2024/03/09 更新

写真a

コスギ シンイチ
小杉 伸一
KOSUGI Shinichi
所属
医歯学総合病院 魚沼地域医療教育センター 特任教授
職名
特任教授
外部リンク

学位

  • 博士(医学) ( 1999年3月   新潟大学 )

研究キーワード

  • Oncology

  • Upper gastrointestinal surgery

  • 上部消化管外科

  • 腫瘍学

研究分野

  • ライフサイエンス / 消化器外科学

  • ライフサイエンス / 病態医化学

経歴

  • 新潟大学   医歯学総合病院 魚沼地域医療教育センター   特任教授

    2014年12月 - 現在

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 機能再建医学   講師

    2013年6月 - 2014年11月

  • 新潟大学   医歯学総合研究科 医科学専攻   助教

    2012年11月 - 2013年5月

  • 新潟大学   医歯学総合病院 消化器外科   助教

    2012年11月 - 2013年5月

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻   助教

    2012年11月 - 2013年5月

  • 新潟大学   第一外科   助教

    2007年11月 - 2012年11月

  • 新潟大学   医歯学総合病院   助教

    2005年4月 - 2007年10月

▶ 全件表示

 

論文

  • Ulcer Scarring in the Gastric Conduit Is a Risk Factor for Anastomotic Leakage After Esophagectomy for Esophageal Cancer. 国際誌

    Daisuke Motegi, Hiroshi Ichikawa, Takeo Bamba, Yusuke Muneoka, Yosuke Kano, Kenji Usui, Takaaki Hanyu, Takashi Ishikawa, Yuki Hirose, Kohei Miura, Yosuke Tajima, Yoshifumi Shimada, Jun Sakata, Satoru Nakagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract   27 ( 2 )   250 - 261   2023年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL. METHODS: Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively. RESULTS: AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004). CONCLUSIONS: Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.

    DOI: 10.1007/s11605-022-05545-0

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  • Retraction Note to: Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer.

    Yoshifumi Shimada, Tomoki Kido, Hitoshi Kameyama, Mae Nakano, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Masayuki Nagahashi, Takashi Kobayashi, Masahiro Minagawa, Shin-Ichi Kosugi, Toshifumi Wakai, Yoichi Ajioka

    Surgery today   52 ( 3 )   519 - 519   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00595-022-02466-y

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  • Comprehensive Assessment of Swallowing Function Before and After Abdominal Surgery Including Thoracoabdominal Esophagectomy

    Shin-ichi Kosugi, Naotaka Aizawa, Hiroshi Ichikawa, Jin Magara, Takaaki Hanyu, Takashi Ishikawa

    Indian Journal of Surgery   2021年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    DOI: 10.1007/s12262-020-02586-0

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  • Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer. 国際誌

    Takuya Ando, Jun Sakata, Tatsuya Nomura, Kabuto Takano, Kazuyasu Takizawa, Kohei Miura, Yuki Hirose, Takashi Kobayashi, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Masayuki Nagahashi, Shin-Ichi Kosugi, Toshifumi Wakai

    Langenbeck's archives of surgery   406 ( 5 )   1521 - 1532   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS: Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS: Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION: The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

    DOI: 10.1007/s00423-021-02165-1

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  • Feasibility and educational value of fluorescence cholangiography in laparoscopic cholecystectomy.

    Tomo Oiwa, Motoko Takahashi, Kenichiro Hirano, Yo Sato, Eiji Sunami, Shin-Ichi Kosugi

