Novel treatment and experimental etiology of intestinal failure-associated liver disease following massive bowel resection

• Project/Area Number: 17K10555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kagoshima University
• Principal Investigator: MUKAI Motoi 鹿児島大学, 医歯学総合研究科, 客員研究員 (80468024)
• Co-Investigator(Kenkyū-buntansha): 家入 里志 鹿児島大学, 医歯学域医学系, 教授 (00363359) ; 大西 峻 鹿児島大学, 鹿児島大学病院, 特任助教 (10614638) ; 山田 和歌 鹿児島大学, 鹿児島大学病院, 特任助教 (20457659) ; 川野 孝文 鹿児島大学, 医歯学総合研究科, 客員研究員 (40457651) ; 加治 建 鹿児島大学, 鹿児島大学病院, 特任教授 (50315420) ; 武藤 充 鹿児島大学, 鹿児島大学病院, 講師 (70404522) ; 中目 和彦 鹿児島大学, 鹿児島大学病院, 講師 (70448570) ; 町頭 成郎 鹿児島大学, 医歯学総合研究科, 客員研究員 (80404523) ; 矢野 圭輔 鹿児島大学, 鹿児島大学病院, 特任助教 (30757919)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IFALD / NAFLD / ghrelin / fish oil / soybean oil / 短腸症候群 / 胆汁酸

Outline of Final Research Achievements

The AST and LDH levels significantly increased, and the accumulation of lipids in the liver was observed in the short bowel syndrome Rat. The accumulation of lipids in the liver of the rats in the short bowel syndrome Rat was attenuated by the administration of ghrelin. The administration of ghrelin has a therapeutic potential for intestinal failure-associated liver disease.
No significant differences in the serum liver or biliary enzymes were noted between the soybean oil and fish oil groups. The pathological findings and non-alcoholic fatty liver dysfunction score in the fish oil group did not show steatosis and were significantly lower than in the soybean oil group. An analysis soybean oil of the fatty acids profile in the both the soybean oil and fish oil groups did not indicate essential fatty acid deficiency. Fish oil lipid emulsion may have a protective role against steatosis of intestinal failure-associated liver disease without essential fatty acid deficiency.

Academic Significance and Societal Importance of the Research Achievements

短腸症候群ラットを用いた実験で広範囲腸管切除後の腸管不全関連肝障害の病理学的変化が非アルコール性肝障害と類似することがわかり、広範囲腸管切除後の腸管不全関連肝障害の実験的病態解明と新規治療法開発は成人領域で頻繁にみられる非アルコール性肝障害にも応用できるものと思われる。グレリンや魚油が広範囲腸管切除後の腸管不全関連肝障害を軽減することがわかり臨床での応用が期待できる。

