Establishment of evaluation method for endoscopic esophageal mucosa permeability and its clinical application

• Project/Area Number: 26461050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Manabe Noriaki 川崎医科大学, 医学部, 教授 (50403572)
• Co-Investigator(Kenkyū-buntansha): 畠 二郎 川崎医科大学, 医学部, 教授 (00368630) ; 春間 賢 川崎医科大学, 医学部, 教授 (40156526)
• Project Period (FY): 2014-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2016: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2014: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 胃食道逆流症 / 慢性微細炎症 / プロトンポンプ阻害薬 / 治療抵抗 / 電気抵抗 / 臨床研究 / GERD

Outline of Final Research Achievements

BACKGROUND & AIMS: The first aim of this study is to validate the newly developed bioelectrical admittance method (BAM) in-vitro and in-vivo experiment. METHOD: Impedance was measured using a frequency response analyzer with Caco-2 monolayer and 3D tissue. Next, BAM was clinically applied to the evaluation of esophageal mucosal permeability in heartburn patients without esophageal mucosal break. RESULTS: Impedance was highest with monolayer Caco-2 on 8 layers of normal human dermal fibroblasts. In addition, the admittance value varied depending on the treatment course of the patient. CONCLUSION: BAM detected an abnormality of the subepithelial layer of the esophagus. This measurement was also clinically useful in assessing the permeability of the esophageal mucosa under upper gastrointestinal endoscopy.

Academic Significance and Societal Importance of the Research Achievements

本手法が確立されると、内視鏡検査で観察できる全ての消化管各部位の粘膜透過性が測定できる検査法となる。また、これまでの研究から消化管粘膜透過性の変調は、非びらん性胃食道逆流症のみならず機能性胃腸症，薬剤性消化管粘膜障害，過敏性腸症候群，潰瘍性大腸炎，クローン病などの慢性炎症性腸疾患など各種消化管疾患に幅広く関係している可能性があり、これらの疾患の病態解明にも繋がることになる。上記のことから、今後の各種消化管疾患の病態解明、治療方針決定のために幅広く臨床応用される可能性が考えられ、臨床上の有用性は極めて高いと考えられる。

Research Products

• [Journal Article] Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study. (2019)
  • Author(s): Isshi K, Matsuhashi N, Joh T, Higuchi K, Iwakiri K, Kamiya T, Manabe N, Ogawa M, Arihiro S, Haruma K, Nakada K.
  • Journal Title: J Gastroenterol. Volume: NA Issue: 6 Pages: 480-483
  • DOI: 10.1007/s00535-019-01546-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Differences in salivary secretory function between patients with erosive esophagitis and those with nonerosive reflux disease. (2018)
  • Author(s): Manabe N, Haruma K, Kusunoki H, Kamada T, Hata J.
  • Journal Title: J Gastroenterol Hepatol. Volume: 4(33) Issue: 4 Pages: 807-813
  • DOI: 10.1111/jgh.14002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 軽症・重症逆流性食道炎の治療 (2018)
  • Author(s): 眞部紀明，春間 賢
  • Journal Title: BIO Clinica Volume: 33 Pages: 329-333
• [Journal Article] SSBEとLSBE，どこがちがう？どうして違う？ (2017)
  • Author(s): 眞部紀明，春間 賢
  • Journal Title: 消化器内視鏡 Volume: 29 Pages: 1680-1685
• [Journal Article] Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study. (2017)
  • Author(s): Sakaguchi M, Manabe N, Ueki N, Miwa J, Inaba T, Yoshida N, Sakurai K, Nakagawa M, Yamada H, Saito M, Nakada K, Iwakiri K, Joh T, Haruma K.
  • Journal Title: World J Gastroenterol. Volume: 23 Issue: 2 Pages: 318-327
  • DOI: 10.3748/wjg.v23.i2.318
  • Peer Reviewed
• [Journal Article] Optimal acid suppressive treatment for adequate symptom relief and prevention of the complications of gastroesophageal reflux disease: differences in long-term clinical course and pathophysiology among disease subtypes (2017)
  • Author(s): Manabe N, Haruma K.
  • Journal Title: Esophagus Volume: 14 Issue: 2 Pages: 113-121
  • DOI: 10.1007/s10388-016-0558-0
  • NAID: 40021166161
  • Peer Reviewed
• [Journal Article] GERD治療における胃酸分泌抑制の役割 (2016)
  • Author(s): 眞部紀明
  • Journal Title: Progress in Medicine Volume: 36 Pages: 1687-1693
• [Journal Article] Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015 (2016)
  • Author(s): Katsuhiko Iwakiri, Yoshikazu Kinoshita, Yasuki Habu, Tadayuki Oshima, Noriaki Manabe, et al.
  • Journal Title: Journal of Gastroenterology Volume: 51 Issue: 8 Pages: 751-67
  • DOI: 10.1007/s00535-016-1227-8
  • Peer Reviewed
• [Presentation] 重症型逆流性食道炎の治療戦略 ―PPI抵抗例の特徴像― (2016)
  • Author(s): 眞部紀明
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザ（東京都新宿区）
  • Year and Date: 2016-04-23
• [Presentation] Differences in responsiveness of PPI in patients with NERD from the viewpoint of micro inflammation and bioelectrical admittance on esophageal mucosa (2015)
  • Author(s): 眞部紀明
  • Organizer: 第69回日本食道学会学術集会
  • Place of Presentation: パシフィコ横浜（ 神奈川県横浜市 ）
  • Year and Date: 2015-07-02