Application of novel gastrointestinal hormone ghrelin for improvement of QOL after upper digestive tract surgery

• Project/Area Number: 20390343
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: DOKI Yuichiro Osaka University, 医学系研究科, 教授 (20291445)
• Co-Investigator(Kenkyū-buntansha): TAKIGUCHI Shuji 大阪大学, 医学系研究科, 助教 (00301268) ; FUJIWARA Yoshiyuki 大阪大学, 医学系研究科, 講師 (40314330) ; MIYATA Hiroshi 大阪大学, 医学系研究科, 助教 (80362713) ; YAMASAKI Makoto 大阪大学, 医学系研究科, 助教 (50444518) ; KUROKAWA Yukinori 大阪大学, 医学系研究科, 助教 (10470197)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: グレリン / 体重減少 / 胃癌 / 食道癌 / 上部消化管手術 / 手術侵襲

Research Abstract

Body weight loss and appetite loss are specificically observed after upper digestive tract surgery including carcinomas of the stomach and esophagus, and strongly impaired post operative QOL. We have performed randomized clinical trial and proved that administration of synthetic ghrelin, a novel gastrointestinal hormone, successfully improved these symptoms. The clinical application of ghrelin is promising for these patients.

Research Products

• [Journal Article] Effects of ghrelin administration after total gastrectomy: a prospective, randomized, placebo-controlled phase II study. (2010)
  • Author(s): Adachi S., Takiguchi S., Okada K., Yamamoto K., Yamasaki M., Miyata H., Nakajima K., Fujiwara Y., Hosoda H., Kangawa K., Mori M., Doki Y.
  • Journal Title: Gastroenterology. 138(4) Pages: 1331-1337
• [Journal Article] Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. (2010)
  • Author(s): Yamamoto K., Takiguchi S., Miyata H., Adachi S., Hiura Y., Yamasaki M., Nakajima K., Fujiwara Y., Mori M., Kangawa K., Doki Y.
  • Journal Title: Surgery. 148(1) Pages: 31-38
• [Journal Article] Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer. (2010)
  • Author(s): Takeno A., Takemasa I., Seno S., Yamasaki M., Motoori M., Miyata H., Nakajima K., Takiguchi S., Fujiwara Y., Nishida T., Okayama T., Matsubara K., Takenaka Y., Matsuda H., Monden M., Mori M., Doki Y.
  • Journal Title: Ann Surg Oncol. 17(4) Pages: 1033-1042
• [Journal Article] Pre- and post-therapy nodal status equally affects survival of patients with oesophageal squamous cell carcinoma receiving preoperative chemoradiation. (2010)
  • Author(s): Miyata H., Yamasaki M., Takiguchi S., Nakajima K., Fujiwara Y., Mori M., Doki Y.
  • Journal Title: Oncol Rep 23(5) Pages: 1331-1337
• [Journal Article] p53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus. (2010)
  • Author(s): Makino T., Yamasaki M., Miyata H., Fujiwara Y., Takiguchi S., Nakajima K., Nishida T., Yasuda T., Matsumiya J., Mori M., Doki Y.
  • Journal Title: Ann Surg Oncol. 17 Pages: 634-642
• [Journal Article] Feasibility study of S-1 and intraperitoneal docetaxel combination chemotherapy for gastric cancer with peritoneal dissemination. (2010)
  • Author(s): Fujiwara Y., Nishida T., Takiguchi S., Nakajima K., Miyata H., Yamasaki M., Yamamoto K., Moon JH., Mori M., Doki Y.
  • Journal Title: Anticancer Research 30(4) Pages: 1335-1339
• [Journal Article] The utility of pre-operative peritoneal lavage examination in serosa-invading gastric cancer patients. (2010)
  • Author(s): Makino T., Fujiwara Y., Takiguchi S., Miyata H., Yamasaki M., Nakajima K., Nishida T., Mori M., Doki Y.
  • Journal Title: Surgery. 148(1) Pages: 96-102
• [Journal Article] Effects of ghrelin administration after total gastrectomy : aprospective, randomized, placebo-controlled phase II study. (2010)
  • Author(s): Adachi S., Takiguchi S., Okada K., Yamamoto K., Yamasaki M., Miyata H., Nakajima K., Fujiwara Y., Hosoda H., Kangawa K., Mori M., Doki Y.
