重岡 宏典 (シゲオカ ヒロノリ)

  • 医学科 教授
Last Updated :2024/03/24

コミュニケーション情報 byコメンテータガイド

  • コメント

    これまで消化器および一般外科領域の外科治療を専門に行っておりましたが、現在は救命救急センターで急性腹症だけでなく広い領域における救急患者の診断と治療に従事しています。

研究者情報

学位

  • 医学博士(近畿大学)

ホームページURL

J-Global ID

プロフィール

  • 2018年 4月 - 現在 近畿大学医学部附属病院 救命救急センター 教授

    2016年 4月 - 現在 近畿大学医学部堺病院外科 教授

    2011年 4月 - 2016年3月 大阪府立呼吸器・アレルギー医療センター 消化器・乳腺外科 主任部長

    2010年 4月 - 2011年3月 近畿大学医学部堺病院外科 講師

    2009年10月 - 2010年3月 近畿大学医学部附属病院 上部消化管外科 講師

研究キーワード

  • 救急医学   

現在の研究分野(キーワード)

    これまで消化器および一般外科領域の外科治療を専門に行っておりましたが、現在は救命救急センターで急性腹症だけでなく広い領域における救急患者の診断と治療に従事しています。

研究分野

  • ライフサイエンス / 救急医学

研究活動情報

論文

  • 気道確保手技の客観的評価のために
    植嶋 利文; 布谷 早樹子; 岩本 博司; 石部 琢也; 松島 知秀; 太田 育夫; 重岡 宏典; 福田 隆人; 浦瀬 篤史; 濱口 満英; 篠崎 広一郎
    日本救急医学会雑誌 34 12 865 - 865 (一社)日本救急医学会 2023年12月
  • Ikuo Ota; Hitoshi Takahashi; Megumi Ono; Seiki Yamamoto; Akihiro Kogita; Hiroshi Tsuda; Sadao Funai; Hironori Shigeoka; Atsushi Hiraide
    Case reports in gastroenterology 16 2 488 - 495 2022年 
    Liver abscess caused by some kinds of Streptococcus group such as Streptococcus bovis group has been recognized to associate with colorectal cancer. Streptococcus milleri group with liver abscess has not been received much attention in this point of view. Here, we report the case of a 63-year-old man who developed liver abscess with S. intermedius, which belongs to the S. milleri group. We confirmed that this case was accompanied by cecal carcinoma by colonoscopy. The tumor was a pathological lead point of intussusception of cecum. On the 26th day, open right hemicolectomy was performed. In this case, bacterial endophthalmitis was a complication due to bacteremia. The patient underwent ophthalmic surgery on the 98th day. Research investigating 16S rRNA of the mucosal colon microbiome reported that the S. intermedius gene was upregulated in patients with colorectal carcinoma. It is recommended that liver abscess with S. intermedius bacteremia should alert the clinician about the risks of carcinoma of the colon and abscess formation in distant organs. We here list the case reports of liver abscess caused by Streptococcus other than S. bovis group, which was associated with colonic carcinoma, and suggest the need for further research about S. milleri group.
  • Toshifumi Uejima; Ikuo Ota; Mitsuhide Hamaguchi; Hironori Shigeoka; Takashi Kurita; Atsushi Hiraide
    Acute Medicine & Surgery 9 1 e747  2022年01月 
    AIM: Understanding how medical students perceive emergency medical care is important in promoting education and recruitment in the field of emergency medicine. This study aimed to clarify the perceptions of undergraduate medical students on emergency medical care with a focus on comparing their perceptions before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Fourth-year undergraduate medical students were invited to complete a self-administered questionnaire in 2017 and 2020. Free comments on emergency medical care were analyzed via text mining. The relationships among categorical words were evaluated via correlation matrix and correspondence analysis. RESULTS: The number of written words per student were not significantly different between 2017 (4.9 ± 3.4) and 2020 (5.3 ± 4.1). In 2017, the most frequently used word was "busy," and the words "patients," "life," and "care" were not related to each other significantly. In 2020, the frequency of the word "busy" decreased and the word "patients" was related to "life" (P < 0.01) and "care" (P < 0.01). In the correspondence analysis, seven words including "life" and "care" were associated with "patients," which demonstrates that these words tended to occur together. CONCLUSIONS: Although the responses of the medical students regarding emergency medical care before and during the COVID-19 pandemic included similar words, their expressions tended to be related to patient care or patient life during the pandemic. This change in perception might cultivate a sense of mission and responsibility and an interest in emergency medical care among medical students.
  • 呼吸困難および起坐呼吸を呈した感染性多発性肝嚢胞の1例
    小野 恵; 太田 育夫; 福田 隆人; 重岡 宏典; 平出 敦; 大西 勝博; 高橋 均
    日本腹部救急医学会雑誌 41 7 551 - 555 (一社)日本腹部救急医学会 2021年11月
  • Takaaki Kimura; Yoshie Kubota; Yukihiro Ikeda; Hironori Shigeoka; Tomomi Inoue; Takeshi Kotake; Atsushi Hiraide
    Japanese Journal of Disaster Medicine 26 43 - 49 2021年10月 [査読有り]
  • 福田 隆人; 太田 育夫; 小野 恵; 重岡 宏典; 平出 敦; 船井 貞往; 高橋 均
    日本救急医学会雑誌 32 9 453 - 458 (一社)日本救急医学会 2021年09月 
    ガス産生性肝膿瘍は致死率の高い疾患である。起因菌はKlebsiella pneumoniaeが主体であるが,稀にC.perfringensによるものがある。急性胆嚢炎に伴いC.perfringensによるガス産生性肝膿瘍を発症し,敗血症となりDICを合併したが,救命し得た1例を経験したので報告する。症例は83歳の男性で,腹痛と発熱を主訴として受診した。来院時,白血球増多と肝逸脱酵素の上昇および黄疸を認めるとともに,低酸素血症を認めた。線溶系も亢進しており,画像上は,胆嚢頸部に胆石嵌頓が疑われるとともに,肝右葉に内部不均一なガスを伴う膿瘍形成を認め,門脈ガス血症も伴っていた。急性胆嚢炎に伴うガス産生性肝膿瘍と診断した。カルバペネム系の抗菌薬投与を含む全身的なケアを行い,第10病日に開腹下膿瘍ドレナージおよび胆嚢摘出術を施行した。術後は順調に経過し,第65病日に自宅退院となった。C.perfringensによるガス産生性肝膿瘍は,高齢者に多くみられる非外傷性の深部組織の感染症で,しかも進行が早いことから救命が難しい病態である。しかし,画像診断の活用が救急外来においてもさらに進むことにより,早期に診断される例も増加すると考えられる。今後,救命への手がかりが蓄積して系統的なアプローチが整備されることが期待される。(著者抄録)
  • Rie Kojima; Tatsuya Nishiuchi; Yoshie Kubota; Ikuo Ota; Kohei Ichinohashi; Tomohide Matsushima; Toshifumi Uejima; Hironori Shigeoka; Atsushi Hiraide
    Resuscitation plus 3 100023 - 100023 2020年09月 
    Aim: The aim of this study was to assess the perceptions of medical students with respect to out-of-hospital cardiac arrests focusing on the frequency and survival and to identify potential problems in resuscitation education. Methods: Fourth-year medical students in a six-year undergraduate educational system were asked to guess the number of out-of-hospital cardiac arrests with cardiac etiology per year in Japan, related data such as the one-month survival rate from out-of-hospital cardiac arrests with cardiac etiology and the number of deaths from traffic accidents for comparison. The guesses of students were compared with actual statistical data. Results: The incidence of out-of-hospital cardiac arrests was clearly underestimated by the students compared to the real statistics. The median guessed number of out-of-hospital cardiac arrests ranged from 6000 to 20,000 while the real statistics ranged from 73.023 to 78.302 by year (P ​< ​0.001 for all years). In contrast, the guessed number of deaths from traffic accidents was markedly overestimated: the median guessed number ranged from 8000 to 20,000 and the real statistics were 3694 to 4438 (P ​< ​0.001 for all years). The one-month survival rate was also underestimated: the guessed number was 50% and the real rate was 11.5 to 13.5% (P ​< ​0.001 for all years). Conclusions: Out-of-hospital cardiac arrests are underestimated in frequency, and survival after an arrest is overestimated by medical students. To recognize and to understand the heuristic bias in perception of learners is needed for resuscitation education in addition to promote resuscitation skills of learners.
  • Kohei Ichinohashi; Tomoaki Natsukawa; Takahiro Ueda; Hirotaka Sawano; Yasuyuki Hayashi; Hironori Shigeoka; Yasuhide Kitazawa; Atsushi Hiraide
    Open Journal of Emergency Medicine 1 9 1 - 7 2019年03月 [査読有り]
  • Ota, Ikuo; Kubota, Yoshie; Uejima, Toshifumi; Shigeoka, Hironori; Hiraide, Atsushi
    Acute Medicine & Surgery 7 1 e458  2019年 [査読有り]
     
    AIM: The objective of this study was to focus on outcomes of anaphylaxis-associated out-of hospital cardiac arrest (OHCA) in non-cardiac cases. METHODS: All residents with OHCA due to non-cardiac cause in Japan from 2013 to 2015 were included for analysis. Propensity score matching and logistic regression analyses were used to assess outcome-related factors in anaphylaxis cases and non-anaphylaxis cases. The comparison group was comprised of non-anaphylaxis cases, which consisted of other cases of non-cardiac etiology. RESULTS: A total of 375,874 OHCA cases were included, of which 148,598 were due to non-cardiac cause. In these non-cardiac OHCA cases, 147 were due to anaphylaxis, with an annual incidence of 0.04 per 100,000. In the patients' characteristics, witnessed ratio, shockable rhythm, defibrillation by emergency medical services (EMS), and treatment with adrenaline by EMS were significantly greater in the anaphylaxis cases compared with the non-anaphylaxis cases. In anaphylaxis cases, the crude 1-month survival rate (32.7% versus 5.3%) and crude favorable neurological outcomes rate (24.5% versus 2.2%) were higher compared with non-anaphylaxis cases (P < 0.001). The differences in outcomes between the two types of cases were also marked after we adjusted these variables by propensity score matching. By logistic regression analyses, administration of a drug by EMS was negatively associated with good neurological outcomes (odds ratio, 0.27; 95% confidence interval, 0.09-0.87), but bystander cardiopulmonary resuscitation was positively associated with good neurological outcomes (odds ratio, 2.33; 95% confidence interval, 0.99-5.52). CONCLUSION: Neurological outcome was markedly more favorable in cases with anaphylaxis than non-anaphylaxis cases. Further studies are needed to explain this result.
  • 重岡 宏典
    近畿大学医学雑誌 43 3-4 135 - 141 近畿大学医学会 2018年12月
  • Motohiro Tamiya; Hidekazu Suzuki; Takayuki Shiroyama; Ayako Tanaka; Naoko Morishita; Norio Okamoto; Kenichi Sakai; Hironori Shigeoka; Kunimitsu Kawahara; Tomonori Hirashima
    Investigational New Drugs 36 4 696 - 701 2018年08月 [査読有り]
     
    © 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37–51.63, p = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37–54.50, p = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98–42.49, p = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01–21.04, p = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.
  • Motohiro Tamiya; Hidekazu Suzuki; Takayuki Shiroyama; Ayako Tanaka; Naoko Morishita; Norio Okamoto; Kenichi Sakai; Hironori Shigeoka; Kunimitsu Kawahara; Tomonori Hirashima
    JOURNAL OF CLINICAL ONCOLOGY 36 15 2018年05月
  • Tomonori Hirashima; Takayuki Nagai; Hironori Shigeoka; Yoshitaka Tamura; Hiroko Yoshida; Kunimitsu Kawahara; Yoko Kondoh; Kenichi Sakai; Shoji Hashimoto; Makoto Fujishima; Takayuki Shiroyama; Motohiro Tamiya; Naoko Morishita; Hidekazu Suzuki; Norio Okamoto; Ichiro Kawase
    BMC Cancer 14 1 770  2014年 [査読有り]
     
    © 2014 Hirashima et al. Although active Mycobacterium tuberculosis (MTB) or Mycobacterium Kansasii (MK) infection could be present in patients with metastatic colorectal cancer (m-CRC), no study is available on the clinical courses and chemotherapy outcomes of these patients. The present study therefore aimed to retrospectively examine whether m-CRC patients with and without active MTB or MK infection could receive cancer chemotherapy similarly. Methods: This study enrolled 30 m-CRC patients who received first-line chemotherapy between January 31, 2006 and January 31, 2013 at our institution, The clinical courses and tumor response of those with and without active MTB or MK infection were examined and compared. Results: Of 30 m-CRC patients, 6 had active MTB infection, 1 with active MK and the other 23 had neither MTB nor MK. No significant demographic differences were observed between patients with MTB or MK and those without. Chemotherapy response rates of all patients, those with MTB or MK, and those without were 40.0%, 28.6% and 43.5%, respectively. Among patients with MTB or MK, 1 treated with bevacizumab experienced grade-3 hemoptysis while others did not report any severe toxicity. Median survival time of all studied patients, those with MTB or MK, and those without was 26.3, 36.7 and 22.6 months, respectively. No significant difference in overall survival was observed between patients with MTB or MK and those without. Multivariate analysis revealed that performance status and liver metastasis were significant prognostic factors of overall survival (P = 0.004 and 0.030, respectively), whereas other factors, including MTB or MK infection, were not. In our study, all 7 patients with MTB or MK did not experience infection relapse during or after cancer chemotherapy. Conclusions: Our results indicate that m-CRC patients with MTB or MK should be able to safely and effectively continue cancer chemotherapy to subsequently achieve comparable survival duration to those without the infection if they receive proper MTB or MK treatment.
  • 胃癌術後十二指腸皮膚瘻に対しソマトスタチンアナログが有効であった1例
    北野 義徳; 船井 貞往; 重岡 宏典; 大和 宗一; 中野 敬次; 田中 晃
    外科 73 9 1001 - 1005 (株)南江堂 2011年09月 
    62歳女。心窩部痛の出現で近医にて胃癌と診断され入院となった。圧痛はなく腫瘤も触知せず、血液、生化学、腫瘍マーカーに異常は認めなかった。上腹部正中切開で開腹したところ、肝下面に20年前の胆摘の影響による強固な癒着を認めた。M領域小彎前壁に母指頭大の腫瘍を触知し、幽門側胃切除術、Roux-en-Y再建を行い、癒着のため十二指腸断端部にPenroseドレーンを留置した。第7病日の発熱、ドレーン排液の混濁に抗生物質を投与したが著変はなく、その後ドレーン排液が消化液様に変化し、第26病日のCTで十二指腸断端周囲にfluidの貯留を認め、十二指腸瘻と診断した。絶飲食、高カロリー輸液で管理し、ドレーンから500〜800ml/日の排液および正中創離開部から滲出液を認め、ドレナージを続けたが著明な改善は認めなかった。第43病日のソマトスタチンアナログ(SMS)200μg/日の持続投与開始後よりドレーン排液量および正中創排液は減少し、300μg/日の増量でさらに減少し、第64病日の瘻孔造影でcavityは消失し正中創も閉鎖し、第99病日には十二指腸も造影されなくなりドレーンを抜去した。瘻孔閉鎖後1年6ヵ月現在、再燃の徴候は認めていない。
  • Kiyotaka Okuno; Tetsuya Horiuchi; Takashi Ishibashi; Hironori Shigeoka; Akira Hayashibe; Hideaki Tsubakihara
    HEPATO-GASTROENTEROLOGY 58 110 1598 - 1602 2011年09月 [査読有り]
     
    Background/Aims: Postoperative complications associated with gastrointestinal (GI) perforation may lead to a poor prognosis. The goal of the study was to identify factors required for the establishment of appropriate perioperative procedures in such cases.Methodology: The subjects were 51 patients with GI perforation treated from July 2007 to June 2008 in six hospitals in the Minamikawachi district.Results: The perforation sites were the large intestine in 22 cases, small intestine in 15, stomach in 7 and duodenum in 7. Postoperative complications developed in 25 cases (49%), including infection in 20 and respiratory dysfunction in 13. Hospital mortality was 25% and the major causes of death were infection and respiratory dysfunction. The mortality was 52% and 0% in patients with and without postoperative complications, respectively. The mortality was 69% in the 13 patients with postoperative respiratory dysfunction compared to 11% for patients without respiratory dysfunction. Of the 7 patients with large intestine perforation, 4 were treated with sivelestat sodium. These 4 patients had a high mean SOFA score (11.5 +/- 1.3), but 2 out of 4 survived.Conclusions: Postoperative complications occurred in approximately half of the patients with GI perforation and were associated with a poor prognosis. Prevention of respiratory dysfunction is particularly important for an improvement of outcome.
  • Tohru Takeshita; Teruhisa Ninoi; Hironori Shigeoka; Yukiyoshi Hirayama; Yukio Miki
    Osaka city medical journal 56 2 37 - 45 2010年12月 [査読有り]
     
    Small bowel obstruction caused by an internal hernia involving the sigmoid mesocolon is rare, and this condition is difficult to diagnose clinically. We herein report a case of small bowel obstruction due to an intramesosigmoid hernia that was diagnosed by a 64-row multidetector computed tomography and surgically treated.
  • M. Imano; T. Itoh; T. Satou; Y. Sogo; H. Hirai; H. Kato; A. Yasuda; Y. F. Peng; M. Shinkai; T. Yasuda; H. Imamoto; K. Okuno; H. Shiozaki; H. Ohyanagi
    EJSO 36 10 963 - 968 2010年10月 [査読有り]
     
    Background: We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients. Methods: Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (Al) and an MIB-1 index (MI) were also calculated. Results: There were no differences in Al or MI in biopsy tissue between the groups. The Al of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC. Conclusion: Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.
  • 胸部食道癌における術前・術後補助療法の有用性 胸部食道癌に対する成績向上を目指した積極的補助療法
    安田 卓司; 今本 治彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 今野 元博; 重岡 宏典; 塩崎 均
    日本消化器外科学会総会 65回 46 - 46 (一社)日本消化器外科学会 2010年07月
  • 食道粘膜下腫瘍に対する鏡視下手術の工夫
    重岡 宏典; 今本 治彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 今野 元博; 安田 卓司; 塩崎 均
    日本消化器外科学会総会 65回 73 - 73 (一社)日本消化器外科学会 2010年07月
  • 術前合併症を有する食道癌手術の治療成績
    新海 政幸; 安田 卓司; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 今野 元博; 重岡 宏典; 今本 治彦; 塩崎 均
    日本消化器外科学会総会 65回 98 - 98 (一社)日本消化器外科学会 2010年07月
  • 食道癌手術再建の工夫と実績
    白石 治; 安田 卓司; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 彭 英峰; 安田 篤; 岩間 密; 塩崎 均
    日本消化器外科学会総会 65回 152 - 152 (一社)日本消化器外科学会 2010年07月
  • 食道癌根治切除後pN(+)症例に対するJCOG9204術後補助化学療法の有用性の検証
    岩間 密; 安田 卓司; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 重岡 宏典; 今野 元博; 今本 治彦; 塩崎 均
    日本消化器外科学会総会 65回 374 - 374 (一社)日本消化器外科学会 2010年07月
  • Hironori Shigeoka; Haruhiko Imamoto; Yasumasa Nishimura; Taro Shimono; Hiroshi Furukawa; Hiroshi Imamura; Takushi Yasuda; Hitoshi Shiozaki
    World journal of gastrointestinal oncology 2 6 282 - 6 2010年06月 [査読有り]
     
    This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Roux-en-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers.
  • 【外科当直医必携】 救急外来当直医必携 症状別の初療と診断のすすめ方 吐血
    重岡 宏典; 今本 治彦; 塩崎 均
    消化器外科 33 5 661 - 663 (株)へるす出版 2010年04月
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 1 - 6 2008年 [査読有り]
     
