of consciousness 3 years earlier, and despite subsequent drug treatment, he still had recurrent epileptic seizures. Imaging studies revealed a meningoencephalocele with protrusion of the temporal lobe from the middle cranial fossa to the lateral fossa of the sphenoid sinus. Since this was thought to be the focus of the temporal lobe epilepsy, he was admitted to our hospital for resection of the meningoencephalocele. The patient underwent transnasal endoscopic resection of the meningoencephalocele in the lateral fossa of the sphenoid bone, followed by multilayer skull base reconstruction using a pedicled middle turbinate mucosal (MT) flap. Postoperatively, the epileptic seizures disappeared, and the patient has recovered without cerebrospinal fluid leakage or wound complications. If the area is localized near the sphenopalatine foramen, such as the lateral fossa of the sphenoid sinus, an MT flap can be used instead of a nasal septal mucosal flap. Furthermore, by using a minimal transpterygoid approach and preserving the sphenopalatine artery and its branch, the middle turbinate artery, it was possible to use the MT flap during skull base reconstruction.</p>

DOI： 10.11334/jibi.69.2_116

CiNii Research

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>We herein report four operative cases of temporal bone glomus tumors encountered between 2016 and 2021. Two of the cases were glomus jugulare, and the other two were glomus tympanicum. Characteristic symptoms included pulsatile tinnitus in the two patients with glomus tympanicum. Preoperative audiometry revealed conductive hearing loss on the affected side and air-bone gap in three patients. One of the glomus jugulare cases required three surgeries: a biopsy, resection, and reoperation. Vascular embolization was performed in all four cases. There was no evidence of pre- or postoperative neurologic deficit in any cases. No postoperative recurrence or regrowth was observed in any cases, and the patients are under follow-up. Because glomus tumors are rich in blood vessels, preoperative embolization and the use of a high-frequency bipolar coagulator may aid in performing safe surgery.</p>

DOI： 10.11334/jibi.69.2_89

CiNii Research

Language：English  

DOI： 10.7759/cureus.35932

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PubMed

Language：Japanese   Publisher：日本顔面神経学会  

福岡県内で顔面神経麻痺リハビリテーション(VIIリハ)を実際に行う言語聴覚士を対象に意識調査を行った。2022年3月～4月に福岡県内で従事していた言語聴覚士634名を対象に調査を依頼し95名から回答を得た。顔面神経麻痺患者を見たことがあるものは90%で、実際にVIIリハを行ったものは87%であった。顔面神経麻痺の評価法として知っているのは柳原法が83%と最も多く、Sunnybrook法やFaCE Scaleはそれぞれ28%、13%であり、柳原法以外はほとんど評価できないと回答していた。VIIリハ頻度は74%が週1回程度としており、比較的頻度高くリハを施行していた。VIIリハを行っている施設は65%あったが、ボツリヌス毒素療法併用VIIリハを行っている施設はわずか6%であった。95%が顔面神経麻痺リハビリテーション技術講習会を受講希望していたが、その存在を知っていたものは33%にとどまっていた。

Language：Japanese   Publisher：大道学館出版部  

食道癌手術症例における入院前周術期支援の介入の有無と術後合併症との関連について検討し、入院前周術期支援の有用性について検証した。2018年4月～2020年9月にかけて、食道癌手術症例120例を、入院前周術期支援を開始した2019年10月前後で入院時支援介入なし群75例と介入あり群45例に分類した。術後合併症は全体で51例(43%)に認められ、内容としては最多が肺炎で16例(13.9%)、嚥下障害・反回神経麻痺が14例(12.2%)、不整脈8例(7.0%)であった。介入なし群での合併症頻度は75例中37例(49%)であったのに対して、介入あり群で45例中14例(31%)と介入あり群の方が合併症の発生頻度が低かった。周術期支援による術後合併症の減少が示唆される結果が得られ、他癌腫への応用も視野に、周術期支援の充実を図ることが重要と考えられた。

Language：Japanese   Publisher：日本顔面神経学会  

無料表情分析ソフトウェアが回復過程の表情の推移も評価できるか、治療途中の点数と表情の相関について検討した。10点以下の完全麻痺から34点以上に改善した末梢性顔面神経麻痺9例のうち途中経過を評価できていた8例(男性3名、女性5名)を対象とした。顔面神経麻痺リハビリテーションによって点数の上昇とともに有意に「頬を膨らまし」では若く見えるようになり、「額のしわ寄せ」「口をへの字にまげる」では逆に上の年齢にみられるようになった。「イーと歯を見せる」では「喜び」が有意に上昇し、「普通」「驚き」は低下した。閉眼はどの感情とも相関がみられなかった。「イーと歯を見せる」では有意に「喜び」が上昇し「驚き」が減少したため、「イー」は治療経過を追うのに最適な項目となる可能性が考えられた。

Language：Japanese   Publisher：日本顔面神経学会  

小児顔面神経麻痺症例について検討した。2014年4月～2021年3月までの7年間に当科を受診した15歳以下の顔面神経麻痺58例(男性30例、女性28例、平均5.0±4.5歳)を対象とした。後天性麻痺が53例で、そのうちHunt症候群が4例、Bell麻痺が38例、急性中耳炎が9例、外傷性が1例、腫瘍性が1例であった。先天性麻痺は5例で、そのうち上・下行枝麻痺が1例、下顎縁枝のみの麻痺が4例であった。後天性麻痺53例のうち完全麻痺が21例、不全麻痺が32例であり、聴力やめまい・眼振についての記載があったのは半数程度で、このうちHunt症候群の1例に軽度感音難聴を認めた。後天性麻痺の53例中51例にステロイドを投与し、抗ウイルス薬を併用した割合は66%であった。後天性麻痺53例のうち、治癒・非治癒の予後を確認できたものが38例あり、治癒が36例、非治癒が2例で、治癒率は94.7%を示していた。

Language：Japanese   Publisher：耳鼻と臨床会  

上咽頭癌は、ほかの頭頸部癌とは異なる側面を持つことから、予後因子も通常の頭頸部扁平上皮癌とは異なる。2018年にTNM分類が改訂され、上咽頭癌も変更されたため、今回われわれは、新TNM分類を用いて、当科で加療を行った上咽頭癌症例について予後の検討を行った。対象は、2010年1月から2020年1月に九州大学病院耳鼻咽喉・頭頸部外科で一次療法を施行した上咽頭癌45例である。男性31例、女性14例、年齢は12-88歳、中央値59歳であった。これらのうち、上咽頭扁平上皮癌であった40例における5年全生存率(以下OS)、無増悪生存率(PFS)、予後関連因子などについて後方視的に解析を行った。その結果、5年OSは75.5%、5年PFSは64.3%であった。予後関連因子として、Stage別や組織型、Epstein-Barr Virus陽性か否かによる有意差は認められなかった。また、上咽頭癌治療の軸となるシスプラチン併用化学放射線療法については、シスプラチンの至適投与量についてさらなる検討が必要と考えられた。(著者抄録)