    Asian journal of endoscopic surgery   14 ( 4 )   767 - 774   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Near-infrared fluorescence cholangiography during a laparoscopic cholecystectomy has become widely accepted as a useful auxiliary tool to visualize the extrahepatic biliary structures. We investigated the feasibility and educational value of a method with longer interval between the administration of indocyanine green and the imaging of these structures. METHODS: Approximately 18 hours before their surgery, patients (n = 51) were intravenously administered 0.25 mg/kg of indocyanine green. Each laparoscopic cholecystectomy was performed under fluorescence imaging in combination with white-light imaging. Operative outcomes including visualization of the extrahepatic biliary structures and operative time were compared between the patients on whom board-certified surgeons operated (feasibility phase; n = 18) and the patients on whom a surgery resident operated (educational phase; n = 33). RESULTS: There were no adverse events related to the longer interval method. The visualization rates of extrahepatic biliary structures were comparable between the two phases. Both the mean time to divide the cystic duct and the mean time to remove the gallbladder in the educational phase were significantly longer than those in the feasibility phase (68.2 vs 24.4 minutes and 30.2 vs 15.8 minutes, P < .001 each). There was no significant difference in other operative outcomes. The operative time learning curve did not decrease with a resident's experience. CONCLUSIONS: Fluorescence cholangiography with the longer interval method was feasible and could identify the extrahepatic biliary structures irrespective of the surgeon's experience; however, it did not decrease the operative time with experience.

    DOI: 10.1111/ases.12939

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  • 食道癌手術における胃管再建 当科の標準術式と短期成績

    市川 寛, 羽入 隆晃, 加納 陽介, 石川 卓, 茂木 大輔, 宗岡 悠介, 須藤 翔, 小柳 英人, 廣瀬 雄己, 三浦 宏平, 田島 陽介, 中野 麻恵, 滝沢 一泰, 中野 雅人, 島田 能史, 永橋 昌幸, 坂田 純, 小林 隆, 小杉 伸一, 若井 俊文

    日本外科学会定期学術集会抄録集   121回   PS - 6   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • 食道癌手術における食道胃管吻合部狭窄の検討

    茂木 大輔, 市川 寛, 番場 竹生, 加納 陽介, 羽入 隆晃, 須藤 翔, 石川 卓, 宗岡 悠介, 廣瀬 雄己, 三浦 宏平, 田島 陽介, 滝沢 一泰, 中野 雅人, 永橋 昌幸, 島田 能史, 坂田 純, 小林 隆, 小杉 伸一, 中川 悟, 若井 俊文

    日本外科学会定期学術集会抄録集   121回   PS - 3   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • 肝内胆管癌に対するリンパ節郭清 リンパ節郭清による恩恵を受ける症例は?

    峠 弘治, 坂田 純, 滝沢 一泰, 三浦 宏平, 須藤 翔, 石川 博補, 廣瀬 雄己, 油座 築, 安藤 拓也, 長櫓 宏規, 加納 陽介, 市川 寛, 羽入 隆晃, 中野 雅人, 島田 能史, 永橋 昌幸, 石川 卓, 若井 俊文, 小林 隆, 小杉 伸一

    日本外科学会定期学術集会抄録集   121回   PS - 4   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本外科学会  

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  • Clinical Utility of ypTNM Stage Grouping in the 8th Edition of the American Joint Committee on Cancer TNM Staging System for Esophageal Squamous Cell Carcinoma. 国際誌

    Natsuru Sudo, Hiroshi Ichikawa, Yusuke Muneoka, Takaaki Hanyu, Yosuke Kano, Takashi Ishikawa, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Takeo Bamba, Satoru Nakagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Annals of surgical oncology   28 ( 2 )   650 - 660   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. OBJECTIVE: This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. RESULTS: Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. CONCLUSIONS: ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

    DOI: 10.1245/s10434-020-09181-3

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  • ASO Author Reflections: ypTNM Stage Grouping in the 8th Edition of the AJCC Cancer Staging Manual Refines the Prognostic Prediction for Patients with Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy. 国際誌

    Natsuru Sudo, Hiroshi Ichikawa, Yusuke Muneoka, Takaaki Hanyu, Yosuke Kano, Takashi Ishikawa, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Takeo Bamba, Satoru Nakagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Annals of surgical oncology   28 ( 2 )   661 - 662   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1245/s10434-020-09184-0

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  • Vitamin D Deficiency-induced Osteomalacia in a Patient with Anorexia Nervosa