    We prospectively compared changes in function between colonic J-pouch and straight anastomoses from 1 to 5 years after low anterior resection for rectal cancer. At 1, 3, and 5 years after surgery, functional outcome was compared between 48 patients with J-pouch reconstruction (J group) and 51 with straight anastomosis (S group), using a 17-item questionnaire (overall best, 0; overall worst, 26). At 5 years, patients with ultralow anastomoses (less than 4 cm from anal verge), had fewer bowel movements during day or night, and less urgency and soiling in the J than S group. At that time, patients with low anastomoses (5 to 8 cm above the verge) had fewer bowel movements at night and less urgency in the J than S group. Functional scores improved significantly over time for both anastomotic levels, especially in the S group. Mean scores with ultralow anastomoses were J-group, 5.6 at 1 year vs. 5.3 at 3 years (P=0.0304) vs. 3.7 at 5 years (P<0.0001); and S group, 10.2 at 1 year vs. 9.6 at 3 years (P=0.0063) vs. 7.3 at 5 years (P<0.0001). Mean scores with low anastomoses were J group, 3.4 at 1 year vs. 3.1 at 3 years (P=0.0052) vs. 2.1 at 5 years (P=0.0003); and S group, 5.2 at 1 year vs. 3.8 at 3 years (P<0.0001) vs. 2.7 at 5 years (P<0.0001). Functional outcome improved in the J and especially the S group over 5 years. However, function was better in the J than S group at all time points.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 19 - 25 2008年 [査読有り]
     
    Patients with rectal cancer who undergo an abdominoperineal resection (APR) are physically handicapped by the presence of a permanent colostomy. We compared physical conditions of patients treated by APR with those of patients treated by anterior resection (AR), and found out whether the choice of operation technique had any influence on their social and psychological conditions. We compared the postoperative physical, social, and psychological conditions of 40 patients who underwent an APR with those of 116 patients who received an AR using a questionnaire. Physical conditions in the APR group were significantly worse than those in the AR group. There were no significant differences in social conditions between the two groups and social conditions were satisfactory in both groups. However, the will to carry on life in the APR group was significantly emptier than that in the AR group. While most patients who undergo an APR return to their normal level of social condition following surgery, their will to carry on life are empty due to physical discomforts including bowel dysfunction, urinary dysfunction, and sexual dysfunction. The quality of life is impacted by multiple factors, one of which may be the presence of the colostomy.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 27 - 33 2008年 [査読有り]
     
    Functional outcome after anterior resection (AR) for rectal cancer is improved by colonic J-pouch reconstruction compared with straight anastomosis. The indications for colonic J-pouch reconstruction have yet to be determined. Therefore, we attempted to determine the level at which J-pouch reconstruction provides an advantage over straight anastomosis. There were 48 patients who underwent 5-cm colonic J-pouch reconstruction (J-pouch group) and 80 patients who underwent straight anastomosis (straight group) who were subjected to functional assessment 1 year postoperatively. The functional outcome in the J-pouch group was significantly better than that in the straight group when the distance of the anastomosis from the anal verge was less than 8 cm. The difference was particularly obvious when the level of the anastomosis was below 4 cm. However, functional outcome in the straight group when the anastomosis was between 9-12 cm from the anal verge also was satisfactory, and did not differ from that in the J-pouch group when the anastomosis was between 5 and 8 cm from the anal verge. Colonic J-pouch reconstruction is indicated when the distance of anastomosis from the anal verge is less than 8 cm, and it is particularly essential when less than 4 cm.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 13 - 18 2008年 [査読有り]
     
    In colon cancer surgery, it is recommended to perform en bloc resection involving extended lymphadenectomy, characterized as a hemicolectomy, by ligating the primary feeding artery at a high position and resecting proximal and distal 5 to 10 cm bowel margins. However, there is little evidence to unequivocally support such extensive lymphovascular resection. The distribution of nodal metastases was obtained by the clearing method in 164 patients with colon cancer. For pericolic spread: for pT1 tumors, the distance from the primary tumor to a diseased node was 2.5 cm; for pT2, the distance was less than 5 cm; for 97.0% of pT3 tumors and 93.3% of pT4 tumors with nodes involved, the distance was less than 7 cm. For central spread: for pT1 tumors, the rate of spread to central nodes was 0%; for pT2, the rate of spread was 20.0% to intermediate nodes (for tumors more than 5 cm from the feeding artery, the rate for central nodes was 0%); for pT3, the rate was 30.6% to intermediate nodes and 15.3% to main nodes; for pT4, the rate was 44.4 % to intermediate nodes and 22.2% to main nodes. For curative resection cases with pT3 tumors more than 7 cm from the feeding artery, the rate to central nodes was 0%. In T1 tumors, central node dissection is not required, but proximal and distal 3-cm margins of resection are required; in T2, central node dissection that includes the intermediate node should be performed, as well as proximal and distal 5-cm margins of resection. In T3 and T4, central node dissection that includes the main node should be performed, as well as proximal and distal 7-cm margins of resection. However, for T2 more than 5 cm from the primary feeding artery, and for T3 more than 7 cm from the primary feeding artery, proximal and distal resection alone may be adequate.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 35 - 38 2008年 [査読有り]
     
    It hits been reported that functional outcome following low anterior resection of rectal cancer is improved by construction of a colonic J-pouch compared with straight anastomosis. Hence, we tried to justify use of the sigmoid colon in the construction of a J-pouch by the analysis of regional lymph node metastases. A total of 198 patients underwent resection for rectal cancer. Node metastases were examined by the clearing method. According to Japanese General Rules, nodes were classified into the perirectal nodes (PR-N), pericolic nodes (PC-N), central intermediate nodes (C-IM-N), central main nodes (C-M-N). Metastatic rate (number of patients with node metastases/total number of patients) of PR-N was 56.6%. Metastatic rate of C-IM-N was 19.2% and that of C-M-N was 8.6%. Metastatic rate of PC-N was only 1.0%. In low anterior resection, high ligation of the inferior mesenteric artery and dissection of C-M-N, C-IM-N and PR-N are necessary. Resection of sigmoid colon is not required, and therefore, a J-pouch can be constructed using the sigmoid colon.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shiozaki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 7 - 11 2008年 [査読有り]
     
    We examined the survival benefit of pelvic exenteration for locally advanced colorectal cancer with lymph node metastases, because this issue remains controversial. Medical records of 56 patients who underwent curative pelvic exenteration for colorectal cancer were reviewed retrospectively. Nodal metastases were examined by the clearing method in 29 patients and by the conventional manual method in 27 patients. Invasion to contiguous pelvic organs was present in 45 patients (80.4%) and absent in 11 patients (19.6%). Node metastases were present in 38 patients (67.9%). Operative morbidity and mortality rates were 23.2% (13 patients) and 5.4% (3 patients), respectively. Respective 5-year survival rates were 62.2 and 81.8% in the groups with and without organ invasion (no significant difference). Five-year survival in patients with nodal metastases was 56.4% but was significantly higher, 84.6%, in patients without nodal metastases. Five-year survival in 32 patients with both organ invasion and nodal metastases was 55.6%. Long-term survival was afforded by pelvic exenteration for locally advanced colorectal cancer with nodal metastases.
  • J. Hida; T. Yoshifuji; F. Sugiura; M. Takemoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; M. Yasutomi; H. Shioraki; K. Okuno
    PROCEEDINGS OF THE XXII BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS - ISUCRS 39 - 43 2008年 [査読有り]
     
    In rectal cancer surgery, preservation of urinary and sexual function is attempted by means of operations preserving the autonomic nerves of the pelvic plexus. Emergence of residual cancer because of a more shallow plane of dissection is a problem feared with these methods, so we examined indications for pelvic plexus preservation. We studied 198 patients with rectal carcinoma who underwent abdominopelvic lymphadenectomy. Lymph nodes along the superior hemorrhoidal artery and middle hemorrhoidal artery medial to the pelvic plexus were defined as perirectal nodes (PRN), and nodes along the middle hemorrhoidal artery lateral to the pelvic plexus and along the internal iliac artery represented lateral intermediate nodes (LIN). Node metastases were examined by the clearing method. Metastasis to PRN occurred in 12.5% in patients with pT1 tumors, 28.9% of those with pT2, and 50.0% of those with rectosigmoid junctional cancer. Metastasis to LIN was absent in patients with pT1 or pT2 and was as rare as 2.5% in patients with rectosimoid junctional cancer. In patients with T1, T2 and rectosigmoid junctional cancer, perirectal node dissection is necessary, but chances of residual cancer should remain minimal when the pelvic plexus is preserved.
  • 【腫瘍外科治療の最前線】 食道の腫瘍性疾患 稀な組織型の食道腫瘍 食道悪性黒色腫、悪性リンパ腫と神経鞘腫
    重岡 宏典; 彭 英峰; 平井 紀彦; 新海 政幸; 川西 賢秀; 今野 元博; 今本 治彦; 安田 卓司; 塩崎 均
    外科治療 96 増刊 417 - 421 (株)永井書店 2007年04月 
    本邦では食道に発生する悪性腫瘍の大部分は扁平上皮癌であり、少数であるが腺癌もみられる。その他ごくまれな悪性腫瘍として、悪性黒色腫や悪性リンパ腫、GIST、癌肉腫などがあり本稿ではわれわれが経験した食道悪性黒色腫と悪性リンパ腫について述べる。食道の良性腫瘍には筋腫、ポリープ、線維腫、嚢胞、血管腫、乳頭腫、脂肪腫などがあり、平滑筋腫が最も頻度が高く、良性腫瘍の約70%を占める。非常にまれな良性腫瘍として食道神経鞘腫についても紹介する。(著者抄録)
  • Naoki Hashimoto; Tikao Yasuda; Masato Inayama; Hidemine Ho; Masayuki Shinkai; Kenshu Kawanishi; Norihiko Hirai; Motohiro Imano; Hironori Shigeoka; Haruhiko Imamoto; Hitoshi Shiozaki
    HEPATO-GASTROENTEROLOGY 54 75 796 - 798 2007年04月 [査読有り]
     
    Background/Aims: Persistence of dyspeptic symptoms after choledochoduodenostomy (CDD) is common. There is evidence that at least some of these symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study was to quantify DGR after CDD.Methodology: A total of 6 patients who had undergone cholecystectomy with a standard side-to-end CDD for choledocholithiasis or Lemmel syndrome were studied by symptom evaluation, biliary scintigraphy and endoscopy at least 6 months after surgery. Duodenogastric reflux was quantified using continuous intravenous infusion of Tc-99m-HIDA.Results: The incidence of DGR after CDD was 67% compared to healthy control. In the majority of the patients the DGR was mild to moderate, but not with the clinical symptoms.Conclusions: 99mTc-HIDA scanning of the hepatobiliary system is a reasonable and reliable method for the quantitative evaluation of DGR. CDD is associated with a high incidence of DGR, but its occurrence does not produce significant clinical symptoms.
  • 手術症例報告 食道癌術後に胸壁穿通で発症した胸骨後経路再建胃管潰瘍の1手術例
    平井 紀彦; 杉浦 史哲; 今本 治彦; 重岡 宏典; 今野 元博; 塩崎 均
    手術 60 7 1083 - 1087 金原出版(株) 2006年06月 
    63歳男.6年前に他院にて食道亜全摘(2領域郭清)+胸骨後経路胃管利用頸部吻合術を施行され,術後経過は良好であったが,10ヵ月前から右前胸部の傍胸骨に発赤と疼痛を認め,切開排膿が行われた.その後,食物通過障害も出現し入院となり精査の結果,胃管潰瘍が胸壁を穿通して皮膚瘻を形成していることが明らかとなり,保存的に9ヵ月治療したが軽快せず,紹介転院となった.入院時上部消化管造影では胃管上部に狭窄を認め,瘻孔部からの造影で胃管が造影され,内視鏡では門歯列から約36cmの前壁に潰瘍を認め,同部に瘢痕による狭窄を認め,胸部CTでは胃管の壁肥厚とそれに続いて胸骨を穿通するように胸壁に瘻孔を認めた.手術では胸骨下部及び胃管切除術+血行再建付加有茎空腸再建術を施行した.切除標本の病理組織所見では胃管中央部にUL-IVの潰瘍形成があり,胸骨を穿通するように皮膚瘻を形成していた.術後経過は順調で術後第10病日の上部消化管造影では縫合不全なく通過良好で経口摂取を開始,第27病日に退院となった
  • J Hida; T Yoshifuji; K Okuno; T Matsuzaki; T Uchida; E Ishimaru; T Tokoro; M Yasutomi; H Shiozaki
    SURGERY TODAY 36 5 441 - 449 2006年05月 [査読有り]
     
    Purpose: To evaluate the long-term functional outcome of colonic J-pouch reconstruction after low anterior resection (LAR) for rectal cancer in a prospective study. Methods: We compared the functional outcome of 46 patients who underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function using a 17-item questionnaire about different aspects of bowel function. Physiologic reservoir function was evaluated by manovolumetry. Results: Among the patients with an ultralow anastomosis (<= 4 cm from the anal verge), those in the J-group had fewer bowel movements during the day and at night, and less urgency, soiling, protective pad use, incontinence, and dissatisfaction with bowel function than those in the S-group. Among the patients with a low anastomosis (5-8 cm from the verge), those in the J-group had fewer bowel movements at night, and less urgency and soiling than those in the S-group. Moreover, reservoir function (reflected by the maximum tolerable volume, threshold volume, and compliance) was better in the J-group than in the S-group in both the ultralow and low anastomosis groups. Conclusions: J-pouch reconstruction after low anterior resection creates a better stool reservoir than straight anastomosis, especially when the anastomosis is less than 4 cm from the anal verge, resulting in a better quality of life 3 years after rectal cancer resection.
  • Shiozaki H; Imamoto H; Shigeoka H
    Nihon Geka Gakkai zasshi 107 2 73 - 76 2006年03月 [査読有り]
  • 【悪性腫瘍に対する内視鏡外科の現状とその評価】 食道癌
    塩崎 均; 今本 治彦; 重岡 宏典
    日本外科学会雑誌 107 2 73 - 76 (一社)日本外科学会 2006年03月
  • J. Hida; T. Yoshifuji; K. Okuno; M. Matsumoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; H. Shiozaki; M. Yasutomi
    ISUCRS: PROCEEDINGS OF THE XXI BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS 79 - + 2006年 [査読有り]
     
    Creation of a neorectum by constructing a colonic J-pouch has been shown to improve bowel function during the first year following low anterior resection. However, few studies of long-term reservoir function have been published. This prospective study compared the reservoir function of J-pouch and straight anastomosis 5 years after low anterior resection for rectal cancer. Bowel function was compared in 46 patients who underwent J-pouch reconstruction (J-group) and 48 patients with a straight anastomosis (S-group). Clinical status was evaluated using a 17-item questionnaire inquiring about different aspects of bowel function. Reservoir function was evaluated by manovolumetry. Among patients with a ultralow anastomosis (less than 4 cm from the anal verge), the number of bowel movements during the day and at night and urgency and soiling were less in the J-group than in the S-group. Among patients with a low anastomosis (5 to 8 cm from the verge), patients in the J-group had fewer bowel movements at night and less urgency. Reservoir function was better in the J-group than in the S-group in both the ultralow and low anastomosis groups. J-pouch reconstruction increased reservoir function and provided better a functional outcome than straight anastomosis, even 5 years after low anterior resection.
  • J. Hida; K. Okuno; T. Yoshifuji; M. Matsumoto; T. Hattori; K. Ueda; E. Ishimaru; T. Tokoro; H. Shiozaki; M. Yasutomi
    ISUCRS: PROCEEDINGS OF THE XXI BIENNIAL CONGRESS OF THE INTERNATIONAL SOCIETY OF UNIVERSITY COLON AND RECTAL SURGEONS 73 - + 2006年 [査読有り]
     
    Bowel function after low anterior resection for rectal cancer with colonic J-pouch reconstruction is more normal than after conventional straight anastomosis. However, few reports have examined the function of colonic J-pouch reconstruction in the elderly. Good function would obviate the need for colostomy, which is sometimes performed because of concern over fecal incontinence, which increases with age. The present study evaluated the function of colonic J-pouch reconstruction in elderly individuals 75 years or older. Functional outcome was compared in 20 patients 75 years or older (older group) and 87 patients 74 years or younger (younger group) 3 years after colonic J-pouch reconstruction, using a functional scoring system with a 17-item questionnaire (score range, 0 (overall good) to 26 (overall poor)). Function in the older group was satisfactory and was similar to that in the younger group (functional score: older group, 4.2 vs. younger group, 4.1). Of the 17 items in the questionnaire, only the use of laxatives or glycerine enemas was more common in the older than in the younger group (85.0% vs. 59.8%; P= 0.0335). Elderly patients with low anterior resection with colonic J-pouch reconstruction provides excellent functional outcome, including continence. Colonic J-pouch reconstruction is a highly preferable alternative to permanent colostomy in elderly patients undergoing low anterior resection.
  • N. Hashimoto; M. Inayama; M. Fujishima; H. Ho; M. Shinkai; N. Hirai; K. Kawanishi; M. Imano; H. Shigeoka; H. Imamoto; H. Shiozaki
    DISEASES OF THE ESOPHAGUS 19 5 346 - 349 2006年 [査読有り]
     
    The effect of gastrectomy on the subsequent development of esophageal cancer was investigated. Duodenogastroesophageal reflux is thought to be common in patients after distal gastrectomy, but whether this contributes to the development of esophageal cancer in such patients is controversial. We retrospectively evaluated 153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer between January 2002 and July 2005. They were divided into two groups, according to whether or not they had previously undergone a gastrectomy: group 1, comprising 14 patients who had undergone gastrectomy and group 2, comprising 139 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6 years) compared with Billroth II (29.7 +/- 3.2 years), although the difference did not reach its statistical significance (P = 0.11). Moreover, the proportion of lower third tumors in patients after gastrectomy was significantly higher compared with that of the patients with intact stomach. These findings suggest that a history of gastrectomy is associated with more lower-third squamous cell esophageal carcinoma.
  • 塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 平井 紀彦; 新海 政幸; 川西 賢秀; 彭 英峰
    臨床外科 60 13 1541 - 1547 (株)医学書院 2005年12月
  • J Hida; K Okuno; M Yasutomi; T Yoshifuji; T Matsuzaki; T Uchida; E Ishimaru; T Tokoro; H Shiozaki
    JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 201 2 217 - 222 2005年08月 [査読有り]
     
    BACKGROUND: Metastasis to regional lymph nodes from colon cancer is an important prognostic factor. In the TNM classification, node metastases are classified into three grades based on the number of metastatic nodes. In the japanese General Rules for Clinical and Pathologic Studies on Cancer of the Colon, Rectum, and Anus (JGR), node metastases are classified into four grades based on the distribution of metastatic nodes. STUDY DESIGN: Based on the findings of node metastases in 164 patients with colon cancer obtained by the clearing method, node classifications by the JGR and TNM classifications were compared. RESULTS: The case distribution by the JGR grading was 41.5% in n (-), 29.3% in n1 (+), 18.3% in n2 (+), and 11.0% in n3 (+) disease. In the TNM classification, the distribution was 23.8% in pN1 and 34.8% in pN2 disease. The 5-year survival rate by the JGR was 98.4% in n (-), 74.3% in n1 (+), 51.2% in n2 (+), and 30.0% In n3 (+) disease; in TNM classification, this rate was 76.0% in pN1 and 45.0% in pN2 disease. CONCLUSIONS: In the classification of regional node metastases from colon cancer, the JGR classification showed a wider range in distribution and 5-year survival rate compared with the TNM system.
  • 糸・針・持針器
    重岡 宏典; 今本 治彦; 塩崎 均
    オペナーシング 20 6 94 - 95 メディカ出版 2005年06月 
    手術時に使用する糸,針,持針器について絹糸と吸収糸の違いやそれぞれの使用法と種類など,さらに針と持針器の種類と特徴について解説した。
  • 早期胃癌に対する空腸間置再建を伴う噴門側胃切除術のQOLからみた評価
    田中 晃; 重岡 宏典; 橋本 直樹; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 塩崎 均
    Acta Med Kinki Univ 30 1 31 - 37 近畿大学 2005年06月 
    噴門部早期胃癌に対する逆流防止機構の付加を伴う噴門側胃切除,空腸間置再建術は,食道胃吻合術と比較し、術後のQOLの面から優れた方法である。(英文)
  • 【外科手術教育の方法と実践 積極的に学ぶ系統的手術教育】 助手の役割と場の作り方
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 平井 紀彦
    手術 59 5 607 - 612 金原出版(株) 2005年05月
  • 【外科専門医に必要な消化管・腹部内臓手術手技】 下咽頭・頸部食道癌手術(切除)
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 川西 賢秀; 彭 英峰
    手術 59 6 711 - 718 金原出版(株) 2005年05月
  • 【術中損傷のリカバリー法】 損傷修復のための基本手技
    塩崎 均; 今本 治彦; 新海 政幸; 重岡 宏典; 今野 元博; 平井 紀彦
    手術 59 3 303 - 308 金原出版(株) 2005年03月
  • 川西 賢秀; 彭 英峰; 新海 政幸; 平井 紀彦; 今野 元博; 重岡 宏典; 今本 治彦; 塩崎 均
    臨床外科 60 2 187 - 192 (株)医学書院 2005年02月
  • J Hida; T Yoshifuji; T Tokoro; K Inoue; T Matsuzaki; K Okuno; H Shiozaki; M Yasutomi
    DISEASES OF THE COLON & RECTUM 47 10 1578 - 1585 2004年10月 [査読有り]
     
