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

BACKGROUND: In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points. RESULTS: We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity. CONCLUSION: A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study.

DOI： 10.1371/journal.pone.0148339

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The mouse inner ear develops from a simple epithelial pouch, the otocyst, with the dorsal and ventral portions giving rise to the vestibule and cochlea, respectively. The otocyst undergoes a morphological change to generate flattened saclike structures, known as outpocketings, in the dorsal and lateral regions. The semicircular canals of the vestibule form from the periphery of the outpocketings, with the central region (the fusion plate) undergoing de-epithelialization and disappearing. However, little is known of the mechanism that orchestrates formation of the semicircular canals. We now show that the area of canonical Wnt signaling changes dynamically in the dorsal otocyst during its morphogenesis. The genes for several Wnt ligands were found to be expressed in the dorsal otocyst according to specific patterns, whereas those for secreted inhibitors of Wnt ligands were expressed exclusively in the ventral otocyst. With the use of whole-embryo culture in combination with potent modulators of canonical Wnt signaling, we found that forced persistence of such signaling resulted in impaired formation both of the lateral outpocketing and of the fusion plates of the dorsal outpocketing. Canonical Wnt signaling was found to suppress Netrin1 expression and to preserve the integrity of the outpocketing epithelium. In addition, inhibition of canonical Wnt signaling reduced the size of the otocyst, likely through suppression of cell proliferation and promotion of apoptosis. Our stage-specific functional analysis suggests that strict regulation of canonical Wnt signaling in the dorsal otocyst orchestrates the process of semicircular canal formation.

DOI： 10.1016/j.ydbio.2011.11.019

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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)

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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)

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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)

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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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2013年1月から2021年7月の期間に手術治療を行った錐体尖病変15例を検討した。コレステリン肉芽腫4例では、1例が経乳突的に、3例は経鼻的にドレナージルートを作成した。錐体尖真珠腫11例では初発例5例、再手術例が6例であり、進展経路は迷路上型が7例、広範迷路型2例、迷路下型2例であった。迷路上型では進展範囲の小さな症例は経上半規管法により低侵襲に摘出し得たが、進展例や再手術例では中頭蓋窩法や、中頭蓋窩法と経迷路法のcombined approachが必要であった。広範迷路型では経蝸牛+中頭蓋窩法のcombined approachを行い、迷路下型では進展範囲に応じて蝸牛下法や迷路下法を用いた。コレステリン肉芽腫全例と錐体尖真珠腫の3例で聴力温存できた。錐体尖は側頭骨最深部に位置し、手術アプローチの選択が重要である。聴力や病変と解剖学的構造の位置関係を考慮して術式を選択する必要がある。(著者抄録)

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ANCA関連血管炎は腎障害や肺病変などの全身疾患で発症することが多い自己免疫性血管炎であるが、近年、中耳炎初発・耳限局型のANCA関連血管炎の報告が増加している。本症例は結核の既往がある52歳女性で、主症状は抗菌薬無効の中耳炎と難聴、頭痛であった。難治性中耳炎としてANCA関連血管炎性中耳炎(OMAAV)を鑑別に挙げてはいたものの、ANCA抗体陰性で生検組織は血管炎の所見が得られず、また、結核性中耳炎の可能性を懸念し診断に苦慮した。最終的に、OMAAVに特徴的とされる肥厚性硬膜炎の合併や、ANCA関連血管炎やその他自己免疫疾患の診療経験が豊富な膠原病内科医による他臓器評価により除外診断を行いOMAAVの診断を得た。診断までに1年を要したOMAAVの症例を経験したため、主にその診断について若干の文献的考察を加えて報告する。(著者抄録)

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

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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DOI： 10.3950/jibiinkotokeibu.125.5_916

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DOI： 10.1172/jci.insight.139171

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DOI： 10.1172/jci.insight.139171

