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1 様式 C-19 科学研究費助成事業 ( 科学研究費補助金 ) 研究成果報告書 平成 24 年 5 月 7 日現在 機関番号 :32607 研究種目 : 基盤研究 (C) 研究期間 :2008~2011 課題番号 : 研究課題名 ( 和文 ) 喉頭機能温存手術 SCL-CHEP の術後音声嚥下機能に関わる生理的エビデンスの解析 研究課題名 ( 英文 ) Physiological evidence of supracricoid laryngectomy with CHEP 研究代表者中山明仁 (NAKAYAMA MEIJIN) 北里大学 医学部 講師研究者番号 : 研究成果の概要 ( 和文 ): 喉頭機能温存手術 SCL-CHEP では病変を含む甲状軟骨を中心に 3/4 の喉頭が切除され 輪状軟骨と披裂軟骨からなる 1/4 の喉頭が温存される 再建の過程で温存喉頭部は舌骨まで引き上げられ喉頭蓋 舌根部との相互作用により音声 嚥下機能を可能にしている 新声門が機能するために Cricoarytenoid Unit( 以下 CAU) の温存は不可欠である CAU は輪状軟骨と披裂軟骨 ( 両側 片側 ) と内喉頭筋 ( 後輪状披裂筋 : 後筋, 外側輪状披裂筋 : 側筋, 披裂筋 : 横筋 ) と上喉頭神経 反回神経からなる CAU に関わる組織が生理的にどのように作用するかを研究し 下記の結果を明らかにした 1)Cricoarytenoid Unit (CAU) の術中筋電図検査 : 術中喉頭筋電図の計測による解析を行い CAU に関わる閉鎖筋と開大筋の相反的収縮が確認された また 内喉頭筋の中でしばしば切除の対象となる LC が欠損し IA と PCA のみでも披裂軟骨が機能することも確認した 2)Multi Detector CT scan による新声門の形態的評価 :CAU に関わる内喉頭筋の役割と実際の新声門 ( 披裂部 ) の可動性を検証するために MDCT による披裂軟骨の可動性の検証を行った 発声時と吸気時の披裂部の動きの解析にて片側披裂部残存症例は両側残存例に比べて可動性が有意に大きいことが確認された 3) 新声門の高速度撮影と音声機能検査による音源同定 : 高速度撮影の解析では残存披裂部内側と喉頭蓋の相互作用が音源として機能していることが確認された 研究成果の概要 ( 英文 ): Three projects were conducted and the results reported. 1) Electromyography of cricoarytenoid unit: Mobility of the arytenoid was attributed to interaction between the interarytenoid muscle and posterior cricoarytenoid muscle. Reciprocal interaction between the interarytenoid muscle and posterior cricoarytenoid muscle alone is also capable of maintaining post-operative laryngeal functions after supracricoid laryngectomy with cricohyoidoepiglottopexy. 2) MDCT analysis of CAU: Anterior shifting of the unilateral arytenoid plays an important role in compensating for the inability to achieve neoglottic closure. These two results demonstrate that the unilateral arytenoid alone is capable of achieving sufficient neoglottic narrowing to compensate for the resected arytenoid. Three-dimensional analysis was useful to evaluate the physiological status of the neoglottis after supracricoid laryngectomy with cricohyoidoepiglottopexy. 3) High-speed digital imaging laryngoscopy of neoglottis: High-speed digital imaging analysis is effective in locating the sites responsible for voice production in patients who have undergone supracricoid laryngectomy with cricohyoidoepiglottopexy. This is the first study to clearly identify the neoglottal sound source in such patients, using a high-speed digital imaging system.