Language：Japanese   Publisher：耳鼻と臨床会  

2016年から2021年にかけて当科で手術を行った側頭骨グロムス腫瘍の4例について報告する。4例の内訳として鼓室型2例、頸静脈球型2例に対し治療を行った。鼓室型の2例では拍動性耳鳴を認めた。術前聴力検査では3例で患側の聴力低下と気骨導差を認めた。頸静脈球型のうち1例では生検、切除、再手術と3回の手術を必要とした。血管塞栓術は鼓室型、頸静脈球型それぞれ1例ずつ施行し、すべての症例において、術前後の神経脱落所見は認めなかった。1例は残存病変があるものの増大なく経過しており、その他3例は再発・再々発なく経過している。グロムス腫瘍は血流豊富であり、栄養血管の塞栓や高周波バイポーラの使用が安全な手術に有用と考えられる。(著者抄録)

Language：Japanese   Publisher：日本顔面神経学会  

人工内耳(CI)植込術前に得られる情報から顔面神経刺激(FNS)発生リスク因子を抽出することを目的とした。2013年1月～2021年11月に当科でCIを植え込んだ196名238耳(女性101名120耳、男性95名118耳)を対象とした。CI植込術後のFNS発生数は13名17耳(女性9名13耳、男性4名4耳)、発生率は7.1%であった。FNS群は女性が多く、平均年齢は対照群より高く、併存症を有する割合に有意差はなかった。植込電極を蝸牛軸近接型と蝸牛外側壁近接型に分類した結果、FNS群は蝸牛軸型が多かった。単変量解析において有意差を認めた性別、年齢、植込電極型、原因疾患について多変量解析を行った。その結果、性別(女性)と原因疾患(髄膜炎、内耳奇形)がFNSのリスク因子として有意に高い確率であった。

Language：English   Publisher：In Vivo  

Background/Aim: The advent of immune checkpoint inhibitor (ICI) treatment has transformed the treatment of recurrent or metastatic head and neck cancer; however, nasopharyngeal carcinoma (NPC) has not been included in major phase III trials. The clinical outcomes of ICI for NPC in real-world practice remain to be fully elucidated. Patients and Methods: We retrospectively reviewed 23 patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab at 6 institutions from April 2017 to July 2021 and investigated the correlation of clinicopathological factors and immune-related adverse events with the effects of ICI therapy and the prognosis. Results: The objective response rate was 39.1% and the disease control rate was 78.3%. The median progression-free survival was 16.8 months and overall survival has not been reached. As with other treatment procedures, the efficacy and the prognosis tended to be better in EBER-positive cases than in EBER-negative cases. The rate of significant immune-related adverse events that necessitated discontinuation of treatment was only 4.3%. Conclusion: ICI monotherapy (e.g., nivolumab and pembrolizumab) was effective and tolerable for NPC in a real-world setting.

DOI： 10.21873/invivo.13137

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

High-risk human papillomavirus (HPV) is a risk factor for the development of several head and neck squamous cell carcinomas (SCCs). However, there have been few reports of high-risk HPV infection in temporal bone squamous cell carcinomas (TBSCCs), and thus the prevalence and clinicopathologic significance of high-risk HPV in TBSCCs are still unclear. We retrospectively collected 131 TBSCCs and analyzed them for transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization; we also assessed the utility of p16-immunohistochemistry (IHC) and Rb-IHC to predict HPV infection. Eighteen (13.7%) of the 131 TBSCCs were positive for p16-IHC, and five of them were positive for high-risk HPV infection (the estimated high-risk HPV positivity rate was 3.8% [5/131]). Interestingly, all five HPV-positive patients were male and had TBSCC on the right side. In the p16-IHC+/HPV+ cases (n = 5), the Rb-IHC showed a partial loss pattern (n = 4) or complete loss pattern (n = 1). In contrast, all p16-IHC-negative cases (n = 113) showed an Rb-IHC preserved pattern. The positive predictive value (PPV) of p16-IHC positivity for high-risk HPV infection was low at 27.8%, while the combination of p16-IHC+/Rb-IHC partial loss pattern showed excellent reliability with a PPV of 100%. The prognostic significance of high-risk HPV infection remained unclear. High-risk HPV-related TBSCC is an extremely rare but noteworthy subtype.

DOI： 10.1007/s00428-023-03497-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Voice  

INTRODUCTION: Typical singing registers are the chest and falsetto; however, trained singers have an additional register, namely, the mixed register. The mixed register, which is also called "mixed voice" or "mix," is an important technique for singers, as it can help bridge from the chest voice to falsetto without noticeable voice breaks. OBJECTIVE: The present study aims to reveal the nature of the voice-production mechanism of the different registers (chest, mix, and falsetto) using high-speed digital imaging (HSDI), electroglottography (EGG), and acoustic and aerodynamic measurements. STUDY DESIGN: Cross-sectional study. METHODS: Aerodynamic measurements were acquired for twelve healthy singers (six men and women) during the phonation of a variety of pitches using three registers. HSDI and EGG devices were simultaneously used on three healthy singers (two men and one woman) from which an open quotient (OQ) and speed quotient (SQ) were detected. Audio signals were recorded for five sustained vowels, and a spectral analysis was conducted to determine the amplitude of each harmonic component. Furthermore, the absolute (not relative) value of the glottal volume flow was estimated by integrating data obtained from the HSDI and aerodynamic studies. RESULTS: For all singers, the subglottal pressure (PSub) was the highest for the chest in the three registers, and the mean flow rate (MFR) was the highest for the falsetto. Conversely, the PSub of the mix was as low as the falsetto, and the MFR of the mix was as low as the chest. The HSDI analysis showed that the OQ differed significantly among the registers, even when the fundamental frequency was the same; the OQ of the mix was higher than that of the chest but lower than that of the falsetto. The acoustic analysis showed that, for the mix, the harmonic structure was intermediate between the chest and falsetto. The results of the glottal volume-flow analysis revealed that the maximum volume velocity was the least for the mix register at every fundamental frequency. The first and second harmonic (H1-H2) difference of the voice source spectrum was the greatest for the falsetto, then the mix, and finally, the chest. CONCLUSIONS: We found differences in the registers in terms of the aeromechanical mechanisms and vibration patterns of the vocal folds. The mixed register proved to have a distinct voice-production mechanism, which can be differentiated from those of the chest or falsetto registers.

