Papers - NISHIO Naoki

Anxiety, Depression and Cancer-Related Post-Traumatic Stress in Patients Undergoing Total Laryngectomy Reviewed International journal Open Access

Yokoi, M; Nishio, N; Kimura, H; Tokura, T; Kishi, S; Tsuzuki, H; Mukoyama, N; Yokoi, S; Wada, A; Shigeyama, M; Fujimoto, Y; Ikeda, M; Sone, M

LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY   Vol. 10 ( 2 ) page： e70109   2025.4

　More details

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

DOI： 10.1002/lio2.70109

Open Access

Web of Science

PubMed

Re-Emergent Vocal Tremor in a Patient with Parkinson's Disease. Reviewed International journal Open Access

Tsuboi T, Tanaka Y, Kobayasi K, Hashimoto R, Ito Y, Nishio N, Tsuboi T, Sone M, Katsuno M, Aiba I

Movement disorders clinical practice     2025.3

　More details

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

DOI： 10.1002/mdc3.70043

Open Access

PubMed

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008. Reviewed International journal

Hidetoshi Shimizu, Takeshi Kodaira, Naomi Kiyota, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Yuuji Hirayama, Yusuke Onozawa, Naoki Nishio, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Takashi Fujii, Kaoru Tanaka, Akihiro Homma, Seiichi Yoshimoto, Nobuhiko Oridate, Koichi Omori, Tsutomu Ueda, Kenji Okami, Hirokazu Uemura, Kiyoto Shiga, Mitsuhiko Nakahira, Takahiro Asakage, Yuki Saito, Keita Sasaki, Ryo Kitabayashi, Satoshi Ishikura, Yasumasa Nishimura, Makoto Tahara

Oral oncology   Vol. 157   page： 106976 - 106976   2024.10

　More details

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

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

DOI： 10.1016/j.oraloncology.2024.106976

Web of Science

PubMed

Anxiety, depression and quality of life in patients with head and neck cancer undergoing laryngectomy: A long-term prospective evaluation. Reviewed International journal

Nobuaki Mukoyama, Naoki Nishio, Hiroyuki Kimura, Tatsuya Tokura, Shinichi Kishi, Kazuyoshi Ogasawara, Hidenori Tsuzuki, Sayaka Yokoi, Akihisa Wada, Mayu Shigeyama, Norio Ozaki, Yasushi Fujimoto, Michihiko Sone

International journal of language & communication disorders   Vol. 59 ( 5 ) page： 1865 - 1877   2024.9

　More details

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

BACKGROUND: This study aimed to assess anxiety, depression and quality of life (QoL) in patients with head and neck cancer undergoing laryngectomy using comprehensive self-reported questionnaires for a period of up to 5 years. METHODS: This prospective observational study enrolled 150 consecutive patients with locally advanced head and neck cancer who underwent laryngectomy at Nagoya University Hospital between 2007 and 2020. Anxiety, depression and QoL were assessed at baseline (preoperative) and at 3, 6, 12, 24, 36, 48 and 60 months after surgery using two brief self-reported questionnaires, such as the eight-item Short Form Health Survey (SF-8) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: The surgical procedures were total laryngectomy, pharyngo-laryngectomy and pharyngo-laryngo-oesophagectomy in 97 (65%), 41 (27%) and 12 (8%) patients, respectively. All eight items of the SF-8 were significantly worse than those of the normal population at baseline and at 3 months after surgery. However, general health, vitality, mental health and bodily pain improved to normal levels within 1 year after surgery and were maintained for 5 years. In this study, 35% of patients were categorised as potential cases of depression, and 35% were potential cases of anxiety. During the follow-up period, the proportion of patients with anxiety gradually decreased after surgery. Further analysis revealed that the SF-8 and HADS scores and trends in 89 patients without tumour recurrence were similar to those in the total enrolled 150 patients. CONCLUSION: Anxiety, depression and QoL in laryngectomised patients improved at 1 year after surgery and were maintained for up to 5 years. WHAT THIS PAPER ADDS: What is already known on the subject Laryngectomy is associated with prolonged functional and psychological effects and has a major impact on patient quality of life (QoL). Several prospective studies evaluating the QoL in laryngectomised patients have been reported, in which significant deterioration in social functioning was found even 1 year after surgery. What this paper adds to existing knowledge One year is not a sufficient period for laryngectomised patients to return to normal life and spend their time in a social community. A recent review showed that most studies on QoL in laryngectomised patients were conducted under 1 year after the procedure, and there were not enough studies of sufficient quality. This is the first long-term prospective observational study of Japanese patients with head and neck cancer who underwent laryngectomy up to 5 years after surgery. What are the potential or actual clinical implications of this work? Our long-term observational study showed that the scores for anxiety, depression and QoL in laryngectomised patients improved at 1 year after surgery and were maintained for up to 5 years. Clinicians should recognize the importance of psychosocial risk factors in their QoL and multidisciplinary management, including social and psychological support, is essential for long-term laryngectomised survivors.

DOI： 10.1111/1460-6984.13036

Web of Science

PubMed

Effect of acute kidney injury and overall survival in patients with postoperative head and neck cancer who received chemoradiotherapy with cisplatin: A supplementary analysis of the phase II/III trial of JCOG1008. Reviewed International journal Open Access

Yoshinori Imamura, Naomi Kiyota, Makoto Tahara, Takeshi Kodaira, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Shigemichi Iwae, Naoki Nishio, Yusuke Onozawa, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Ryo Kitabayashi, Keita Sasaki, Akihiro Homma

Cancer medicine   Vol. 13 ( 18 ) page： e70235   2024.9

　More details

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

BACKGROUND: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non-inferior to 3-weekly cisplatin (100 mg/m2) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). METHODS: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. RESULTS: The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). CONCLUSIONS: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting.

DOI： 10.1002/cam4.70235

Open Access

Web of Science

PubMed

Development of a plant-based surgical training model for fluorescence-guided cancer surgery. Reviewed International coauthorship International journal Open Access

Mayu Shigeyama, Naoki Nishio, Akihisa Wada, Sohei Mitani, Gaku Morimoto, Sayaka Yokoi, Nobuaki Mukoyama, Mai Yokoi, Stan van Keulen, Eben Rosenthal, Michihiko Sone

Head & neck   Vol. 46 ( 9 ) page： 2274 - 2283   2024.9

　More details

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

BACKGROUND: Fluorescence-guided surgery (FGS) can help surgeons to discriminate tumor tissue from adjacent normal tissues using fluorescent tracers. METHODS: We developed a surgical training model, manufactured using sustainable vegetable organic material with indocyanine green (ICG)-containing "tumor." Surgeons evaluated the model with both the closed-field and endoscopic fluorescence imaging devices and assessed its efficacy to identify residual tumor after enucleation using electrocautery. RESULTS: Strong correlations of fluorescence were obtained at all working distance (3, 5, 7, and 10 cm), showing the robustness of fluorescence signal for the closed-field and endoscopic fluorescence imaging devices. The higher fluorescence signals were obtained in the wound bed in the closed-field fluorescence imaging device and the residual tumor could be clearly identified by fluorescence endoscopy. CONCLUSIONS: Our FGS training model may provide experience for surgeons unfamiliar with optical surgery and subsequent tissue interactions. The model seemed particularly helpful in teaching surgeons the principles of FGS.

DOI： 10.1002/hed.27835

Open Access

Web of Science

PubMed

Risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer receiving chemoradiotherapy: A re-analysis of a phase II/III JCOG1008 trial. Reviewed International journal

Yoshinori Imamura, Naomi Kiyota, Makoto Tahara, Takeshi Kodaira, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Shigemichi Iwae, Naoki Nishio, Yusuke Onozawa, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Ryo Kitabayashi, Keita Sasaki, Akihiro Homma

Oral oncology   Vol. 154   page： 106868 - 106868   2024.7

　More details

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

OBJECTIVES: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008. MATERIALS AND METHODS: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m2 (weekly arm) or 3-weekly cisplatin at 100 mg/m2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration. RESULTS: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %. CONCLUSIONS: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen.

DOI： 10.1016/j.oraloncology.2024.106868

Web of Science

PubMed

Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study. Reviewed International journal Open Access

Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Tetsushi Izuchi, Koji Suzuki, Koki Otake, Yoshinori Yasuda, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Naoki Nishio, Shoichiro Mori, Tomoya Shimokata, Tomoyasu Sano, Kaoru Niimi, Nobuhisa Yoshikawa, Shusuke Akamatsu, Yuichi Ando, Masashi Akiyama, Michihiko Sone, Makoto Ishii, Hiroshi Arima

Cancer immunology, immunotherapy : CII   Vol. 73 ( 8 ) page： 146 - 146   2024.6

　More details

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

BACKGROUND: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

DOI： 10.1007/s00262-024-03733-2

Open Access

PubMed

アンドロゲン受容体(AR)陽性唾液腺癌に対するAR阻害薬Darolutamide(ODM-201)の第II相試験:単剤パート

大塚 倫之, 岡野 晋, 今村 善宣, 瓜生 英興, 大越 明, 佐野 大佑, 塚原 清彰, 大野 十央, 花澤 豊行, 加納 里志, 西尾 直樹, 長岡 真人, 長尾 俊孝, 久野 博文, 尾尻 博也, 齋藤 尚子, 篠田 覚, 三角 俊裕, 清田 尚臣, 田原 信

頭頸部癌   Vol. 50 ( 2 ) page： 138 - 138   2024.5

　More details

Language：Japanese   Publishing type：Research paper (international conference proceedings)   Publisher：(一社)日本頭頸部癌学会  

Identification of Optimal Tissue-Marking Dye Color for Pathological Evaluation in Fluorescence Imaging Using IRDye800CW. Reviewed International coauthorship International journal

Takahito Kondo, Naoki Nishio, Jason S Park, Lucas D Mani, Abdullah Naveed, Hidenori Tanaka, James S Lewis Jr, Eben L Rosenthal, Marisa E Hom

Molecular imaging and biology   Vol. 26 ( 1 ) page： 162 - 172   2024.2

　More details

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

PURPOSE: Fluorescence-guided surgery using a tumor-specific antibody-dye conjugate is useful in various cancer types. Fluorescence imaging is a valuable tool both intraoperatively and postoperatively for ex vivo imaging. The color of inks used for tumor specimens during ex vivo specimen processing in pathology is an important consideration for fluorescence imaging since the absorption/emission of the dyes may interfere with the fluorescent dye. This study assesses suitable ink colors for use specifically with IRDye800CW fluorescence imaging. PROCEDURES: Eight tissue-marking inks or dyes (TMDs) commonly used for pathological evaluation were assessed. Agarose tissue-mimicking phantoms containing Panitumumab-IRDye800CW were used as an initial model. Mean fluorescence intensity was measured at 800 nm using both Pearl Trilogy as a closed-field fluorescence imaging system and pde-neo II as an open-field fluorescence imaging system before and after TMD application. An in vivo mouse xenograft model using the human head and neck squamous cell carcinoma FaDu cell line was then used in conjunction with TMDs. RESULTS: The retained IRDye800CW fluorescence on Pearl Trilogy was as follows: yellow at 91.0 ± 4.5%, red at 90.6 ± 2.7%, orange at 88.2 ± 2.2%, violet at 56.6 ± 1.1%, lime at 40.9 ± 1.8%, green at 19.3 ± 2.8%, black at 13.3 ± 0.6%, and blue at 8.1 ± 0.2%. The retained IRDye800CW fluorescence on pde-neo II was as follows: yellow at 86.5 ± 6.4%, red at 77.0 ± 6.2%, orange at 76.9 ± 2.8%, lime at 72.5 ± 9.5%, violet at 59.7 ± 0.4%, green at 30.1 ± 6.9%, black at 17.0 ± 2.7%, and blue at 6.7 ± 1.7%. The retained IRDye800CW fluorescence in yellow and blue TMDs was 42.1 ± 14.9% and 0.2 ± 0.2%, respectively in the mouse experiment (p = 0.039). CONCLUSION: Yellow, red, and orange TMDs should be used, and blue and black TMDs should be avoided for evaluating tumor specimens through fluorescence imaging using IRDye800CW.

DOI： 10.1007/s11307-023-01882-x

Web of Science

PubMed

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study. Reviewed International journal

Yosuke Ariizumi, Nobuhiro Hanai, Takahiro Asakage, Akira Seto, Toshifumi Tomioka, Junji Miyabe, Hisashi Kessoku, Takashi Mukaigawa, Go Omura, Masanori Teshima, Daisuke Nishikawa, Yuki Saito, Yukinori Asada, Takuo Fujisawa, Takuma Makino, Hiroshi Nishino, Daisuke Sano, Mitsuhiko Nakahira, Kunihiko Tokashiki, Hirokazu Uemura, Tsutomu Ueda, Akihiro Sakai, Muneyuki Masuda, Takahiro Tsujikawa, Yusuke Hiei, Naoki Nishio, Hidetoshi Matsui, Naomi Kiyota, Akihiro Homma

Head & neck   Vol. 46 ( 2 ) page： 269 - 281   2024.2

　More details

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

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

DOI： 10.1002/hed.27572

Web of Science

PubMed

喉頭摘出者における音声収録アプリを用いた術前音声の保存 Save the Voiceプロジェクト Reviewed

西尾 直樹, 戸田 智基, 小林 和弘, 三谷 壮平, 飴矢 美里, 向山 宣昭, 木村 宏之, 徳倉 達也, 坪井 崇, 藤本 保志, 曾根 三千彦

喉頭   Vol. 35 ( 2 ) page： 142 - 147   2023.12

　More details

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本喉頭科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J02852&link_issn=&doc_id=20231226240021&doc_link_id=10.5426%2Flarynx.35.142&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.35.142&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

喉頭摘出術後患者の合成音声を用いた代用音声の満足度調査 Reviewed

飴矢 美里, 三谷 壮平, 勢井 洋史, 木谷 卓史, 西尾 直樹, 羽藤 直人

喉頭   Vol. 35 ( 2 ) page： 148 - 154   2023.12

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本喉頭科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J02852&link_issn=&doc_id=20231226240022&doc_link_id=10.5426%2Flarynx.35.148&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.35.148&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Efficacy of endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope in patients with sporadic inclusion body myositis: four retrospective case reviews. Reviewed International journal Open Access

Mayu Shigeyama, Naoki Nishio, Sayaka Yokoi, Nobuaki Mukoyama, Akihisa Wada, Takashi Maruo, Seiya Noda, Ayuka Murakami, Takashi Tsuboi, Masahisa Katsuno, Yasushi Fujimoto, Michihiko Sone

Nagoya journal of medical science   Vol. 85 ( 4 ) page： 866 - 874   2023.11

　More details

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

Sporadic inclusion body myositis (s-IBM) is an acquired degenerative inflammatory myopathy that leads to slowly progressive muscle weakness and atrophy of the limbs, face, and pharynx. Owing to the slow progression of the disease, the indications for surgical intervention remain unclear. Herein, we retrospectively reviewed the records of four patients with s-IBM who had undergone cricopharyngeal myotomy for severe dysphagia at our institution between 2016 and 2021. Among these, one patient underwent transcervical cricopharyngeal myotomy and laryngeal suspension, as videofluoroscopic examination of swallowing revealed poor laryngeal elevation. The remaining three patients underwent endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope. Preoperatively, the mean Hyodo score was 8 points (range: 6-10) using a flexible endoscope. The mean surgical duration was 104 min, and no severe complications were observed. Postoperatively, all patients achieved improvement in swallowing function and food intake. Moreover, swallowing function was maintained in all four patients even 6-12 months postoperatively. Cricopharyngeal myotomy may be a safe surgical procedure with the potential to improve swallowing function, and a Hyodo score of 6 may be considered a surgical indication for cricopharyngeal myotomy in patients with s-IBM.

