内視鏡的組織切除法における最適な粘膜下局注液の開発

• Project/Area Number: 17790438
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: 藤城 光弘 東京大学, 医学部附属病院, 助手 (70396745)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 内視鏡的組織切除術 / 局注液 / 粘膜下膨隆 / 組織障害性 / ヒアルロン酸 / グリセリン / 糖 / 内視鏡的粘膜下層剥離術 / 内視鏡的組織切除法 / 組織傷害性

Research Abstract

内視鏡的組織切除法時の最適な局注液の開発の前段階として、現在市販され臨床応用報告のある各種局注液の隆起保持能を検討した結果、ヒアルロン酸溶液、グリセオール液の隆起保持能が良好なこと、ヒアルロン酸に糖を添加することでヒアルロン酸溶液の隆起保持能を高めことができることをすでに報告してきた(Endoscopy.36:579-583,2004、Endoscopy.36:584-589,2004)。これを発展させるべく、17年度は、まず、各種局注液の組織傷害性についても検討を加え、高張液でありながらグリセオール液には組織傷害性がみられないことを明らかにした(GastrointestEndosc.62:933・42,2005)。これらの基礎的検討から、1%高分子量(1900KDa)ヒアルロン酸製剤(スベニール)とグリセオール液の混合溶液が、Best Availableな局注液であり、実際にこの溶液を用いて内視鏡的粘膜下層剥離術を行ってみると非常に良好な治療成績を示すことが、臨床例でも確認された(Gastrointest Endosc.63:178-83,2006,Gastrointest Endosc.63:243-9,2006)。18年度には、さらに、独自の局注液開発に着手すべく、ビーグル犬を用いた動物実験を精力的に行った。これにより得られた成果を述べると以下のごとくである。1.組織傷害性が認めらない最大グリセリン濃度は15%、安全域を考えると10%が妥当である、2.組織傷害性が認められない最大ブドウ糖濃度は15%、安全域を考えると10%が妥当である、3.以上より、0.125%1900KDaヒアルロン酸、10%ブドウ糖、10%グリセリン混合液が理論上、安全かつ有用な局注液である。実際に本局注液を用いて、ビーグル犬の食道および胃で内視鏡的粘膜下層剥離術を施行したところ、十分な粘膜下膨隆とともに組織傷害性のない切除標本が得られ、切除後潰瘍にも明らかな治癒遅延が見られないことが確認された。本研究成果は2006年米国消化器病週間にて発表し、本研究の内容は2007年1月、Digestive Endoscopyに原著として掲載された(Dig Endosc 19:26-31,2007)。

