2024/09/18 更新

写真a

ムコウヤマ ノブアキ
向山 宣昭
MUKOYAMA Nobuaki
所属
医学部附属病院 耳鼻いんこう科 助教
大学院担当
大学院医学系研究科
職名
助教

学位 1

  1. 医学博士 ( 2019年3月   名古屋大学 ) 

 

論文 34

  1. Development of a plant-based surgical training model for fluorescence-guided cancer surgery

    Shigeyama, M; Nishio, N; Wada, A; Mitani, S; Morimoto, G; Yokoi, S; Mukoyama, N; Yokoi, M; van Keulen, S; Rosenthal, E; Sone, M

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   46 巻 ( 9 ) 頁: 2274 - 2283   2024年9月

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    記述言語:英語   出版者・発行元:Head and Neck  

    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

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  2. Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma

    Tsujikawa, T; Ohno, K; Morita, K; Saburi, S; Mitsuda, J; Yoshimura, K; Kimura, A; Morimoto, H; Ogi, H; Shibata, S; Akashi, T; Kurata, M; Imoto, I; Shimizu, Y; Kano, S; Watanabe, A; Yamazaki, T; Asada, Y; Hayashi, R; Saito, Y; Ozawa, H; Tsukahara, K; Oridate, N; Sano, D; Horii, A; Ueki, Y; Maruo, T; Mukoyama, N; Hanai, N; Fukusumi, T; Iwai, H; Fujisawa, T; Fujii, T; Nibu, K; Iwae, S; Ueda, T; Chikuie, N; Yasumatsu, R; Matsuo, M; Umeno, H; Ono, T; Masuda, M; Toh, S; Itoh, K; Hirano, S; Asakage, T

    FRONTIERS IN IMMUNOLOGY   15 巻   頁: 1390873   2024年7月

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    記述言語:英語   出版者・発行元:Frontiers in Immunology  

    Background: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. Methods: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. Conclusion: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

    DOI: 10.3389/fimmu.2024.1390873

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  3. STING activator 2′3′-cGAMP enhanced HSV-1-based oncolytic viral therapy

    Sibal, PA; Matsumura, S; Ichinose, T; Bustos-Villalobos, I; Morimoto, D; Eissa, IR; Abdelmoneim, M; Aboalela, MAM; Mukoyama, N; Tanaka, M; Naoe, Y; Kasuya, H

    MOLECULAR ONCOLOGY   18 巻 ( 5 ) 頁: 1259 - 1277   2024年5月

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    記述言語:英語   出版者・発行元:Molecular Oncology  

    Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)-interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING-IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV-1-based OV, C-REV, with a membrane-impermeable STING agonist, 2′3′-GAMP. Our results demonstrated that tumor cells harbor a largely defective STING-IFN pathway, thereby preventing significant antiviral IFN induction regardless of the permeability of the STING agonist. In vivo, the combination therapy induced more proliferative KLRG1-high PD1-low CD8+ T-cells and activated CD103+ DC in the tumor site and increased tumor-specific CD44+ CD8+ T-cells in the lymph node. Overall, the combination therapy of C-REV with 2′3′-cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non-treated distal tumors.

    DOI: 10.1002/1878-0261.13603

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

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

    INTERNATIONAL JOURNAL OF LANGUAGE & COMMUNICATION DISORDERS     2024年4月

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    記述言語:英語   出版者・発行元:International Journal of Language and Communication Disorders  

    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

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  5. 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—

    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   35 巻 ( 2 ) 頁: 142 - 147   2023年12月

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    記述言語:日本語   出版者・発行元:日本喉頭科学会  

    DOI: 10.5426/larynx.35.142

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  6. Efficacy of endoscopic cricopharyngeal myotomy using a curved rigid laryngoscope in patients with sporadic inclusion body myositis: four retrospective case reviews

    Shigeyama, M; Nishio, N; Yokoi, S; Mukoyama, N; Wada, A; Maruo, T; Noda, S; Murakami, A; Tsuboi, T; Katsuno, M; Fujimoto, Y; Sone, M

    NAGOYA JOURNAL OF MEDICAL SCIENCE   85 巻 ( 4 ) 頁: 866 - 874   2023年11月

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    記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    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