DOI： 10.18999/nagjms.85.4.866

Open Access

Web of Science

PubMed

Hypopharyngeal Injury by Transesophageal Echocardiography During Cardiac Surgery. Reviewed International journal Open Access

Yohei Aoki, Takahiro Tamura, Wataru Uchida, Hiroshi Morioka, Mayumi Yamamoto, Satoshi Yuhara, Naoki Nishio, Masato Mutsuga, Satoshi Furune, Shogo Suzuki, Kimitoshi Nishiwaki

Journal of cardiothoracic and vascular anesthesia   Vol. 37 ( 10 ) page： 2027 - 2031   2023.10

　More details

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

DOI： 10.1053/j.jvca.2023.06.023

Web of Science

PubMed

Impact of acute kidney injury on overall survival in postoperative patients with head and neck cancer who received chemoradiotherapy with cisplatin: A supplementary analysis of a phase II/III trial of JCOG1008. Open Access

Imamura, Y; Kiyota, N; Tahara, M; Kodaira, T; Hayashi, R; Nishino, H; Asada, Y; Mitani, H; Iwae, S; Nishio, N; Onozawa, Y; Hanai, N; Ohkoshi, A; Hara, H; Monden, N; Nagaoka, M; Minami, S; Kitabayashi, R; Sasaki, K; Homma, A

JOURNAL OF CLINICAL ONCOLOGY   Vol. 41 ( 16 )   2023.6

　More details

Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1200/JCO.2023.41.16_suppl.6079

Open Access

Web of Science

A risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer who receive chemoradiotherapy: A supplement analysis of a phase II/III trial of JCOG1008 Reviewed International journal Open Access

Imamura, Y; Kiyota, N; Tahara, M; Kodaira, T; Hayashi, R; Nishino, H; Asada, Y; Mitani, H; Iwae, S; Nishio, N; Onozawa, Y; Hanai, N; Ohkoshi, A; Hara, H; Monden, N; Nagaoka, M; Minami, S; Kitabayashi, R; Sasaki, K; Homma, A

JOURNAL OF CLINICAL ONCOLOGY   Vol. 41 ( 16 )   2023.6

　More details

Language：English   Publishing type：Research paper (international conference proceedings)  

DOI： 10.1200/JCO.2023.41.16_suppl.1210

Open Access

Web of Science

Darolutamide for patients with androgen receptor positive salivary gland cancers (DISCOVARY): The results of phase 2 study of darolutamide monotherapy

Okano, S; Tahara, M; Imamura, Y; Uryu, H; Otsuka, T; Ohkoshi, A; Sano, D; Tsukahara, K; Ono, K; Hanazawa, T; Kano, S; Nishio, N; Nagaoka, M; Kiyota, N

JOURNAL OF CLINICAL ONCOLOGY   Vol. 41 ( 16 )   2023.6

　More details

Language：English   Publishing type：Research paper (international conference proceedings)  

Web of Science

Comparison of quality of life and psychological distress in patients with tongue cancer undergoing a total/subtotal glossectomy or extended hemiglossectomy and free flap transfer: a prospective evaluation Reviewed

K. Suzuki, N. Nishio, H. Kimura, T. Tokura, S. Kishi, N. Ozaki, Y. Fujimoto, M. Sone

International Journal of Oral and Maxillofacial Surgery   Vol. 52 ( 6 ) page： 621 - 629   2023.6

　More details

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

DOI： 10.1016/j.ijom.2022.11.010

Web of Science

PubMed

Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis. Reviewed International journal Open Access

Takafumi Yamamoto, Kazuyuki Mizuno, Takanori Ito, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Takuya Ishikawa, Akira Kanamori, Satoshi Yasuda, Hidenori Toyoda, Kenji Yokota, Tetsunari Hase, Naoki Nishio, Osamu Maeda, Makoto Ishii, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Masatoshi Ishigami, Hiroki Kawashima

Investigational new drugs   Vol. 41 ( 3 ) page： 512 - 521   2023.6

　More details

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

Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics.

DOI： 10.1007/s10637-023-01366-3

Web of Science

PubMed

＜Editors' Choice＞ Long-term outcomes of lateral skull base reconstruction with a free omental flap and facial nerve reconstruction. Reviewed International journal Open Access

Miki Kambe, Kazunobu Hashikawa, Keisuke Takanari, Shunjiro Yagi, Kazuhiro Toriyama, Katsumi Ebisawa, Naoki Nishio, Takashi Maruo, Nobuaki Mukoyama, Yasushi Fujimoto, Masazumi Fujii, Kiyoshi Saito, Masakatsu Takahashi, Yuzuru Kamei

Nagoya journal of medical science   Vol. 85 ( 2 ) page： 255 - 264   2023.5

　More details

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

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005-2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

DOI： 10.18999/nagjms.85.2.255

Open Access

Web of Science

PubMed

喉頭摘出者に対する術前の自己音声の保存の重要性について「Save the Voiceプロジェクト」

西尾 直樹, 向山 宣昭, 横井 紗矢香, 重山 真由, 和田 明久, 三谷 壮平, 藤本 保志, 曾根 三千彦

日本耳鼻咽喉科頭頸部外科学会会報   Vol. 126 ( 4 ) page： 591 - 591   2023.4

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

喉頭摘出者に対する術前の自己音声の保存の重要性について「Save the Voiceプロジェクト」

西尾 直樹, 向山 宣昭, 横井 紗矢香, 重山 真由, 和田 明久, 三谷 壮平, 藤本 保志, 曾根 三千彦

日本耳鼻咽喉科頭頸部外科学会会報   Vol. 126 ( 4 ) page： 591 - 591   2023.4

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Safety and Clinical Benefits of Laryngeal Closure in Patients with Amyotrophic Lateral Sclerosis. Reviewed International journal

Sayaka Yokoi, Naoki Nishio, Takashi Maruo, Mariko Hiramatsu, Nobuaki Mukoyama, Hidenori Tsuzuki, Akihisa Wada, Naoki Atsuta, Daisuke Ito, Takashi Tsuboi, Gen Sobue, Masahisa Katsuno, Yasushi Fujimoto, Michihiko Sone

Dysphagia   Vol. 38 ( 1 ) page： 211 - 219   2023.2

　More details

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

This study evaluated the safety of laryngeal closure and post-surgical changes in swallowing function of patients with amyotrophic lateral sclerosis (ALS) and proposed an appropriate surgical strategy for patients with ALS. Clinical and surgical data of 26 consecutive patients with ALS who underwent laryngeal closure at Nagoya University Hospital in Japan between 2003 and 2020 were retrospectively analyzed. Changes in swallowing functions were evaluated before and approximately 1 month post-surgery using Neuromuscular Disease Swallowing Status Scale (NdSSS), and Functional Oral Intake Scale (FOIS). The median operation time was 126 min (range, 51-163 min), and the median intraoperative blood loss was 20 mL (range, 0-88 mL). Among the 26 ALS patients who underwent laryngeal closure, grade 1 (mild) complications occurred in three patients (12%); however, no severe complications were observed. After surgery, 25 patients (96%) maintained the swallowing function and only one patient (4%) had deteriorating NdSSS and FOIS scores. No patients were referred to our hospital due to severe aspiration pneumonia after the surgery. Two patients did not require a feeding tube after the surgery and returned to oral intake. Laryngeal closure may be a safe surgical procedure for preventing chronic aspiration and may also maintain swallowing function of patients with ALS. Further multicenter prospective studies using the gold standard videofluoroscopic swallowing examination are required to support our findings.

DOI： 10.1007/s00455-022-10454-0

Web of Science

PubMed

Surgical Strategy for Squamous Cell Carcinoma of the External Auditory Canal: Management of Locally Advanced Cases with Skull Base Involvement. Reviewed International journal

Seiya Goto, Naoki Nishio, Kenichiro Iwami, Tadao Yoshida, Takashi Maruo, Nobuaki Mukoyama, Hidenori Tsuzuki, Sayaka Yokoi, Akihisa Wada, Mariko Hiramatsu, Yuichiro Hayashi, Yuzuru Kamei, Masazumi Fujii, Michihiko Sone, Yasushi Fujimoto

Journal of neurological surgery. Part B, Skull base   Vol. 84 ( 01 ) page： 69 - 78   2023.2

　More details

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

Objective  Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification. Methods  Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification. Results  In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS ( p  = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors ( p  = 0.007 and 0.03, respectively). Conclusion  The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.

DOI： 10.1055/a-1733-2585

Web of Science

PubMed

New, safe and simple endoscopic cricopharyngeal myotomy with a curved rigid laryngoscope: A case report. Reviewed International journal Open Access

Takashi Maruo, Yasushi Fujimoto, Sayaka Yokoi, Mayu Shigeyama, Naoki Nishio, Mariko Hiramatsu, Michihiko Sone

Molecular and clinical oncology   Vol. 18 ( 2 ) page： 10 - 10   2023.2

　More details

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

Endoscopic cricopharyngeal myotomy (ECPM) is a safe and minimally invasive technique that is used to treat patients whose esophageal inlet fails to open because of specific diseases, such as Wallenberg's syndrome and neuromuscular diseases. The present study described the performance of a new, safe and simple ECPM using a curved rigid laryngoscope, which is used for endoscopic laryngopharyngeal surgery for patients with dysphagia due to pharyngeal residue after swallowing. The patient was an 80-year-old woman with laryngeal palsy caused by lower cranial nerve palsy after cranial base schwannoma surgery. ECPM was performed with a curved rigid laryngoscope. The postoperative course was good; postoperative rehabilitation eliminated the residue after swallowing a thickened solution and mealtimes were shorter than before surgery. This procedure allows the hypopharynx to be widely expanded and it is possible to develop a wider surgical field than when using a direct laryngoscope. In addition, this procedure appears to be relatively easy to perform if the surgeon is familiar with the curved rigid laryngoscope technique.

DOI： 10.3892/mco.2023.2606

Open Access

Web of Science

PubMed

頭頸部外科手術の基盤となる技術スキルに対する認識 若手医師と熟達医との違い

三谷 壮平, 西尾 直樹, 松木 崇, 木谷 卓史, 佐藤 恵里子, 坂本 佳代, 細川 裕貴, 鵜久森 徹, 脇坂 浩之, 羽藤 直人

頭頸部外科   Vol. 32 ( 3 ) page： 257 - 263   2023.2

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(NPO)日本頭頸部外科学会  

頭頸部外科手術の基盤となる技術スキルに対する認識について多施設アンケート調査を行った。先行研究の7つのカテゴリーに分類されている60個の技術スキルを用いて,若手医師69名と熟達医15名の回答を比較した。若手医師は,熟達医よりも技術スキル全体を重要と評価しており(P=0.027),熟達医が重要視しているスキルだけでなく,全ての技術スキルに対して気を配っていることが示唆された。熟達医は,「カウンタートラクション」が全カテゴリー中最も難易度が高いと評価していたが,若手医師は自身のスキルに7カテゴリー中3番目に高い自信を持っていた。このような認識の乖離が,技術伝承のひとつの障壁になっている可能性がある。(著者抄録)

喉頭摘出後代用音声の進歩 音声合成スマートフォンアプリを用いた新しい代用音声 Reviewed

飴矢 美里, 勢井 洋史, 三谷 壮平, 西尾 直樹, 羽藤 直人

喉頭   Vol. 34 ( 2 ) page： 51 - 57   2022.12

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本喉頭科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02852&link_issn=&doc_id=20230111160002&doc_link_id=10.5426%2Flarynx.34.51&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.34.51&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

喉頭摘出後代用音声の進歩 音声合成スマートフォンアプリを用いた新しい代用音声 Open Access

飴矢 美里, 勢井 洋史, 三谷 壮平, 西尾 直樹, 羽藤 直人

喉頭   Vol. 34 ( 2 ) page： 51 - 57   2022.12

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本喉頭科学会  

DOI： 10.5426/larynx.34.51

Open Access

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02852&link_issn=&doc_id=20230111160002&doc_link_id=10.5426%2Flarynx.34.51&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.34.51&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Factors for differential outcome across cancers in clinical molecular-targeted fluorescence imaging. Reviewed International coauthorship International journal

Quan Zhou, Nynke S van den Berg, Wenying Kang, Jacqueline Pei, Naoki Nishio, Stan van Keulen, Myrthe A Engelen, Yu-Jin Lee, Marisa Hom, Johana C M Vega Leonel, Zachary Hart, Hannes Vogel, Romain Cayrol, Brock A Martin, Mark Roesner, Glenn Shields, Natalie Lui, Melanie Hayden Gephart, Roan C Raymundo, Grace Yi, Monica Granucci, Gerald A Grant, Gordon Li, Eben L Rosenthal

Journal of nuclear medicine : official publication, Society of Nuclear Medicine   Vol. 63 ( 11 ) page： 1693 - 1700   2022.11

　More details

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

Clinical imaging performance using a fluorescent antibody was compared across three cancers to elucidate physical and biological factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23) or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg panitumumab-IRDye800, 1 - 3 days prior to surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, where imaging device settings and operating room lighting conditions were tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surface. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histological structures. Integrity of the blood-brain barrier (BBB) was examined via tight junction protein (claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biological variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78 - 97% of at-risk resection margins ex vivo. In 4 µm-thick tissue sections, fluorescence detected tumor with 0.85 - 0.89 areas under the receiver operating characteristic curves. Preferential breakdown of BBB in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs 80%) despite its reduced concentration (3.9 ng/mg tissue) compared to HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration with 0.62 goodness-of-fit of prediction. Conclusion: In multi-cancer clinical imaging of receptor-ligand based molecular probe, plasma antibody concentration, delivery barrier, as well as intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density, led to heterogeneous intratumoral antibody accumulation and spatial distribution while tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

DOI： 10.2967/jnumed.121.263674

Web of Science

PubMed

Primary laryngeal cryptococcosis mimicking laryngeal malignancy: a case report. Reviewed International journal Open Access

Kazuya Tonai, Naoki Nishio, Sayaka Yokoi, Masumi Kobayashi, Michihiko Sone

Nagoya journal of medical science   Vol. 84 ( 4 ) page： 900 - 905   2022.11

　More details

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

Primary laryngeal cryptococcosis is an extremely rare infection and presents with non-specific symptoms such as hoarseness or sore throat, resulting in delayed diagnosis. Here, we report the patient of a 56-year-old female patient with primary laryngeal cryptococcosis, who was being treated with oral and inhaled steroids for rheumatoid arthritis and bronchial asthma. The patient suffered from prolonged hoarseness and sore throat, and endoscopic biopsy was performed several times under local anesthesia, demonstrating only inflammatory cell infiltration. Considering the possibility of laryngeal malignancy, a third biopsy was performed by endoscopic laryngomicrosurgery under general anesthesia. Intraoperative frozen section revealed non-neoplastic laryngeal mucosa with erosion and severe inflammatory cell infiltration. However, we could not confirm the definite diagnosis of the lesion in the intraoperative consultation. Postoperative histopathological examination revealed a small number of yeast-type fungi and a definitive diagnosis was established by special stains including Alcian blue stain. Finally, the patient was diagnosed as primary laryngeal cryptococcosis. Daily oral administration of fluconazole (400 mg/day) was performed for 6 months according to the treatment protocol for pulmonary cryptococcosis. The symptoms gradually improved, and endoscopy revealed no recurrence 6 months post-treatment. Clinicians should consider the possibility of laryngeal cryptococcosis when severe inflammation is found in the larynx and discuss the disease history and pathological results with pathologists more closely.

DOI： 10.18999/nagjms.84.4.900

Open Access

Web of Science

PubMed

Fluorescent molecular imaging can improve intraoperative sentinel margin detection in oral squamous cell carcinoma. Reviewed International coauthorship International journal

Giri Krishnan, Nynke S van den Berg, Naoki Nishio, Shrey Kapoor, Jaqueline Pei, Laura Freeman, Yu-Jin Lee, Stan van Keulen, Shayan Fakurnejad, James Condon, Fred Back, Brock Martin, Eben L Rosenthal

Journal of nuclear medicine : official publication, Society of Nuclear Medicine   Vol. 63 ( 8 ) page： 1162 - 1168   2022.8

　More details

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

Rationale: In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen where tumour lies closest to the resected edge in real-time during frozen section analysis. Methods: Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50mg of panitumumab-IRDye800CW 1-5 days prior to surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near-real time, and custom designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin blinded to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results: Resected specimens were imaged in the operating room and fluorescence had a higher interobserver agreement with pathology (Cohen kappa value 0.96) than the surgeon (Cohen kappa values of 0.82) for the location of the closest margin. Plotting margin distance at the predicted sentinel margin location of each observer versus the actual closest margin distance at pathology demonstrated best correlation between fluorescence and pathology (R2 = 0.98), with surgeon (R2 = 0.75). Principal Conclusion: Fluorescence imaging can improve identification of the sentinel margin in head and neck cancer resections, holding promise for rapid identification of positive margins and improved oncological outcomes.

DOI： 10.2967/jnumed.121.262235

Web of Science

PubMed

Validation of a surgical training model containing indocyanine green for near-infrared fluorescence imaging. Reviewed International coauthorship International journal

Naoki Nishio, Sohei Mitani, Kayo Sakamoto, Gaku Morimoto, Sayaka Yokoi, Mayu Shigeyama, Akihisa Wada, Nobuaki Mukoyama, Eben L Rosenthal, Michihiko Sone

Laryngoscope investigative otolaryngology   Vol. 7 ( 4 ) page： 1011 - 1017   2022.8

　More details

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

Objective: To determine the efficacy of a surgical training model for fluorescence-guided cancer surgery and validate its utility to detect any residual tumors after tumor resection using electrocautery. Methods: We developed surgical training models containing indocyanine green (ICG) for near-infrared (NIR) fluorescence imaging using a root vegetable organic material (konjac). After the fluorescence assessment for the models, the surgical simulation for fluorescence-guided cancer surgery using electrocautery was performed. ICG-containing tumors were divided into two surgical groups: "Enucleation" (removal of the entire visible tumor) and "Complete resection" (removal of the tumor with an appropriate 5-mm surgical margin). Results: All 12 ICG-containing tumors were clearly visible from the normal view but not from the flipped view. The tumor resection time was significantly longer in the "Complete resection" group than in the "Enucleation" group (p < .001). The ICG-containing tumors showed a high tumor-to background ratio from the normal (average = 45.8) and flipped (average = 19.2) views, indicating that the models including ICG-containing tumors were useful for a surgical simulation in fluorescence-guided surgery. The average mean fluorescence intensity of the wound bed was significantly higher in the "Enucleation" group than in the "Complete resection" group (p < .01). No decrease in fluorescence signal was found in the wound bed even at 2 days postresection. Conclusion: Our surgical training model containing a fluorescent agent is safe, inexpensive, not harmful for humans, and easy to dispose after use. Our model would be beneficial for surgeons to learn NIR fluorescence imaging and to accelerate fluorescence-guided cancer surgery into clinical application.