  • Journal Title: Gastroenterology Volume: 138(4) Pages: 1312-1320
  • Peer Reviewed
• [Journal Article] Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction. (2010)
  • Author(s): Yamamoto K., Takiguchi S., Miyata H., Adachi S., Hiura Y., Yamasaki M., Nakajima K., Fujiwara Y., Mori M., Kangawa K., Doki Y
  • Journal Title: Surgery Volume: 148(1) Pages: 31-38
  • Peer Reviewed
• [Journal Article] Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer (2010)
  • Author(s): Takeno A., Takemasa I, Seno S., Yamasaki M., Motoori M., Miyata H., Nakajima K., Takiguchi S., Fujiwara Y., Nishida T., Okayama T., Matsubara K., Takenaka Y., Matsuda H., Monden M., Mori M., Doki Y
  • Journal Title: Ann Surg Oncol Volume: 17(4) Pages: 1033-1042
  • Peer Reviewed
• [Journal Article] Feasibility study of S-1 and intraperitoneal docetaxel combination chemotherapy for gastric cancer with peritoneal dissemination (2010)
  • Author(s): Fujiwara Y., Nishida T., Takiguchi S., Nakajima K., Miyata H., Yamasaki M., Yamamoto K., Moon JH., Mori M., Doki Y
  • Journal Title: Anticancer Research Volume: 30 Pages: 1335-1340
  • Peer Reviewed
• [Journal Article] The utility of pre-operative peritoneal lavage examination in serosa-invading gastric cancer patients (2010)
  • Author(s): Makino T., Fujiwara Y., Takiguchi S., Miyata H., Yamasaki M., Nakajima K., Nishida T., Mori M., Doki Y
  • Journal Title: Surgery Volume: 148(1) Pages: 96-102
  • Peer Reviewed
• [Journal Article] Current Limitations in endoscopic CO2 insufflation for NOTES : flow and pressure study. (2010)
  • Author(s): Nakajima K., Nishida T., Jeffrey W M., Takahashi T., Souma Y., Miyazaki Y., Iijima H., Mori M., Doki Y
  • Journal Title: Gastroenterol Endosc Volume: 72(5) Pages: 1036-1042
  • Peer Reviewed
• [Journal Article] Preoperative T staging of gastric cancer by Multi-Detector Row Computed Tomography (2010)
  • Author(s): Makino T., Fujiwara Y., Takiguchi S., Tsuboyama T., Kim T., Nushijima Y., Yamasaki M., Miyata H., Nakajima K., Mori M., Doki Y
  • Journal Title: Surgery Volume: (in press)
  • Peer Reviewed
• [Journal Article] MicroRNA-125a-5p is an independent prognostic factor in gastric cancer, and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab (2010)
  • Author(s): Nishida N., Mimori K., Fabbri M., Yokobori T., Sudo T., Tanaka F., Shibata K., Ishii H., Doki Y., Mori M
  • Journal Title: Clin Cancer Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Effects of GhrelinAdministration After Total Gastrectomy: A Prospective, Randomized. Placebo-Controlled Phase 2 Study. (2010)
  • Author(s): Adachi S., et al
  • Journal Title: Gastroenterology In Press
  • Peer Reviewed
• [Journal Article] Randomized phase II study of clinical effects of ghrelin after esophage ctomv with gastric tube reconstruction. (2010)
  • Author(s): Yamamoto K., et al
  • Journal Title: Surgery. Epub
  • Peer Reviewed
• [Journal Article] Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgerv of Gastric Cancer (2010)
  • Author(s): Takeno A., et al
  • Journal Title: Ann Surg Oncol 17(4) Pages: 1033-42
  • Peer Reviewed
• [Journal Article] Myelotoxicity of preoperative chemoradiotherapy is a significant determinant of poor prognosis in patients with T4 esophageal cancer. (2009)
  • Author(s): Miyoshi N., (Yano M)., (Takachi K)., (Kishi K)., (Noura S)., Eguchi H., (Yamada T)., (Miyashiro I)., (Ohue M)., (Ohigashi H)., (Sasaki Y)., (Ishikawa O)., Doki Y., (Imaoka S)
  • Journal Title: J Surg Oncol. 99 Pages: 302-306
• [Journal Article] Effects of neoadjuvant chemotherapy on primary tumor and lymph node metastasis in esophageal squamous cell carcinoma : additive association with prognosis. (2009)
  • Author(s): Akita H., Doki Y., Yano M., Miyata H., Miyashiro I., Ohigashi H., Ishikawa O., Nishiyama A., Imaoka S.
