研究者総覧

小野 滋 (オノ シゲル)

  • 外科学講座(小児外科学部門) 教授
Last Updated :2021/12/04

研究者情報

ホームページURL

J-Global ID

研究キーワード

  • 胆嚢発癌   発生分化   分子標的療法   融合遺伝子   融合遺云子   シグナル伝達   血清診断   PAX3-FKHR   microRNA   

研究分野

  • ライフサイエンス / 外科学一般、小児外科学

経歴

  • 2011年  自治医科大学医学部准教授

学歴

  • 1985年04月 - 1991年03月   京都府立医科大学

所属学協会

  • 日本周産期・新生児医学会   日本癌学会   日本小児血液・がん学会   日本癌治療学会   日本外科学会   日本小児外科学会   

研究活動情報

論文

  • Shigeru Ono, Yuki Tsuji, Katsuhisa Baba, Yoshiko Usui, Satohiko Yanagisawa, Kosaku Maeda
    SURGERY TODAY 44 6 1184 - 1187 2014年06月 [査読有り][通常論文]
     
    The optimal management of microcystic lymphatic malformations (LMs) in children has not been established. We describe how we used the Ligasure (TM) Vessel Sealing System (LVSS) to achieve partial resection of refractory microcystic LMs in a 1-year-old boy. The child was admitted in respiratory distress caused by infection and swelling of cervical LMs. The LMs had been diagnosed prenatally, but had not decreased in size despite three treatments with OK-432 sclerotherapy. We performed direct dissection of the microcystic LMs using the LVSS with minimal intraoperative blood loss or lymphatic leakage. The LMs were resected as completely as possible without damage to the jugular vein or major nerves. His postoperative course was uneventful. Histological examination revealed complete sealing of the lymphovascular channels with obliterated lumens. Resection using the LVSS is effective and easy to perform for partial resection of microcystic LMs. We recommend the combination of initial OK-432 injection therapy and subsequent partial resection using the LVSS for refractory microcystic LMs.
  • Shigeru Ono, Kosaku Maeda, Katsuhisa Baba, Yoshiko Usui, Yuki Tsuji, Tomonori Yano, Wataru Hatanaka, Hironori Yamamoto
    Pediatric Surgery International 29 11 1103 - 1107 2013年11月 [査読有り][通常論文]
     
    Introduction: Intrahepatic bile duct (IHBD) stones are one of the most complicated morbidities that occur after Roux-en-Y hepaticojejunostomy (RYH) however, the optimal therapeutic approach is controversial. Methods: Double-balloon enteroscopy (DBE) has been widely and frequently performed even in pediatric patients. We herein report the successful management of IHBD stones by biliary lithotripsy using DBE after RYH for a choledochal cyst (CC). DBE has made it possible to perform endoscopic therapeutic intervention, including balloon dilatation of an anastomotic stricture and removal of IHBD stones, without any major complications. Conclusion: DBE is a less invasive and safe treatment method for IHBD stones in pediatric patients, which is capable of reaching the bilioenteric anastomosis after RYH for CC. © 2013 Springer-Verlag Berlin Heidelberg.
  • Kosaku Maeda, Shigeru Ono, Katsuhisa Baba
    PEDIATRIC SURGERY INTERNATIONAL 29 10 1001 - 1006 2013年10月 [査読有り][通常論文]
     
    Although many advances have improved the treatment of congenital and acquired laryngotracheal stenosis in children over the past two decades, the therapeutic decision-making process remains challenging for pediatric surgeons and otolaryngologists. Severe subglottic stenosis is a complex laryngeal injury that necessitates multiple airway procedures, and the approach depends on the exact nature of the cicatricial lesion and its effect on the vocal cord mobility. Therefore, it is imperative that the pediatric surgeons and otolaryngologists dealing with this situation should be well trained in endoscopy and laser treatment, in addition to open surgical intervention. Open re-do surgery remains the best choice in cases of severe congenital stenosis, glottic immobility, or after two to three endoscopic procedures have been performed without any significant improvement.
  • Kosaku Maeda, Shigeru Ono, Katsuhisa Baba, Insu Kawahara
    Pediatric Surgery International 29 10 1019 - 1022 2013年10月 [査読有り][通常論文]
     