DOI： 10.1002/lio2.858

Web of Science

PubMed

近赤外光が導く新たな腫瘍切除トレーニングモデルの開発

西尾 直樹, 三谷 壮平, 坂本 佳代, 重山 真由, 横井 紗矢香, 向山 宣昭, 曾根 三千彦

頭頸部癌   Vol. 48 ( 2 ) page： 196 - 196   2022.5

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

喉頭摘出者における音声変換技術を用いた自己音声の再獲得 Save the Voiceプロジェクト

西尾 直樹, 向山 宣昭, 横井 紗矢香, 三谷 壮平, 勢井 洋史, 藤本 保志, 曾根 三千彦

日本耳鼻咽喉科頭頸部外科学会会報   Vol. 125 ( 4 ) page： 739 - 739   2022.4

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

頭頸部外科手術に必要な技術スキルに対する認識 熟達医と若手医師とのギャップ

三谷 壮平, 西尾 直樹, 松木 崇, 木谷 卓史, 佐藤 恵里子, 坂本 佳代, 相原 栞, 細川 裕貴, 鵜久森 徹, 脇坂 浩之, 羽藤 直人

日本耳鼻咽喉科頭頸部外科学会会報   Vol. 125 ( 4 ) page： 764 - 764   2022.4

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Increased risk of thyroid dysfunction by PD-1 and CTLA-4 blockade in patients without thyroid autoantibodies at baseline. Reviewed International journal

Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Keiko Wakahara, Kenji Yokota, Masashi Kato, Naoki Nishio, Chie Tanaka, Kazushi Miyata, Atsushi Ogura, Takanori Ito, Tsunaki Sawada, Tomoya Shimokata, Kaoru Niimi, Fumiharu Ohka, Masatoshi Ishigami, Momokazu Gotoh, Naozumi Hashimoto, Ryuta Saito, Hitoshi Kiyoi, Hiroaki Kajiyama, Yuichi Ando, Hideharu Hibi, Michihiko Sone, Masashi Akiyama, Yasuhiro Kodera, Hiroshi Arima

The Journal of clinical endocrinology and metabolism   Vol. 107 ( 4 ) page： E1620 - E1630   2022.3

　More details

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

BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction (thyroid immune-related adverse events [irAEs]) induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2-7% in patients negative for anti-thyroid-antibodies (ATAs) at baseline, it was much higher (30-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab plus CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid-irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) with CTLA-4-Ab, and 10 of 27 (37.0%) with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid-irAEs was significantly higher in patients who were positive versus negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs. 13/329 (4.0%), p < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs. 4/17 (23.5%), p < 0.05] treatments. The risk of thyroid-irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid-irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

DOI： 10.1210/clinem/dgab829

Web of Science

PubMed

Management of bilateral locally advanced squamous cell carcinoma of the external auditory canal Reviewed

Nishio, N; Okazaki, Y; Wada, A; Tsuzuki, H; Kambe, M; Fujimoto, Y; Sone, M

ACTA OTO-LARYNGOLOGICA CASE REPORTS   Vol. 7 ( 1 ) page： 8 - 13   2022.2

　More details

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

DOI： 10.1080/23772484.2022.2033122

Web of Science

【二次出版】ANL Secondary Publication 耳鼻咽喉科医のための結紮縫合カリキュラムの開発

佐藤 恵里子, 三谷 壮平, 西尾 直樹, 木谷 卓史, 真田 朋昌, 鵜久森 徹, Holsinger F. Christopher, Baik Fred M., 羽藤 直人

日本耳鼻咽喉科頭頸部外科学会会報   Vol. 124 ( 11 ) page： 1543 - 1544   2021.11

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J07551&link_issn=&doc_id=20211201440017&doc_link_id=10.3950%2Fjibiinkotokeibu.124.11_1543&url=https%3A%2F%2Fdoi.org%2F10.3950%2Fjibiinkotokeibu.124.11_1543&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies. Reviewed International journal

Takanori Ito, Masatoshi Ishigami, Takafumi Yamamoto, Kazuyuki Mizuno, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Takashi Honda, Hiroki Kawashima, Satoshi Yasuda, Hidenori Toyoda, Kenji Yokota, Tetsunari Hase, Naoki Nishio, Osamu Maeda, Masashi Kato, Naozumi Hashimoto, Hideharu Hibi, Yasuhiro Kodera, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Yoshie Shimoyama, Mitsuhiro Fujishiro

Hepatology international   Vol. 15 ( 5 ) page： 1278 - 1287   2021.10

　More details

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

BACKGROUND: The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. METHODS: We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. RESULTS: During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. CONCLUSION: The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

DOI： 10.1007/s12072-021-10238-y

Web of Science

PubMed

外耳道扁平上皮がんに対する手術治療について 頭蓋底浸潤例を中心に

西尾 直樹, 後藤 聖也, 岩味 健一郎, 吉田 忠雄, 向山 宣昭, 横井 紗矢香, 丸尾 貴志, 藤井 正純, 亀井 譲, 藤本 保志, 曾根 三千彦

日本癌治療学会学術集会抄録集   Vol. 59回   page： O41 - 2   2021.10

　More details

Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本癌治療学会  

Dilatation of the Endolymphatic Space in the Ampulla of the Posterior Semicircular Canal: A New Clinical Finding Detected on Magnetic Resonance Imaging. Reviewed International journal

Masaru Morioka, Satofumi Sugimoto, Tadao Yoshida, Masaaki Teranishi, Masumi Kobayashi, Naoki Nishio, Naomi Katayama, Shinji Naganawa, Michihiko Sone

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology   Vol. 42 ( 6 ) page： E643 - E647   2021.7

　More details

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

OBJECTIVES: To investigate the clinical features of ears with dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal on magnetic resonance imaging. STUDY DESIGN: Retrospective study. SETTING: A university hospital. METHODS: This study included 1,842 ears from 934 patients who underwent 3-T magnetic resonance imaging with gadolinium to investigate the presence of endolymphatic hydrops. Age, sex distribution, hearing thresholds on pure-tone audiometry, and vestibular symptoms were compared between cases of unilateral and bilateral dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. RESULTS: Forty-eight ears (17 men and 14 women; mean age 49.9 yrs) showed dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. Age and the rate of chronic sensorineural hearing loss were significantly higher in the unilateral group (14 ears) than in the bilateral group (34 ears). The average hearing thresholds and rates of vestibular symptoms reported did not differ between unilateral and bilateral cases, but some patients showed positional nystagmus. CONCLUSIONS: Dilatation of the endolymphatic space in the ampulla was observed selectively in the posterior semicircular canal, though its pathogenesis was not clear. Such dilatation is not usually accompanied by vestibular endolymphatic hydrops, and it may be a cause of vertigo and dizziness.

DOI： 10.1097/MAO.0000000000003073

Web of Science

PubMed

Surgical Classification of Radical Temporal Bone Resection and Transcranial Tympanotomy: A Retrospective Study from the Neurosurgical Perspective. Reviewed International journal

Kenichiro Iwami, Masazumi Fujii, Naoki Nishio, Takashi Maruo, Tadao Yoshida, Nobuaki Mukoyama, Koji Osuka, Keisuke Takanari, Kenta Murotani, Yuzuru Kamei, Michihiko Sone, Yasushi Fujimoto, Kiyoshi Saito

World neurosurgery   Vol. 151   page： E192 - E207   2021.7

　More details

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

OBJECTIVE: To review the authors' surgical experience with radical temporal bone resection (TBR) with an emphasis on the classification of skull base osteotomy and transcranial tympanotomy (TCT) that is required for middle ear transection. METHODS: We reviewed the records of 25 patients who underwent radical TBR at our facilities between 2011 and 2020. RESULTS: The osteotomy line of radical TBR was divided into 3 segments: anterior (A), medial (M), and posterior (P). Each segment was further classified as follows: A1, through the glenoid fossa (1 patient); A2, in front of the glenoid fossa (23 patients); A3, through the greater wing of the sphenoid bone (1 patient); M1, through the middle ear (16 patients); M2, through the inner ear (9 patients); P1, through the mastoid (9 patients); and P2, through the posterior cranial fossa (16 patients). The M segment was significantly associated with operation time and intraoperative blood loss. In all patients with M1 osteotomy, TCT was performed; TCT was classified into superior and far posterior approaches. A superior approach was performed in all 16 patients, whereas the far posterior approach was performed in only 7 patients with both M1 and P2 osteotomy. CONCLUSIONS: Our newly proposed osteotomy classification of radical TBR is suitable for minute but clinically important adjustment of the osteotomy line. TCT is an indispensable technique for M1 osteotomy; our newly proposed classification expands our understanding of TCT and how to incorporate this technique into radical TBR.

DOI： 10.1016/j.wneu.2021.04.002

Web of Science

PubMed

Skull Base Invasion Patterns of Malignant Head and Neck Tumors: A Neurosurgical Perspective. Reviewed International journal

Kenichiro Iwami, Masazumi Fujii, Naoki Nishio, Takashi Maruo, Yasushi Fujimoto, Keisuke Takanari, Yuzuru Kamei, Masayuki Yamada, Tetsuya Ogawa, Koji Osuka, Kiyoshi Saito

Journal of neurological surgery. Part B, Skull base   Vol. 82 ( Suppl 3 ) page： E120 - E130   2021.7

　More details

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

Objective  Craniofacial resection (CFR) and temporal bone resection (TBR) on malignant head and neck tumors (MHNTs) invading skull base require accurate and precise determination of the tumor invasion. We investigated tumor skull base invasion patterns and surgical results in CFR and TBR cases. Methods  We performed either CFR or TBR for 75 selected patients with the possibility of en bloc resection over the period between 2011 and 2018. The medical charts of the selected patients were reviewed. Results  Primary tumor onset site (TOS) groups were: (1) nasal cavity/ethmoid sinus, 20 cases; (2) orbit, 10 cases; (3) maxillary sinus, 28 cases; and (4) external ear/temporomandibular joint, 17 cases. Grades for tumor invasion depth (TID) included: (I) extracranial invasion and skull base bone invasion; (II) extradural invasion; or (III) intradural invasion. Patients in groups 1 and 2 had a significantly higher frequency of grade II and III invasions than patients in groups 3 and 4. The main invasion site was nasal cavity superior wall and ethmoid sinus superior wall for group 1 tumors, orbit superior wall, and lateral skull base sphenoid bone for group 2 and 3 tumors, and lateral skull base temporal bone for group 4 tumors. Positive resection margins represented a significant negative prognostic factor. TID and TOS did not affect skull base margin status. Conclusion  Skull base invasion of MHNTs exhibits certain fixed patterns in sites susceptible to invasion based on the TOS. The frequencies of extradural and intradural invasions differed, indicating the importance for accurate preoperative tumor evaluation.

DOI： 10.1055/s-0039-3402034

Web of Science

PubMed

Surgical strategy and optimal timing of tracheostomy in patients with COVID-19: Early experiences in Japan. Reviewed International journal

Naoki Nishio, Mariko Hiramatsu, Yukari Goto, Yuichiro Shindo, Takanori Yamamoto, Naruhiro Jingushi, Keiko Wakahara, Michihiko Sone

Auris, nasus, larynx   Vol. 48 ( 3 ) page： 518 - 524   2021.6

　More details

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

OBJECTIVE: Tracheostomy is an important surgical procedure for coronavirus disease-2019 (COVID-19) patients who underwent prolonged tracheal intubation. Surgical indication of tracheostomy is greatly affected by the general condition of the patient, comorbidity, prognosis, hospital resources, and staff experience. Thus, the optimal timing of tracheostomy remains controversial. METHODS: We reviewed our early experience with COVID-19 patients who underwent tracheostomy at one tertiary hospital in Japan from February to September 2020 and analyzed the timing of tracheostomy, operative results, and occupational infection in healthcare workers (HCWs). RESULTS: Of 16 patients received tracheal intubation with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, five patients (31%) received surgical tracheostomy in our hospital. The average consultation time for surgical tracheostomy was 7.4 days (range, 6 - 9 days) from the COVID-19 team to the otolaryngologist. The duration from tracheal intubation to tracheostomy ranged from 14 to 27 days (average, 20 days). The average time of tracheostomy was 27 min (range, 17 - 39 min), and post-wound bleeding occurred in only one patient. No significant differences in hemoglobin (Hb) levels were found between the pre- and postoperative periods (mean: 10.2 vs. 10.2 g/dl, p = 0.93). Similarly, no difference was found in white blood cell (WBC) count (mean: 12,200 vs. 9,900 cells /µl, p = 0.25). After the tracheostomy, there was no occupational infection among the HCWs who assisted the tracheostomy patients during the perioperative period. CONCLUSION: We proposed a modified weaning protocol and surgical indications of tracheostomy for COVID-19 patients and recommend that an optimal timing for tracheostomy in COVID-19 patients of 2 - 3 weeks after tracheal intubation, from our early experiences in Japan. An experienced multi-disciplinary tracheostomy team is essential to perform a safe tracheostomy in patients with COVID-19 and to minimize the risk of occupational infection in HCWs.

DOI： 10.1016/j.anl.2020.11.004

Web of Science

PubMed

Verbalization, Categorization, and Evaluation of Fundamental Surgical Skills: An Expert Consensus in Open Head and Neck Surgery. Reviewed International coauthorship

Mitani S, Nishio N, Kitani T, Ugumori T, Wakisaka H, Tanaka K, Miao B, Chan JYK, Holsinger FC, Hato N

Annals of surgery open : perspectives of surgical history, education, and clinical approaches   Vol. 2 ( 2 ) page： e059   2021.6

　More details

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

DOI： 10.1097/AS9.0000000000000059

PubMed

Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer using an anti-EGFR Antibody-Dye Conjugate. Reviewed International coauthorship International journal

Naoki Nishio, Nynke S van den Berg, Brock A Martin, Stan van Keulen, Shayan Fakurnejad, Eben L Rosenthal, Katheryne E Wilson

Journal of nuclear medicine : official publication, Society of Nuclear Medicine   Vol. 62 ( 5 ) page： 648 - 655   2021.5

　More details

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

The presence of lymph node (LN) metastases is an essential prognostic indicator in patients with head and neck squamous cell carcinoma (HNSCC). This study assessed photoacoustic molecular imaging (PAMI) of the anti-epidermal growth factor receptor (EGFR) antibody (panitumumab) conjugated to a near-infrared fluorescent dye, IRDye800CW (panitumumab-IRDye800CW; pan800) for the identification of occult metastatic LNs in patients with HNSCC (n=7). After in vitro photoacoustic imaging characterization of pan800, PAMI was performed on excised neck specimens of patients infused with pan800 prior to surgery. Freshly obtained neck specimens were imaged with three-dimensional, multiwavelength spectroscopic PAMI (680, 686, 740, 800, 860, 924, and 958 nm wavelengths). Harvested LNs were then imaged with a closed-field near-infrared fluorescence imager and histologically examined by the pathologist to determine their metastatic status. A total of 53 LNs with a maximum diameter of 10 mm were analyzed with photoacoustic and fluorescence imaging, of which four were determined to be metastatic on final histopathology. Photoacoustic signal in the LNs corresponding to accumulated pan800 were spectrally unmixed using a linear least square error classification algorithm. Metastatic LNs had a five-fold higher average thresholded photoacoustic signal intensity corresponding to pan800 compared to benign LNs (2.50 ± 1.09 a.u. vs. 0.53 ± 0.32 a.u., p<0.001). Fluorescence imaging showed that metastatic LNs had a two-fold increase in fluorescence signal compared to benign LNs ex vivo (p<0.01, 0.068 ± 0.027 a.u. vs. 0.035 ± 0.018 a.u.) Moreover, the ratio of the average of the highest 10% photoacoustic signal intensity over total average, representative of degree of heterogeneity of pan800 signal in LNs, showed a significant difference between metastatic LNs vs. benign LNs (11.6 ± 13.4 vs. 1.8 ± 0.7, p<0.01) and an area under the receiver operating characteristic (ROC) curve of 0.96 (95% CI; 0.91-1.00). The data indicate that PAMI of IRDye800-labeled tumor-specific antibody may have the potential to identify occult LN metastasis perioperatively in HNSCC patients.

