研究者詳細 - 安藤　瑞生

論文 - 安藤　瑞生

分割表示 146 件中 61 - 80 件目／全件表示 >>

Subclinical obstructive lung function changes in patients with sinus fungus ball. 査読国際誌

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

Allergology international : official journal of the Japanese Society of Allergology 71 ( 4 ) 539 - 541 2022年4月

The fine-needle aspiration cytology and clinical findings of Kikuchi-Fujimoto disease in pediatric patients: a retrospective clinical study. 査読国際誌

Yuto Naoi, Tomoyasu Tachibana, Yoji Wani, Machiko Hotta, Katsuya Haruna, Yasutoshi Komatsubara, Kazunori Kuroda, Soichiro Fushimi, Tami Nagatani, Yuko Kataoka, Kazunori Nishizaki, Yasuharu Sato, Mizuo Ando

Acta oto-laryngologica 142 ( 3-4 ) 1 - 5 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Histological evaluation of lymph node is crucial for the definitive diagnosis of Kikuchi-Fujimoto disease (KFD). However, lymph node biopsy under local anesthesia is often difficult in pediatric patients. OBJECTIVES: We evaluated cytological findings for pediatric patients with prolonged cervical lymphadenitis clinically suggestive of KFD and investigated the clinical characteristics of patients diagnosed with KFD by fine-needle aspiration cytology (FNAC). METHODS: This retrospective clinical study included 58 Japanese pediatric patients with cervical lymphadenitis who underwent FNAC. RESULTS: Cytological diagnosis was KFD for 22 and suspicion of KFD for 11 patients. The remaining 25 patients were diagnosed with non-specific lymphadenitis (NSL). Tenderness was independently associated with a higher frequency of both KFD in narrow and broad senses, compared with NSL (p = .009; p = .038). The percentage of patients who underwent FNAC within 28 days from symptom onset tended to be higher among patients with KFD in a narrow sense than those with NSL (p = .052). CONCLUSION: This study indicated that the period from symptom onset to FNAC (<28 days) and the symptom of tenderness were associated with the cytological diagnosis of KFD.

DOI： 10.1080/00016489.2022.2040744

Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report. 査読国際誌

Marie Yamashita, Mahoko Ikeda, Ito Kato, Yuki Ohama, Mizuo Ando, Masako Ikemura, Daisuke Jubishi, Yoshiaki Kanno, Koh Okamoto, Takashi Umeyama, Shigeki Nakamura, Yoshitsugu Miyazaki, Shu Okugawa, Kyoji Moriya

Annals of clinical microbiology and antimicrobials 21 ( 1 ) 5 - 5 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals. CASE PRESENTATION: We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period. CONCLUSIONS: Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus.

DOI： 10.1186/s12941-022-00495-6

Clinicopathologic Analysis of Sinonasal Inverted Papilloma, with Focus on Human Papillomavirus Infection Status 査読

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

Diagnostics 12 ( 2 ) 454 - 454 2022年2月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.

DOI： 10.3390/diagnostics12020454

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy 査読

Natsuki Saigusa, Hideaki Hirai, Yuichiro Tada, Daisuke Kawakita, Masato Nakaguro, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Takahito Kondo, Kenji Okami, Takafumi Togashi, Yukiko Sato, Makoto Urano, Manami Kajiwara, Tomotaka Shimura, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Takuro Okada, Takayoshi Suzuki, Yorihisa Imanishi, Yoshihiro Watanabe, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Yoshitaka Honma, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Hideaki Takahashi, Mizuo Ando, Shinji Kohsaka, Takashi Matsuki, Toshitaka Nagao

Frontiers in Oncology 11 2022年2月

掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

<sec><title>Objective</title>Salivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only <italic>de novo</italic> but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.

</sec><sec><title>Materials and Methods</title>The EZH2 and H3K27me3 immunohistochemical expression and <italic>EZH2</italic> Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).

</sec><sec><title>Results</title>EZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. <italic>EZH2</italic> Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.

</sec><sec><title>Conclusions</title>A high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

</sec>

DOI： 10.3389/fonc.2021.779882

Dermatomyositis With Carcinoma of Unknown Primary Disease in the Head and Neck Diagnosed by Muscle Biopsy During Neck Dissection. 査読国際誌

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

JAMA otolaryngology-- head & neck surgery 148 ( 2 ) 195 - 196 2022年2月

Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer. 査読国際誌

Ken Akashi, Toshihiko Sakai, Osamu Fukuoka, Yuki Saito, Masafumi Yoshida, Mizuo Ando, Takeshi Ito, Yoshinori Murakami, Tatsuya Yamasoba

Scientific reports 12 ( 1 ) 572 - 572 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

In head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.