Research Products

• [Journal Article] Appropriate mixture of hyaluronic acid, glucose and glycerin for a submucosal fluid cushion during endoscopic submucosal dissection in the dog stomach. (2007)
  • Author(s): Fujishiro M, Kakushima N, Kodashima S, Kashimura K, Matsuura T, Muraki Y, Tateishi A, Omata M
  • Journal Title: Dig Endosc 19 Pages: 26-31
  • NAID: 10021273122
• [Journal Article] Technical feasibility of endoscopic submucosal dissection for stomach neoplasms in the elderly Japanese population. (2007)
  • Author(s): Kakushima N, Fujishiro M, Kodashima S, Muraki Y, Tateishi A, Yahagi N, Omata M
  • Journal Title: J Gastroenterol Hepatol 22 Pages: 311-314
• [Journal Article] Successful endoscopic en-bloc resection of a large laterally spreading tumor in the recto-sigmoid junction by endoscopi submucosal dissection. (2006)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Ichinose M, Omata M
  • Journal Title: Gastrointest Endosc. 63 Pages: 178-183
• [Journal Article] Successful treatment outcomes of a novel endoscopic treatment or GI tumors- endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose M, Omata M
  • Journal Title: Gastrointest Endosc. 63 Pages: 243-249
• [Journal Article] The useful combination of a higher frequency miniprobe and endoscopic submucosal dissection for the treatment of T1 esophageal cancer. (2006)
  • Author(s): Shimoyama S, Imamura K, Takeshita Y, Tatsutomi Y, Yoshikawa A, Fujishiro M, Yahagi N
  • Journal Title: Surg Endosc. 20 Pages: 434-438
• [Journal Article] The efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction (2006)
  • Author(s): Kakushima N, Yahagi N, Fujishiro M, Kodashima S, Nakamura M, Omata M
  • Journal Title: Endoscopy 38 Pages: 170-174
• [Journal Article] Multifocal nodular Fatty infiltration of the liver mimicking metastatic liver tumors : diagnosis using the liver-specific late phase of levovist-enhanced sonography. (2006)
  • Author(s): Tamai H, Shingaki N, Oka M, Shiraki T, Inoue I, Magari H, Fujishiro M, Iguchi M, Yanaoka K, Arii K, Shimizu Y, Ichinose M
  • Journal Title: J Ultrasound Med. 25 Pages: 403-406
• [Journal Article] Hemosuccus Pancreaticus : Clearly indentified by timely duodenoscopy, multiplanar volume reformation of CT image and celiac angiography. (2006)
  • Author(s): Enomoto S, Yahagi N, Fujishiro M, Oka M, Kakushima N, Iguchi M, Isayama H, Yanaoka K, Arii K, Tamai H, Shimizu Y, Ichinose M, Omata M
  • Journal Title: JMAJ (Japan Medical Association Journal) 49 Pages: 128-131
• [Journal Article] Endoscopic submucosal dissection for recurrent gastric tumor. (2006)
  • Author(s): Kodashima S, Yahagi N, Fujishiro M, Kakushima N, Nakamura M, Omata M
  • Journal Title: Dig Endosc. 18 Pages: 151-153
  • NAID: 10020342106
• [Journal Article] A case of double gastric tumors treated by endoscopic submucosal dissection plus pylorus preserving gastrectomy as a less radical treatment strategy. (2006)
  • Author(s): Nakamura M, Kakushima N, Fujishiro M
  • Journal Title: Clin Gastroenterol Hepatol
• [Journal Article] Histopathologic characteristics of gastric ulcers after endoscopic submucosal dissection. (2006)
  • Author(s): Kakushima N, Fujishiro M, Kodashima S, Kobayashi K, Tateishi A, Iguchi M, Imagawa A, Motoi T, Yahagi N, Omata M
  • Journal Title: Endoscopy 38 Pages: 412-415
• [Journal Article] Endoscopic submucosal dissection for rectal epithelial neoplasia. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose M, Omata M
  • Journal Title: Endoscopy 38 Pages: 493-497
• [Journal Article] Endoscopic submucosal dissection using flexknife. (2006)
  • Author(s): Kodashima S, Fujishiro M, Yahagi N, Kakushima N, Omata M
  • Journal Title: J Clin Gastroenterol 40 Pages: 378-384
• [Journal Article] Endoscopic submucosal dissection of esophageal squamous cell neoplasms. (2006)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Muraki Y, Ono S, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose M, Omata M
  • Journal Title: Clin Gastroenterol Hepatol 4 Pages: 688-694
• [Journal Article] Novel endoscopic hemostasis technique for use during endoscopic submucosal dissection. (2006)
  • Author(s): Enomoto S, Yahagi N, Fujishiro M, Oka M, Kakushima N, Iguchi M, Yanaoka K, Arii K, Tamai H, Shimizu Y, Omata M, Ichinose M
  • Journal Title: Endoscopy Jun 14
• [Journal Article] Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ichinose M, Omata M
  • Journal Title: Surg Laparosc Endosc Percutan Tech 16 Pages: 137-140
• [Journal Article] Management of bleeding concerning endoscopic submucosal dissection with the flex knife for stomach neoplasm. (2006)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Muraki Y, Tateishi A, Omata M
  • Journal Title: Dig Endosc 18
  • NAID: 10019376556
• [Journal Article] Endoscopic submucosal dissection for gastric neoplasia : experience with the flex-knife. (2006)
  • Author(s): Kodashima S, Fujishiro M, Yahagi N, Kakushima N, Ichinose M, Omata M
  • Journal Title: Acta Gastroenterol. Belg 69 Pages: 224-229
• [Journal Article] Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer. (2006)
  • Author(s): Fujishiro M, Oka M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Kobayashi K, Hashimoto T, Yamamichi N, Moriyama Y, Tateishi A, Ono S, Shimizu Y, Ichinose M, Miki K, Omata M
  • Journal Title: J Exp Clin Cancer Res 25 Pages: 207-212
• [Journal Article] Helicobacter pylori status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal dissection. (2006)