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  7. Indications for sentinel lymph node biopsy in node-negative oral cancers

    Ozawa, T; Oze, I; Matsuzuka, T; Sasaki, E; Yokoyama, J; Sano, Y; Tomifuji, M; Araki, K; Kogashiwa, Y; Tateya, I; Agena, S; Sakashita, T; Tsuzuki, H; Terada, H; Suzuki, H; Nishikawa, D; Beppu, S; Matoba, T; Mukoyama, N; Oguri, K; Hasegawa, Y

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   45 巻 ( 10 ) 頁: 2533 - 2543   2023年10月

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    記述言語:英語   出版者・発行元:Head and Neck  

    Background: We aimed to define the indications for sentinel lymph node biopsy (SLNB), the third option for cervical treatment in oral cancer with negative cervical lymph nodes. Methods: The greatest depth of invasion (DOI) and long diameter (LD) of the primary site were used as exposures. SLN metastasis was considered the outcome. Results: In three trials conducted between 2009 and 2016, 158 patients were eligible and reassigned to this study group. The scatterplot based on the respective values of DOI and LD would eventually be divided into three sections. In cases of sections T1, T2, and T3, the proportions of SLN metastasis positivity were 21.3%, 35.3%, and 51.2%, respectively. In certain cases of T1 with 2 mm < DOI ≤ 5 mm and 8 mm < LD ≤ 20 mm, the proportion of SLN metastasis positivity was 40.9%. Conclusions: SLNB-navigated or assisted neck dissection can be added as an effective procedure for N0 neck control.

    DOI: 10.1002/hed.27477

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  8. Long-term outcomes of lateral skull base reconstruction with a free omental flap and facial nerve reconstruction

    Kambe, M; Hashikawa, K; Takanari, K; Yagi, S; Toriyama, K; Ebisawa, K; Nishio, N; Maruo, T; Mukoyama, N; Fujimoto, Y; Fujii, M; Saito, K; Takahashi, M; Kamei, Y

    NAGOYA JOURNAL OF MEDICAL SCIENCE   85 巻 ( 2 ) 頁: 255 - 264   2023年5月

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    記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    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

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  9. 咽頭喉頭食道全摘術の再建法と治療成績に関する全国調査

    岡村 明彦, 渡邊 雅之, 向山 宣昭, 太田 喜洋, 白石 治, 新橋 渉, 馬場 祥史, 松居 秀敏, 四宮 弘隆, 藤 也寸志, 塩谷 彰浩

    日本気管食道科学会会報   74 巻 ( 2 ) 頁: 75 - 75   2023年4月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本気管食道科学会  

    DOI: 10.2468/jbes.74.75

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

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

    JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE   84 巻 ( 01 ) 頁: 69 - 78   2023年2月

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    記述言語:英語   出版者・発行元:Journal of Neurological Surgery, Part B: Skull Base  

    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

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  11. Safety and Clinical Benefits of Laryngeal Closure in Patients with Amyotrophic Lateral Sclerosis

    Yokoi, S; Nishio, N; Maruo, T; Hiramatsu, M; Mukoyama, N; Tsuzuki, H; Wada, A; Atsuta, N; Ito, D; Tsuboi, T; Sobue, G; Katsuno, M; Fujimoto, Y; Sone, M

    DYSPHAGIA   38 巻 ( 1 ) 頁: 211 - 219   2023年2月

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    記述言語:英語   出版者・発行元:Dysphagia  

    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

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  12. Validation of a surgical training model containing indocyanine green for near-infrared fluorescence imaging

    Nishio, N; Mitani, S; Sakamoto, K; Morimoto, G; Yokoi, S; Shigeyama, M; Wada, A; Mukoyama, N; Rosenthal, EL; Sone, M

    LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY   7 巻 ( 4 ) 頁: 1011 - 1017   2022年8月

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    記述言語:英語   出版者・発行元:Laryngoscope Investigative Otolaryngology  

    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

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  13. Oncolytic HSV HF10 (canerpaturev, C-REV) promotes accumulation of CD8+PD-1-tumor-infiltrating T cells in a SCC model