    Ryo Koda, Satoru Miyazaki, Noriaki Iino, Yo Sato, Kenichiro Hirano, Eiji Sunami, Shinichi Kosugi, Tsutomu Kanefuji, Akira Ogose, Ichiei Narita

    Internal Medicine   2021年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.5911-20

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  • A giant pelvic solitary fibrous tumor with Doege-Potter syndrome successfully treated with transcatheter arterial embolization followed by surgical resection: a case report. 国際誌

    Kizuki Yuza, Jun Sakata, Hiroki Nagaro, Takuya Ando, Yuki Hirose, Kohei Miura, Kazuyasu Takizawa, Takashi Kobayashi, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Masayuki Nagahashi, Shin-Ichi Kosugi, Toshifumi Wakai

    Surgical case reports   6 ( 1 )   299 - 299   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Solitary fibrous tumor (SFT), a mesenchymal fibroblastic tumor with a hypervascular nature, rarely develops in the pelvis. Resection of a giant SFT occupying the pelvic cavity poses an increased risk of developing massive hemorrhage during resection, although surgical resection is the most effective treatment method for this tumor to achieve a potential cure. SFT rarely develops with Doege-Potter syndrome, which is known as a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) secondary to SFT that secretes insulin-like growth factor-II (IGF-II). We present a case of a giant pelvic SFT with Doege-Potter syndrome, which was successfully treated with transcatheter arterial embolization (TAE) followed by surgical resection. CASE PRESENTATION: A 46-year-old woman presented with a disorder of consciousness due to refractory hypoglycemia. Images of the pelvis showed a giant and heterogeneously hypervascular mass displacing and compressing the rectum. Endocrinological evaluation revealed low serum levels of insulin and C-peptide consistent with NICTH. Angiography identified both the inferior mesenteric artery and the bilateral internal iliac artery as the main feeders of the tumor. To avoid intraoperative massive bleeding, super-selective TAE was performed for the tumor 2 days prior to surgery. Hypoglycemia disappeared after TAE. The tumor was resected completely, with no massive hemorrhage during resection. Histologically, it was diagnosed as IGF-II-secreting SFT. Partial necrosis of the rectum in the specimen was observed due to TAE. The patient was followed up for 2 years and no evidence of disease has been reported. CONCLUSIONS: Preoperative angiography followed by TAE is an exceedingly helpful method to reduce intraoperative hemorrhage when planning to resect SFT occupying the pelvic cavity. Complications related to ischemia should be kept in mind after TAE, which needs to be planned within 1 or 2 days before surgery. TAE for tumors may be an option in addition to medical and surgical treatment for persistent hypoglycemia in Doege-Potter syndrome.

    DOI: 10.1186/s40792-020-01076-5

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  • Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer.

    Nobumasa Ohara, Michi Kobayashi, Yohei Ikeda, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Kazuyoshi Yagi, Takeshi Suda, Toshinori Takada, Go Hasegawa, Yo Sato, Kenichiro Hirano, Shin-Ichi Kosugi

    Internal medicine (Tokyo, Japan)   59 ( 4 )   551 - 556   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

    DOI: 10.2169/internalmedicine.3208-19

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  • Long-Term Trends in Respiratory Function After Esophagectomy for Esophageal Cancer. 国際誌

    Takahiro Otani, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Yosuke Kano, Tatsuo Kanda, Shin-Ichi Kosugi, Toshifumi Wakai

