詳細

若崎　高裕 （ワカサキ　タカヒロ）

  • 医学科　講師
Last Updated :2024/04/28

コミュニケーション情報 byコメンテータガイド

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    患者さんによりそった医療の提供を心がけています

研究者情報

学位

  • 博士（医学）（2011年03月 九州大学大学院　医学系学府）

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ORCID ID

J-Global ID

現在の研究分野（キーワード）

    患者さんによりそった医療の提供を心がけています

経歴

  • 2023年04月 - 現在  近畿大学医学部 医学科

学歴

  • 2006年04月 - 2011年03月   九州大学   大学院医学研究院
  • 1994年04月 - 2000年03月   九州大学   医学部

研究活動情報

論文

  • Rina Jiromaru; Mioko Matsuo; Hidetaka Yamamoto; Ryosuke Kuga; Takahiro Hongo; Tomomi Manako; Kazuki Hashimoto; Takahiro Wakasaki; Ryuji Yasumatsu; Takashi Nakagawa
    JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY 33 1 59 - 65 2023年
  • Takahiro Wakasaki; Ryuji Yasumatsu; Mika Tanabe; Hiroshi Yoshikawa; Rina Jiromaru; Kazuki Hashimoto; Mioko Matsuo; Akiko Fujimura; Takashi Nakagawa
    In vivo (Athens, Greece) 37 3 1219 - 1225 2023年 
    BACKGROUND/AIM: Lacrimal sac tumors are rare tumor types, with a long time interval from disease onset to diagnosis. We aimed to investigate the characteristics and outcomes of patients with lacrimal sac tumors. PATIENTS AND METHODS: The medical records of 25 patients with lacrimal sac tumors initially treated at the Kyushu university hospital from January 1996 to July 2020 were reviewed. RESULTS: Our analysis included 3 epithelial benign tumors (12.0%) and 22 malignant (88.0%) tumors (squamous cell carcinoma, n=6; adenoid cystic carcinoma, n=2; sebaceous adenocarcinoma, n=2; mucoepidermoid carcinoma, n=1; malignant lymphoma, n=10). The average time from symptom onset to diagnosis was 14.7 months (median=8 months; range=1-96 months). The analysis of patients revealed that lacrimal sac mass (22/25, 88.0%) was the most frequent symptom and a possible tumor marker. Most epithelial benign (n=3) and malignant epithelial (n=12) tumors were treated surgically (14/15, 93.3%). One malignant case was treated with heavy ion beam therapy. Eight patients were treated with postoperative (chemo)radiation therapy because of positive surgical margins (including one unanalyzed case). Local control was ultimately achieved in all but one case. The patient survived for 24 months with immune checkpoint inhibitors and subsequent chemotherapy for local and metastatic recurrence. CONCLUSION: We report our experience in the diagnosis and treatment of lacrimal sac tumors and analyze the clinical trends in cases involving these tumors. Postoperative radiotherapy and pharmacotherapy, including immune checkpoint inhibitors, may be useful for recurrent cases.
  • 副咽頭間隙を貫いた歯ブラシ杙傷の1例
    宮崎 孝; 松尾 美央子; 次郎丸 梨那; 橋本 和樹; 若崎 高裕; 安松 隆治; 中川 尚志
    耳鼻と臨床 68 5 346 - 351 耳鼻と臨床会 2022年09月 
    杙創は,先端の鈍な棒状の物体が身体に突き刺さる外傷形態の一つである。口腔・咽頭外傷は、器具を口腔内に挿入したまま,転倒した際に発症することが多く、原因器具は、歯ブラシが最多とされる。今回、われわれは、副咽頭間隙を貫通した歯ブラシ杙傷の1例を経験した。症例は67歳の女性で、歯ブラシをくわえたまま転倒した。歯ブラシは中咽頭左側壁から副咽頭間隙を貫通し、左後頸部の筋間に刺入していた。また異物によって内頸動脈は著しく狭窄していた。頸部外切開によって歯ブラシのヘッド側から異物を摘出したが、抜去による出血はなく、その後の感染症の併発もなく治癒した。咽頭杙創の場合、不用意な抜去は血管損傷による大出血や神経障害の可能性があるため、造影CTや血管造影等で正常構造物との関係を把握した上で、適切な抜去法を選択する必要がある。また杙創は受傷後数日経過してから、膿瘍等の感染症や外傷性内頸動脈閉塞症などの重篤な合併症を来すこともあり、適切な抗菌薬治療や神経学的所見の経過観察などを怠らないことが重要であると考えられた。(著者抄録)
  • Rina Jiromaru; Ryuji Yasumatsu; Hidetaka Yamamoto; Ryosuke Kuga; Takahiro Hongo; Takafumi Nakano; Tomomi Manako; Kazuki Hashimoto; Takahiro Wakasaki; Mioko Matsuo; Takashi Nakagawa
    European Archives of Oto-Rhino-Laryngology 279 7 3717 - 3725 2022年07月 
    Purpose: We herein report the treatment outcome of oropharyngeal squamous cell carcinoma (OPSCC) at Kyushu University Hospital, the total number of OPSCC cases, and changes in the proportion of human papilloma virus (HPV)-related carcinomas over time. Method: We performed a retrospective analysis of 237 cases treated for OPSCC at Kyushu University Hospital between 2013 and 2019. We performed HPV-mRNA in situ hybridization and p16 immunohistochemistry. Result: This study included 197 males (82.1%) and 40 females (17.9%). The disease-specific, progression-free and overall survival (OS) were 69%, 62% and 61%, respectively, over the decade-long study period. p16-Immunohistochemistory and highrisk HPV mRNA in situ hybridization were positive in 114 (48.1%) and 105 (44.3%) cases, respectively. The number of HPV-related OPSCC cases increased according to an annual analysis. HPV+ cases had a significantly better prognosis than HPV− cases. In addition, p16+/HPV− cases had a significantly worse prognosis than p16+/HPV+ cases (OS: p = 0.0484). HPV+ OPSCC cases were associated with a younger age (< 60 years old) (p = 0.0429), non-smoker (p = 0.0001), lateral tumor site (< 0.00001), lymphoid metastasis (< 0.0001) and low clinical stage (< 0.0001). Conclusion: The frequency of HPV-related OPSCC cases is increasing in Japan as well as worldwide, and such cases are characterized by no smoking habit, a young age, and a good prognosis. Even in p16+ OPSCC, HPV− cases had a poor prognosis, suggesting the importance of accurate HPV determination. To determine the intensity of treatment for HPV-related and non-related OPSCC, it is necessary to accumulate cases for the accurate HPV determination and comparison of treatment effects.
  • Mioko Matsuo; Ryuji Yasumatsu; Muneyuki Masuda; Moriyasu Yamauchi; Takahiro Wakasaki; Kazuki Hashimoto; Rina Jiromaru; Tomomi Manako; Takashi Nakagawa
    In Vivo 36 4 1881 - 1886 2022年07月 
    Background/Aim: A long-term effect has been confirmed in clinical practice since the introduction of nivolumab for treating various malignant tumors. A similar phenomenon is speculated to occur in head and neck cancer; however, details remain unclear due to the lack of long-term reports. We aimed to investigate the five-year outcomes in long-term responders for over two years, and evaluate the optimal duration of therapy with nivolumab. Patients and Methods: In this retrospective observational study, we analyzed 203 cases of recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC), including 33 long-term responders. Results: The median overall survival (OS), 5-year OS, median progression-free survival (PFS), and 5-year PFS values in the 203 cases were 13.1 months, 19.2%, 3.1 months, and 13.2%, respectively. Of the 33 long-term responders, 14 (42.4%) continued using nivolumab for more than 2 years. The remaining 19 patients (57.6%) discontinued nivolumab. The most common reason for discontinuation was severe immune-related adverse events (irAEs) (9 cases; 27.3%); in these 9 cases, the median disease-free survival was 33.2 (range=10.7-44.3) months. Nine patients (21.2%) were considered to have progressive disease (PD) after at least 2 years of administration, and 3 patients (9.1%) requested to discontinue treatment because a complete response (CR) was achieved. Conclusion: This study demonstrated the durable and long-term benefit of nivolumab in R/MHNSCC. In the future, we aim to accumulate real-world data for the establishment of criteria for completion of nivolumab treatment in long-term responders.
  • Takafumi Nakano; Ryuji Yasumatsu; Kazuki Hashimoto; Ryosuke Kuga; Takahiro Hongo; Hidetaka Yamamoto; Mioko Matsuo; Takahiro Wakasaki; Rina Jiromaru; Tomomi Manako; Satoshi Toh; Muneyuki Masuda; Moriyasu Yamauchi; Yuichiro Kuratomi; Masahiko Taura; Toranoshin Takeuchi; Takashi Nakagawa
    Anticancer Research 42 7 3653 - 3664 2022年07月 
    Background/Aim: This study investigated the effectiveness of pembrolizumab with or without chemotherapy on advanced-stage head and neck cancer (HNC), including nasopharyngeal, sinonasal cavity and external auditory canal cancer, in a real-world setting. Patients and Methods: We retrospectively collected data from 97 HNC patients who were treated with pembrolizumab alone (n=60) or with chemotherapy (n=37), and we investigated the association between clinicopathological findings and treatment response or prognosis. Results: Patients treated with pembrolizumab and chemotherapy had a 1-year overall survival (OS) of 72.8%, objective response rate (ORR) of 48.6%, and serious (≥G3) adverse events (AEs) of 29.7%. Patients treated with pembrolizumab alone had a 1-year OS of 51.9%, ORR of 21.7%, and ≥G3 AEs of 6.7%. Both the ORR and disease control rate (DCR) in the pembrolizumab with chemotherapy group were significantly better than those in the pembrolizumab group (p=0.074 and p=0.00101, respectively). Among patients with distant metastasis, patients on pembrolizumab with chemotherapy achieved significantly better OS than pembrolizumab alone (p=0.0039). Among patients in the pembrolizumab group, both AE-positive and better performance status were associated with longer OS (p=0.011 and p=0.0037, respectively). Conclusion: Our real-world experience reinforces the durability and effectiveness of pembrolizumab for HNC patients. Additionally, our results suggest that pembrolizumab with chemotherapy might be recommended for patients with distant metastasis and no prior treatment. Further studies are needed to determine the optimal treatment strategy for HNC.
  • Takahiro Wakasaki; Tomomi Manako; Ryuji Yasumatsu; Hirotaka Hara; Satoshi Toh; Muneyuki Masuda; Moriyasu Yamauchi; Yuichiro Kuratomi; Emi Nishimura; Toranoshin Takeuchi; Mioko Matsuo; Rina Jiromaru; Kazuki Hashimoto; Noritaka Komune; Takashi Nakagawa
    PLoS ONE 17 7 July 2022年07月 
    Objectives The benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration. Materials and methods We retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45). Results The objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B. Conclusion Although PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DIIP, is recommended.
  • Teppei Noda; Noritaka Komune; Ryuji Yasumatsu; Nana Akagi Tsuchihashi; Akihiro Tamae; Nozomu Matsumoto; Kuniaki Sato; Ryutaro Uchi; Kensuke Koike; Takahiro Wakasaki; Risa Tanaka; Takashi Nakagawa
    Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho(Tokyo) 125 5 916 - 917 2022年05月
  • 野田 哲平; 小宗 徳孝; 安松 隆治; 土橋 奈々; 玉江 昭裕; 松本 希; 佐藤 晋彰; 内 龍太郎; 小池 健輔; 若崎 高裕; 田中 吏佐; 中川 尚志
    日本耳鼻咽喉科頭頸部外科学会会報 125 5 916 - 917 (一社)日本耳鼻咽喉科頭頸部外科学会 2022年05月
  • Takafumi Nakano; Ryuji Yasumatsu; Kazuki Hashimoto; Ryosuke Kuga; Takahiro Hongo; Hidetaka Yamamoto; Mioko Matsuo; Takahiro Wakasaki; Rina Jiromaru; Tomomi Manako; Satoshi Toh; Muneyuki Masuda; Moriyasu Yamauchi; Yuichiro Kuratomi; Hideoki Uryu; Torahiko Nakashima; Akihiro Tamae; Risa Tanaka; Masahiko Taura; Toranoshin Takeuchi; Takamasa Yoshida; Takashi Nakagawa
    In Vivo 36 2 979 - 984 2022年03月 
    Background/Aim: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). Patients and Methods: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. Results: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. Conclusion: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.
  • Mioko Matsuo; Ryuji Yasumatsu; Muneyuki Masuda; Satoshi Toh; Takahiro Wakasaki; Kazuki Hashimoto; Rina Jiromaru; Tomomi Manako; Takashi Nakagawa
    In Vivo 36 2 907 - 917 2022年03月 
    Background/Aim: The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. Patients and Methods: Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. Results: Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. Conclusion: Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.
  • Kazuki Hashimoto; Ryuji Yasumatsu; Ryosuke Kuga; Takahiro Hongo; Hidetaka Yamamoto; Mioko Matsuo; Takahiro Wakasaki; Rina Jiromaru; Tomomi Manako; Satoshi Toh; Muneyuki Masuda; Moriyasu Yamauchi; Yuichiro Kuratomi; Hideoki Uryu; Torahiko Nakashima; Akihiro Tamae; Risa Tanaka; Masahiko Taura; Toranoshin Takeuchi; Takamasa Yoshida; Takashi Nakagawa
    Anticancer Research 42 2 981 - 989 2022年02月 
    Background/Aim: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. Patients and Methods: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. Results: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. Conclusion: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.
  • Takahiro Hongo; Hidetaka Yamamoto; Rina Jiromaru; Ryuji Yasumatsu; Ryosuke Kuga; Yui Nozaki; Kazuki Hashimoto; Mioko Matsuo; Takahiro Wakasaki; Akihiro Tamae; Kenichi Taguchi; Satoshi Toh; Muneyuki Masuda; Takashi Nakagawa; Yoshinao Oda
    Modern Pathology 34 11 1966 - 1978 2021年11月 