DOI： 10.2967/jnumed.120.245241

Web of Science

PubMed

Effect of Formalin Fixation for Near-Infrared Fluorescence Imaging with an Antibody-Dye Conjugate in Head and Neck Cancer Patients. Reviewed International coauthorship International journal

Shrey Kapoor, Guolan Lu, Nynke S van den Berg, Giri Krishnan, Jacqueline Pei, Quan Zhou, Brock A Martin, Fred M Baik, Eben L Rosenthal, Naoki Nishio

Molecular imaging and biology   Vol. 23 ( 2 ) page： 270 - 276   2021.4

　More details

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

PURPOSE: This study evaluated the effect of formalin fixation for near-infrared (NIR) fluorescence imaging of an antibody-dye complex (panitumumab-IRDye800CW) that was intravenously administered to patients with head and neck squamous cell carcinoma (HNSCC) scheduled to undergo surgery of curative intent. PROCEDURES: HNSCC patients were infused with 25 or 50 mg of panitumumab-IRDye800CW followed by surgery 1-5 days later. Following resection, primary tumor specimens were imaged in a closed-field fluorescence imaging device, before and after formalin fixation. The fluorescence images of formalin-fixed specimens were compared with images prior to formalin fixation. Regions of interest were drawn on the primary tumor and on the adjacent normal tissue on the fluorescence images. The mean fluorescence intensity (MFI) and tumor-to-background ratios (TBRs) of the fresh and formalin-fixed tissues were compared. RESULTS: Of the 30 enrolled patients, 20 tissue specimens were eligible for this study. Formalin fixation led to an average of 10 % shrinkage in tumor specimen size (p < 0.0001). Tumor MFI in formalin-fixed specimens was on average 10.9 % lower than that in the fresh specimens (p = 0.0002). However, no statistical difference was found between the TBRs of the fresh specimens and those of the formalin-fixed specimens (p = 0.85). CONCLUSIONS: Despite the 11 % decrease in MFI between fresh and formalin-fixed tissue specimens, the relative difference between tumor and normal tissue as measured in TBR remained unchanged. This data suggests that evaluation of formalin-fixed tissue for assessing the accuracy of fluorescence-guided surgery approaches could provide a valid, yet more flexible, alternative to fresh tissue analysis. TRIAL REGISTRATION: NCT02415881.

DOI： 10.1007/s11307-020-01553-1

Web of Science

PubMed

Safety and feasibility of fat injection therapy with adipose-derived stem cells in a rabbit hypoglossal nerve paralysis model: A pilot study. Reviewed International journal

Akihisa Wada, Naoki Nishio, Sayaka Yokoi, Hidenori Tsuzuki, Nobuaki Mukoyama, Takashi Maruo, Mariko Hiramatsu, Tokunori Yamamoto, Momokazu Goto, Yasushi Fujimoto, Michihiko Sone

Auris, nasus, larynx   Vol. 48 ( 2 ) page： 274 - 280   2021.4

　More details

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

OBJECTIVE: The aim of this study is to establish a unilateral tongue atrophy model by cutting the hypoglossal nerve and to evaluate the safety and feasibility of a fat injection of adipose-derived stem cells (ADSCs) to restore swallowing function. METHODS: A total of 12 rabbits were randomized to three groups; the ADSCs+fat group (n=4), the fat group (n=4) and the control group (n=4). All rabbits were treated with denervation of the left hypoglossal nerve and their conditions including body weight and food intake were checked during follow-up periods (8 weeks). At 4 weeks after the transection of the nerve, rabbits received the injection therapy into the denervated side of the tongue with 1.0mL fat tissue premixed with 0.5mL ADSCs in the ADSCs+fat group, 1.0mL fat tissue premixed with 0.5mL PBS in the fat group and 1.5mL PBS in the control group. Rabbits were euthanized 8 weeks post-treatment and resected tongues were collected, formalin-fixed and paraffin embedded. To evaluate the change of the intrinsic muscles of the tongue, muscle fibers around the treatment area was analyzed by evaluating 5 consecutive hematoxylin-eosin slides per rabbit. RESULTS: Food intake did not decrease upon nerve denervation, and none of the rabbits displayed adverse effect such as aspiration, surgical wound dehiscence or infection. No significant body weight changes were found between the three groups at 4 and 8 weeks after nerve transection (p>0.05). In the control group, the denervated side of tongue had significantly smaller muscle fiber areas and diameters compared to the non-denervated side (p<0.05). The ADSCs+fat group demonstrated a larger area of inferior longitudinal muscle fibers compared to the control and the fat groups (582±312µm2 vs. 405±220µm2 and 413±226µm2; p<0.05). A significant thicker lesser diameter of inferior longitudinal muscle fibers was found in the ADSCs+fat group compared to the control and the fat groups (24±8µm vs. 20±6µm and 20±7µm; p<0.05). CONCLUSION: The rabbit tongue atrophy model was found suitable for the assessment of muscle change after nerve transection. Fat injection therapy with ADSCs demonstrated great potential to prevent the muscle atrophy after denervation and to promote the muscle regeneration around the injection area.

DOI： 10.1016/j.anl.2020.08.003

Web of Science

PubMed

Feasibility of virtual surgical simulation in the head and neck region for soft tissue reconstruction using free flap: a comparison of preoperative and postoperative volume measurement Reviewed

S. Yokoi, N. Nishio, Y. Fujimoto, M. Fujii, K. Iwami, Y. Hayashi, K. Takanari, M. Hiramatsu, T. Maruo, N. Mukoyama, H. Tsuzuki, A. Wada, Y. Kamei, M. Sone

International Journal of Oral and Maxillofacial Surgery   Vol. 50 ( 3 ) page： 316 - 322   2021.3

　More details

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

In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154–315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.

DOI： 10.1016/j.ijom.2020.07.025

Web of Science

Scopus

PubMed

Intraoperative Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma. Reviewed International coauthorship International journal

Yu-Jin Lee, Giri Krishnan, Naoki Nishio, Nynke S van den Berg, Guolan Lu, Brock A Martin, Stan van Keulen, Alexander D Colevas, Shrey Kapoor, Jonathan T C Liu, Eben L Rosenthal

The Laryngoscope   Vol. 131 ( 3 ) page： 529 - 534   2021.3

　More details

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

The rate of positive margins in head and neck cancers has remained stagnant over the past three decades and is consistently associated with poor overall survival. This suggests that significant improvements must be made intraoperatively to ensure negative margins. We discuss the important role of fluorescence imaging to guide surgical oncology in head and neck cancer. This review includes a general overview of the principles of fluorescence, available fluorophores used for fluorescence imaging, and specific clinical applications of fluorescence-guided surgery, as well as challenges and future directions in head and neck surgical oncology. Laryngoscope, 131:529-534, 2021.

DOI： 10.1002/lary.28822

Web of Science

PubMed

Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Reviewed International coauthorship International journal

Jacqueline Pei, Georgina Juniper, Nynke S van den Berg, Naoki Nisho, Trevor Broadt, Anthony R Welch, Grace S Yi, Roan C Raymundo, Stefania U Chirita, Guolan Lu, Giri Krishnan, Yu-Jin Lee, Shrey Kapoor, Quan Zhou, A Dimitrios Colevas, Natalie S Lui, George A Poultsides, Gordon Li, Kurt R Zinn, Eben L Rosenthal

Molecular imaging and biology   Vol. 23 ( 1 ) page： 109 - 116   2021.2

　More details

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

PURPOSE: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients. PROCEDURES: Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis. RESULTS: Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria. CONCLUSIONS: Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

DOI： 10.1007/s11307-020-01536-2

Web of Science

PubMed

Lesion-specific prognosis by magnetic resonance imaging in sudden sensorineural hearing loss. Reviewed International journal

Cheng-Jui Yang, Tadao Yoshida, Satofumi Sugimoto, Masaaki Teranishi, Masumi Kobayashi, Naoki Nishio, Shinji Naganawa, Michihiko Sone

Acta oto-laryngologica   Vol. 141 ( 1 ) page： 5 - 9   2021.1

　More details

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

BACKGROUND: High signals in the inner ear of idiopathic sudden sensorineural hearing loss (ISSNHL) on magnetic resonance imaging (MRI) have been reported, but no quantitative evaluation has yet been done. OBJECTIVES: To evaluate hearing outcomes and cochlear signal intensities on 3-T heavily T2-weighted three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (hT2W-3D-FLAIR) in patients with ISSNHL. MATERIALS AND METHODS: Twenty-nine patients with ISSNHL were included. Patients underwent hT2W-3D-FLAIR with intravenous gadolinium injection and pure tone audiometry (PTA) at initial visits and 3 months later. Signal intensity ratios (SIRs) were measured in the basal or apical-middle turns of the affected cochlea. A statistical analysis of relationships between SIRs and the average hearing levels (HLs) at low (125, 250, and 500 Hz) and high (2, 4, and 8 kHz) tone frequencies was performed. RESULTS: Hearing improvements at high-tone frequencies in ears with HLs ≥60 dB were significantly worse in those with high SIRs at the basal turns on pre-contrast images. Similarly, hearing improvements at low-tone frequencies in ears with HLs ≥60 dB were significantly worse in those with high SIRs at the apical-middle turns on post-contrast images. CONCLUSIONS AND SIGNIFICANCE: High SIRs on hT2W-3D-FLAIR indicate cochlear disturbances with severe ISSNHL and could provide lesion-specific prognostic information.

DOI： 10.1080/00016489.2020.1827159

Web of Science

PubMed

EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial. Reviewed International coauthorship International journal

Quan Zhou, Nynke S van den Berg, Eben L Rosenthal, Michael Iv, Michael Zhang, Johana C M Vega Leonel, Shannon Walters, Naoki Nishio, Monica Granucci, Roan Raymundo, Grace Yi, Hannes Vogel, Romain Cayrol, Yu-Jin Lee, Guolan Lu, Marisa Hom, Wenying Kang, Melanie Hayden Gephart, Larry Recht, Seema Nagpal, Reena Thomas, Chirag Patel, Gerald A Grant, Gordon Li

Theranostics   Vol. 11 ( 15 ) page： 7130 - 7143   2021

　More details

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

Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.

DOI： 10.7150/thno.60582

Web of Science

PubMed

Metastatic and sentinel lymph node mapping using intravenously delivered Panitumumab-IRDye800CW. Reviewed International coauthorship International journal

Giri Krishnan, Nynke S van den Berg, Naoki Nishio, Georgina Juniper, Jaqueline Pei, Quan Zhou, Guolan Lu, Yu-Jin Lee, Kimberly Ramos, Andrei H Iagaru, Fred M Baik, Alexander D Colevas, Brock A Martin, Eben L Rosenthal

Theranostics   Vol. 11 ( 15 ) page： 7188 - 7198   2021

　More details

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

Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

DOI： 10.7150/thno.55389

Web of Science

PubMed

Investigation of parotid gland cancer surgery that preserved the facial nerve Reviewed

Ryoki Hamabata, Nobuaki Mukoyama, Naoki Nishio, Takashi Maruo, Mariko Hiramatsu, Sayaka Yokoi, Michihiko Sone, Yasushi Fujimoto

Japanese Journal of Head and Neck Cancer   Vol. 47 ( 3 ) page： 316 - 321   2021

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

Summary There are few reports on the transition and prognosis of postoperative facial nerve paralysis in patients undergoing parotid gland cancer surgery that preserves the facial nerve. The treatment policy for parotid gland cancer in our department is, in principle, combined resection of the facial nerve and one-stage reconstruction of the nerve if there is facial nerve paralysis before surgery, and preservation of the nerve if there is no paralysis regardless of histological type. We examined 31 cases of parotid gland cancer surgery that preserved the facial nerve over the past 15 years. The median observation period was 60 months. Total resection was performed in 24 cases, and lobectomy was performed in 7 cases. The average score of postoperative facial nerve paralysis was 24 points, and the median score was 27 points. The transition of postoperative facial nerve paralysis, although there were cases of transient complete paralysis, eventually recovered to an average of 39.5 points. The recovery period was 6 months after surgery in many cases. The treatment results were good, with 5-year overall survival rate, 5-year disease-free survival rate, and local control rate of 96.0％, 89.5％, and 93.5％, respectively. In cases of parotid gland cancer without facial nerve paralysis, treatment results are considered to be guaranteed even if the nerve is preserved regardless of the pathological type.

DOI： 10.5981/jjhnc.47.316

Scopus

Endoscopic Fluorescence-Guided Surgery for Sinonasal Cancer Using an Antibody-Dye Conjugate. Reviewed International coauthorship International journal

Zachary P Hart, Naoki Nishio, Giri Krishnan, Guolan Lu, Quan Zhou, Shayan Fakurnejad, Peter John Wormald, Nynke S van den Berg, Eben L Rosenthal, Fred M Baik

The Laryngoscope   Vol. 130 ( 12 ) page： 2811 - 2817   2020.12

　More details

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

OBJECTIVE: Endoscopic resection of sinonasal squamous cell carcinoma has become the standard of care, but challenges remain in obtaining clear resection margins. The current study evaluated the feasibility of endoscopic fluorescence-guided surgery (FGS) to improve surgical resection in a human sinus surgical model. METHODS: A fluorescence endoscope optimized for near-infrared (NIR) fluorescence detection was evaluated in a phantom study. Various endoscope diameters (4 and 10 mm) and viewing angles (0, 30, and 45 degrees) were evaluated to determine the sensitivity of the system for IRDye800CW detection at various working distances (1-5 cm). Endoscopic FGS was then validated in a three-dimensional human sinus surgical model to which squamous cell tumors derived from mice were inserted. Mice had received intravenous panitumumab-IRDye800CW and upon fluorescence-guided tumor resection, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were calculated in in situ and ex vivo settings. RESULTS: A significantly higher fluorescence intensity was found when using the 10-mm diameter endoscope compared to the 4mm diameter endoscope (P < .001). No significant difference in MFI was found among the viewing angles of the 4-mm diameter endoscope. Using the human sinus model, the highest MFI and TBR were obtained at a 1-cm working distance compared to longer working distances. CONCLUSION: We demonstrate that clinically acceptable TBRs were obtained with several working distances to discriminate tumor tissue from adjacent normal tissue in a human sinus model, and that endoscopic FGS may have great potential in identifying residual tumor tissue regions during surgery. Laryngoscope, 2019.

DOI： 10.1002/lary.28483

Web of Science

PubMed

Co-administered antibody improves penetration of antibody-dye conjugate into human cancers with implications for antibody-drug conjugates. Reviewed International coauthorship International journal Open Access

Guolan Lu, Naoki Nishio, Nynke S van den Berg, Brock A Martin, Shayan Fakurnejad, Stan van Keulen, Alexander D Colevas, Greg M Thurber, Eben L Rosenthal

Nature communications   Vol. 11 ( 1 ) page： 5667 - 5667   2020.11

　More details

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

Poor tissue penetration remains a major challenge for antibody-based therapeutics of solid tumors, but proper dosing can improve the tissue penetration and thus therapeutic efficacy of these biologics. Due to dose-limiting toxicity of the small molecule payload, antibody-drug conjugates (ADCs) are administered at a much lower dose than their parent antibodies, which further reduces tissue penetration. We conducted an early-phase clinical trial (NCT02415881) and previously reported the safety of an antibody-dye conjugate (panitumumab-IRDye800CW) as primary outcome. Here, we report a retrospective exploratory analysis of the trial to evaluate whether co-administration of an unconjugated antibody could improve the intratumoral distribution of the antibody-dye conjugate in patients. By measuring the multiscale distribution of the antibody-dye conjugate, this study demonstrates improved microscopic antibody distribution without increasing uptake (toxicity) in healthy tissue when co-administered with the parent antibody, supporting further clinical investigation of the co-administration dosing strategy to improve the tumor penetration of ADCs.

