Development and clinical application of confocal laser endomicroscopy for visualization of the enteric nervous system in Hirschsprung's disease.

• Project/Area Number: 16K11354
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Keio University
• Principal Investigator: Shimojima Naoki 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (30317151)
• Co-Investigator(Kenkyū-buntansha): 藤ヶ崎 純子 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (60312021) ; 炭山 和毅 東京慈恵会医科大学, 医学部, 教授 (90385328)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸管神経 / 共焦点内視鏡 / 可視化 / ヒルシュスプルング病 / 腸管運動 / 術中迅速病理診断 / 神経叢 / 神経節細胞 / 共焦点顕微鏡 / 病理診断

Outline of Final Research Achievements

Our project has been focusing on the visualization of enteric nervous system by confocal laser endomicroscopy (CLE). The main target disease is Hirschsprung’s disease in which distal intestines lack their enteric nervous system, resulting severe constipation since early in life. We examined using resected intestines in the beginning. We confirmed clear and characteristic visualization of ladder-like enteric nervous system, smooth muscles and extrinsic thick nerve bundles. Later, we undertook the in vivo visualization. We achieved the visualization of enteric nervous system for the first time in human in 2 patients with Hirschsprung’s disease.

Academic Significance and Societal Importance of the Research Achievements

本研究を開始した動機は外科医としてより質の高い医療を提供したいという思いである。ヒルシュスプルング病の治療は遠位側の無神経節腸管を切除して正常部を肛門部に吻合することである。切除範囲を選定する方法としてこれまでは術中に腸管の一部を生検して迅速病理診断で判断していた。この病理診断は一部のみで判断せざるを得ないため正確性にかけ、正常部と無神経節部の中間である移行部で吻合してしまい、術後に頑固な便秘症状が遷延する事例が後を絶たない。これに対して光を当てることでより簡便、迅速、低侵襲に腸管神経の範囲を評価可能なCLEによる可視化技術は小児外科の教科書を書き換えるほどのインパクトがある研究である。

Research Products

• [Journal Article] TECHNICAL FEASIBILITY OF VISUALIZING MYENTERIC PLEXUS USING CONFOCAL LASER ENDOMICROSCOPY (2017)
  • Author(s): Kobayashi M, Sumiyama K, Shimojima N, Shimojima N, Ieiri S, Okano H, Kamba S, Fujimura T, Hirobe S, Kuroda T, Takahashi-Fujigasaki J.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: Epub ahead of print Issue: 9 Pages: 1604-1610
  • DOI: 10.1111/jgh.13754
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Visualization of human enteric nervous system by confocal endomicroscopy in Hirschsprung’s disease: An alternative to intraoperative histopathological diagnosis ? (2018)
  • Author(s): Shimojima Naoki
  • Organizer: PAPS 2018
  • Int'l Joint Research
• [Presentation] Visualization of human enteric nervous system using confocal endomicroscopy: As an alternative to intraoperative pathological diagnosis for Hirschsprung disease. (2018)
  • Author(s): Shimojima Naoki
  • Organizer: ENS meeting
  • Int'l Joint Research
• [Presentation] 共焦点内視鏡によるヒルシュスプルング病腸管の神経ネットワーク可視化に関する研究 (2018)
  • Author(s): 下島直樹1,2, 小林雅邦3, 樺俊介3, 藤村匠1, 家入里志4, 広部誠一1, 黒田達夫2, 藤ヶ崎純子5, 炭山和毅3
  • Organizer: 小児外科学会総会
• [Presentation] Comparison of confocal endomircoscopy analyisis of the enteric nervous system (ENS) in patients with known abnormalities and without known abnormality (2016)
  • Author(s): Kobayashi M, Shimojima N, Fujigasaki J. Kamba S, Sumiyama K
  • Organizer: Asian Pacific Digestive Week (APDW2016)
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2016-11-05
  • Int'l Joint Research
• [Book] Chapter 11 Examinations for Diagnosis. Hirschsprung's Disease and the Allied Disorders Status. Quo and Future Prospects of Treatment. (2019)
  • Author(s): Shimojima N.
  • Total Pages: 292
  • Publisher: Springer
  • ISBN: 9811336059