  • Journal Title: Dis Esophagus. 22(4) Pages: 291-297
• [Journal Article] Dickkopf-1 expression as a marker for predicting clinical outcome in esophageal squamous cell carcinoma. (2009)
  • Author(s): Makino T., Yamasaki M., Takemasa I., Takeno A., Nakamura Y., Miyata H., Takiguchi S., Fujiwara Y., Matsuura N., Mori M., Doki Y.
  • Journal Title: Ann Surg Oncol. 16(7) Pages: 2058-2064
• [Journal Article] Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy. (2009)
  • Author(s): Miyata H., (Yoshioka A)., Yamasaki M., Nushijima Y., Takiguchi S., Fujiwara Y., Nishida T., (Mano M)., Mori M., Doki Y.
  • Journal Title: Cancer. 115(14) Pages: 3324-3334
• [Journal Article] The feasibility of using biopsy samples from esophageal cancer for comprehensive gene expression profiling. (2009)
  • Author(s): (Motoori M)., Takemasa I., Yamasaki M., (Komori T)., Takeno A., Miyata H., Takiguchi S., Fujiwara Y., (Yasuda T)., (Yano M)., Matsuura N., (Matsubara K)., Monden M., Mori M., Doki Y.
  • Journal Title: Int J Oncol. 35(2) Pages: 265-271
• [Journal Article] The role of intraoperative carbon dioxide insufflating upper gastrointestinal endoscopy during laparoscopic surgery. (2009)
  • Author(s): Souma Y., Nakajima K., Takahashi T., (Nishimura J)., Fujiwara Y., Takiguchi S., Miyata H., Yamasaki M., Doki Y., Nishida T.
  • Journal Title: Surg Endosc. 23(10) Pages: 2279-2285
• [Journal Article] Sclerosing epithelioin fibrosarcoma of the liver infiltrating the inferior vena cava (2009)
  • Author(s): Tomimaru Y., Nagano H., Marubashi S., Kobayashi S., Eguchi H., Takeda Y., Tanemura M,. Kitagawa T., Umeshita K., (Hashimoto N)., (Yoshikawa H)., (Wakasa K)., Doki Y., Mori M.
  • Journal Title: World J Gastroenterol. 15(33) Pages: 4204-4208
• [Journal Article] Salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer. (2009)
  • Author(s): Miyata H., Yamasaki M, Takiguchi S, Nakajima K, Fujiwara Y, Nishida T, Mori M, Doki Y.
  • Journal Title: J Surg Oncol. 100(6) Pages: 442-446
  • NAID: 40016882370
• [Journal Article] Induction chemotherapy with docetaxel, 5-FU and CDDP (DFP) for advanced gastric cancer. (2009)
  • Author(s): Yamamoto K., Fujiwara Y., Nishida T., Takiguchi S., Nakajima K., Miyata H., Yamasaki M., Mori M., Doki Y.
  • Journal Title: Anticancer Res. 29(10) Pages: 4211-4215
• [Journal Article] A suspected [18F]fluorodeoxyglucose positron emission tomography-negative metastatic lymph node successfully diagnosed by laparoscopic staging in esophageal cancer : report of two cases. (2009)
  • Author(s): Takeno A., Takiguchi S., Yamasaki M., Miyata H., Kawabata R., (Nushijima Y)., Makino T., Fujiwara Y., Nakajima K., Nishida T., Mori M., Doki Y.
  • Journal Title: Surg Today. 39(10) Pages: 888-891
  • NAID: 10025555304
• [Journal Article] Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. (2009)
  • Author(s): Makino T., Yamasaki M., Takeno A., Shirakawa M., Miyata H., Takiguchi S., Nakajima K., Fujiwara Y., Nishida T., Matsuura N., Mori M., Doki Y.
  • Journal Title: Br J Cancer. 101(8) Pages: 1298-1306
• [Journal Article] Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma. (2009)
  • Author(s): Akita H., Zheng Z, Takeda Y, Kim C, Kittaka N, Kobayashi S, Marubashi S, Takemasa I, Nagano H, Dono K, Nakamori S, Monden M, Mori M, Doki Y, Bepler G.