DOI： 10.1038/s41467-020-19498-y

Open Access

Web of Science

PubMed

FIRST-IN-HUMAN FLUORESCENCE GUIDED SURGERY OF HIGH-GRADE GLIOMAS USING PANITUMUMAB-IRDYE800 International coauthorship International journal

Zhou, Q; van den Berg, N; Nishio, N; Lu, GL; Chirita, S; Raymundo, R; Yi, G; Vogel, H; Cayrol, R; Rosenthal, E; Li, G

NEURO-ONCOLOGY   Vol. 22   page： 52 - 52   2020.11

　More details

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

Web of Science

Significance of high signal intensity in the endolymphatic duct on magnetic resonance imaging in ears with otological disorders. Reviewed International journal

Kyoko Morimoto, Tadao Yoshida, Masumi Kobayashi, Satofumi Sugimoto, Naoki Nishio, Masaaki Teranishi, Shinji Naganawa, Michihiko Sone

Acta oto-laryngologica   Vol. 140 ( 10 ) page： 818 - 822   2020.10

　More details

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

BACKGROUND: High signal intensity in the endolymphatic duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders. OBJECTIVE: The signal intensity (SI) in the ED on post-contrast MRI was investigated in subjects with various otological disorders, and the meaning of high SI in the ED was evaluated. MATERIAL AND METHODS: 392 patients with otological disorders and 21 controls without otological symptoms underwent 3 T MRI. The SIs of the ED and the cerebellum were measured, the SI ratio (SIR) was calculated, and ears with SIR ≥4 were identified. RESULTS: A high SIR was identified in the ED of 3.7% of ears affected by definite Meniere's disease (dMD), 100% of ears affected by large vestibular aqueduct syndrome (LVAS), and 7.1% of ears with no otological symptoms. On the whole, a significant relationship was found between the existence of vestibular or cochlear EH and the SIR in the ED. CONCLUSION: The MRI finding of high SI in the ED may indicate the mechanism of inner ear disturbances in ears with otological disorders, especially in those with LVAS, and it may suggest an underlying disorder in some ears in which otological symptoms are not apparent.

DOI： 10.1080/00016489.2020.1781927

Web of Science

PubMed

Prospective Evaluation of Health-Related Quality of Life in Patients Undergoing Anterolateral Craniofacial Resection with Orbital Exenteration. Reviewed International journal

Nobuaki Mukoyama, Naoki Nishio, Hiroyuki Kimura, Shinichi Kishi, Tatsuya Tokura, Hiroki Kimura, Mariko Hiramatsu, Takashi Maruo, Hidenori Tsuzuki, Masazumi Fujii, Kenichiro Iwami, Keisuke Takanari, Yuzuru Kamei, Norio Ozaki, Michihiko Sone, Yasushi Fujimoto

Journal of neurological surgery. Part B, Skull base   Vol. 81 ( 05 ) page： 585 - 593   2020.10

　More details

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

Objective  This study was aimed to evaluate health-related quality of life in patients undergoing anterolateral craniofacial resection (AL-CFR) with orbital exenteration (OE) for malignant skull base tumors and to investigate the effects of early psychiatric intervention. Design  Present study is a prospective, observational study. Setting  The study took place at the hospital department. Participants  Twenty-six consecutive patients were selected who underwent AL-CFR with OE at our hospital between 2005 and 2015. Main Outcome Measures  Health-related quality of life was assessed preoperatively and 3, 6, 12, and 24 months after surgery using the Hospital Anxiety and Depression Scale (HADS) and medical outcomes study 8-items Short Form health survey (SF-8). In all cases, psychiatric intervention was organized by the consultation liaison psychiatry team preoperatively and postoperatively. Results  Ten (38.0%) of the 26 patients died and 16 (62.0%) were alive and disease-free at the end of the study. The 3-year overall and disease-free survival rates were 64.9% and 53.3%, respectively. Twenty-one patients (80.8%) developed psychiatric complications after surgery and needed treatment with psychotropic medication. Before surgery, 28% of patients had HADS scores ≥8 for anxiety and 20% had scores ≥8 for depression. Seven of the eight items in the SF-8 were significantly lower than those for the general Japanese population. However, scores for all the SF-8 items gradually improved during postoperative follow-up, reaching approximately 50 points, which is the national standard value, at 2 years after surgery. Conclusions  Craniofacial resection with OE was feasible and well tolerated in patients with malignant skull base tumors who received early psychiatric intervention to decrease the considerable psychological impact of this procedure.

DOI： 10.1055/s-0039-1694010

Web of Science

PubMed

鼻副鼻腔腫瘍モデルに対するPanitumumab-IRDye800CWを用いた内視鏡下蛍光ガイド手術

西尾 直樹, 藤本 保志, 平松 真理子, 丸尾 貴志, 向山 宣昭, 横井 紗矢香, 和田 明久, 曾根 三千彦

日本耳鼻咽喉科学会会報   Vol. 123 ( 4 ) page： 1050 - 1050   2020.9

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科学会  

当科におけるニボルマブ治療の状況 Salvage therapyを中心に

丸尾 貴志, 藤本 保志, 平松 真理子, 西尾 直樹, 向山 宣昭, 横井 紗矢香, 和田 明久, 石田 彩乃, 楊 承叡, 小林 万純, 鈴木 克尚, 曾根 三千彦

日本耳鼻咽喉科学会会報   Vol. 123 ( 4 ) page： 1137 - 1137   2020.9

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科学会  

Tumour-specific fluorescence-guided surgery for pancreatic cancer using panitumumab-IRDye800CW: a phase 1 single-centre, open-label, single-arm, dose-escalation study. Reviewed International coauthorship International journal

Guolan Lu, Nynke S van den Berg, Brock A Martin, Naoki Nishio, Zachary P Hart, Stan van Keulen, Shayan Fakurnejad, Stefania U Chirita, Roan C Raymundo, Grace Yi, Quan Zhou, George A Fisher, Eben L Rosenthal, George A Poultsides

The lancet. Gastroenterology & hepatology   Vol. 5 ( 8 ) page： 753 - 764   2020.8

　More details

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

BACKGROUND: Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time. METHODS: In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238. FINDINGS: Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients. INTERPRETATION: To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis. FUNDING: National Institutes of Health and the Netherlands Organization for Scientific Research.

DOI： 10.1016/S2468-1253(20)30088-1

Web of Science

PubMed

Bronchial wall thickening is associated with severity of chronic rhinosinusitis Reviewed International journal Open Access

Suguru Majima, Keiko Wakahara, Tomoko Nishio, Naoki Nishio, Masaaki Teranishi, Shingo Iwano, Akihiro Hirakawa, Naozumi Hashimoto, Michihiko Sone, Yoshinori Hasegawa

Respiratory Medicine   Vol. 170   page： 106024   2020.8

　More details

Language：English   Publishing type：Research paper (scientific journal)   Publisher：W.B. Saunders Ltd  

Background: Though the relationship between chronic rhinosinusitis (CRS) and lower airway diseases is well recognized, the impact of CRS on bronchial wall structure has not been elucidated. Here, we evaluated the bronchial wall structure of CRS patients with or without diagnosed airway diseases by three-dimensional computed tomography (3D-CT). Methods: Subjects who underwent both chest CT and sinus CT within a year were recruited from consecutive medical records. CRS was defined as a Lund-Mackay score (LMS) of over 5 points. Airway dimensions were measured using validated software. Standard blood tests and pulmonary function tests were performed, and their correlation with airway thickness was examined. Results: One-hundred-seventy-two patients were recruited (93 CRS subjects and 79 non-CRS subjects). The bronchial walls of CRS subjects were significantly thicker than those of non-CRS subjects. CRS and asthma were related to bronchial wall thickening by multivariate linear regression analysis adjusted for age, smoking status, and chest symptoms. In addition, LMS was significantly correlated with bronchial wall thickening. Conclusion: Airway walls in CRS subjects were thicker than those in non-CRS subjects and associated with the severity of CRS. These data indicate strong relationship between upper and lower airways regardless of chest symptoms or diagnosed airway diseases.

DOI： 10.1016/j.rmed.2020.106024

Web of Science

Scopus

PubMed

蛍光イメージングを用いた頭頸部癌切除におけるセンチネルマージン 安全な切除マージンを目指して

西尾 直樹, 藤本 保志, 平松 真理子, 丸尾 貴志, 向山 宣昭, 横井 紗矢香, 和田 明久, 曾根 三千彦

頭頸部癌   Vol. 46 ( 2 ) page： 147 - 147   2020.7

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

320列面検出型CTスキャン(320列ADCT)による頭頸部癌術後嚥下機能の評価

丸尾 貴志, 藤本 保志, 平松 真理子, 西尾 直樹, 向山 宣昭, 横井 紗矢香, 和田 明久, 石田 彩乃, 鈴木 克尚, 曾根 三千彦

頭頸部癌   Vol. 46 ( 2 ) page： 192 - 192   2020.7

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers. Reviewed International coauthorship International journal

Guolan Lu, Shayan Fakurnejad, Brock A Martin, Nynke S van den Berg, Stan van Keulen, Naoki Nishio, Ashley J Zhu, Stefania U Chirita, Quan Zhou, Rebecca W Gao, Christina S Kong, Nancy Fischbein, Mrudula Penta, Alexander D Colevas, Eben L Rosenthal

Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 26 ( 11 ) page： 2582 - 2594   2020.6

　More details

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

PURPOSE: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. EXPERIMENTAL DESIGN: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery. RESULTS: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery. CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.

DOI： 10.1158/1078-0432.CCR-19-3717

Web of Science

PubMed

Anesthetic and surgical management of tracheostomy in a patient with COVID-19. Reviewed International journal

Mariko Hiramatsu, Naoki Nishio, Masayuki Ozaki, Yuichiro Shindo, Katsunao Suzuki, Takanori Yamamoto, Yasushi Fujimoto, Michihiko Sone

Auris, nasus, larynx   Vol. 47 ( 3 ) page： 472 - 476   2020.6

　More details

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

OBJECTIVE: The ongoing pandemic coronavirus disease-2019 (COVID-19) infection causes severe respiratory dysfunction and has become an emergent issue for worldwide healthcare. Since COVID-19 spreads through contact and droplet infection routes, careful attention to infection control and surgical management is important to prevent cross-contamination of patients and medical staff. Tracheostomy is an effective method to treat severe respiratory dysfunction with prolonged respiratory management and should be performed as a high-risk procedure METHOD: The anesthetic and surgical considerations in this case involved difficult goals of the patient safety and the management of infection among health care workers. Our surgical procedure was developed based on the previous experiences of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: We described the management procedures for tracheostomy in a patient with COVID-19, including the anesthesia preparation, surgical procedures, required medical supplies (a N95 mask or powered air purifying respirator, goggles, face shield, cap, double gloves, and a water-resistant disposable gown), and appropriate consultation with an infection prevention team. CONCLUSION: Appropriate contact, airborne precautions, and sufficient use of muscle relaxants are essential for performing tracheostomy in a patient with COVID-19.

DOI： 10.1016/j.anl.2020.04.002

Web of Science

PubMed

Development of proficiency-based knot-tying and suturing curriculum for otolaryngology residents: A pilot study. Reviewed International coauthorship International journal

Eriko Sato, Sohei Mitani, Naoki Nishio, Takashi Kitani, Tomoyoshi Sanada, Toru Ugumori, F Christopher Holsinger, Fred M Baik, Naohito Hato

Auris, nasus, larynx   Vol. 47 ( 2 ) page： 291 - 298   2020.4

　More details

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

OBJECTIVE: Basic surgical skills such as knot-tying and suturing are important for all otolaryngologists, regardless of subspecialty. The present study was undertaken in order to assess basic surgical techniques such as knot-tying and suturing required for novice otolaryngology residents with taking the variety of subspecialties into consideration, and evaluate the impact of a proficiency-based training curriculum based on these techniques. METHODS: A prospective study was performed for developing of proficiency-based knot-tying and suturing curriculum for otolaryngology residents in the third post-graduate year (PGY-3). The proficiency-based training curriculum was developed based on the tasks selected by RAND/UCLA method with expert panel, which is an iterative and anonymous survey used to establish consensus among participants. Expert panelists were selected from various divisions to reflect variety of their subspecialties. PGY-3 residents trained with the developed curriculum that included proctored pre-test, self-training to proficiency, and proctored post-test. Visual analogue scale (VAS) of trainees' overall competence in the operating room was self-assessed by each resident, before and after completing the training curriculum. RESULTS: Nine PGY-3 residents were enrolled as trainees. Eleven experts chosen as panelists had various subspecialty, including 2 from otology, 2 from rhinology, 2 from laryngology, 2 from head and neck surgery, and 3 from general otolaryngology. Seven tasks were selected from RAND/UCLA method and used to develop the curriculum. Trainee scores at pre-test were significantly lower than expert scores for all 7 tasks (p < 0.01) and each coefficient of variation of trainee score was larger than that of expert score (p < 0.05), supporting construct validity. The mean of composite scores between pre-test and post-test had statistical significance (68.6 ± 11.6 vs 95.9 ± 3.6, p < 0.01), documenting substantial improvement after training. Self-assessment VAS was also improved pre- to post-training (1.2 ± 0.9 vs 4.5 ± 1.4, p < 0.01). A follow-up questionnaire showed that trainees felt the educational curriculum to be beneficial. CONCLUSION: In the present study, seven basic technical skills were selected using the RAND/UCLA method and used to create a proficiency-based training curriculum. Our results indicate that this curriculum significantly improves proficiency of basic surgical skills of junior otolaryngology residents.

DOI： 10.1016/j.anl.2019.11.005

Web of Science

PubMed

Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer. Reviewed International coauthorship International journal

Naoki Nishio, Nynke S van den Berg, Stan van Keulen, Brock A Martin, Shayan Fakurnejad, Quan Zhou, Guolan Lu, Stefania U Chirita, Michael J Kaplan, Vasu Divi, Alexander D Colevas, Eben L Rosenthal

Molecular imaging and biology   Vol. 22 ( 1 ) page： 156 - 164   2020.2

　More details

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

PURPOSE: To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW. PROCEDURES: Patients (n = 24) received either 0.5 or 1.0 mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50 mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging. RESULTS: A total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate-strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2 = 0.42) and for dose/weight (mg/kg) (R2 = 0.54). Results indicated that the optimal MFI was at approximately 50 mg for fixed dose and 0.75 mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2 days (vs. 3 days or more, p < 0.05). CONCLUSIONS: Antibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50 mg is an appropriate diagnostic dose for successful surgical fluorescence imaging.

DOI： 10.1007/s11307-019-01358-x

Web of Science

PubMed

Intraoperative Molecular Imaging for ex vivo Assessment of Peripheral Margins in Oral Squamous Cell Carcinoma. Reviewed International coauthorship International journal

Shayan Fakurnejad, Giri Krishnan, Stan van Keulen, Naoki Nishio, Andrew C Birkeland, Fred M Baik, Michael J Kaplan, A Dimitrios Colevas, Nynke S van den Berg, Eben L Rosenthal, Brock A Martin

Frontiers in oncology   Vol. 9   page： 1476 - 1476   2020.1

　More details

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

Objective: Complete surgical resection is the standard of care for treatment of oral cancer although the positive margin rate remains 15-30%. Tissue sampling from the resected specimen and from the wound bed for frozen section analysis (FSA) remains the mainstay for intraoperative margin assessment but is subject to sampling error and can require the processing of multiple samples. We sought to understand if an ex vivo imaging strategy using a tumor-targeted fluorescently labeled antibody could accurately identify the closest peripheral margin on the mucosal surface of resected tumor specimen, so that this "sentinel margin" could be used to guide pathological sampling. Materials and Methods: Twenty-nine patients with oral squamous cell carcinoma scheduled for surgical resection were consented for the study and received systemic administration of a tumor-targeted fluorescently labeled antibody (Panitumumab IRDye800CW). After surgical resection, the tumor specimen was imaged using a closed-field fluorescent imaging device. Relevant pathological data was available for five patients on retrospective review. For each of these five patients, two regions of highest fluorescence intensity at the peripheral margin and one region of lowest fluorescence intensity were identified, and results were correlated with histology to determine if the region of highest fluorescence intensity along the mucosal margin (i.e., the sentinel margin) was truly the closest margin. Results: Imaging acquisition of the mucosal surface of the specimen immediately after surgery took 30 s. In all of the specimens, the region of highest fluorescence at the specimen edge had a significantly smaller margin distance than other sampled regions. The average margin distance at the closest, "sentinel," margin was 3.2 mm compared to a margin distance of 8.0 mm at other regions (p < 0.0001). Conclusions: This proof-of-concept study suggests that, when combined with routine FSA, ex vivo fluorescent specimen imaging can be used to identify the closest surgical margin on the specimen. This approach may reduce sampling error of intraoperative evaluation, which should ultimately improve the ability of the surgeon to identify the sentinel margin. This rapid sentinel margin identification improves the surgeon's orientation to areas most likely to be positive in the surgical wound bed and may expedite pathology workflow.