DOI： 10.1016/j.jvoice.2020.12.028

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

難聴者にとっては,新型コロナウイルス感染対策のマスクや遮蔽板がさらなる聴き取りづらさを招く。音声認識AIとCI2004日常会話文を組み合わせたアプリケーションを用いて聴き取りづらさを定量化し,聴取環境を評価する試みを行った。評価対象語60語を正確に聴き取れた数で正解率を算出した。静寂下に検査を行うと正解率は95%であった。劣化音源や雑音下では正解率が低下した。この検査系を用いて院内コンビニエンスストアの聴取環境の評価を行ったところ,著明に正解率が低下した。雑音の有無,マスクと遮蔽板,補助スピーカーの有無で検討を行うと,マスク単体では正解率の有意な低下はなかったが,マスクおよび遮蔽板を設置し雑音下で検査を行うと著明に正解率が低下した。うるさい場所でマスクをした相手が遮蔽板の向こうで話す言葉は聞き取りづらいという難聴者の感覚と矛盾のない結果であった。同じ検査条件を用いれば環境ごとの聴き取りにくさの評価も可能である。(著者抄録)

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>We experienced 15 surgical cases of petrous apex-11 cholesteatomas and 4 cholesterin granulomas-between January 2013 and July 2021. Among the four cases of cholesterin granuloma, one underwent transmastoid surgery, while the others received intranasal endoscopic surgery to create drainage routes. Among the 11 cases of cholesteatoma, 5 received initial surgery, and 6 were reoperations. The extent of the lesion based on Sanna's classification was supralabyrinthine in seven patients, massive in two, and infralabyrinthine in two. In the supralabyrinthine type, the middle fossa approach or combined approach of the middle cranial fossa and translabyrinthine approach was necessary in cases with severe extensions or those receiving reoperation. The minimally invasive procedure through the superior semicircular canal approach was performed in cases with a small extension. In the massive type, the transcochlear and middle fossa combined approach was used, while in the infralabyrinthine type, the infracochlear or infralabyrinthine approach was performed, depending on the localization and degree of the extension. The hearing was preserved in all cases of cholesterin granuloma and three cases of cholesteatomas. Since the petrous apex is located in the deepest part of the temporal bone, it is crucial to have a thorough understanding of the anatomy and select a surgical approach that considers the lesion and hearing.</p>

DOI： 10.11334/jibi.69.1_1

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Language：English   Publisher：Anticancer Research  

Background/Aim: Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. Patients and Methods: We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and ¹⁸F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. Results: The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between ¹⁸F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and ¹³¹I accumulation at initial RIT (p=0.577). However, ¹⁸F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. Conclusion: ¹⁸F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. ¹⁸F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the ¹⁸F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.

DOI： 10.21873/anticanres.16148

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

吃音を主訴として受診した中・高校生を対象に、不登校と社交不安障害(SAD)の関連について検討するとともに(研究1)、発話に関連する10項目とSADの関連について検討した(研究2)。研究1において、84名中22名(26%)が不登校群、62名(74%)が登校群であった。不登校群では登校群に比べてリボビッツ社交不安尺度(LSAS-CA)日本語版の得点が有意に高かった(p=0.004)。研究1の参加者のうち40名を対象とした研究2において、LSAS-CA日本語版による評価で40名中20名がSAD群、20名が非SAD群であった。SAD群では非SAD群に比べて「人前で話をする際に手足が震えることがありますか」および「吃音が出た後に自己否定する思考に陥ることがありますか」の項目の得点が有意に高かった。

Language：Japanese   Publisher：JAPAN SOCIETY FOR HEAD AND NECK SURGERY  

Inflammatory myofibroblastic tumor （IMT） is a rare intermediate malignant tumor characterized by inflammatory cell infiltration and proliferation of myofibroblastic and fibroblastic spindle cells. In the present study, we experienced three cases of laryngeal IMT. The first case was a 60-year-old man. He underwent laryngomicrosurgery for a right vocal cord tumor, 7mm in size. One year after the surgery, no evidence of recurrence was seen. The second case was a 53-year-old man with a left vocal cord polyp-like lesion 15mm in diameter with a tendency to enlarge. He underwent laryngomicrosurgery. One year after the surgery, no evidence of recurrence was seen. The third case was a 40-year-old man with IMT diagnosed by a biopsy of a subglottic mass. The case was placed on observation and has remained unaffected for four years. Anaplastic lymphoma kinase （ALK） gene rearrangement was confirmed by fluorescence in situ hybridization in all cases. Preoperative diagnosis of IMT is usually difficult because of the lack of characteristic findings. Surgical resection is the first-line treatment. Although it can cause asphyxia, the increase is generally slow and the choice of timing of treatment needs to be tailored to the pathology. IMT usually has a benign course, but cases with local recurrence or distant metastasis have been reported. In laryngeal IMT, local recurrence was reported in about 20％ of cases, and no metastasis was reported. Surgical treatment should be considered in the presence of a hard, enlarging laryngeal mass, with the possibility of IMT.

DOI： 10.5106/jjshns.33.59

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Language：Japanese   Publisher：Japan Otological Society  

<p>Among recently developed electrode arrays, slim modiolar electrode arrays are prone to folding within the cochlea, a condition known as tip fold-over. One of the mechanisms that cause tip fold-over is the misalignment between the electrode array’s coiling direction and the cochlea’s curving direction. Thus, surgeons should be careful during slim modiolar electrode insertion and align the coiling planes of the electrode array and the cochlea. However, successful alignment of the electrode array’s coiling direction and the cochlea’s curving direction largely depends on the surgeon’s imagination. We recommended preoperative three-dimensional simulation to determine the correct coiling plane of the cochlea. However, not all surgeons are familiar with preoperative simulations using computers. Therefore, we developed a method of determining the coiling plane of the cochlea using anatomical landmarks that can be visualized during cochlear implantation.</p><p>We retrospectively investigated preoperative CT data of 65 ears of patients who underwent cochlear implantation by one surgeon during the period of 2017–2021. Revision cases and inner ear anomaly cases were excluded. The preoperative CT dataset was three-dimensionally reconstructed. A plane was defined containing short and long processes of the incus, as “plane of the incus”. The angle between the plane of the incus and the coiling plane of the cochlea (incudocochlear angle) were measured and collected. The incudocochlear angle was averaged at 34.6 degrees. No statistical differences were noted between the left and right ears. No statistical differences were noted in terms of age at surgery. The 95% confidence interval of the angle was 23.4–45.7 degrees. Thus, once the incus is visualized during surgery, it is possible to correctly determine the coiling plane of the cochlea. This simple method does not require the surgeon’s ability of computer simulation and may help prevent misalignment and subsequent electrode tip fold-over.</p>