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中頭蓋より発生し中耳進展した髄膜腫の1例を経験した。髄膜腫はクモ膜細胞より発生する良性腫瘍でクモ膜顆粒の分布領域に沿って発生しやすいとされており、頭蓋外に発生する頻度は低く中耳腫瘍として経験することは少ない。本症例は、難聴を主訴に耳鼻咽喉科を受診したところ中耳腫瘍を指摘された。当院での画像所見および組織生検時の術中所見から、中頭蓋窩髄膜腫が上鼓室天蓋を介して中耳進展を来したと考えられた。中頭蓋窩法を併用した乳突洞削開を行い、中頭蓋窩腫瘍、中耳・乳突洞内の腫瘍を全摘し得た。(著者抄録)

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BACKGROUND: There is no guideline for hearing compensation after temporal bone resection. This study aimed to retrospectively analyze surgical cases with reconstruction for hearing preservation after temporal bone malignancy resection and propose a new alternative to compensate for hearing loss. METHODS: We retrospectively reviewed the medical records of 30 patients who underwent lateral temporal bone surgery for temporal bone malignancy at our institution and examined their hearing abilities after surgery. RESULT: The hearing outcomes of patients with an external auditory meatus reconstruction varied widely. The mean postoperative air-bone gap at 0.5, 1, 2, and 4 kHz ranged from 22.5 dB to 71.25 dB. On the other hand, the average difference between the aided sound field thresholds with cartilage conduction hearing aid and bone conduction thresholds at 0.5, 1, 2, and 4 kHz ranged from -3.75 to 41.25. More closely located auricular cartilage and temporal bone resulted in smaller differences between the aided sound field and bone conduction thresholds. CONCLUSIONS: There is still room for improvement of surgical techniques for reconstruction of the auditory meatus to preserve hearing after temporal bone resection. The cartilage conduction hearing aid may provide non-invasive postoperative hearing compensation after lateral temporal bone resection.

DOI： 10.3390/audiolres11020024

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

OBJECTIVES: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. DESIGN: Multi-institutional prospective single-arm observational study. SETTING AND PARTICIPANTS: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. METHODS: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). RESULTS: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. CONCLUSIONS AND IMPLICATIONS: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family.

DOI： 10.1016/j.jamda.2021.02.035

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OBJECTIVE/HYPOTHESIS: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC. STUDY DESIGN: Case reries with chart review. METHODS: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival. RESULTS: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers. CONCLUSIONS: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs. LEVEL OF EVIDENCE: 4 Laryngoscope, 2021.

DOI： 10.1002/lary.29421

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軟骨伝導補聴器は耳介の軟骨に振動子を当てることで外耳道内で軟骨が音を発生させ補聴効果をもたらす新しい原理の補聴器である。九州大学病院で軟骨伝導補聴器外来の運用を開始して約2年経過した現在までの軟骨伝導補聴器試聴と仮フィッティングした例の統計、購入者と非購入者の傾向を検討した。試聴した人の中で軟骨伝導補聴器を購入した人の割合は外耳道閉鎖/狭窄症、および中耳炎術後/慢性耳漏例の患者に高かった。聴力では、裸耳音場閾値に比べ装用閾値が低い患者に購入が多かった。しかし、それまで補聴器を使っていた人の装用閾値と比べて軟骨伝導補聴器の装用閾値が必ずしも低くなくても購入する人が多く、他の補聴器との比較の際は、装用閾値だけで決めていないことが示唆された。(著者抄録)

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Objective: 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.
Method: 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.
Results: 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 cases, 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%).
Conclusion: 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.

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

Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1&#37;) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9&#37;) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2&#37;, 85.7&#37;, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.

DOI： 10.3390/cancers12082299

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External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6&#37;). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm-level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.