    The Journal of surgical research   245   168 - 178   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Esophagectomy for esophageal cancer is known to lead to deterioration in respiratory function (RF). The aim of this study was to assess long-term trends in RF after esophagectomy and the impact of different operative procedures. METHODS: A total of 52 patients with thoracic esophageal cancer who were scheduled for esophagectomy from 2003 to 2012 were enrolled. We prospectively evaluated patients for vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and 6-min walk distance (6MWD) before and after esophagectomy at 3, 6, 12, 24, and 60 mo. RESULTS: Patients had mostly recovered their VC and FEV1.0 after 12 mo. After that point, VC and FEV1.0 declined again, reaching levels lower than baseline at 60 mo, with a median change ratio of 0.85 and 0.86, respectively. Although the 6MWD after open esophagectomy declined, patients treated with transhiatal esophagectomy and minimally invasive esophagectomy maintained above baseline levels throughout the follow-up period. Furthermore, we identified transhiatal esophagectomy (odds ratio [OR] = 0.03, 95% confidence interval [CI] 0.002-0.43, P = 0.01) and minimally invasive esophagectomy (OR = 0.14, 95% CI 0.02-0.94, P = 0.04) as favorable factors and postoperative pulmonary complication (OR = 9.14, 95% CI 1.22-68.6, P = 0.03) as an unfavorable factor for RF after 12 mo. Operative procedures had no significant impact on RF after 60 mo. CONCLUSIONS: Our results support the notion that RF does not recover to the baseline level, and operative procedures have no significant impact on RF at late phase after esophagectomy.

    DOI: 10.1016/j.jss.2019.07.040

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  • Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study. 国際誌

    Eliza R C Hagens, Mark I van Berge Henegouwen, Johanna W van Sandick, Miguel A Cuesta, Donald L van der Peet, Joos Heisterkamp, Grard A P Nieuwenhuijzen, Camiel Rosman, Joris J G Scheepers, Meindert N Sosef, Richard van Hillegersberg, Sjoerd M Lagarde, Magnus Nilsson, Jari Räsänen, Philippe Nafteux, Piet Pattyn, Arnulf H Hölscher, Wolfgang Schröder, Paul M Schneider, Christophe Mariette, Carlo Castoro, Luigi Bonavina, Riccardo Rosati, Giovanni de Manzoni, Sandro Mattioli, Josep Roig Garcia, Manuel Pera, Michael Griffin, Paul Wilkerson, M Asif Chaudry, Bruno Sgromo, Olga Tucker, Edward Cheong, Krishna Moorthy, Thomas N Walsh, John Reynolds, Yuji Tachimori, Haruhiro Inoue, Hisahiro Matsubara, Shin-Ichi Kosugi, Haiquan Chen, Simon Y K Law, C S Pramesh, Shailesh P Puntambekar, Sudish Murthy, Philip Linden, Wayne L Hofstetter, Madhan K Kuppusamy, K Robert Shen, Gail E Darling, Flávio D Sabino, Peter P Grimminger, Sybren L Meijer, Jacques J G H M Bergman, Maarten C C M Hulshof, Hanneke W M van Laarhoven, Banafsche Mearadji, Roel J Bennink, Jouke T Annema, Marcel G W Dijkgraaf, Suzanne S Gisbertz

    BMC cancer   19 ( 1 )   662 - 662   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

    DOI: 10.1186/s12885-019-5761-7

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  • Palliative interventions for patients with incurable locally advanced or metastatic thoracic esophageal carcinoma.

    Tomoyuki Kakuta, Shin-Ichi Kosugi, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Tatsuo Kanda, Toshifumi Wakai

    Esophagus : official journal of the Japan Esophageal Society   16 ( 3 )   278 - 284   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The aim of this study was to assess the clinical outcomes of palliative interventions for patients with incurable locally advanced or metastatic esophageal carcinoma. METHODS: A total of 131 patients with thoracic esophageal carcinoma who underwent palliative interventions were enrolled. Insertion of a self-expandable metallic stent (SEMS), tube enterostomy for enteral nutrition (EN), and palliative esophagectomy (PE) were performed in 38, 65, and 28 patients, respectively. The clinicopathological characteristics and clinical outcomes of each group were retrospectively reviewed. RESULTS: Patients in the EN group frequently received chemoradiotherapy (P < 0.01). SEMS insertion, but not PE or EN, improved the mean dysphagia score after the intervention (P < 0.01). For the SEMS, EN, and PE groups, the occurrence of intervention-related complications was 31.6, 10.8, and 96.4%, respectively, the median survival time was 88, 208, and 226 days (P < 0.01), and the mean ratio of duration of home care to survival time was 28.9, 38.5, and 39.6% (P = 0.95). CONCLUSIONS: SEMS insertion effectively relieved obstructive symptoms, but had no survival benefit. Tube enterostomy showed a low complication rate and has the potential to improve survival in combination with additional treatment, with no palliation of obstructive symptoms.