    Few reports on the long-term functional outcome of colonic J-pouch reconstruction have been published, and data comparing J-pouch and straight reconstruction are contradictory. This prospective study compares the functional outcome of colonic J-pouch and straight anastomosis five years after low anterior resection for rectal cancer. METHODS: Functional outcome was compared in 46 patients with J-pouch reconstruction (J-group) and 48 patients with straight anastomosis (S-group). Clinical status was evaluated with a 17-item questionnaire inquiring about different aspects of bowel function. Reservoir function was evaluated by manovolumetry. The Fisher's exact test and Wilcoxon's rank-sum test were used to compare categoric and quantitative data, respectively. RESULTS: Among patients with an ultralow anastomosis (less than or equal to4 cm from the anal verge), the number of bowel movements during the day (greater than or equal to5, 4.3 vs. 29.2 percent; P = 0.028)and at night (>1/week, 4.3 vs. 33.3 percent; P = 0.013) and urgency (4.3 vs. 33.3 percent; P = 0.013) and soiling (21.7 vs. 50.0 percent; P = 0.043) were less in the J-group than in the S-group. Among patients with a low anastomosis (5 to 8 cm from the verge), patients in the J-group had fewer bowel movements at night (>1/week, 0 vs. 20.8 percent; P = 0.028) and less urgency (0 vs. 20.8 percent; P = 0.028). Reservoir function was better in the J-group than in the S-group in both the ultralow (maximum tolerable volume (mean), 101.7 vs. 76.3 ml; P = 0.004; threshold volume (mean), 46.5 vs. 30.4 ml; P < 0.001; compliance (mean), 4.9 vs. 2.5 ml/cm H2O; P < 0.001) and low-anastomosis (maximum tolerable volume, 120.4 vs. 97.9 ml; P < 0.001; threshold volume, 58.3 vs. 40.8 ml; P < 0.001; compliance, 5.2 vs. 3.1 ml/cm H2O; P < 0.001) groups. CONCLUSIONS: J-pouch reconstruction increased reservoir function and provided better functional outcome than straight anastomosis, even five years after surgery, especially in patients whose anastomosis is less than 4 cm from the anal verge.
  • 【手術で役立つ臨床局所解剖の知識】 喉頭摘出を伴う頸部食道癌手術
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 平井 紀彦; 川西 賢秀; 西川 正康
    手術 58 10 1533 - 1539 金原出版(株) 2004年09月
  • 【はじめての消化器外科手術】 頸部食道癌手術
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 平井 紀彦; 川西 賢秀; 西川 正康
    手術 58 6 777 - 784 金原出版(株) 2004年05月
  • Shiozaki H; Shigeoka H; Imamoto H; Imano M
    Nihon Geka Gakkai zasshi 105 4 275 - 280 2004年04月 [査読有り]
  • 【救急マニュアル2004】 主要疾患の救急対応 消化器系 食道穿孔・食道狭窄
    塩崎 均; 重岡 宏典; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 西川 正康
    綜合臨床 53 増刊 1107 - 1112 (株)永井書店 2004年04月
  • 【Oncogenic emergencyとその対応】 食道癌
    塩崎 均; 重岡 宏典; 今本 治彦; 今野 元博
    日本外科学会雑誌 105 4 275 - 280 (一社)日本外科学会 2004年04月 
    食道悪性腫瘍による食道穿孔や食道狭窄は経験することが比較的多いが,食道異物による食道穿孔や特発性食道破裂は稀な疾患である.悪性腫瘍による穿孔の治療法は現状においては穿孔部位によって異なると考えている.異物による食道穿孔の治療は,異物の除去,起炎菌の同定と適切な抗生剤使用ならびにドレナージである.いずれの疾患にせよ,刻々と変化する患者の状況を正しく把握し,次の手を考えながら治療することが大切である
  • Hironori Shigeoka; Hitoshi Shiozaki
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 10 2 69 - 70 2004年04月 [査読有り]
  • 食道穿孔・食道狭窄
    塩﨑 均; 重岡 宏典; 今本 治彦; 今野 元博; 平井 紀彦; 新海 政幸; 川西 賢秀; 西川正康
    総合臨床 53 487 - 492 2004年
  • 胃および十二指腸
    塩﨑 均; 今本 治彦; 重岡 宏典; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸
    ナースのための消化器外科 57 - 85 メディカ出版 2004年
  • 咽頭摘出を伴う頚部食道癌手術
    塩﨑 均; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 平井 紀彦; 川西 賢秀
    手術 58 4 1533 - 1540 2004年
  • 吉田 敏郎; 大東 弘治; 重岡 宏典; 今本 治彦
    近畿大学医学雑誌 28 4 359 - 367 近畿大学医学会 2003年12月 
    悪性腫瘍の増殖,進展にエリスロポエチン(EPO)およびエリスロポエチンレセプター(EPOR)が関与している可能性があることに着目し,原発性胃癌を対象として,腫瘍組織,正常組織,患者および正常人血清中のEPO値を測定し各々の比較検討を行った.さらに,ヌードマウスに原発性胃癌組織を移植しEPOR拮抗剤投与を行い,移植腫瘍に対する薬物の影響について評価した.血清EPO値は胃癌症例で有意に高値を示し,リンパ節転移の有無と有意に相関した.組織中のEPO値は腫瘍および正常組織間に有意差を認めなかった.ヌードマウス移植腫瘍においてはEMP9投与群で有意にEPOR陽性細胞および新生血管数が減少し,その40%に石灰沈着像を認めた.EPO値は原発性胃癌において,リンパ節転移と有意な相関を認め,EPO・EPOR情報伝達を阻害することにより腫瘍細胞の増殖および血管新生を抑制する可能性を有することが示唆された
  • 【手術助手の全て 経験を無駄にしないコツ,役割,配慮】 助手の心構えと「べからず集」
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博
    消化器外科 26 10 1451 - 1455 (株)へるす出版 2003年09月 
    手術は術者,麻酔医,看護師,助手の共同作業であり,チームワークが求められる作業である.助手は術者,麻酔医,看護師のチームワークをまとめる役割を担うと共に,手術をリードするくらいの心構えが必要である.そこで,手術手技研究会でまとめた約28年前と10年前の「べからず」集を参照しながら,助手としての役割と配慮を通してのよい手術とはというテーマについて述べた.この「べからず」集を見直すことによって,よりよい助手になることが優れた術者になる近道であることが改めて認識された
  • 【食道癌治療の進歩】 食道癌の手術治療の最前線 手術侵襲の軽減化(小切開手術)
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 矢野 雅彦
    癌と化学療法 30 7 923 - 928 (株)癌と化学療法社 2003年07月 
    著者等は,胸腔鏡を併用することにより良好な光量(視野)を得ることができることから,10cmの小開胸創で食道癌手術を行っている.又,腹部操作も腹腔鏡補助下の小切開創で行う術式(HALS)を基本術式としている.胸部食道癌の手術の第一のポイントは,両側反回神経沿いリンパ節(No.106-rec)の郭清である.第二のポイントは,癌の浸潤がない場合は両側迷走神経の肺枝や両側気管支動脈の温存,また奇静脈弓や胸管を温存し,侵襲を最小限度にとどめていることである.開胸,開腹創の大きさは創部痛を介して術後早期の呼吸機能とも重大な関連性をもっており,手術創を小さくすることが術後の合併症の軽減に関与すると予測される
  • 【頸胸境界部食道癌の治療方針と手術手技】 音声を考慮した切除・再建術
    塩崎 均; 重岡 宏典; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀
    手術 57 8 795 - 802 金原出版(株) 2003年07月
  • 【ここまで知っておきたい癌の薬物療法】 各臓器癌における薬物療法の実際 食道癌の化学療法と化学放射線療法
    重岡 宏典; 塩崎 均
    臨牀と研究 80 7 1213 - 1215 大道学館出版部 2003年07月
  • Yasumasa Nishimura; Ryuta Koike; Kiyoshi Nakamatsu; Shuichi Kanamori; Minoru Suzuki; Hironori Shigeoka; Hitoshi Shiozaki
    Japanese journal of clinical oncology 33 7 341 - 5 2003年07月 [査読有り]
     
    BACKGROUND: We carried out the present study to investigate the feasibility and effectiveness of concurrent chemoradiotherapy (CT-RT) for postoperative recurrent esophageal cancer, which are, at present, unclear. METHODS: Between 1998 and 2002, 16 patients with postoperative loco-regional recurrence of esophageal cancer, and two patients with incompletely resected esophageal cancer were treated with concurrent CT-RT. Patients received protracted infusion of 5-FU 250-300 mg/m(2) on days 1 to 14, 1 hour infusion of cisplatin 10 mg/body on days 1 to 5 and 8 to 12, and a concurrent radiotherapy (RT) dose of 30 Gy in 15 fractions over 3 weeks. This treatment schedule was repeated twice with a gap of 1 week, for a total RT dose of 60 Gy administered over 7 weeks. RESULTS: Of the 18 patients, 13 (72%) completed the CT-RT protocol. A total RT dose of 60 Gy was administered for all except two patients, and doses of chemotherapy were reduced for five patients. Although grade 3 hematological toxicities were frequently noted, non-hematological toxicities of grades 3 and 4 were few. Of the 18 tumors, five (28%) showed complete response (CR). For patients without prior chemotherapy, the CR rate was 40% (4/10). The 2-year survival rate of 13 patients without distant metastases was 19%, with a median survival time of 9.5 months. CONCLUSION: The concurrent CT-RT protocol appears feasible and effective for patients with postoperative recurrent or residual esophageal cancer.
  • K Okuno; Kawai, I; N Hirai; H Narimatsu; M Yasutomi
    HEPATO-GASTROENTEROLOGY 50 51 756 - 760 2003年05月 [査読有り]
     
    Background/Aims: As sialyl Lewis X is a ligand of the selectin family, it has been proposed that sialyl Lewis X-rich colon cancer cells metastasize to the liver by adhesion to selectins on hepatic endothelial cells. However, little is known about the interaction between sialyl Lewis X and hepatic immune cells. We evaluated the role of sialyl Lewis X in liver metastasis in view of liver-associated immunity. Methodology: RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, which exhibited high metastatic potential to the liver, were used. In an attempt to investigate the underlying basis for the difference in hepatic metastasis formation, we assessed the susceptibility of both cell lines to lysis by hepatic sinusoidal lymphocytes in Cr-51-release assays, and the expression of a number of carbohydrate antigens by both cell lines by flow cytometry. Results: Hepatic sinusoidal lymphocytes mainly consist of natural cytotoxic lymphocytes, including NKT cells. The H4 colonic cancer subclone showed decreased susceptibility to lysis by hepatic sinusoidal lymphocytes, as compared to the parent cell line. In addition, a significant increase of sialyl Lewis X expression was noted in the H4 subclone. Neuraminidase treatment of H4 cells increased their susceptibility to hepatic sinusoidal lymphocyte-mediated killing. Furthermore, rats inoculated with neuraminidase-treated H4 cells produced fewer metastatic nodules in the liver than those inoculated with untreated H4 cells. Conclusions: Sialyl Lewis X expression in tumor cells reduced their susceptibility to hepatic sinusoidal lymphocyte-mediated killing, and thus, may facilitate the ability of the tumor cells to metastasize to the liver.
  • 胃切除後の食道癌
    塩﨑 均; 重岡 宏典; 今野 元博; 今本 治彦
    臨床と研究 80 5 99 - 102 大道學館出版部 2003年05月
  • 胃切除後の食道癌
    塩崎 均; 重岡 宏典; 今野 元博; 今本 治彦
    臨牀と研究 80 5 917 - 920 大道学館出版部 2003年05月
  • 【施設別胸部食道癌手術のプロトコール 我々の手術方針と手技】 近畿大学の手術方針と手技 手術侵襲の軽減化 小切開手術
    塩崎 均; 今本 治彦; 重岡 宏典; 平井 紀彦; 黒田 幸作; 川西 賢秀
    手術 57 4 443 - 448 金原出版(株) 2003年04月
  • 【安全・確実に行うための縫合・吻合法の全て】 縫合・吻合法の実際 食道切除後の再建術 遊離空腸間置術
    塩崎 均; 今本 治彦; 重岡 宏典; 平井 紀彦; 川西 賢秀
    外科治療 88 増刊 493 - 498 (株)永井書店 2003年03月 
    食道再建術としての遊離空腸間置術は,microsurgeryの進歩がもたらした術式である.顕微鏡下の血管吻合手技が安全,確実に行われるようになり,食道切除(とくに頸部食道癌に対する頸部食道切除)後の食道再建術の1つの術式として確立した.遊離空腸間置術の実際(遊離空腸脚の採取,血管吻合の血管の選択,咽頭空腸吻合,空腸食道吻合),再建胃管の部分壊死に対する術式,合併症と対策について概説した
  • 【食道・胃穿孔の治療方針と手術】 異物による食道穿孔
    塩崎 均; 田中 晃; 今本 治彦; 重岡 宏典; 平井 紀彦; 川西 賢秀
    手術 56 12 1893 - 1899 金原出版(株) 2002年11月
  • 【食道癌治療とQOL】 手術侵襲の軽減化 小切開手術
    塩崎 均; 田中 晃; 今本 治彦; 重岡 宏典; 川西 賢秀; 平井 紀彦; 石川 真平; 奥野 清隆; 矢野 雅彦
    外科治療 87 4 356 - 362 (株)永井書店 2002年10月 
    食道癌手術においては胸管,奇静脈弓,迷走神経肺枝,気管支動脈などを温存することが,機能温存手術であり,縮小手術であると考えている.その一環として10cm開胸創での手術を位置づけている.食道切除術を胸腔鏡補助下で行うことにより,10cmの開胸創での手術操作が可能になった.開胸創は小さいものの,胸腔鏡の光により十分に明るい視野での直視下の手術操作が可能となり,誰にでもできる安全な術式である.助手はテレビ画面での拡大視された術野を観察でき,教育面からも利点が多い.更に,術後の創部痛が軽減され,歩行開始時期が早くなり,合併症も改善された
  • H Otsuka; S Funai; T Azumi; S Hara; K Okuno; M Yasutomi
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 124 2 293 - 298 2002年08月 [査読有り]
     
    Objective: The purpose of this study was to clarify the significance of bivariate cytokeratin and DNA flow cytometry for analysis of the biologic aggressiveness of resectable non-small cell lung cancer. Methods: In 92 patients who underwent curative operations, the DNA ploidy status and S-phase fractions of the cancer cell populations inside the tumors were analyzed by a cytokeratin gating technique with paraffin-embedded specimens and were correlated with the surgical results. Results: Ninety tumors yielded assessable DNA histograms. DNA diploidy was detected in 25 tumors with a mean S-phase fraction of 14.3% +/- 4.7%, and DNA aneuploidy was detected in 65 tumors with a mean S-phase fraction of 15.1% +/- 7.1%. The 5-year overall and recurrence-free survivals were 73.3% and 70.3%, respectively, Multivariate analysis showed that only TNM staging was a prognostic factor after surgery. There was a negative correlation between the logarithms of S-phase fraction and the disease-free interval for 22 patients with proven recurrence (P =.006). The tumors with high S-phase fractions recurred more rapidly than did those with low S-phase fractions. Conclusion: In a bivariate analysis of cytokeratin and DNA How cytometry in resectable non-small cell lung cancer, the S-phase fraction appeared to be correlated with the disease-free interval. However, DNA ploidy and S-phase fraction were not predictive of either recurrence or survival after operation. Thus DNA How cytometry may be of limited use for the analysis of the biologic aggressiveness of lung cancer.
  • 消化器外科手術アトラス 胸部食道癌手術
    塩崎 均; 田中 晃; 今本 治彦; 重岡 宏典; 平井 紀彦; 川西 賢秀
    消化器外科 25 6 661 - 672 (株)へるす出版 2002年06月
  • Yasumasa Nishimura; Minoru Suzuki; Kiyoshi Nakamatsu; Shuichi Kanamori; Yukinobu Yagyu; Hironori Shigeoka
    International journal of radiation oncology, biology, physics 53 1 134 - 9 2002年05月 [査読有り]
     
    PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.
  • State of the Art 食道癌治療 QOLの向上を目指して
    塩崎 均; 矢野 雅彦; 田中 晃; 今本 治彦; 重岡 宏典; 大塚 浩史; 川西 賢秀; 平井 紀彦; 石川 真平; 奥野 清隆
    Frontiers in Gastroenterology 7 2 110 - 119 (株)メディカルレビュー社 2002年04月
  • 日常診療の指針 食道表在癌に対する治療方針
    重岡 宏典; 田中 晃; 塩崎 均
    外科治療 86 2 213 - 214 (株)永井書店 2002年02月
  • 【消化器癌に対する標準的治療・21 我々はこう考える】 下咽頭・頸部食道癌
    塩崎 均; 田中 晃; 重岡 宏典; 平井 紀彦; 大塚 浩史; 奥野 清隆
    消化器外科 24 13 1845 - 1851 (株)へるす出版 2001年12月 
    現在の下咽頭・頸部食道癌に対する標準治療は咽頭喉頭食道切除術である.しかしながら,本術式は音声の喪失という大きなQOLの障害を伴う.近年,術前化学放射線療法が著効を示す症例が多く報告されるようになり,これらの症例には喉頭温存手術が行われるようになってきた.本術式が標準治療となりうる可能性について述べると共に,根治的化学放射線療法,或いは音声再建術を伴った咽頭喉頭食道切除術についても紹介し,21世紀標準治療についてその抱負を述べた
  • M Shiomi; T Kamisako; Yutani, I; M Kudo; H Shigeoka; A Tanaka; K Okuno; M Yasutomi
    TUMORI 87 3 191 - 195 2001年05月 [査読有り]
     
    We report two cases of early gastric cancer with distant metastases (stage IV). At our institute 1428 cases of primary gastric cancer were resected between 1980 and 1997; 536 were diagnosed as early gastric cancer based on the resected specimens (304 cases of mucosal cancer, Tis - TNM classification - and 232 of submucosal cancer, T1), 528 of these 536 cases were classified as histological stage I, six as stage II, none as stage III and two as stage IV. The incidence of stage IV early gastric cancer was 0.14% of all gastric cancers and 0.37% of the early gastric cancers,The two patients with stage IV early gastric cancer were women. Both tumors were defined as early cancer because they were confined to the submucosa, One was a type 0 IIc + III early cancer, histologically classifiable as a small, moderately differentiated adenocarcinoma (tub2 according to the Japanese Classification of Gastric Carcinoma(1,2), G2; TNM classification: ICD-O C16), size 10 x 8 mm; the other was a surface spreading type 0 lie, classifiable as a signet-ring cell carcinoma (sig, G3), size 50 x 35 mm. Stage IV factors were N3 in the first and ovarian metastasis (Krukenberg tumor) in the second case.
  • K Okuno; H Shigeoka; A Tanaka; N Hirai; E Matsumura; M Yasutomi
    HEPATO-GASTROENTEROLOGY 47 34 1180 - 1182 2000年07月 [査読有り]
     