DOI： 10.11289/otoljpn.33.170

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Language：English   Publisher：Journal of Voice  

Introduction: Singers use a whistle register to sing at a fundamental frequency above 1000 Hz. In previous studies, vocal fold vibrations with or without complete closure and partial vocal fold vibrations were observed depending on the subject. However, the production mechanism of the whistle register is not yet clearly understood because of the limitations of the imaging device for the glottis and subjects. Objectives: This study aims to examine vocal fold vibrations in a whistle register. Methods: The dynamic behavior of the glottis was recorded for six singers (four females and two males) using a high-speed digital imaging device with a frame rate above 10,000 fps. Audio signals were recorded simultaneously. The data were analyzed in the form of topography, glottal area waveforms, spectrograms, and phonovibrography to examine spatiotemporal patterns of glottal motion. Results: The vibratory motion of the vocal folds was classified into six patterns. The first pattern was the entire vocal fold vibration with complete closure during the closed phase. The second to fifth was the entire vocal fold vibration without complete closure, where a gap was observed for the full length of the vocal folds for the second, at the posterior part of the glottis for the third, at the anterior for the fourth, and at both ends for the fifth. In the sixth pattern, the vocal folds vibrated partially. Our results support the previous findings on the vibration of the vocal folds. In addition, we identified novel vibratory patterns in the vocal folds. Conclusion: We conclude that the production of the whistle register is not just an extension of the falsetto register to the higher fundamental-frequency region; rather, the production mechanism of the whistle register appeared to be diverse as a means of vocalization.

DOI： 10.1016/j.jvoice.2023.08.026

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Language：Japanese   Publisher：The Japan Society of Logopedics and Phoniatrics  

<p>Dysarthria is a collective name of speech disorders defined as "abnormalities of speech sounds caused by disturbances in the neuromuscular systems involved in the process of speech execution.” The term "運動障害性構音障害" (literally, “articulation disorders caused by motor disorders”) has long been used as a translation of “dysarthria” in the Japanese Health Insurance reimbursement system and in the national examination criteria for speech-language-hearing therapists. However, there have been various discussions about the validity of this translation. For example, the definitional distinction from "運動性構音障害” (literally, “motor-related articulation disorders”), which is the translation of "motor speech disorders," has not been properly adopted, resulting in confusion in usage, or inappropriate use of "構音," “articulation,” for all coordinated motor functions related to speech. The Speech, Language and Development Committee of the Japan Society of Logopedics and Phoniatrics (JSLP) has examined the need for a proper translation for “dysarthria” which can be shared by researchers and is understandable not only to specialists but also to the public, including patients. Here, we reviewed how the definition of dysarthria has evolved in Europe and the U.S., as well as how discussions have developed regarding the translated name in Japan. As our conclusion, we have proposed the term "発語運動障害," literally, “motor disorders of speech,” as an appropriate translation of “dysarthria.” </p>

DOI： 10.5112/jjlp.64.24

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Language：English   Publisher：Plastic and Reconstructive Surgery  

Surgeons have traditionally believed that swallowing is mainly dependent on gravity after total glossolaryngectomy. However, swallowing function after total glossolaryngectomy varies widely among patients, and a thorough analysis is lacking. The authors aimed to clarify the swallowing function after total glossolaryngectomy and determine whether it is primarily dependent on gravity. The authors retrospectively analyzed videofluorographic examinations of patients who underwent total glossolaryngectomy and free or pedicle flap reconstruction. The authors enrolled 20 patients (12 male; mean age, 61 years; age range, 43 to 89 years). All patients demonstrated constriction of the reconstructed pharynx to some degree, and no patient's ability to swallow was dependent on gravity alone. Videofluorography showed excellent barium clearance in eight patients and poor clearance in 12. All patients with excellent clearance showed strong constriction of the posterior pharyngeal wall, whereas only 8.3 percent of the patients with poor clearance showed adequate constriction, which was significantly different (p = 0.0007). Velopharyngeal closure and lip closure also contributed significantly to excellent clearance (p = 0.041). The shape of the reconstructed pharynx (depressed, flat, protuberant) showed no statistically significant association with excellent clearance. Contrary to previous understanding, constriction of the remnant posterior pharyngeal wall played an important role in swallowing after total glossolaryngectomy, and gravity played a secondary role. Dynamic posterior pharyngeal wall movement might result from the increased power of the pharyngeal constrictor muscle and compensate for the immobility of the transferred flap. A well-functioning pharyngeal constrictor muscle and complete velopharyngeal and lip closures can contribute to excellent barium clearance in patients after total glossolaryngectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

DOI： 10.1097/PRS.0000000000009639

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Language：English   Publisher：Cancer Medicine  

There is no useful biomarker to evaluate treatment response and early relapse in head and neck squamous cell carcinoma (HNSCC). Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual diseases and monitoring treatment effect. We investigated whether individualized ctDNA analysis could help monitor treatment response and relapse in HNSCC. Mutation analysis of tumor and peripheral blood mononuclear cell (PBMC) DNAs of 26 patients with HNSCC was performed using a custom squamous cell carcinoma (SCC) panel. The identified individualized mutated genes were defined as ctDNA candidates. We investigated whether frequent ctDNA monitoring via digital PCR (dPCR) is clinically valid for HNSCC patients. TP53 was the most frequently mutated gene and was detected in 14 of 24 cases (58.2%), wherein two cases were excluded owing to the absence of tumor-specific mutations in the SCC panel. Six cases were excluded because of undesignable and unusable primer-probes for dPCR. Longitudinal ctDNA was monitored in a total of 18 cases. In seven cases, ctDNA tested positive again or did not test negative, and all seven cases relapsed after initial curative treatment. In 11 cases, after initial curative treatment, ctDNA remained negative and patients were alive without recurrence. Patients who remained negative for ctDNA during follow-up after initial curative treatment (n = 11) had a significantly better prognosis than those who reverted to ctDNA positivity (n = 7; p < 0.0001; log-rank test). Individualized ctDNA monitoring using SCC panel and dPCR might be a novel and promising biomarker for HNSCC.