    The antitumor efficacies of immune checkpoint inhibitors (ICIs) and the usefulness of potential predictive markers such as programmed death-ligand 1 (PD-L1) expression, density of tumor-infiltrating lymphocytes (TILs) and microsatellite instability (MSI) in sinonasal squamous cell carcinoma (SNSCC) have not been fully elucidated. We retrospectively analyzed 131 SNSCCs with immunohistochemistry for PD-L1 expression, TIL subpopulations and loss of mismatch repair (MMR) proteins as a surrogate for MSI-high. We also comprehensively evaluated the mutual relationships among these immuno-markers, high-risk human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) gene status, and KRAS mutation. PD-L1 expression (tumor proportion score ≥ 1%) was detected in 60 (45.8%) SNSCC cases and was significantly associated with worse overall survival (OS) (p = 0.0240). High density of cluster of differentiation 8 (CD8)-positive TILs was significantly associated with better progression-free survival (PFS) (p = 0.0368), and high density of forkhead box protein P3-positive TILs was significantly associated with better PFS and OS (p = 0.0007 and 0.0143, respectively). With respect to the combination of CD8 + TIL and PD-L1 expression, the high-CD8/PD-L1-negative group showed the most favorable prognosis, whereas the low-CD8/PD-L1-positive group showed the worst prognosis. MMR loss was detected in 3 (2.3%) of the 131 cases. HPV infection (6.1%), EGFR mutation (14.5%), EGFR copy number gain (26%), and MMR loss were essentially mutually exclusive; patients in these molecular groups showed significant differences in prognosis but not in the degree of PD-L1 expression or TILs. Among the nine ICI-treated patients, three (33.3%) were responders, and the EGFR-wild type cases (n = 7) showed better clinical responses to an ICI compared to the EGFR-mutant cases (n = 2). Among the patients with residual/recurrent EGFR-wild type tumors (n = 43), ICI treatment significantly improved OS (p = 0.0281). The results suggest that the evaluation of immuno-markers and molecular subclassification may be helpful for prognostic prediction and selecting an individualized therapeutic strategy for patients with SNSCC.
  • 口蓋腫瘍切除後の口蓋全層欠損に対し硬口蓋粘骨膜弁および鼻中隔粘膜弁で再建を行った1例
    押領司 親史; 門田 英輝; 嶋本 涼; 吉田 聖; 小宗 徳孝; 若崎 高裕; 安松 隆治; 中川 尚志
    日本形成外科学会会誌 41 10 576 - 581 (一社)日本形成外科学会 2021年10月 
    症例は72歳男性で、左側口蓋部の腺様嚢胞癌と診断され、全身麻酔下に口腔内アプローチ・鼻腔内視鏡アプローチを併用して腫瘍切除術を施行した。腫瘍摘出術後、硬口蓋・軟口蓋移行部の口腔側左寄りに40×40mm程度、軟口蓋鼻腔側に20×20mmほどの粘膜欠損が生じ、口腔内と鼻腔内との交通が生じたため、口腔側は右側茎の硬口蓋粘膜骨膜弁、鼻腔側左鼻中隔粘膜弁で再建した。術後9日目に硬口蓋粘膜弁に小範囲の表層壊死および小瘻孔を認めデブリードマンおよび再縫合を施行したが、その後経過は良好で、術後20日目に経管栄養併用で経口摂取を再開し、術後27日目には食事全量摂取が可能となった。術後8ヵ月経過現在、鼻咽腔逆流はなく経口摂取も可能であり、開鼻声などの機能障害も認めていない。
  • 木田 裕太郎; 松尾 美央子; 次郎丸 梨那; 橋本 和樹; 若崎 高裕; 安松 隆治; 中川 尚志
    耳鼻と臨床 67 5 318 - 324 耳鼻と臨床会 2021年09月 
    BCGは、抗酸菌の結核菌群の一つであるBacillus Calmette-Guerin菌を弱毒化したワクチンである。結核発病予防や膀胱癌治療に広く使用され、有効性は高く有害事象は少ない薬剤であるが、まれに重篤な感染症を引き起こし、診断や治療に難渋することがある。本症例は84歳の男性で、BCG膀胱内注入治療から約1年後に左頸部にBCGリンパ節炎を発症した。2ヵ月間の抗結核剤投与を行ったが、徐々に皮膚が自壊し深頸部膿瘍となったため、デブリードメントを行った。その後も抗結核剤の投与を持続していたが、デブリードメントから約2ヵ月後に感染性頸動脈瘤にまで発展した。BCG感染症は、そのまれさ故、確定診断がつけにくく、その上治療法も確立していないため、治療にも難渋することがある。今回われわれは、BCG感染症を経験し、その診断方法と治療方法について若干の文献とともに報告する。(著者抄録)
  • Noritaka Komune; Kuniaki Sato; Takahiro Hongo; Masaru Miyazaki; Shogo Masuda; Kensuke Koike; Ryutaro Uchi; Nana Akagi Tsuchihashi; Teppei Noda; Ryunosuke Kogo; Takahiro Wakasaki; Ryuji Yasumatsu; Takashi Nakagawa
    Laryngoscope 131 8 1782 - 1789 2021年08月 
    Objective/Hypothesis: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC. Study Design: Case reries with chart review. Methods: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival. Results: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers. Conclusions: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs. Level of Evidence: 4 Laryngoscope, 131:1782–1789, 2021.
  • Mioko Matsuo; Ryuji Yasumatsu; Sei Yoshida; Rina Jiroumaru; Kazuki Hashimoto; Takahiro Wakasaki; Takashi Nakagawa
    Case Reports in Oncology 14 2 1097 - 1102 2021年07月 
    Re-irradiation with X-rays and particle beams can be used to treat localized recurrence of unresectable head and neck cancer after initial irradiation therapy. However, re-irradiation therapy increases the risk of severe and late sequelae by 4-to 8-fold. It can also result in fatal outcomes, such as rupture of the carotid artery and cerebral necrosis or abscess. A 41-year-old woman was diagnosed with squamous cell carcinoma of the external auditory canal. The patient was initially treated with X-ray irradiation. However, the patient underwent re-irradiation with heavy particle beams and neutron rays for a recurrent tumor. The patient developed necrosis of the skull base involving the facial skin and temporal bone 2 months after the last session of re-irradiation therapy. The tissue in the parapharyngeal and masticatory regions also became completely necrotic, resulting in extensive exposure of the brain parenchyma. Although the patient underwent conservative and surgical treatment, necrosis of the tissue progressed, and a large part of the brain was exposed. Approximately 2.5 years later, although the brain is still exposed, the patient is alive without disease. Although the tumor had subsided and long-term survival was achieved, our patient developed serious osteoradionecrosis of the skull base with extensive brain exposure. For patients who are not candidates for surgery, re-irradiation alone is an option, albeit with poor prospects. This approach should be discussed with the patient while balancing the potential survival gain against the burden of treatment and the risk of complications.
  • Yojiro Kotake; Natsumi Matsunaga; Takahiro Wakasaki; Ryotaro Okada
    Cancer Genomics and Proteomics 18 4 543 - 548 2021年07月 
    Background/Aim: The long noncoding RNA OIP5 antisense RNA 1 (OIP5-AS1) is overexpressed in various cancer types, such as lung cancer, hepatoblastoma and cervical cancer, and functions to accelerate cell proliferation, invasion and migration. Here, we investigated the roIe of OIP5-AS1 in cell-cycle progression of H1299 and A549 non-small cell lung cancer cells, and FaDu and CAL27 head and neck squamous cell carcinoma cells. Materials and Methods: The cells were transfected with small interfering RNA and subjected to cell-cycle analysis and reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Results: Silencing of OIP5-AS1 suppressed the proliferation of H1299, A549, FaDu and CAL27 cells. RT-qPCR and cell-cycle analysis revealed that silencing OIP5-AS1 increased the expression of CDK inhibitors, such as p15, p16, p18 and p19, resulting in G1-phase arrest. Conclusion: OIP5-AS1 regulates G1-phase progression by repressing CDK inhibitors and, thus, promotes the proliferation of H1299, A549, FaDu and CAL27 cells.
  • 白根 茉利子; 田邉 美香; 吉川 洋; 高木 健一; 長谷川 英一; 若崎 高裕; 末藤 大明; 園田 康平
    日本眼科学会雑誌 125 2 117 - 121 (公財)日本眼科学会 2021年02月 
    背景:脂腺癌の好発部位は眼瞼であり,涙嚢部に発生した症例の報告はまれである.今回,急速増大を来した涙嚢部原発脂腺癌の症例を経験したので報告する.症例:76歳女性.半年前から左涙嚢部の腫瘤を自覚し,九州大学病院眼科を受診した.左涙嚢部皮下に腫瘤を触知し,磁気共鳴画像法(MRI)で長径14mmの境界不明瞭な腫瘤を認めた.3ヵ月後に腫瘤は26×21×33mmに増大し,左眼窩内側,鼻涙管,篩骨洞,前頭洞に進展しており,生検で脂腺癌と診断した.眼瞼や涙丘に病変は認めず,全身ポジトロン断層法(PET)でも他の病巣を認めなかった.総線量64Gyの重粒子線治療を施行し腫瘍は縮小したが,左顎下部にリンパ節転移を来し,頸部郭清術と化学放射線療法を施行した.結論:涙嚢に脂腺癌が発生することがある.急速な経過をたどることがあり,注意が必要である.(著者抄録)
  • Noritaka Komune; Teppei Noda; Ryunosuke Kogo; Masaru Miyazaki; Nana A. Tsuchihashi; Takahiro Hongo; Kensuke Koike; Kuniaki Sato; Rhutaro Uchi; Takahiro Wakasaki; Nozomu Matsumoto; Ryuji Yasumatsu; Takashi Nakagawa
    Laryngoscope 131 2 E583 - E589 2021年02月 
    Objectives/Hypothesis: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors. Study Design: Retrospective chart review. Methods: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment. Results: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins. Conclusions: Definitive treatments can offer disease-specific 5-year survival of over 85% in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC. Level of Evidence: 4 Laryngoscope, 131:E583–E589, 2021.
  • Mioko Matsuo; Ryuji Yasumatsu; Muneyuki Masuda; Satoshi Toh; Takahiro Wakasaki; Kazuki Hashimoto; Ryutaro Uchi; Rina Jiromaru; Kuniaki Sato; Tomomi Manako; Takashi Nakagawa
    Oral Oncology 113 2021年02月 
    Background: Drug-induced interstitial lung disease (DI-IP) is one of the most serious adverse reactions associated with the use of anticancer drugs. DI-IP prevalence among molecular-targeting drugs and immune checkpoint inhibitors (ICIs) is relatively high in Japanese patients. To assess the risk of cetuximab and/or nivolumab-related IP is important. Patients and Methods: The medical records of 138 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with cetuximab-containing chemotherapy and/or nivolumab monotherapy were retrospectively reviewed. Results: The incidence of DI-IP with R/M HNSCC was 7.2%. DI-IP occurred more frequently in patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy than in patients with other regimens. However, tumor suppression was detected in all patients treated with cetuximab-containing chemotherapy following nivolumab monotherapy, and two achieved a complete response. Conclusions: Although patients treated with cetuximab-containing chemotherapy following nivolumab showed dramatic efficacy, careful monitoring should be recommended.
  • 若崎 高裕
    耳鼻と臨床 67 1 44 - 47 耳鼻と臨床会 2021年01月
  • 犬塚 杏子; 池村 巧; 門田 英輝; 内 龍太郎; 田浦 政彦; 若崎 高裕; 松尾 美央子; 安松 隆治; 中川 尚志
    耳鼻と臨床 67 1 31 - 36 耳鼻と臨床会 2021年01月 
    プロヴォックスは喉頭摘出後の代用音声として用いられるが、抜去が必要となる場合がある。今回われわれはプロヴォックス抜去後の気管食道瘻孔の閉鎖に難渋したので報告する。症例は78歳、男性で、プロヴォックスを抜去した後、単純縫縮で閉鎖に至らず、大胸筋皮弁の筋体を食道と気管の間に充填することで瘻孔を閉鎖した。抜去後の瘻孔閉鎖には、気管食道間を分離する手技や皮弁を用いた手術が必要となる可能性があり、安易な抜去は避けるべきと考えられた。(著者抄録)
  • RYUTARO UCHI; RINA JIROMARU; RYUJI YASUMATSU; HIDETAKA YAMAMOTO; TAKAHIRO HONGO; TOMOMI MANAKO; KUNIAKI SATO; KAZUKI HASHIMOTO; TAKAHIRO WAKASAKI; MIOKO MATSUO; TAKASHI NAKAGAWA
    Anticancer Research 41 1 71 - 79 2021年01月 
    Background: The genetic basis of sinonasal inverted papilloma (SNIP)-derived squamous cell carcinoma (SCC) has not yet been well characterized. Aim: To characterize the genetic abnormalities of SNIP and SNIP-derived SCC and to uncover their differences. Materials and Methods: Mutations of 409 genes were analyzed using amplicon targeted sequencing in a total of six papilloma/carcinoma samples from four patients with SNIP-derived SCC. Results: The genes that were mutated in multiple cases were epidermal growth factor receptor (EGFR) (3/6), cyclin-dependent kinase inhibitor 2A (CDKN2A) (3/6), lysine methyltransferase 2D (KMT2D) (3/6), tumor protein p53 (TP53) (3/6), neurofibromin 1 (NF1) (3/6), phosphodiesterase 4D interacting protein (PDE4DIP) (3/6), cytochrome P450 family 2 subfamily D member 6 (CYP2D6) (2/6), fms-related receptor tyrosine kinase 4 (FLT4) (2/6) and myosin heavy chain 9 (MYH9) (2/6). Of the two cases analyzed in the papilloma-oncology carcinoma pair, one did not have any common mutations; the other showed a staged functional deletion of TP53 during the process of malignant transformation from SNIP to SCC. Conclusion: CDKN2A, KMT2D, NF1, PDE4DIP, CYP2D6, FLT4, and MYH9 were identified as candidate novel SNIP-derived SCC-related genes.
  • Ryuji Yasumatsu; Tomomi Manako; Rina Jiromaru; Kazuki Hashimoto; Takahiro Wakasaki; Mioko Matsuo; Takashi Nakagawa
    Ear, Nose and Throat Journal 102 7 NP313 - NP318 2021年 
    Objective: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs. Methods: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed. Results: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively. Conclusions: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended.
  • Teppei Noda; Noritaka Komune; Ryuji Yasumatsu; Nana Akagi Tsuchihashi; Akihiro Tamae; Nozomu Matsumoto; Kuniaki Sato; Ryutaro Uchi; Kensuke Koike; Takahiro Wakasaki; Risa Tanaka; Takashi Nakagawa
    Auris Nasus Larynx 47 5 864 - 869 2020年10月 
    Objective: The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC. Method: Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined. Results: We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2–54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%). Conclusion: We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC.