    Background/Aims: Although the recent results of surgical treatments for T2-gastric cancer (defined as: tumor invasion of the muscularis propria or the subserosa) have been comparatively favorable, frequency of lymph node metastasis is high and recurrence often happens. Methodology: A retrospective study on T2-gastric cancer in 347 patients who underwent curative resection between 1975 and 1995 was performed to address this issue. These 347 patients were divided into 3 groups according to age: group I (72 cases) <50 years old; group II (202 cases) not <50 years but <70 years old; and group III (73 cases) greater than or equal to 70 years old. Results: There was an apparent tendency that gastric cancer in aged patients is more likely to become differentiated cancer and spread easily to the liver. Conclusions: The data suggest that aged patients should be more carefully followed for any hematogenous metastases including liver metastases. Removal of hepatic metastases or regional hepatic infusion chemotherapy may then salvage some patients even elderly patients.
  • K Okuno; N Hirai; Y Takemoto; Kawai, I; M Yasutomi
    HEPATO-GASTROENTEROLOGY 47 32 487 - 491 2000年03月 [査読有り]
     
    Background/Aims: Hepatic arterial infusion of interleukin-2-based immunochemotherapy has yielded a high response rate (>75%) in patients with unresectable liver metastases. In order to clarify the mechanisms that underlie the apparent benefit of combination treatment, the role of IL-2 as a modulator of 5-fluorouracil metabolism was investigated. Methodology: A single dose of Ei-fluorouracil (50mg/kg) with or without IL-2 (3500 Japan Reference Units/kg) was given via the hepatic artery to rats bearing liver metastases. Thirty minutes later samples of liver metastatic foci or surrounding normal liver tissue were removed for the measurement of thymidylate synthase, thymidine kinase and dihydropyrimidine dehydrogenase activity, and 5-fluorouracil content. Results: 5-fluorouracil levels in tumor were significantly higher than in normal liver. Although the addition of IL-2 reduced 5-fluorouracil levels in both tumor and normal liver tissues by the activation of dihydropyrimidine dehydrogenase, the ratio of tumor/normal liver 5-fluorouracil levels was unchanged. Both thymidylate synthase and thymidine kinase activities were significantly inhibited in tumor tissue when the combination of 5-fluorouracil and IL-2 was administered. Conclusions: IL-2 increases 5-fluorouracil cytotoxicity through the inhibition of thymidylate synthase/thymidine kinase activities in the hepatic arterial infusion.
  • 奥野 清隆
    J. Am. Coll. Surg. 189 3 300 - 304 1999年09月 [査読有り]
     
    Background: For hepatic resection, intraoperative bleeding is reduced by clamping the afferent blood flow. Selective clamping at the hepatic hilum can be accomplished using the standard controlled method or Glisson's pedicle transection method. The safety and efficacy of these two methods have not previously been compared. Study Design: The intraoperative findings and complications were ret respectively reviewed in 90 patients who underwent major hepatectomy with selective inflow clamping between 1988 and 1997. Results: Blood loss and operative time did not differ between the two groups. Bile leakage was observed in 3 of 43 patients (7.0%) in the standard controlled method group and 11 of 47 patients (23.4%) in the Glisson's pedicle transection method group (p = 0.031). In the Glisson's pedicle transection method group, bile leakage occurred more frequently in patients who underwent left lobectomy than in those who underwent right lobectomy (p = 0.023). Conclusions: There were no differences in intraoperative findings and postoperative complications analyzed between the standard controlled method and Glisson's pedicle transection method for major hepatectomy except for the rate of bile leakage. In particular, attention must be paid to the bile duct injuries when the Glisson's pedicle is dissected. (J Am Coil Surg 1993;183:300-304. (C) 1999 by the American College of-Surgeons).
  • K Okuno; K Kaneda; M Yasutomi
    HEPATO-GASTROENTEROLOGY 46 1263 - 1267 1999年05月 [査読有り][招待有り]
  • H Shigeoka; U Karsten; K Okuno; M Yasutomi
    TUMOR BIOLOGY 20 3 139 - 146 1999年05月 
    Thomsen-Friedenreich antigen (TF; Gal beta 1-3GalNAc alpha 1-) is expressed on many human carcinomas. Evidence suggests that TF-carrying tumor cells specifically bind asialoglycoprotein receptors on hepatocytes resulting in metastasis formation in the liver. We used an animal model to examine the feasibility of preventing metastasis formation by an antibody to TF. Treatment of Colon 26 cells with neuraminidase led to the exposure of TF, and consequently to a higher frequency of liver metastases in syngeneic Balb/c mice. This could be prevented by an antibody to TF (A78-G/A7), but not by a control antibody. The results may open up a new strategy for the prophylaxis of metastatic spread to the liver.
  • H Shigeoka; U Karsten; K Okuno; M Yasutomi
    TUMOR BIOLOGY 20 3 139 - 146 1999年05月 [査読有り]
     
    Thomsen-Friedenreich antigen (TF; Gal beta 1-3GalNAc alpha 1-) is expressed on many human carcinomas. Evidence suggests that TF-carrying tumor cells specifically bind asialoglycoprotein receptors on hepatocytes resulting in metastasis formation in the liver. We used an animal model to examine the feasibility of preventing metastasis formation by an antibody to TF. Treatment of Colon 26 cells with neuraminidase led to the exposure of TF, and consequently to a higher frequency of liver metastases in syngeneic Balb/c mice. This could be prevented by an antibody to TF (A78-G/A7), but not by a control antibody. The results may open up a new strategy for the prophylaxis of metastatic spread to the liver.
  • Kiyotaka Okuno; Akira Tanaka; Hironori Shigeoka; Norihiko Hirai; Isao Kawai; Yoshinori Kitano; Masayuki Yasutomi
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2 1 20 - 25 1999年05月 [査読有り]
     
    Background. In Japan since the 1960s, patients with gastric cancer have routinely had splenectomy combined with gastrectomy to ensure that lymph node dissection is complete. However, the influence of splenectomy on long-term immunity is unclear.METHODS: Forty-nine gastric cancer patients who underwent total gastrectomy for cure with ( n = 25) and without ( n = 24) splenectomy were assessed for immunologic function, including the proportion of lymphocyte subsets, purified protein derivative from tuberculin (PPD) response, natural killer (NK) activity, and phytohemagglutinin (PHA) response.RESULTS: Peripheral T-cell mediated functions, e.g., PPD and PHA response, were significantly suppressed in patients who underwent gastrectomy with splenectomy compared with those who had gastrectomy alone. Decreased T-cell subsets (CD 3+, 4+, 8+) and increased NK cell subsets (CD 16+, 57+) were observed in patients who underwent splenectomy. Patients who did not undergo splenectomy had immunologic responses within the normal range.CONCLUSIONS: Splenectomy decreased T-cell mediated responses over the long term. As a potential means to co-rrect this T-cell dysfunction in patients with splenectomy, splenic autotransplantation should be considered in future research.
  • K Okuno; M Yasutomi; M Kon; K Hatakeyama; T Muto; M Kitajima; Y Koyanagi; K Hamano; H Ohta; K Aiba; Y Arai; M Sowa; N Kikkawa; Y Takayasu; H Isomoto
    HEPATO-GASTROENTEROLOGY 46 26 1116 - 1121 1999年03月 [査読有り]
     
    BAGKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1x10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7x10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response-rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.
  • 肥田仁一; 安富正幸; 丸山; 中島; 内田; 久保; 若野; 所; 梅村; 進藤勝久; 藤本
    Surgery Today 29 1 93 - 94 1999年 [査読有り]
  • J Hida; M Yasutomi; T Maruyama; T Yoshifuji; T Tokoro; T Wakano; T Uchida; K Ueda
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 29 12 1237 - 1242 1999年 [査読有り]
     
    The functional outcome after a low anterior resection for rectal cancer is improved by a colonic J-pouch reconstruction. One functional problem with J-pouches is difficulty in evacuation, which is more common with large reconstructions. Since rectoceles are common findings on defecography in patients with evacuation difficulties, we proposed that a rectocele-like prolapse may be thus found in patients with large J-pouches. Pouchography was used to identify a rectocele-like prolapse (RP) in 26 patients with a 10-cm J-pouch (10-J group) and 27 patients with a 5-cm J-pouch (5-J group). Pouchography was performed at 3 months, 1 year, and 2 years after surgery. Functional assessments were performed 1 year postoperatively. Clinical function was evaluated using a questionnaire. The evacuation function was evaluated by the balloon expulsion and saline evacuation test. No patients had an RP at 3 months or 1 year after surgery. An RP was significantly more common in the 10-5 group than in the 5-5 group at 2 years after surgery (P = 0.0374). An evacuation difficulty was significantly more common in the 10-5 group than in the 5-5 group. The evacuation function in the 10-J group was also significantly inferior to that in the 5-J group. An RP appearing 2 years after surgery is more common in patients with evacuation difficulties and large colonic J-pouch reconstructions.
  • K Okuno; A Tanaka; H Shigeoka; N Hirai; Kawai, I; Y Kitano; T Hirohata; M Yasutomi
    3RD INTERNATIONAL GASTRIC CANCER CONGRESS 985 - 989 1999年 [査読有り]
     
    Splenectomy is often performed to facilitate complete lymphadenectomy in gastric cancer patients, but the immunologic role of the spleen in cancer patients remains unclear. Forty-nine gastric cancer patients who underwent total gastrectomy for I cure with (n=25) and without (n=24) splenectomy were assessed for immunologic function, including the proportion of lymphocyte subsets, purified protein derivative from tuberculin (PPD) response, natural killer (NK) activity, and phytohemagglutinin (PHA) response. Decreased T-cell subsets (CD 3+, 4+, 8+) and increased NK cell subsets (CD 16+, 57+) were observed in patients who underwent splenectomy. In accordance with the change of phenotypic patterns of PBL, peripheral T-cell mediated functions, e.g. PPD and PHA response, were significantly suppressed and NK activities were stronger in patients who underwent gastrectomy with splenectomy compared to gastrectomy alone. Patients who did not undergo splenectomy had immunologic responses within the normal range.
  • S Honda; T Takasaki; K Okuno; M Yasutomi; Kurane, I
    ACTA VIROLOGICA 42 5 307 - 313 1998年11月 [査読有り]
     
    We developed a simple method for establishing Epstein-Barr virus (EBV)-specific, human CD4+ T cell clones. The method originates from our experience that the regression of cell growth in in vitro EBV transformation of B cells occurs when round lymphoid cells appear in the culture. Peripheral blood mononuclear cells (PBMCs) were cultured with EBV and IL-2 (20 U/ml) was added to the culture on day 17 after the virus addition. The phenotype of the growing cells was CD3+, CD4+, and CD8-. The cells were cytotoxic for autologous lymphoblastoid B cell line (LCL) and EBV-superinfected autologous LCL. The cytotoxic T lymphocytes (CTLs) were confirmed to be CD4+ T cells but not CD8+ T cells in the culture. CTL clones were established by a limiting dilution method. All the CTL clones had the phenotype of CD3+, CD4+ and CD8-, and proliferated in response to autologous LCL. They produced interferon (IFN);gamma, interleukin 2 (IL-2) and tumour necrosis factor (TNF)-beta but not IL-4. All but one clone responded to both autologous, EBV-superinfected and non-superinfected LCLs. Proliferative and cytotoxic responses to allogenic LCLs were heterogeneous. These results suggest that this method induces heterogeneous, EBV-specific CD4+ CTL clones and is useful for analysis of CD4+ T cells in EBV infections.
  • K Okuno; N Hirai; YS Lee; D Tarabar; H Ueno; M Yasutomi
    CANCER CHEMOTHERAPY AND PHARMACOLOGY 42 4 341 - 344 1998年09月 [査読有り]
     
    Purpose: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using noninvasive in vive F-19 nuclear magnetic resonance (NMR) spectroscopy. Methods: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. Results: With systemic i.v. (tail vein) infusion, the F-19-NMR signal for 5-FU from the liver region peaked in the first spectrum (0-5.5 min), and then gradually decreased. The signal for the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) gradually increased to the sixth spectrum (0-33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v, infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion. Conclusions: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic areterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully.
  • 肥田仁一; 安富正幸; 進藤勝久ら
    Diseases Colon & Rectum 41 8 989 - 991 1998年08月 [査読有り]
  • 高度手術侵襲後の臓器障害に係わるparameter変化とUlinastatin投与効果
    中居 卓也; 川辺 高史; 黒田 幸作; 香山 仁志; 重岡 宏典; 田中 晃; 康 謙三; 奥野 清隆; 安富 正幸
    臨牀と研究 75 8 1868 - 1872 大道学館出版部 1998年08月 
    手術侵襲後のSIRS状態や,MODの発症にはIL-8によるPMNEの放出が強く係わり,臓器障害の発生予防にはUlinastatin投与は重要と考えられた
  • K Okuno; A Tanaka; H Yoshikawa; H Shigeoka; H Jinnai; YS Lee; N Hirai; E Matsumura; Kawai, I; M Yasutomi
    HEPATO-GASTROENTEROLOGY 45 22 950 - 953 1998年07月 [査読有り]
     
    A promising preoperative immunochemotherapy regimen for locally advanced esophageal cancer is herein described. A 67-year-old man suffering from severe dysphagia was diagnosed with unresectable esophageal cancer at initial examination because of a tumor of 11 cm in length and suspicion of trachea invasion. Neoadjuvant immunochemotherapy was undertaken for the down-staging. Interleukin-2 (IL-2) (3.5 x 10(5) Japan reference units), nedaplatin (7 mg/m(2)) and 5-FU (300 mg/m2) were administered intravenously daily for 5 days a week for three weeks. The gross findings of a barium esophagogram and esophagoscopy revealed significant tumor regression in both size and shape. The patient underwent an esophagectomy through a laparotomy followed by a right thoracotomy. The surgical specimens were serially sectioned and examined microscopically. All of the surgical margins were clear (upper and lower margins as well as the adventitia), and there was no evidence of lymph node metastasis. The surgical specimen revealed neoplastic squamous ghost cells surrounding significant lymphocyte infiltration. This appears to be a unique feature of this particular neoadjuvant immunochemotherapy.
  • 【QOL重視型胃手術】 自家脾移植
    奥野 清隆; 重岡 宏典; 田中 晃
    手術 52 7 1005 - 1012 金原出版(株) 1998年06月
  • K Okuno; N Hirai; YS Lee; Kawai, I; H Shigeoka; M Yasutomi
    JOURNAL OF SURGICAL RESEARCH 75 2 148 - 152 1998年03月 [査読有り]
     
    Aims. Hepatic metastasis formation and prevention were studied from the viewpoint of liver-associated immunity. Methods. RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, in which the cancer is highly metastatic to the liver, were used. Fischer rats that were inoculated with parent RCN-9 colonic cancer cells (5 x 10(6)) via the portal vein showed liver metastasis in less than 60% of the animals. In contrast, all rats (100%) that received RCN-H4 produced multiple liver metastases. To investigate the difference of hepatic metastasis formation, we assessed the susceptibility of both cell lines against hepatic sinusoidal lymphocytes (HSL) by Cr-51-release assay, and the expression of MHC class I and class II of both cell lines by flow cytometry. In addition, we examined whether activation of HSL by interleukin-12 (IL-12) can prevent liver metastasis of highly metastatic clone RCN-H4. Results. The RCN-H4 clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL. This decrease in susceptibility was attributable to an increase in cell surface expression of MHC class I antigen. Administration of IL-12, a potent NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4 clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein. Conclusions. Liver metastasis formation is positively correlated with the strength of the hepatic immune system which mainly consists of ontogenetically primitive T cells. As these effecters exert their cytotoxicity in a MHC-nonrestricted fashion, tumor cells that highly express MHC class I antigen can readily avoid hepatic surveillance and apt to cause liver metastasis. Augmentation of the hepatic immune system, for instance, with IL-12 administration, can prevent liver metastasis even in tumor cells with a high potential for liver metastasis. (C) 1998 Academic Press.
  • K Okuno; K Nakamura; A Tanaka; K Yachi; M Yasutomi
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 28 1 64 - 69 1998年 [査読有り]
     
    To activate hepatic sinusoidal lymphocytes (HSL) and increase the local antitumor activity in the liver, we developed a liver-targeted interleukin-2 (IL-2) compound using a galactose residue-entrapped liposome, We prepared various kinds of IL-2-containing liposomes made by the hydration of pondered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 followed by the combination with galactose residues to facilitate the selective uptake by liver parenchymal cells bearing galactose receptors, The IL-2 liposomes were given to C3H/He mice followed by the determination of: (1) organ distribution by I-125-labeled IL-2, (2) antitumor activity of hepatic sinusoidal lymphocytes by Cr-51-release assay, and (3) in vivo antitumor efficacy by the measurement of hepatic metastases, When galactose-entrapped IL-2 liposomes (Gallip-IL-2) were administered, a significantly greater hepatic accumulation of IL-2 was seen for up to 2 weeks compared to IL-2 liposomes or free IL-2, According to these results, the antitumor activity of HSL was significantly augmented, Moreover, when mice with hepatic micrometastases were treated with Gal-lip-IL-2, the area of hepatic metastases was significantly reduced, These findings thus indicate that Gal-lip-IL-2 may enhance the therapeutic efficacy of IL-2 against hepatic metastases and thereby facilitate a more practical daily dosing regimen.
  • A Tanaka; E Matsumura; H Yosikawa; T Uchida; N Machidera; R Kubo; K Okuno; K Koh; M Watatani; M Yasutomi
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 28 9 873 - 878 1998年 [査読有り]
     
    It is well known that the operative results for esophageal cancer, especially thoracic esophageal cancer, are not favorable. We analyzed the relationship between neural invasion (NI) and histopathologic factors and recurrence types in 104 patients who underwent resection of esophageal cancers with T2 or greater depth of invasion of the esophageal wall. The implications of NI as a prognostic indicator were also examined. Of the 104 patients, 48 (46.2%) were NI-positive (NI(+)) and 56 (53.8%) were NI-negative (NI(-)). The NI(+) patients had a higher ratio of type 3 cancer. Concerning the histopathologic factors, there was a significant relationship between NI and lymph node metastasis (N) and between PI(TI and lymphatic vessel invasion (ly) (P < 0.05). Examining the types of recurrence, namely hematogenous, lymphogenous, and local/stump, as well as pleural or peritoneal dissemination, a relationship was observed between lymphogenous recurrence and N or ly, and between local/stump recurrence and NI. The prognosis of the NI(+) patients was significantly different from that of the NI(-) patients. According to a multivariate analysis, NI and N were significant prognostic factors. These findings demonstrate that NI is an important prognostic factor closely related to local recurrence in patients with esophageal cancer. Thus, when treating advanced esophageal cancer with T2 or greater depth of invasion, NI, and lymph node excision should be considered.
  • 川辺高史; 中居卓也; 進藤勝久; 安富正幸
    Microsurgery 18 5 344 - 347 1998年 [査読有り]
     
    A venous cuff technique was applied only for venous drainage in orthotopic small bowel transplantation of rats. Rates of technical failure (death within 4 days) and in clinical signs were compared between the groups with (group A) and without (group B) venous cuff technique. Technical failures with and without venous cuff technique were 5% and 25%, respectively. Mean survival days, excluding deaths from technical failure, were 9.2 +/- 2.3 in group A and 8.1 +/- 2.6 days in group B. No significant differences were observed in mean survival days or in weight loss between the two groups. Acute rejection was the cause of death in both groups. Since the model with venous cuff technique showed low mortality, it could be widely employed in small bowel transplantation studies. (C) 1998 Wiley-Liss, Inc.
  • 肥田仁一; 安富正幸; 進藤勝久ら
    Surgery Today 28 7 768 - 769 1998年 [査読有り]
     