DOI： 10.3389/fonc.2019.01476

Web of Science

PubMed

Probe-based fluorescence dosimetry of an antibody-dye conjugate to identify head and neck cancer as a first step to fluorescence-guided tissue preselection for pathological assessment. Reviewed International coauthorship International journal

Naoki Nishio, Stan van Keulen, Nynke S van den Berg, Guolan Lu, Ethan P LaRochelle, Scott C Davis, Brock A Martin, Shayan Fakurnejad, Quan Zhou, Andrew C Birkeland, Michael J Kaplan, Vasu Divi, A Dimitrios Colevas, Brian W Pogue, Eben L Rosenthal

Head & neck   Vol. 42 ( 1 ) page： 59 - 66   2020.1

　More details

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

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

DOI： 10.1002/hed.25964

Web of Science

PubMed

Diagnosis of cervical lymph node metastases in head and neck cancer with ultrasonic measurement of lymph node volume. Reviewed International journal

Naoki Nishio, Yasushi Fujimoto, Mariko Hiramatsu, Takashi Maruo, Hidenori Tsuzuki, Nobuaki Mukoyama, Sayaka Yokoi, Akihisa Wada, Madoka Kaneko Furukawa, Masaki Furukawa, Michihiko Sone

Auris, nasus, larynx   Vol. 46 ( 6 ) page： 889 - 895   2019.12

　More details

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

OBJECTIVE: The purpose of this study was to evaluate the usefulness of ultrasound (US) volume measurement of the cervical lymph nodes for diagnosing nodal metastasis in patients with head and neck cancer using a node-by-node comparison. METHODS: Thirty-four consecutive patients with head and neck cancer from one tertiary university hospital were prospectively enrolled from 2012 to 2017. Patients with histologically proven squamous cell primary tumors in the head and neck region scheduled to undergo a therapeutic neck dissection were eligible. For each patient, 1-4 target lymph nodes were selected from the planned neck dissection levels. Lymph nodes with thickness >20 mm or in a cluster were excluded. Node-by-node comparisons between the pre-operative US assessment, the post-operative actual measurements and histopathological results were performed for all target lymph nodes. Quantitative measurements, such as three diameters, ratios of the three diameters and volume were analyzed in this study. Lymph node volume was calculated using the ellipsoid formula. RESULTS: Patients comprised 28 men and 6 women with a mean age of 60.0 years (range, 29-80 years) at the time of surgery. In total, 67 target lymph nodes were analyzed in this study and the thickness ranged from 3.9 to 20.0 mm (mean 8.0 mm). There was a strong correlation between the US volume and post-operative actual volume (ρ = 0.87, p < 0.01). The US volume measured 2156 ± 2156 mm3 for the tumor positive nodes, which was significantly greater than the US volume of 512 ± 315 mm3 for tumor negative nodes (p < 0.01). Significant differences between tumor positive and tumor negative nodes were found in five variables (volume, thickness, major axis, minor axis and ratio of minor axis to thickness) for total lymph nodes. To identify predictors of lymph node metastasis, ROC curves of the US variables of target lymph nodes were compared, of which 4 variables were considered acceptable for predicting the lymph node metastasis: volume (AUC 0.86), thickness (AUC 0.86), major axis (AUC 0.79), and minor axis (AUC 0.79) for total lymph nodes. The optimal cut-off level for US volume in total lymph nodes was found to be 1242 mm3, whereby a 62% sensitivity and 98% specificity was reached (likelihood ratio: 25.2). CONCLUSION: Pre-operative ultrasonic volume measurement of the cervical lymph nodes was useful for early detection of cervical nodal metastasis in head and neck cancer.

DOI： 10.1016/j.anl.2019.02.003

Web of Science

PubMed

Intraoperative Tumor Assessment Using Real-Time Molecular Imaging in Head and Neck Cancer Patients. Reviewed International coauthorship International journal

Stan van Keulen, Naoki Nishio, Shayan Fakurnejad, Nynke S van den Berg, Guolan Lu, Andrew Birkeland, Brock A Martin, Tymour Forouzanfar, A Dimitrios Colevas, Eben L Rosenthal

Journal of the American College of Surgeons   Vol. 229 ( 6 ) page： 560 - +   2019.12

　More details

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

BACKGROUND: In head and neck cancer, surgical resection using primarily visual and tactile feedback is considered the gold standard for solid tumors. Due to high numbers of tumor-involved surgical margins, which are directly correlated to poor clinical outcomes, intraoperative optical imaging trials have rapidly proliferated over the past 5 years. However, few studies report on intraoperative in situ imaging data that could support surgical resection. To demonstrate the clinical application of in situ surgical imaging, we report on the imaging data that are directly (ie in real-time) available to the surgeon. STUDY DESIGN: Fluorescence intensities and tumor-to-background ratios (TBRs) were determined from the intraoperative imaging data-the view as seen by the surgeon during tumor resection-of 20 patients, and correlated to patient and tumor characteristics including age, sex, tumor site, tumor size, histologic differentiation, and epidermal growth factor receptor (EGFR) expression. Furthermore, different lighting conditions in regard to surgical workflow were evaluated. RESULTS: Under these circumstances, intraoperative TBRs of the primary tumors averaged 2.2 ± 0.4 (range 1.5 to 2.9). Age, sex, tumor site, and tumor size did not have a significant effect on open-field intraoperative molecular imaging of the primary tumors (p > 0.05). In addition, variation in EGFR expression levels or the presence of ambient light did not seem to alter TBRs. CONCLUSIONS: We present the results of successful in situ intraoperative imaging of primary tumors alongside the optimal conditions with respect to both molecular image acquisition and surgical workflow. This study illuminates the potentials of open-field molecular imaging to assist the surgeon in achieving successful cancer removal.

DOI： 10.1016/j.jamcollsurg.2019.09.007

Web of Science

PubMed

Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer. Reviewed International coauthorship International journal

Naoki Nishio, Nynke S van den Berg, Stan van Keulen, Brock A Martin, Shayan Fakurnejad, Nutte Teraphongphom, Stefania U Chirita, Nicholas J Oberhelman, Guolan Lu, Crista E Horton, Michael J Kaplan, Vasu Divi, A Dimitrios Colevas, Eben L Rosenthal

Nature communications   Vol. 10 ( 1 ) page： 5044 - 5044   2019.11

　More details

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

Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the identification of metastatic LNs in the ex vivo setting for head and neck cancer patients. Molecular imaging demonstrates a significantly higher mean fluorescence signal in metastatic LNs compared to benign LNs in head and neck cancer patients undergoing an elective neck dissection. Molecular imaging to preselect at-risk LNs may thus allow a more rigorous examination of LNs and subsequently lead to improved prognostication than regular neck dissection.

DOI： 10.1038/s41467-019-13076-7

Web of Science

PubMed

Role of transcranial sphenoidotomy in skull base surgery: classification of surgical techniques based on the surgical anatomy of the sphenoid sinus. Reviewed International journal

Kenichiro Iwami, Masazumi Fujii, Yugo Kishida, Shinya Jinguji, Masayuki Yamada, Mudathir Bakhit, Naoki Nishio, Yasushi Fujimoto, Tetsuya Ogawa, Keisuke Takanari, Yuzuru Kamei, Kiyoshi Saito

Journal of neurosurgery   Vol. 131 ( 5 ) page： 1658 - 1667   2019.11

　More details

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

OBJECTIVEAlthough sphenoidotomy is more commonly performed via the transnasal approach than via the transcranial approach, transcranial sphenoidotomy (TCS) remains indispensable for en bloc resection of locally advanced sinonasal malignant tumors (SNMTs) extending to the skull base. TCS also enables transsphenoidal transposition of the temporoparietal galeal flap (TPGF) to compensate for the lack of vascularized reconstructive tissue after endoscopic transnasal skull base surgery. The objective of this study was to review the authors' surgical experience using TCS with an emphasis on the surgical anatomy of the sphenoid sinus and on the purpose of TCS. Relevant anatomy is further illustrated through cadaveric dissection and photo documentation.METHODSThe authors reviewed the records of 50 patients who underwent TCS at the Nagoya University Hospital, Fukushima Medical University Hospital, or Aichi Medical University Hospital over the course of 7 years (between January 2011 and November 2017). The authors also performed cadaveric dissection in 2 adult cadaveric skull base specimens.RESULTSOf the 50 patients included in this study, 44 underwent craniofacial resection (CFR) for en bloc resection of SNMTs involving the anterior and/or lateral skull base, and 6 underwent transsphenoidal transposition of the TPGF flap. The authors categorized the TCS procedures according to the portion of the sphenoid sinus wall involved (i.e., superior, lateral, and superolateral). Superior sphenoidotomy was used in patients requiring anterior CFR. Lateral sphenoidotomy was further divided into 2 subtypes, with type 1 procedures performed for the transsphenoidal transpositioning of the TPGF, and type 2 procedures used in patients requiring lateral CFR. Superolateral sphenoidotomy was used in anterolateral CFR.CONCLUSIONSTCS still represents a useful tool in the armamentarium of neurosurgeons treating central skull base lesions. The newly proposed surgical classification facilitates a profound understanding of TCS and how to incorporate this technique into clinical practice.

DOI： 10.3171/2018.6.JNS181013

Web of Science

PubMed

Fluorescence molecular imaging for identification of high-grade dysplasia in patients with head and neck cancer. Reviewed International coauthorship International journal

Shayan Fakurnejad, Stan van Keulen, Naoki Nishio, Myrthe Engelen, Nynke S van den Berg, Guolan Lu, Andrew Birkeland, Fred Baik, A Dimitrios Colevas, Eben L Rosenthal, Brock A Martin

Oral oncology   Vol. 97   page： 50 - 55   2019.10

　More details

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

OBJECTIVE: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. RESULTS: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia. CONCLUSION: Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.

DOI： 10.1016/j.oraloncology.2019.08.008

Web of Science

PubMed

Mixed cell type in airway inflammation is the dominant phenotype in asthma patients with severe chronic rhinosinusitis. Reviewed International journal

Tomoko Nishio, Keiko Wakahara, Yoshihiro Suzuki, Naoki Nishio, Suguru Majima, Saya Nakamura, Masaaki Teranishi, Masahiro Nakatochi, Michihiko Sone, Yoshinori Hasegawa

Allergology international : official journal of the Japanese Society of Allergology   Vol. 68 ( 4 ) page： 515 - 520   2019.10

　More details

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

BACKGROUND: Asthma often coexists with chronic rhinosinusitis (CRS). Recent studies revealed that sinus inflammation in asthmatic patients was related to eosinophilic inflammation. However, the relationship between the severity of CRS and four different sputum inflammatory phenotypes as defined by the proportion of eosinophils and neutrophils is unknown. The aim of this study was to examine the impact of the severity of CRS on lower airway and systemic inflammation in asthmatic patients. METHODS: We enrolled 57 adult asthmatic patients who underwent sinus computed tomography (CT). The severity of CRS was evaluated by the Lund-Mackay score (LMS). The induced sputum inflammatory phenotype was defined by eosinophils (≥/<2%) and neutrophils (≥/<60%). Peripheral blood mononuclear cells (PBMC) were collected to examine cytokine productions. RESULTS: The median LMS of subjects was 6 (interquartile range, 0-11.5). The sputum inflammatory cell phenotype was categorized as paucicellular (n = 14), neutrophilic (n = 11), eosinophilic (n = 20), or mixed (n = 12). LMS was positively correlated with the percentage of blood eosinophils, sputum eosinophils, and mean fluorescence intensity (MFI) of IL-5 on CD4+ T cells. In the severe CRS group (LMS, 12-24), the number of mixed cellular phenotypes was higher than that in the group without CRS (LMS, 0-4) and mild-to-moderate CRS group (LMS, 5-11). CONCLUSIONS: In asthmatic patients with severe CRS, the proportion of the mixed cellular inflammatory phenotype was increased as well as eosinophilic inflammation.

DOI： 10.1016/j.alit.2019.05.004

Web of Science

PubMed

The Sentinel Margin: Intraoperative Ex Vivo Specimen Mapping Using Relative Fluorescence Intensity. Reviewed International coauthorship International journal

Stan van Keulen, Naoki Nishio, Andrew Birkeland, Shayan Fakurnejad, Brock Martin, Tim Forouzanfar, Kristen Cunanan, A Dimitrios Colevas, Nynke S van den Berg, Eben Rosenthal

Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 25 ( 15 ) page： 4656 - 4662   2019.8

　More details

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

PURPOSE: Despite major advancements in surgical oncology, the positive margin rate for primary head and neck cancer resection remains around 15%-30%. In particular, the deep surface margin is the most challenging to adequately assess. Inadequate margins are directly correlated to poor survival, and as such, mitigation of these rates is critical to improve patient outcomes. We have developed an ex vivo imaging strategy that utilizes fluorescence intensity peaks (relative to background signal) of an injected anti-EGFR antibody conjugated to a fluorescent probe to locate potential close or positive margins on the deep surface of the resected tumor specimen. EXPERIMENTAL DESIGN: Twelve patients with head and neck cancer scheduled for surgery received systemic administration of a tumor-specific contrast-agent (panitumumab-IRDye800CW). After surgical resection, the tumor specimen was imaged using a fluorescence imager. The three highest fluorescence intensity-peaks on the deep surface of the specimen were isolated and correlated to histology to determine the margin distance at these regions. RESULTS: Relative fluorescence peak intensities identified the closest margin on the deep surface of the specimen within 2.5 minutes. The highest intensity peak consistently (100%) detected the closest margin to the tumor. The difference in tumor margin distance between the first and second highest fluorescence intensity peak averaged 2.1 ± 1.4 mm. The tumor-margin difference between the second and third highest peak averaged 1.6 ± 0.6 mm. CONCLUSIONS: Fluorescence intensity peaks can identify the region on the specimen where tumor is closest to specimen's edge on the deep surface. This technique could have broad applications in obtaining adequate margins in oncological surgery.

DOI： 10.1158/1078-0432.CCR-19-0319

Web of Science

PubMed

The Clinical Application of Fluorescence-Guided Surgery in Head and Neck Cancer. Reviewed International coauthorship International journal

Stan van Keulen, Naoki Nishio, Shayan Fakurnejad, Andrew Birkeland, Brock A Martin, Guolan Lu, Quan Zhou, Stefania U Chirita, Tymour Forouzanfar, A Dimitrios Colevas, Nynke S van den Berg, Eben L Rosenthal

Journal of nuclear medicine : official publication, Society of Nuclear Medicine   Vol. 60 ( 6 ) page： 758 - 763   2019.6

　More details

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

Although surgical resection has been the primary treatment modality of solid tumors for decades, surgeons still rely on visual cues and palpation to delineate healthy from cancerous tissue. This may contribute to the high rate (up to 30%) of positive margins in head and neck cancer resections. Margin status in these patients is the most important prognostic factor for overall survival. In addition, second primary lesions may be present at the time of surgery. Although often unnoticed by the medical team, these lesions can have significant survival ramifications. We hypothesize that real-time fluorescence imaging can enhance intraoperative decision making by aiding the surgeon in detecting close or positive margins and visualizing unanticipated regions of primary disease. The purpose of this study was to assess the clinical utility of real-time fluorescence imaging for intraoperative decision making. Methods: Head and neck cancer patients (n = 14) scheduled for curative resection were enrolled in a clinical trial evaluating panitumumab-IRDye800CW for surgical guidance (NCT02415881). Open-field fluorescence imaging was performed throughout the surgical procedure. The fluorescence signal was quantified as signal-to-background ratios to characterize the fluorescence contrast of regions of interest relative to background. Results: Fluorescence imaging was able to improve surgical decision making in 3 cases (21.4%): identification of a close margin (n = 1) and unanticipated regions of primary disease (n = 2). Conclusion: This study demonstrates the clinical applications of fluorescence imaging on intraoperative decision making. This information is required for designing phase III clinical trials using this technique. Furthermore, this study is the first to demonstrate this application for intraoperative decision making during resection of primary tumors.

DOI： 10.2967/jnumed.118.222810

Web of Science

PubMed

Exploration of coping styles in male patients with head and neck cancer: a prospective cohort study. Reviewed

Naohiro Sato, Hiroyuki Kimura, Yasunori Adachi, Naoki Nishio, Masahiko Ando, Tatsuya Tokura, Wataru Nagashima, Shinichi Kishi, Aya Yamauchi, Keizo Yoshida, Mariko Hiramatsu, Yasushi Fujimoto, Norio Ozaki

Nagoya journal of medical science   Vol. 81 ( 2 ) page： 249 - 258   2019.5

　More details

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

Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

DOI： 10.18999/nagjms.81.2.249

Web of Science

PubMed

Mixed cellular inflammation is increased in adult asthma with severe chronic rhinosinusitis

Nishio Tomoko, Wakahara Keiko, Suzuki Yoshihiro, Majima Suguru, Nishio Naoki, Teranishi Masaaki, Sone Michihiko, Hasegawa Yoshinori

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY   Vol. 143 ( 2 ) page： AB189 - AB189   2019.2

　More details

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

DOI： 10.1016/j.jaci.2018.12.579

Web of Science

Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma. Reviewed International coauthorship International journal

Stan van Keulen, Nynke S van den Berg, Naoki Nishio, Andrew Birkeland, Quan Zhou, Guolan Lu, Han-Wei Wang, Lyle Middendorf, Tymour Forouzanfar, Brock A Martin, A Dimitrios Colevas, Eben L Rosenthal

Oral oncology   Vol. 88   page： 58 - 65   2019.1

　More details

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

OBJECTIVE: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (<5 mm) are found in 15-30% of head and neck cancer patients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. MATERIALS AND METHODS: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. RESULTS: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. CONCLUSION: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.