DOI： 10.1111/cas.14515

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Objective: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. Our objective here was to explore anatomical factors associated with the prognosis of T4 TB-SCC cases. Study Design: Case series with chart review. Setting: Two academic tertiary care medical centers. Subjects and Methods: The medical records of all TB-SCC cases were retrospectively reviewed in two institutions. The resulting data set contained 30 cases of primary T4 cancer eligible for initial definitive (curative) treatment. Disease-specific survival was calculated according to the Kaplan-Meier method. Cox proportional hazards model was used to identify anatomical prognosis factors. Results: The disease-specific 5-years survival rate of 30 cases of T4 TB-SCC was 53.9&#37;. The tumor invasion to the pterygoid muscle, posterior fossa dura, and sigmoid sinus and destruction of the ossicles were associated with poor prognosis in univariate analysis. The multivariate analysis reveals that the invasion of the ossicles, posterior fossa dura, and sigmoid sinus is an independent prognostic factor [hazard ratio (HR): 4.528 (95&#37; CI: 1.161-17.658), p = 0.030; HR: 5.135 (95&#37; CI: 1.616-16.315), p = 0.006; HR: 4.292 (95&#37; CI: 1.385-13.303), p = 0.012]. The invasion of the carotid canal, petrous apex, middle fossa dura, otic capsule, pterygoid muscle, and middle ear had a high HR (HR > 2). The more invaded anatomical factors present in patients resulted in a poorer patient disease-specific prognosis, with a statistically significant difference. Conclusions: Assessing which anatomical structures are susceptible to invasion by tumors may be important for predicting TB-SCC patient prognosis and selecting appropriate treatment planning, especially surgical intervention. In addition to previously reported factors, the destruction of the ossicles in the middle ear cavity can be an anatomical prognosis factor.

DOI： 10.3389/fonc.2020.01229

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OBJECTIVES/HYPOTHESIS: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors. STUDY DESIGN: Retrospective chart review. METHODS: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment. RESULTS: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100&#37;, T2: 92&#37;, T3: 86&#37;, T4: 51&#37;). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins. CONCLUSIONS: Definitive treatments can offer disease-specific 5-year survival of over 85&#37; in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

DOI： 10.1002/lary.28653

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We retrospectively reviewed the records of 68 patients with oropharyngeal squamous cell carcinoma who had undergone initial treatment in the Department of Otolaryngology, Head and Neck Surgery, Hamanomachi Hospital between 2009 and 2017. We compared therapeutic outcomes of p16-positive with p16-negative cases, referring to Unio Internationalis Contra Cancrum（UICC）diagnostic criteria version 7 and 8. Of 68（58.5％）patients, 38 were diagnosed as p16-positive. The 3-year disease-specific survival rate of all patients, p16-positive, and p16-negative patients were 78.5％, 74.1％, and 84.7％, respectively. Referring to UICC version 8, the 3-year disease-specific survival rate（3DSS）of p16-negative patients in each clinical stage was stage Ⅱ: 100％, stageⅢ: 66.7％, and stage Ⅳa: 70.6％, whereas 3DSS of p16-positive patients was stage I: 93.8％, stageⅡ: 83.3％, stageⅢ: 77.1％, and stage Ⅳ: 0％.

DOI： 10.5981/jjhnc.46.59

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Language：Japanese  

Language：Japanese  

ダイレクトリプログラミングによるラセン神経節細胞の再生を目指し、Ascl 1とNeuroD1の共発現がよりラセン神経節に近似した神経の誘導できると仮説を立てた。内因性のラセン神経節細胞、ラセン神経節非神経細胞、リプログラミングされた神経細胞の3者を比較してトランスクリプトーム解析を行った。著者らがラセン神経節非神経細胞(SGNNC)から作製した一部の誘導神経細胞(iN)は内因性のTau-EGFP陽性内因性ラセン神経節細胞(PAN)に酷似した性質を有した。これらのiNはPANと同じ双極性ニューロンでありかつPAN特異的タンパクを発現した。しかし、トランスクリプトーム解析によるとiNには起源細胞であるSGNNCの特徴が残存していた。これは、本研究において、リプログラミングのために培養した期間は1週間と他の報告より比較的短かった故、リプログラミングが不完全であった可能性がある。加えて、起源細胞の中で細胞種特異的なリプログラミング因子があることが想定されている。SGNNCはヘテロな細胞集団から構成されるために各々の細胞集団のリプログラミングの品質に差異が生じる可能性がある。RNA-seqのデータによると、iNはシュワン細胞あるいは線維芽細胞のトランスクリプトームプロファイルを残していた。このことはシュワン細胞も線維芽細胞も共に神経にリプログラムされる能力(competence)があることを示している。