  • Kenta Nio; Kenji Tsuchihashi; Keisuke Taguchi; Tomoyasu Yoshihiro; Kyoko Yamaguchi; Mamoru Ito; Shohei Moriyama; Mitsuhiro Fukata; Toshifumi Fujiwara; Nokitaka Setsu; Makoto Endo; Yoshihiro Matsumoto; Yasuharu Nakashima; Takahiro Wakasaki; Ryuji Yasumatsu; Hiroshi Ariyama; Hitoshi Kusaba; Junji Kishimoto; Koichi Akashi; Eishi Baba
    INTERNATIONAL JOURNAL OF SURGERY-ONCOLOGY 5 4 2020年08月 
    Tyrosine kinase inhibitors (TKI) work against various types of cancer by inhibiting angiogenic signaling. Little is understood about the incidence, characteristics, and risk factors associated with thromboembolism induced by TKI in routine clinical practice. We retrospectively analyzed data derived from 29 patients with thyroid cancer or soft tissue sarcoma (STS) treated with lenvatinib (n=10) and pazopanib (n=19). Eight (arterial n=4; venous n=4) thromboembolic events developed in 6 (20%) patients. Thromboembolisms occurred during a mean of 149 (range, 42-847) days from starting TKI. The primary disease progressed in all patients with thromboembolism. The overall survival durations of patients with and without improved thromboembolism were 572 [95% confidence interval (CI), 225- 918] and 176 (95% CI, 84-394) days, respectively, which did not significantly differ (P=0.33). Patients with and without improved thromboembolism survived after onset for 122 (95% CI, 71-173) versus 27 (95% CI, 21-42) days (P=0.049), which significantly differed. Univariate analysis and variate selection for multivariate analysis selected a history of thromboembolism as the most powerful risk factor for new thromboembolism. In summary, the frequency of thromboembolism in clinical practice was higher than that in previous clinical trials. Furthermore, a history of thromboembolism was a risk factor for the development of new thromboembolism in patients treated with TKI. Thromboembolism developed particularly as the primary disease progressed. Our findings require validation in a large-scale study.
  • Takahiro Wakasaki; Ryuji Yasumatsu; Muneyuki Masuda; Toranoshin Takeuchi; Tomomi Manako; Mioko Matsuo; Rina Jiromaru; Ryutaro Uchi; Noritaka Komune; Teppei Noda; Takashi Nakagawa
    Cancers 12 8 1 - 11 2020年08月 
    Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received S1, an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR This is the first report on biomarkers of SCT in R/M HNSCC.
  • Ryuji Yasumatsu; Rina Jiromaru; Takahiro Hongo; Ryutaro Uchi; Takahiro Wakasaki; Mioko Matsuo; Masahiko Taura; Takashi Nakagawa
    Acta Oto-Laryngologica 140 8 706 - 711 2020年07月 
    Background: Sinonasal squamous cell carcinoma (SCC) is a rare tumor arising either de novo or in association with inverted papillomas (IPs). Objectives: The aim of this study was to investigate and compare the oncological features and prognosis of patients with sinonasal SCCs based on their etiology. Material and methods: The medical records of 117 patients who had been diagnosed with de novo SCC or those arising from IP (IP-SCC) were retrospectively reviewed. In situ hybridization analyses to detect HPV 16/18DNA and p16 immunohistochemistry were also performed in 10 cases with IP-SCC. Results: The three-year disease-specific survival (DSS) rate was higher in cases with T1, 2 and 3 than in cases with T4 in both tumor groups. T4 cases with de novo SCC had a better DSS than those with IP-SCCs. HPV16/18 was not detected in any of the 10 IP-SCCs. Conclusions and significance: T4 cases with de novo SCC tended to have a better DSS than those with IP-SCC. Since some T4 patients with IP-SCC were found to have a highly aggressive disease, careful treatment planning should be performed. High-risk HPV may not play a vital role in the carcinomatous transformation of most IP-SCC cases.
  • 真子 知美; 安松 隆治; 古後 龍之介; 若崎 高裕; 中川 尚志
    耳鼻と臨床 66 4 121 - 126 耳鼻と臨床会 2020年07月 
    滑膜肉腫は悪性軟部肉腫の一つであり、多能性間葉系細胞が発生母地と考えられている四肢に好発するが、滑膜組織を認めない部位にも発生することがあり、10％以下が頭頸部領域に発生するとされている。今回われわれは、頸部に発生した滑膜肉腫の 2 例を経験した。症例 1 は 20 歳女性で、頸部神経鞘腫が疑われ腫瘍摘出術を施行したところ、術後病理組織検査で滑膜肉腫と診断された。後治療として術後照射を施行した。症例 2 は 26 歳男性で、23 歳時に前医にて顎下腺腫瘍に対して顎下腺全摘術を施行された。術後病理組織検査で滑膜肉腫の診断であったため、追加で頸部郭清術を施行された。その後、当科で経過観察中、頸部再発を認めたため、腫瘍摘出術を施行した。両症例とも 2 年以上再発を認めず経過している。滑膜肉腫の診断には SS18-SSX 融合遺伝子の検出が有用である。 治療は外科的切除が第一選択であるが、頭頸部領域では十分に切除マージンを確保した根治的切除が困難な場合があり、放射線治療や化学療法を施行することがあるが、その有効性は示されていない。局所再発や肺転移を生じやすく、厳重な経過観察が必要である。
  • Mioko Matsuo; Masahiko Taura; Takahiro Wakasaki; Ryuji Yasumatsu; Takashi Nakagawa
    Otolaryngology Case Reports 14 2020年03月 
    Immune-related adverse events due to immune checkpoint inhibitors (ICIs) are seen in systemic organs; the incidence of endocrine disorders is reported to be 3.8–29%. However, thyroid disorders are the most common, while the incidence of pituitary disorders is not as high. Nivolumab treatment was initiated in a 42-year-old male patient due to recurrent oropharyngeal squamous cell carcinoma. After four months, he experienced marked malaise, and blood tests revealed decreased levels of both adrenocorticotropic hormone and cortisol. From the above findings, pituitary-adrenal insufficiency was diagnosed, and glucocorticoid replacement therapy was initiated. This resulted in a rapid improvement in the symptoms. The patient is currently undergoing nivolumab treatment while still on continued glucocorticoid replacement therapy. Malaise is a symptom that is experienced by all cancer patients; as it is not a characteristic symptom of endocrine disorders, we tend to consider it as insignificant. However, when an ICI is used, the onset of endocrine disorders is always suspected, and it is important not to neglect the rapid addition of hormone tests. Proper diagnosis of immune-related adverse events and rapid initiation of treatment are beneficial to the patient even with respect to anti-tumor efficacy with continued ICI treatment.
  • Takahiro Wakasaki; Ryuji Yasumatsu; Ryutaro Uchi; Masahiko Taura; Mioko Matsuo; Noritaka Komune; Takashi Nakagawa
    Auris Nasus Larynx 47 1 116 - 122 2020年02月 
    Objective: Although nivolumab treatment is effective in extending the overall survival (OS) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), only a few patients benefit from this treatment. Recent studies have reported that chemotherapy and cetuximab might be effective for R/M HNSCC after nivolumab treatment. In the present study, we aimed to elucidate the effectiveness of chemotherapy after nivolumab treatment in patients with R/M HNSCC. Methods: This retrospective study included 10 patients with R/M HNSCC who were mainly treated with paclitaxel plus cetuximab (7/10, 70%) or S-1 (3/10, 30%) following nivolumab treatment. Chemotherapy was administered as a second-line or higher palliative treatment. The performance status of all patients ranged from 0 to 2. The progression-free survival (PFS) was analyzed using the Kaplan–Meier method. Results: The response rate (RR), clinical benefit rate, and median PFS were 60%, 90%, and 5.4 months, respectively. Regarding adverse effects, Grade 3 neutropenia and hypomagnesemia due to salvage chemotherapy administered after immunotherapy were observed in one patient. The treatment significantly increased the RR compared to that achieved with other palliative chemotherapies reported so far. Conclusion: A higher RR and clinical benefit rate were observed for our strategy than for any first-line regimen, suggesting that our strategy might improve the PFS. Palliative chemotherapy with/without cetuximab after nivolumab treatment might be useful in patients with R/M HNSCC. Although the results of this retrospective study are limited, this strategy can be a good treatment option for patients with R/M HNSCC because of its strong clinical benefits and acceptable toxicity.
  • Mioko Matsuo; Ryuji Yasumatsu; Muneyuki Masuda; Satoshi Toh; Takahiro Wakasaki; Kazuki Hashimoto; Masahiko Taura; Ryutaro Uchi; Takashi Nakagawa
    Oral Oncology 101 2020年02月 
    Objectives: Immune-related adverse events (irAEs) have been shown to be associated with higher antitumor responses and a clinical benefit in non-small cell lung carcinoma, renal cell carcinoma, and melanoma patients. However, little is known regarding the association between irAEs and the clinical effect of nivolumab for recurrent/metastatic head and neck squamous cell carcinoma (R/MHNSCC). Materials and methods: We evaluated 108 patients treated with nivolumab for R/MHNSCC at 2 participating institutions. IrAEs were identified and profiled. We analyzed the association of each immune-related adverse effect with the clinical outcome of the patients. Results: Among 108 patients, the objective response rate (ORR) was 29.6% (32/108 patients), and the disease control rate (DCR) was 50.0% (54/108 patients). IrAEs were observed in 41 patients (38.0%). Patients with irAEs had a significantly higher ORR and DCR than those without irAEs (46.3% vs. 19.4%, P = 0.004 and 75.6% vs. 34.3%, P < 0.001, respectively). The median progression-free and overall survival rates in patients with irAEs were significantly longer than in those without irAEs. Conclusions: There was a significant relationship between irAEs and efficacy in R/MHNSCC patients treated with nivolumab. Our results indicate that the development of irAEs may aid in the earlier prediction of anticancer effects in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.
  • 安松 隆治; 内 龍太郎; 若崎 高裕; 田浦 政彦; 松尾 美央子; 中川 尚志
    頭頸部外科 29 3 273 - 278 特定非営利活動法人 日本頭頸部外科学会 2020年 
    UICCから新たな悪性腫瘍TNM分類が発表された。口腔癌における改訂のポイントとして，腫瘍深達度と節外浸潤の概念が加えられた。当科で治療を行った舌癌93例について，新分類に基づいた治療成績を解析しその妥当性を検討した。新分類における全体の疾患特異的3年生存率は72.3％であり，stageⅠ：89.9％，stageⅡ：80％，stageⅢ：70％，stageⅣA：64.2％，stageⅣB：20％であった。再発は29例に認められ，10例（36％）で救済可能であった。新TNM分類は旧分類と比較して予後をより明確に反映していた。
  • 安松 隆治; 中野 貴史; 橋本 和樹; 古後 龍之介; 若崎 高裕; 中川 尚志
    日本耳鼻咽喉科学会会報 123 2 135 - 136 一般社団法人 日本耳鼻咽喉科学会 2020年
  • 松尾 美央子; 内 龍太郎; 田浦 政彦; 若崎 高裕; 安松 隆治; 中川 尚志
    頭頸部癌 46 1 41 - 45 日本頭頸部癌学会 2020年 
    悪性腫瘍細胞は，凝固促進物質の産生や血小板凝集能の亢進をひきおこすため，担癌患者は過凝固状態にある。この状態に加え，抗腫瘍薬の投与などの治療行為が血管内皮障害をひきおこすため，担癌患者は血栓症を発症しやすい。
    今回頭頸部癌の治療中に血栓症を発症した4例を報告する。原発部位は口腔癌と咽頭癌が2例づつで，組織型は全例扁平上皮癌であった。3例は抗腫瘍薬による治療中で1例は再発が判明し精査中であった。血栓形成部位は下肢動脈が2例，肺動脈が1例，上腕静脈が1例で，2例は回復し現在も生存中だが，2例は血栓症発症から数日で急死した。
    血栓症は原因や血栓形成部位によって様々な種類があり，治療法や重篤度も異なる。しかしいずれにせよ血栓症の発症は，癌治療中断を余儀なくし患者の急死もあり得る。担癌状態で長期生存する症例が今後も増加していく事が予測される以上，血栓症は担癌患者の無視できない注意を要する病態と考える。
  • 松尾 美央子; 若崎 高裕; 安松 隆治; 中川 尚志
    耳鼻咽喉科臨床 113 5 309 - 314 耳鼻咽喉科臨床学会 2020年 
    Differentiated thyroid cancer can be treated using surgical resection, TSH suppression therapy, and radioactive iodine therapy. For patients who are resistant to these therapies, the molecularly targeted drug lenvatinib is now available as a treatment option. Although lenvatinib is highly effective against these tumors, this treatment results in a high rate of adverse events. Although rare, some adverse events, such as cardiovascular toxicity, can be fatal. A 71-year-old woman had undergone a total thyroidectomy for thyroid cancer with lung metastasis. Afterwards, she developed a pancreatic metastasis. Lenvatinib treatment was initiated, and a good antineoplastic effect was observed. However, she developed heart failure eight months after the start of lenvatinib treatment. Lenvatinib was discontinued, and the patient's heart failure recovered. She was able to restart lenvatinib treatment and has survived for 15 months after the restart of lenvatinib. Therapies targeting vascular endothelial growth factor increase the risk of cardiotoxicity by 2-to 3-fold. However, lenvatinib therapy has a very low frequency of cardiotoxicity, since the present case of drug-induced-cardiotoxicity caused by lenvatinib is, to our knowledge, the first report.
  • Ryuji Yasumatsu; Mioko Matsuo; Takahiro Wakasaki; Muneyuki Masuda; Toranoshin Takeuchi; Tomomi Manako; Rina Jiromaru; Ryutaro Uchi; Kazuki Hashimoto; Takashi Nakagawa
    Acta Oto-Laryngologica 140 12 1043 - 1048 2020年 
