Pathophysiology and growth control of the microenvironment in colorectal cancer with highly invasive growth

• Project/Area Number: 18K08668
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hirosaki University
• Principal Investigator: Morohashi Hajime 弘前大学, 医学部附属病院, 講師 (30598628)
• Co-Investigator(Kenkyū-buntansha): 袴田 健一 弘前大学, 医学研究科, 教授 (30271802) ; 三浦 卓也 弘前大学, 医学部附属病院, 講師 (30722136) ; 坂本 義之 弘前大学, 医学研究科, 准教授 (60361010) ; 鬼島 宏 弘前大学, 医学研究科, 教授 (90204859)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 癌微小環境 / リンパ節転移 / 腹膜播種 / 大腸癌 / ロボット手術 / 癌周囲微小環境 / 時計遺伝子 / ヒアルロン酸 / 微小循環

Outline of Final Research Achievements

Colorectal cancer with highly invasive growth is known to have fibrosis around the cancer cells, and vascular and nerve invasion is prominent. The results of this study, which focused on this form of development and the cancer microenvironment, have elucidated the form of development of lateral lymph node metastasis of rectal cancer and developed a treatment method that combines preoperative treatment and lymph node dissection.

Academic Significance and Societal Importance of the Research Achievements

本研究により癌細胞増殖、癌細胞・間質との相互作用の機序を解明し、高浸潤性増殖を呈する大腸癌における癌微小環境の病態解明と、その増殖制御についての手がかりを解明した。その結果、進行直腸癌の側方リンパ節転移の進展形式に対して、癌微小環境をターゲットとした治療の重要性を解明した。臨床応用として早期からの癌微小環境をターゲットとした術前化学療法とロボット手術を組み合わせた新たな治療戦略の開発に至った。

Research Products

• [Journal Article] Short‐term outcomes of robotic‐assisted surgery following neoadjuvant chemotherapy for lower rectal cancer (2022)
  • Author(s): Morohashi Hajime、Sakamoto Yoshiyuki、Miura Takuya、Ichinohe Daichi、Kubota Shunsuke、Yamazaki Keisuke、Ichisawa Aika、Mitsuhashi Yuto、Wakiya Taiichi、Hakamada Kenichi
  • Journal Title: Asian Journal of Endoscopic Surgery Volume: - Issue: 3 Pages: 577-584
  • DOI: 10.1111/ases.13055
  • Peer Reviewed / Open Access
• [Journal Article] A Prospective Multicenter Phase II Study on the Feasibility and Efficacy of S-1 and Oxaliplatin Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer (2022)
  • Author(s): Sakamoto Yoshiyuki、Morohashi Hajime、Miura Takuya、Tsutsumi Shinji、Takahashi Seiji、Hirama Kimiaki、Wakiya Taiichi、Hakamada Kenichi
  • Journal Title: Diseases of the Colon & Rectum Volume: 65 Issue: 5 Pages: 663-671
  • DOI: 10.1097/dcr.0000000000001927
  • Peer Reviewed
• [Journal Article] Effective dissection for rectal cancer with lateral lymph node metastasis based on prognostic factors and recurrence type (2021)
  • Author(s): Morohashi Hajime、Sakamoto Yoshiyuki、Miura Takuya、Ichinohe Daichi、Umemura Kotaro、Akaishi Takanobu、Sato Kentaro、Kuwata Daisuke、Yamazaki Keisuke、Wakiya Taiichi、Hakamada Kenichi
  • Journal Title: International Journal of Colorectal Disease Volume: - Issue: 6 Pages: 1-11
  • DOI: 10.1007/s00384-021-03870-5
  • Peer Reviewed / Open Access
• [Journal Article] Short-term outcomes of robotic-assisted laparoscopic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer (2020)
  • Author(s): Morohashi Hajime、Sakamoto Yoshiyuki、Miura Takuya、Kagiya Takuji、Ogasawara Kenta、Takahashi Yoshiya、Sato Kentaro、Hara Yutaro、Ogasawara Hirokazu、Hakamada Kenichi
  • Journal Title: Surgical Endoscopy Volume: - Issue: 9 Pages: 5001-5008
  • DOI: 10.1007/s00464-020-07979-6
  • Peer Reviewed / Open Access
• [Journal Article] Organ/space infection is a common cause of high output stoma and outlet obstruction in diverting ileostomy. (2020)
  • Author(s): Hara Y, Miura T, Sakamoto Y, Morohashi H, Nagase H, Hakamada K.
  • Journal Title: BMC Surg. Volume: 20 Issue: 1 Pages: 83-83
  • DOI: 10.1186/s12893-020-00734-7
  • Peer Reviewed / Open Access
• [Journal Article] Dual energy CT is useful for the prediction of mesenteric and lateral pelvic lymph node metastasis in rectal cancer (2019)
  • Author(s): Sato, K. Morohashi, H. Tsushima, F. Sakamoto, Y. Miura, T. Fujita, H. Umemura, K. Suzuki, T. Tsuruta, S. Kura, R. Ono, S. Aoki, M. Hakamada, K.
  • Journal Title: Mol Clin Oncol Volume: 10 Pages: 625-630
  • DOI: 10.3892/mco.2019.1834
  • Peer Reviewed / Open Access
• [Journal Article] Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis (2018)
  • Author(s): Morohashi H, Uchida C, Ogasawara H, Hara Y, Akaishi T, et al.
  • Journal Title: Gan To Kagaku Ryoho Volume: 45 Pages: 1922-1924
  • Peer Reviewed / Open Access
• [Journal Article] Necrotizing fasciitis of the thigh due to penetrated descending colon cancer: a case report. (2018)
  • Author(s): Sato K, Miura T, Ishido K, Kakamoto Y, Kudo D, Kimura N, Morohashi H, et al.
  • Journal Title: Surg Case Rep Volume: 26 Issue: 1 Pages: 136-136
  • DOI: 10.1186/s40792-018-0544-y
  • Peer Reviewed / Open Access
• [Presentation] 保険収載後に直腸癌に対するロボット支援下手術で得られた知識と拡大手術への応用 (2021)
  • Author(s): 諸橋 一
  • Organizer: 日本外科学会
• [Presentation] 予後規定因子から考える側方郭清の適応 (2018)
  • Author(s): 諸橋 一, 坂本義之, 佐藤健太郎, 三浦卓也, 袴田健一
  • Organizer: 2018大腸肛門病学会