    Mohamed, AA; Eissa, IR; Mukoyama, N; Abdelmoneim, M; Naoe, Y; Matsumura, S; Bustosvillalobos, I; Ichinose, T; Miyajima, N; Morimoto, D; Tanaka, M; Fujimoto, Y; Sone, M; Kodera, Y; Kasuya, H

    CANCER SCIENCE   113 巻   頁: 526 - 526   2022年2月

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    記述言語:日本語  

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  14. A Nationwide Survey on Digestive Reconstruction Following Pharyngolaryngectomy With Total Esophagectomy: A Multicenter Retrospective Study in Japan

    Okamura, A; Watanabe, M; Mukoyama, N; Ota, Y; Shiraishi, O; Shimbashi, W; Baba, Y; Matsui, H; Shinomiya, H; Sugimura, K; Morita, M; Sakai, M; Sato, H; Shibata, T; Nasu, M; Matsumoto, S; Toh, Y; Shiotani, A

    ANNALS OF GASTROENTEROLOGICAL SURGERY   6 巻 ( 1 ) 頁: 54 - 62   2022年1月

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    記述言語:英語   出版者・発行元:Annals of Gastroenterological Surgery  

    Aim: Digestive reconstruction after pharyngolaryngectomy with total esophagectomy (PLTE) remains challenging, with the optimal method remaining unclear. The current study aimed to clarify the short-term outcomes after PLTE and determine the optimal digestive reconstruction method. Methods: Based on a nationwide survey of 151 patients who underwent PLTE, outcomes of digestive reconstruction methods are described. Results: Among digestive reconstruction methods, a simple gastric tube was most frequently used (37.1%), followed by gastric tube combined with free graft transfer (FGT) (35.1%), gastric tube with microvascular anastomosis (22.5%), and other procedures (5.3%). Intraoperative evaluation of microcirculation (IOEM) was utilized in 29 patients (19.2%). Among the included patients, 66.9% developed any-grade complications, 41.0% developed severe complications, and 23.8% developed digestive reconstruction-related complications (DRRCs; leakage or necrosis). Reoperation within 30 days for any complications and DRRCs was required in 13.9% and 8.6% of the patients, respectively. Mortality within 90 days was observed in 4.6%. Among the three major methods, gastric tube combined with FGT promoted the least DRRCs in the gastric tube (P =.005), although the overall incidence of DRRCs was comparable. The use of IOEM was significantly associated with a reduction of severe DRRCs (P =.005). Conclusions: Pharyngolaryngectomy with total esophagectomy is a high-risk surgery significantly associated with the occurrence of postoperative morbidity and mortality. Nonetheless, the addition of FGT can help prevent gastric tip complications, while IOEM can be an effective method for improving outcomes.

    DOI: 10.1002/ags3.12509

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  15. S-1 facilitates canerpaturev (C-REV)-induced antitumor efficacy in a triple-negative breast cancer model

    Miyajima, N; Eissa, IR; Abdelmoneim, M; Naoe, Y; Ichinose, T; Matsumura, S; Bustos-Villalobos, I; Mukoyama, N; Morimoto, D; Shibata, M; Takeuchi, D; Tsunoda, N; Kikumori, T; Tanaka, M; Kodera, Y; Kasuya, H

    NAGOYA JOURNAL OF MEDICAL SCIENCE   83 巻 ( 4 ) 頁: 683 - 696   2021年11月

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    記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    Canerpaturev (C-REV) is a highly attenuated, replication-competent, mutant strain of oncolytic herpes simplex virus type 1 that may be an effective new cancer treatment option. S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer. Although the antitumor effects of oncolytic viruses combined with 5-FU in vivo have been reported, the detailed mechanisms are unknown. Here, we investigated the antitumor mechanism of the combination of C-REV and S-1 in triple-negative breast cancer (TNBC) in the context of tumor immunity. The combined effect of C-REV and S-1 was evaluated in a bilateral tumor model of murine TNBC 4T1 in vivo. S-1 enhanced the TNBC growth inhibitory effects of C-REV, and decreased the number of tumor-infiltrating, myeloid-derived suppressor cells (MDSCs), which suppress both innate and adaptive immune responses. Moreover, C-REV alone and in combination with S-1 significantly increased the number of CD8+ T cells in the tumor and the production of interferon γ (IFNγ) from these cells. Our findings indicate that C-REV suppresses TNBC tumor growth by inducing the expansion of effector CD8+ T cell subsets in tumors in which S-1 can inhibit MDSC function. Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC.