    Background: Significant immune-related adverse events (irAEs) requiring therapy discontinuation sometimes occur. The influence of discontinuation on disease control after an irAE is unclear. Objectives: The aim of this study was to investigate whether or not patients continued to show a response or durable disease control even after stopping therapy following an irAE. Material and Methods: The response after nivolumab monotherapy discontinuation was examined for 14 patients in whom therapy was stopped without progression. Results: The best response was CR in 5 (36%) patients, PR in 8 (57%) patients and SD in 1 (7%) patient. The estimated 1-year overall and progression-free survival rates were 92.9% and 78.6%, respectively. The best response during nivolumab therapy in patients who developed PD was CR in 0 of 5 patients (0%), PR in 3 of 8 patients (38%) and SD in 1 patient (100%). Patients obtaining CR tended to have a lower risk of PD than those with PR or SD. Conclusions and Significance: Patients with CR status may continue to show a response or durable disease control even after stopping therapy due to an irAE.
  • 松尾 美央子; 内 龍太郎; 田浦 政彦; 若崎 高裕; 安松 隆治; 中川 尚志
    頭頸部癌 46 4 385 - 389 日本頭頸部癌学会 2020年 
    甲状腺分化癌の遠隔転移は，肺への単独転移が多く，次いで骨転移が多い。甲状腺分化癌がその他の臓器へ転移することはめずらしく，特に膵臓への転移は稀で，今までに報告されているのは16例のみである。
    症例は71歳の女性で，甲状腺乳頭癌肺転移の状態で甲状腺全摘を行った後に，TSH抑制療法のみ行っていたところ，膵臓に転移をきたした。分子標的薬であるレンバチニブの導入にて，肺転移も膵臓転移も縮小し，15ヶ月経過した現在も，効果を認め続けている。
    今回のような内分泌臓器である膵臓に転移をきたした場合，血糖への悪影響が急速に出現する事が懸念される。このため，手術の適応が低いと判断した場合や，RAI治療まで数ヶ月の待機が必要である場合，分子標的薬剤の導入も選択肢の一つとしてよいのではないかと考えられた。
  • 中島 紘一郎; 安松 隆治; 高良 佳江; 古後 龍之介; 若崎 高裕; 中川 尚志
    耳鼻と臨床 65 6 175 - 180 耳鼻と臨床会 2019年11月 
    免疫チェックポイント阻害剤の一つである Nivolumab を投与した再発・転移頭頸部扁平上皮癌症例 38 例について治療効果を解析するとともに、有害事象を来した症例について呈示した。最良治療効果は PR 9例、SD 10 例、PD 12 例であった。奏効率は 27.3％、臨床的有用率は 57.6％であった。1 年粗生存率は 32.3％、1 年無増悪生存率は 18.2％であった。免疫関連有害事象として間質性肺炎 1 例、甲状腺機能亢進 1 例、肝機能障害 2 例、甲状腺機能低下 2 例、関節炎 1 例を認めた。重篤な有害事象として grade 3 の間質性肺炎、grade 4 の肝機能障害を認めた。Nivolumab は優れた治療効果が望める一方、投与に際しては注意深い経過観察も必要である。
  • Takahiro Wakasaki; Ryuji Yasumatsu; Muneyuki Masuda; Mioko Matsuo; Akihiro Tamae; Kazuhiko Kubo; Ryunosuke Kogo; Ryutaro Uchi; Masahiko Taura; Takashi Nakagawa
    Annals of Otology, Rhinology and Laryngology 128 11 1006 - 1012 2019年11月 
    Objectives: Small cell carcinomas in extrapulmonary sites (ESmCCs) are very rare. ESmCCs originating in the head and neck account for approximately 10% of all ESmCCs, and there are few reports about this disease. ESmCCs have an aggressive natural history characterized by widespread metastasis. The aim of this study was to investigate the characteristics and outcomes of patients with ESmCCs of the head and neck. Methods: The outcomes of 21 patients with ESmCCs of the head and neck treated between January 2001 and December 2015 at the authors’ hospital and associated facilities were reviewed. Results: There were 18 men and 3 women, and the median age was 74 years (range, 53-91 years). The tumor site was the larynx in 6 patients; the paranasal sinus in 5; the hypopharynx in 3; the oropharynx in 2; the nasopharynx in 2; and the oral cavity, salivary gland, and primary unknown in 1 patient each. The extent of the disease was staged as follows: stage I or II, 3 cases; stage III, 4 cases; stage IVA, 9 cases; stage IVB, 1 case; and stage IVC, 4 cases. The median observation time was 17 months (range, 1-103 months). Four patients (19%) had distant metastasis at initial treatment, and 13 patients (62%) developed distant metastasis within 3 years. Treatments were administered, including radical surgery (9 patients), radiation therapy (5 patients), chemoradiotherapy (7 patients), and chemotherapy (6 patients). The 1- and 3-year overall survival rates of patients were 56% and 37%, respectively. More than half of the patients died of distant metastasis. Conclusions: ESmCCs of the head and neck have a poor prognosis, similar to those of carcinomas in many other sites. Control of distant metastasis would contribute to improving the prognosis of ESmCCs of the head and neck. Further studies are required for better understanding these disease entities and their response to treatment modalities.
  • Hirofumi Omori; Kuniaki Sato; Takafumi Nakano; Takahiro Wakasaki; Satoshi Toh; Kenichi Taguchi; Takashi Nakagawa; Muneyuki Masuda
    Journal of Cancer Research and Clinical Oncology 145 10 2433 - 2444 2019年10月 
    Purpose: The clinical importance of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) is well recognized. However, a reliable method for the detection of functioning CSC has not yet been established. We hypothesized that YAP1, a transcriptional coactivator, and SOX2, a master transcription factor of SCC, may cooperatively induce stemness through transcriptional reprogramming. Methods: We immunohistochemically examined the expression of SOX2 and YAP1 in the CD44 variant 9 (CD44v9)-positive invasion front. A CSC-inducible module was identified through a combination of siRNAs and sphere formation assays. YAP1 and SOX2 interactions were analyzed in vitro. Results: The triple overexpression of SOX2, YAP1, and CD44v9 was significantly associated with poor prognosis. TCGA data revealed that the CSC-inducible module, which was related to EMT and angiogenesis, was significantly correlated with poor prognosis. The KLF7 expression, representatively chosen from the module, also correlated with poor prognosis and was essential for sphere formation and CSC propagation. Sphere stress-activated YAP1 enhanced SOX2 activity. Conclusions: The stress-triggered activation of YAP1/SOX2 transcriptionally reprograms HNSCC for the acquisition of stemness. Triple SOX2, YAP1, and CD44v9 immunostaining assays may be useful for the selection of high-risk patients with functioning CSCs, and YAP1 targeting may lead to the development of a CSC-targeting therapy.
  • Ryuji Yasumatsu; Takahiro Wakasaki; Kazuki Hashimoto; Koichiro Nakashima; Tomomi Manako; Masahiko Taura; Mioko Matsuo; Takashi Nakagawa
    Head and Neck 41 8 2610 - 2618 2019年08月 
    Background: Predicting the response to treatment with nivolumab and the survival in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) remains a challenge. We investigated whether or not the neutrophil-to-lymphocyte ratio (NLR) kinetics could be used to predict the anticancer effect of nivolumab. Patients and Methods: Forty-one patients with recurrent or metastatic HNSCC who had been treated with nivolumab were retrospectively analyzed. The NLR was calculated using pretreatment blood test results until the end of the treatment. Results: The posttreatment NLR was higher than the pretreatment value in 13 of 17 patients (76%) patients with progressive disease within the first 3 months, whereas the posttreatment NLR was lower than the pretreatment value in 10 of 11 patients (91%) with stable disease or partial response during the follow-up period. Conclusion: Our results indicate that monitoring the NLR may aid in the earlier confirmation of treatment failure in patients with recurrent or metastatic HNSCC during nivolumab monotherapy.
  • 原 大貴; 松尾 美央子; 内 龍太郎; 若崎 高裕; 田浦 政彦; 安松 隆治; 中川 尚志
    耳鼻と臨床 65 4 111 - 114 耳鼻と臨床会 2019年07月 
    遠隔転移を伴う場合の頭頸部癌の主治療は抗腫瘍薬の投与である。投与にあたってさまざまな有害事象が発生するが、致死的なものはまれである。今回、シスプラチンとセツキシマブの投与によって、総腸骨動脈に巨大な血栓を来し、急性下肢虚血に至った口腔癌の症例を経験した。本症例は、シスプラチン、5-FU、セツキシマブ投与継続中に、急に左下肢の痺れから麻痺に至ったが、速やかに血栓除去を行うことで救命および下肢温存が可能であった。担癌患者は、それ単独でも 4 − 7 倍の血栓症のリスクを伴うが、シスプラチンとセツキシマブの併用レジメンの抗腫瘍薬投与時は、よりそのリスクが高まる。血栓塞栓症は、発症すると急速に致死的な結果になる場合もあることから、まれで遭遇することが少ない病態とはいえ、念頭に置いた上で、抗腫瘍薬による治療を行っていく必要があると思われた。
  • 若崎 高裕
    耳鼻と臨床 65 3 96 - 100 耳鼻と臨床会 2019年05月
  • Ryuji Yasumatsu; Takafumi Nakano; Kazuki Hashimoto; Ryunosuke Kogo; Takahiro Wakasaki; Takashi Nakagawa
    Auris Nasus Larynx 46 1 135 - 140 2019年02月 
    Objective: The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC. Methods: Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA. Results: Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15. Conclusion: The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.
  • 内 龍太郎; 安松 隆治; 田浦 政彦; 若崎 高裕; 松尾 美央子; 中川 尚志
    頭頸部外科 29 2 143 - 147 特定非営利活動法人 日本頭頸部外科学会 2019年 
    2015年5月～ 2018年7月にシスプラチン（CDDP）併用根治的化学放射線療法を施行した頭頸部癌症例計87例におけるCDDPの忍容性について検討した。2016年まではCDDP 80mg/m2，2017年1月以降は100mg/m2を3週毎に投与した。80mg/m2群は63例，100mg/m2群は24例，予定投与量完遂率は61.9％および66.7％，総投与量200mg/m2以上の投与率は68.3％および91.7％，G3以上の有害事象発生割合は52.4％および70.8％であった。CDDP 100mg/m2投与は本邦においても忍容性を保ちつつ高容量投与を行える有効な治療であると考えられた。
  • 若崎 高裕; 安松 隆治; 古後 龍之介; 橋本 和樹; 中川 尚志
    頭頸部外科 28 3 271 - 276 特定非営利活動法人 日本頭頸部外科学会 2019年 
    UICC/AJCC TNM分類第8版による中咽頭癌TNM分類では，①HPV関連の有無 ②N節外浸潤の有無が，重要な要素となった。本邦の症例でも検証が必要であり，今回の改定に含まれない喫煙の予後への影響も含めて後方視的検討を行った。2010年1月から2015年12月に当科で根治治療を行ったHPV検索済の中咽頭扁平上皮癌110例を対象とした。HPV関連癌は52例だった。旧分類ではStageⅣが全体の60％を占めていたが，新分類ではStageⅠおよびⅡが倍増しStageⅣが減ったことで各病期症例数のバランスが改善した。粗生存率解析では新分類のほうが病期毎予後をより反映しており，喫煙の予後に対する影響も示唆された。
  • Natsumi Matsunaga; Takahiro Wakasaki; Ryuji Yasumatsu; Yojiro Kotake
    Anticancer Research 39 8 4073 - 4077 2019年 
    Background/Aim: ANRIL is a long noncoding RNA located on INK4 locus, which encodes p15 and p16 that cause G1 phase arrest in the cell cycle. ANRIL positively regulates proliferation of several kinds of cancer cells such as lung and gastric cancers. This study, examined the effect of ANRIL in head and neck squamous cell carcinoma cells. Materials and Methods: Cells were transfected with siRNA oligonucleotides targeting ANRIL. Transfected cells were subjected to cell-cycle and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Results: Depletion of ANRIL increased p15 mRNA in FaDu cells, and p15 and p16 mRNA in CAL27 cells and inhibited proliferation of these cells. Cell cycle analysis showed that depletion of ANRIL caused arrest at the G1 phase of the cell cycle. Conclusion: ANRIL promotes G1 phase progression by repressing p15 and p16, and thus promotes FaDu and CAL27 cell proliferation.
  • Ryuji Yasumatsu; Takafumi Nakano; Masanobu Sato; Rina Jiroumaru; Kazuki Hashimoto; Ryunosuke Kogo; Takahiro Wakasaki; Torahiko Nakashima; Takashi Nakagawa
    Head and Neck 40 12 2583 - 2589 2018年12月 
    Background: Differentiating inverted papilloma from squamous cell carcinoma (SCC) is sometimes difficult. We evaluated the clinical usefulness of serum SCCA1 and SCCA2 in the management of patients with inverted papilloma or SCC. Methods: Serum and tissue samples for the analysis of SCCA1, SCCA2, and SCC antigen were taken from 18 patients with sinonasal inverted papilloma and 23 cases with sinonasal SCC. The SCCA1, SCCA2, and SCC antigen levels were determined. Results: The serum SCCA1 concentration was significantly higher in the inverted papilloma group than in the SCC group, whereas the serum SCCA2 level was significantly higher in the SCC group than in the inverted papilloma group. Conclusion: Patients with sinonasal inverted papilloma predominantly express SCCA1 protein, whereas those with SCC predominantly express SCCA2. This suggests that combined measurements of both serum SCCA1 and SCCA2 concentrations can be very useful for distinguishing sinonasal inverted papilloma from SCC.
  • 安松 隆治; 佐藤 方宣; 若崎 高裕; 古後 龍之介; 中川 尚志
    耳鼻と臨床 64 6 223 - 227 耳鼻と臨床会 2018年11月 
    2007 年 1 月から 2016 年 12 月までの 10 年間に、初回治療開始時に精査を行ったにもかかわらず原発巣が不明であり頸部リンパ節転移を認めた 26 例を対象とした。内訳は N1：1 例、N2：23 例、N3：2 例であった。遠隔転移を認めた症例は 4 例であった。26 例のうち、原発巣が初回手術後に判明した症例が 4 例、治療終了後経過観察中に判明した症例が 2 例、原発巣が不明のままであった症例が 20 例であった。全体の 3 年粗生存率は 52％であり、N 分類の進行とともに予後も不良な傾向であった。免疫組織染色が可能であった 22 例中 7 例（32％）において p16 陽性所見が認められた。7 例中 5 例で最終的に原発巣が判明しており、内訳は中咽頭（扁桃）4 例、下咽頭（梨状陥凹）1 例であった。原発不明癌頸部リンパ節転移症例で p16 陽性であった場合、p16 陽性中咽頭癌と同様に取り扱うことが妥当なのか大規模な検証が必要と思われる。
  • 安井 徹郎; 安松 隆治; 若崎 高裕; 古後 龍之介; 藤 賢史; 中島 寅彦; 次郎丸 梨那; 山元 英崇; 中川 尚志
    頭頸部外科 28 2 191 - 197 特定非営利活動法人 日本頭頸部外科学会 2018年 
    副咽頭間隙腫瘍は，画像検査の普及により近年その報告は増加している。手術治療が第1選択だが解剖学的特殊性から手術アプローチ法の選択に苦慮することもある。今回，われわれは1994年から2017年の24年間に当科にて手術加療した副咽頭間隙腫瘍症例76例について腫瘍部位（茎突前区・後区）と術後合併症を中心に臨床検討を行った。全体で53例（70％）になんらかの合併症が認められ，特に後区発生腫瘍では迷走神経麻痺が17例（63％），Horner症候群は9例（33％）にみられ，また長期経過においても症状が遷延しやすかった。
  • 若崎 高裕
    耳鼻と臨床 63 6 234 - 237 耳鼻と臨床会 2017年11月
  • Muneyuki Masuda; Takahiro Wakasaki; Satoshi Toh; Yoshinori Uchida; Hidefumi Rikimaru; Naonobu Kunitake; Yuichiro Higaki
    Molecular and Clinical Oncology 7 6 965 - 970 2017年10月 [査読有り]
  • Takahiro Wakasaki; Hiroaki Niiro; Siamak Jabbarzadeh-Tabrizi; Mitsuru Ohashi; Takashi Kimitsuki; Takashi Nakagawa; Shizuo Komune; Koichi Akashi
    BMC Neuroscience 18 1 2017年08月 
    Background: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p=0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.
  • Takahiro Wakasaki; Hideyuki Kiyohara; Hirofumi Omori; Kensuke Nishi; Kenichi Taguchi; Fumihide Rikimaru; Satoshi Toh; Yuichiro Higaki; Muneyuki Masuda
    Oral and Maxillofacial Surgery 21 1 69 - 74 2017年03月 