    DOI: 10.1007/s10388-019-00665-0

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  • Pyloroantrectomy and Pedunculated Short Gastric-Tube Interposition in Esophageal Carcinoma Patients Associated With Early Gastric Adenocarcinoma 査読

    Yu Sato, Tatsuo Kanda, Shin-ichi Kosugi, Takashi Ishikawa, Tetsuya Tada, Toshifumi Wakai

    International Surgery   104 ( 3-4 )   143 - 148   2019年3月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:International College of Surgeons  

    Gastric carcinoma is one of the most common secondary malignancies in esophageal cancer patients. We herein report our surgical procedure for esophageal reconstruction in esophageal cancer patients associated with synchronous or metachronous early gastric adenocarcinoma. Gastric adenocarcinoma was removed by pyloroantrectomy with preservation of the right gastroepiploic artery and vein, and a pedunculated short gastric tube was used as an esophageal substitute in a Roux-en-Y fashion. Surgical data of 6 esophageal cancer patients who underwent this type of surgery between 1993 and 2012 were analyzed. Three patients had synchronous early gastric carcinoma and the remaining 3 patients had metachronous early gastric adenocarcinoma. The gastric tube was easily pulled up to the neck and no problems occurred during this procedure. Postoperative complications, including leakage of esophagogastrostomy, acute respiratory failure, and diffuse peritonitis, were observed in 3 patients. No patients suffered from necrosis of the gastric tube. Although 3 patients died of other diseases, gastric cancer recurrence has not been observed to date. Despite the need for precaution to ensure technical safety, pyloroantrectomy and esophageal reconstruction using a pedunculated short gastric-tube are oncologically feasible as a potential curative surgery for esophageal cancer patients with early gastric adenocarcinoma.

    DOI: 10.9738/intsurg-d-16-00011.1

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  • Hyperbilirubinemia predicts the infectious complications after esophagectomy for esophageal cancer. 国際誌

    Yusuke Muneoka, Hiroshi Ichikawa, Shin-Ichi Kosugi, Takaaki Hanyu, Takashi Ishikawa, Yosuke Kano, Yoshifumi Shimada, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Kohei Akazawa, Toshifumi Wakai

    Annals of medicine and surgery (2012)   39   16 - 21   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Surgical stress and inflammation can cause hyperbilirubinemia, which sometimes occurs after esophagectomy for esophageal cancer (EC). The aim of this study was to elucidate the clinical significance of postoperative hyperbilirubinemia in the management of EC patients. Materials and methods: We retrospectively reviewed records of 81 EC patients who underwent esophagectomy from 2009 to 2014. We compared the clinicopathological and perioperative factors, including the presence of hyperbilirubinemia (total bilirubin ≥1.5 mg/dL), between patients with postoperative infectious complications (PIC group) and those without (Non-PIC group). Results: PIC developed in 52 patients (64.2%). There were significant differences in incidence of postoperative hyperbilirubinemia between the PIC group and the non-PIC group (34.6% vs. 3.4%, P = 0.002), as well as the approach of esophagectomy (P = 0.045), the surgical duration (469 vs. 389 min, P < 0.001), the amount of blood loss (420 vs. 300 mL, P = 0.018), the frequency of intraoperative blood transfusions (32.7% vs. 6.9%, P = 0.012) and the peak postoperative C-reactive protein level (17.3 vs. 8.6 mg/dL, P = 0.007). Multivariate analysis revealed hyperbilirubinemia was independently associated with the occurrence of PICs (odds ratio: 38.6, P = 0.010). The median time to the diagnosis of hyperbilirubinemia was significantly shorter than that of PICs (3.0 vs. 4.5 days, P = 0.025). Conclusions: Postoperative hyperbilirubinemia was associated with the occurrence of PICs and frequently occurred before any PICs become apparent. More attention should be paid to the serum bilirubin level in the management after esophagectomy for EC.