    DOI: 10.18999/nagjms.83.4.683

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  16. Oncolytic herpes simplex virus HF10 (canerpaturev) promotes accumulation of CD8<SUP>+</SUP>PD-1<SUP>-</SUP> tumor-infiltrating T cells in PD-L1-enriched tumor microenvironment

    Eissa, IR; Mukoyama, N; Abdelmoneim, M; Naoe, Y; Matsumura, S; Bustos-Villalobos, I; Ichinose, T; Miyajima, N; Morimoto, D; Tanaka, M; Fujimoto, Y; Sone, M; Kodera, Y; Kasuya, H

    INTERNATIONAL JOURNAL OF CANCER   149 巻 ( 1 ) 頁: 214 - 227   2021年7月

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    記述言語:英語   出版者・発行元:International Journal of Cancer  

    Oncolytic viruses (OVs) remodel the tumor microenvironment by switching a “cold” tumor into a “hot” tumor with high CD8+ T-cell infiltration. CD8+ T-cell activity plays an essential role in the antitumor efficacy of OVs. However, the activity of T cells is impaired by the programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) interaction. To date, it remains unclear why OVs alone have a significant antitumor activity even when PD-L1 expression persists on tumor or immune cells. In this study, we found that canerpaturev (C-REV) treatment significantly suppressed tumor growth, even though it induced a significant increase in PD-L1 expression in tumors in vivo as well as persistence of high PD-L1 expression on antigen-presenting cells (macrophage and dendritic cells [DCs]). Surprisingly, we observed that C-REV treatment increased the abundance of activated CD8+PD-1− tumor-infiltrating lymphocytes (TILs) in the tumor on both the injected and contralateral sides, although infiltration of CD8+PD-1high TILs into the tumor was observed in the control group. Moreover, the difference in PD-1 expression was observed only in tumors after treatment with C-REV, whereas most CD8+ T cells in the spleen, tumor-draining lymph nodes and blood were PD-1-negative, and this did not change after C-REV treatment. In addition, changes in expression of T-cell immunoglobulin and mucin-domain containing-3 and T-cell immune-receptor with Ig and ITIM domains were not observed on CD8+ TILs after C-REV treatment. Taken together, our findings may reveal mechanisms that allow OVs to trigger an antitumor immune response, irrespective of a PD-L1-enriched tumor microenvironment, by recruitment of CD8+PD-1− TILs.

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

    Iwami, K; Fujii, M; Nishio, N; Maruo, T; Yoshida, T; Mukoyama, N; Osuka, K; Takanari, K; Murotani, K; Kamei, Y; Sone, M; Fujimoto, Y; Saito, K

    WORLD NEUROSURGERY   151 巻   頁: E192 - E207   2021年7月

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    記述言語:英語   出版者・発行元:World Neurosurgery  

    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

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  18. C-REV Retains High Infectivity Regardless of the Expression Levels of cGAS and STING in Cultured Pancreatic Cancer Cells

    Morimoto, D; Matsumura, S; Bustos-Villalobos, I; Sibal, PA; Ichinose, T; Naoe, Y; Eissa, IR; Abdelmoneim, M; Mukoyama, N; Miyajima, N; Tanaka, M; Kodera, Y; Kasuya, H