    Purpose: Tumor thrombosis of the internal jugular vein (IJV) is an extremely rare disease, and the reported cases have been exclusively associated with differentiated thyroid cancer. In the present study, we describe two cases of IJV tumor thrombosis originated from squamous cell carcinoma (SCC), which is the first case report. Methods: Case 1 was a 67-year-old man diagnosed with advanced supraglottic SCC with a massive tumor thrombus in the IJV. He was treated with bio-radiotherapy followed by radical surgery. Case 2 was a 65-year-old woman who underwent radical surgery for SCC of thyroid with tumor thrombosis in the IJV. Results: These cases rapidly developed local recurrences and distant metastases and died within 10 months after surgery. Conclusions: IJV tumor thrombosis originated from SCC apparently reflects extremely aggressive state of the tumor. Recognition and precaution to this condition is essential for the development of a clinically effective treatment strategy.
  • Muneyuki Masuda; Takeichiro Aso; Takahiro Wakasaki; Hirofumi Omori; Fumihide Rikimaru; Satoshi Toh; Yuichiro Higaki
    JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY 26 3 431 - 436 2017年
  • Takahiro Wakasaki; Marie Kubota; Yutaka Nakashima; Eri Tomonobe; Takenao Mihara; Junichi Fukushima
    BMC Cancer 16 1 2016年10月 
    Background: Myoepithelial carcinoma (MEC) is a rare salivary gland tumor. Its long-term prognosis remains unknown because of the paucity of reported cases with long-term follow-up. Although some case series exist, the clinical features of MEC vary considerably depending on the site of origin. Therefore, accumulation of these rare cases is important. Case presentation: Case 1: An 89-year-old man presented with a 10-year history of a mass originating from the right parotid gland and involving the neck. The mass grew rapidly for 3 months, reaching approximately 8 cm. There was no facial paralysis. MEC ex pleomorphic adenoma (PA) was suspected. Superficial parotid gland resection was performed in 2013; the tumor grade was pT3N0M0, and the resection margins were free of carcinoma. Because of several high-risk factors for metastasis (i.e., invasive carcinoma ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. Although the patient refused adjuvant therapy, he was recurrence-free at 36 months after surgery. Case 2: A 54-year-old woman presented with a >10-year history of a right submandibular mass, which grew rapidly for 1 year, reaching approximately 6 cm. Preoperative diagnosis was PA of the right submandibular gland. Submandibular gland resection was performed in 2013. Pathological analysis revealed invasive MEC ex PA, pT3N0M0; in addition, the carcinoma portion had an extra capsule and had invaded the platysma muscle close to the margin. An MIB1 index of 40 % and mutant p53 protein positivity indicated a high risk for metastasis. Additional resection and right neck dissection revealed no residual carcinoma. The patient refused adjuvant chemotherapy. One year after surgery, metastasis to the right pulmonary hilar node and both lungs were detected. Chemotherapy prevented recurrent growth of the lesion and extended survival. The patient was alive with cancer 30 months after the first surgery. Conclusions: High expression of the Ki67 labeling index might reflect prognosis of these cases. Chemotherapy for distant metastasis was effective, as expected. Further accumulation of cases and long follow-up data are needed to elucidate the pathophysiology and prognosis of MEC ex PA.
  • Takahiro Wakasaki; Hirofumi Omori; Shintaro Sueyoshi; Fumihide Rikimaru; Satoshi Toh; Kenichi Taguchi; Yuichiro Higaki; Masaru Morita; Muneyuki Masuda
    World Journal of Surgical Oncology 14 1 2016年10月 
    Background: Advanced head and neck squamous cell carcinomas frequently develop distant metastases to limited organs, including the lungs, bone, mediastinal lymph nodes, brain, and liver. Peritoneal carcinomatosis as an initial distant metastasis from hypopharyngeal squamous cell carcinoma is quite rare. Case presentation: A 75-year-old man diagnosed with hypopharyngeal squamous cell carcinoma and his clinical stage was determined as T2N2cM0. Notably, the right retropharyngeal lymph node surrounded more than half of the right internal carotid artery. Concomitant conformal radiation therapy was administered for the primary hypopharyngeal lesion, and the whole neck and tumor response was evaluated at this point according to our algorithm-based chemoradioselection protocol. As the tumor responses at both the primary and lymph nodes were poor, with the right retropharyngeal lymph node in particular demonstrating mild enlargement, we performed a radical surgery: pharyngolaryngectomy, bilateral neck dissection, and reconstruction of the cervical esophagus with a free jejunal flap. Then, postoperative CRT was performed. During these therapies, the patient developed a fever and mild abdominal pain, which was associated with an increased C-reactive protein level. Contrast-enhanced computed tomography from the neck to the pelvis demonstrated mild peritoneal hypertrophy and ascites with no evidence of recurrent and/or metastatic tumor formation. We initially diagnosed acute abdomen symptoms as postoperative ileus. However, cytological examination of the refractory ascites resulted in a diagnosis of peritoneal carcinomatosis. Owing to rapid disease progress, the patient died 1.5 months after abdominal symptom onset. Conclusions: The present case is the second reported case of head and neck squamous cell carcinoma with peritoneal carcinomatosis as an incipient distant metastasis. Therefore, peritoneal carcinomatosis should be considered a differential diagnosis when acute abdomen is noted during treatment for head and neck cancers.
  • Takahiro Wakasaki; Seiji Gotoh; Eri Tomonobe; Takenao Mihara; Junichi Fukushima
    Annals of Otology, Rhinology and Laryngology 125 10 844 - 849 2016年10月 
    Objectives: Posterior reversible encephalopathy syndrome (PRES) is a rare and acute disease with central nervous system symptoms. Without appropriate therapy, patients may exhibit a poor prognosis. PRES should be recognized as a possible problem during therapy for head and neck squamous cell carcinoma (HNSCC). Methods: A 56-year-old female developed PRES during combined modality therapy for HNSCC. On the fourth day after surgery and following chemoradiotherapy, PRES developed with a sudden visual disorder, followed by headache located at the back of the head and convulsions accompanied by impaired consciousness. We diagnosed PRES based on the clinical manifestations and magnetic resonance imaging data. Results: The patient recovered from PRES by appropriate treatment. Conclusion: This is the first case report of PRES developed during treatment for HNSCC. Masked by other cerebrovascular disorders, more cases of PRES could exist than usually expected; therefore, we should consider PRES as a differential diagnosis for central nervous system disorders developing during high-intensity therapy.
  • 大森 裕文; 松尾 美央子; 若崎 高裕; 藤 賢史; 益田 宗幸
    耳鼻と臨床 62 4 136 - 140 耳鼻と臨床会 2016年07月 
    S-1 投与後に、腸炎を始めとした重篤な有害事象を認めた症例を経験した。症例は 73 歳、男性。声門上癌 cT2N0M0 に対し、根治的放射線化学療法として CDDP 併用の CRT を開始した。腫瘍は速やかに縮小傾向となり治療反応性は良好であったものの、CDDP 投与後に Grade3 の低ナトリウム血症や骨髄抑制を来し、さらには薬剤性腎障害によりクレアチニンクリアランスは 60 mℓ/min を切る状態となったため、以降の併用化学療法として S-1 を選択した。S-1 投与開始後 13 日目に 40 ℃近い発熱や 1 日 30 回を超える下痢を認めたため、S-1 による薬剤性消化管障害と判断し同日で中止した。しかしその後も約 2 カ月にわたり下痢や骨髄抑制が遷延した。重篤化した副作用の原因として dihydropyrimidine dehydrogenase（以下、DPD）欠損も疑われたが、精査の結果、DPD 欠損の診断には至らなかった。フッ化ピリミジン系薬剤は現在においても頭頸部癌化学療法において主たる役割を果たしているが、本邦においてはまれではあるが DPD 活性低下ないしは欠損の患者に遭遇することがある。その場合には非常に重篤な副作用を呈する可能性が高く、留意が必要である。本症例においてはその診断には至らなかったが、非常に重篤な副作用を呈し、DPD 欠損症も疑われた。その臨床経過および精査結果も含めて報告する。
  • 大森 裕文; 若崎 高裕; 西 憲祐; 力丸 文秀; 藤 賢史; 福島 淳一; 檜垣 雄一郎; 益田 宗幸
    頭頸部外科 26 2 271 - 276 特定非営利活動法人 日本頭頸部外科学会 2016年 
    縦隔気管孔造設後に腕頭動脈出血を来し，血管内ステントグラフト留置にて止血を得られた症例を経験した。症例は61歳男性。頸部食道癌cT4N2M0に対し根治的CRTを施行し，一旦はCRを得たが治療後5か月で原発巣再発rT3N0M0を来し，咽頭喉頭頸部食道全摘出術，両側頸部郭清術，遊離空腸再建術とあわせて縦隔気管孔を造設した。術後10日目に縦隔気管孔の気管断端壊死を契機として腕頭動脈の露出を認めたため，壊死した気管を切除し大胸筋皮弁を充填し直した。しかし再手術後15日目，縦隔気管孔の腕頭動脈が露出していた部位付近から腕頭動脈出血を来した。一時止血を得た後に腕頭動脈内に血管内ステントグラフトを挿入し，救命し得た症例を経験したため報告する。
  • Muneyuki Masuda; Takahiro Wakasaki; Satoshi Toh
    American Journal of Cancer Research 6 6 1149 - 1166 2016年 
    Recent results of the Cancer Genome Atlas on head and neck squamous cell carcinoma (HNSCC) revealed that HNSCC lacked predominant gain-of-function mutations in oncogenes, whereas an essential role for epigenetics in oncogenesis has become apparent. In parallel, it has gained general acceptance that cancer is considered as complex adaptive system, which evolves responding environmental selective pressures. This somatic evolution appears to proceed concurrently with the acquisition of an atavistic pluripotent state (i.e., "stemness"), which is inducible by intrinsic epigenetic reprogramming program as demonstrated by induced pluripotent stem (iPS) cells. This Nobel prize-winning discovery has markedly accelerated and expanded cancer stem cell research from the point of epigenetic reprogramming. Taken together, we hypothesize that stress-triggered atavistic reprogramming (STAR) may be the major driving force of HNSCC evolution. In this perspective, we discuss the possible mechanisms of STAR in HNSCC, focusing on recent topics of epigenetic reprogramming in developmental and cancer cell biology.
  • 久保田 万理恵; 若崎 高裕; 三原 丈直; 福島 淳一
    日本耳鼻咽喉科学会会報 117 10 1258 - 1263 一般社団法人 日本耳鼻咽喉科頭頸部外科学会 2014年 
    皮膚筋炎に対しステロイド治療中の61歳男性. 上部消化管内視鏡検査で左披裂部の隆起性病変を指摘され当科を初診したが, 既に隆起性病変は消退していた. 以後, 下咽頭領域の異なる部位で, 多彩な様相を呈する潰瘍性病変が増悪と軽快を繰り返し, 急性出血を来した際には緊急止血術を要した. CMV 感染による咽頭潰瘍の診断でガンシクロビルを投与し病変は消失した. 経過中, 皮膚筋炎による咽頭筋の筋力低下と粘膜病変による瘢痕の両者が原因と思われる嚥下障害を来した. これまでの文献報告と併せて検討し, CMV 感染による下咽頭潰瘍では, ① 急性出血, ② 声帯麻痺や出血による呼吸困難, ③ 深部組織への貫通に特に留意する必要があると考察した.
  • Muneyuki Masuda; Satoshi Toh; Takahiro Wakasaki; Masumi Suzui; Andrew K. Joe
    Molecular Oncology 7 1 14 - 28 2013年02月 
    Despite recent advancements in multidisciplinary treatments, the overall survival and quality of life of patients with advanced head and neck squamous cell carcinoma (HNSCC) have not improved significantly over the past decade. Molecular targeted therapies, which have been addressed and advanced by the concept of " oncogene addiction" , have demonstrated only limited successes so far. To explore a novel clue for clinically effective targeted therapies, we analyzed the molecular circuitry of HNSCC through the lens that HNSCC is an evolving system. In the trajectory of this somatic evolution, HNSCC acquires biological robustness under a variety of selective pressures including genetic, epigenetic, micro-environmental and metabolic stressors, which well explains the major mechanism of " escaping from oncogene addiction" . On the other hand, this systemic view appears to instruct us approaches to target latent vulnerability of HNSCC that is masked behind the plasticity and evolvability of this complex adaptive system. © 2012 Federation of European Biochemical Societies.
  • Ryuji Yasumatsu; Torahiko Nakashima; Moriyasu Yamauchi; Takahiro Wakasaki; Muneyuki Masuda; Shizuo Komune
    Auris Nasus Larynx 38 3 387 - 391 2011年06月 
    Objective: The aim of this study was to evaluate the immunohistochemical TS expression in patients with maxillary sinus SCC. Methods The value of immunohistochemical TS expression as a predictive indicator for 5-FU efficacy was retrospectively examined in 47 patients with maxillary sinus SCC. Results Of the 47 patients, 29 (62%) showed complete response for 5-FU based chemoradiotherapy. Seventeen of 19 (89%) TS low cases showed a complete response, whereas 12 of 28 (43%) TS high cases showed complete response for 5-FU based chemoradiotherapy. Low TS patients had significantly better response rates compared with high TS patients. Conclusion These findings suggest that TS expression affects the chemotherapeutic effect of 5-FU in patients with maxillary sinus SCC and the assessment of TS expression level might be useful both in the management and in the treatment of maxillary sinus SCC. © 2010 Elsevier Ireland Ltd.
  • Muneyuki Masuda; Takahiro Wakasaki; Satoshi Toh; Masahito Shimizu; Seiji Adachi