    In anterior resection with anastomosis using the double-staple technique for low-lying rectal cancer in male patients, the approach to the anal canal with a stapling instrument ria the abdominal area is limited by the narrow pelvis. The stapling and transection of the anal canal via the posterior transsacral approach prior to performing an anterior resection thus enables the lower rectum and anal canal to be visualized, so that the anal canal can bet accurately stapled and transected even in male patients with a narrow pelvis.
  • I. Kawai; K. Okuno; A. Tanaka; H. Yoshikawa; H. Shigeoka; H. Jinnai; N. Hirai; Yung Sun Lee; E. Matsumura; M. Yasutomi
    Biotherapy 12 123 - 125 1998年01月 
    A 67-year-old man suffering from severe dysphagia was diagnosed with locally advanced esophageal cancer at the initial examinations. We designed neoadjuvant immunochemotherapy with interleukin-2 (IL-2), nedaplatin and 5- FU. A dramatic reduction in the tumor mass was observed. The surgical specimen revealed cancer cell degeneration and necrosis surrounding significant lymphocyte infiltration. This early result encouraged us to continue with this neoadjuvant immunochemotherapy.
  • N. Hirai; K. Okuno; Y. S. Lee; S. Honda; H. Shigeoka; I. Kawai; M. Yasutomi
    Biotherapy 12 772 - 774 1998年01月 
    Hepatic metastases formation and prevention were studied from the viewpoint of liver-associated immunity. RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4. In which the cancer is highly metastatic to the liver, were used. The RCN-H4 clone showed a decreased susceptibility to lysis by hepatic sinusoidal lymphocytes. This decrease was attributable to an increase in cell surface expression of MHC class I antigen. In addition, administration of interleukin-12 (IL-12), a potent NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4 clone.
  • J Hida; M Yasutomi; T Maruyama; K Fujimoto; T Uchida; K Okuno
    CANCER 80 2 188 - 192 1997年07月 [査読有り]
     
    BACKGROUND. The surgeon is no longer able to palpate the mesocolon for lymph node metastases during laparoscopic colectomy. The extent of lymph node dissection should be determined beforehand for cancer control. METHODS. The distribution of lymph node metastases was obtained by the clearing method on colon carcinomas for 164 patients. RESULTS. For pericolic spread: for pT1 tumors, the distance from the primary tumor to a metastatic lymph node was 2.5 cm; for pT2, the distance was within 5 cm; for 97.0% of pT3 tumors with lymph node metastases, the distance was within 7 cm; for 93.3% of pT4 tumors with lymph node metastases, the distance was within 7 cm. For central spread: for pT1 tumors, the rate of metastasis to central lymph nodes was 0%; for pT2, the rate of metastasis was 20.0% to intermediate lymph nodes; for pT3, the rate of metastasis was 30.6% to intermediate lymph nodes and 15.3% to main lymph nodes; for pT4, the rate of metastasis was 44.4% to intermediate lymph nodes and 22.2% to main lymph nodes. CONCLUSIONS. Central lymph node dissection is not required for patients with T1 carcinomas, but proximal and distal 3-cm margins of resection are required. For T2, central lymph node dissection that includes the intermediate lymph node should be performed, as well as 5-cm proximal and distal margins of resection. For T3 and T4, central lymph node dissection including the main lymph node should be performed, as well as 7-cm proximal and distal margins of resection. (C) 1997 American Cancer Society.
  • J Hida; M Yasutomi; T Maruyama; K Fujimoto; T Uchida; K Okuno
    JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 184 6 584 - 588 1997年06月 [査読有り]
     
    BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.
  • 肥田仁一; 安富正幸; 進藤勝久ら
    J Am Coll Surg 184 5 475 - 480 1997年05月 [査読有り]
     
    BACKGROUND: The treatment of rectal carcinoma by lateral lymph node dissection has risks and benefits, Therefore, we investigated the therapeutic efficacy of lateral lymph node dissection. STUDY DESIGN: We studied 198 patients with rectal carcinoma who underwent lateral lymph node dissection. Metastases to the lymph nodes were examined by the clearing method. The incidence of urinary and male sexual dysfunction was determined by measuring the residual urine volume and individual interview 1 year after operation. RESULTS: The rate of metastasis to lateral lymph nodes was 11.1 percent, and metastasis to the lateral lymph nodes occurred more frequently with lower rectal carcinoma classified as pT3 or pT4 in the TNM system. The rate of local recurrence was 12.5 percent and the B-year survival rate after curative resection was 70.1 percent. The 5-year survival rate in patients with metastasis to the lateral lymph nodes was 25.1 percent, and this rate was significantly lower than the 5-year survival rate of 74.3 percent in patients without metastasis to the lateral lymph nodes. Urinary dysfunction was observed in 67.5 percent of patients, and male sexual dysfunction was found in 97.4 percent of men younger than 60 years of age with prior sexual ability. CONCLUSIONS: The prognosis for patients with metastasis to the lateral lymph nodes is poor, and the improvement in survival rate from lateral lymph node dissection is minimal.
  • A Tanaka; H Yoshikawa; K Okuno; K Koh; M Watatani; E Matsumura; M Yasutomi
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 27 8 692 - 695 1997年 [査読有り]
     
    The relationship between histological factors, including neural invasion (NI), and survival rates in patients with Borrmann type IV diffuse invasive gastric cancer was examined to determine the significance of NI as a prognostic factor. NI was studied histochemically in 75 patients who underwent resection after 1982, 37 of whom underwent curative resection. The 3-year and 5-year survival rates of the 37 patients who underwent curative resection were 37.2% and 12.7%, respectively. Recurrence was detected as peritoneal dissemination in 19 of those patients (82.6%), and the most significant prognostic factor was the depth of wall invasion (P < 0.01). While NI (P = 0.06) and lymph node metastasis (P = 0.09) appeared to be prognostic factors, there were no significant differences. Therefore, the depth of wall invasion was classified as T2 and T3 or 4 to examine the association of NI and lymph node metastasis with prognosis, whereby NI was shown to be a significant prognostic factor in T2. In conclusion, NI may be a significant prognostic factor in patients with wall invasion of T2 without serosal invasion, as it provides a pathway for the progression to peritoneal dissemination.
  • 大塚 正彦; 穴沢 貞夫; 進藤 勝久; 安富 正幸; 大村 裕子; 沼田 悟; 久保 善規; 西出 薫; 吉川 隆造
    日本大腸肛門病学会雑誌 50 6 423 - 428 1997年 [査読有り]
     
    To evaluate the histological changes, biopsies were conducted at the site where a skin harrier had been attached in 27 patients who had used the agents for an extended period. Furthermore, these histological findings were compared to their gross appearance, relief images, and functional changes. In the histological examinations, separation of the horny layer was seen in 26 cases the thickness of epidermis was greater than the normal section in 19 cases and the melanin content had increased in 10 cases, remained the same in 10 cases, and was reduced in 7 cases. These findings did not necessarily correspond with the result of the gross appearance. Infiltration by inflammatory cell was noted in 16 cases. Eosinophils were present in 6 cases, among which 4 had used an adhesive-type apparatus. The findings suggested a relationship with an allergic reaction. The major histological changes seen among the patients who used a skin barrier for an extended period were separation of the horny layer, thickness of epidermis, and infiltration by inflammatory cells. No correlations were found among gross appearance, physiological functions, and replica with histological findings.
  • H. Jinnai; Yung Sun Lee; K. Okuno; H. Shigeoka; N. Hirai; S. Honda; M. Yasutomi
    Biotherapy 11 423 - 425 1997年01月 
    We have compared the antitumor effects of interleukin (IL) 12, which is supposed to be a new type of antitumor agent, with those of IL-2, which is used clinically for liver metastasis, using rat liver metastasis as a model. There were an accumulation of NK cells and an enhancement of cytotoxic activities of lymphocytes against cancer cells in the hepatic sinusoid of rats injected with IL-12 intraperitoneally. There were an accumulation of Tc cells in the sinusoid and an accumulation of NK cells in the periportal area, outside the sinusoid, in the case of IL 2 treatment. IL-12 treatment also prohibited experimental liver metastasis in the micrometastatic phase. However, IL-2 treatment had a greater efficacy than IL-12 treatment in the macrometastatic phase. This study suggests a different effect of IL-12 and IL-2 on the lymphocytes of rats and also the importance for cancer therapy of selecting a suitable cytokine for the different phases of cancer.
  • Yung Sun Lee; H. Jinnai; K. Okuno; H. Shigeoka; K. Nakamura; S. Honda; M. Yasutomi
    Biotherapy 11 631 - 633 1997年01月 
    In IL-12 in vivo treated rat liver, the number of metastatic nodules significantly decreased, so we investigated the in vivo effects of IL-12 on hepatic sinusoidal lymphocytes of rats and compared the results with the effects of IL-2. By flow cytometry, the proportion of CD3 - CD8 + (=NK cells) and CD3 + CD8 + cells (= cytotoxic T cells) increased in IL-2 treated liver. On the other hand, in IL-12 treated liver, the proportion of NK cells among total liver lymphocytes increased significantly. Histologically, there was quite a difference in the type of cells accumulating in the liver depending on treatment by IL-12 or IL-2. These data suggest that, in IL-12 treated liver, antitumor activity is augmented by a system that is different from the system augmented by IL-2.
  • 肥田仁一; 安富正幸; 進藤勝久ら
    Diseases Colon Rectum 39 11 1282 - 1285 1996年11月 [査読有り]
     
    PURPOSE: It has been reported that functional outcome following low anterior resection of rectal cancer is improved by construction of a colonic J-pouch compared with straight anastomosis. Hence, we tried to justify use of the sigmoid colon in the construction of a J-pouch by the analysis of regional lymph node metastases. METHODS: A total of 182 patients underwent resection for rectal cancer. Node metastases were examined by the clearing method. According to Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus (JGR), nodes were classified into the perirectal nodes (PR-N), pericolic nodes (PC-N), central intermediate nodes (C-IM-N), central main nodes (C-M-N), lateral intermediate nodes (L-IM-N), and lateral main nodes (L-M-N). RESULTS: Metastatic rate (number of patients with node metastases/total number of patients) of PR-N was 57.1 percent. Metastatic rate of C-IM-N was 18.7 percent and that of C-M-N was 7.1 percent. Metastatic rates of L-LM-N and L-M-N were 8.8 and 3.3 percent, respectively, and both were highest in the case of lower rectal cancer. Metastatic rate of PC-N was only 1.1 percent. The number of cases without node metastases (n(-) cases) was 78, that with only PR-N metastases (PR-N cases) was 63, that with intermediate but not main node metastases (IM-N cases) was 29, and that with main node metastases (M-N cases) was 12. Five-year survival rate after curative resection was 88.5 percent for n(-) cases, 70.9 percent for PR-N cases, 65.9 percent for IM-N cases, and 41.7 percent for M-N cases. CONCLUSIONS: In low anterior resection, high ligation of the inferior mesenteric artery and dissection of C-M-N, C-IM-N and PR-N are necessary, with the addition of the L-IM-N and L-M-N in the case of lower rectal cancer. Resection of sigmoid colon is not required, and therefore, a J-pouch can be constructed using the sigmoid colon. Nodal classification according to the JGR was predictive of case distribution and five-year survival rate.
  • K Okuno; H Jinnai; YS Lee; K Kaneda; M Yasutomi
    HEPATO-GASTROENTEROLOGY 43 11 1196 - 1202 1996年09月 [査読有り]
     
    Background/Aims: It has been reported recently that in vivo administration of interleukin-12 (IL-12) augments the cytotoxic activity of natural killer (NK)/T cells and shows a powerful anti-tumor activity. In this study, we evaluated that the IL-12 effect on liver-associated immunity and in vivo efficacy on the hepatic metastases in a rat model. Materials and Methods: Varying amounts of mouse recombinant IL-12 were injected intraperitoneally for 5 days to adult male Fischer rats and hepatic sinusoidal lymphocytes (HSL) were collected. Purified HSL are spontaneously cytolytic to both conventional NK-sensitive target (YAC-1) and NK-resistant target (RCN-H4) tumor cells. Results: IL-12 was found to increase the number of HSL and the cytolytic activity against these target cells in a dose-dependent fashion. Flow cytometric analysis showed that IL-12 caused an increase of CD8+ subpopulation in HSL and a double staining study revealed that the increased subpopulation was not CD3+8+ (cytotoxic T cell) fraction, but actually CD3-8+ (NK cell) fraction. Experimental liver metastases was markedly reduced in rats treated intraperitoneally with IL-12. Conclusion: These results demonstrate that IL-12 augments the cytolytic activity of HSL and suggests this cytokine as an attractive choice for Liver metastases therapy.
  • K Okuno; H Shigeoka; YS Lee; E Son; H Kayama; T Nakai; K Koh; M Yasutomi
    HEPATO-GASTROENTEROLOGY 43 9 688 - 691 1996年05月 [査読有り]
     
    Background/Aims: Based on our favorable results of interleukin-2-based immuno-chemotherapy in the treatment of unresectable liver metastases from colorectal cancer, we utilized this therapy for the prevention of liver recurrence after liver resection. Materials and Methods: Eighteen patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant immunochemotherapy that included hepatic arterial infusion of interleukin-2 and mitomycin C, 5-fluorouracil. The regimen consisted of weekly interleukin-2 (1.4 - 2 x 10(6) units), 5-fluorouracil (250 mg) by 2-hour infusion and bolus mitomycin C (4 mg) for 6 months. Results: Fourteen of 18 patients are alive and disease-free with a median postoperative follow-up of 28.5 months. Recurrent cancer has developed in 4 of the 18 patients (22%). The site of first recurrence was the lung in three patients (17%) and the pelvis in one (6%); no patients recurred in the liver. Conclusions: We recommend this adjuvant immuno-chemotherapy for the prevention of fiver recurrence after curative resection of colorectal liver metastases.
  • 肥田仁一; 安富正幸; 進藤勝久ら
    Diseases Colon Rectum 39 1 74 - 79 1996年01月 [査読有り]
     
    PURPOSE: The usefulness of postoperative carcinoembryonic antigen (CEA) monitoring and improvements in imaging techniques have renewed enthusiasm for second-look operations (SLO) as the most effective treatment, for recurrent colorectal cancer by reresection following early detection. The aim of our study is to evaluate the role of CEA and imaging techniques-directed SLO. METHODS: Seven hundred fifty-six patients with Dukes Stages B and C, who had undergone curative resection, were monitored postoperatively using CEA and imaging techniques. An SLO was performed on any potentially resectable recurrence, and in addition, an SLO was done when a persistently rising CEA. value was detected. RESULTS: Recurrence developed in 18.8 percent (142/756) of patients, and 90.8 percent (129/ 142) of the recurrences mere detected within the first three years following curative resection. When comparing carcinomas of the colon with that of the rectum, the former were associated with significantly more hepatic and intraabdominal recurrences, whereas the latter had significantly more locoregional and pulmonary recurrences. Seventy-two patients underwent SLO. Of these patients, 54.2 percent (39/72) had all of their disease resected, and 1.4 percent (1/72) had no detectable disease at the SLO. Among the 142 patients with recurrence, 71 (50 percent) patients underwent SLO. The resectable group at SLO carried a significantly better survival than the unresectable recurrence group (41.3 vs. 5.2 percent; P < 0.01). CONCLUSIONS: Complete removal of colorectal cancer recurrences by SLO, on the basis of postoperative, follow-up CEA and imaging technique findings, results in improved survival.
  • Yung Sun Lee; H. Jinnai; K. Okuno; K. Kaneda; H. Shigeoka; K. Nakamura; S. Honda; M. Yasutomi
    Biotherapy 10 350 - 352 1996年01月 
    Interleukin 12 (IL-12) is supposed to be a new type of cytokine to vigorously stimulate the killer cells. We have investigated the ability of IL-12 injected intraperitoneally to enhance antitumor activities of the lymphocytes in rats. Cytotoxic activities of the liver lymphocytes against YAC-1 and RCN-114 cancer cells for 4 hours were remarkably enhance/induced by IL-12 treatment. In phenotypical analysis of liver and spleen lyphocytes, it was observed tha CD3 CD8 + cells responded greatly to IL-12 treatment whereas there was no change regarding CD3 CD8 + cells, also there was an observed increase of CD3 CD8 + cells with the IL-2 treatment. This study suggests a different effect of IL-12 and IL-12 on rat lymphocytes, and also suggests a possibilityof a new immunotherapy for liver metastasis of cancer.
  • K. Okuno; A. Tanaka; H. Shigeoka; K. Nakamura; H. Jinnai; L. Y. Sung; M. Yasutomi
    Asian Journal of Surgery 19 225 - 232 1996年01月 
    In order to assess the immunological significance of splenectomy in gastric cancer surgery, we examined the immunological function of splenic lymphocytes according to the clinical stage of gastric cancer patients. Spleens from 30 patients with gastric cancer that was classified according to clinical stage and spleens from five patients with benign disease were examined for cytotoxic activity against tumour cells, interleukin-2 (IL-2)-producing activity, phenotypic analysis using flow cytometry, prostaglandin E 2 (PGE 2 )production and suppressive activity against lymphokine-activated killer (LAK) cells. The cytotoxic activity against tumour cells was generally augmented in the spleen of cancer patients compared to those with benign disease. IL-2-producing activity was also preserved in the splenic lymphocytes of patients with all stages of cancer. However, the percentage of CD11 + cells was increased in patients with advanced-stage gastric cancer (IIIB and IV) and resulted in increased endogenous PGE 2 production. The high production of endogenous PGE 2 suppressed LAK activity. We conclude that the spleen should be preserved in patients with early clinical stage disease (stages I, II and IIIA), while, in patients with advanced-stage disease (stages IIIB and IV), splenectomy may be beneficial because the splenic lymphocytes act as suppressors via endogenous PGE 2 production.
  • K Okuno; S Kobayashi; H Jinnai; YS Lee; H Shigeoka; M Yasutomi
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 26 8 662 - 664 1996年 [査読有り]
     
    A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results indicating that this treatment modality is more effective than either of the anticancer drugs used alone, To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anticancer drugs were examined in a rat model. Adult rats mere given 5-fluorouracil (5-FU) or mitomycin C (MMC) combined with various doses of IL-2 up to 7500 JRU/kg per minute for the measurement of hepatic extraction rates (HER). The HER of 5-FU was significantly increased (P < 0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability caused by IL-2 results in augmentation of the HER of associated anticancer drugs. This effect may improve the delivery of anticancer drugs to the liver and alleviate general toxicity by reducing the amount of circulating anticancer agents.
  • M Takahashi; W Chen; DR Byrd; ML Disis; ES Huseby; HL Qin; L McCahill; H Nelson; H Shimada; K Okuno; M Yasutomi; DJ Peace; MA Cheever
    CLINICAL CANCER RESEARCH 1 10 1071 - 1077 1995年10月 [査読有り]
     
    The current study examined sera from 160 colon cancer patients and 60 normal individuals to determine whether antibody to mutated p21 ras protein was present, Studies focused on the aspartic acid substitution at amino acid position 12 (denoted D12), one of the most common mutations in colon adenocarcinoma, IgA antibodies directed against mutated p21 ras-D12 protein were detected in 51 (32%) of 160 colon cancer patients, but only in 1 (2.5%) of 40 normal individuals, The greater incidence of antibody in cancer patients provides presumptive evidence that immunization to the ras proteins occurred as a result of the malignancy, Examination of sera for antibody reactivity to wild-type p21 ras protein (denoted p21 ras-G12) as web as p21 ras proteins bearing the D12, V12, S12, or L61 mutations showed that antibody detected was largely to normal segments of the p21 ras protein, Epitope mapping, using peptide neutralization assays with mutated or normal ras peptides as competitors, demonstrated that in 10 (67%) of 15 sera examined the antibody reactivity to p21 ras-G12 protein was neutralized by peptides near the carboxyl terminus of p21 ras protein, but not by peptides spanning the specific point mutation region, Antibody reactivities correlated with peripheral blood lymphocyte count, but did not correlate with patient age, sex, histology, stage, tumor locus, lymph node metastasis, or serum carcinoembryonic antigen.
  • K OKUNO; A TANAKA; T HIROHATA; H SHIGEOKA; H JINNAI; K NAKAMURA; K KURODA; YS LEE; M YASUTOMI
    1ST INTERNATIONAL GASTRIC CANCER CONGRESS, VOL 1-2 1623 - 1627 1995年 [査読有り]
  • K OKUNO; H JINNAI; YS LEE; K NAKAMURA; T HIROHATA
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 25 11 954 - 958 1995年 [査読有り]
     