    Blunt trauma to the abdomen accounts for the majority of abdominal injuries in children. Pancreatic injury is the fourth most common solid organ injury, following injuries to the spleen, liver and kidneys. The most common complications are the formation of pancreatic fistulae, pancreatitis and the development of pancreatic pseudocysts, which usually present several weeks after injury. The nonoperative management of minor pancreatic injury is well accepted however, the treatment of more serious pancreatic injuries with capsular, ductal or parenchymal disruption in pediatric patients remains controversial. Based on the data presented in this literature review, although children with pancreatic injuries (without ductal disruption) do not appear to suffer increased morbidity following conservative management, patients with ductal disruption may benefit from operative intervention. © 2013 Springer-Verlag Berlin Heidelberg.
  • Yuki Tsuji, Kosaku Maeda, Shigeru Ono, Yuko Tazuke, Satohiko Yanagisawa, Yoshiko Usui, Katsuhisa Baba, Tomonori Yano, Hironori Yamamoto
    PEDIATRIC SURGERY INTERNATIONAL 29 4 357 - 361 2013年04月 [査読有り][通常論文]
     
    Double-balloon enteroscopy (DBE) is a useful and feasible modality for evaluating small intestinal lesions, even in children. DBE makes it possible to perform biopsy, diagnosis, polypectomy and endoscopic therapies including hemostasis, tattooing and clipping of the small intestinal lesions. However, endoscopic procedures in the small intestines of children are more difficult than in adults, because the intestinal wall is thin and the lumen is narrow. A novel hybrid treatment was developed using DBE for small bowel lesions combined with transumbilical minimal incision surgery. This hybrid treatment is safe, effective, provides excellent cosmetic results and can be used as an alternative for traditional open laparotomy or endoscopic surgery.
  • Kosaku Maeda, Shigeru Ono, Yuko Tazuke, Katsuhisa Baba
    JOURNAL OF PEDIATRIC SURGERY 48 2 293 - 296 2013年02月 [査読有り][通常論文]
     
    Aim: Congenital tracheal stenosis is an obstructive airway lesion that often presents as a life-threatening emergency. We had introduced the balloon dilatation and placement of the expandable metallic airway stent as a therapeutic option, and this study aimed to clarify the long-term outcomes in pediatric patients. Methods: A retrospective review of five infants in whom balloon expandable metallic airway stents (10-40 mm long and 6-8 mm in diameter) were inserted in 1997 to 2000 was conducted. Results: There was an immediate improvement of respiratory obstruction in all five infants (aged 7 days to 12 months) with four weaned from ventilation. One child died after 9 months of palliative treatment. In all inflammation and granulation tissue developed over the stents, but this could be managed by scraping or balloon compression. Metallic stents have been in place a mean of 12 years (range 6 months to 13 years) after insertion without other complications. Four children are alive and well with their stents in place. Recently, an attempt to remove the stent was done in two patients who showed dyspnea on exertion. They underwent tracheoplasty following successful complete removal of metallic stent using cardiopulmonary bypass. Conclusion: Use of expandable metallic airway stents following balloon dilatation can be left for long periods to relieve tracheal obstruction. Development of granulation tissue is a major treatable complication. Removal of the stent was safely completed by open surgical intervention using a cardiopulmonary bypass. The airway stent may provide an important therapeutic option in selected cases with congenital tracheal stenosis. (C) 2013 Elsevier Inc. All rights reserved.
  • Yuki Tsuji, Kosaku Maeda, Yuko Tazuke, Shigeru Ono, Satohiko Yanagisawa
    PEDIATRIC SURGERY INTERNATIONAL 28 9 939 - 942 2012年09月 [査読有り][通常論文]
     
    A mesenchymal hamartoma of the chest wall is a rare benign tumor. Each case has a different clinical course as well as different radiological imaging findings, and various histopathological diagnoses. In addition, mesenchymal hamartoma is sometimes mistaken for a malignant tumor. This report presents a neonatal case of mesenchymal hamartoma of the bilateral chest wall.
  • Takuji Yamagami, Hiroshi Miura, Rika Yoshimatsu, Osamu Tanaka, Shigeru Ono, Tomoko Iehara, Hajime Hosoi, Tsunehiko Nishimura
    JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY 55 4 401 - 403 2011年08月 [査読有り][通常論文]
     
    We report the case of a 12-year-old boy with a huge liver tumour 20 cm in diameter with multiple lung metastases. Six months after systemic chemotherapy was initiated, all tumours had disappeared with the exception of the liver tumour and a tiny lung tumour 2.5 mm in diameter. Fluoroscopy-assisted thoracoscopic resection of the pulmonary nodule was performed to evaluate whether viable tumour tissue remained in the lung lesion. Before moving the patient to the operating room, the nodule was marked by Lipiodol under CT fluoroscopic guidance with the patient under local anaesthesia. This procedure allowed correct visualisation of the area that should be resected.
  • Shigehisa Fumino, Shigeru Ono, Osamu Kimura, Eiichi Deguchi, Naomi Iwai
    JOURNAL OF PEDIATRIC SURGERY 46 7 1373 - 1378 2011年07月 [査読有り][通常論文]
     