    Journal of Oncology 2011年 
    Over the past decade dose-intensified chemo-radiotherapy or molecular targeted therapy has been introduced into the treatments of head and neck squamous cell carcinoma (HNSCC) to improve the outcomes of this dismal disease. However, these strategies have revealed only limited efficacy so far. Moreover, the frequent occurrences of second primary tumor further worsen the prognosis of patients. In this context, early detection and chemoprevention appear to be a realistic and effective method to improve the prognosis as well as quality of life in patients with HNSCC. In this short paper, we discuss the potential of green tea extract, (-)-epigallocatechin-3-galate (EGCG) in HNSCC chemoprevention, focusing on two aspects that are provided recently: (1) evidence of clinical efficacy and (2) unique biological effects on lipid raft that emerged as an important platform of numerous biophysical functions, for example, receptor tyrosin kinases (RTKs) signalings including epidermal growth factor receptor (EGFR), which play critical roles in HNSCC carcinogenesis. © 2011 Muneyuki Masuda et al.
  • Takahiro Wakasaki; Muneyuki Masuda; Hiroaki Niiro; Siamak Jabbarzadeh-Tabrizi; Kumiko Noda; Tadayoshi Taniyama; Shizuo Komune; Koichi Akashi
    Neoplasia 12 10 789 - 796 2010年10月 
    Activation of the transforming growth factor (TGF) α/epidermal growth factor receptor (EGFR)-mediated signaling pathway is a common mechanism for dysregulated growth of head and neck squamous cell carcinoma (HNSCC). c-Cbl-interacting protein of 85 kDa (CIN85) is an adaptor protein that facilitates EGFR internalization. Little is known, however, about a role of CIN85 in EGFR signaling as well as its relevance to tumor development and progression of HNSCC. Here, we demonstrate that CIN85 is highly expressed in HNSCC tumor samples compared with adjacent normal tissues, and this overexpression is significantly correlated with advanced clinical stage. The experiments using CIN85-overexpressing and knockdown HNSCC cell lines showed that CIN85 promotes HNSCC growth and facilitates EGFR internalization without apparently affecting phosphorylation of EGFR. Moreover, CIN85 promoted TGF-α-induced activation of Ras and phosphorylation of downstream molecules such as c-Raf, MEK, and extracellular signal-regulated kinase, leading to expression of c-Myc that is critical for sustained proliferation of HNSCC. Taken together, these findings suggest that CIN85 not only controls EGFR internalization but also promotes the EGFRmediated tumor development and progression, and thus, CIN85 may serve as a potential therapeutic target in a subset of HNSCC. © 2010 Neoplasia Press, Inc.
  • Ryuji Yasumatsu; Torahiko Nakashima; Takahiro Wakasaki; Toranoshin Ayada; Hideki Kadota; Muneyuki Masuda; Satoshi Toh; Hideki Shiratsuchi; Shizuo Komune
    European Archives of Oto-Rhino-Laryngology 267 4 581 - 586 2010年04月 
    Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the degradation of 5-FU. There are no studies investigating the comparison of TS and DPD mRNA expressions in oral tongue SCC (OSCC) and nontumor tissues obtained from the same patients. In addition, increased interest has been focused on the biological roles of TS and DPD as the independent prognostic factors as well as responsive determinants for cancer patients with 5-FU based therapy. We determined the expression levels of TS and DPD in tumor (T) and nontumor squamous epithelial tissues (N) of OSCC using real-time reverse transcription-polymerase chain reaction and evaluated whether the T/N ratio would correlate with clinicopathological factors. The mRNA expressions of TS and DPD were significantly higher in tumor areas than in nontumor areas. No correlation was found between the T/N ratio of each mRNA expression and gender, clinical stage, T classification, N classification or differentiation. The T/N ratio of TS in patients that died of disease was significantly higher than in patients with free of disease, whereas there were no relationships between The T/N ratio of DPD and disease status. Clinical follow-up data showed shorter overall survival periods for cases with high T/N ratio of TS than for cases with low T/N ratio of TS with the statistically significant. Our study showed that TS but not DPD seems to have prognostic value in OSCC. These findings suggest that the assessment of TS activity may be useful both in the management and in the treatment of OSCC. © 2009 Springer-Verlag.
  • M. Masuda; T. Wakasaki; M. Suzui; S. Toh; A. K. Joe; I. B. Weinstein
    Current Cancer Drug Targets 10 1 117 - 126 2010年02月 
    Despite recent advancements in treatment modalities, the overall survival and quality of life of patients with head and neck squamous cell carcinoma (HNSCC) have not significantly improved over the past decade. With the increasing emergency of new biological agents, the development of novel treatment schemes based on cancer cell biology may be promising for this group of patients. We previously introduced the "oncogene addiction" concept as a rationale for molecular targeting in cancer therapy and prevention. In this context, an increasing number of preclinical studies have demonstrated that the Signal Transducers and Activators of transcription 3 (Stat3) transcription factor play critical roles in the development and progression of a variety of tumors including HNSCC, by regulating cell proliferation, cell cycle progression, apoptosis, angiogenesis, immune evasion, Epithelial-Mesenchymal Transition (EMT) and through effects in cancer stem cells. The purpose of this review is to summarize current experimental and clinical evidence that suggests that HNSCC might be addicted to Stat3 and describes the molecular mechanisms that may explain this phenomenon. In addition, we discuss whether this addiction is an exploitable target for developing approaches for the treatment and prevention of HNSCC. © 2010 Bentham Science Publishers Ltd.
  • Takashi Kimitsuki; Takahiro Wakasaki; Ayako Nawate; Noritaka Komune; Kazutaka Takaiwa; Mitsuru Ohashi; Shizuo Komune
    ORL 71 3 157 - 162 2009年07月 
    Objective: This study evaluated the ability of dihydrostreptomycin (DHSM) to go through the mechano-electric transduction (MET) channels in hair cells under physiological conditions. Materials and Methods: Tall hair cells were isolated from the chick basilar membrane (cochlea). Mechanical stimulation was applied by a glass rod attached to a piezoelectric bimorph, and MET currents were recorded with a whole-cell patch technique. The voltage-dependent block of DHSM to MET channel was estimated by calculating the relative conductances (the ratio of MET current in DHSM saline to DHSM-free saline) at various membrane potentials. Results and Conclusion: At membrane potentials between -100 and +50 mV, DHSM behaves as a voltage-dependent blocker according to a partial block model. At membrane potentials more negative than -100 mV, however, DHSM blocking decreased. This finding differed from the partial block model, but indicated that DHSM escaped through the channel pore into the cytoplasm by acting as a permeant channel blocker due to the large electrical driving force. Copyright © 2009 S. Karger AG.
  • Siamak Jabbarzadeh Tabrizi; Hiroaki Niiro; Mariko Masui; Goichi Yoshimoto; Tadafumi Iino; Yoshikane Kikushige; Takahiro Wakasaki; Eishi Baba; Shinji Shimoda; Toshihiro Miyamoto; Toshiro Hara; Koichi Akashi
    Journal of Immunology 182 3 1490 - 1499 2009年02月 
    BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells. Copyright © 2009 by The American Association of Immunologists, Inc.
  • Ryuji Yasumatsu; Torahiko Nakashima; Hideoki Uryu; Toranoshin Ayada; Takahiro Wakasaki; Ryunosuke Kogo; Muneyuki Masuda; Masakazu Fukushima; Shizuo Komune
    Chemotherapy 55 1 36 - 41 2008年12月 
    Background: 5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC. Methods: An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FU cytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients. Results: Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cellsin vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC. Conclusions: These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy. Copyright © 2008 S. Karger AG.
  • 益田 宗幸; 若崎 高裕; 玉江 昭裕; 小宗 徳孝; 原 崇
    耳鼻と臨床 54 4 186 - 194 2008年 
    比較的大きな副咽頭間隙腫瘍 (PPST) に対しては下顎骨正中離断によるアプローチがとられる傾向が見られたが,現在では,下顎骨正中離断を行わなくても,経頸部アプローチ (transcervical approach〔TCA〕) あるいは経耳下腺-頸部アプローチ (transparotid -cervical approach〔TPCA〕) で,大半のPPSTが比較的安全に摘出できることが確認されている。これらの手技に伴う適応,限界,ピットフォールを7cm以上のPPST3例を通して解説したい。症例1は10cmの神経鞘腫,症例2は耳下腺深葉の悪性腫瘍,症例3は再発性の多形腺腫である。
  • 益田 宗幸; 若崎 高裕; 玉江 昭裕; 小宗 徳孝; 原 崇; 内山 明彦
    日本耳鼻咽喉科学会会報 110 12 758 - 761 一般社団法人 日本耳鼻咽喉科頭頸部外科学会 2007年12月 
    食道癌取り扱い規約による, 106以下の縦隔リンパ節に転移を来した分化型甲状腺癌の2症例に対し, 各々胸骨・鎖骨切除による上方・前方からのアプローチと, 胸腔鏡下のVATS (video assisted thoracoscopic surgery) を用いて縦隔郭清を行った. 胸骨柄と胸骨の右半分 (第二肋間の高さまで) ・右鎖骨内側半分を合併切除した症例1では, 右鎖骨下静脈周囲のリンパ節, 105R, 106pre, 106recRまでを明視下に郭清したが, 前方からのアプローチによる106tbR郭清の困難さを再認識させられた. これに対し, 107の高さまで縦隔リンパ腫脹を認めた症例2に対しては, 頸部およびVATSによるコンバインドアプローチで腫瘍摘出を行った. VATSにより, 106tbR, 107領域の郭清が良好な視野で行えた. en blocな郭清が困難, 開胸・術中の体位変換・挿管チューブの交換が必要などの欠点もあるが, 106tb以下のリンパ節に転移を来した分化型甲状腺癌症例に対する, VATSの有用性が確認された.
  • Muneyuki Masuda; Hong Ying Ruan; Aya Ito; Torahiko Nakashima; Satoshi Toh; Takahiro Wakasaki; Ryuji Yasumatsu; Yuichiro Kutratomi; Shizuo Komune; I. Bernard Weinstein
    Oral Oncology 43 8 785 - 790 2007年09月 
    Overexpression of vascular endothelial growth factor (VEGF) is associated with angiogenic phenotypes and poor prognosis of numerous tumors, including head and neck squamous cell carcinoma (HNSCC). However, the precise mechanism that causes VEGF overexpression in HNSCC remains unknown. Since there is evidence that a transcriptional factor, signal transducers and activators of transcription 3 (Stat3), is constitutively activated in HNSCC and this activation is significantly associated with aggressive phenotypes of this disease, we investigated the roles of Stat3 activation on VEGF production and tumor angiogenesis in HNSCC both in vitro and in clinical samples. VEGF promoter assays with YCU-H891 cells demonstrated that dominant negative Stat3 significantly inhibited VEGF promoter activity in the full length (-2279 to +54) and two truncated forms of VEGF promoter luciferase-reporter construct (-1179 to 54) or (-1014 to +54), which retain the putative Stat3 responsive elements (-849 to -842). However, this was not seen in the shorter construct (-794 to +54), which lacks the putative Stat3 responsive elements. In the derivative of YCU-891 cells that stably express dominant negative Stat3 protein, cellular levels of VEGF mRNA and VEGF protein were significantly inhibited. In the 51 clinical samples obtained from the patients with tongue carcinoma, the expression levels of phosphorylated (activated) form of Stat3 protein were significantly correlated with VEGF (P < 0.05) production and intratumoral microvessel density IMVD (P < 0.01). These results strongly indicate that Stat3 directly up-regulates VEGF transcription and thereby promotes angiogenesis in HNSCC. Inhibition of Stat3 activity may provide a new anti-angiogenic therapy in HNSCC. © 2006 Elsevier Ltd. All rights reserved.
  • 若崎 高裕; 新里 祐一; 小宗 静男
    耳鼻と臨床 51 6 449 - 455 耳鼻と臨床会 2005年11月 
    47歳男性.患者は起床時の咽頭痛が徐々に増悪し,翌日には嚥下障害の出現で救急外来となった.咽頭後壁に発赤を認めたが,明らかな扁桃炎は認めず,下咽頭への著明な唾液貯留を認めた.喉頭ファイバースコピーで喉頭蓋舌面の著明な腫脹と咽頭腔の狭小化を認め,急性喉頭蓋炎と診断し,入院の上でdexathametasoneと抗生剤を投与した.しかし,来院3時間後に呼吸困難と口唇チアノーゼの出現で輪状甲状間膜穿刺による気道確保を行い,その後,気管切開を施行した.入院3日目,右頸部の発赤・腫脹が出現し,造影CTで右扁桃周囲,右副咽頭間膜,舌骨周囲の正中を越える広範な深頸部膿瘍が認められ,頸部外切開で膿瘍を開放し排膿(後日嫌気性菌検出)した.以後,10日目より発熱と白血球数,CRPの上昇を認めるも,抗菌薬の変更で解熱快方へ向かい,20日目に気管切開カニューレ抜去,気切孔閉鎖を行い,右頸部創部は肉芽増生後の28日目に創閉鎖を行った
  • 若崎 高裕; 中川 尚志; 賀数 康弘; 中島 寅彦; 小池 浩次; 白土 秀樹; 野口 敦子; 大庭 典子; 小宗 静男
    耳鼻と臨床 51 4 263 - 268 耳鼻と臨床会 2005年07月 
    様々な感音難聴症例にグリセロールテストを施行し,グリセロールに対する反応結果をもとに個々の症例を検討した.男性25名29耳,女性27名28耳,平均年齢46.3歳を対象にした.耳の平均聴力閾値は3分法で41.5dBであった.Metz,SISIテストではグリセロールテストの結果に関わらず特徴的な所見は認められなかった.グリセロールテスト陽性例と陰性例の間で,イソソルビド治療効果に有意差は認めなかった.高音障害型感音難聴でグリセロールテストを行い,陰性であったらイソソルビドは無効と考えられた.グリセロールテスト活用して,低音障害型以外の感音難聴にも内リンパ水腫に対する治療を行うべきであると考えられた
  • 中川 尚志; 賀数 康弘; 中条 恭子; 菅 孝文; 柴田 修明; 若崎 高裕; 大庭 典子; 野口 敦子; 小宗 静男
    ＡＵＤＩＯＬＯＧＹ ＪＡＰＡＮ 47 5 361 - 362 一般社団法人 日本聴覚医学会 2004年

