Establishment of the collagen patch devise against for lethal stricture following endoscopic circumferential submucosal dissection of the esophagus

• Project/Area Number: 16K09284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Saga University
• Principal Investigator: Aoki Shigehisa 佐賀大学, 医学部, 准教授 (10448441)
• Co-Investigator(Kenkyū-buntansha): 竹澤 俊明 国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門, 主席研究員 (50301297) ; 坂田 資尚 佐賀大学, 医学部, 助教 (50404158)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 食道癌 / 内視鏡的粘膜剥離術 / 筋線維芽細胞 / 線維化 / コラーゲン / コラーゲンビトリゲル / 内視鏡治療

Outline of Final Research Achievements

Extensive excision of the esophageal mucosa by endoscopic submucosal dissection (ESD) frequently evokes a luminal stricture. This study aimed to determine the efficacy of a collagen vitrigel patch (CVP) for the prevention of esophageal stricture in extensive ESD. Animals underwent circumferential esophageal ESD under general anesthesia. In CVP treatment group, artificial ulcers were covered by two CVPs. The control group underwent circumferential ESD only. The CVP-treated group showed significantly better patency rates on both the oral and anal sides of the wound area compared with the control group at day 14. The mucosal re-epithelization ratio was significantly promoted, and the extents of mucosal inflammation and fibrosis were significantly decreased by CVP treatment in the wound area. The frequency of α-smooth muscle actin-positive cells was significantly reduced in the CVP-treated group compared with the control group.

Academic Significance and Societal Importance of the Research Achievements

早期食道癌患者に対して実施される内視鏡的粘膜剥離術(ESD)では、従来の外科的食道摘出術と比較して劇的に患者への侵襲性を軽減したが、術後合併症として強固な食道狭窄が生じるため、切除面積は限定されており予防法も現在確立されていない。本研究課題で完成させた食道粘膜再生用高密度コラーゲンデバイスはESD後の食道狭窄を予防し食道癌ESDの適応範囲を拡大するものであり、患者QOLの拡大と医療費の削減が期待される。

Research Products

• [Journal Article] A high-density collagen xerogel thread prevents the progression of peritoneal fibrosis. (2018)
  • Author(s): Aoki S, Takezawa T, Nagase K, Oshikata-Mitazaki A, Morito S, Sakumoto T, Masuda M, Yamamoto-Rikitake M, Akutagawa T, Toda S.
  • Journal Title: Biomater Sci. Volume: 18 Issue: 1 Pages: 125-138
  • DOI: 10.1039/c8bm00536b
  • Peer Reviewed / Open Access
• [Journal Article] High-density collagen patch prevents stricture after endoscopic circumferential submucosal dissection of the esophagus: a porcine model (2017)
  • Author(s): Aoki S, Sakata Y, Shimoda R, Takezawa T, Oshikata-Miyazaki A, Kimura H, Yamamoto M, Iwakiri R, Fujimoto K, Toda S
  • Journal Title: Gastrointest Endosc Volume: 85 Issue: 5 Pages: 1076-1085
  • DOI: 10.1016/j.gie.2016.10.012
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 内視鏡的粘膜層剥離術後の食道狭窄を予防するコラーゲン新素材治療デバイスの開発 (2017)
  • Author(s): 青木茂久 竹澤俊明 坂田資尚 戸田修二
  • Organizer: 日本再生医療学会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-07
• [Presentation] 内視鏡的粘膜層剥離術後の食道狭窄を予防するコラーゲン新素材治療デバイスの開発 (2017)
  • Author(s): 青木茂久 竹澤俊明 坂田資尚 戸田修二
  • Organizer: 日本再生医療学会総会
• [Presentation] Collagen vitrigel patch prevents stricture following circumferential ESD of the esophagus (2017)
  • Author(s): Shigehisa Aoki, Toshiaki Takezawa, Takashi Akutagawa, Mihoko Yamamoto, Hajime Sugihara, Shuji Toda
  • Organizer: 日本病理学会
• [Presentation] 広範囲の内視鏡的粘膜層剥離術後に生じる 高度食道狭窄を予防する革新的コラーゲンデバイスの開発 (2017)
  • Author(s): 青木茂久 竹澤俊明 芥川剛至 山本美保子 戸田修二
  • Organizer: 第47回日本創傷治癒学会