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  • Unusual lymph node metastasis from cancer of the thoracic esophagus. 国際誌

    Shin-Ichi Kosugi, Hiroshi Ichikawa, Yo Sato, Eiji Sunami, Kenichiro Hirano, Takeaki Matsuzawa, Motoko Takahashi

    Journal of surgical case reports   2018 ( 8 )   rjy214   2018年8月

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    記述言語:英語  

    A 76-year-old male received concurrent chemoradiotherapy, at a dose of 60 Gy with low-dose 5-fluorouracil, for cT1bN0M0 squamous cell carcinoma of the mid-thoracic esophagus. Because his primary tumor relapsed with mediastinal and right supraclavicular node metastasis 4 months after completion of chemoradiotherapy, right transthoracic esophagectomy with mediastinal and right cervical lymphadenectomy was performed. However, metastatic tumors developed deep beneath the anterior border of the trapezius muscle 2 months after esophagectomy. En bloc dissection of the adipose tissue including the tumor and the transverse cervical artery was performed, followed by adjuvant radiotherapy of 50.4 Gy to the area of dissection. The patient died of pneumonia 11 months after metastasectomy, with locally recurrent disease. We have had three cases of this unusual lymph nodes metastasis from cancer of the thoracic esophagus to date and here present the characteristic imaging findings and the possible mechanism of this unusual lymph node metastasis.

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  • Small Bowel Obstruction After Ileal Pouch-Anal Anastomosis With a Loop Ileostomy in Patients With Ulcerative Colitis. 国際誌

    Hitoshi Kameyama, Yoshifumi Hashimoto, Yoshifumi Shimada, Saki Yamada, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Kohei Miura, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Shin-Ichi Kosugi, Toshifumi Wakai

    Annals of coloproctology   34 ( 2 )   94 - 100   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. METHODS: The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. RESULTS: The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14-72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009-8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. CONCLUSION: The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.

    DOI: 10.3393/ac.2017.06.14

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  • Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303) 査読

    Tatsuya Okuno, Masashi Wakabayashi, Ken Kato, Masayuki Shinoda, Hiroshi Katayama, Hiroyasu Igaki, Yasuhiro Tsubosa, Takashi Kojima, Hiroshi Okabe, Yusuke Kimura, Tatsuyuki Kawano, Shinichi Kosugi, Yasushi Toh, Hoichi Kato, Kenichi Nakamura, Haruhiko Fukuda, Satoshi Ishikura, Nobutoshi Ando, Yuko Kitagawa

    International Journal of Clinical Oncology   22 ( 6 )   1042 - 1049   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    BACKGROUND: The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. METHODS: One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. RESULTS: The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). CONCLUSIONS: Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. CLINICAL TRIAL INFORMATION: UMIN000000861.

    DOI: 10.1007/s10147-017-1154-6

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    その他リンク: http://link.springer.com/content/pdf/10.1007/s10147-017-1154-6.pdf

  • Prophylactic lateral pelvic lymph node dissection in stage IV low rectal cancer. 国際誌

    Hiroshi Tamura, Yoshifumi Shimada, Hitoshi Kameyama, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Shin-Ichi Kosugi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Toshifumi Wakai

    World journal of clinical oncology   8 ( 5 )   412 - 419   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: To assess the clinical significance of prophylactic lateral pelvic lymph node dissection (LPLND) in stage IV low rectal cancer. METHODS: We selected 71 consecutive stage IV low rectal cancer patients who underwent primary tumor resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis. The patients had distant metastasis such as liver, lung, peritoneum, and paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter of 10 mm or more on preoperative pelvic computed tomography scan. All patients underwent primary tumor resection, 27 patients underwent total mesorectal excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME group). Bilateral LPLND was performed simultaneously with primary tumor resection in LPLND group. R0 resection of both primary and metastatic sites was achieved in 20 of 50 patients. We evaluated possible prognostic factors for 5-year overall survival (OS), and compared 5-year cumulative local recurrence between the LPLND and TME groups. RESULTS: For OS, univariate analyses revealed no significant benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523); multivariate analysis revealed that R0 resection was an independent prognostic factor. Regarding cumulative local recurrence, the LPLND group showed no significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833). CONCLUSION: Prophylactic LPLND shows no oncological benefits in patients with Stage IV low rectal cancer without clinical LPLN metastasis.