DOI： 10.1038/s41598-021-04307-3

Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma. 査読国際誌

Maki Akamatsu, Takuma Makino, Shinya Morita, Yohei Noda, Shin Kariya, Tomoo Onoda, Mizuo Ando, Yoshihiro Kimata, Kazunori Nishizaki, Mitsuhiro Okano, Aiko Oka, Kengo Kanai, Yoshihiro Watanabe, Yorihisa Imanishi

Frontiers in oncology 12 1010252 - 1010252 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Although patients with oral squamous cell carcinoma who develop contralateral neck metastasis (CLNM) have worse survival outcomes than those without CLNM, accurate prediction of occult CLNM in clinically negative contralateral neck (contralateral cN0) remains difficult. This study aimed to identify clinicopathological factors that could reliably predict CLNM in patients with locally advanced (clinical T3 and T4a) tongue squamous cell carcinoma (TSCC). PATIENTS AND METHODS: The medical data of 32 patients with cT3-4a TSCC who underwent curative surgery between 2010 and 2017 were retrospectively analyzed. The correlation of clinicopathological variables with CLNM was examined using logistic regression analysis. The diagnostic performance of significant variables was evaluated using the area under the receiver operating characteristic curves (AUC). Overall survival (OS) and disease-free survival (DFS) were assessed using a Cox proportional hazards model. RESULTS: CLNM was eventually confirmed in 11 patients (34.4%). Multivariate logistic regression showed that midline involvement [odds ratio (OR) = 23.10, P = 0.017] and perineural invasion (PNI, OR = 14.96, P = 0.014) were independent predictors of CLNM. Notably, the prediction model comprising a combination of midline involvement and PNI exhibited superior diagnostic performance with an even higher OR of 80.00 (P < 0.001), accuracy of 90.3%, and AUC of 0.876. The multivariate Cox hazards model revealed independent significance of CLNM as an unfavorable prognostic factor for both OS [hazard ratio (HR) = 5.154, P = 0.031] and DFS (HR = 3.359, P = 0.038), as well as that of PNI for OS (HR = 5.623, P = 0.033). CONCLUSION: Our findings suggest that coexisting midline involvement and PNI of the primary tumor is highly predictive of CLNM development, which independently affects both OS and DFS in patients with locally advanced TSCC. Such reliable prediction enables efficient control of CLNM by optimizing management of the contralateral cN0 neck, which will likely contribute to improved prognosis of those patients without unnecessarily compromising their quality of life.

DOI： 10.3389/fonc.2022.1010252

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma. 査読国際誌

Daisuke Kawakita, Toshitaka Nagao, Hideaki Takahashi, Satoshi Kano, Yoshitaka Honma, Hideaki Hirai, Natsuki Saigusa, Kohei Akazawa, Kaori Tani, Hiroya Ojiri, Kiyoaki Tsukahara, Hiroyuki Ozawa, Kenji Okami, Takahito Kondo, Takafumi Togashi, Chihiro Fushimi, Tomotaka Shimura, Akira Shimizu, Isaku Okamoto, Takuro Okada, Yorihisa Imanishi, Yoshihiro Watanabe, Kuninori Otsuka, Akihiro Sakai, Koji Ebisumoto, Yuichiro Sato, Keisuke Yamazaki, Yushi Ueki, Toyoyuki Hanazawa, Yuki Saito, Mizuo Ando, Takashi Matsuki, Masato Nakaguro, Yukiko Sato, Makoto Urano, Yoshitaka Utsumi, Shinji Kohsaka, Takashi Saotome, Yuichiro Tada

Therapeutic advances in medical oncology 14 17588359221119538 - 17588359221119538 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. METHODS: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. RESULTS: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. CONCLUSION: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

DOI： 10.1177/17588359221119538

Static posturographic balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing process. 査読国際誌

Yukihide Maeda, Soshi Takao, Iku Abe-Fujisawa, Shin Kariya, Mizuo Ando

Acta oto-laryngologica 142 ( 3-4 ) 280 - 284 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Understanding how sensorineural hearing loss (SNHL) impacts postural balance in patients is important, as postural balance predicts the risk of falls. AIMS/OBJECTIVES: We aimed to clarify the relationship between characteristics in the configuration of audiograms and static postural balance as measured by posturography. MATERIALS AND METHODS: We evaluated 385 outpatients (mean [± standard deviation] age, 58.4 ± 18.4 years) with SNHL by audiometry and posturography. Data were analysed by multiple regression models with the outcome of postural sway area with eyes closed (PSA) and predictive variables of audiometric data, adjusted for sex, age and the presence of nystagmus. RESULTS: The increased hearing threshold in the better hearing ear was associated with poorer or higher PSA (beta coefficient [β] = 0.39, 95% confidence interval [CI] = 0.03-0.75, per 10-dB increment). No difference in PSA was detected between patients with asymmetric or symmetric SNHL. None of the frequent diagnoses (presbyacusis, Meniere's disease, and idiopathic sudden SNHL) were associated with poorer PSA. Hearing thresholds at middle (β = 0.39, 95%CI = 0.10-0.67) and high frequencies (β = 0.31, 95%CI = 0.07-0.55) were associated with poorer PSA, whereas those at low frequencies was not. CONCLUSIONS AND SIGNIFICANCE: Postural balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing.

