Papers - Ando Mizuo

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

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

Acta medica Okayama   76 ( 5 )   527 - 533   2022.10

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DOI： 10.18926/AMO/64033

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Subcutaneous axillary primary epithelioid hemangioendothelioma: report of a rare case. Reviewed International journal

Takayoshi Niwa, Takaaki Konishi, Asako Sasahara, Ayaka Sato, Arisa Morizono, Mayumi Harada, Kotoe Nishioka, Osamu Fukuoka, Naohiro Makise, Yuki Saito, Mizuo Ando, Takako Yoshimoto, Takeshi Shikama, Satoshi Yamashita, Masahiko Tanabe, Yasuyuki Seto

Surgical case reports   8 ( 1 )   166 - 166   2022.9

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BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare and slow-growing malignant vascular neoplasm composed of epithelioid endothelial cells within a distinctive myxohyaline stroma. It most commonly involves somatic soft tissue, lungs, liver and bone. Herein, we describe a case of EHE arising in the axillary region. CASE PRESENTATION: A 61-year-old man was under observation for multiple hepatic hemangiomas. Fluorodeoxyglucose-positron emission tomography/computed tomography showed specific uptake in a right axillary tumor. The patient was referred to our department for further investigation of the axillary tumor. An elastic-soft and poorly mobile tumor was palpable in the right axilla. Contrast-enhanced computed tomography showed a right axillary tumor and enlarged hepatic hemangiomas. In addition, multiple nodules in both lungs, a left renal angiomyolipoma, and left adrenal adenoma were revealed. Ultrasonography showed masses in both lobes of the thyroid gland, and a 30-mm lobulated hypoechoic mass in the axilla with well-defined and rough borders, showing internal heterogeneity. Fine-needle aspiration cytology was performed on the thyroid and axillary tumors: the thyroid tumor was class V, raising suspicion of papillary thyroid cancer (PTC); the left superior internal jugular node was class V, raising suspicion of metastasis of PTC; and the axillary tumor was class III, raising suspicion of a mesenchymal tumor with few epithelioid cells. The multiple lung nodules were diagnosed as metastatic tumors derived from thyroid cancer. We diagnosed these diseases as PTC of T1b(m)N1bM1(lung) Stage IVB and a right axillary tumor of unclear origin. However, it was assumed to be a primary mesenchymal tumor or a lymph node metastasis from lung cancer or occult breast cancer. We performed total thyroidectomy, left cervical lymph node dissection, and right axillary tumor excision. Histopathologic examination revealed the thyroid tumor as a PTC and the axillary tumor as an EHE. The EHE showed nuclear atypia, necrosis and high mitotic figures. Hence, it was considered to be a high-risk EHE. CONCLUSIONS: We experienced a rare primary subcutaneous axillary EHE with metastatic thyroid cancer in the lung. Since our case was classified as a high-risk EHE, a close follow-up would be appropriate.

DOI： 10.1186/s40792-022-01521-7

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Candidemia in patients with head and neck cancer: mortality and a novel risk factor. Reviewed International journal

Kensuke Uraguchi, Takuma Makino, Shin Kariya, Youhei Noda, Hidenori Marunaka, Akira Doi, Kenichi Kozakura, Soshi Takao, Mizuo Ando

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer   30 ( 7 )   5921 - 5930   2022.7

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PURPOSE: Candidemia is a bloodstream infection (BSI) by Candida spp. and is associated with high mortality. However, there have been few reports about BSI in head and neck cancer (HNC). We aimed to evaluate the impact of candidemia in patients with HNC and compared it with bacteremia. STUDY DESIGN: A multicenter retrospective study. METHODS: We retrospectively analyzed 83 BSI episodes in HNC (2011 to 2020) and divided them into the candidemia and bacteremia groups. We then compared the survival rate and risk factors for candidemia between the groups. RESULTS: The overall cumulative incidence (risk) of candidemia in BSI was 12 out of 83 episodes (14.5%). The 1-year mortality for the bacteremia and candidemia groups was 33.3% and 58.3%, respectively (log-rank p = 0.041). Broad-spectrum antibiotics (odds ratio [OR]: 29.5; 95% confidence interval [CI], 2.49-350), mucositis (OR 11.0; 95% CI, 1.52-80.1), and malignant wounds (OR 79.5; 95% CI 1.33-4737) were significant risk factors for candidemia in HNC. CONCLUSIONS: Candidemia causes high mortality in patients with HNC. To our knowledge, malignant wounds have not been previously reported as a risk factor for candidemia. For early diagnosis and treatment of candidemia, risk factors should be considered, and antifungal therapy started earlier.