    CELLS   10 巻 ( 6 )   2021年6月

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    記述言語:英語   出版者・発行元:Cells  

    Oncolytic virus (OV) therapy is widely considered as a major breakthrough in anti-cancer treatments. In our previous study, the efficacy and safety of using C-REV for anti-cancer therapy in patients during stage I clinical trial was reported. The stimulator of interferon genes (STING)– TBK1–IRF3–IFN pathway is known to act as the central cellular host defense against viral infection. Recent reports have linked low expression levels of cGAS and STING in cancer cells to poor prognosis among patients. Moreover, downregulation of cGAS and STING has been linked to higher susceptibility to OV infection among several cancer cell lines. In this paper, we show that there is little correlation between levels of cGAS/STING expression and susceptibility to C-REV among human pancreatic cancer cell lines. Despite having a responsive STING pathway, BxPC-3 cells are highly susceptible to C-REV infection. Upon pre-activation of the STING pathway, BxPc-3 cells exhibited resistance to C-REV infection. However, without pre-activation, C-REV completely suppressed the STING pathway in BxPC-3 cells. Additionally, despite harboring defects in the STING pathway, other high-grade cancer cell lines, such as Capan-2, PANC-1 and MiaPaCa-2, still exhibited low susceptibility to C-REV infection. Furthermore, overexpression of STING in MiaPaCa-2 cells altered susceptibility to a limited extent. Taken together, our data suggest that the cGAS– STING pathway plays a minor role in the susceptibility of pancreatic cancer cell lines to C-REV infection.

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

    Wada, A; Nishio, N; Yokoi, S; Tsuzuki, H; Mukoyama, N; Maruo, T; Hiramatsu, M; Yamamoto, T; Goto, M; Fujimoto, Y; Sone, M

    AURIS NASUS LARYNX   48 巻 ( 2 ) 頁: 274 - 280   2021年4月

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    記述言語:英語   出版者・発行元:Auris Nasus Larynx  

    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.

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  20. 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

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

    INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   50 巻 ( 3 ) 頁: 316 - 322   2021年3月

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    記述言語:英語   出版者・発行元:International Journal of Oral and Maxillofacial Surgery  

    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

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  21. 当院における気管切開術の現状と問題点

    横井 麻衣, 平松 真理子, 向山 宣昭, 藤本 保志, 曾根 三千彦

    日本気管食道科学会会報   72 巻 ( 1 ) 頁: 10 - 15   2021年2月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本気管食道科学会  

    <p>経皮的気管切開術(PDT)は外科的気管切開術(ST)と比べて手術時間が短く簡便でありICU等のベッドサイドで施行される例が増えている。当院におけるSTとPDTについて比較検討すると,STが157例,PDTは25例施行されており,抜管困難による気管切開術を選択する症例が最も多かった。合併症は創部感染12例,術後出血6例,チューブ閉塞8例,交換困難4例,気道肉芽5例であり,創部感染率はSTの方が高かった。術後出血と交換困難については,それぞれPDT術後の出血が持続し処置に難渋した症例と,穿刺時の輪状軟骨前壁損傷による交換困難を生じた症例を経験した。当院におけるPDTは主科(他科)が行う傾向がある。われわれが経験した術後治療に難渋した2症例は,ともに最初の穿刺場所が問題点と考えられ,穿刺前に体表からメルクマールとなる甲状軟骨,輪状軟骨などがわかりにくい症例はSTの方が安全である可能性が示唆される。また,安全性を高めるためには,適応を十分に考慮する必要がある。</p>

    DOI: 10.2468/jbes.72.10

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  22. Investigation of parotid gland cancer surgery that preserved the facial nerve

    Hamabata R., Mukoyama N., Nishio N., Maruo T., Hiramatsu M., Yokoi S., Sone M., Fujimoto Y.

    Japanese Journal of Head and Neck Cancer   47 巻 ( 3 ) 頁: 316 - 321   2021年

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    記述言語:日本語   出版者・発行元:Japanese Journal of 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

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

    Mukoyama, N; Nishio, N; Kimura, H; Kishi, S; Tokura, T; Kimura, H; Hiramatsu, M; Maruo, T; Tsuzuki, H; Fujii, M; Iwami, K; Takanari, K; Kamei, Y; Ozaki, N; Sone, M; Fujimoto, Y

    JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE   81 巻 ( 05 ) 頁: 585 - 593   2020年10月

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    記述言語:英語   出版者・発行元:Journal of Neurological Surgery, Part B: Skull Base  

    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.