DOI： 10.1080/00016489.2022.2047222

Transcript-targeted analysis reveals isoform alterations and double-hop fusions in breast cancer. 査読国際誌

Shinichi Namba, Toshihide Ueno, Shinya Kojima, Kenya Kobayashi, Katsushige Kawase, Yosuke Tanaka, Satoshi Inoue, Fumishi Kishigami, Shusuke Kawashima, Noriko Maeda, Tomoko Ogawa, Shoichi Hazama, Yosuke Togashi, Mizuo Ando, Yuichi Shiraishi, Hiroyuki Mano, Masahito Kawazu

Communications biology 4 ( 1 ) 1320 - 1320 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although transcriptome alteration is an essential driver of carcinogenesis, the effects of chromosomal structural alterations on the cancer transcriptome are not yet fully understood. Short-read transcript sequencing has prevented researchers from directly exploring full-length transcripts, forcing them to focus on individual splice sites. Here, we develop a pipeline for Multi-Sample long-read Transcriptome Assembly (MuSTA), which enables construction of a transcriptome from long-read sequence data. Using the constructed transcriptome as a reference, we analyze RNA extracted from 22 clinical breast cancer specimens. We identify a comprehensive set of subtype-specific and differentially used isoforms, which extended our knowledge of isoform regulation to unannotated isoforms including a short form TNS3. We also find that the exon-intron structure of fusion transcripts depends on their genomic context, and we identify double-hop fusion transcripts that are transcribed from complex structural rearrangements. For example, a double-hop fusion results in aberrant expression of an endogenous retroviral gene, ERVFRD-1, which is normally expressed exclusively in placenta and is thought to protect fetus from maternal rejection; expression is elevated in several TCGA samples with ERVFRD-1 fusions. Our analyses provide direct evidence that full-length transcript sequencing of clinical samples can add to our understanding of cancer biology and genomics in general.

DOI： 10.1038/s42003-021-02833-4

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study. 査読

Ryuji Yasumatsu, Yasushi Shimizu, Nobuhiro Hanai, Shin Kariya, Tomoya Yokota, Takashi Fujii, Kiyoaki Tsukahara, Mizuo Ando, Kenji Hanyu, Tsutomu Ueda, Hitoshi Hirakawa, Shunji Takahashi, Takeharu Ono, Daisuke Sano, Moriyasu Yamauchi, Akihito Watanabe, Koichi Omori, Tomoko Yamazaki, Nobuya Monden, Naomi Kudo, Makoto Arai, Syuji Yonekura, Takahiro Asakage, Takahiro Nekado, Takayuki Yamada, Akihiro Homma

International journal of clinical oncology 27 ( 1 ) 95 - 104 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy. METHODS: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs). RESULTS: Overall, 256 patients received a median of 6.0 doses (range: 1-52) of nivolumab over a median duration of 72.5 days (range: 1-736). Median OS was 9.5 months [95% confidence interval (CI) 8.2-12.0] and median PFS was 2.1 months (95% CI 1.8-2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9-11.9) and 3.5 months (95% CI 2.3-5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis. CONCLUSIONS: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.

DOI： 10.1007/s10147-021-02047-y

Underwater posterior nasal neurectomy compared to resection of peripheral branches of posterior nerve in severe allergic rhinitis. 査読国際誌

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

Acta oto-laryngologica 141 ( 8 ) 780 - 785 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

DOI： 10.1080/00016489.2021.1925151

Apocrine Hidrocystoma of the External Auditory Canal in a Child. 査読国際誌

Tomoyasu Tachibana, Tomoaki Sasaki, Yoji Wani, Yuto Naoi, Yuko Kataoka, Kazunori Nishizaki, Mizuo Ando

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 42 ( 8 ) e1181-e1183 2021年6月