    Background/Purpose: The aim of this study was to investigate the diagnostic potential of computed tomography cholangiography (CTC) and magnetic resonance cholangiopancreatography (MRCP) in children with pancreaticobiliary maljunction (PBM). Methods: Fifty-three children with PBM were consecutively treated between 1997 and 2009. Among them, the patients who underwent CTC and/or MRCP preoperatively were enrolled in this study. Computed tomography cholangiography was examined after infusion of meglumine iodoxamate with subsequent 3-dimensional rendering. The visualization of the biliary and pancreatic duct systems was evaluated and compared with that visualized with MRCP. The findings of direct cholangiography were used as the standard of reference. Results: Of the 53 cases with PBM, 17 cases were examined by CTC, 10 cases by MRCP, and 17 with both. The extrahepatic bile tract was visualized in 32 (94.1%) of 34 patients in CTC and in all 27 patients in MRCP. The intrahepatic bile duct was more frequently demonstrated by MRCP than by CTC (96.3% vs 70.6%, P = .02). Pancreaticobiliary maljunction was noted in 13 (38.2%) of 34 with CTC and in 12 (44.4%) of 27 with MRCP. The minimum age for visualization of PBM was at 10 months in CTC and at 1 year and 11 months in MRCP, respectively. The main pancreatic duct was more frequently visualized by MRCP than by CTC (81.5% vs 8.8%, P < .001). Conclusions: Magnetic resonance cholangiopancreatography provides superior visualization of the intrahepatic duct and the pancreatic system when compared with CTC. However, it is still challenging to perform a good-quality examination in young infant. The great advantage of CTC is its ability to produce high-quality images without respiratory artifacts and that it allows accurate assessment of the presence of PBM equivalent to MRCP. (C) 2011 Elsevier Inc. All rights reserved.
  • Yasunari Sasaki, Naomi Iwai, Osamu Kimura, Shigeru Ono, Tomoki Tsuda, Eiichi Deguchi
    JOURNAL OF PEDIATRIC SURGERY 46 7 1396 - 1399 2011年07月 [査読有り][通常論文]
     
    Aims of Study: Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice. Methods: Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining. Results: In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C. Conclusion: The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future. (C) 2011 Elsevier Inc. All rights reserved.

MISC

共同研究・競争的資金等の研究課題

  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    研究期間 : 2011年 -2012年 
    代表者 : 小野 滋, 佐々木 康成
     
    本研究の目的である、小児外科の代表的疾患である難治性A型食道閉鎖症の食道-食道吻合に再生医療を用いた治療法確立を目指し、催奇形性物質であるRetinoic Acid(RA)を妊娠9日目(E9)に過剰投与して直腸肛門奇形マウスを作成を試みる予定であった。Retinoic acid 単独投与食道閉鎖症ウサギコロニーの確立従来から所属施設にて行ってきた鎖肛モデルの作成方法に準じて食道閉鎖症ウサギの作成を以下の実施計画に基づき試みる予定であった。生後8ヶ月目のNZW の雌雄を交配させ、交尾12 時間後の受精時を妊娠0日と定める。食道閉鎖症を誘導するため、20mg/kg、50mg/kg、80mg/kg、100mg/kg の4通りでRAをsesame oil を溶媒として妊娠10、11、12、13、14 日目のウサギの腹腔内に過剰投与する。妊娠25 日目から30 日目に妊娠ウサギを犠牲死させ、実体顕微鏡(ニコン製:SMZ-U)下にそれぞれの子宮より胎仔を摘出し、さらに胎仔を開胸して食道閉鎖症の有無を確認する。これらのデータを解析し、食道閉鎖症モデルウサギ作成に対するRAの至適投与量並びに投与日を検討する。実際には、所属施設の異動に伴い、各種申請の再提出や資格再取得に時間と労力を必要とし、平成23年度は研究を実施通りに進める事は、極めて困難であった。
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 2010年 -2012年 
    代表者 : 細井 創, 菊地 顕, 家原 知子, 小野 滋, 土屋 邦彦
     
