Development of a ghrelin supportive therapy for patients with high invasive surgery and highly morbidity risks

• Project/Area Number: 15K10099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya City University (2017); Osaka University (2015-2016)
• Principal Investigator: Takiguchi Shuji 名古屋市立大学, 大学院医学研究科, 教授 (00301268)
• Co-Investigator(Kenkyū-buntansha): 宮崎 安弘 大阪大学, 医学系研究科, 助教 (00571390) ; 黒川 幸典 大阪大学, 医学系研究科, 助教 (10470197) ; 新野 直樹 大阪大学, 医学部附属病院, 医員 (10724122) ; 土岐 祐一郎 大阪大学, 医学系研究科, 教授 (20291445) ; 山崎 誠 大阪大学, 医学系研究科, 准教授 (50444518) ; 高橋 剛 大阪大学, 医学部附属病院, その他 (50452389) ; 柳本 喜智 大阪大学, 医学部附属病院, 医員 (70645085) ; 宮田 博志 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 副部長 (80362713) ; 牧野 知紀 大阪大学, 医学部附属病院, その他 (80528620)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: グレリン / 外科侵襲 / 胃癌 / 高齢者

Outline of Final Research Achievements

Preoperative and postoperative ghrelin change after pancreatoduodenectomy (PD) and distal pancreatectomy were examined in this study. Our research revealed less change of ghrelin concentration in plasma than gastrectomy PD patients with severe morbidity, which corresponded to over Grade 3 complications according to Clavien-Dindo classification, showed a higher reduction rate of ghrelin level at postoperative day 1 compared to preoperative level than other patients. Conclusion of this study was that the individual ghrelin ration relative to preoperative value (IGR) on POD 1 after PD may be a useful marker for predicting postoperative complications.
In summary, concentration measurement of plasma ghrelin level may be useful and ghrelin administration for geriatric patients were safe as a supportive therapy in the multidisciplinary approach for gastrointestinal cancer patients.

Research Products

• [Journal Article] Plasma ghrelin suppression as an early predictor for postoperative complications after pancreatoduodenectomy. (2018)
  • Author(s): Sasaki K, Asaoka T, Eguchi H, Fukuda Y, Iwagami Y, Yamada D, Miyazaki Y, Noda T, Takahashi T, Gotoh K, Kawamoto K, Kurokawa Y, Kobayashi S, Takiguchi S, Mori M, Doki Y.
  • Journal Title: Pancreatology. Volume: 18 Issue: 1 Pages: 73-78
  • DOI: 10.1016/j.pan.2017.12.002
  • Peer Reviewed / Open Access
• [Journal Article] 高齢者外科手術の成績向上を目指した合成グレリン製剤の有用性についての検討 (2017)
  • Author(s): 瀧口 修司, 山下 公太郎, 柳本 喜智, 宮崎 安弘, 土岐 祐一郎
  • Journal Title: 大和証券ヘルス財団研究業績集 Volume: 40 Pages: 89-92
• [Journal Article] 消化器がん特に上部消化管がん治療におけるグレリンの役割 (2017)
  • Author(s): 宮﨑安弘、瀧口修司、高橋剛、黒川幸典、田中晃司、牧野知紀、山崎誠、中島清一、森正樹、土岐祐一郎
  • Journal Title: 日本静脈経腸栄養学会雑誌 Volume: 32 Pages: 811-816
  • NAID: 130007040811
• [Journal Article] Improvement of cisplatin-related renal dysfunction by synthetic ghrelin: a prospective randomised phase II trial. (2016)
  • Author(s): Yanagimoto Y, Takiguchi S, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Hosoda H, Kangawa K, Mori M, Doki Y
  • Journal Title: Br J Cancer Volume: 114 Issue: 12 Pages: 1318-1325
  • DOI: 10.1038/bjc.2016.160
  • Peer Reviewed
• [Journal Article] Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer. (2016)
  • Author(s): Yanagimoto Y, Takiguchi S, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Mori M, Doki Y
  • Journal Title: Jpn J Clin Oncol. Volume: 46 Issue: 5 Pages: 421-426
  • DOI: 10.1093/jjco/hyw004
  • Peer Reviewed
• [Journal Article] Impact of synthetic ghrelin administration for patients with severe body weight reduction more than 1 year after gastrectomy: a phase II clinical trial. (2016)
  • Author(s): Takiguchi S, Miyazaki Y, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Miyata H, Hosoda H, Kangawa K, Mori M, Doki Y.
  • Journal Title: Surg Today Volume: 46 Issue: 3 Pages: 379-385
  • DOI: 10.1007/s00595-015-1187-2
  • Peer Reviewed
• [Journal Article] Randomized Phase II Study of the Anti-inflammatory Effect of Ghrelin During the Postoperative Period of Esophagectomy. (2015)
  • Author(s): Takata A, Takiguchi S, Miyazaki Y, Miyata H, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Mori M, Kangawa K, Doki Y.
  • Journal Title: Ann Surg Volume: 262 Issue: 2 Pages: 230-236
  • DOI: 10.1097/sla.0000000000000986
  • Peer Reviewed
• [Journal Article] Effects of ghrelin administration on the early postoperative inflammatory response after esophagectomy. (2015)
  • Author(s): Takata A, Takiguchi S, Murakami K, Miyazaki Y, Miyata H, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Mori M, Kangawa K, Doki Y.
  • Journal Title: Surg Today. Volume: 45 Issue: 8 Pages: 1025-1031
  • DOI: 10.1007/s00595-014-1076-0
  • Peer Reviewed
• [Journal Article] Clinical application of ghrelin in the field of surgery. (2015)
  • Author(s): Takiguchi S, Murakami K, Yanagimoto Y, Takata A, Miyazaki Y, Mori M, Doki Y.
  • Journal Title: Surg Today. Volume: 45 Issue: 7 Pages: 801-807
  • DOI: 10.1007/s00595-014-1040-z
  • Peer Reviewed
• [Journal Article] Clinical application of ghrelin in the field of surgery. (2015)
  • Author(s): Murakami K, Takiguchi S, Miyazaki Y, Kurokawa Y, Yamasaki M, Nagano H, Mori M, Doki Y
  • Journal Title: J Surg Res. Volume: 199 Issue: 2 Pages: 450-457
  • DOI: 10.1016/j.jss.2015.06.032
  • Peer Reviewed
• [Presentation] 膵頭十二指腸切除術の合併症予測における血漿中グレリン値の有用性 (2017)
  • Author(s): 佐々木一樹, 瀧口修司 ほか
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 病的肥満症に対するLSG後リバウンド克服に向けて モデルマウスを用いたグレリン産生能変化の検討 (2017)
  • Author(s): 新野直樹, 瀧口修司 ほか
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 穹窿部およびスリーブ状胃切除後残胃におけるグレリン発現状況と体重減少および術後リバウンドの関連 (2017)
  • Author(s): 宮崎安弘, 瀧口修司 ほか
  • Organizer: 日本外科代謝栄養学会学術集会
• [Presentation] 膵切除例における周術期グレリン値の推移と臨床的意義 (2016)
  • Author(s): 佐々木一樹，瀧口修司ほか
  • Organizer: 日本消化器外科学会総会 71回
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-13
• [Presentation] 上部消化管 食道癌DCF療法におけるグレリン値と腎障害の検討 (2016)
  • Author(s): 柳本喜智，瀧口修司ほか
  • Organizer: 日本外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14