Research Products

• [Journal Article] Novel effect of glucagon-like peptide-2 for hepatocellular injury in a parenterally fed rat model of short bowel syndrome. (2019)
  • Author(s): Yano K, Kaji T, Onishi S, Machigashira S, Nagai T, Harumatsu T, Yamada K, Yamada W, Muto M, Nakame K, Mukai M, Ieiri S.
  • Journal Title: Pediatric Surgery International Volume: 35 Issue: 12 Pages: 1345-1351
  • DOI: 10.1007/s00383-019-04560-8
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcomes of surgery for choledochal cysts: a single-institution study focusing on follow-up and late complications (2018)
  • Author(s): Mukai Motoi、Kaji Tatsuru、Masuya Ryuta、Yamada Koji、Sugita Koshiro、Moriguchi Tomoe、Onishi Shun、Yamada Waka、Kawano Takafumi、Machigashira Seiro、Nakame Kazuhiko、Takamatsu Hideo、Ieiri Satoshi
  • Journal Title: Surgery Today Volume: 48 Issue: 9 Pages: 835-840
  • DOI: 10.1007/s00595-018-1660-9
  • Peer Reviewed / Open Access
• [Journal Article] Ghrelin Stimulates Intestinal Adaptation Following Massive Small Bowel Resection (2018)
  • Author(s): Onishi S, Kaji T, Yamada W, Nakame K, Machigashira S, Yano K, Kawano M, Harumatsu T,Masuya R, Kawano T, Mukai M, Yoshioka T, Souda M, Hamada T, Tanimoto A, Ieiri S
  • Journal Title: Peptide Volume: 106 Pages: 264-267
  • DOI: 10.1016/j.peptides.2018.06.009
  • Peer Reviewed / Open Access
• [Journal Article] The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection (2018)
  • Author(s): Onishi Shun、Kaji Tatsuru、Machigashira Seiro、Yamada Waka、Masuya Ryuta、Nakame Kazuhiko、Kawano Masato、Yano Keisuke、Yamada Koji、Kawano Takafumi、Mukai Motoi、Yoshioka Takako、Tanimoto Akihide、Ieiri Satoshi
  • Journal Title: Journal of Pediatric Surgery Volume: 53 Issue: 12 Pages: 2444-2448
  • DOI: 10.1016/j.jpedsurg.2018.08.019
  • Peer Reviewed / Open Access
• [Journal Article] 回腸切除後にビタミンB12欠乏性巨赤芽球性貧血をきたした2例 (2017)
  • Author(s): 大西 峻, 向井 基, 中目和彦, 矢野圭輔, 山田耕嗣, 山田和歌, 川野孝文, 加治 建, 家入里志
  • Journal Title: 日本小児外科学会雑誌 Volume: 53 Pages: 277-281
  • NAID: 130006856044
  • Peer Reviewed / Open Access
• [Journal Article] 胆道拡張症術後の膵石合併慢性膵炎に対してDouble Roux-en-Yを用いたFrey手術が奏効した1例 (2017)
  • Author(s): 矢野圭輔, 川野孝文, 山田耕嗣, 中目和彦, 向井 基, 加治 建, 家入里志
  • Journal Title: 日本小児外科学会雑誌 Volume: 53 Pages: 925-929
  • NAID: 130006856001
  • Peer Reviewed / Open Access
• [Journal Article] Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience (2017)
  • Author(s): Kaji Tatsuru、Nakame Kazuhiko、Machigashira Seiro、Kawano Takafumi、Masuya Ryuta、Yamada Waka、Yamada Koji、Onishi Shun、Moriguchi Tomoe、Sugita Koshiro、Mukai Motoi、Ieiri Satoshi
  • Journal Title: Surgery Today Volume: 47 Issue: 11 Pages: 1391-1396
  • DOI: 10.1007/s00595-017-1534-6
  • Peer Reviewed / Open Access
• [Journal Article] A comparison of the characteristics and precision of needle driving for right-handed pediatric surgeons between right and left driving using a model of infant laparoscopic diaphragmatic hernia repair (2017)
  • Author(s): Ikee Takamasa、Onishi Shun、Mukai Motoi、Kawano Takafumi、Sugita Koshiro、Moriguchi Tomoe、Yamada Koji、Yamada Waka、Masuya Ryuta、Machigashira Seiro、Nakame Kazuhiko、Kaji Tatsuru、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 33 Issue: 10 Pages: 1103-1108
  • DOI: 10.1007/s00383-017-4144-x
  • Peer Reviewed / Open Access
• [Journal Article] The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats (2017)
  • Author(s): Shinyama Shin、Kaji Tatsuru、Mukai Motoi、Nakame Kazuhiko、Matsufuji Hiroshi、Takamatsu Hideo、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 33 Issue: 10 Pages: 1109-1114
  • DOI: 10.1007/s00383-017-4145-9
  • Peer Reviewed / Open Access
• [Journal Article] Current characteristics and management of congenital esophageal stenosis: 40 consecutive cases from a multicenter study in the Kyushu area of Japan (2017)
  • Author(s): Suzuhigashi Masaya、Kaji Tatsuru、Noguchi Hiroyuki、Muto Mitsuru、Goto Michiko、Mukai Motoi、Nakame Kazuhiko、Kawano Takafumi、Yamada Waka、Yamada Koji、Onishi Shun、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 33 Issue: 10 Pages: 1035-1040
  • DOI: 10.1007/s00383-017-4133-0
  • Peer Reviewed / Open Access
• [Presentation] The efficiency and mechanism of ω3 fatty acid on improving intestinal failure-associated liver disease in a rat model of short bowel syndrome (2019)
  • Author(s): Machigashira S, Kaji T, Onishi S, Murakami M, Yano K, Baba T, Harumatsu T, Yamada K, Yamada W, Masuya R, Kawano T, Nakame K, Mukai M, Ieiri S
  • Organizer: The 52nd Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Int'l Joint Research
• [Presentation] ω3系脂肪乳剤の腸管不全合併肝障害に対する肝予防効果 (2019)
  • Author(s): 町頭 成郎、加治 建、大西 峻、村上雅一、矢野圭輔、馬場徳朗、春松敏夫、山田耕嗣、山田和歌、 桝屋隆太、中目和彦、向井基、家入里志
  • Organizer: 第34回日本静脈経腸栄養学会定期学術集会
• [Presentation] 短腸ラットモデルにおける腸管不全合併肝障害（IFALD）に対するω３系脂肪乳剤の予防効果の検討 (2019)
  • Author(s): 町頭 成郎、加治 建、大西峻、村上雅一、矢野圭輔、馬場徳朗、春松敏夫、山田耕嗣、山田和歌、桝屋隆太、中目和彦、向井 基、家入里志
  • Organizer: 第56回日本小児外科学会学術集会
• [Presentation] A randomized trial to compare the conventional three-port laparoscopic appendectomy (2018)
  • Author(s): Mukai M, Moriguchi T, Machigashira S, Kaji T, Sugita K, Yano K, Onishi S, Yamada K,Masuya R, Kawano T, Kawano M, Nakame K, Ieiri S
  • Organizer: IPEG’s 27th Annual Congress for Endosurgery in Children（IPEG2018）
  • Int'l Joint Research
• [Presentation] The postoperative health-related quality of life of choledochal cyst patients who reach 18 years of age or older - Complications would affect mental health- (2018)
  • Author(s): Mukai M, Masuya R, Kawano M, Yano K, Onishi S, Yamada K, Yamada W, Kawano T,Machigashira S, Nakame K, Kaji T, Ieiri S
  • Organizer: Pacific Association of Pediatric Surgeons 51st Conference 2018(PAPS2018)
  • Int'l Joint Research
• [Presentation] 総排泄腔遺残における膣形成術. Postoperative observation for congenital biliary dilatation focusing on late (2018)
  • Author(s): 向井 基、山田和歌、川野孝文、加治 建、川野正人、矢野圭輔、大西 峻、山田耕嗣、桝屋隆太、町頭成郎、中目和彦、家入里志
  • Organizer: 第55回日本小児外科学会学術集会
• [Presentation] Long-term postoperative outcome of choledochal cyst focusing on follow up period and late complications: current status and problem of 110 consecutive cases in single institution (2017)
  • Author(s): Mukai M
  • Organizer: Pacific Association of Pediatric Surgeons 50th Conference 2017
  • Int'l Joint Research
• [Presentation] Characteristics and preciseness of needle driving for right handed pediatric surgeon comparing right driving with left driving using infant laparoscopic diaphragmatic hernia repair model (2017)
  • Author(s): Mukai M
  • Organizer: IPEG’s 26th Annual Congress for Endosurgery in Children
  • Int'l Joint Research