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  24. 気管切開術─安全な管理を導けるコツはなにか

    藤本 保志, 横井 麻衣, 平松 真理子, 向山 宣昭, 丸尾 貴志, 曾根 三千彦

    日本気管食道科学会会報   71 巻 ( 2 ) 頁: 82 - 82   2020年4月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本気管食道科学会  

    DOI: 10.2468/jbes.71.82

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

    Nishio, N; Fujimoto, Y; Hiramatsu, M; Maruo, T; Tsuzuki, H; Mukoyama, N; Yokoi, S; Wada, A; Furukawa, MK; Furukawa, M; Sone, M

    AURIS NASUS LARYNX   46 巻 ( 6 ) 頁: 889 - 895   2019年12月

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    記述言語:英語   出版者・発行元:Auris Nasus Larynx  

    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.

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  26. Combination of Cetuximab and Oncolytic Virus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth

    Wu, ZW; Ichinose, T; Naoe, Y; Matsumura, S; Villalobos, IB; Eissa, IR; Yamada, S; Miyajima, N; Morimoto, D; Mukoyama, N; Nishikawa, Y; Koide, Y; Kodera, Y; Tanaka, M; Kasuya, H

    MOLECULAR THERAPY-ONCOLYTICS   13 巻   頁: 107 - 115   2019年6月

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    記述言語:英語   出版者・発行元:Molecular Therapy Oncolytics  

    The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer.

    DOI: 10.1016/j.omto.2019.04.004

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  27. The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers

    Eissa, IR; Bustos-Villalobos, I; Ichinose, T; Matsumura, S; Naoe, Y; Miyajima, N; Morimoto, D; Mukoyama, N; Wu, ZW; Tanaka, M; Hasegawa, H; Sumigama, S; Aleksic, B; Kodera, Y; Kasuya, H

    CANCERS   10 巻 ( 10 )   2018年10月

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    記述言語:英語   出版者・発行元:Cancers  

    Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

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  28. Peak of Standardized Uptake Value in Oral Cancer Predicts Survival Adjusting for Pathological Stage

    Suzuki, H; Tamaki, T; Nishio, M; Beppu, S; Mukoyama, N; Hanai, N; Nishikawa, D; Koide, Y; Hasegawa, Y

    IN VIVO   32 巻 ( 5 ) 頁: 1193 - 1198   2018年9月

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    記述言語:英語   出版者・発行元:In Vivo  

    Background/Aim: To predict survival outcomes of different patients with the same stage of disease is difficult. The possible correlation between 18F-fluorodeoxyglucose (18F-FDG) uptake parameters and survival outcomes was investigated in oral squamous cell carcinoma patients by multivariate analysis adjusted for the pathological stage according to the 8th edition of the tumor-node-metastasis (TNM) classification of the Union for International Cancer Contro. Patients and Methods: 18F-FDG-uptake parameters of 28 patients were assessed by positron emission tomography with computed tomography (PET/CT). Results: A peak of standardized uptake value of primary tumor (p-SUVpeak) of ≥14.1 was significantly correlated with shorter overall survival by univariate and multivariate analyses adjusted for the pathological TNM stage. A p-SUVpeak of ≥14.1 was significantly associated with shorter local recurrence-free survival and disease-free survival. Conclusion: A higher p-SUVpeak on pretreatment 18F-FDG-PET/CT is a prognostic parameter of identifying lower survival outcomes.

    DOI: 10.21873/invivo.11363

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  29. Pathological tumor volume predicts survival outcomes in oral squamous cell carcinoma

    Mukoyama, N; Suzuki, H; Hanai, N; Sone, M; Hasegawa, Y

    ONCOLOGY LETTERS   16 巻 ( 2 ) 頁: 2471 - 2477   2018年8月

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    記述言語:英語   出版者・発行元:Oncology Letters  

    The present study examined whether the pathological tumor volume (PTV) was correlated with the survival outcomes in patients with oral squamous cell carcinoma (SCC) and clinical lymph node metastasis. Forty-seven patients who underwent radical surgery without preoperative treatment were enrolled. The PTV of the primary tumor, which was surgically resected without preoperative treatment, was calculated based on the diameters in three dimensions. A survival analysis was performed using a Cox proportional hazards model. A PTV of ≥18 cm3 was significantly correlated with shorter overall survival (P<0.01) and local recurrence-free survival (P<0.01) in a univariate analysis. A multivariate analysis with adjustment for the pathological stage (stage I-II/III-IV), primary site (tongue/others) and positive surgical margin and/or extracap-sular extension (absent/present) showed that a PTV of ≥18 cm3 was significantly correlated with shorter overall survival (P<0.01) and local recurrence-free survival (P<0.01). The present findings suggested that PTV in oral SCC provides a prognostic parameter that may predict shorter or longer overall and local recurrence-free survival.