Language：Japanese  

同種造血幹細胞移植後に出現した浸潤性副鼻腔真菌症に対して、眼球摘出により救命し得た症例を経験した。抗真菌薬の薬物治療および眼球摘出を行わない副鼻腔手術のみでは感染がコントロールできず、3回目の手術で眼球を摘出した。重度の免疫不全状態を伴う浸潤性副鼻腔真菌症に対してはより積極的な手術が必要で、経過次第で眼窩内に病変が及ぶ場合は病勢のコントロールのために眼球摘出も選択肢に挙げるべきと考えられた。(著者抄録)

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In 102 patients who performed contrast―enhanced MRI and underwent surgery for a tumor of the parotid gland, we compared the preoperative diagnoses made by fine needle aspiration cytology（FNAC）and imaging diagnoses made by enhanced MRI, including a dynamic study and calculation of the apparent diffusion coefficient（ADC）. In contrast―enhanced MRI, the ADC values of pleomorphic adenomas were significantly higher than those of Warthin's tumors. In addition, the ADC values of carcinomas were significantly lower than those of pleomorphic adenomas and significantly higher than those of Warthin's tumors. The patterns of the time―signal intensity curve in the dynamic study were as follows: persistent pattern in 23 cases, washout pattern in 38 cases, and the plateau pattern in 41 cases. Contrast―enhanced MRI was performed in 102 cases and a pathological diagnosis was available for 85 cases. The diagnostic accuracy rate of contrast―enhanced MRI in the 85 cases for which a pathological diagnosis was available was 82.3&#37;（70 cases/ 85 cases）, 70 cases with the correct diagnosis was 68.6&#37;（70 cases/102 cases）in which contrast―enhanced MRI was performed. FNAC was performed in 93 cases and pathological diagnosis was available for 46 cases. The diagnostic accuracy rate of FNAC in the 46 cases for which a pathological diagnosis was available was 84.7&#37;（39 cases/46 cases）. 39 cases with the correct diagnosis was 41.9&#37;（39 cases/93 cases）of cases in which FNAC was performed. There were 34 cases in which the preoperative diagnosis made by FNAC and that made by MRI were in agreement and the diagnostic accuracy rate in them was 94.1&#37;（32 cases/34 cases）.

DOI： 10.3950/jibiinkoka.121.1063

Language：Japanese  

術前に造影MRIを撮影し耳下腺の手術を施行した102例について、造影MRIによるdynamic studyおよびapparent diffusion coefficient(ADC値)を含めた総合的な術前画像診断と、穿刺吸引細胞診(FNAC)による術前診断の比較を行うとともにその相乗効果について検討した。多形腺腫のADC値はワルチン腫瘍のADC値と比較して有意に高値であった。また、癌腫のADC値は多形腺腫よりも有意に低値で、ワルチン腫瘍よりも有意に高値であった。dynamic studyのTime-signal intensity curveはPersistent patternが23例、Wash-out patternが38例、Plateau patternが41例であった。造影MRIの放射線科レポートで組織型診断できた85例の正診率は82.3&#37;で、正診を得た70例は造影MRIを撮影した症例の68.6&#37;に相当した。93例においてFNACが施行され、組織型診断ができた症例は46例で正診率は84.7&#37;であった。正診を得た39例はFNACを施行した症例の41.9&#37;に相当した。MRIによる術前画像診断とFNACによる術前診断とが一致していた症例は34例あり、94.1&#37;にあたる32例で病理組織診断とも一致した。(著者抄録)

