研究

学術活動

教育・研究業績データベース

【外科学講座　呼吸器外科（大森）】教育・研究業績データベース へ

概要

外科は、診療が第一であるのは当然です。しかしながら、医療は日々進歩しており、外科学も同様に発展することによって、より有効で、低侵襲な治療方法へと進化する可能性があります。研究により新しい可能性を追求することは外科学の進歩にとっても非常に重要であり、研究を行うことによって診療のレベルも向上すると考えています。

個別化医療を目指した肺癌治療に関する研究

間質性肺炎合併肺癌

当院は国内大学病院初の間質性肺炎センターを有しています。間質性肺炎は高い頻度で肺癌を合併するため、当科では専門施設として、全国各地から紹介された多くの間質性肺炎合併肺癌を治療してきました。間質性肺炎合併肺癌は手術リスクが高く、予後も不良で治療が難しい領域ですが、根治率を向上させるため、診療と研究を行っています。

1. Iyoda A, Azuma Y, Sakamoto S, Homma S, Sano A. Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: Postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes. Surg Today 2021. 2022 May;52(5):736-744.
2. Azuma Y, Sakamoto S, Homma S, Sano A, Sakai T, Koezuka S, Otsuka H, Tochigi N, Kishi K, Iyoda A. Impact of accurate diagnosis of interstitial lung diseases on postoperative outcomes in lung cancer. Gen Thorac Cardiovasc Surg. 2022 Aug 23. doi: 10.1007/s11748-022-01868-6.
3. 肥塚 智, 東 陽子, 坂井 貴志，佐藤 史朋, 栃木 直文, 伊豫田 明. 在宅酸素療法導入を要する重症度IV度の間質性肺炎を合併した肺癌の1切除例. 日呼外会誌. 2022;36(5):567-74.
4. Sugino K, Otsuka H, Matsumoto Y, Nakamura Y, Matsumoto K, Azuma Y, Makino T, Iyoda A, Shibuya K, Homma S. The role of video-assisted thoracoscopic surgery in the diagnosis of interstitial lung disease. Sarcoidosis vasculitis and diffuse lung disease. 2019;36:148-56
5. Isobe K, Kaburaki K, Kobayashi H, Sano G, Sakamoto S, Takai Y, Makino T, Tochigi N, Iyoda A, Homma S. New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia. Lung Cancer 2018;125:253-7
6. Otsuka H, Sugino K, Hata Y, Makino T, Koezuka S, Isobe K, Tochigi N, Shibuya K, Homma S, Iyoda A. Clinical features and outcomes of patients with lung cancer and combined pulmonary fibrosis and emphysema. Mol Clin Onc 2016;5:273-8
7. 磯部和順，秦　美暢，鏑木教平，坂本　晋，高井雄二郎，栃木直文，伊豫田　明，本間　栄. 間質性肺炎合併肺癌に対する2nd line化学療法の検討．肺癌，2014;54:761-6
8. Iyoda A, Jiang SX, Amano H, Ogawa F, Matui Y, Kurouzu N, Hara H, Nezu K, Mikami T, Saegusa M, Satoh Y. Prediction of postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease. Exp Ther Med. 2011;2:1073-6
9. Isobe K, Hata Y, Sakamoto S, Takai Y, Shibuya K, Homma S. Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology, 2010;15:88-92
10. Iyoda A, Moriya Y, Hiroshima K, Shibuya K, Yoshino I. Successful management of postoperative acute respiratory distress syndrome in a patient with lung cancer. Gen Thorac Cardiovasc Surg. 2008;56:354-6

肺癌多様性に関する研究

画像検査では一見同じように見える肺癌も、実際は非常に多彩な病理組織像を有しており、治療効果や予後も様々です。当科では肺癌の多様性に着目し、画像検査所見と病理組織像、予後との関連などを解析しています。

1. Koezuka S, Sano A, Azuma Y, Sakai T, Matsumoto K, Shiraga N, Mikami T, Tochigi N, Murakami Y, Iyoda A. Combination of mean CT value and maximum CT value as a novel predictor of lepidic predominant lesions in small lung adenocarcinoma presenting as solid nodules. Sci Rep. 2022 Mar 31;12(1):5450.
2. Koezuka S, Mikami T, Tochigi N, Sano A, Azuma Y, Makino T, Otsuka H, Keiko Matsumoto, Nobuyuki Shiraga, Iyoda A. Toward improving prognosis prediction in patients undergoing small lung adenocarcinoma resection: Radiological and pathological assessment of diversity and intratumor heterogeneity. Lung Cancer. 2019;135:40-6
3. Sakai T, Aokage K, Neri S, Nakamura H, Nomura S, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Iyoda A, Tsuboi M, Ishii G. Link between tumor-promoting fibrous microenvironment and an immunosuppressive microenvironment in stage I lung adenocarcinoma. Lung Cancer 2018;126:64-71