    DOI: 10.3892/ol.2018.8951

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  30. Maxillary sinus carcinoma outcomes over 60 years: experience at a single institution

    Nishio, N; Fujimoto, Y; Hiramatsu, M; Maruo, T; Tsuzuki, H; Mukoyama, N; Shimono, M; Sone, M; Kawabe, Y; Saito, K; Fujii, M; Nakashima, T

    NAGOYA JOURNAL OF MEDICAL SCIENCE   80 巻 ( 1 ) 頁: 91 - 98   2018年2月

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    記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    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

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  31. A case of large ectopic hamartomatous thymoma of the neck

    Yokoi S., Nishio N., Fujimoto Y., Mukoyama N., Kinoshita W., Sone M.

    Practica Oto-Rhino-Laryngologica   111 巻 ( 9 ) 頁: 645 - 649   2018年

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    記述言語:日本語   出版者・発行元:Practica Oto-Rhino-Laryngologica  

    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

    CiNii Research

  32. Computed tomographic assessment of autologous fat injection augmentation for vocal fold paralysis.

    Nishio N, Fujimoto Y, Hiramatsu M, Maruo T, Suga K, Tsuzuki H, Mukoyama N, Shimono M, Toriyama K, Takanari K, Kamei Y, Sone M

    Laryngoscope investigative otolaryngology   2 巻 ( 6 ) 頁: 459 - 465   2017年12月

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    記述言語:英語   出版者・発行元:Laryngoscope Investigative Otolaryngology  

    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

    Scopus

    PubMed

  33. Genomic Signature of the Natural Oncolytic Herpes Simplex Virus HF10 and Its Therapeutic Role in Preclinical and Clinical Trials.

    Eissa IR, Naoe Y, Bustos-Villalobos I, Ichinose T, Tanaka M, Zhiwen W, Mukoyama N, Morimoto T, Miyajima N, Hitoki H, Sumigama S, Aleksic B, Kodera Y, Kasuya H

    Frontiers in oncology   7 巻 ( JUL ) 頁: 149   2017年

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    記述言語:英語   出版者・発行元:Frontiers in Oncology  

    Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54. In preclinical studies, HF10 replicated efficiently within tumor cells with extensive cytolytic effects and induced increased numbers of activated CD4+ and CD8+ T cells and natural killer cells within the tumor, leading to a significant reduction in tumor growth and prolonged survival rates. Investigator-initiated clinical studies of HF10 have been completed in recurrent breast carcinoma, head and neck cancer, and unresectable pancreatic cancer in Japan. Phase I trials were subsequently completed in refractory superficial cancers and melanoma in the United States. HF10 has been demonstrated to have a high safety margin with low frequency of adverse effects in all treated patients. Interestingly, HF10 antigens were detected in pancreatic carcinoma over 300 days after treatment with infiltration of CD4+ and CD8+ T cells, which enhanced the immune response. To date, preliminary results from a Phase II trial have indicated that HF10 in combination with ipilimumab (anti-CTLA-4) is safe and well tolerated, with high antitumor efficacy. Improvement of the effect of ipilimumab was observed in patients with stage IIIb, IIIc, or IV unresectable or metastatic melanoma. This review provides a concise description of the genomic functional organization of HF10 compared with talimogene laherparepvec. Furthermore, this review focuses on HF10 in cancer treatment as monotherapy as well as in combination therapy through a concise description of all preclinical and clinical data. In addition, we will address approaches for future directions in HF10 studies as cancer therapy.