    1.横紋筋肉腫の腫瘍マーカーの同定と患者血清による診断への応用現在、横紋筋肉腫に血清や体液で測定可能な腫瘍マーカーは存在しない。我々は、積紋筋肉腫患児の血清中のmiR-206の発現レベルは、他の小児がん患児に比べて高く、感度1.0、特異度0.913と高い診断精度を示し、新規腫瘍マーカーになりうることを明らかにした。また、横紋筋肉腫の存在する体腔の体腔液(脳脊髄液や胸水)においても、miR-206の発現が亢進していることを明らかにした。さらに、横紋筋肉腫の治療後にmiR-206の発現の低下を認め、後に再発した症例では発現の再上昇を認めた。miR-206は、体液全般において、横紋筋肉腫の診断や病勢における腫瘍マーカーであることが明らかになった。2.横紋筋肉腫の病態解明に基いた新規分子標的治療薬の開発胞巣型横紋筋肉腫の5年生存率は50%以下で予後不良である。我々は、胎児型横紋筋肉腫自験例に認めたキメラ遺伝子PAX3-NCO42と、胞巣型横紋筋肉腫に認めるキメラ遺伝子PAX3-FKHRと比較して検討を行った。PAX3-NCO42とPAX3-FKHRをマウス筋芽細胞に強制発現させ比較したところ、両遺伝子共に増殖を促進し、分化を抑制することを明らかにした。さらに、発現アレイを用いた解析より、両遺伝子に共通して発現の上昇している遺伝子を同定しており、これに対する阻害剤を用いて抗腫瘍効果の確認を行う。
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2010年 -2012年 
    代表者 : 佐々木 康成, 岩井 直躬, 小野 滋
     
    従来から行ってきた妊娠9日目のマウスに催奇形性物質であるレチノイン酸(RA)を過剰投与し直腸肛門奇形マウスを作成した。一方、妊娠8日目および妊娠9日目に、RA Receptor antagonistであるLE135(Kagechika H.Folia Pharmacol Jpn.132.2008)を投与した。妊娠10日目から16日目の胎仔において直腸肛門奇形や尾の形態異常誘導の可否につき検討した。また、発生異常を予防するための至適投与量ならびに至適投与日を検討した。さらに骨盤内臓器群が協調発生するメカニズムについて、マウス子宮内胎仔エレクトロポレーション法を用いることにより遠位尿道上皮近傍の上皮に特異的に発現するCre遺伝子を取り込んだShh受容細胞の位置をin vivoで追跡し、直腸肛門領域のみならず泌尿生殖系器官も含めどのようにして細胞移動、増殖を経て性質の異なる複数の器官に分化していくかを検討した。まず妊娠マウスに麻酔をかけ、下腹部の皮膚を約2cm縦方向に切開して開腹し左右いずれかの子宮を体外に出す。膀胱の位置を確認する。マイクロピペットを子宮壁、腹壁に対して垂直方向に貫通し針先が膀胱内に達したら、あらかじめ作成しておいた核酸液1μLを注入する。同様にして他の胎仔にも核酸液を注入する。PBSで電極を湿らせ、子宮の外から胎仔を挟む。33Vを50m秒、インターバルを950m秒で計5回のパルスを当てる。腹膜を鑷子で軽く持ち上げて子宮を腹腔内に還納する。反対側の子宮を取り出し、同様の操作を繰り返し施行した。
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2002年 -2002年 
    代表者 : 小野 滋
  • 文部科学省:科学研究費補助金(奨励研究(A))
    研究期間 : 2000年 -2001年 
    代表者 : 小野 滋
     
    膵胆管合流異常症における発癌機序を解明する目的で,ハムスターを用いた胆嚢癌の発癌モデルを作成し,その発癌過程における胆汁酸(ケノデオキシコール酸)および膵酵素(トリプシン)の影響を組織学的および免疫組織化学を用いて検討した.胆嚢発癌モデルの作製では高率にかつ確実に胆嚢癌を得ることができた.発癌率の調整は今後の課題であるが,発癌過程における様々な環境因子や薬剤の影響を検討するには価値のある実験モデルと考える.今回胆汁酸および膵酵素であるトリプシンは誘発胆嚢癌の発癌過程においてプロモーターとしての役割を有している可能性が示唆された.また,その組織学的検討から誘発胆嚢癌は乳頭型および管状型腺癌を呈し,周囲への浸潤性も多々認められたが,胆汁酸および膵酵素下の環境ではより浸潤性の強い組織像を呈しており興味深い結果であった.さらに免疫組織染色を用いて誘発胆嚢癌および背景胆嚢粘膜の細胞増殖活性を検討したが,胆汁酸および膵酵素の環境下では組織学的に正常と思われる胆嚢粘膜においても有意に細胞増殖活性が亢進しており,発癌における背景粘膜としての可能性を有していると考えられた.以上の結果について第24回日本膵管胆道合流異常研究会におけるシンポジウムにて発表した.


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