肺気腫合併肺癌

当院では肺気腫合併肺癌の患者さんが多く来院され、COPD II期、III期でも外来にて理学療法を行い、呼吸機能を改善したうえで手術を施行しています。間質性肺炎も併存したCombined Pulmonary Fibrosis and Emphysema （CPFE）合併肺癌の患者様も他の施設と比べて多く、その病態を解析しています。

1. Azuma Y, Sano A, Sakai T, Koezuka S, Otsuka H, Tochigi N, Isobe K, Sakamoto S, Takai Y, Iyoda A. Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease. BMC Pulmonary Medicine. 2021;21;21:174.
2. Ogura R, Iribe S, Suzuki T, Kuroda H, Sugisawa T, Okuni I, Otsuka H, Azuma Y, Iyoda A, Ebihara S.Persistence of the Postoperative Change in the Six-minute Walking Distance of Lung Cancer Patients with Chronic Obstructive Pulmonary Disease. Prog Rehabil Med. 2021;11;6:20210022.
3. Makino T, Otsuka H, Hata Y, Koezuka S, Azuma Y, Isobe K, Sugino K, Ebihara S, Homma S, Iyoda A. Long‑acting muscarinic antagonist and long‑acting β2‑agonist therapy to optimize chronic obstructive pulmonary disease prior to lung cancer surgery. Mol Clin Onc 2018;8:647-52
4. 牧野　崇，笹本修一，秦　美暢，高木啓吾. 術前1秒量0.8Lであった重症COPD合併肺癌の1切除例．日本呼吸器外科学会雑誌，2012;26:157-61

気道狭窄に対するインタ‐ベンション、ステント治療に関する研究

前任の髙木啓吾教授は気道狭窄の治療方法に関して日本におけるleaderであったため、これまでも他の施設から多くの患者さんをご紹介いただき治療してきました。気道狭窄の治療に関しては、標準治療といえるものがないため、その確立のために診療、研究を行っています。

1. Iyoda A, Azuma Y, Sano A, Sakai T, Koezuka S, Otsuka H, Tochigi N, Isobe K, Sakamoto S, Takagi K. Contributions of Airway Stent for Long-term Outcome in Patients With Malignant Central Airway Stenosis or Obstruction. J Bronchology Interv Pulmonol. 2021;28:228-34.
2. Iyoda A, Azuma Y, Sano A, Sakai T, Koezuka S, Otsuka H, Isobe K, Sakamoto S, Takai Y, Takagi K. Long-term survival of airway silicone stents in patients with central airway stenosis or obstruction due to thoracic malignancy. Gen Thorac Cardiovasc Surg. 2021;69:1303-7.
3. Iyoda A, Azuma Y, Sano A, Sakai T, Koezuka S, Otsuka H, Isobe K, Sakamoto S, Hata Y, Takagi K. Long-term outcomes in patients with benign central airway stenosis or obstruction after stenting. World Acad Sci J. 2020;2:20
4. Nakamura Y, Hata Y, Koezuka S, Makino T, Otsuka H, Sato F, Sasamoto S, Okubo Y, Shibuya K, Iyoda A. Tracheal leiomyoma resected with endobronchial electrocautery snare. J Bronchology Interv Pulmonol. 2015;22:90-3
5. Yuasa R, Hata Y, Otsuka H, Makino T, Koezuka S, Sato F, Tamaki K, Sasamoto S, Takagi K, Iyoda A. Placement of self-expandable metallic stents for tracheal stenosis secondary to thyroid cancer. Mol Clin Oncol. 2014;2:1003-8
6. Hata Y, Takagi K, Sato F, Isobe K, Mitsuda A, Shibuya K, Goto H, Sasamoto S, Otsuka H. Therapeutic bronchoscopy followed by lobectomy for pulmonary sarcoma. J Bronchology Interv Pulmonol, 2013;20:281-4
7. 高木啓吾，秦　美暢，笹本修一，高橋祥司，佐藤史朋，田巻一義，後藤英典，湯浅玲奈. 食道癌による気管浸潤の治療戦略　ステント治療．日本気管食道科学会会報. 2011;62:349-54
8. Takagi K, Takahashi S, Hata Y, Tamaki K, Kato N, Sasamoto S. Use of emergency rigid bronchoscopy to reduce tumour mass prior to surgical resection. Respirology, 2007;12:777-9
9. 高木啓吾，秦　美暢，笹本修一，佐藤史朋，大塚　創，田巻一義，清水邦彦，木村一博，本間　栄. Dumon-Yステント留置の成績とその問題点．気管支学，2007;29:221-6