講演・口頭発表等

  • 膵癌舌転移の1例
    宮崎 孝; 若崎 高裕; 次郎丸 梨那; 橋本 和樹; 松尾 美央子; 中川 尚志
    口腔・咽頭科 2022年08月 日本口腔・咽頭科学会
  • 直腸癌中咽頭転移の1例
    東原 雅明; 若崎 高裕; 松尾 美央子; 中川 尚志
    耳鼻咽喉科臨床 補冊 2022年06月 耳鼻咽喉科臨床学会
  • 進行口腔癌の下顎骨区域切除における術中迅速骨髄捺印細胞診の意義
    橋本 和樹; 安松 隆治; 松尾 美央子; 若崎 高裕; 次郎丸 梨那; 真子 知美; 山元 英崇; 本郷 貴大; 久我 亮介; 門田 英輝; 吉田 聖; 上薗 健一; 中川 尚志
    頭頸部癌 2022年05月 (一社)日本頭頸部癌学会
  • 簡便かつ安価なHPV関連頭頸部癌同定方法の確立にむけて
    次郎丸 梨那; 安松 隆治; 山元 英崇; 久我 亮介; 本郷 貴大; 真子 知美; 橋本 和樹; 若崎 高裕; 松尾 美央子; 中川 尚志
    頭頸部癌 2022年05月 (一社)日本頭頸部癌学会
  • 東原 雅明; 橋本 和樹; 松尾 美央子; 若崎 高裕; 次郎丸 梨那; 門田 英輝; 安松 隆治; 中川 尚志
    日本気管食道科学会会報 2022年04月 (NPO)日本気管食道科学会
  • 当科における早期下咽頭癌の臨床的検討
    嬉野 悠太; 若崎 高裕; 次郎丸 梨那; 橋本 和樹; 松尾 美央子; 安松 隆治; 中川 尚志
    口腔・咽頭科 2021年08月 日本口腔・咽頭科学会
  • 唾液腺癌に対する免疫チェックポイント阻害薬の臨床効果に関する検討
    橋本 和樹; 安松 隆治; 松尾 美央子; 若崎 高裕; 次郎丸 梨那; 真子 知美; 山元 英崇; 久我 亮介; 益田 宗幸; 倉富 勇一郎; 瓜生 英興; 玉江 昭裕; 田浦 政彦; 竹内 寅之進; 吉田 崇正; 中川 尚志
    頭頸部癌 2021年05月 (一社)日本頭頸部癌学会
  • 頭頸部癌患者に対する抗腫瘍薬投与後に発症した間質性肺炎の11症例
    松尾 美央子; 次郎丸 梨那; 橋本 和樹; 若崎 高裕; 安松 隆治; 中川 尚志
    頭頸部癌 2021年05月 (一社)日本頭頸部癌学会
  • 次郎丸 梨那; 安松 隆治; 松尾 美央子; 若崎 高裕; 橋本 和樹; 真子 知美; 山元 秀崇; 中川 尚志
    日本耳鼻咽喉科学会会報 2021年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 松尾 美央子; 次郎丸 梨那; 橋本 和樹; 若崎 高裕; 安松 隆治; 中川 尚志
    日本耳鼻咽喉科学会会報 2021年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 真子 知美; 安松 隆治; 松尾 美央子; 若崎 高裕; 橋本 和樹; 次郎丸 梨那; 益田 宗幸; 竹内 寅之進; 中川 尚志
    日本耳鼻咽喉科学会会報 2021年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 木田 裕太郎; 松尾 美央子; 次郎丸 梨那; 橋本 和樹; 若崎 高裕; 安松 隆治; 中川 尚志
    日本耳鼻咽喉科学会会報 2021年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 口腔癌症例の嚥下障害に関する検討
    田浦 政彦; 菊池 良和; 内 龍太郎; 若崎 高裕; 松尾 美央子; 安松 隆治; 中川 尚志
    日本癌治療学会学術集会抄録集 2020年10月 (一社)日本癌治療学会
  • 田浦 政彦; 菊池 良和; 内 龍太郎; 若崎 高裕; 松尾 美央子; 村上 大輔; 安松 隆治; 中川 尚志
    日本耳鼻咽喉科学会会報 2020年09月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 再発・転移頭頸部扁平上皮癌に対するNivolumab投与後化学療法の効果
    真子 知美; 若崎 高裕; 安松 隆治; 内 龍太郎; 松尾 美央子; 益田 宗幸; 中川 尚志
    頭頸部癌 2020年07月 (一社)日本頭頸部癌学会
  • 下咽頭癌症例の嚥下障害に関する検討
    田浦 政彦; 菊池 良和; 内 龍太郎; 若崎 高裕; 松尾 美央子; 安松 隆治; 中川 尚志
    頭頸部癌 2020年07月 (一社)日本頭頸部癌学会
  • 鼻副鼻腔乳頭腫由来癌の遺伝子変異解析
    内 龍太郎; 次郎丸 梨那; 安松 隆治; 本郷 貴大; 山元 英崇; 若崎 高裕; 松尾 美央子; 中川 尚志
    頭頸部癌 2020年07月 (一社)日本頭頸部癌学会
  • 食道癌の嚥下障害に関する検討
    田浦 政彦; 菊池 良和; 澤津橋 基広; 内 龍太郎; 若崎 高裕; 松尾 美央子; 安松 隆治; 中川 尚志
    日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
  • 頭頸部領域の小細胞癌
    若崎 高裕; 安松 隆治; 田浦 政彦; 松尾 美央子; 益田 宗幸; 中川 尚志
    日本癌治療学会学術集会抄録集 2019年10月 (一社)日本癌治療学会
  • 口腔癌症例の嚥下障害に関する検討  [通常講演]
    田浦 政彦; 菊池 良和; 澤津橋 基広; 内 龍太郎; 若崎 高裕; 松尾 美央子; 安松 隆治; 中川 尚志
    頭頸部癌 2019年05月 (一社)日本頭頸部癌学会
  • 若崎 高裕; 増田 智也; 安松 隆治; 松尾 美央子; 内 龍太郎; 田浦 政彦; 中川 尚志
    日本耳鼻咽喉科学会会報 2019年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 真子 知美; 若崎 高裕; 安松 隆治; 内 龍太郎; 田浦 政彦; 松尾 美央子; 中川 尚志
    日本耳鼻咽喉科学会会報 2019年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 松尾 美央子; 内 龍太郎; 田浦 政彦; 若崎 高裕; 安松 隆治; 中川 尚志
    日本耳鼻咽喉科学会会報 2019年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 吉田 聖; 門田 英輝; 安松 隆治; 松尾 美央子; 若崎 高裕; 益田 宗幸; 中川 尚志
    日本耳鼻咽喉科学会会報 2019年04月 (一社)日本耳鼻咽喉科頭頸部外科学会
  • 内視鏡的粘膜下層剥離術を施行した下咽頭脂肪肉腫の一例  [通常講演]
    永松 諒介; 荻野 治栄; 林 康代; 和田 将史; 大塚 宣寛; 小森 圭司; 畑 佳孝; 岩佐 勉; 知念 孝敏; 伊原 栄吉; 小川 佳宏; 若崎 高裕; 山元 英崇; 野崎 優衣; 次郎丸 梨那; 小田 義直
    日本消化器病学会九州支部例会プログラム・抄録集 2018年11月 日本消化器病学会-九州支部
  • 益田 昌吾; 古後 龍之介; 福嶋 晴太; 小宗 徳孝; 若崎 高裕; 中島 雄一郎; 佐伯 浩司; 門田 英輝; 安松 隆治; 中川 尚志
    日本耳鼻咽喉科学会会報 2018年04月 (一社)日本耳鼻咽喉科学会
  • R/MHNSCCに対するExtremeレジメン治療後のwPTX, Cmabと療法の成績  [通常講演]
    Takahiro Wakasaki; Ryuji Yasumatsu; Takashi Nakagawa
    American academy of otolaryngology head and neck surgery 2018年 ポスター発表
  • Chemoradioselectionによる進行喉頭下咽頭癌の治療強度適正化戦略  [通常講演]
    益田 宗幸; 本郷 貴大; 打田 義則; 若崎 高裕; 力丸 文秀; 藤 賢史; 國武 直信; 檜垣 雄一郎
    頭頸部癌 2017年05月 (一社)日本頭頸部癌学会
  • 同時性食道扁平上皮癌・咽頭喉頭扁平上皮癌の治療戦略 九州がんセンター案  [通常講演]
    若崎 高裕; 打田 義則; 本郷 貴大; 力丸 文秀; 藤 賢史; 池部 正彦; 森田 勝; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2017年05月 (一社)日本頭頸部癌学会
  • ヒト乳頭腫ウイルス関連中咽頭癌に対する新TNM分類の適用  [通常講演]
    藤 賢史; 若崎 高裕; 本郷 貴大; 打田 義則; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2017年05月 (一社)日本頭頸部癌学会
  • 当科における筋上皮癌の臨床的検討  [通常講演]
    本郷 貴大; 力丸 文秀; 打田 義則; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    日本耳鼻咽喉科学会会報 2017年04月 (一社)日本耳鼻咽喉科学会
  • Cetuximab+FP療法の治療効果判定時期の検討  [通常講演]
    打田 義則; 本郷 貴大; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    日本耳鼻咽喉科学会会報 2017年04月 (一社)日本耳鼻咽喉科学会
  • 喉頭扁平上皮癌(声門上)T3症例の検討  [通常講演]
    力丸 文秀; 西 憲祐; 佐野 仁紀; 大森 裕文; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2016年05月 (一社)日本頭頸部癌学会
  • 局所進行喉頭癌・下咽頭癌に対する初期治療としての外科治療の有効性に関する検討  [通常講演]
    藤 賢史; 大森 裕文; 西 憲祐; 佐野 仁紀; 若崎 高裕; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2016年05月 (一社)日本頭頸部癌学会
  • 当科にて加療を行った下顎骨区域切除術症例の検討  [通常講演]
    力丸 文秀; 吉田 聖; 打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2015年05月 (一社)日本頭頸部癌学会
  • S-1投与により重篤な小腸炎が出現した1例  [通常講演]
    大森 裕文; 松尾 美央子; 打田 義則; 末吉 慎太郎; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2015年05月 (一社)日本頭頸部癌学会
  • アルゴリズムに基づいたChemoradio-selectionによる進行喉頭・下咽頭癌の治療戦略  [通常講演]
    藤 賢史; 力丸 文秀; 打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 檜垣 雄一郎; 益田 宗幸
    頭頸部癌 2015年05月 (一社)日本頭頸部癌学会
  • 当科における再発転移性頭頸部扁平上皮癌に対するCetuximabの治療成績  [通常講演]
    打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸
    日本耳鼻咽喉科学会会報 2015年04月 (一社)日本耳鼻咽喉科学会
  • 同時性頭頸部癌食道癌症例に対する治療アルゴリズム 九州がんセンター試案  [通常講演]
    益田 宗幸; 大森 裕文; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 國武 直信; 江頭 明典; 森田 勝; 藤 也寸志
    日本耳鼻咽喉科学会会報 2015年04月 (一社)日本耳鼻咽喉科学会
  • 舌扁平上皮癌におけるNotch1発現量と臨床データの解析  [通常講演]
    若崎 高裕; 益田 宗幸; 小宗 静男
    頭頸部癌 2012年05月 (一社)日本頭頸部癌学会
  • HNSCC細胞株由来のがん幹細胞様細胞の表現型解析
    T. Wakasaki; M. Masuda; H. Niiro; S. Komune
    American head and neck society 2012 RESEARCH WORKSHOP 2012年 ポスター発表
  • Matrigel selectionによる頭頸部扁平上皮癌細胞株の表現形・遺伝子発現形の解析  [通常講演]
    若崎 高裕; 益田 宗幸; 藤 賢史; 小宗 静男
    頭頸部癌 2011年05月 (一社)日本頭頸部癌学会
  • Gene expression profiling of supporting cells in the chick inner ear
    T. Wakasaki; M. Masuda; H. Niiro; S. Komune
    Association for research in otolaryngology 2010年 ポスター発表
  • Ras-ERK経路を介した頭頸部扁平上皮癌の発生と進行におけるCIN85の機能解析
    T. Wakasaki; M. Masuda; H. Niiro; S. Komune
    American head and neck society 2010 RESEARCH WORKSHOP 2010年 ポスター発表
  • 頭頸部癌におけるCIN85の発現とEGFR-MAPKシグナル伝達に関する検討(CIN85 predominantly transmits EGFR signal to MAPK cascade, and enhance tumor progression in HNSCC)  [通常講演]
    若崎 高裕; 益田 宗幸; 新納 宏昭; 小宗 静男; 赤司 浩一
    日本癌学会総会記事 2009年08月 日本癌学会
  • T. Wakasaki; M. Masuda; H. Niiro; S. Komune; K. Akashi
    ORAL ONCOLOGY 2009年07月 ELSEVIER SCIENCE BV
  • 頭頸部癌におけるCIN85蛋白のEGFRシグナル伝達制御の解析  [通常講演]
    若崎 高裕; 益田 宗幸; 新納 宏昭; 赤司 浩一; 小宗 静男
    頭頸部癌 2009年05月 (一社)日本頭頸部癌学会
  • 多機能アダプタータンパク質, CIN85のMAPKカスケードを介したHNSCC腫瘍進行について
    T. Wakasaki; M. Masuda; H. Niiro; S. Komune; K. Akashi
    International academy of oral oncology 2009年 ポスター発表
  • 側方開胸下に深部縦隔郭清を行った甲状腺濾胞状癌の一例  [通常講演]
    益田 宗幸; 若崎 高裕; 原 崇; 内山 明彦
    頭頸部癌 2006年05月 (一社)日本頭頸部癌学会