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan. 査読国際誌

Chikatoshi Katada, Manabu Muto, Satoshi Fujii, Tetsuji Yokoyama, Tomonori Yano, Akihito Watanabe, Toshiro Iizuka, Shigetaka Yoshinaga, Ichiro Tateya, Hiroki Mitani, Yuichi Shimizu, Akiko Takahashi, Tomoyuki Kamijo, Noboru Hanaoka, Makoto Abe, Akihiro Shiotani, Koichi Kano, Yukinori Asada, Tamotsu Matsuhashi, Hirohito Umeno, Kenji Okami, Kenichi Goda, Shinichiro Hori, Yoichiro Ono, Shuji Terai, Yasuaki Nagami, Kenichi Takemura, Kenro Kawada, Mizuo Ando, Naoto Shimeno, Akihito Arai, Yasutoshi Sakamoto, Masaaki Ichinoe, Tetsuo Nemoto, Masahiro Fujita, Hidenobu Watanabe, Tadakazu Shimoda, Atsushi Ochiai, Takakuni Kato, Ryuichi Hayashi

Cancer medicine 10 ( 12 ) 3848 - 3861 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

DOI： 10.1002/cam4.3927

A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma. 査読国際誌

Atsuto Katano, Ryousuke Takenaka, Hideomi Yamashita, Mizuo Ando, Masafumi Yoshida, Yuki Saito, Takahiro Asakage, Osamu Abe, Keiichi Nakagawa

Molecular and clinical oncology 14 ( 3 ) 45 - 45 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.

DOI： 10.3892/mco.2021.2207

Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma. 査読国際誌

Takahito Fukusumi, Theresa W Guo, Shuling Ren, Sunny Haft, Chao Liu, Akihiro Sakai, Mizuo Ando, Yuki Saito, Sayed Sadat, Joseph A Califano

International journal of oncology 58 ( 2 ) 226 - 237 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated. The present study investigated the NOTCH4/HEY1/SOX2 axis in HNSCC using in vitro models and the Cancer Genome Atlas (TCGA) database. To explore the association, reporter and ChIP RT‑qPCR assays using SOX2‑overexpressing (SOX2‑OE) cells were performed. The association between NOTCH4 and HEY1 was examined in the same manner using HEY1‑overexpressing (HEY1‑OE) cells. The results of the in vitro experiments indicated that HEY1 promoted EMT in the HNSCC cells. Furthermore, the overexpression of HEY1 also promoted sphere formation and increased murine xenograft tumorigenicity. Reporter assays and ChIP RT‑qPCR experiments indicated that SOX2 regulated HEY1 expression via direct binding of the HEY1 promoter. HEY1 expression significantly correlated with SOX2 expression in primary lung SCC and other SCCs using the TCGA database. HEY1 also regulated NOTCH4 expression to create a positive reciprocal feedback loop. On the whole, the present study demonstrates that HEY1 expression in HNSCC is regulated via the promotion of SOX2 and promotes EMT. The NOTCH4/HEY1 pathway is specifically upregulated via a positive reciprocal feedback loop mediated by the HEY1‑medaited regulation of NOTCH4 transcription, and SOX2 correlates with HEY1 expression in SCC from other primary sites.

DOI： 10.3892/ijo.2020.5156

Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence. 査読国際誌

Kenya Kobayashi, Seiichi Yoshimoto, Mizuo Ando, Fumihiko Matsumoto, Naoya Murakami, Go Omura, Yoshitaka Honma, Yoshifumi Matsumoto, Atsuo Ikeda, Azusa Sakai, Kohtaro Eguchi, Akiko Ito, Eigitsu Ryo, Yasushi Yatabe, Taisuke Mori

Oral oncology 113 105091 - 105091 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

DOI： 10.1016/j.oraloncology.2020.105091

Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss. 査読国際誌

Kensuke Uraguchi, Yukihide Maeda, Junko Takahara, Ryotaro Omichi, Shohei Fujimoto, Shin Kariya, Kazunori Nishizaki, Mizuo Ando

PloS one 16 ( 10 ) e0258977 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-κB subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-κB would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-κB-interacting inflammatory molecules, TNFα and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.

DOI： 10.1371/journal.pone.0258977

HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers. 査読国際誌

Shuling Ren, Daria A Gaykalova, Theresa Guo, Alexander V Favorov, Elana J Fertig, Pablo Tamayo, Juan Luis Callejas-Valera, Mike Allevato, Mara Gilardi, Jessica Santos, Takahito Fukusumi, Akihiro Sakai, Mizuo Ando, Sayed Sadat, Chao Liu, Guorong Xu, Kathleen M Fisch, Zhiyong Wang, Alfredo A Molinolo, J Silvio Gutkind, Trey Ideker, Wayne M Koch, Joseph A Califano

Oncogene 39 ( 40 ) 6327 - 6339 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.

DOI： 10.1038/s41388-020-01431-8

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