    DOI: 10.3389/fonc.2017.00149

    Scopus

    PubMed

  34. 口腔咽頭癌手術症例における気管切開の検討

    都築 秀典, 藤本 保志, 平松 真理子, 西尾 直樹, 向山 宣昭, 曾根 三千彦

    日本気管食道科学会会報   68 巻 ( 2 ) 頁: 166 - 166   2017年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本気管食道科学会  

    DOI: 10.2468/jbes.68.166

    CiNii Research

▼全件表示

科研費 3

  1. 新規細胞療法CAR-DCの頭頸部癌に対する抗腫瘍効果機序解析

    研究課題/研究課題番号:24K12645  2024年4月 - 2027年3月

    科学研究費助成事業  基盤研究(C)

    向山 宣昭, 西尾 直樹

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    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    CAR-T細胞は血液悪性腫瘍に顕著な有効性を示しているが、固形腫瘍に対する効果は散発的かつ一過性である。申請者の研究室では腫瘍抗原を認識するキメラ抗原受容体 (chimeric antigen receptor : CAR)を介して樹状細胞 (dendritic cell : DC)を活性化させるCAR発現DC (CAR-DC)療法を開発し、その抗原特異的なCAR-DCの抗腫瘍効果を様々な抗原発現固形腫瘍動物モデルで確認した。本研究は新規細胞療法CAR-DCがいかにEGFR発現頭頸部扁平上皮癌に対して抗腫瘍効果を発揮するか明らかにすることを目的とする。

  2. キメラ抗原受容体を樹状細胞に組み込んだ新規細胞療法の抗腫瘍効果機序解析

    研究課題/研究課題番号:22K15602  2022年4月 - 2024年3月

    科学研究費助成事業  若手研究

    向山 宣昭

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    近年、腫瘍内で樹状細胞 (Dendritic cell : DC)を活性化させることにより、腫瘍内にT細胞が集積することが明らかになった。そこで、申請者の研究室では腫瘍表面抗原を特異的に認識するキメラ抗原受容体 (chimeric antigen receptor : CAR)を介しDCを活性化させるCAR発現DC (CAR-DC)療法を開発(特許申請中:2021-005337)し、腫瘍内T細胞の増加と抗原特異的な抗腫瘍効果を確認した。本研究は、新規細胞療法CAR-DCの抗原特異的な抗腫瘍効果の機序解析、またCAR-DCと免疫チェックポイント阻害剤の併用効果の検証を目的とする。

  3. 強力な免疫チェックポイント分子阻害能を有する新たな腫瘍溶解性ウイルスの開発

    研究課題/研究課題番号:20K16438  2020年4月 - 2022年3月

    科学研究費助成事業  若手研究

    向山 宣昭

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    本研究は、T細胞の機能を抑制する免疫チェックポイント分子を阻害する新たな腫瘍溶解性ウイルスの開発を目的とする。具体的には、腫瘍溶解性単純ヘルペスウイルスであるC-REVに、PD-L1に対する抗PD-L1抗体の一本鎖抗体(single chain Fv;scFv)ならびにPD-1細胞外領域(PD-1(1-239))を産生させることにより、ウイルスが腫瘍に感染、破壊するだけでなく、PD-1/PD-L1結合を阻害する新規ウイルスを作製する。
    腫瘍溶解性ウイルスは腫瘍特異的に感染し、腫瘍を崩壊する。さらに、破壊された腫瘍が癌抗原を放出することにより癌免疫応答を惹起する。本研究は、T細胞の機能を抑制する免疫チェックポイント分子を阻害する新たな腫瘍溶解性ウイルスの開発を目的とした。
    抗マウスPD-L1 scFvならびにPD-1(1-239)を発現する新規腫瘍溶解性ウイルスC-REV-PD-L1-PD-1(1-239)を作成した。また、C-REV投与により腫瘍内に浸潤したT細胞のPD-1発現が減少することを明らかにした。
    PD-1阻害剤の投与の可否を判断するにあたり、腫瘍細胞のPD-L1発現率を調べる診断薬が承認されている。一方、PD-L1低発現の腫瘍に対してPD-1阻害剤が効果を発揮する報告もある。また、動物実験においてPD-L1を発現しない腫瘍に対して免疫チェックポイント阻害剤が効果を発揮することも報告されている。従って、腫瘍内のPD-1/PD-L1結合阻害と抗腫瘍効果の関係は明らかではない。本研究によって、腫瘍局所内におけるPD-1/PD-L1結合を直接阻害することにより、その阻害が抗腫瘍効果にどのように関与するか明らかになることにより、今後の免疫チェックポイント阻害治療に貢献できる。