DOI： 10.1016/j.oraloncology.2018.11.012

Web of Science

PubMed

Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss. Reviewed International journal

Yusuke Koide, Masaaki Teranishi, Saiko Sugiura, Yasue Uchida, Naoki Nishio, Ken Kato, Hironao Otake, Tadao Yoshida, Rei Otsuka, Fujiko Ando, Hiroshi Shimokata, Yasuhisa Hasegawa, Tsutomu Nakashima, Michihiko Sone

The journal of international advanced otology   Vol. 14 ( 2 ) page： 166 - 169   2018.8

　More details

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

OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk. MATERIALS AND METHODS: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene. RESULTS: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex. CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.

DOI： 10.5152/iao.2018.5442

Web of Science

PubMed

Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas Reviewed International journal

Kana Kimura, Yoshiyuki Itoh, Tohru Okada, Seiji Kubota, Mariko Kawamura, Rie Nakahara, Yumi Oie, Yuka Kozai, Yuuki Takase, Hidenori Tsuzuki, Naoki Nishio, Mariko Hiramatsu, Yasushi Fujimoto, Takefumi Mizutani, Akihiro Hirakawa, Shinji Naganawa

Asian Pacific journal of cancer prevention : APJCP   Vol. 19 ( 5 ) page： 1195 - 1199   2018.5

　More details

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

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are
primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory.
We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed
this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have
treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to
improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no
local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With
the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we
changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30
fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will
be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2
/day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started
on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is
the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free
survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center,
non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to
be conducted. The trial will evaluate the efficacy and safety of our protocol.

DOI： 10.22034/APJCP.2018.19.5.1195

PubMed

＜Editors' Choice＞ Maxillary sinus carcinoma outcomes over 60 years: experience at a single institution. Reviewed

Naoki Nishio, Yasushi Fujimoto, Mariko Hiramatsu, Takashi Maruo, Hidenori Tsuzuki, Nobuaki Mukoyama, Mariko Shimono, Michihiko Sone, Yoshitaka Kawabe, Kiyoshi Saito, Masazumi Fujii, Tsutomu Nakashima

Nagoya journal of medical science   Vol. 80 ( 1 ) page： 91 - 98   2018.2

　More details

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

Advances in the diagnosis and treatment of patients with maxillary sinus carcinoma have improved patient prognosis. This study investigated changes in demographic and clinical characteristics, treatment methods, and outcomes of patients with maxillary sinus carcinomas during three different 10-year periods spanning 60 years at our university hospital. Of the 233 patients with maxillary sinus carcinomas managed at Nagoya University Hospital, 135 were treated between 1951 and 1960 (first period), 35 between 1981 and 1990 (second period), and 63 between 2003 and 2012 (third period). Patient age, sex, TN classifications, treatment methods, and survival rates were compared among patients treated during these time periods. Of the 135, 35, and 63 patients with maxillary sinus carcinomas treated during these time periods, 86 (63.7%), 21 (51.4%), and 48 (76.2%), respectively, were men; 14 (10.4%), six (17.1%), and 14 (22.2%), respectively, were aged ≥70 years; and 135 (100%), 28 (80.0%), and 43 (68.3%), respectively, were treated surgically. The 5-year overall survival rates in patients treated during the first, second, and third periods were 29.7%, 44.3%, and 57.5%, respectively. These findings indicated that advances in the diagnosis and treatment of patients with maxillary sinus carcinoma, including computed tomography and craniofacial resection, have contributed to improvements in patient survival rates.

DOI： 10.18999/nagjms.80.1.91

Web of Science

PubMed

Sonographic detection of a lingual node metastasis from early squamous cell cancer of the tongue. Reviewed International journal

Naoki Nishio, Yasushi Fujimoto, Mariko Hiramatsu, Yoko Yamamoto, Michihiko Sone

Journal of clinical ultrasound : JCU   Vol. 46 ( 1 ) page： 69 - 72   2018.1

　More details

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

Lingual node metastasis from early-stage squamous cell carcinoma of the tongue is uncommon and difficult to detect. We present a case of a lingual lymph node metastasis from an early tongue cancer. Sonography demonstrated a small nonpalpable lingual node on the floor of the mouth. The patient underwent complete surgical resection and had no evidence of recurrence 5 years later. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:69-72, 2018.

DOI： 10.1002/jcu.22486

Web of Science

PubMed

A case of large ectopic hamartomatous thymoma of the neck Reviewed International journal

Sayaka Yokoi, Naoki Nishio, Yasushi Fujimoto, Nobuaki Mukoyama, Wakako Kinoshita, Michihiko Sone

Practica Oto-Rhino-Laryngologica   Vol. 111 ( 9 ) page： 645 - 649   2018

　More details

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

© 2018 Society of Practical Otolaryngology. All rights reserved. An ectopic hamartomatous thymoma (EHT) is an extremely rare benign soft tumor most commonly occurring in the lower neck region, that can be difficult to differentiate (preoperatively) from malignant tumors. We report a case of EHT of the neck diagnosed in a 42-year-old man. The patient presented with a 10-year history of a tumor in the lower neck region that had rapidly increased in size over the previous 3 years. Fine-needle aspiration biopsy findings suggested lipoma. As the clinical findings and CT/MRI images indicated the possibility of a malignant tumor, an open biopsy was performed. The biopsy revealed EHT and resection of the tumor was performed. Although there were slight adhesions between the tumor and mediastinum, the tumor had not invaded the thymus or thyroid, and could be successfully resected. Histopathological examination of the tumor revealed the characteristic features of EHT, including spindle cells, epithelial cells, and fat tissue mixed. The postoperative course was uneventful, and there was no evidence of recurrence during the 18-month follow up period. When encountering lesions in the lower neck, it is important to consider EHT in the differential diagnosis.

DOI： 10.5631/jibirin.111.645

Scopus

Computed tomographic assessment of autologous fat injection augmentation for vocal fold paralysis. Reviewed International journal

Naoki Nishio, Yasushi Fujimoto, Mariko Hiramatsu, Takashi Maruo, Kenji Suga, Hidenori Tsuzuki, Nobuaki Mukoyama, Mariko Shimono, Kazuhiro Toriyama, Keisuke Takanari, Yuzuru Kamei, Michihiko Sone

Laryngoscope investigative otolaryngology   Vol. 2 ( 6 ) page： 459 - 465   2017.12

　More details

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

Objective: To perform a quantitative computed tomography (CT) assessment of short- and long-term outcomes of autologous fat injection augmentation in patients with unilateral vocal fold paralysis. Study Design: Retrospective case series. Methods: Twelve patients who had undergone autologous fat injection augmentation for unilateral vocal fold paralysis in our hospital between 2011 and 2015 were enrolled in this study. The autologous fat for injection was acquired from periumbilical subcutaneous tissue and was injected orally using a special-purpose laryngeal injection needle. To evaluate the injected fat at the follow-up assessments, CT was performed at several times after surgery in clinical practice. All thin-section CT images were transferred to a workstation, and the volume of the injected fat was calculated. Results: Patients comprised 6 men and 6 women with a mean age at the time of surgery of 62.9 years (range, 46-82 years). The actual injected fat volume was 1.1-2.5 ml (mean, 1.6 ml). In seven patients assessed by CT two days after surgery, the average residual rate of the injected fat was 63.9%. The mean residual rates of the injected fat were 30.0% at 3 months, 33.7% at 6 months, 29.2% at 12 months, and 32.0% at 24 months. Conclusions: Although the injected fat volume decreased within the first three months and the residual rate of the injected fat was 30.0% at three months after injection, the residual fat volume remained at the same level for 24 months after injection. Level of Evidence: 4.

DOI： 10.1002/lio2.125

Web of Science

PubMed

Optimized treatment strategy of radiotherapy for early glottic squamous cell carcinomas: An initial analysis. Reviewed

Kana Kimura, Yoshiyuki Itoh, Tohru Okada, Seiji Kubota, Mariko Kawamura, Rie Nakahara, Yumi Oie, Yuka Kozai, Yuuki Takase, Hidenori Tsuzuki, Naoki Nishio, Mariko Hiramatsu, Yasushi Fujimoto, Takefumi Mizutani, Shinji Naganawa

Nagoya journal of medical science   Vol. 79 ( 3 ) page： 331 - 338   2017.8

　More details

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

The purpose of this study was to evaluate the clinical outcomes of radiotherapy for patients with T1/T2 glottic carcinoma. Patients with T1/T2 glottic carcinoma histopathologically diagnosed with squamous cell carcinoma and treated at our hospital between 2007 and 2015 were analyzed retrospectively. Our strategy for T1/T2 glottic carcinoma was as follows: radiotherapy alone with 2.25 Gy per fraction to a total of 25-28 fractions for patients with non-bulky T1 glottic carcinoma; concurrent chemoradiotherapy with oral S-1 and radiotherapy with 2 Gy per fraction to a total of 30 fractions for patients with T1 bulky/T2 favorable glottic carcinoma; or chemoradiotherapy with high-dose cisplatin and radiotherapy with 2 Gy per fraction to a total of 35 fractions for T2 unfavorable glottic carcinoma. Forty-eight patients were eligible. The median follow-up period among surviving patients was 38 months (range, 11-107). The disease was T1a in 23%, T1b in 13%, and T2 in 65% of patients. The 3-year local control rate in all patients, T1a, T1b, and T2 was 96.7%, 100%, 100%, and 96.0%, respectively. Of the 46 patients, one with T2 glottic carcinoma developed recurrent disease at the primary site, and one with T2 glottic carcinoma had lymph node recurrences in the neck. Acute Grade 3 dermatitis occurred in 8 (17%) patients and late Grade 2 hypothyroidism occurred in 2 (4%) patients. This retrospective study shows that our optimized treatment strategy of radiotherapy depending on the stage of early glottic carcinoma is not only effective but also well-tolerated.

DOI： 10.18999/nagjms.79.3.331

Web of Science

PubMed

Preoperative surgical simulation and validation of the line of resection in anterolateral craniofacial resection of advanced sinonasal sinus carcinoma Reviewed

Nishio Naoki, Fujii Masazumi, Hayashi Yuichiro, Hiramatsu Mariko, Maruo Takashi, Iwami Kenichiro, Kamei Yuzuru, Yagi Shunjiro, Takanar Keisuke, Fujimoto Yasushi

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   Vol. 39 ( 3 ) page： 512-519   2017.3

　More details

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

DOI： 10.1002/hed.24653

Web of Science

PubMed

Preoperative surgical simulation and validation of the line of resection in anterolateral craniofacial resection of advanced sinonasal sinus carcinoma Reviewed

Nishio N, Fujii M, Hayashi Y, Hiramatsu M, Maruo T, Iwami K, Kamei Y, Yagi S, Takanari K, Fujimoto Y

Head and Neck   Vol. 39 ( 3 ) page： 512-519   2016.12

　More details

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

DOI： 10.1002/hed.24653

Autologous fat injection therapy including a high concentration of adipose-derived regenerative cells in a vocal fold paralysis model: Animal pilot study Reviewed International journal

N. Nishio, Y. Fujimoto, K. Suga, Y. Iwata, K. Toriyama, K. Takanari, Y. Kamei, T. Yamamoto, M. Gotoh

Journal of Laryngology and Otology   Vol. 130 ( 10 ) page： 914 - 922   2016.10

　More details

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

Objectives: To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. Methods: Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. Results: Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. Conclusion: The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.

DOI： 10.1017/S0022215116008707

Web of Science

Scopus

PubMed

Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy Reviewed International journal

Y. Niwa, M. Koike, Y. Fujimoto, H. Oya, N. Iwata, N. Nishio, M. Hiramatsu, M. Kanda, D. Kobayashi, C. Tanaka, S. Yamada, T. Fujii, G. Nakayama, H. Sugimoto, S. Nomoto, M. Fujiwara, Y. Kodera

Diseases of the Esophagus   Vol. 29 ( 6 ) page： 598 - 602   2016.8

　More details

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc.  

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

DOI： 10.1111/dote.12362

Web of Science

Scopus

PubMed

Relationship between BMI and Postoperative Complications with Free Flap in Anterolateral Craniofacial Reconstruction. Reviewed International journal

Yang Hoi Heo, Shunjiro Yagi, Kazuhiro Toriyama, Keisuke Takanari, Yasushi Fujimoto, Naoki Nishio, Masazumi Fujii, Kiyoshi Saito, Masakatsu Takahashi, Yuzuru Kamei

Plastic and reconstructive surgery. Global open   Vol. 4 ( 3 ) page： e636   2016.3

　More details

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

BACKGROUND: Although we have seen tremendous advancement in microsurgery over the last 2 decades and free tissue transfer has become standard for head and neck reconstruction, surgeons still struggle to prevent postoperative complications. We examined the relationship between body mass index (BMI) and postoperative complications in patients undergoing rectus abdominis free flap transfer after anterolateral craniofacial resection. METHODS: This was a retrospective review of reconstructive surgery using rectus abdominis musculocutaneous free flap in patients with locally advanced maxillary sinus carcinoma from 2003 to 2014 (n = 35, 27 men and 8 women; average age, 60.9 ± 7.8 years). All patients underwent craniofacial reconstruction after anterior and middle cranial fossa skull base resection and maxillectomy (class IV, subtype a) with palatal resection. Patients were categorized based on sex, BMI, and other parameters. RESULTS: Recipient-site infection occurred in 11 patients (31.4%), cerebrospinal fluid leakage in 6 (17.1%), partial flap necrosis in 2 (5.7%), total flap necrosis in 1 (2.9%), and facial fistula in 4 (11.4%). Women showed partial flap necrosis significantly more frequently (P = 0.047), probably owing to poor vascular supply of the subcutaneous fat layer. Patients with low BMI (<20 kg/m(2)) showed recipient-site infection (P = 0.02) and facial fistula (P = 0.01) significantly more frequently owing to insufficient tissue volume and poor vascular supply. CONCLUSION: Postoperative recipient-site infection and facial fistula occurred mainly in low-BMI patients. Surgeons should take care to achieve sufficient donor tissue on low-BMI patients. Using a prosthetic obturator in low-BMI patients for craniofacial reconstruction can be a good alternative option to reduce postoperative complications due to insufficient donor tissue volume.

DOI： 10.1097/GOX.0000000000000645

Web of Science

PubMed

Craniofacial Resection for T4 Maxillary Sinus Carcinoma: Managing Cases with Involvement of the Skull Base. Reviewed International journal

Naoki Nishio, Yasushi Fujimoto, Masazumi Fujii, Kiyoshi Saito, Mariko Hiramatsu, Takashi Maruo, Kenichiro Iwami, Yuzuru Kamei, Shunjiro Yagi, Masakatsu Takahashi, Yuichiro Hayashi, Atsushi Ando, Tsutomu Nakashima

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery   Vol. 153 ( 2 ) page： 231 - 238   2015.8

　More details

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

OBJECTIVE: The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. STUDY DESIGN: Case series with chart review. SETTING: Tertiary university hospital. SUBJECTS AND METHODS: We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. RESULTS: Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and disease-free survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. CONCLUSION: This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates.

DOI： 10.1177/0194599815586770

Web of Science

PubMed

Craniofacial Resection for T4 Maxillary Sinus Carcinoma :Managing Cases with Involvement of the Skull Base. Reviewed

Nishio N, Fujimoto Y, Fujii M, Saito K, Hiramatsu M, Maruo T, Iwami K, Kamei Y, Yagi S, Takahashi M, Hayashi Y, Ando A, Nakashima T.

Otolaryngology Head and Neck Surgery   Vol. 153 ( 2 ) page： 231-238   2015.6

　More details

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

Changes in endolymphatic hydrops in patients with Ménière's disease treated conservatively for more than 1 year. Reviewed International journal

Kenji Suga, Masahiro Kato, Tadao Yoshida, Naoki Nishio, Takafumi Nakada, Saiko Sugiura, Hironao Otake, Ken Kato, Masaaki Teranishi, Michihiko Sone, Shinji Naganawa, Tsutomu Nakashima

Acta oto-laryngologica   Vol. 135 ( 9 ) page： 866 - 870   2015

　More details

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

CONCLUSION: This study revealed that endolymphatic hydrops (EH) reduced in some cases with Ménière's disease (MD) treated conservatively. It appears that the EH reduction was associated with improvement of the clinical symptoms. OBJECTIVES: The relationship between the degree of EH and clinical symptoms is not clear at present. The purpose of the present study was to investigate the time course of the relationship in patients with MD treated conservatively. PATIENTS: Twelve patients with MD treated conservatively for more than 1 year in a university hospital. METHODS: Twenty ears of 12 patients with MD treated conservatively were evaluated. The presence or absence of vertigo, tinnitus and ear fullness was confirmed when magnetic resonance imaging (MRI) was performed. Using a 3 T MRI scanner, three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI was performed 2 or 3 times 24 hours after intra-tympanic gadolinium injection or 4 hours after intravenous gadolinium injection. RESULTS: In the three ears in which the symptoms alleviated, EH was reduced in two ears, but EH was reduced in only one of 17 ears in which the symptoms did not alleviate. The Fisher exact test revealed that EH reduction occurred more frequently in ears with alleviation of the symptoms (p < 0.05).