  • Author(s): Kakushima N, Fujishiro M, Yahagi N, Kodashima S, Nakamura M, Omata M
  • Journal Title: J Gastroenterol Hepatol 21 Pages: 1586-1589
• [Journal Article] En bloc resection of a large semicircular esophageal cancer by endoscopic submucosal dissection. (2006)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Ichinose M, Omata M
  • Journal Title: Surg Laparosc Endosc Percutan Tech 16 Pages: 237-241
• [Journal Article] Endoscopic submucosal dissection for stomach neoplasms. (2006)
  • Author(s): Fujishiro M.
  • Journal Title: World J Gastroenterol 12 Pages: 5108-5112
• [Journal Article] Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation : an experimental study using resected porcine esophagus, stomach, and colon. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ichinose M, Omata M
  • Journal Title: Surg Laparosc Endosc Percutan Tech 16 Pages: 307-311
• [Journal Article] A learning curve of endoscopic submucosal dissection for gastric epithelial neoplasms. (2006)
  • Author(s): Kakushima N, Fujishiro M, Kodashima S, Muraki Y, Tateishi A, Omata M
  • Journal Title: Endoscopy 38 Pages: 991-995
• [Journal Article] Successful nonsurgical management of perforation complicating endoscopic submucosal dissection of gastrointestinal epithelial neoplasms. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose M, Omata M
  • Journal Title: Endoscopy 38 Pages: 1001-1006
• [Journal Article] Ex-vivo study of high-magnification chromoendoscopy in the gastrointestinal tract to determine the optimal staining conditions for endocytoscopy (2006)
  • Author(s): Kodashima S, Fujishiro M, Takubo K, Kammori M, Nomura S, Kakushima N, Muraki Y, Tateishi A, Kaminishi M, Omata
  • Journal Title: Endoscopy 38 38 Pages: 1115-1121
• [Journal Article] Successful endoscopic en-bloc resection of a large laterally spreading tumor in the recto-sigmoid junction by endoscopic submucosal dissection. (2006)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Ichinose M, Omata M.
  • Journal Title: Gastrointestinal Endoscopy 63 Pages: 177-183
• [Journal Article] Successful treatment outcomes of a novel endoscopic treatment for GI tumors- endoscopic submucosal dissection using a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar. (2006)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ogura K, Kawabe T, Ichinose M, Omata M.
  • Journal Title: Gastrointestinal Endoscopy 63 Pages: 243-249
• [Journal Article] The useful combination of a higher frequency miniprobe and endoscopic submucosal dissection for the treatment of T1 esophageal cancer. (2006)
  • Author(s): Shimoyama S, Imamura K, Takeshita Y, Tatsutomi Y, Yoshikawa A, Fujishiro M, Yahagi N.
  • Journal Title: Surgical Endoscopy 20 Pages: 434-438
• [Journal Article] The efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction. (2006)
  • Author(s): Kakushima N, Yahagi N, Fujishiro M, Kodashima S, Nakamura M, Omata M.
  • Journal Title: Endoscopy 38 Pages: 170-174
• [Journal Article] Multifocal nodular Fatty infiltration of the liver mimicking metastatic liver tumors : diagnosis using the liver-specific late phase of levovist-enhanced sonography. (2006)
  • Author(s): Tamai H, Shingaki N, Oka M, Shiraki T, Inoue I, Magari H, Fujishiro M, Iguchi M, Yanaoka K, Arii K, Shimizu Y, Ichinose M.
  • Journal Title: Journal of Ultrasound in Medicine 25 Pages: 403-406
• [Journal Article] Endoscopic submucosal dissection for recurrent gastric tumor. (2006)
  • Author(s): Kodashima S, Yahagi N, Fujishiro M, Kakushima N, Nakamura M, Omata M.
  • Journal Title: Digestive Endoscopy 18 Pages: 151-153
  • NAID: 10020342106
• [Journal Article] Early detection of asymptomatic gastric cancers using serum pepsinogen levels to indicate endoscopic submucosal dissection for better quality of life. (2005)
  • Author(s): Fujishiro M, Yahagi N, Kakushima N, Kodashima S, Nakamura M, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Miyoshi H, Moriyama Y, Shimizu Y, Oka M, Ichinose M, Omata M, Miki K.
  • Journal Title: Proceedings of 6^<th> international gastric cancer congress Pages: 145-150
• [Journal Article] Clinical evaluation of the multi-bending scope in various endoscopic procedures of the upper GI tract. (2005)
  • Author(s): Yahagi N, Fujishiro M, Kakushima N, Kodashima S, Nakamura M, Omata M.
  • Journal Title: Digestive Endoscopy 17
  • NAID: 10017137984
• [Journal Article] Contrast harmonic sonographically guided radio frequency ablation for spontaneous ruptured hepatocellular carcinoma. (2005)
  • Author(s): Tamai H, Oka M, Maeda H, Shingaki N, Kanno T, Enomoto S, Shiraki T, Iguchi M, Nakazawa K, Arii K, Yanaoka K, Shimizu Y, Nakata H, Fujishiro M, Yahagi N, Shiina S, Ichinose M.
  • Journal Title: Journal of Ultrasound in Medicine 24 Pages: 1021-1026
• [Journal Article] Tissue damage of different submucosal injection solutions for endoscopic mucosal resection. (2005)
  • Author(s): Fujishiro M, Yahagi N, Nakamura M, Kashimura K, Matsuura T, Kakushima N, Kodashima S, Ono S, Kobayashi K, Hashimoto T, Yamamichi N, Tateishi A, Shimizu Y, Oka M, Ichinose M, Omata M.
  • Journal Title: Gastrointestinal Endoscopy 62 Pages: 933-942
• [Book] Endoscopic resection for early gastric cancer. (Kaminishi M, Takubo K, Mafune K (Eds).) The diversity of gastric carcinoma ; Pathogenesis, diagnosis, and therapy. (2005)
  • Author(s): Fujishiro M
  • Publisher: Springer-Verlag Tokyo