MISC

  • 放射線性下顎骨壊死に対し腓骨皮弁再建施行した症例の移植部感染に関する検討
    吉田 聖; 門田 英輝; 安松 隆治; 松尾 美央子; 若崎 高裕; 益田 宗幸; 中川 尚志 日本耳鼻咽喉科学会会報 122 (4) 597 -597 2019年04月
  • Chemoradioselectionによる進行喉頭下咽頭癌の治療強度適正化戦略
    益田 宗幸; 本郷 貴大; 打田 義則; 若崎 高裕; 力丸 文秀; 藤 賢史; 國武 直信; 檜垣 雄一郎 頭頸部癌 43 (2) 185 -185 2017年05月
  • 同時性食道扁平上皮癌・咽頭喉頭扁平上皮癌の治療戦略 九州がんセンター案
    若崎 高裕; 打田 義則; 本郷 貴大; 力丸 文秀; 藤 賢史; 池部 正彦; 森田 勝; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 43 (2) 216 -216 2017年05月
  • ヒト乳頭腫ウイルス関連中咽頭癌に対する新TNM分類の適用
    藤 賢史; 若崎 高裕; 本郷 貴大; 打田 義則; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 43 (2) 264 -264 2017年05月
  • 当科における筋上皮癌の臨床的検討
    本郷 貴大; 力丸 文秀; 打田 義則; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 日本耳鼻咽喉科学会会報 120 (4) 580 -580 2017年04月
  • Cetuximab+FP療法の治療効果判定時期の検討
    打田 義則; 本郷 貴大; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 日本耳鼻咽喉科学会会報 120 (4) 643 -643 2017年04月
  • 喉頭扁平上皮癌(声門上)T3症例の検討
    力丸 文秀; 西 憲祐; 佐野 仁紀; 大森 裕文; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 42 (2) 155 -155 2016年05月
  • 局所進行喉頭癌・下咽頭癌に対する初期治療としての外科治療の有効性に関する検討
    藤 賢史; 大森 裕文; 西 憲祐; 佐野 仁紀; 若崎 高裕; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 42 (2) 156 -156 2016年05月
  • 当科にて加療を行った下顎骨区域切除術症例の検討
    力丸 文秀; 吉田 聖; 打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 41 (2) 187 -187 2015年05月
  • S-1投与により重篤な小腸炎が出現した1例
    大森 裕文; 松尾 美央子; 打田 義則; 末吉 慎太郎; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 41 (2) 194 -194 2015年05月
  • アルゴリズムに基づいたChemoradio-selectionによる進行喉頭・下咽頭癌の治療戦略
    藤 賢史; 力丸 文秀; 打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 檜垣 雄一郎; 益田 宗幸 頭頸部癌 41 (2) 199 -199 2015年05月
  • 当科における再発転移性頭頸部扁平上皮癌に対するCetuximabの治療成績
    打田 義則; 大森 裕文; 末吉 慎太郎; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 益田 宗幸 日本耳鼻咽喉科学会会報 118 (4) 500 -500 2015年04月
  • 同時性頭頸部癌食道癌症例に対する治療アルゴリズム 九州がんセンター試案
    益田 宗幸; 大森 裕文; 若崎 高裕; 力丸 文秀; 藤 賢史; 檜垣 雄一郎; 國武 直信; 江頭 明典; 森田 勝; 藤 也寸志 日本耳鼻咽喉科学会会報 118 (4) 609 -609 2015年04月
  • 舌扁平上皮癌におけるNotch1発現量と臨床データの解析
    若崎 高裕; 益田 宗幸; 小宗 静男 頭頸部癌 38 (2) 186 -186 2012年05月
  • Matrigel selectionによる頭頸部扁平上皮癌細胞株の表現形・遺伝子発現形の解析
    若崎 高裕; 益田 宗幸; 藤 賢史; 小宗 静男 頭頸部癌 37 (2) 274 -274 2011年05月
  • 頭頸部癌におけるCIN85の発現とEGFR-MAPKシグナル伝達に関する検討(CIN85 predominantly transmits EGFR signal to MAPK cascade, and enhance tumor progression in HNSCC)
    若崎 高裕; 益田 宗幸; 新納 宏昭; 小宗 静男; 赤司 浩一 日本癌学会総会記事 68回 203 -203 2009年08月
  • T. Wakasaki; M. Masuda; H. Niiro; S. Komune; K. Akashi ORAL ONCOLOGY 211 -211 2009年07月
  • 頭頸部癌におけるCIN85蛋白のEGFRシグナル伝達制御の解析
    若崎 高裕; 益田 宗幸; 新納 宏昭; 赤司 浩一; 小宗 静男 頭頸部癌 35 (2) 86 -86 2009年05月
  • 側方開胸下に深部縦隔郭清を行った甲状腺濾胞状癌の一例
    益田 宗幸; 若崎 高裕; 原 崇; 内山 明彦 頭頸部癌 32 (2) 226 -226 2006年05月

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 神武 洋二郎; 若崎 高裕
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2020年04月 -2023年03月 
    代表者 : 若崎 高裕; 神武 洋二郎
     
    頭頸部扁平上皮癌（以下 頭頸部癌）は全癌の4-5%と少なく、腫瘍の部位、発癌の機序も多岐にわたるため、特異的な治療ターゲットや有用なバイオマーカー研究が進んでいない。ポストゲノム時代に入り、頭頸部癌の発生・進化にもエピジェネティックな機構が大きく関与する事が注目されており、lncRNAは発がん及び癌の進展に重要な役割を担っている報告が増えている。がん進展に重要と考えられる3つのlncRNAに注目した。ANRIL(antisense non-coding RNA in the INK4 lucus), OIP5-AS1（OPA-interacting protein 5 antisense transcript 1）およびPANDA(p21 associated ncRNA DNA damage activated)に注目し、解析を進める。これらのlncRNAは、細胞周期およびアポトーシス制御に関与すること、肺癌や胃癌で高発現していることなどが明らかとなっている。頭頸部癌におけるこれらlncRNAの機能を解明し、頭頸部癌の予後、治療耐性度を予測・反映するバイオマーカーの開発、新規治療につなげたい。本研究では、①頭頸部癌での作用機序②頭頸部癌の進行・再発のモニタリングや予後予測における有用性の有無を解析する。 今回の研究において、2020年度頭頸部癌バイオマーカーに関する論文（Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma）を執筆し、Cancers誌に掲載された。2021年度 頭頸部癌細胞株であるFaDu と CAL27 頭頸部扁平上皮がん細胞の細胞周期進行における OIP5-AS1 の役割について検討し、 OIP5-AS1 は、CDK 阻害因子を抑制することにより G1 期進行を制御し、FaDu, CAL27 細胞の増殖を促進させることを示し、Cancer Genomics Proteomics誌に掲載された。
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 2018年04月 -2023年03月 
    代表者 : 中川 尚志; 安松 隆治; 若崎 高裕; 鍋島 一樹; 松本 希; 小宗 徳孝; 古後 龍之介; 安井 徹郎; 内 龍太郎
     
    A. RNAseqを用いた網羅的遺伝子発現解析 外耳道扁平上皮癌検体のトランスクリプトーム解析をRNAseqを用いて行った。遺伝子オントロジー解析を行ったところ、細胞外マトリックスに関連する遺伝子が、側頭骨扁平上皮癌で高発現していることが判明した。また腫瘍高発現遺伝子のうち、高発現遺伝子群の中に、ラミニン5γ2（LAMC2)やMMPといった細胞外マトリックスリモデリングに関与する遺伝子に加え、IL-１βといった炎症に関与する遺伝子が含まれていた。GSEA解析を行ったところ、LAMC2の発現と、EMTに関与する遺伝子setが正の相関をすることを見出した。またLAMC2の発現がKi67の発現と正の相関を示すことが明らかになった。さらに、カプランマイヤー曲線では、LAMC2の高発現症例では有意に予後が悪いことを確認した。この結果を踏まえ、LAMC2の発現は、これまで報告されてきた癌浸潤能だけではなく、癌増殖能にも関与する可能性があることが考えられた。 B． ヒト由来側頭骨扁平上皮癌細胞株の樹立 ２０１８年度までに患者由来の組織からprimary culture colonyの作成に成功していた。その培養方法を用いて、培養細胞を継代する中で、安定して継代可能なコロニーを認め、そのコロニーからヒト由来側頭骨扁平上皮癌細胞株の作成に成功した。側頭骨扁平上皮癌の細胞株は、世界で初めてである（現在論文作成中）。これまで、側頭骨扁平上皮癌研究において、細胞株が存在しないことが、 In vitroの研究の遅延につながっていたが、今後の分子生物学的研究に大きく寄与することが期待できる。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 益田 宗幸; 二階堂 愛; 藤 賢史; 若崎 高祐
     
    1. 転写調節因子YAP1蛋白の条件的な活性化により２週間で癌化する、世界初の頭頸部癌（口腔）epigenetic発がんマウスモデルの樹立に成功した。ヒト口腔癌病理サンプル、頭頸部癌培養細胞による実験結果と併せてYAP1蛋白が口腔発がん・進展に大きく関与する因子であることを見いだし。そのepigeneticなメカニズムをさらに解析中である。本研究の結果の一部を2018年度の日本癌学会シンポジウムで報告し、第1報を英文投稿中である。 2. 頭頸部癌の幹細胞性の維持誘導に、YAP1とSOX2が協調的に働き、一連の標的遺伝子の転写活性を亢進することを見いだした。この結果は現在英文として投稿中である。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 若崎 高裕; 益田 宗幸; 大森 裕文
     
    口腔扁平上皮癌の臨床検体で癌幹細胞が多く存在する癌先進部において、YAP1とSOX2の核内同時発現が顕著であった。これにCD44v7を加えた、免疫染色での三重共発現は予後不良因子であることを示した。さらに、頭頸部扁平上皮癌において、ストレス誘発性のYAP1の活性化がSOX2と協調し、エピジェネティックリプログラミングを介してステムネスの獲得に寄与することを示した。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 若崎 高裕
     
    今回の研究では頭頸部扁平上皮癌細胞株では、CIN85が増殖能以外に浸潤能にも正に相関していることを示した。EMT関連遺伝子には有意な変化を証明できなかった。頭頸部扁平上皮癌細胞株のマイクロアレイおよびウエスタンブロッティング実験結果から、PI3K/Akt経路の関与が新たに示すことができた。CIN85はアダプター遺伝子であり、その接合分子は多岐にわたる。多用な経路をたどり、表現型に寄与していると考えられる。 今回の研究結果から、CIN85は頭頸部扁平上皮癌においてMAPK経路以外にPI3K/Akt経路も介して腫瘍増勢、進展に寄与していることが考えられた。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2012年04月 -2015年03月 
    代表者 : 益田 宗幸; 酒々井 真澄; 若崎 高裕
     
    １．The Cancer Genome Atlas (TCGA)の頭頸部癌組織のデーターの解析をおこないSox2が頭頸部癌の多分化能誘導に重要な役割を果たしている事をみいだした。頭頸部癌培養細胞にSox2を強制発現させgenome-wideな解析を行う予備段階に入っている。 ２．九州がんセンターでchemoradioselction戦略に基づいて治療を行った標本を使用して固形癌の癌細胞のマーカーとして有用視されているCC44v9の発現と臨床病理学的因・予後との相関解析をおこない。CD44v9の発現が患者の予後を不良とする因子である事を頭頸部癌では世界ではじめて明らかにした（PlosOne）

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