分子標的薬治療に関する研究

肺癌の増殖や転移にかかわる分子生物学的機序の解明と治療への応用が進められており、当院でも分子標的治療に関する研究を進めています。

1. Azuma Y, Yokobori T, Mogi A, Yajima T, Kosaka T, Iijima M, Shimizu K, Shirabe K, Kuwano H. Cancer Exosomal microRNAs From Gefitinib-Resistant Lung Cancer Cells Cause Therapeutic Resistance in Gefitinib-Sensitive Cells. Surg Today. 2020 Sep;50(9):1099-1106.
2. Nakano Y, Isobe K, Kobayashi H, Kaburaki K, Isshiki T, Sakamoto S, Takai Y, Tochigi N, Mikami T, Iyoda A, Homma S, Kishi K. Clinical Importance of Long Non coding RNA LINC00460 Expression in EGFR mutant Lung Adenocarcinoma. Int J Oncol. 2020;56:243-57
3. Isobe K, Kakimoto A, Mikami T, Kaburaki K, Kobayashi H, Yoshizawa T, Makino T, Otsuka H, Sano G, Sugino K, Sakamoto S, Takai Y, Tochigi N, Iyoda A, Homma S. PD-L1 mRNA Expression in EGFR-mutant Lung Adenocarcinoma. Oncol Rep 2018;40:331-8
4. Isobe K, Hata Y, Tochigi N, Kaburaki K, Kobayashi H, Makino T, Otsuka H, Ishida F, Kikuchi N, Hirota N, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Shibuya K, Iyoda A, Homma S. Usefulness of nanofluidic digital PCR arrays to quantify T790M mutation in EGFR-mutant lung adenocarcinoma. Cancer Genomics Proteomics. 2015;12:31-7
5. Isobe K, Hata Y, Tochigi N, Kaburaki K, Kobayashi H, Yamamoto A, Makino T, Otsuka H, Sato F, Ishida F, Kikuchi N, Hirota N, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Shibuya K, Iyoda A, Homma S. Clinical significance of BIM deletion polymorphism in non–small-cell lung cancer with Epidermal Growth Factor Receptor mutation. J Thorac Oncol, 2014;9:483-7

進行肺癌に対する術前化学放射線療法

縦隔リンパ節転移や縦隔臓器浸潤を伴う進行肺癌に対しても、術前化学放射線療法などの集学的治療を行ない、治療成績の向上のための研究を行っています。

1. Isobe K, Hata Y, Sakaguchi S, Sato F, Takahashi S, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Mitsuda A, Terahara A, Shibuya K, Takagi K, Homma S. Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation. Asia-Pacific JCO. 2012;8:260-6

大細胞神経内分泌癌に関する研究

1999年、WHOが新しい肺癌組織分類を提示し、肺大細胞神経内分泌癌という組織型が存在することを明らかにしました。肺大細胞神経内分泌癌は小細胞癌と同様、high grade neuroendocrine tumorとして分類されるべき、予後不良な組織型です。WHOの分類において明文化されるとともにその研究は活発となり、世界各国で進められています。

伊豫田教授は前任地の千葉大学、北里大学において肺大細胞神経内分泌癌の研究に取り組み、肺大細胞神経内分泌癌に対する術後補助化学療法の有用性を示唆する論文を世界で初めて発表し、世界的な英文論文の誌上でも引用され、高い評価を受けています。当科でも、肺大細胞神経内分泌癌を中心とした研究を積極的に進めています。今後、さらに新しいエビデンスを世界に発信できるように研究を継続していきます。