DOI： 10.3109/00016489.2015.1015607

Web of Science

PubMed

良好な嚥下機能温存を目指した中咽頭・下咽頭再建 良好な機能温存を目指した下咽頭部分切除に対する再建の経験

八木 俊路朗, 鳥山 和宏, 高成 啓介, 蛯沢 克巳, 澤村 尚, 神戸 未来, 中村 優, 藤本 保志, 西尾 直樹, 亀井 譲

日本マイクロサージャリー学会学術集会プログラム・抄録集   Vol. 41回   page： 124 - 124   2014.12

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本マイクロサージャリー学会  

Laryngeal sensation and pharyngeal delay time after (chemo)radiotherapy. Reviewed International journal

Takashi Maruo, Yasushi Fujimoto, Kikuko Ozawa, Mariko Hiramatsu, Atsushi Suzuki, Naoki Nishio, Tsutomu Nakashima

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery   Vol. 271 ( 8 ) page： 2299 - 2304   2014.8

　More details

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

The objective of the study was to evaluate the association between changes in laryngeal sensation and initiation of swallowing reflex or swallowing function before and after (chemo)radiotherapy. A prospective study was conducted in a tertiary referral university hospital. Thirteen patients who received (chemo)radiotherapy for treatment of laryngeal or hypopharyngeal cancer were included. Laryngeal sensation was evaluated at the tip of the epiglottis before and 1, 3 months, and 1 year after (chemo)radiotherapy. Videofluoroscopy was performed at the same time. Quantitative determinations included changes in laryngeal sensation, computed analysis of pharyngeal delay time, the distance and velocity of hyoid bone movement during the phase of hyoid excursion, and pharyngeal residue rate (the proportion of the bolus that was left as residue in the pharynx at the first swallow). Laryngeal sensation significantly deteriorated 1 month after (chemo)radiotherapy, but there was a tendency to return to pretreatment levels 1 year after treatment. Neither pharyngeal delay time nor displacement of the hyoid bone changed significantly before and after (chemo)radiotherapy. In addition, there was no significant difference in the mean velocity of hyoid bone movement and the amount of stasis in the pharynx at the first swallow before and after (chemo)radiotherapy. After (chemo)radiotherapy, laryngeal sensation deteriorated. But, in this study, videofluoroscopy showed that swallowing reflex and function were maintained.

DOI： 10.1007/s00405-013-2775-7

Web of Science

PubMed

Inflammatory Pseudotumor of the Infratemporal Fossa Leading to Orbital Apex Syndrome. Reviewed

Nishio N, Fujimoto Y, Nakashima T.

Journal of Craniofacial Surgery   Vol. 25 ( 4 ) page： 1324-6   2014.7

　More details

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

Inflammatory pseudotumor of the infratemporal fossa leading to orbital apex syndrome. Reviewed International journal

Naoki Nishio, Yasushi Fujimoto, Tsutomu Nakashima

The Journal of craniofacial surgery   Vol. 25 ( 4 ) page： 1324 - 1326   2014.7

　More details

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

An inflammatory pseudotumor is a rare benign disease presenting with non-specific chronic inflammation, and reported occurrences involving the skull base are relatively rare. A 65-year-old man became aware of pain around the right temporomandibular joint and mild trismus, and palsies of the cranial nerves III, IV, V, and VI were observed. A biopsy was performed under general anesthesia with an infratemporal fossa approach, and he was diagnosed with inflammatory pseudotumor of the infratemporal fossa. There was a rapid improvement in symptoms after the start of steroid administration, and 29 months after the initial consultation, the patient remained under strict observation. The 3 criteria in our department for confirming progression of the disease are (1) clinical symptoms, (2) C-reactive protein levels in blood tests, and (3) contrast effect of the tumor on magnetic resonance imaging. This is a rare case report to demonstrate the inflammatory pseudotumor of the infratemporal fossa leading to orbital apex syndrome.

DOI： 10.1097/SCS.0000000000000789

Web of Science

PubMed

Effect of clinical symptoms on the indication for selective neck dissection for N0 carcinomas of the parotid gland. Reviewed International journal Open Access

Takashi Maruo, Yasushi Fujimoto, Kenji Yoshida, Mariko Hiramatsu, Atsushi Suzuki, Naoki Nishio, Mariko Shimono, Tsutomu Nakashima

Oncology letters   Vol. 8 ( 1 ) page： 335 - 338   2014.7

　More details

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

Lymph node metastasis is a major prognostic factor in parotid carcinoma, however, the pre-operative diagnosis of occult nodal metastasis is difficult in clinical N0 (cN0) parotid cancer patients. In addition, the indication of neck dissection in T1-3 cN0 patients is controversial. The current study investigated 17 patients with clinical T1-3 cN0 parotid cancer, and analyzed the correlation between patient symptoms/findings and pathological N status/tumor histological grade. In the statistical analysis, pain was found to significantly correlate with neck metastasis. Furthermore, cN0-staged patients without pain exhibited no neck metastasis. However, no significant correlation was identified between patient symptoms or findings and histological grade. These results indicate the possibility that selective neck dissection can be omitted for T1-3 cN0-staged patients without pain.

DOI： 10.3892/ol.2014.2137

Open Access

Web of Science

PubMed

永久気管孔造設患者におけるNAIM(Nasal Airflow Inducing Maneuver)法を用いた嗅覚改善訓練効果(第2報)

片山 直美, 藤本 保志, 平松 真理子, 丸尾 貴志, 西尾 直樹, 小出 悠介, 須賀 研治, 下野 真理子, 中田 隆文, 曾根 三千彦, 中島 務

頭頸部癌   Vol. 40 ( 2 ) page： 192 - 192   2014.5

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Analysis of post-operative complications and function in patients with cervical esophageal reconstruction using free jejunal flap International journal

Yagi Shunjiro, Toriyama Kazuhiro, Ono Masashi, Fujimoto Yasushi, Hiramatsu Mariko, Maruo Takashi, Nishio Naoki, Kamei Yuzuru

Toukeibu Gan   Vol. 40 ( 1 ) page： 1 - 4   2014

　More details

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

We reviewed 47 patients who underwent cervical esophageal reconstruction using a free jejunal flap transfer between July 2001 and December 2011. There were 40 males and 7 females with an average age of 64.3. Fifteen patients had radiotherapy preoperatively, and 24 patients postoperatively. The patients who underwent preoperative radiotherapy tended to suffer postoperative complications including surgical site infection and leakage, whereas those who underwent postoperative radiotherapy tended to suffer contracture at the anastomosed site between the free jejunal flap and the esophagus. We consider that free jejunal flap transfer in patients with cervical esophageal cancer is a safe procedure.

DOI： 10.5981/jjhnc.40.1

Scopus

Endothelin-1 gene polymorphism in sudden sensorineural hearing loss. Reviewed International journal

Yasue Uchida, Masaaki Teranishi, Naoki Nishio, Saiko Sugiura, Mariko Hiramatsu, Hidenori Suzuki, Ken Kato, Hironao Otake, Tadao Yoshida, Mitsuhiko Tagaya, Hirokazu Suzuki, Michihiko Sone, Fujiko Ando, Hiroshi Shimokata, Tsutomu Nakashima

The Laryngoscope   Vol. 123 ( 11 ) page： E59 - E65   2013.11

　More details

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

OBJECTIVES/HYPOTHESIS: Endothelin-1 is a potent vasoconstrictor peptide that is widely distributed throughout the mammalian body including the spiral modiolar artery, vestibule, and cochlea. This study aimed to investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) of the endothelin-1 gene and sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Case-control study. METHODS: Seventy-two SSNHL patients (mean age, 58.3 ± 14.0 years) were compared with 2,159 controls included in a community-based study of aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL. In subgroup analysis, patients with SSNHL who visited to the hospital within the first month of onset were selected to assess audiometric features according to genotype. Pure-tone averages at 250, 500, 1,000, 2,000, and 4,000 Hz were calculated in the affected ear. RESULTS: Under the recessive genetic model, after adjustment for age, sex, histories of hypertension, dyslipidemia and diabetes, the crude and adjusted ORs for SSNHL risk were 2.209 (95% confidence interval [CI]: 1.140-4.281) and 2.173 (95% CI: 1.086-4.348), respectively. No significant ORs were observed under the additive and dominant models. The severity of SSNHL differed significantly between genotypes. The mean pure-tone averages at the initial visit were 78.6, 66.4, and 57.8 dB for the GG, GT, and TT genotypes, respectively (P = .034). CONCLUSIONS: Our study indicates that the recessive genotype was significantly associated with increased SSNHL risk; however, the severity was lower in these individuals than it was in those with the wild-type genotype. Endothelin-1 may be implicated in SSNHL.

DOI： 10.1002/lary.24298

Web of Science

PubMed

Polymorphisms in genes involved in the free-radical process in patients with sudden sensorineural hearing loss and Ménière's disease Reviewed International journal

Masaaki Teranishi, Yasue Uchida, Naoki Nishio, Ken Kato, Hironao Otake, Tadao Yoshida, Hirokazu Suzuki, Michihiko Sone, Saiko Sugiura, Fujiko Ando, Hiroshi Shimokata, Tsutomu Nakashima

Free Radical Research   Vol. 47 ( 6-7 ) page： 498 - 506   2013.7

　More details

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

The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that free radicals are related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the association between genetic polymorphisms located in genes related to the free-radical process and susceptibility to SSNHL and Ménière's disease. We compared 83 patients affected by SSNHL and 83 patients affected by Ménière's disease with 2048 adults (for SSNHL) and 1946 adults (for Ménière's disease) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios (ORs) for SSNHL and Ménière's disease in individuals with polymorphisms in the genes: methionine synthase (MTR
rs1805087)
methionine-synthase reductase (MTRR
rs1801394)
nitric oxide synthase 3 (NOS3
rs1799983)
caveolin 1 (Cav1
rs3840634)
melatonin receptor 1B (MTNR1B
rs1387153)
NAD(P)H oxidase p22(phox) subunit (NADH/NADPHp22phox
rs4673)
and mitochondria 5178 (MT5178
rs28357984). The NOS3 polymorphism was significantly associated with a risk of SSNHL
in addition, the OR for the NOS3 polymorphism and SSNHL risk was 2.108 (CI, 1.343-3.309) with adjustment for age and sex. The Cav1 polymorphism was significantly associated with a risk of Ménière's disease
moreover, the OR for the Cav1 polymorphism and Ménière's disease risk was 1.849 (CI, 1.033-3.310) with adjustment for age and sex. In conclusion, the NOS3 and Cav1 polymorphisms were significantly associated with the risk of SSNHL and Ménière's disease, respectively. © 2013 Informa UK, Ltd.

DOI： 10.3109/10715762.2013.793319

Web of Science

Scopus

PubMed

Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease. Reviewed International journal

Yang Huang, Masaaki Teranishi, Yasue Uchida, Naoki Nishio, Ken Kato, Hironao Otake, Tadao Yoshida, Michihiko Sone, Saiko Sugiura, Fujiko Ando, Hiroshi Shimokata, Tsutomu Nakashima

Journal of neurogenetics   Vol. 27 ( 1-2 ) page： 5 - 10   2013.6

　More details

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

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD.

DOI： 10.3109/01677063.2013.770510

Web of Science

PubMed

Polymorphisms in genes encoding aquaporins 4 and 5 and estrogen receptor α in patients with Ménière's disease and sudden sensorineural hearing loss. Reviewed

Nishio N, Teranishi M, Uchida Y, Sugiura S, Ando F, Shimokata H, Sone M, Otake H, Kato K, Yoshida T, Tagaya M, Hibi T, Nakashima T.

Life Sciences   Vol. 92 ( 10 ) page： 541-6   2013.3

　More details

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

Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Ménière's disease in a Japanese population. Reviewed International journal

Masaaki Teranishi, Yasue Uchida, Naoki Nishio, Ken Kato, Hironao Otake, Tadao Yoshida, Hirokazu Suzuki, Michihiko Sone, Saiko Sugiura, Fujiko Ando, Hiroshi Shimokata, Tsutomu Nakashima

DNA and cell biology   Vol. 31 ( 10 ) page： 1555 - 1562   2012.10

　More details

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

The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that oxidative stress is related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the associations between genetic polymorphisms located in oxidative stress response genes and susceptibility to SSNHL and Ménière's disease. We compared 84 patients affected by SSNHL, 82 patients affected by Ménière's disease, and 2107 adults (1056 men and 1051 women; mean age, 59.2 years; range, 40-79 years) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios for SSNHL and Ménière's disease in individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1) (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu, rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala, rs4880), with adjustment for age and gender. No significant differences in the distribution of the genotypes at these polymorphisms were observed among individuals with SSNHL and Ménière's disease and controls. No significant risk for SSNHL and Ménière's disease was observed in the additive genetic model, regardless of moderating variables. The C allele of SOD2 (rs4880) was more frequent in Ménière's disease cases with a hearing level over 50 dB compared with cases with a hearing level below 50 dB, suggesting that this polymorphism is associated with progression of a hearing loss in Ménière's disease. In conclusion, no significant associations between the polymorphisms of GPX1, PON1, PON2, and SOD2 and risk of SSNHL and Ménière's disease were observed in this Japanese case-control study.

DOI： 10.1089/dna.2012.1631

Web of Science

PubMed

Polymorphisms in genes involved in inflammatory pathways in patients with sudden sensorineural hearing loss. Reviewed International journal

Mariko Hiramatsu, Masaaki Teranishi, Yasue Uchida, Naoki Nishio, Hidenori Suzuki, Ken Kato, Hironao Otake, Tadao Yoshida, Mitsuhiko Tagaya, Hirokazu Suzuki, Michihiko Sone, Saiko Sugiura, Fujiko Ando, Hiroshi Shimokata, Tsutomu Nakashima

Journal of neurogenetics   Vol. 26 ( 3-4 ) page： 387 - 396   2012.9

　More details

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

Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40-79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFα C - 863A, TNFRSF1B G593A, VEGF C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035-2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.

DOI： 10.3109/01677063.2011.652266

Web of Science

PubMed

Contribution of complement factor H Y402H polymorphism to sudden sensorineural hearing loss risk and possible interaction with diabetes. Reviewed

Nishio N, Teranishi M, Uchida Y, Sugiura S, Ando F, Shimokata H, Sone M, Otake H, Kato K, Yoshida T, Tagaya M, Hibi T, Nakashima T.

GENE   Vol. 499 ( 1 ) page： 226-30   2012.5

　More details

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

Association of interleukin-1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease Reviewed International journal

T. Furuta, M. Teranishi, Y. Uchida, N. Nishio, K. Kato, H. Otake, T. Yoshida, M. Tagaya, H. Suzuki, M. Sugiura, M. Sone, M. Hiramatsu, S. Sugiura, F. Ando, H. Shimokata, T. Nakashima

International Journal of Immunogenetics   Vol. 38 ( 3 ) page： 249 - 254   2011.6

　More details

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

Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T
rs1800587) and interleukin 1B (IL1B) (-511C/T
rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1744-313X.2011.01004.x

Web of Science

Scopus

PubMed

Endolymphatic hydrops revealed by intravenous gadolinium injection in patients with Ménière's disease. Reviewed International journal

Tsutomu Nakashima, Shinji Naganawa, Masaaki Teranishi, Mitsuhiko Tagaya, Seiichi Nakata, Michihiko Sone, Hironao Otake, Ken Kato, Tomoyuki Iwata, Naoki Nishio

Acta oto-laryngologica   Vol. 130 ( 3 ) page： 338 - 343   2010.3

　More details

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

CONCLUSION: Visualization of endolymphatic hydrops became possible after intravenous gadolinium (Gd) injection in patients with Ménière's disease. OBJECTIVE: To visualize endolymphatic hydrops after intravenous Gd injection. METHODS: Gd (gadoteridol; 0.2 mmol/kg) was injected intravenously in three patients with unilateral Ménière's disease. We performed three-dimensional fluid attenuated inversion recovery (3D-FLAIR) and three-dimensional real inversion recovery (3D-real IR) magnetic resonance imaging (MRI) 4 h after the injection using a 3-Tesla MRI unit. We used a 32-channel array coil to obtain a high signal-to-noise ratio. RESULTS: Endolymphatic hydrops was observed in the ears of patients with Ménière's disease. However, Gd concentration in the perilymph was lower compared with that obtained after intratympanic Gd injection.

DOI： 10.3109/00016480903143986

Web of Science

PubMed