DOI： 10.1002/cam4.4726

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Medical Case Reports  

BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

DOI： 10.1186/s13256-022-03621-2

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Scopus

PubMed

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

<p>　側頭骨悪性腫瘍に対する側頭骨一塊切除術は, 外側側頭骨切除術 (lateral temporal bone resection: LTBR), 側頭骨亜全摘術 (subtotal temporal bone resection: STBR), 側頭骨全摘術 (total temporal bone resection: TTBR) の3つの方法が報告されているが, 実臨床では, LTBR と STBR の二つが主に用いられる. STBR は, 頭蓋底チームが手術対応できる施設でのみ施行可能な術式である. 一方, LTBR は耳鼻咽喉科医単独で施行可能な術式で, 非常に洗練された画一的な手術手技である. 通常の乳突洞削開術を含む耳科手術の手技に加え, 側頭骨鼓室部の骨削除の方法を理解することで, 安全に手術を完遂できる. 本術式は通常の耳科手術に必要な外科解剖と手術手技を学ぶことができるため, 経験の浅い耳鼻咽喉科医にも積極的に関与してもらいたい術式である.</p><p>　手術手技の構成は, 通常の乳突洞削開術に後鼓室開放後の鼓室内操作, 上/前鼓室開放, 後鼓室開放の拡大と側頭骨鼓室部の骨削除などの手技を組み合わせたものとなっている. 通常の耳科手術で馴染みの少ない側頭骨鼓室部の削除が Key となる手技と思われる. 安全に側頭骨の鼓室部の削除を行うためには, 錐体鼓室縫合と鼓索神経の関係, 骨部耳管と内頸動脈との関係, そして下鼓室と vaginal process との関係を正確に知る必要がある.</p><p>　本稿では, LTBR を施行する上で必要な骨学と, 術前の留意点などに加えて, 実際の手術手技の手順について概説する.</p>

DOI： 10.3950/jibiinkotokeibu.125.10_1459

CiNii Research

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>An impalement wound is a form of traumatic injury in which a blunt-tipped, stick-like object pierces the body. Oral and pharyngeal trauma often occurs when a person falls with an instrument in their mouth, and the most common causative instrument is a toothbrush. In this study, we experienced a case of toothbrush impalement injury that penetrated the parapharyngeal space. The patient was a 67-year-old woman who fell while holding a toothbrush in her mouth. The toothbrush penetrated the parapharyngeal space from the left wall of the middle pharynx and reached the left posterior cervical muscles. The internal carotid artery was significantly narrowed by the toothbrush. The toothbrush was removed from the head side of the toothbrush through an external neck incision. There was no bleeding during removal and the wound healed without subsequent infection. When treating patients with pharyngeal impalement wounds, inadvertent removal may result in massive bleeding due to vascular injury or nerve damage. Thus, it is necessary to select an appropriate removal method after observing the anatomical structures by contrast-enhanced CT or angiography. In addition, impalement wounds can cause serious complications, including abscess and other infections, and traumatic internal carotid artery occlusion a few days after injury. It is therefore important to provide appropriate antimicrobial treatment and follow-up of neurological findings.</p>

DOI： 10.11334/jibi.68.5_346

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.65.353

CiNii Research

Language：Japanese   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.65.427

CiNii Research

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

BACKGROUND/AIM: Influenza A virus (IAV) infection causes an inflammatory response to the respiratory mucosa. The viral glycoprotein hemagglutinin (HA) binds to the sialylated voltage-dependent Ca2+ channel (Cav1.2) in ciliated epithelium. The binding of HA and sialylated Cav1.2 is considered essential to IAV infection, entry, and IAV-induced Ca2+ oscillation. The epipharynx comprises the ciliated epithelium, which is the initial target for viruses that cause upper respiratory tract infections. Previously, we showed that epipharyngeal abrasive therapy (EAT), a treatment for chronic epipharyngitis in Japan, which scratches the epipharyngeal mucosa with a cotton swab containing zinc chloride, induces squamous metaplasia. In this study, we evaluated whether squamous metaplasia by EAT affects the expression patterns of Cav1.2. PATIENTS AND METHODS: The study subjects were seven patients who had not been treated with EAT and 11 patients who had. For the immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of Cav1.2 was described using the immunohistochemical score (IHC score). RESULTS: The IHC scores for Cav1.2 in the EAT-treated group was 4.19-fold lower than those in the non-treated group (p=0.0034). CONCLUSION: EAT down-regulates the expression of Cav1.2, a key cell surface molecule in influenza virus entry via squamous metaplasia. Thus, EAT may be a simple method for preventing influenza infection.

DOI： 10.21873/invivo.12967

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PubMed

Language：English  

DOI： 10.1097/ONO.0000000000000017

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Molecular Sciences  

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

DOI： 10.3390/ijms23169205

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PubMed

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

OBJECTIVES: The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). RESULTS: The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. CONCLUSION: Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.

DOI： 10.1371/journal.pone.0271907

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PubMed

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

<p>ANCA-associated vasculitis is an autoimmune vasculitis that often develops in systemic diseases, such as renal disorders and pulmonary lesions. However, there have been increasing reports of ANCA-associated vasculitis of otitis media origin and ear-localized type in recent years. A 52-year-old woman with a history of tuberculosis presented with otitis media refractory to antimicrobial agents as well as hearing loss and headache. Although otitis media with ANCA-associated vasculitis (OMAAV) is mentioned as a differential diagnosis for refractory otitis media, the diagnosis was difficult, as ANCA antibodies were negative, biopsy tissue showed no evidence of vasculitis, and there was concern about the possibility of tuberculous otitis media. We ultimately diagnosed the patient with OMAAV by excluding other diseases thorough a collaborative evaluation of other organs, considering the complication of hypertrophic pachymeningitis, which is characteristic of OMAAV. Since we experienced a case of OMAAV that took one year to be diagnosed, we herein report this diagnosis with some discussion of the literature.</p>

DOI： 10.11334/jibi.68.4_266

CiNii Research

Publisher：東京医学社  

DOI： 10.24479/ohns.0000000182

CiNii Research

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

難聴疑いで精査機関に紹介された0歳児に関する調査、精査機関で発見された1～6歳の難聴児に関する調査を実施した。精密聴力検査機関147ヶ所、二次聴力検査機関261ヶ所から報告された0歳で難聴が疑われた6118例について検討を行った。両側難聴の3割以上に補聴器が適合されておらず、両側難聴で補聴器を適合された例のなかには療育・教育を受けていない例、補聴器の適合の要否が判断できていない例が少数ながら報告された。1～6歳で初診となった片側難聴402例、両側難聴389例、聴神経難聴スペクトラム9例、聴覚情報処理障害22例、機能性難聴66例が報告され、補聴器の適合状況、療育・教育の適応の有無について問題のある例が中等度難聴に多くみられた。中等度難聴に対するアプローチのあり方は検討されるべき課題と考えられた。

Language：English   Publisher：Anticancer Research  

Background/Aim: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. Patients and Methods: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. Results: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). Conclusion: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.