    Prostaglandin E(2) (PGE(2)) is generally accepted to be an immunosuppressant produced by cancer cells and their surrounding macrophages. Although several investigators have reported detecting high concentrations of PGE(2) in the portal veins of patients with colorectal cancer, the relationship between these high concentrations of PGE(2) in the portal vein and liver-associated immunity remains unclear. In this study, we attempted to determine if the portal administration of PGE(2) suppresses the immune function of the liver in a rat model. Donryu rats were administered PGE(2) via the portal vein for 7 days, following which the cytotoxic activity of hepatic sinusoidal lymphocytes (HSL) against natural killer (NK)-sensitive YAC-1 and rat syngeneic AH60C tumor cells was assessed. Purified HSL are spontaneously cytolytic; however, the continuous administration of PGE(2) dramatically suppressed the cytotoxic activity of HSLs in a dose-dependent fashion, Flow cytometric analysis showed that the targe granular lymphocyte (LGL) fraction, hepatic natural killer (pit) cells, and CD4(-)8(+) killer/suppressor T cells were mainly reduced in number in the HSLs following PGE(2) infusion. In this rat AH60C metastasis model, the continuous administration of PGE(2) increased the number and size of metastatic tumor nodules in the liver, suggesting that high concentrations of PGE(2) in the portal vein suppress liver-associated immunity and promote the formation of hepatic metastasis.
  • K OKUNO; M OZAKI; H SHIGEOKA; NAKAJIMA, I; K NAKAMURA; T HIROHATA; H JINNAI; M YASUTOMI
    AMERICAN JOURNAL OF SURGERY 168 4 340 - 344 1994年10月 [査読有り]
     
    In order to clarify the effect of allogeneic blood transfusion on liver metastases from primary cancer, liver-associated immune function after blood transfusion was evaluated in a muring model. Hepatic sinusoidal lymphocytes (HSL) were strongly cytotoxic to conventional natural killer cell-sensitive target (YAC-1), as well as to natural killer cell-resistant solid adeno-carcinoma cells (colon 26), compared with splenic lymphocytes. Allogeneic whole blood transfusion strikingly suppressed the cytotoxic activities of HSL. Red blood cell transfusions also suppressed cytotoxicity to the same degree. In an animal model, allogeneic transfusion increased the rate of liver metatases. Flow cytometric analysis showed that transfusion caused a temporary decrease in the class II antigen positive cell fraction, mainly Kupffer's cells. This phenomenon occurred in parallel with changes in hepatic antitumor activity, indicating the possible importance of the involvement of Kupffer's cell in the development of the killer activity of HSL. These results suggest that blood transfusion may be a significant risk factor for hepatic metastasis by transiently suppressing the immunocompetence of the liver.
  • A TANAKA; T WATANABE; K OKUNO; M YASUTOMI
    CANCER 73 3 550 - 555 1994年02月 [査読有り]
     
    Background. Perineural invasion (PNI) plays a role in local invasion of pancreatic, biliary tract, and large intestine cancers and greatly affects the prognosis. Although PNI of gastric cancer has been reported rarely, the authors previously reported the usefulness of immunohistochemical staining with laminin in evaluating PNI. Method. PNI was studied histochemically in 283 patients with gastric tumors of T2 or greater depth of invasion resected between 1982 and 1989. The relationships between PNI and histopathologic findings, type of recurrence, and prognosis also were studied. Results. Of the 216 patients who underwent resection for cure, 103 experienced tumor recurrence. Recurrence correlated significantly with lymphatic vessel invasion, lymph node metastasis, and PNI. Peritoneal recurrence was found in 65 (63.1%) of the 103 patients with tumor recurrence and correlated most significantly with PNI in T2 tumors. The 5-year survival rate was 71.3% for patients with PNI-negative tumors, significantly higher than the 5-year survival rate (23.7%) for patients with PNI-positive tumors. A multivariate analysis using a Cox regression model of the relationship between histopathologic findings and prognosis demonstrated that the presence of PNI had the greatest influence on prognosis. Conclusion. The evaluation of PNI is useful in determining the prognosis of gastric cancer of T2 class with no serosal invasion.
  • K. Nakamura; K. Okuno; T. Hirohata; H. Shigeoka; H. Jinnai; M. Yasutomi
    Japanese Journal of Cancer and Chemotherapy 21 13 2105 - 2107 1994年 [査読有り]
     
    We have performed immunochemical intraarterial infusion immunochemotherapy containing IL-2, mitomycin C and 5-FU as the main active ingredient for metastatic liver tumor and obtained favorable results. However, we are obliged to perform intrahepatic arterial infusion once or twice a week, because of the short half-life of IL-2. Thus, we are using a drug delivery system to activate lymphocytes of the liver. We noticed many galactose-receptors in the liver and prepared galactose-containing liposome preparations using various carriers/bases. As a result, galactose-containing liposome preparations showed the highest accumulation and the highest localized enhancing effect on the antitumor activity of lymphocytes in the liver sites.
  • K OKUNO; T HIROHATA; K NAKAMURA; H JINNAI; H SHIGEOKA; K KOH; K SHINDO; M YASUTOMI
    CLINICAL THERAPEUTICS 15 4 672 - 683 1993年07月 [査読有り]
     
    In preclinical studies. hepatic arterial infusion of interleukin-2 (IL-2) in dogs significantly induced lymphocyte proliferation and augmented antitumor killing activity in the liver. Based on these findings, a pilot study of hepatic arterial infusions of (L-2-based immunochemotherapy was conducted in 21 patients (15 men, 6 women) with unresectable liver metastases from colorectal cancer, to determine whether the addition of IL-2 improved the therapeutic efficacy of chemotherapy alone. Interleukin-2 was given to all patients as 7 to 8 x 10(5) Japanese reference units (JRU) in addition to 5-fluorouracil (5-FU) 250 mg daily and mitomycin C (MMC) 4 mg once weekly, through a subcutaneous port for 3 weeks, After completion of the initial course, patients were discharged from the hospital and continued on a modified regimen for outpatient therapy: IL-2, 2.0 to 2.1 x 10(6) JRU and 5-FU 250 mg twice weekly; MMC 4 mg once weekly. Patient response rate was 76%, and the median survival from initiation of treatment was 24 months. Toxicity of the combined regimen was minimal. Peripheral lymphocyte phenotype study showed notable decreases in CD8+, CD16+, and CD57+ cells and an increase in CD4+ cells (ie, elevation of 4:8 ratio) during therapy. Electron microscopic analysis of the resected liver of a patient receiving the IL-2-mitomycin-C/5-fluorouracil (IL-2MF) infusion showed a pronounced accumulation of lymphocytes, penetrating from the space of Disse, around the cancer cells. The present study explores hepatic arterial infusion of IL-2-based immunochemotherapy as a new strategy, based on the activation of liver-associated immune response; this technique may provide improved response and survival for unresectable liver metastases.
  • Okuno K; Ozaki M; Onishi H; Hirohata T; Nakamura K; Shigeoka H; Yasutomi M
    Nihon Geka Gakkai zasshi 94 5 539  1993年05月 [査読有り]
  • H. Ohnishi; K. Okuno; M. Yasutomi
    Cancer Biotherapy 8 3 213 - 222 1993年 [査読有り]
     
    We studied the efficacy of infusing human recombinant interleukin-2 (IL- 2) through the splenic artery for generation of lymphokine activated killer (LAK) cells in vivo in a canine system. Catheters were inserted into the splenic artery, portal vein and inferior vena cava (IVC) in Beagle dogs. IL- 2 was administered continuously through either the splenic artery or IVC by portable infusion pump and the cytotoxic activity of portal vein blood lymphocytes (PVBL) and peripheral blood lymphocytes (PBL) against canine osteosarcoma D-17 target cells was monitored. Following administration low- dose IL-2 (8x105 IU/day) for 6 days through the splenic artery, LAK precursor cells were present, but not following administration intravenously. Interestingly, when a high dose of IL-2 (4x106 IU/day on days 1-6 and 13- 18) was administered through the splenic artery, strong cytotoxicity was detected in PVBL and PBL without subsequent culture in vitro with IL-2, suggesting that an infusion rate of 4x106 IU/day IL-2 may be sufficient for generation of LAK cells in vivo. These results suggest that continuous infusion of IL-2 through the splenic artery can generate LAK cells more easily and may prove especially useful for the immunotherapy of hepatic micrometastasis.
  • I. Nakajima; M. Ozaki; H. Jinnai; Y. Shilayama; T. Hirohata; K. Okuno; M. Yasutomi
    Cancer Biotherapy 8 4 319 - 326 1993年 [査読有り]
     
    The antitumor activity of Interleukin-1 (IL-1), was assessed against the murine adenocarcinoma colon 26 tumor model in combination with Interleukin-2 (IL-2). Colon 26 tumor cells were inoculated on the back of syngeneic BALB/c mice. Fourteen days after inoculation, when the tumor nodule reached approximately 10 mm in diameter, tumor nodules were resected and Hank's solution, IL-2, IL-1, or IL-2 plus IL-1 were injected directly into the mouse spleen. One week after treatment, potent natural killer (NK) and enhanced lymphokine activated killer (LAK) cell activities were seen in the splenocytes treated by the combination of IL-2 plus IL-1. Furthermore the combination treatment by IL-2 plus IL-1 resulted in a significantly prolonged survival. Phenotypic analysis showed an increased number of percent positive cells expressing asialo GM 1 and IL-2 receptor after treatment with IL-2 plus IL-1. A possible role of IL-1 in augmentation of IL-2 dependent antitumor activity in vivo is discussed.
  • 綿谷M; 大島M; 和田T; 寺下H; 松田T; 進藤勝久; 安富M
    Surgery Today 23 5 444 - 448 1993年 [査読有り]
     
    We report herein three cases of patients with adrenal metastases from colorectal carcinoma. Recurrent disease was suspected following markedly elevated levels of serum carcinoembryonic antigen (CEA), and adrenal metastases were confirmed by computed tomography (CT) scanning in all three patients. The adrenal metastasis was solitary in one patient and this patient is still alive and free from disease 1 year after undergoing complete removal of the adrenal metastasis. On the other hand, metastatic disease was not limited to the adrenal gland in the other two patients and both died of recurrent disease, 33 months and 4 months after undergoing removal of the adrenal metastases, respectively. Thus, although the prognosis of adrenal metastasis from colorectal cancer is usually poor, we believe that patients with a solitary adrenal metastasis will benefit from complete removal of the metastasis.
  • Masatomo Otsuka; Hironori Shigeoka; Henry C. Yang
    Cancer Chemotherapy and Pharmacology 30 5 407 - 411 1992年09月 [査読有り]
     
    The ability of doxorubicin to inhibit kinase C in vivo in cultured BALB/c 3T3 mouse fibroblasts was determined by the phosphorylation of the myristoylated alanine-rich C kinase substrate (MARCKS) and the induction of c-fos transcription following treatment with 200 nM phorbol 12-myristate 13-acetate. A concentration of 60 μM doxorubicin did not inhibit MARCKS phosphorylation but completely inhibited c-fos expression. The inhibition of c-fos expression was not specifically mediated via kinase C, since both the total RNA synthesis as measured by [3H]-uridine uptake and the fraction of serum-induced c-fos expression that was not attributable to kinase C were inhibited by doxorubicin. The present data do not support the hypothesis that the cytotoxic effect of doxorubicin is attributable to the inhibition of kinase C in vivo. © 1992 Springer-Verlag.
  • K OKUNO; H OHNISHI; K KOH; H SHINDO; H YOSHIOKA; M YASUTOMI
    BIOTHERAPY 4 4 257 - 265 1992年06月 [査読有り]
     
    We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 x 10(5) JRU/day) for 25-40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leu11 (CD16)+, OKM1(CD11)+ and OKIa1(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment. We conclude that continuous IS-IL-2 administration can result in an increase of their therapeutic efficacy of IL-2 administration and in a decrease its toxicity.
  • Hironori Shigeoka; Henry C. Yang
    Mechanisms of Ageing and Development 57 1 63 - 70 1991年01月 [査読有り]
     
    Cell cycle expression of the retinoblastoma (RB) gene was investigated in young and aging IMR 90 human diploid fibroblasts and in the immortalized but untrasformed A31 BALB/c 3T3 mouse fibroblasts. RB RNA levels incresed about 75% during late G1/S in both the young and old IMR 90 cells. Young and old cells had similar normalized amounts of RB RNA per cell. Kinase C activation did not stimulate RB transcription. The A31 cells showed a constant RB RNA level throughout G0/S. The data is consistent with the hypothesis that RB activity is regulated primarily post-transcriptionally and indicates that a change in the regulation of RB transcription is not part of the senescence phenomenon. © 1991.
  • Hironori Shigeoka; Henry C. Yang
    Mechanisms of Ageing and Development 55 1 49 - 59 1990年07月 [査読有り]
     
    Two early kinase C dependent events, the induction of c-fos transcription and the phosphorylation of an 87 kDa protein, were investigated in aging IMR 90 human diploid fibroblasts. C-fos induction and 87-kDa protein phosphorylation were similarly regulated in aging cells and their young counterparts. The data suggests that G0 exit or the competence phenomenon is intact in aging cells and that the proliferative block occurs later in G0/S. © 1990.
  • H. Shigeoka; H. C. Yang
    Oncogene 5 5 741 - 745 1990年 [査読有り]
     
    The regulation of c-fos expression was studied in the untransformed A31 Balb/c 3T3 mouse fibroblast cell line and in the derivative benzo(a)pyrene (BPA31), dimethylbenz(a)anthracene (DA31) and the Kirsten sarcoma virus (KA31) transformed cell lines. The peak induced c-fos RNA levels varied by about 20-fold among the cell lines. Differences in the peak level of c-fos RNA were due primarily to differences in the de novo transcriptional rate rather than in the stability of the message. Superinduction of 6-12x occurred after combined cycloheximide and phorbol ester treatment in the 4 cell lines. Superinduction of 20x in the untransformed A31 cells but only 1-3x in the transformed cells occurred when cycloheximidine and 10% serum were used. Superinduction of 5x in the A31 cells and of 1-2x in the transformed cells was found using cycloheximide and A23187. The data suggest the possibility that a labile protein which degrades the c-fos RNA is stabilized or increased in the transformed cells.
  • K. Kurooka; T. Matsuda; J. Maruyama; E. Morikawa; R. Kubo; J. Hida; K. Ko; K. Shindo; M. Yasutomi
    Japanese Journal of Cancer and Chemotherapy 16 8 2940 - 2943 1989年 [査読有り]
  • K. Shindo; M. Yasutomi; T. Matsuda; E. Morikawa; R. Kubo; J. Hida; T. Wada; N. Sagara
    Japanese Journal of Cancer and Chemotherapy 16 4 1283 - 1288 1989年 [査読有り]
  • K OKUNO; H TAKAGI; T NAKAMURA; Y NAKAMURA; Z IWASA; M YASUTOMI
    CANCER 58 5 1001 - 1006 1986年09月 [査読有り]

講演・口頭発表等

  • 診断後11年間保存的に良好な経過をたどっている真性腸石の1例  [通常講演]
    白山 玲奈; 重岡 宏典; 上田 敬博; 横山 恵一; 一ノ橋 紘平; 村尾 佳則; 北澤 康秀
    第46回日本救急医学会総会 2018年11月 ポスター発表
  • 腸結核により急性腹症を呈した4症例の検討  [通常講演]
    宮崎 知; 重岡 宏典; 酒井 健一; 西谷 暁子
    日本臨床外科学会雑誌 2016年10月
  • 当院における超音波ガイド下吸引式乳房組織生検の病理結果からみたセンチネルリンパ節生検の省略について  [通常講演]
    藤島 成; 重岡 宏典; 河原 邦光
    日本乳癌学会総会プログラム抄録集 2016年06月
  • 当院における穿刺吸引細胞診の検体採取の工夫  [通常講演]
    藤島 成; 河原 邦光; 安江 智美; 重岡 宏典
    日本乳癌学会総会プログラム抄録集 2015年07月
  • 終末期がん患者の経口摂取におけるQOL関連因子の検討  [通常講演]
    森本 恭子; 嶋田 和貴; 白山 敬之; 山東 真寿美; 嶋津 史恵; 中島 理恵; 重岡 宏典
    日本静脈経腸栄養学会雑誌 2015年01月
  • 当院における乳腺超音波診断と穿刺吸引細胞診の診断能の検討  [通常講演]
    藤島 成; 武本 昌子; 重岡 宏典; 河原 邦光
    日本乳癌学会総会プログラム抄録集 2014年07月
  • 当院における高齢者肺癌患者の予後因子の検討 栄養不良がもたらす影響  [通常講演]
    武岡 佐和; 白山 敬之; 森本 恭子; 金銅 葉子; 島津 史江; 山東 真寿美; 河原 邦光; 重岡 宏典
    静脈経腸栄養 2014年01月
  • 呼吸器専門病院におけるPEG継続使用できない要因についての検討  [通常講演]
    深川 喜久子; 重岡 宏典; 松本 智成; 黒川 雅史; 森本 恭子; 金銅 葉子; 西田 京子; 山東 真寿美; 嶋津 史恵
    静脈経腸栄養 2013年01月
  • S状結腸間膜内ヘルニア(intramesosigmoid hernia)のCT所見  [通常講演]
    久保 友宏; 竹下 徹; 島 英樹; 武田 良祝; 小林 洋明; 河原 正樹; 二ノ井 照久; 重岡 宏典; 望月 邦三; 田中 茂子; 前田 裕子; 崔 朝理; 下野 太郎; 三木 幸雄
    日本医学放射線学会秋季臨床大会抄録集 2012年08月
  • いずれもStage3Aであった3重複癌(胃、肺、大腸)の1例  [通常講演]
    新崎 亘; 吉藤 竹仁; 河原 邦光; 重岡 宏典
    日本外科系連合学会誌 2012年05月
  • 大腸癌肝転移再肝切除後の難治性胆汁瘻に対する瘻孔空腸吻合術後に合併した胆管気管支瘻の1例  [通常講演]
    船井 貞往; 北野 義徳; 田中 晃; 亀井 敬子; 重岡 宏典; 大和 宗久
    日本消化器外科学会総会 2011年07月
  • 胸部食道癌における術前・術後補助療法の有用性 胸部食道癌に対する成績向上を目指した積極的補助療法  [通常講演]
    安田 卓司; 今本 治彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 今野 元博; 重岡 宏典; 塩崎 均
    日本消化器外科学会総会 2010年07月
  • 食道粘膜下腫瘍に対する鏡視下手術の工夫  [通常講演]
    重岡 宏典; 今本 治彦; 新海 政幸; 彭 英峰; 安田 篤; 白石 治; 岩間 密; 今野 元博; 安田 卓司; 塩崎 均
    日本消化器外科学会総会 2010年07月
  • 術前合併症を有する食道癌手術の治療成績  [通常講演]
    新海 政幸; 安田 卓司; 岩間 密; 白石 治; 安田 篤; 彭 英峰; 今野 元博; 重岡 宏典; 今本 治彦; 塩崎 均
    日本消化器外科学会総会 2010年07月
  • 食道癌手術再建の工夫と実績  [通常講演]
    白石 治; 安田 卓司; 今本 治彦; 重岡 宏典; 今野 元博; 新海 政幸; 彭 英峰; 安田 篤; 岩間 密; 塩崎 均
    日本消化器外科学会総会 2010年07月
  • 食道癌根治切除後pN(+)症例に対するJCOG9204術後補助化学療法の有用性の検証  [通常講演]
    岩間 密; 安田 卓司; 白石 治; 安田 篤; 彭 英峰; 新海 政幸; 重岡 宏典; 今野 元博; 今本 治彦; 塩崎 均
    日本消化器外科学会総会 2010年07月
  • 胃癌外科治療(鏡視下)のState of the art 胃がんに対する腹腔鏡下胃切除術の検討  [通常講演]
    今本 治彦; 安田 篤; 安田 卓司; 新海 政幸; 彭 英峰; 白石 治; 岩間 密; 中森 康浩; 上田 和毅; 今野 元博; 重岡 宏典; 塩崎 均
    日本胃癌学会総会記事 2010年03月
  • ITPに合併した前庭部の胃癌に対し幽門側胃切除術と脾摘を行った1例  [通常講演]
    重岡 宏典; 塚本 義貴; 酒井 健一; 平井 昭彦; 中尾 照逸
    日本臨床外科学会雑誌 2009年10月
  • 腹膜播種陽性胃癌症例に対してのPaclitaxel腹腔内投与と逐次S-1+Weekly Paclitaxel療法  [通常講演]
    今野 元博; 今本 治彦; 塩崎 均; 彭 英峰; 川西 賢秀; 新海 政幸; 平井 紀彦; 重岡 宏典; 橋本 直樹; 大柳 治正
    日本消化器外科学会雑誌 2006年07月