  • Journal Title: Oncogene. 28(32) Pages: 1903-2909
• [Journal Article] Partial gastrectomy using natural orifice translumenal endoscopic surgery (NOTES) for gastric submucosal tumors: early experience in humans. (2009)
  • Author(s): Nakajima K., Nishida T., Takahashi T., Souma Y., Hara J., (Yamada T)., (Yoshio T)., (Tsutsui T)., (Yokoi T)., Mori M., Doki Y.
  • Journal Title: Surg Endosc. 23 Pages: 2650-2655
• [Journal Article] p53 Mutation status predicts pathological response to chemoradiotherapy in locally advanced esophageal cancer. (2009)
  • Author(s): Makino T., et al
  • Journal Title: Ann Surg Oncol. 17(3): Pages: 804-11
  • Peer Reviewed
• [Journal Article] Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus.. (2009)
  • Author(s): Makino T., et al
  • Journal Title: Br J Cancer 101(8): Pages: 1298-306
  • Peer Reviewed
• [Journal Article] Injection of LPS causes transient suppression of biological clock genes in rats. (2008)
  • Author(s): Okada K.,Yano M., Doki Y., Azama T., Iwanaga H., Miki H., Nakayama M., Miyata H., Takiguchi S., Fujiwara Y., Yasuda T., Ishida N., Monden M.
  • Journal Title: J Surg Res. 145(1) Pages: 5-12
• [Journal Article] Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination. (2008)
  • Author(s): Wada H.,Sato E., Uenaka A., Isobe M., Kawabata R., Nakamura Y., Iwae S., Yonezawa K., Yamasaki M., Miyata H., Doki Y., Shiku H., Achim A. Jungbluth, Gerd Ritter, Roger Murphy, Eric W. Hoffman, Lloyd J. Old, Monden M., Nakayama E.
  • Journal Title: Int.J.Cancer 123 Pages: 2362-2369
• [Journal Article] Use of 18F-fluorodeoxyglucose-positron emission tomography to evaluate responses to neo-adjuvant chemotherapy for primary tumor and lymph node metastasis in esophageal squamous cell carcinoma. (2008)
  • Author(s): Makino T.,Doki Y., Miyata H., Yasuda T., Yamasaki M., Fujiwara Y., Takiguchi S., Higuchi I., Hatazawa J., Monden M.
  • Journal Title: Surgery. 144(5) Pages: 793-802
• [Journal Article] Injection of LPS causes transient suppression of biological clock genes in rats. (2008)
  • Author(s): Okada K., Yano M., Doki Y., Azama T., Iwanaga H, . Miki H., Nakayama M., Miyata H., Takiguchi S., Fujiwara Y., Yasuda T., Is hida N., Modnen M.
  • Journal Title: J Sure Res. 145(1) Pages: 5-12
  • Peer Reviewed
• [Journal Article] Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination (2008)
  • Author(s): Wada H., Sato E., Uenaka Iso be M., Kawabata R., NakamuraY., Iwae S., Yonezawa K., Yamasaki M., Miyata H., Doki Y., Shiku H., Achim A. Jungbluth, Gerd Ritter, Roger Murphy, eric W. Hoffman, Lloyd J. Old, Monden M., Nakayama E.
  • Journal Title: Int. J. Cancer 123 Pages: 2362-2369
  • Peer Reviewed
• [Journal Article] Use of 18F-fluorodeoxyglucose-positron emission tomography to evaluate responses to neo-adjuvant chemotherapy for primary tumor and lymph node metastasis mesophageal squamous cell carcinoma (2008)
  • Author(s): Makino T., Doki Y., Miyata H., Yasuda T., Yamasaki M., Fujiwara Y., Takiguchi S., Higuchi I., Hatazawa J., Monden M.
  • Journal Title: Surgery 144(5) Pages: 793-802
  • Peer Reviewed
• [Presentation] 胃切除術後長期経過した体重減少患者に対するグレリン投与の臨床効果に関する臨床試験 (2010)
  • Author(s): 足立真一、瀧口修司、山崎誠、宮田博志、中島清一、藤原義之、森正樹、土岐祐一郎
  • Organizer: 第110回 日本外科学会定期学術集会
  • Place of Presentation: 名古屋
• [Presentation] 食道切除胃管再建術後患者に対するグレリン投与のランダム化第II相臨床試験 (2010)
  • Author(s): 山本和義、瀧口修司、宮田博志、日浦祐一郎、山崎誠、中島清一、藤原義之、森正樹、土岐祐一郎
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