DOI： 10.21873/anticanres.15854

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Journal of Surgical Pathology  

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

DOI： 10.1097/PAS.0000000000001857

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PubMed

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

BACKGROUND/AIM: A long-term effect has been confirmed in clinical practice since the introduction of nivolumab for treating various malignant tumors. A similar phenomenon is speculated to occur in head and neck cancer; however, details remain unclear due to the lack of long-term reports. We aimed to investigate the five-year outcomes in long-term responders for over two years, and evaluate the optimal duration of therapy with nivolumab. PATIENTS AND METHODS: In this retrospective observational study, we analyzed 203 cases of recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), including 33 long-term responders. RESULTS: The median overall survival (OS), 5-year OS, median progression-free survival (PFS), and 5-year PFS values in the 203 cases were 13.1 months, 19.2%, 3.1 months, and 13.2%, respectively. Of the 33 long-term responders, 14 (42.4%) continued using nivolumab for more than 2 years. The remaining 19 patients (57.6%) discontinued nivolumab. The most common reason for discontinuation was severe immune-related adverse events (irAEs) (9 cases; 27.3%); in these 9 cases, the median disease-free survival was 33.2 (range=10.7-44.3) months. Nine patients (21.2%) were considered to have progressive disease (PD) after at least 2 years of administration, and 3 patients (9.1%) requested to discontinue treatment because a complete response (CR) was achieved. CONCLUSION: This study demonstrated the durable and long-term benefit of nivolumab in R/MHNSCC. In the future, we aim to accumulate real-world data for the establishment of criteria for completion of nivolumab treatment in long-term responders.

DOI： 10.21873/invivo.12907

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Archives of Oto Rhino Laryngology  

PURPOSE: We herein report the treatment outcome of oropharyngeal squamous cell carcinoma (OPSCC) at Kyushu University Hospital, the total number of OPSCC cases, and changes in the proportion of human papilloma virus (HPV)-related carcinomas over time. METHOD: We performed a retrospective analysis of 237 cases treated for OPSCC at Kyushu University Hospital between 2013 and 2019. We performed HPV-mRNA in situ hybridization and p16 immunohistochemistry. RESULT: This study included 197 males (82.1%) and 40 females (17.9%). The disease-specific, progression-free and overall survival (OS) were 69%, 62% and 61%, respectively, over the decade-long study period. p16-Immunohistochemistory and highrisk HPV mRNA in situ hybridization were positive in 114 (48.1%) and 105 (44.3%) cases, respectively. The number of HPV-related OPSCC cases increased according to an annual analysis. HPV+ cases had a significantly better prognosis than HPV- cases. In addition, p16+/HPV- cases had a significantly worse prognosis than p16+/HPV+ cases (OS: p = 0.0484). HPV+ OPSCC cases were associated with a younger age (< 60 years old) (p = 0.0429), non-smoker (p = 0.0001), lateral tumor site (< 0.00001), lymphoid metastasis (< 0.0001) and low clinical stage (< 0.0001). CONCLUSION: The frequency of HPV-related OPSCC cases is increasing in Japan as well as worldwide, and such cases are characterized by no smoking habit, a young age, and a good prognosis. Even in p16+ OPSCC, HPV- cases had a poor prognosis, suggesting the importance of accurate HPV determination. To determine the intensity of treatment for HPV-related and non-related OPSCC, it is necessary to accumulate cases for the accurate HPV determination and comparison of treatment effects.

DOI： 10.1007/s00405-021-07236-z

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Neurological Surgery Part B Skull Base  

Objective  En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the outcomes of surgical cases of advanced TB-SCC (T3-T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule. Design  This is a case series study with chart review. Setting  The study was conducted at two academic tertiary care medical centers. Participants  Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan-Meier method. Main Outcome Measure  This study shows disease-specific 5-year DSS rate. Results  The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%). Conclusion  En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension.

DOI： 10.1055/s-0041-1722930

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PubMed

Language：English   Publisher：Biomedicines  

Background: Accurate data on the prevalence of hearing impairment and severity across age and gender are paramount to formulate hearing health policies. Here, we sought to analyze audiometric data from a large group of age-diverse people in Japan, which has not been previously described in detail. Methods: We analyzed retrospective hearing threshold data of 23,860 participants (10–99 years; left-right hearing threshold difference <15 dB; air-bone gap ≤10 dB) at 500, 1000, 2000, and 4000 Hz, and then classified them for hearing impairment severity according to the WHO Classification. Findings: There was a significant gender difference in median hearing thresholds, starting in 20-year-olds up to early 80-year-olds. Twenty-five percent of men in their late 50s had some level of HI, ~50% in their late 60s, and ~75% in their late 70s. For women, 25% had some level of HI in their early 60s, ~50% in their early 70s, and ~75% in their late 70s. For participants in their early 80s, 50% of either gender had moderate or more severe HI. Interpretation: Our results, derived from a large number of participants, provide basic information about the prevalence of hearing loss by age decade. Since people can expect to live longer than those in previous generations, our detailed data can inform national social systems responsible for hearing screening in making decisions about hearing-aid qualification, which may reduce barriers to older people’s independence, productivity, and quality of life.

DOI： 10.3390/biomedicines10061431

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PubMed

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC.Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined.We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2-54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%).We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC.

DOI： 10.3950/jibiinkotokeibu.125.5_916

PubMed

CiNii Research

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

COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.

DOI： 10.3390/v14050907

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Language：Japanese   Publisher：日本顔面神経学会  

末梢性顔面神経麻痺で柳原法の最悪麻痺スコア10点以下の完全麻痺が34点以上に回復した9例(34～83歳、平均50.8歳)を対象に、無料表情分析ソフトを用いて治療前後の顔画像180枚を解析し、怒り・喜び・普通・悲しみ・驚きの数値化、推定年齢の算出を試みた。その結果、無料ソフトは顔面神経麻痺の表情改善の数値化が可能で有用であると考えられた。

Language：Japanese   Publisher：日本顔面神経学会  

FaCE Scaleを改定した「ちどり版」を作成し、顔面神経麻痺リハビリテーションを行っている言語聴覚士8名(男性1名、女性7名、23～39歳)を対象に改訂版使用に関する意識についてアンケート調査を行った。その結果、言語聴覚士にも患者にもFaCE Scale改訂版は役立つと実感していることが分かった。