MISC

  • 複数台のビデオカメラとビデオスイッチャーを用いた救急医学教育
    植嶋 利文; 布谷 早樹子; 岩本 博司; 福田 隆人; 豊田 甲子男; 石部 琢也; 横山 恵一; 木村 貴明; 松島 知秀; 重岡 宏典 日本救急医学会雑誌 33 (10) 862 -862 2022年10月
  • 【禍難を乗り越えて】コロナ禍におけるER感染対策 サージカルマスクでN95に負けない感染防御を目指して
    植嶋 利文; 一ノ橋 絋平; 福田 隆人; 浦瀬 篤史; 岩本 博司; 濱口 満英; 石部 琢也; 木村 貴明; 松島 知秀; 村尾 佳則; 重岡 宏典 日本救急医学会雑誌 32 (12) 1253 -1253 2021年11月
  • 心肺停止蘇生後に患者家族の価値観を大切にした症例
    濱口 満英; 村尾 佳則; 植嶋 利文; 松島 知秀; 木村 貴明; 石部 琢也; 一ノ橋 紘平; 浦瀬 篤史; 福田 隆人; 岩本 博司; 重岡 宏典 日本救急医学会雑誌 32 (12) 2304 -2304 2021年11月
  • 黒色食道に虚血性十二指腸炎を合併した一例
    太田 育夫; 高橋 均; 小野 恵; 重岡 宏典; 平出 敦 日本救急医学会雑誌 32 (12) 2465 -2465 2021年11月
  • 化膿性胸鎖関節炎に対し外科的ドレナージ術が著効した1例
    岩本 博司; 濱口 満英; 浦瀬 篤史; 福田 隆人; 一ノ橋 紘平; 石部 琢也; 木村 貴明; 松島 知秀; 植嶋 利文; 村尾 佳則; 重岡 宏典 日本救急医学会雑誌 32 (12) 2537 -2537 2021年11月
  • Clostridium perfringensによるガス産生性肝膿瘍の1救命例
    高橋 均; 平出 敦; 太田 育夫; 小野 恵; 福田 隆人; 重岡 宏典; 中尾 彰太; 小北 晃弘; 津田 宏; 船井 貞往; 山本 誠巳 日本救急医学会雑誌 32 (12) 2580 -2580 2021年11月
  • 小野 恵; 太田 育夫; 福田 隆人; 重岡 宏典; 平出 敦; 大西 勝博; 高橋 均 日本腹部救急医学会雑誌 41 (7) 551 -555 2021年11月
  • 石部 琢也; 松島 知秀; 重岡 宏典 手術 = Operation 75 (6) 965 -970 2021年05月
  • 植嶋利文; 木村貴明; 布川知史; 松島知英; 横山恵一; 石部琢也; 一ノ橋紘平; 浦瀬篤史; 福田隆人; 重岡宏典 日本脳神経外傷学会プログラム・抄録集 44th 2021年
  • 胸腔ドレーン挿入における新しいチューブ誘導鉗子の考案
    一ノ橋 紘平; 植嶋 利文; 浦瀬 篤史; 福田 隆人; 石部 琢也; 濱口 満英; 横山 恵一; 木村 貴明; 松島 知秀; 上田 敬博; 重岡 宏典 日本救急医学会雑誌 31 (11) 1870 -1870 2020年11月
  • 熱傷治療における人工真皮の有用性 当院における人工真皮を用いた下肢深達性II度・III度熱傷の治療効果の検討
    一ノ橋 紘平; 上田 敬博; 浦瀬 篤史; 福田 隆人; 豊田 甲子男; 濱口 満英; 布川 知史; 松島 知秀; 植嶋 利文; 重岡 宏典 熱傷 46 (4) 133 -133 2020年11月
  • 盲腸癌による腸重積とStreptococcus milleriによる化膿性肝膿瘍を合併し敗血症を呈した1例
    高橋 均; 太田 育夫; 小野 恵; 山本 誠己; 重岡 宏典; 平出 敦; 小北 晃弘; 津田 宏; 船井 貞往; 小川 翔吾; 安井 絢子 日本救急医学会雑誌 31 (11) 1273 -1273 2020年11月
  • 鈍的外傷における頻脈からの脈拍数の減少は線溶亢進の指標となる
    濱口 満英; 松島 知秀; 木村 貴明; 横山 恵一; 石部 琢也; 一ノ橋 紘平; 浦瀬 篤史; 福田 隆人; 植嶋 利文; 村尾 佳則; 重岡 宏典 日本救急医学会雑誌 31 (11) 2153 -2153 2020年11月
  • 心不全徴候を主訴に来院した感染性多発性肝嚢胞の1例
    小野 恵; 太田 育夫; 平出 敦; 重岡 宏典; 高橋 均; 大西 勝博; 高場 雄久; 東 哲明; 小北 晃弘; 中尾 彰太; 松岡 哲也 日本救急医学会雑誌 31 (11) 2209 -2209 2020年11月
  • 南 民衛; 四ヶ所 正紀; 前本 了一; 本山 正将; 木村 貴明; 植嶋 利文; 重岡 宏典 日本臨床救急医学会雑誌 23 (3) 368 -368 2020年08月
  • 巨大な膿瘍形成性虫垂炎に対して保存的治療後に腹腔鏡下虫垂切除術を施行した1例
    横山 恵一; 上田 敬博; 重岡 宏典; 津田 宏; 北澤 康秀 日本救急医学会雑誌 31 (7) 243 -248 2020年07月
  • 人工真皮による母床構築と分層植皮により救肢することができた両下腿III度熱傷の1例
    一ノ橋 紘平; 上田 敬博; 福田 隆人; 浦瀬 篤史; 豊田 甲子男; 横山 恵一; 布川 知史; 松島 知秀; 植嶋 利文; 重岡 宏典 熱傷 45 (4) 176 -176 2019年11月
  • 穿孔性腹膜炎の術後創に対する持続洗浄を併用した陰圧閉鎖療法の経験
    一ノ橋 紘平; 諸富 公昭; 西脇 仁; 平野 成彦; 福田 智一; 磯貝 典孝; 横山 恵一; 重岡 宏典 日本形成外科学会会誌 39 (10) 521 -522 2019年10月
  • 不断前進、敗血症診療 敗血症に対するトレミキシン施行例の解析
    濱口 満英; 村尾 佳則; 植嶋 利文; 松島 知秀; 布川 知史; 木村 貴明; 石部 琢也; 豊田 甲子男; 一ノ橋 紘平; 福田 隆人; 重岡 宏典 日本救急医学会雑誌 30 (9) 599 -599 2019年09月
  • 外傷後の血液凝固機能異常についての研究 血腫モデルによる検討
    横山 恵一; 北澤 康秀; 上田 敬博; 津田 紀子; 重岡 宏典 日本救急医学会雑誌 30 (9) 678 -678 2019年09月
  • 鼻鏡を用いた胸腔ドレーン挿入法
    一ノ橋 紘平; 植嶋 利文; 浦瀬 篤史; 福田 隆人; 豊田 甲子男; 横山 恵一; 布川 知史; 松島 知秀; 上田 敬博; 重岡 宏典 日本救急医学会雑誌 30 (9) 682 -682 2019年09月
  • 気胸の超音波診断を教育するための手軽にできるシミュレーター
    植嶋 利文; 一ノ橋 紘平; 豊田 甲子男; 濱口 満英; 石部 琢也; 横山 恵一; 木村 貴明; 布川 知史; 松島 知秀; 上田 敬博; 重岡 宏典 日本救急医学会雑誌 30 (9) 707 -707 2019年09月
  • 肺癌小腸転移による小腸穿孔の1例
    福田 隆人; 濱口 満英; 豊田 甲子男; 石部 琢也; 横山 恵一; 松島 知秀; 一ノ橋 紘平; 村尾 佳則; 重岡 宏典 日本救急医学会雑誌 30 (9) 776 -776 2019年09月
  • 乳癌術後リンパ浮腫上肢に受傷したIII度熱傷に対して局所陰圧閉鎖療法が著効した1例
    高慶 承史; 上田 敬博; 福田 隆人; 浦瀬 篤史; 白山 玲奈; 一ノ橋 紘平; 豊田 甲子男; 石部 琢也; 中尾 隆美; 横山 恵一; 木村 貴明; 布川 知史; 松島 知秀; 植嶋 利文; 村尾 佳則; 重岡 宏典; 北澤 康秀 熱傷 45 (2) 106 -107 2019年06月
  • 一ノ橋紘平; 上田敬博; 松島知秀; 福田隆人; 浦瀬篤史; 石部琢也; 豊田甲子男; 横山恵一; 木村貴明; 村尾佳則; 北澤康秀; 重岡宏典 日本熱傷学会総会・学術集会プログラム・抄録集 45th 98 2019年05月
  • 鈍的外傷での頻脈からの脈拍数の減少は大量出血の早期認知となる
    濱口 満英; 植嶋 利文; 松島 知秀; 木村 貴明; 中尾 隆美; 石部 琢也; 豊田 甲子男; 村尾 佳則; 重岡 宏典 日本外傷学会雑誌 33 (2) 208 -208 2019年05月
  • 診断後11年間保存的に良好な経過をたどっている真性腸石の1例
    白山 玲奈; 重岡 宏典; 上田 敬博; 横山 恵一; 一ノ橋 紘平; 村尾 佳則; 北澤 康秀 日本救急医学会雑誌 29 (10) 624 -624 2018年10月
  • 田宮 基裕; 鈴木 秀和; 白山 敬之; 田中 彩子; 森下 直子; 岡本 紀雄; 酒井 健一; 河原 邦光; 重岡 宏典; 平島 智徳 肺癌 57 (5) 439 -439 2017年09月
  • 腸結核により急性腹症を呈した4症例の検討
    宮崎 知; 重岡 宏典; 酒井 健一; 西谷 暁子 日本臨床外科学会雑誌 77 (増刊) 777 -777 2016年10月
  • 当院における超音波ガイド下吸引式乳房組織生検の病理結果からみたセンチネルリンパ節生検の省略について
    藤島 成; 重岡 宏典; 河原 邦光 日本乳癌学会総会プログラム抄録集 24回 414 -414 2016年06月
  • Regorafenibを長期投与した結腸癌の一例
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    橋本 直樹; 石川 原; 新海 政幸; 川西 賢秀; 平井 紀彦; 今野 元博; 重岡 宏典; 今本 治彦; 塩崎 均 日本外科学会雑誌 106 (臨増) 457 -457 2005年04月
  • cDNAアレイフィルターを用いた食道癌の包括的遺伝子発現プロファイルの解析
    重岡 宏典; 塩﨑 均; 奥野 清隆; 今本 治彦 2005年02月
  • 【消化器癌治療のコンセンサス 消化管】 胸部食道癌(早期・進行)
    塩崎 均; 今本 治彦; 重岡 宏典; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 土岐 祐一郎 消化器外科 27 (11) 1639 -1646 2004年10月
  • 各科領域における化学療法の工夫(食道) 進行再発食道癌に対する2nd lineとしてのDocetaxel+Nedaplatin併用化学療法の試み
    今本 治彦; 今野 元博; 川西 賢秀; 平井 紀彦; 新海 政幸; 西川 正康; 白石 治; 重岡 宏典; 橋本 直樹; 塩崎 均 日本癌治療学会誌 39 (2) 386 -386 2004年09月
  • 胃癌腹膜転移に対する治療方針 腹膜播種を伴う胃癌症例に対するPaclitaxel腹腔内投与と逐次S-1+weekly Paclitaxel投与の腹水の細胞診断学的な効果と安全性について
    今野 元博; 塩崎 均; 白石 治; 西川 正康; 新海 政幸; 川西 賢秀; 平井 紀彦; 重岡 宏典; 今本 治彦; 橋本 直樹; 大柳 治正 日本癌治療学会誌 39 (2) 390 -390 2004年09月
  • 西川 正康; 今野 元博; 新海 政幸; 川西 賢秀; 平井 紀彦; 重岡 宏典; 今本 治彦; 塩崎 均; 大柳 治正 日本消化器外科学会雑誌 37 (7) 2004年07月
  • Open手術からみた食道癌に対する鏡視下手術の評価 Open手術と鏡視下手術の融合を目指して
    塩崎 均; 重岡 宏典; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 西川 正博 日本消化器外科学会雑誌 37 (7) 931 -931 2004年07月
  • 腹膜播種への対処(診断と治療の工夫) 腹膜播種を伴う4型胃癌に対する治療戦略
    西川 正康; 今野 元博; 新海 政幸; 川西 賢秀; 平井 紀彦; 重岡 宏典; 今本 治彦; 塩崎 均; 大柳 治正 日本消化器外科学会雑誌 37 (7) 1039 -1039 2004年07月
  • 重岡 宏典; 橋本 直樹; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 西川 正康; 安田 篤; 塩崎 均 日本消化器外科学会雑誌 37 (7) 1078 -1078 2004年07月
  • 当科で経験した食道癌術後再建胃管に穿孔を生じた2症例について
    安田 篤; 川西 賢秀; 西川 正康; 新海 政幸; 平井 紀彦; 今野 元博; 重岡 宏典; 今本 治彦; 塩崎 均; 大柳 治正 日本消化器外科学会雑誌 37 (7) 1154 -1154 2004年07月
  • 腹腔鏡補助下幽門側胃切除術における合併症と対策
    今本 治彦; 安田 篤; 新海 政幸; 平井 紀彦; 川西 賢秀; 西川 正康; 今野 元博; 重岡 宏典; 塩崎 均 日本消化器外科学会雑誌 37 (7) 1222 -1222 2004年07月
  • 食道癌に対する小開胸・胸腔鏡補助下手術の手技習熟に対する検討
    今野 元博; 塩崎 均; 西川 正康; 新海 政幸; 白石 治; 川西 賢秀; 平井 紀彦; 重岡 宏典; 今本 治彦; 大柳 治正 日本消化器外科学会雑誌 37 (7) 1226 -1226 2004年07月
  • K Okuno; K Inoue; T Tokoro; JI Hida; H Shiozaki; M Yasutomi DISEASES OF THE COLON & RECTUM 47 (6) 1059 -1059 2004年06月
  • T Tokoro; K Inoue; T Yoshihuji; J Hida; H Inufusa; H Shiozaki; M Yasutomi; K Okuno DISEASES OF THE COLON & RECTUM 47 (6) 1097 -1097 2004年06月
  • 高齢者に対する腹腔鏡補助下胃切除術の有用性
    今本 治彦; 川西 賢秀; 平井 紀彦; 新海 政幸; 西川 正康; 安田 篤; 今野 元博; 重岡 宏典; 塩崎 均 日本外科系連合学会誌 29 (3) 522 -522 2004年06月
  • 膜構造を意識した食道癌の手術
    塩崎 均; 重岡 宏典; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 西川 正康 日本外科学会雑誌 105 (臨増) 157 -157 2004年03月
  • 進行胃癌に対する術前短期化学療法(short NeoadjuvantChemotherapy:s-NAC)の有用性の検討
    十川 佳史; 今野 元博; 里井 俊平; 西川 正康; 酒井 健一; 市川 英明; 石丸 英三郎; 平井 紀彦; 川西 賢秀; 重岡 宏典; 今本 治彦; 塩崎 均; 大柳 治正 日本外科学会雑誌 105 (臨増) 515 -515 2004年03月
  • 【術前・術後のサーベイランスプログラム】 食道 食道アカラシア
    今本 治彦; 安田 篤; 平井 紀彦; 川西 賢秀; 重岡 宏典; 塩崎 均 外科 65 (12) 1378 -1381 2003年11月
  • 大量出血をきたし,食道ステントと大動脈ステントグラフトで止血しえた食道癌の1例
    石川 真平; 田中 晃; 今本 治彦; 重岡 宏典; 川西 賢秀; 平井 紀彦; 前田 宗宏; 柳生 行伸; 塩崎 均 日本消化器外科学会雑誌 36 (10) 1473 -1473 2003年10月
  • 噴門部胃癌に対する噴門側胃切除空腸間置再建術における工夫
    重岡 宏典; 田中 晃; 今本 治彦; 今野 元博; 平井 紀彦; 川西 賢秀; 新海 政幸; 西川 正康; 安田 篤; 塩崎 均 日本臨床外科学会雑誌 64 (増刊) 316 -316 2003年10月
  • 進行胃癌に対する術前短期化学療法(short Neoadjuvant Chemotherapy:s-NAC)の有用性の検討
    十川 佳史; 今野 元博; 西川 正康; 平井 紀彦; 川西 賢秀; 重岡 宏典; 今本 治彦; 加藤 道男; 塩崎 均; 大柳 治正 日本癌治療学会誌 38 (2) 527 -527 2003年09月
  • 進行胃癌転移リンパ節内癌細胞における術前短期化学療法(short Neoadjuvant Chemotherapy:s-NAC)の効果の検討
    今野 元博; 十川 佳史; 西川 正康; 平井 紀彦; 川西 賢秀; 重岡 宏典; 今本 治彦; 加藤 道男; 塩崎 均; 大柳 治正 日本癌治療学会誌 38 (2) 527 -527 2003年09月
  • 進行食道癌による大量出血を食道ステントと大動脈ステントで止血し,長期生存を得た1例
    石川 真平; 田中 晃; 今本 治彦; 重岡 宏典; 平井 紀彦; 川西 賢秀; 塩崎 均 日本消化器外科学会雑誌 36 (7) 1101 -1101 2003年07月
  • 腹腔鏡下手術におけるサージアシストシステムの使用経験
    今本 治彦; 平井 紀彦; 黒田 幸作; 川西 賢秀; 石川 真一; 重岡 宏典; 塩崎 均 日本外科学会雑誌 104 (臨増) 329 -329 2003年04月
  • 胸部食道癌に対する血行再建を付加した皮下経路有茎空腸再建術
    重岡 宏典; 田中 晃; 今本 治彦; 平井 紀彦; 黒田 幸作; 川西 賢秀; 石川 真平; 塩崎 均 日本外科学会雑誌 104 (臨増) 336 -336 2003年04月
  • 進行食道癌における神経浸潤の検討
    石川 真平; 田中 晃; 今本 治彦; 重岡 宏典; 平井 紀彦; 川西 賢秀; 黒田 幸作; 塩崎 均 日本外科学会雑誌 104 (臨増) 417 -417 2003年04月
  • 大動脈ステントグラフト挿入にて止血しえた食道癌の1例
    柳生 行伸; 渡邊 学; 任 誠雲; 西村 恭昌; 重岡 宏典; 塩崎 均; 前田 宗宏 IVR: Interventional Radiology 18 (1) 68 -68 2003年01月
  • 若年者に発症し,術前診断が困難であった巨大な食道神経鞘腫の一切除例
    南 憲司; 川西 賢秀; 今本 治彦; 石川 真平; 黒田 幸作; 平井 紀彦; 重岡 宏典; 田中 晃; 塩崎 均 日本臨床外科学会雑誌 63 (増刊) 482 -482 2002年10月
  • 進行食道癌における神経周囲浸潤からみた化学放射線併用療法の意義
    石川 真平; 田中 晃; 重岡 宏典; 平井 紀彦; 北野 義徳; 塩崎 均 近畿大学医学雑誌 27 (2) 52A -52A 2002年10月
  • T4食道癌に対する化学放射線療法
    西村 恭昌; 鈴木 実; 中松 清志; 金森 修一; 柳生 行伸; 重岡 宏典 日本消化器外科学会雑誌 35 (9) 1578 -1578 2002年09月
  • 噴問部粘膜癌に対する噴問側胃切除術
    田中 晃; 重岡 宏典; 大塚 浩史; 平井 紀彦; 北野 義徳; 石川 真平; 松崎 智彦; 大尾 充剛; 塩崎 均 日本消化器外科学会雑誌 35 (8) 1468 -1468 2002年08月
  • 【検査計画法】 消化器疾患編 逆流性食道炎・食道潰瘍・食道憩室
    塩崎 均; 田中 晃; 今本 治彦; 重岡 宏典 綜合臨床 51 (増刊) 1378 -1385 2002年05月
  • 実用的なcDNAアレイを用いた胃癌細胞株の遺伝子発現解析
    北野 義徳; 奥野 清隆; 井上 潔彦; 石川 真平; 平井 紀彦; 大塚 浩史; 重岡 宏典; 田中 晃; 塩崎 均 日本外科学会雑誌 103 (臨増) 361 -361 2002年03月
  • 肉眼的漿膜浸潤陽性胃癌に対するRandomized Clinical Trialによる術中の腹腔内投与抗癌剤の検討
    重岡 宏典; 田中 晃; 大塚 浩史; 平井 紀彦; 北野 義徳; 石川 真平; 奥野 清隆; 塩崎 均 日本外科学会雑誌 103 (臨増) 480 -480 2002年03月
  • 進行食道癌における神経周囲浸潤からみた化学放射線併用療法の意義
    田中 晃; 石川 真平; 重岡 宏典; 大塚 浩史; 平井 紀彦; 北野 義徳; 松崎 智彦; 大尾 充剛; 塩崎 均 日本外科学会雑誌 103 (臨増) 570 -570 2002年03月
  • 肉眼的漿膜浸潤陽性胃癌に対する術中の腹腔内投与抗癌剤の検討 Randomized Clinical Trialの結果
    重岡 宏典; 田中 晃; 大塚 浩史; 平井 紀彦; 北野 義徳; 石川 真平; 白井 治; 奥野 清隆; 塩崎 均 日本癌治療学会誌 36 (2) 531 -531 2001年10月
  • 併用化学療法の進歩 食道癌の放射線療法に対する化学療法併用の意義 神経周囲浸潤の検討から
    田中 晃; 石川 真平; 重岡 宏典; 大塚 浩史; 平井 紀彦; 北野 義徳; 奥野 清隆; 塩崎 均; 西村 恭昌 日本癌治療学会誌 36 (2) 506 -506 2001年10月
  • 実用的なcDNAアレイを用いた食道癌の遺伝子発現プロファイル解析
    北野 義徳; 奥野 清隆; 井上 潔彦; 平井 紀彦; 大塚 浩史; 重岡 宏典; 田中 晃; 安富 正幸 日本消化器外科学会雑誌 34 (7) 1148 -1148 2001年07月
  • 転移性肝癌に対する5-FU肝動注投与の利点
    平井 紀彦; 奥野 清隆; 重岡 宏典; 本田 哲史; 河合 功; 北野 義徳; 井上 潔彦; 安富 正幸 癌と化学療法 27 (12) 1875 -1875 2000年10月
  • DNAアレイを用いた胃癌細胞株の遺伝子発現プロファイルの解析と臨床病理学的特徴との関連
    北野 義徳; 奥野 清隆; 井上 潔彦; 南 憲司; 重岡 宏典; 田中 晃; 安富 正幸 日本癌治療学会誌 35 (2) 332 -332 2000年09月
  • 接着因子・トピックス 癌細胞表面のシアル酸発現と肝局所免疫機構の関連
    河合 功; 奥野 清隆; 平井 紀彦; 重岡 宏典; 田中 晃; 安富 正幸 Biotherapy 14 (1) 95 -95 2000年01月
  • 癌細胞表面のシアル酸発現が肝局所免疫機構に与える影響
    河合 功; 奥野 清隆; 平井 紀彦; 重岡 宏典; 田中 晃; 安富 正幸 近畿大学医学雑誌 24 (2) 39A -39A 1999年12月
  • 大腸癌表面のシアル酸発現が肝転移に及ぼす影響
    河合 功; 奥野 清隆; 平井 紀彦; 重岡 宏典; 田中 晃; 安富 正幸 日本癌治療学会誌 34 (2) 437 -437 1999年10月
  • 肝転移における大腸癌細胞表面のシアル酸の役割
    奥野 清隆; 河合 功; 平井 紀彦; 重岡 宏典; 安富 正幸 日本癌学会総会記事 58回 235 -235 1999年08月
  • 肝転移成立における肝類洞内リンパ球機能と大腸癌細胞表面抗原の関連
    奥野 清隆; 平井 紀彦; 河合 功; 本田 哲史; 北野 義徳; 重岡 宏典; 田中 晃; 安富 正幸 日本消化器外科学会雑誌 32 (6) 1592 -1592 1999年06月
  • 放射線・化学療法で1年以上CRの状態が持続した食道癌非切除症例
    松村 衛磨; 田中 晃; 奥野 清隆; 吉川 栄人; 河合 功; 李 潤相; 平井 紀彦; 黒田 幸作; 重岡 宏典; 安富 正幸 日本消化器外科学会雑誌 32 (3) 948 -949 1999年03月
  • 肝局所免疫機構からみた肝転移の成立機序
    奥野 清隆; 河合 功; 平井 紀彦; 李 潤相; 陣内 浩喜; 重岡 宏典; 安富 正幸 日本外科学会雑誌 100 (臨増) 66 -66 1999年02月
  • 中居 卓也; 白石 治; 川辺 高史; 船井 貞往; 香山 仁志; 康 謙三; 安富 正幸 日本消化器外科学会雑誌 32 (12) 2674 -2678 1999年
  • Interleukin(IL)-12による抗腫瘍免疫機構についてのIL-2との比較
    李 潤相; 陣内 浩喜; 奥野 清隆; 廣畑 健; 重岡 宏典; 平井 紀彦; 本田 哲史; 河合 功; 安富 正幸 Biotherapy 13 (1) 127 -127 1999年01月
  • 残胃癌の臨床病理的特徴
    梅村 博也; 河合 功; 平井 紀彦; 重岡 宏典; 田中 晃; 奥野 清隆; 進藤 勝久; 安富 正幸 日本臨床外科学会雑誌 59 (増刊) 700 -700 1998年10月
  • 大腸癌肝転移における肝切除術後の補助免疫化学肝動注の意義
    奥野 清隆; 平井 紀彦; 河合 功; 重岡 宏典; 中居 卓也; 康 謙三; 安富 正幸 日本癌治療学会誌 33 (3) 247 -247 1998年08月
  • 局所高度進行食道癌に対する新しいネオアジュバント療法(IL-2,Nedaplatin,5-FU)の試み
    河合 功; 奥野 清隆; 田中 晃; 重岡 宏典; 吉川 栄人; 黒田 幸作; 平井 紀彦; 李 潤相; 松村 衛磨; 本田 哲史 日本癌治療学会誌 33 (3) 216 -216 1998年08月
  • IL-2の転移性肝腫瘍内5-FU代謝に及ぼす影響
    平井 紀彦; 奥野 清隆; 李 潤相; 重岡 宏典; 本田 哲史; 河合 功; 安富 正幸 日本癌治療学会誌 33 (3) 459 -459 1998年08月
  • 奥野 清隆; 平井 紀彦; 河合 功; 本田 哲史; 重岡 宏典; 香山 仁志; 中居 卓也; 田中 晃; 康 謙三; 安富 正幸 日本消化器外科学会雑誌 31 (6) 1320 -1320 1998年06月
  • 奥野 清隆; 田中 晃; 重岡 宏典; 松村 衛磨; 本田 哲史; 李 潤相; 平井 紀彦; 河合 功; 安富 正幸 日本外科学会雑誌 99 307 -307 1998年03月
  • 田中 晃; 松村 衛磨; 吉川 栄人; 所 忠男; 重岡 宏典; 奥野 清隆; 安富 正幸 日本外科学会雑誌 99 (0) 1998年03月
  • マウス肝転移におけるモノクローナル抗Thomsen-Friedenreich(TF)抗体を用いた肝転移機構の解析
    重岡 宏典 日本外科学会雑誌 99 (臨増) 413 -413 1998年03月
  • 奥野 清隆; 平井 紀彦; 李 潤相; 河合 功; 重岡 宏典; 香山 仁志; 肥田 仁一; 田中 晃; 康 謙三; 安富 正幸 日本消化器外科学会雑誌 31 (2) 655 -655 1998年02月
  • 松村 衛磨; 田中 晃; 吉川 栄人; 所 忠男; 内田 寿博; 久保 隆一; 重岡 宏典; 奥野 清隆; 安富 正幸 日本消化器外科学会雑誌 31 (2) 1998年02月
  • 梅村 博也; 中嶋 章浩; 本田 哲史; 李 潤相; 平井 紀彦; 松村 衛麿; 吉川 栄人; 陣内 浩喜; 重岡 宏典; 田中 晃; 奥野 清隆; 進藤 勝久; 安富 正幸 近畿大学医学雑誌 22 (1) 5A 1997年06月
  • Y Cao; P Stosiek; BM Ghadimi; G Pecher; H Shigeoka; U Karsten EUROPEAN JOURNAL OF CANCER 33 95 -95 1997年06月
  • 早期胃癌における再発死亡例の検討
    重岡 宏典 消化器集団検診 35 (3) 439 -439 1997年05月
  • OTSUKA Masatomo; SHIGEOKA Hironori; OKUNO Kiyotaka; WATATANI Masahiro Acta medica Kinki University 22 (1) 27 -34 1997年03月
  • 吉川 栄人; 田中 晃; 村松 衛磨; 内田 寿博; 待寺 則和; 久保 隆一; 重岡 宏典; 奥野 清隆; 安富 正幸 日本消化器外科学会雑誌 30 (2) 383 -383 1997年02月
  • 奥野 清隆; 平井 紀彦; 李 潤相; 重岡 宏典; 肥田 仁一; 奥山 仁志; 中居 卓也; 康 謙三; 進藤 勝久; 安富 正幸 日本消化器外科学会雑誌 30 (2) 306 -306 1997年02月
  • TANAKA Akira; OKUNO Kiyotaka; SHIGEOKA Hironori; KOH Kenzoh; WATATANI Masahiro; FUNAI Sadao; YASUTOMI Masayuki Acta medica Kinki University 21 (4) 283 -288 1996年12月
  • 由谷逸朗; 加減秀樹; 木下道弘; 松井繁長; 中尾起久子; 川端一史; 高幣和郎; 石井望人; 重岡宏典 Proc Soc Surviv Time Stud Cancer Patients 16 (1) 76 -82 1996年05月
  • H. Yamada; K. Kurooka; S. Funai; Y. Fujii; Y. Imanishi; S. Sato; M. Watatani; K. Shindo; M. Yasutomi Japanese Journal of Cancer and Chemotherapy 22 Suppl 2 186 -191 1995年06月
  • 奥野 清隆; 陣内 浩喜; 李 潤相; 中村 勝人; 重岡 宏典; 久保 隆一; 中居 卓也; 康 謙三; 進藤 勝久; 安富 正幸 日本消化器外科学会雑誌 28 (6) 1307 -1307 1995年06月
  • 奥野 清隆; 陣内 浩喜; 李 潤相; 中村 勝人; 重岡 宏典; 廣畑 健; 進藤 勝久; 安富 正幸 日本消化器外科学会雑誌 28 (2) 491 -491 1995年02月
  • K OKUNO; H OHNISHI; NAKAJIMA, I; Y AKABANE; K KUROOKA; K KOH; K SHINDO; M YASUTOMI SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 24 (1) 80 -84 1994年
  • 尾崎 公俊; 奥野 清隆; 大西 博昭; 廣畑 健; 重岡 宏典; 中村 勝人; 進藤 勝久; 安富 正幸 近畿大学医学雑誌 18 (2) 24A 1993年06月
  • M. Yasutomi; K. Shindo; N. Mori; T. Matsuda Japanese Journal of Cancer and Chemotherapy 18 (4) 541 -546 1991年