DOI： 10.1007/s00520-022-07010-9

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The add-on effect of an intranasal antihistamine with an intranasal corticosteroid in Japanese cedar pollinosis. Reviewed International journal

Takenori Haruna, Shin Kariya, Takaya Higaki, Aya Murai, Kengo Kanai, Aiko Oka, Maki Akamatsu, Mizuo Ando, Kazunori Nishizaki, Mitsuhiro Okano

Auris, nasus, larynx   50 ( 1 )   81 - 86   2022.6

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OBJECTIVE: Combination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) METHODS: We performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. RESULTS: The change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. CONCLUSION: The intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

DOI： 10.1016/j.anl.2022.05.007

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Labyrinthitis ossificans following severe acute otitis media. International journal

Kensuke Uraguchi, Shin Kariya, Mizuo Ando

Clinical case reports   10 ( 5 )   e05898   2022.5

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Labyrinthitis occurs because of the inflammation of the inner ear. We present a rare case of labyrinthitis ossificans following an acute otitis media. The T2-weighted magnetic resonance imaging showed decreased signal intensity in the right inner ear due to labyrinthitis ossificans, consistent with the clinical presentation.

DOI： 10.1002/ccr3.5898

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Relationship between spontaneous nystagmus and video Head Impulse Test findings among patients with chronic neurotologic conditions. Reviewed International journal

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

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   99   244 - 247   2022.5

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The vestibulo-ocular reflex (VOR) in neurotologic patients can be evaluated most quickly by spontaneous nystagmus examinations, and the video Head Impulse Test (vHIT) quantitatively evaluates the VOR of the semicircular canals. We aimed to clarify the concordance and discrepancies between spontaneous nystagmus and vHIT findings, to provide guidance on screening vestibular functions by initial spontaneous nystagmus examination then vHIT. We evaluated 169 outpatients by spontaneous nystagmus examination in the dark using a charge-coupled device camera, then by horizontal vHIT the same day. Vestibular loss on vHIT was defined if both reduced VOR gain (<0.8) and corrective saccade were observed. Adjusted logistic regression modelling revealed that differences in right and left VOR gain positively impacted the presence of nystagmus, which suggests lateralised vestibular dysfunction (P<0.05; odds ratio 1.39 [95% confidence interval, 1.1-1.8] per 0.1 increment). When vHIT is regarded as the standard clinical test, the positive predictive value of nystagmus for vestibular loss on vHIT was 44.4%, and the negative predictive value was 93.5%. The adjusted odds ratio of adults ≥65 years old compared to younger patients associated with a discrepancy of nystagmus and vHIT was significant (2.4 [1.1-5.3]). In conclusion, if spontaneous nystagmus is initially observed in patients, further assessment by vHIT could confirm vestibular dysfunction in 40-50% of cases. If no nystagmus is observed, vHIT might also result in a negative finding in >90% of cases. Older adults appear more likely to show discrepancies between nystagmus and vHIT.

DOI： 10.1016/j.jocn.2022.03.018

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

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

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

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DOI： 10.1016/j.alit.2022.03.003

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The fine-needle aspiration cytology and clinical findings of Kikuchi-Fujimoto disease in pediatric patients: a retrospective clinical study. International journal

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   2022.3

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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

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Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report. Reviewed International journal

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   2022.2

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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

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

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   2022.2

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Publishing type：Research paper (scientific journal)   Publisher：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

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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 Reviewed

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   2022.2

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<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.

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DOI： 10.3389/fonc.2021.779882

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

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

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

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DOI： 10.1001/jamaoto.2021.3392

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Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer. Reviewed International journal

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

Scientific reports   12 ( 1 )   572 - 572   2022.1

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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

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Midline involvement and perineural invasion predict contralateral neck metastasis that affects overall and disease-free survival in locally advanced oral tongue squamous cell carcinoma. Reviewed International journal

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

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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

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Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma. Reviewed International journal

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

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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

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Static posturographic balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing process. Reviewed International journal

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

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

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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

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Transcript-targeted analysis reveals isoform alterations and double-hop fusions in breast cancer. Reviewed International journal

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   2021.11

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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

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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. Reviewed

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   2021.11

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

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

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

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

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

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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

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Apocrine Hidrocystoma of the External Auditory Canal in a Child. Reviewed International journal

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   2021.6

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DOI： 10.1097/MAO.0000000000003220

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