Language：Japanese   Publisher：日本顔面神経学会  

過去6年間の人工内耳(CI)植込み術後の顔面神経刺激(FNS)を認めた18例(21耳)について後方視的に検討した。CI植込み時期は小児期9例11耳(1～10歳1ヵ月、平均3歳5ヵ月)、成人期9例10耳(34～75歳、平均59歳)であった。小児期と成人期では難聴の原因疾患、FNS原因電極、FNSの刺激部位や筋が異なる傾向を認めた。聴取成績は小児期FNS症例で内耳形態異常や内耳道狭窄例7例9耳は全例が不良、先天性CMV感染症1例1耳と進行性難聴1例1耳は良好で、成人期は髄膜炎3例3耳全例が不良、他の6例7耳は良好であった。

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

Oropharyngeal swallowing is centrally mediated by a swallowing central pattern generator (Sw-CPG) in the medulla oblongata. The activity of the Sw-CPG depends on the sensory inputs determined by physical and chemical bolus properties. Here we investigate the sensory-motor integration during swallowing arising from different sensory sources. To do so we electrically stimulated the superior laryngeal nerve and we triggered swallowing with oral injections of distilled water or capsaicin solution and extracellularly recorded from swallowing interneurons in arterially perfused brainstem preparations of rats. We recorded the activities of 40 neurons, while monitoring the motor activities of the phrenic, vagal and hypoglossal nerves. Eighteen neurons responded to electrical stimulation of the ipsilateral superior laryngeal nerve, and 6 neurons were excited by oral fluid injection, while 16 non-respiratory neurons did not receive afferent inputs to either electrical or physiological stimuli. The cellular activities displayed by swallowing interneurons during electrical and physiological stimulation of pharyngeal and laryngeal afferent input reveal complex adaptations of the timing of firing patterns and frequencies. The modulation of neuronal activity is likely to contribute to the coordination of efficient bolus transfer during the pharyngeal stage of swallowing.

DOI： 10.1016/j.neures.2021.11.006

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PubMed

Language：English   Publisher：エルゼビア・ジャパン(株)  

嚥下運動により生じる、嚥下関連介在ニューロン(SIN)の神経活動について検討した。Wistarラットの動脈灌流脳幹標本を用いて、上喉頭神経に電気刺激を与え、蒸留水もしくはカプサイシン溶液の経口注水刺激により、嚥下運動を誘発させた。また、40個のニューロン活動を記録し、横隔神経、迷走神経および舌下神経の活動、神経発火パターンや頻度をモニターした。その結果、18個のニューロンが、同側上喉頭神経の電気刺激に反応し、6個のニューロンでは液体の経口注水により興奮が惹起されたが、16個の非呼吸性ニューロンでは、電気的/生理的刺激による求心性入力は受けなかった。他にも、咽頭および喉頭の求心性入力による電気的/生理的刺激時にSINにより示された細胞活動から、神経発火パターンおよび神経発火頻度の各位相下での適応や、複雑なニューロンネットワークを形成していることが明らかにされた。以上の実験結果から、嚥下活動で咽頭期に観察されるニューロン活動の調節が、食塊の効率的な移動の調整に寄与することが示唆された。

Language：English   Publisher：In Vivo  

Background/Aim: The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. Patients and Methods: Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. Results: Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. Conclusion: Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.

DOI： 10.21873/invivo.12780

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Scopus

PubMed

Language：English   Publisher：(一社)インターナショナルハートジャーナル刊行会  

免疫チェックポイント阻害薬(ICI)はアテローム性動脈硬化症を悪化させることが近年報告されている。本研究では、そうしたアテローム性動脈硬化の増悪と関連している特徴を同定することを目的とした。2020年10月～2021年3月に当院で肺癌に対しICI治療を行った患者を後方視的に組み入れた。そのうち、免疫関連有害事象(IRAE)が出現していたIRAE群16名(男性11名)と、出現していなかった非IRAE群16名(男性9名)を比較した。アテローム性動脈硬化症の程度は、CT画像で計測された大動脈弓の石灰化粥腫の体積にて評価した。初回ICIの投与開始時と、その初回投与から少なくとも180日後の2時点での粥腫体積の比をみた場合、IRAE群では非IRAE群よりも有意に増悪していた(P=0.002)。1日当たりの粥腫体積増加速度を算出したところ、IRAE群では、ICI投与前の0.09±0.06mm3/日(平均±95%CI)から投与後には0.29±0.23mm3/日へと有意に加速していた(P=0.06)。以上の結果から、IRAEが生じた症例ではICI投与にてアテローム性動脈硬化の進行が加速する傾向にあり、高リスク心血管患者では心血管事象を懸念すべきであることが示された。加えて、石灰化粥腫体積を根拠にIRAEを予測できる可能性があることも判明した。

Language：English   Publisher：In Vivo  

Background/Aim: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). Patients and Methods: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. Results: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. Conclusion: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

DOI： 10.21873/invivo.12790

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PubMed

Publisher：東京医学社  

DOI： 10.24479/ohns.0000000032

CiNii Research

Web of Science

Language：English   Publisher：Anticancer Research  

Background/Aim: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. Patients and Methods: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. Results: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. Conclusion: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

DOI： 10.21873/anticanres.15558

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PubMed

Language：English   Publisher：International Journal of Environmental Research and Public Health  

This study compared the participants’ physiological responses and subjective evaluations of air scented with different concentrations of common rush (Juncus effusus L. var. decipiens Buchen.) (30 g and 15 g, with fresh air as a control). We asked 20 participants to complete a series of visual discrimination tasks while inhaling two different air samples. We evaluated (1) brain activity, (2) autonomic nervous activity, and (3) blood pressure and pulse rate, (4) in combination with self-evaluation. In addition, we quantified the concentrations of volatile organic compounds. The participants reported the scent to be sour, pungent, and smelly; this impression was likely caused by hexanal and acetic acid. Although the self-evaluations showed that participants did not enjoy the scent, their alpha amplitudes of electroencephalogram and parasympathetic nervous activity were increased, suggesting that participants were relaxed in this atmosphere. Moreover, a lower concentration resulted in a greater induction of relaxation. While the air was not pleasant-smelling, the volatile organic compounds present had a positive psychophysiological impact.

DOI： 10.3390/ijerph19031856

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PubMed

Web of Science

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

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2-associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail-anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR-Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6-mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.