Language：Japanese  

小児の慢性中耳炎に対する鼓室形成術では、手術の時期について統一した見解が得られていない。われわれは当科で鼓室形成術I型を施行した15歳以下の症例を対象に、年齢と鼓膜穿孔閉鎖率、術後聴力との関連について検討した。小児の慢性中耳炎に対する鼓室形成術では小児の耳管機能や、急性上気道炎、滲出性中耳炎などの罹患率を考慮し、待機可能な症例は10歳を目安に待機することが望ましい。また、耳漏を主訴とする症例は術前に炎症コントロールを行ってから手術に望むべきであるが、その際は菌検査を行った上で鼓室洗浄を行い、コントロールが不良であれば抗菌薬の点耳を行うことが推奨される。(著者抄録)

Language：Japanese  

難聴の本質はコミュニケーション障害であり、言語獲得、学業、就労、家庭など人生のさまざまなステージで多大な問題を引き起こしている。現在広く用いられている補聴の機器としては補聴器と人工内耳があり、これらの装用者は難聴患者の増加に伴って今後増加すると予想される。しかし、補聴器はその外見や価格などからすべての難聴者に受け入れられているとは言い難く、また難聴の程度によっては十分な効果が得られないことも多い。反響や残響、周囲の騒音レベルなどによっても、補聴器や人工内耳の効果は減退する。こういった問題を補完するため、2013年冬に難聴支援スピーカーComuoonが発売された。強い指向性と高音域を増強する周波数特性を持ち、聴取改善に寄与するとされる。その有用性を検証しここに報告する。(著者抄録)

Language：Japanese  

ミトコンドリア脳筋症・乳酸アシドーシス・脳卒中様発作症候群(MELAS)は反復する脳卒中様発作を特徴とするミトコンドリア病の一種である。感音難聴はMELASの40-60&#37;に合併するといわれている。時に補聴器装用効果に乏しい重度難聴に陥るケースも経験するが、頻度が低いためか、MELASによる難聴に対し人工内耳埋込み術を行った報告は少ない。今回、われわれはミトコンドリア脳筋症3例に対して人工内耳埋込み術を施行し、2例で良好な聴取成績を得ることができた。ミトコンドリア脳筋症に伴う難聴は一般的に内耳性難聴が多いが、後迷路性難聴も否定できず、後迷路性難聴が疑われる場合の人工内耳適応については、これからも更なる検討が必要と考える。(著者抄録)

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Background: Good outcomes have been reported regarding the use of cochlear implants for mumps deafness. The mumps virus induces meningitis and/or encephalitis, which can cause central nervous system damage resulting in retrolabyrinthine hearing loss, for which a cochlear implant would be less effective. Cases: We installed a cochlear implant in two patients with bilateral mumps deafness; one achieved a good result with the cochlear implant, but the other did not. We discuss two possible reasons for the different outcomes. Case 1 was a three-year-old girl with bilateral parotid swelling, vomiting and walking disorder. One year after cochlear implant insertion, speech perception did not develop despite of good pure tone thresholds. Case 2 was an eight-year-old girl with bilateral parotid swelling. A cochlear implant enabled her to improve hearing perception. Conclusion: Although cochlear implants have been reported to be helpful for mumps deafness, cases that involve central nervous system damage may not achieve good results.

DOI： 10.1017/S0022215114002369

Language：Japanese  

中咽頭癌の発癌メカニズムとして、近年ヒトパピローマウイルス(HPV)の関与が示唆されている。HPVはその発癌性からHPV16、HPV18などの高リスク群と、HPV6、HPV11などの低リスク群に分けられる。これまで本邦では低リスク群が陽性であった中咽頭癌症例の報告はなく、海外の文献でも非常に少数である。今回われわれは、HPV6陽性中咽頭後壁癌の1例を経験した。術前化学療法が著効し、摘出標本に癌細胞を認めなかった。病理組織学的検討を行ったところ、p16は基底層を含む一部の細胞で局在を認めたが、高リスク群のような高発現は認めなかった。発癌の原因は不明であるが、まれな症例であり今後症例を蓄積した上で詳細な検討が必要と考えられる。(著者抄録)

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

BACKGROUND: Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease. CASE SUMMARY: We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40&#37; of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease. DISCUSSION: IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.