2 交付決定額 ( 金額単位 : 円 ) 直接経費 間接経費 合計 2008 年度 1,000, ,000 1,300, 年度 900, ,000 1,170, 年度 900, ,000 1,170, 年度 700, , ,000 年度 総計 3,500,000 1,050,000 4,550,000 研究分野 : 喉頭科学 腫瘍学科研費の分科 細目 : 耳鼻咽喉科学 頭頸部外科キーワード :Cricoarytenoid Unit MDCT 高速度撮影 喉頭機能温存 喉頭癌 1. 研究開始当初の背景進行喉頭癌に対して適応される喉頭機能温存手術 Supracricoid laryngectomy with Cricohyoidoepiglotto-pexy ( 喉頭亜全摘出術 /SCL-CHEP) では病変を含む甲状軟骨を中心に 3/4 の喉頭が切除され 輪状軟骨と披裂軟骨からなる 1/4 の喉頭が温存される 再建の過程で温存喉頭部は舌骨まで引き上げられ喉頭蓋 舌根部との相互作用により音声 嚥下機能を可能にしている 新声門が機能するために Cricoarytenoid Unit( 以下 CAU) の温存は不可欠である CAU は輪状軟骨と披裂軟骨 ( 両側 片側 ) と内喉頭筋 ( 後輪状披裂筋 : 後筋, 外側輪状披裂筋 : 側筋, 披裂筋 : 横筋 ) と上喉頭神経 反回神経からなる しかし CAU に関わる各組織が生理的にどのように作用し機能しているか エビデンスが存在していない 1)Cricoarytenoid Unit (CAU) の術中筋電図検査 : 術中喉頭筋電図の計測による解析を行い CAU に関わる閉鎖筋と開大筋の相反的収縮が確認された また 内喉頭筋の中でしばしば切除の対象となる LC が欠損し IA と PCA のみでも披裂軟骨が機能することも確認した LC は声門の閉鎖には重要な役割を担うない喉頭筋である この筋体が欠損しても IA と PCA だけで喉頭機能が保たれることを証明したことは重要な成果である この成果は世界で最初の証明である 2. 研究の目的 CAU に関わる組織が生理的にどのように作用するかを下記の 3 項目について解析することで 喉頭亜全摘出術 SCL-CHEP の 下記の結果を明らかにした 3. 研究の方法 1)CAU の術中筋電図検査 :SCL-CHEP の術中 喉頭の閉鎖筋 (IA, LCA) と開大筋 (PCA) の喉頭筋電図の計測を行い 閉鎖筋と開大筋の相互作用や相反作用について検討する 2)Multi Detector CT scan による術後喉頭の形態的解析 : 最小 0.625mm のスライス幅にて 残存喉頭 ( 披裂部 輪状軟骨 ) の形態と発声時と吸気時の披裂部の動きの解析を行うことで 披裂軟骨の動きが喉頭機能にどのように関わるかについて検討した 3) 新声門の高速度撮影と音声機能検査を行うことで 新声門での音源同定 音声機能への関与について検討した 4. 研究成果 from sup L-LC, L-IA, L-PCA, R-PCA 2)Multi Detector CT scan による新声門の形態的評価 :CAU に関わる内喉頭筋の役割と実際の新声門 ( 披裂部 ) の可動性を検証するために MDCT による披裂軟骨の可動性の検証を行った 発声時と吸気時の披裂部の動きの解析にて片側披裂部残存症例は両側残存例に比べて可動性が有意に大きいことが確認された 片側披裂部残存例は喉頭機能を維持することは困難であるとされていた ところが我々の検討結果では片側例は披裂部の可動性がよく 効率的に移動して両側残存例に劣
3 らない機能を果たすことができることが明らかとなった よる音源同定 : 高速度撮影の解析では残存披裂部内側と喉頭蓋の相互作用が音源として機能していることが確認された 披裂残存部の遊離縁と喉頭蓋による狭めの間で直接コンタクトが起きるかベルヌイ効果により 音源が生じていることが確認された 症例によっては声帯振動に近い音声効果を示す場合があり 亜全摘術後の新声門は音声機能にも十分に対応していることが確認された 上 : 両側披裂残存例 下 : 片側披裂残存例片側例の方が披裂部の可動性が良好 右披裂部残存例の音源定位 : 右披裂部が内側移動しその遊離縁と左披裂部残存粘膜と喉頭蓋喉頭面で作り出す間隙に気流が起こり ベルヌイ効果の作用により音源が形成されていることが確認された 音源は二つの周波数からなり この二つの周波数はお互いに倍音周波数を形成することで お互いに干渉することなく増幅して有響音に近似した聴覚印象を与えていた 3) 新声門の高速度撮影と音声機能検査に 音源定位した振動部位は Estimated volume flow 曲線により 音源の基本波形が構築されていることが確認され 生理学的にも音源の責任部位であることが実証された この結果は世界で初めての生理的エビデンスの提唱であり 極めて重要なことを実証したといえる
4 5. 主な発表論文等 ( 研究代表者には下線 ) 雑誌論文 ( 計 7 件 ) すべて査読有 1 Nakayama, M., Laccourreye, O., Helsingr, C., Makito, O., Hayakawa, K.: Functional organ preservation for laryngeal cancer: Past, Present, and Future. Jpn J Clin Oncol 42(3): , Seino, Y., Nakayama, M., Okamoto, M., Hayashi, S.: Three-dimensional computed tomography analysis of neoglottis after supracricoid laryngectomy with CHEP. J Laryngol Otol, e-publication, Nakayama, M., Okamoto, M., Iwabuchi, K., Mikami, T., Seino, Y.: Clinical significance of intraoperative surgical margin study in supracricoid laryngectomy. Auris Nasus Larynx, 38: , Nakayama, M., Okamoto, M., Seino, Y., Miyamoto, S., Matsuki, T., Ogawa, A.: Delayed wound infection after supracricoid partial laryngectomy following failure of high dose radiation. Eur Arch Otorhinolaryngol, 268: , Hayashi, S., Hirose, H., Tayama, N., Imagawa, H., Nakayama, M., Seino, Y., Okamoto, M., Kimura, M., Nito, T.: High speed digital imaging laryngoscopy of the neoglottis following supracricoid laryngectomy with cricohyoidoepiglottopexy. J Laryngol Otol, 124: , Nakayama, M., Okamoto, M., Seino, Y., Miyamoto, S., Hayashi, S., Masaki, T., Yokobori, S., Takeda M.: Inverted epiglottis: A postoperative complication of supracricoid laryngectomy with cricohyoidoepiglottopexy. Auris Nasus Larynx, 37: , Nakayama, M., Hirose, H., Miyamoto, S., Yokobori, S., Takeda, M., Seino, Y., Okamoto, M.: Electromyography of the cricoarytenoid unit during supracricoid laryngectomy with a cricohyoidoepiglottopexy procedure. J Laryngol Otol, 121: 87-91, 学会発表 ( 計 7 件 ) 1 Nakayama, M., Watanabe, A., Tamura, e., Okamoto T., Y, Seino., Shunsuke M., Okamoto M.: Autologous fat augmentation for insufficient neoglottal closure after SCL-CHEP: A preliminary report. 14th Japan-Korea ORL-HNS meeting, , Kyoto Hotel Okura. 2 Nakayama, M.: Supracricoid laryngectomy: Is there still a role for salvage SCPL-CHEP. Combined workshop for Head and Neck Surgery, , Seoul, Korea. 3 Nakayama, M., Seino Y., Okamoto M., Shunsuke M., Okamoto T..: Is there still a role for salvage SCPL-CHEP. AAO-HNS Annual meeting, , San Francisco Convention Center, USA. 4 Nakayama, M., Salvage SCPL-CHEP. Annual meeting of Taiwan Head and Neck Cancer Association, , Kaohsiung, Taiwan. 5 Nakayama, M., Seino Y., Okamoto M., Shunsuke M., Okamoto T..: Clinical significance of positive Delphian node in supracricoid laryngectomy with cricohyoidoepiglottopexy. The 12 th Asia-Oceania Otolaryngology Head and Neck Congress, , Aotea Centre, Auckland, New Zealand. 6 Nakayama, M., Okamoto, M., Seino Y., Shunsuke M., Hayashi S.: Delayed wound infection after supracricoid laryngectomy following failure of high dose radiation. The 4 th World Congress of International Federation of Head and Neck Oncologic Societies, IFHNOS 2010, , Lotte Hotel Seoul. 7 Nakayama, M., Matsuki, T., Okamoto, M., Seino Y.: Flaccid neoglottis following supracricoid laryngectomy: laryngoscopic revision assisted by navigation system. The 4 th World Voice Congress 2010, , Coex convention center, Seoul. 図書 ( 計 2 件 ) 1 Nakayama, M.: Atlas of Head and Neck Surgery, Commentary on Chapter 36 Supracricoid partial laryngectomy with cricohyoidopexy or Cricohyoidoepiglottopexy. Elsevier Saunders 中山明仁 岡本牧人 :EBM 耳鼻咽喉科 頭頸部外科の治療 喉頭亜全摘出術 の EBM とは? 中外医学社, 2010.
5 産業財産権 出願状況 ( 計 0 件 ) なし 取得状況 ( 計 0 件 ) なし その他 なし ホームページ等なし 6. 研究組織 (1) 研究代表者中山明仁 (NAKAYAMA MEIJIN) 北里大学 医学部 講師研究者番号 :
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