DOI： 10.1111/cas.15174

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PubMed

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

BCL2関連athanogene 6(BAG6)複合体の構成要素であるguided entry of tail-anchored proteins factor 4(GET4)が、大腸癌においてBAG6の細胞内局在を制御していることを明らかにした。癌ゲノムデータベースのデータセットを解析したところ、大腸癌でGET4遺伝子はしばしば増幅しており、ドライバー遺伝子の候補となることが突き止められた。GET4遺伝子は腫瘍細胞でDNAコピー数が増加しているために過剰発現していることが判明し、GET4高発現は予後不良の独立因子となっていた。BAG6には遺伝子変化が認められ、主に腫瘍細胞の細胞質内で過剰発現していた。大腸癌細胞を用いたノックアウト実験によってGET4の生物学的重要性について検討した。その結果、in vitro、in vivoのいずれでもGET4は腫瘍の増殖を促進することが示された。BAG6が媒介するp53のアセチル化が細胞質内で豊富に生じ、次いでp21発現が減少するために細胞周期の進行が促進されていると思われた。以上から、GET4はBAG6の細胞質移行を誘導して大腸癌の進行を促進する新規ドライバー遺伝子であり、予後バイオマーカーにもなることが明らかになった。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Management and Research  

Nasopharyngeal carcinoma (NPC) has seen improved treatment outcomes and a decrease in incidence worldwide in recent years due to developments in medicine and improved public health. However, 70% of cases are still diagnosed at advanced stages and these advanced NPC cases show a poor prognosis. Reports on current and future treatment in advanced NPC are summarized. Chemoradiotherapy is the mainstay of treatment for advanced NPC. The administration of platinum agents as a concurrent drug and intensity modulated radiotherapy (IMRT) is the most appropriate irradiation method, and is associated with high local control rates. For induction and adjuvant chemotherapy, platinum-based two- or three-drug combination chemotherapy is recommended. The tumour volume, plasma Epstein-Barr virus (EBV)-DNA levels, and the tumour site are used to determine the indication for adjuvant and neo-adjuvant chemotherapy. The tolerability of induction chemotherapy is controversial, and the indications and timing should be carefully considered in each case. Chemotherapy is used for patients with distant metastasis. Gemcitabine/cisplatin is the first-line regimen. The efficacy of immune checkpoint inhibitor (ICI) treatment has recently been reported for NPC and, as in other areas of the head and neck, it is expected to be effective for patients with recurrent/distant metastasis. Trials are underway for various uses of ICIs, including induction chemotherapy, postoperative treatment, and use in combination with chemoradiotherapy. Immunotherapy for NPC, an EBV-associated cancer, has been reported to have some efficacy with immunotherapy used in other EBV-associated cancers. Immunotherapy may be introduced for NPC in the future, depending on the results of clinical trials. Future changes in the treatment of NPC are expected to include risk classification based on plasma EBV-DNA levels and the development of personalized treatment with individual selection of timing and type of therapy.

DOI： 10.2147/CMAR.S341472

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PubMed

Publisher：International Exchange and Innovation Conference on Engineering and Sciences  

Herein we report the atomic model of pseudomorphic Fe monolayer on Ru(0001) surface analyzed by low energy electron diffraction (LEED) followed by the formation of c(4×2) structure upon exposure to oxygen. After deposition of the Fe overlayer on Ru(0001) surface at room temperature, the prepared surface was exposed to molecular oxygen (O<inf>2</inf>). When 2 Langmuir of O<inf>2</inf> is introduced at room temperature on the prepared Fe(111)/Ru(0001) surface, the pseudomorphic p(1×1) structure of the Fe monolayer on the Ru(0001) surface changes to c(4×2) structure.

DOI： 10.5109/5909092

Scopus

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

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

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

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

Language：Japanese  

CiNii Books

Language：Japanese  

CiNii Books

Language：Japanese  

CiNii Books

Language：Japanese   Publisher：大道学館出版部  

Language：Japanese   Publisher：日本音声言語医学会  

Dysarthriaは「発語運動の遂行過程に関与する神経筋系の障害によって起こる話しことばの音の異常」と定義される病態群である.この病態群の翻訳名称として,保険診療での診療名や国家試験出題基準においては,「運動障害性構音障害」が使用されている.しかしこの翻訳名称について,motor speech disordersの和訳である「運動性構音障害」との定義上の区別が適切に普及しておらず,用法に混乱が生じている,あるいは発語にかかわる協調運動全体に「構音」を用いるのは適切でない,などの理由から,さまざまな議論が起こり,複数の翻訳名称が提唱されている.日本音声言語医学会の言語・発達委員会では,研究者に共有されている病態の定義をできる限り適切に表現して,専門家だけでなく患者を含めた社会にも理解しやすい翻訳名称がdysarthriaに対して定められる必要があると考え,検討を行った.欧米における定義の変遷,また,わが国における翻訳名称に関する議論の歴史を総攬し,検討した結果,dysarthriaの翻訳名称として,「発語運動障害」を提案する.(著者抄録)

Language：Japanese   Publisher：(一社)日本耳科学会  

Language：Japanese   Publisher：(一社)日本耳科学会  

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

側頭骨悪性腫瘍に対する側頭骨一塊切除術は,外側側頭骨切除術(lateral temporal bone resection:LTBR),側頭骨亜全摘術(subtotal temporal bone resection:STBR),側頭骨全摘術(total temporal bone resection:TTBR)の3つの方法が報告されているが,実臨床では,LTBRとSTBRの二つが主に用いられる.STBRは,頭蓋底チームが手術対応できる施設でのみ施行可能な術式である.一方,LTBRは耳鼻咽喉科医単独で施行可能な術式で,非常に洗練された画一的な手術手技である.通常の乳突洞削開術を含む耳科手術の手技に加え,側頭骨鼓室部の骨削除の方法を理解することで,安全に手術を完遂できる.本術式は通常の耳科手術に必要な外科解剖と手術手技を学ぶことができるため,経験の浅い耳鼻咽喉科医にも積極的に関与してもらいたい術式である.手術手技の構成は,通常の乳突洞削開術に後鼓室開放後の鼓室内操作,上/前鼓室開放,後鼓室開放の拡大と側頭骨鼓室部の骨削除などの手技を組み合わせたものとなっている.通常の耳科手術で馴染みの少ない側頭骨鼓室部の削除がKeyとなる手技と思われる.安全に側頭骨の鼓室部の削除を行うためには,錐体鼓室縫合と鼓索神経の関係,骨部耳管と内頸動脈との関係,そして下鼓室とvaginal processとの関係を正確に知る必要がある.本稿では,LTBRを施行する上で必要な骨学と,術前の留意点などに加えて,実際の手術手技の手順について概説する.(著者抄録)

Language：Japanese   Publisher：(有)科学評論社  

Language：Japanese   Publisher：(株)東京医学社  

Language：Japanese   Publisher：(公社)日本医師会  

Language：Japanese   Publisher：日本顔面神経学会  

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

Language：Japanese   Publisher：(株)東京医学社  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Type：Academic society, research group, etc. 

Type：Academic society, research group, etc. 

Type：Competition, symposium, etc. 

Number of participants：200

Type：Competition, symposium, etc. 

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