共同研究・競争的資金等の研究課題

  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2002年 -2004年 
    代表者 : 重岡 宏典; 塩崎 均; 奥野 清隆; 今本 治彦
     
    進行食道癌は,いまだ消化器癌の中でももっとも予後の悪い疾患の一つであり,また表在癌といえどもリンパ節転移の頻度も高く,食道癌そのものの悪性度の高さが指摘されている.よってその分子レベルでの解明は急務である。 細胞の性質は複雑なネットワークを介した多数の遺伝子によって規定されており,これら多数の遺伝子変化により癌の生物学的特性が生み出されていると考えられている。近年,多数の遺伝子変化を同時に捉え,総合的に解析するアプローチとしてcDNAアレイが導入され,遺伝子発現解析が飛躍的に進展しつつある。 今回我々は,cDNAフィルターアレイを用いて,食道癌の生物学的特性を解明しようと試み,包括的な遺伝子発現プロファイルにより,食道癌の生物学的特性を分類し臨床に応用したいと考え検討を試みた。 患者に承諾を得たうえで,食道癌の切除標本の一部を切離し,超低温で保存を行った。それらのうち病理組織検査の結果、リンパ節転移を認めた群と無かった群についてDNAアレイ解析結果を比較しリンパ節転移に関与する遺伝子群の抽出を試みた。具体的にはニューラルネットワーク解析法にて転移の有無の予測プログラムを作成しようとしている。これまでに集積した40例以上の切除標本よりRNAを抽出しDNAアレイ解析を行った。しかしながら食道癌の外科的切除では他の消化器癌と違って開胸開腹の手術が必要なことから長時間を要するため、一部の標本からは十分に検討に耐えるレベルでのRNAの抽出ができなかった。このため現時点で有意な解析結果が得られていない。RNAの抽出精度を高めるため,内視鏡による生検標本の集積を行った結果、安定した抽出が可能となっている。今後それらの生検標本を用いて予定していたDNAアレイ解析を行い,さらに予後との関係について調査する。
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 1996年 -1998年 
    代表者 : 安富 正幸; 重岡 宏典; 田中 晃; 奥野 清隆
     
    本研究は種々の癌においてその発現が癌の進行度、転移などと関係が深いと考えられているThomsen-Friedenreich抗原に対するモノクローナル抗体を用いることにより、Colon 26細胞肝転移モデルでの肝転移の抑制効果を見たものである。肝臓は消化器癌の経門脈的血行転移が最も多い転移臓器であり、肝転移の有無が患者の予後を決定するといっても過言ではない。この研究ではneuraminidase処理してガラクトース基(Gal)を露出させた大腸癌細胞は肝転移をきたしやすいという教室のこれまでの結果を踏まえて、その露出させたGalをTF抗原に対するモノクローナル抗体と反応させて覆い隠すと再び肝転移結節数がもとのColon 26大腸癌細胞のそれと同程度に低下するという結果を示した。もちろん肝転移に関連する分子は数多く、シアリルLe^x、ラミニン分子、CEA分子なども関係していると思われる。Colon 26細胞表面にはシアリルLe^xとインテグリンα6が表出されていることを確認しているが、これらの分子は本実験系の肝転移には影響を与えず、TF抗原(Gal分子)の表現が重要であることが示された。TF抗原に対するモノクローナル抗体処理により肝転移が抑制されたという結果は非常に興味深く、TF抗原(Gal分子)が確かに肝転移に関係するという因果関係を直接証明した研究として意義深いものと考える。これらの分子が今後単なる腫瘍マーカーとしてではなくその治療に貢献する可能性が示された。
  • 日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 1994年 -1996年 
    代表者 : 奥野 清隆; 重岡 宏典; 廣畑 健
     
    大腸癌の切除不能肝転移に対してIL-2とMMC,5-FU併用免疫化学肝動注療法が高い奏功率(75%)を示したこと(pilot study)をもとに、その有効性を確認するために多施設共同での無作為化臨床試験(Phase II)を施行した。46例の登録(うち適格42症例)を得た中間解析での奏功率は化学療法単独群が40%であったのに対してIL-2併用群では60-78%と高く、pilot studyを支持する結果が得られたため、さらに大きな規模での臨床治験(後期第II相試験)に進むことになった。これら臨床治験と並行して、本法の作用機序の解析をラットの肝動注の実験系で進めてきた。平成6年度はIL-2肝動注による肝類洞内リンパ球機能の免疫学的変動を、平成7、8年度はおもにIL-2の薬理学的作用に重点をおいて解析を行った。その結果、IL-2肝動注によって肝類洞内リンパ球の^<51>Cr遊離法によって測定されるNK,LAK活性は増強し、さらに総リンパ球数は数倍に増加していた。したがって肝臓全体としての抗腫瘍活性はそれらの積として著明に増強することが判明した。IL-2の薬理学的作用に関する検討では5-FUとMMCの肝抽出率(HER)を測定したところ、IL-2の併用でそれらが上昇することが判明した。この事実は化学療法剤の肝臓での停留率が亢進し、全身的な副作用が軽減することを意味する。さらにIL-2併用による肝臓内5-FU代謝酵素の変動を検討したがIL-2併用によってもTS(thymidylate synthase)やDPD酵素活性に大きな影響は認められずIL-2によってこれらの酵素活性に変動がおこる可能性は低いと考えられた。以上の結果からIL-2の作用は肝類洞リンパ球の抗腫瘍活性の増強効果と化学療法剤の肝抽出率増強作用によるものが主で5-FU代謝酵素に与える影響は少ないと考えられた。
  • 日本学術振興会:科学研究費助成事業 一般研究(B)
    研究期間 : 1991年 -1993年 
    代表者 : 安富 正幸; 重岡 宏典; 奥野 清隆; 中嶋 一三; 広畑 健; 中村 洋介; 大西 博昭
     
    IL-2の生体内代謝を検討した結果、IL-2は腎尿細管に存在するacid proteaseで代謝をうけていることが明らかとなった。さらにこの酵素は分子量が60kDa付近のタンパク質で腎サイトゾール内に存在し、マウスで得たこの分画をウサギに免疫した結果、IL-2代謝酵素分画に対するポリクローナル抗体を得ることができた。この抗体存在下ではin vitroにおけるIL-2degradationがその濃度依存性に抑制され、また、マウスモデルにおいても、0.1mg/マウス以上の抗体を腹腔内投与処置することにより全身投与した^<125>I-IL-2の腎への集積性の低下と腎homogenateにおけるIL-2 degradationの抑制も確認した。しかしながら、現在の抗体価では血中半減期の延長は見られず目標である少量のIL-2による血中IL-2濃度の維持は実現せず、さらに抗体価の高い抗体の回収と純化にはこれまでのところ成功していない。 これとは異なるアプローチでIL-2の投与効率を高める研究は順調に進行してきた。すなわちIL-2の生体内代謝延長と肝局所への効果的な集積を目的として、IL-2を肝類洞壁細胞に多く存在するガラクトースレセプターを利用してIL-2をガラクトースを中心としたリポゾームに封入し、より効果的に肝局所へのIL-2の取り込みを計る実験である。これまでのところ凍結乾燥法によって比較的均一な粒子径(100nm前後)で、IL-2封入率の良好な(60%程度)リポゾーム製剤を作製することができた。この製剤(Gal-lipo.IL-2)は対照群(lipo.IL-2)に比較して、ことに肝臓への集積性が高く、肝類洞内リンパ球の抗腫瘍活性を長期間持続させうることができた。現在、肝転移モデルを用いてin vivo抗腫瘍効果を検討中である。今後は本製剤の臨床応用に向けてさらに安全性、安定性などの基礎研究を続ける予定である。

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