1. Iyoda A, Azuma Y, Sano A. Neuroendocrine Tumors of the Lung: Clinicopathological and Molecular Features. Surg Today. 2020;50:1578-84.
2. Iyoda A. Professor Special Lecture: 71st Annual Meeting of the Medical Society of Toho University Biological and Clinicopathological Features of Pulmonary Large-cell Neuroendocrine Carcinoma-A New Era of Research Toho J Med 2018;4:35-42
3. Makino T, Mikami T, Hata Y, Otsuka H, Koezuka S, Isobe K, Tochigi N, Shibuya K, Homma S, Iyoda A. Comprehensive biomarkers for personalized treatment in pulmonary large-cell neuroendocrine carcinoma: a comparative analysis with adenocarcinoma. Ann Thorac Surg 2016 2016;102:1694-701
4. Iyoda A, Makino T, Koezuka S, Otsuka H, Hata Y. Treatment options for patients with large cell neuroendocrine carcinoma of the lung. Gen Thorac Cardiovasc Surg. 2014 ;62:351-6
5. Iyoda A, Jiang SX, Travis WD, Kurouzu N, Ogawa F, Amano H, Sato Y, Rusch VW, Saegusa M, Satoh Y. Clinicopathological features and the impact of the new TNM classification of malignant tumors in patients with pulmonary large cell neuroendocrine carcinoma. Mol Clin Oncol. 2013;1:437-43
6. Ryuge S, Sato Y, Jiang SX, Wang G, Matsumoto T, Katono K, Inoue H, Iyoda A, Satoh Y, Yoshimura H, Masuda N. Prognostic impact of nestin expression in resected large cell neuroendocrine carcinoma of the lung. Lung Cancer. 2012;77:415-20
7. Matsumoto T, Ryuge S, Kobayashi M, Kageyama T, Hattori M, Goshima N, Jiang SX, Saegusa M, Iyoda A, Satoh Y, Masuda N, Sato Y. Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung. Int J Oncol. 2012;40:1957-62
8. Iyoda A, Travis WD, Sarkaria IS, Jiang SX, Amano H, Sato Y, Saegusa M, Rusch VW, Satoh Y. Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma. Exp Ther Med 2011;2:1041-5.
9. Sarkaria IS, Iyoda A, Roh MS, Sica G, Kuk D, Sima CS, Pietanza MC, Park BJ, Travis WD, Rusch VW. Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg. 2011;92:1180-6
10. Nasgashio R, Sato Y, Matsumoto T, Kageyama T, Hattori M, Iyoda A, Satoh Y, Ryuge S, Masuda N, Jiang SX, Saegusa M. The balance between the expressions of hASH1 and HES1 differs between large cell neuroendocrine carcinoma and small cell carcinoma of the lung. Lung Cancer. 2011;74:405-10
11. Iyoda A, Hiroshima K, Moriya Y, Iwadate Y, Takiguchi Y, Uno T, Nakatani Y, Yoshino I. Postoperative recurrence and the role of adjuvant chemotherapy in patients with pulmonary large-cell neuroendocrine carcinoma. J Thorac Cardiovasc Surg. 2009 ;138:446-53
12. Amin RM, Hiroshima K, Iyoda A, Hoshi K, Honma K, Kuroki M, Kokubo T, Fujisawa T, Miyagi Y, Nakatani Y.LKB1 protein expression in neuroendocrine tumors of the lung. Pathol Int. 2008;58:84-8
13. Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T. Pulmonary large cell neuroendocrine carcinoma: its place in the spectrum of pulmonary carcinoma.　Ann Thorac Surg 2007;84:702-7
14. Hiroshima K, Iyoda A, Shida T, Shibuya K, Iizasa T, Kishi H, Tanizawa T, Fujisawa T, Nakatani Y. Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis. Mod Pathol 2006;19:1358-68
15. Iyoda A, Hiroshima K, Moriya Y, Takiguchi Y, Sekine Y, Shibuya K, Iizasa T, Kimura H, Nakatani Y, Fujisawa T. Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma. Ann Thorac Surg 2006;82:1802-7
16. Iyoda A, Hiroshima K, Moriya Y, Sekine Y, Shibuya K, Iizasa T, Nakatani Y, Fujisawa T. Prognostic impact of large cell neuroendocrine histology in patients with pathologic stage Ia pulmonary non-small cell carcinoma.　J Thorac Cardiovasc Surg 2006;132:312-5
17. 伊豫田明, 廣島健三, 中谷行雄, 藤澤武彦. 肺大細胞神経内分泌癌. 肺癌 2006; 46:315-20
18. Yamada Y, Iyoda A, Suzuki M, Mizobuchi T, Baba M, Hiroshima K, Ohwada H, 　　　　　　　　　Fujisawa T. Double primary lung carcinoma consisting of large cell neuroendocrine 　carcinoma and squamous cell carcinoma: report of a case. Ann Thorac Cardiovasc Surg. 2005;11:397-400. 　
19. Iyoda A, Hiroshima K, Moriya Y, Mizobuchi T, Otsuji M, Sekine Y, Shibuya K, 　　Iizasa T, Saitoh Y, Fujisawa T.　Pulmonary large cell neuroendocrine carcinoma demonstrates high proliferative activity. Ann Thorac Surg. 2004 ;77:1891-5
20. Hiroshima K, Iyoda A, Shibuya K, Haga Y, Toyozaki T, Iizasa T, Nakayama T, Fujisawa T, Ohwada H.Genetic alterations in early-stage pulmonary large cell neuroendocrine carcinoma. Cancer. 2004;100:1190-8.
21. Iyoda A, Baba M, Hiroshima K, Saitoh H, Moriya Y, Shibuya K, Iizasa T, Horiuchi F, Ohwada H, Fujisawa T. Imprint cytologic features of pulmonary large cell neuroendocrine carcinoma: Comparison with classic large cell carcinoma. Oncol Rep. 2004;11:285-8.
22. Hiroshima K, Iyoda A, Shibuya K, Toyozaki T, Haga Y, Fujisawa T, Ohwada H. Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung.　Ann Thorac Surg. 2002;73:1732-5.
23. Iyoda A, Hiroshima K, Baba M, Saitoh Y, Ohwada H, Fujisawa T. Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors.　Ann Thorac Surg. 2002;73:1049-54.
24. Iyoda A, Hiroshima K, Toyozaki T, Haga Y, Baba M, Fujisawa T, Ohwada H.　Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. Cancer. 2001;92:1108-12.
25. Iyoda A, Hiroshima K, Toyozaki T, Haga Y, Fujisawa T, Ohwada H.　Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology.　Cancer. 2001;91:1992-2000.

