Study of exfoliated tumor cells and local recurrence after colorectal endoscopic submucosal dissection

• Project/Area Number: 18K16326
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Inoue Takashi 奈良県立医科大学, 医学部, 助教 (60623478)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸粘膜下層剥離術 / 遊離腫瘍細胞 / 局所再発 / viability / povidone iodine / implantation / 遺伝子変異 / 腸管内洗浄 / 内視鏡的粘膜下層剥離術 / 遊離細胞 / 大腸

Outline of Final Research Achievements

The viability of exfoliated tumor cells in intraluminal lavage samples after 15 colorectal endoscopic submucosal dissection were measured. The viability did not decrease over time, at the end of ESD, 3 hours, 6 hours, and 12 hours after ESD. However, the viability did significantly decrease, when 2 % povidone iodine were added.DNA samples were extracted from resected tumors and exfoliated tumor cells in intraluminal lavage samples with positive cytology. Each extracted sample was analyzed by next gene sequencer. Evaluation of gene mutations between resected tumors and exfoliated tumor cells showed 100% concordance in two patients and 94.3% concordance in two patients in the screening of 19 gene mutations.

Academic Significance and Societal Importance of the Research Achievements

今まで内視鏡治療後における局所再発の機序は証明されていなかったが、今回大腸ESDで切除した腫瘍とESD後の洗浄液中の遊離腫瘍細胞の遺伝子変異の一致率が高く、従来の内視鏡治療よりも比較的長時間の腫瘍に対する物理的刺激を伴うESD操作にて腫瘍から細胞が腸管内に遊離したと考えられ、その遊離腫瘍細胞はviabilityを持っており、大腸ESD後の局所再発の機序がimplantationであることを裏付ける結果となった。遊離腫瘍細胞のviabilityは時間経過では低下せず、消毒液付加で低下したため、大腸ESD後に消毒液を付加した液で洗浄することで大腸ESD後の局所再発の予防につながると考えられた。

Research Products

• [Journal Article] Short-term outcomes of endoscopic submucosal dissection versus laparoscopic surgery for colorectal neoplasms: An observational study (2018)
  • Author(s): Takashi Inoue, Fumikazu Koyama, Hiroyuki Kuge, Takeshi Ueda, Shinsaku Obara, Takayuki Nakamoto, Yoshiyuki Sasaki, Yasuyuki Nakamura, Masayuki Sho
  • Journal Title: Journal of the Anus, Rectum and Colon Volume: 2 Issue: 3 Pages: 97-102
  • DOI: 10.23922/jarc.2017-027
  • NAID: 130007421876
  • ISSN: 2432-3853
  • Year and Date: 2018-07-25
  • Peer Reviewed / Open Access
• [Presentation] 大腸ESD後腸管内洗浄液中遊離細胞の検討 (2018)
  • Author(s): 中本貴透、小山文一、久下博之、井上隆、佐々木義之、石岡興平、福岡晃平、岩佐陽介、松本弥生、庄雅之
  • Organizer: 第109回日本消化器病学会近畿支部例会
• [Presentation] 大腸ESD後腸管内洗浄液中遊離細胞におけるviabilityの検討 (2018)
  • Author(s): 中本貴透、小山文一、久下博之、井上隆、佐々木義之、石岡興平、福岡晃平、岩佐陽介、松本弥生、庄雅之
  • Organizer: 第73回日本大腸肛門病学会
• [Presentation] 大腸ESD後腸管内洗浄液中遊離細胞の検討 (2018)
  • Author(s): 中本貴透、小山文一、久下博之、井上隆、佐々木義之、石岡興平、福岡晃平、岩佐陽介、松本弥生、庄雅之
  • Organizer: 奈良県消化器内視鏡研究会