DOI： 10.1016/j.anl.2013.11.002

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Three cases of tuberculosis otitis media
Tuberculosis is a rare cause of otitis media (called TOM). It often takes time to establish a diagnosis of TOMbecause of the clinical variability of the disease. We herein report three cases of TOM recently treated atHamanomachi Hospital between April 2005 and March 2013. It took seven days, six months and four months toestablish the diagnosis of TOM from the first visit to our hospital and it took one year, eight months and six monthfrom the first visit to a medical institution until the diagnosis. TOM can induce serious complications, likesensorineural hearing loss and facial palsy, so an early diagnosis and early treatment are needed. Therefore, TOMshould be suspected in cases of intractable otitis media, and it benefits patients to start antituberculosis treatmentearly, because it may prevent the development of severe complications.

DOI： 10.11334/jibi.59.290

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Wntシグナルは生命現象の様々な局面で重要な役割を果たすが、内耳発生においても耳プラコード誘導から耳胞形成、半規管形態形成に関与していることがわかってきた。マウス内耳の半規管形態形成におけるWntシグナルの働きについて、最近の自研究成果等を紹介しながら以下の項目で解説した。1)Wntシグナルとは、2)内耳発生、3)内耳形成とWntシグナル活性の経時的変化、4)阻害剤を用いたWntシグナルの機能解析、5)耳胞マーカー遺伝子の変化と基底膜。

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

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

Although salicylate is one of the most widely used nonsteroidal anti-inflammatory drugs, it causes moderate hearing loss and tinnitus at high-dose levels. In the present study, salicylate effects on the K currents in inner hair cells were examined. Salicylate reversibly reduced the outward K currents (I(K,f)), but did not affect the inward current (I(K,n)). Salicylate blocked the outward K currents in a concentration-dependent manner according to Hill equation with a half-blocking concentration of 1.66mM, and the Hill coefficient of 1.86.

DOI： 10.1016/j.neulet.2011.08.050

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Hydrogen peroxide (H₂O₂) is a ubiquitous reactive oxygen species that can induce several inner ear disorders. In this study, we recorded the potassium (K) currents in acutely isolated inner hair cells of guinea pig cochlea, and investigated the effects of H₂O₂. We also observed the morphological changes in inner hair cells induced by H₂O₂. In the H₂O₂ solutions, the amplitude of outward K currents (I(K,f) and I(K,s)) clearly decreased after perfusion for approximately 15 min. Despite the decrease in outward currents, small inward currents (I(K,n)) did not show any reduction. H₂O₂ induced morphological changes in the inner hair cells. All the inner hair cells in the H₂O₂ solutions showed shrinkage and granularity of the cell body and led to loss of viability. These results showed the vulnerability of inner hair cells to reactive oxygen species-induced inner ear disorders.

DOI： 10.1097/WNR.0b013e32833fcb56

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One of the potassium currents, I(K,)(n), is already activated at the resting potential of the cell and thus determines the membrane potential. KCNQ4 channel has been identified as the molecular correlate of I(K,)(n). In the present study, we measured I(K,)(n) in acutely isolated IHCs of guinea-pig cochlea using the whole-cell voltage-clamp techniques, and investigated the properties of the currents. I(K,)(n) was 70&#37; activated around the resting potential of -60 mV and deactivated on hyperpolarization. I(K,)(n) was blocked by the KCNQ-channel blockers, linopirdine (100 microM) and XE991 (10 microM), but was insensitive to both I(K,f) blocker, tetraethylammonium (TEA), and I(K,s) blocker, 4-aminopyridine (4-AP). There was no significant difference in the size of I(K,)(n) between the apical and basal turn IHCs.