悪性胸膜中皮腫に関する研究

悪性胸膜中皮腫はアスベスト曝露が関連した予後不良な腫瘍であり、治療に難渋される患者さんが多い疾患です。当科では、より有効な治療を開発するべく研究を行い、伊豫田教授は重粒子線治療の研究班にも所属しています。

1. Iyoda A, Azuma Y, Sakai T, Koezuka S, Otsuka H, Tochigi N, Isobe K, Sano A. Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma. Mol Clin Oncol. 2021;15:188.


2. Sano A, Azuma Y, Sakai T, Koezuka S, Otsuka H, Iyoda A. Diaphragm reconstruction by GORE DUALMESH in patients undergoing resection for thoracic malignancies. J Cardiothorac Surg. 2021;16:65.



3. Muramatsu Y, Isobe K, Sugino K, Kinoshita A, Wada T, Sakamoto S, Takai Y, Sato F, Hata Y, Wakayama M, Sibuya K, Uekusa T, Iyoda A, Homma S. Malignant pleural mesothelioma mimicking the intrapulmonary growth pattern of epithelioid hemangioendothelioma. Pathol Int. 2014;64:358-60


4. Hiroshima K, Yusa T, Kameya T, Ito I, Kaneko K, Kadoyama C, Kishi H, Saitoh Y, Ozaki D, Itami M, Iwata T, Iyoda A, Kawai T, Yoshino I, Nakatani Y. Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features. Pathol Int. 2009;59:537-45


5. Iyoda A, Yusa T, Kadoyama C, Sasaki K, Kimura H, Yamakawa H, Shiba M, Fujisawa T, Yoshino I. Diffuse malignant pleural mesothelioma: a multi-institutional clinicopathological study. Surg Today. 2008;38:993-8

COVID-19肺炎に関する研究

新型コロナウイルス（COVID-19）感染が肺に与える影響や後遺症は未だ多くが未解明です。COVID-19感染後の患者さんに対する呼吸器外科手術の安全性や対応も定まっておらず早急な解明が必要とされています。当科でもCOVID-19感染後の患者さんに対する手術が増えており、新たなエビデンスを発信すべく診療と研究を行っています。

1. Sakai T, Azuma Y, Aoki K, Wakayama M, Miyoshi S, Kishi K, Tateda K, Homma S, Iyoda A. Elective lung resection after treatment for COVID-19 pneumonia.
   Gen Thorac Cardiovasc Surg. 2021;69:1159-62.

公的研究費

東邦大学医学部倫理委員会および東邦大学医療センター大森病院倫理委員会にて承認されている研究

【学会認定資格】