DOI： 10.1016/j.heares.2010.01.002

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OBJECTIVES: The aim of this study is to investigate the salicylate-induced morphological changes of cochlear inner hair cells (IHCs) and outer hair cells (OHCs). METHODS: IHCs and OHCs were acutely isolated from the guinea-pig cochlea. Cells were observed under the inverted microscope and 10mmol/L sodium salicylate solutions or 0.01mmol/L dexamethasone-plus-salicylate solutions were applied. The cell length or the ratio between the length and width was the indices of the morphological changes in cells. RESULTS: Isolated IHCs did not demonstrate any significant changes in sodium salicylate solutions in 20min and in 40min, whereas OHCs were shortened by the 10mmol/L sodium salicylate to 83&#37; in 20min and 75&#37; in 40min. There were no significant differences between in the dexamethasone-plus-salicylate solutions and in the control solutions after 20min and 40min both in IHCs and OHCs. CONCLUSIONS: Although salicylate affected the isolated OHCs from guinea-pig cochlea, IHCs were not changed morphologically by sodium salicylate applications. Dexamethasone inhibited the salicylate-induced morphological changes of OHCs.

DOI： 10.1016/j.anl.2008.05.005

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内耳機能検査の中で、時間的な患者への負担が少なく実際の外来業務で施行しやすいDPOAE検査、SISI検査、MCL・UCL検査を112名、203耳に施行し比較した。DPOAE検査の異常率は1kHzで41&#37;、4kHzで69&#37;、SISI検査の陽性率は1kHzで20&#37;、4kHzで53&#37;、MCL・UCL検査の陽性率は1kHで43&#37;、4kHzで54&#37;であった。4kHzで聴力レベルの程度による各検査の陽性率(異常率)を比較すると、各検査とも約20dBより陽性を示したが、DPOAE検査では35dBで90&#37;以上が陽性となったのに対して、SISI検査、MCL・UCL検査では上昇は緩やかで55dBで約90&#37;が陽性となった。軽度の感音難聴ではDPOAEのみ異常となることが多いという結果を得た。(著者抄録)

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

Tetraethylammonium (TEA)-sensitive potassium currents in the cochlear inner hair cells (IHCs) possess the kinetics of fast inactivation. IHCs of guinea-pigs were separately isolated from the apical and basal turns and the tonotopic gradient of inactivation kinetics was investigated. TEA-sensitive potassium currents showed voltage-dependent time constant of the inactivation phase both in apical and basal IHCs, however, the degree of inactivation (compared to the ratio between the steady-state current and initial peak current) was voltage-independent. Inactivation time constant was faster in basal IHCs than in apical IHCs and the degree of inactivation was greater in basal IHCs than in apical IHCs, suggesting that inactivation was more predominant in basal IHCs than in apical IHCs.

DOI： 10.1016/j.brainres.2008.06.068

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20歳女性。患者は体重増加、多毛、赤色皮膚線条、創傷治癒遅延、月経不順を主訴に、精査目的で著者らの施設へ入院となった。所見では高血圧、中心性肥満、満月様顔貌、四肢の浮腫がみられ、更に左乳腺に小指頭大結節、および一般検査で耐糖能障害を認めた。一方、内分泌検査では尿中17-OHCS、尿中遊離コルチゾールの高値、血漿ACTH低値、血中コルチゾール高値を認め、血中コルチゾールは日内変動の消失とデキサメタゾンに対する抑制の欠如を認めた。また、腹部CTでは両側副腎に結節が確認された。以上、これらのことより、本症例は両副腎腫瘍によるクッシング症候群と診断され、二期的に両側副腎摘出を施行したところ、病理組織学的にはPPNADで、術後はクッシング徴候や上記症状の改善を認めた。尚、乳房超音波では左乳腺C領域に低エコー結節が認められ、細胞診により乳腺線維腫であった。

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Kremen1 regulates mechanosensory cell development in the mammalian cochlea and the zebrafish lateral line

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Wnt signaling in cochlear development and regeneration

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Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo

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Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo

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Cochlear implant for mumps deafness

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