    DOI: 10.5306/wjco.v8.i5.412

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  • Intravenous Carnitine Administration in Addition to Parenteral Nutrition With Lipid Emulsion May Decrease the Inflammatory Reaction in Postoperative Surgical Patients. 国際誌

    Yu Koyama, Kazuki Moro, Masato Nakano, Kohei Miura, Masayuki Nagahashi, Shin-Ichi Kosugi, Junko Tsuchida, Mayuko Ikarashi, Masato Nakajima, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Toshifumi Wakai

    Journal of clinical medicine research   9 ( 10 )   831 - 837   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: A prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion. METHODS: Patients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously. PPN was performed from postoperative day (POD) 1 to POD4. Clinical and laboratory parameters were compared between the two groups; statistical significance was set at P < 0.05. RESULTS: Serum carnitine concentrations were significantly higher in group LC on POD3 (P < 0.01) and POD7 (P = 0.01). Postoperative changes in laboratory parameters and morbidity were comparable between the two groups. However, the decrease in C-reactive protein from POD3 to POD7 was significantly greater in group LC than in group L (P = 0.011). CONCLUSION: The results show that intravenous carnitine administration in addition to PN is safe and may be beneficial for recovery from postoperative inflammatory reactions.

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  • Cardiac tamponade communicating with a posterior mediastinal chylocele after esophagectomy. 国際誌

    Shin-Ichi Kosugi, Takehisa Hashimoto, Yo Sato, Kenichiro Hirano, Eiji Sunami, Takeaki Matsuzawa, Motoko Takahashi, Hiroshi Ichikawa

    Journal of surgical case reports   2017 ( 10 )   rjx216   2017年10月

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    記述言語:英語  

    A 75-year-old male received neoadjuvant chemotherapy for locally advanced squamous cell carcinoma of the mid-thoracic esophagus, followed by right transthoracic esophagectomy with extended mediastinal lymphadenectomy. Cardiac tamponade developed on postoperative Days 1 and 13, for which emergency ultrasound-guided drainage was required. Pericardial drainage fluid became chylous after administration of polymeric formula. A computed tomography scan demonstrated the presence of a retrocardiac fluid collection, encompassed by the left pulmonary vein and left atrium, descending aorta and vertebral column. Based on these findings, the diagnosis of chylopericardial tamponade communicating with a posterior mediastinal chylocele was made. The ligation of the thoracic duct was successfully performed via the left-sided thoracoscopic approach on postoperative Day 20 and the clinical course after the second operation was uneventful. The possible mechanisms of this exceptionally rare complication after esophagectomy were discussed.

    DOI: 10.1093/jscr/rjx216

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  • Benign esophageal schwannoma: a brief overview and our experience with this rare tumor. 国際誌

    Kazuki Moro, Masayuki Nagahashi, Kotaro Hirashima, Shin-Ichi Kosugi, Takaaki Hanyu, Hiroshi Ichikawa, Takashi Ishikawa, Gen Watanabe, Emmanuel Gabriel, Tsutomu Kawaguchi, Kazuaki Takabe, Toshifumi Wakai

    Surgical case reports   3 ( 1 )   97 - 97   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Benign esophageal tumors are uncommon, comprising approximately 2% of esophageal tumors. Esophageal schwannomas constitute an even rarer entity, with few cases reported in the literature. CASE PRESENTATION: We present a 66-year-old male who was referred for dysphagia. A computed tomography scan showed a well-demarcated, enhancing, and homogenous esophageal tumor measuring 50 mm. The tumor was hypermetabolic on positron emission tomography, and an endoscopic ultrasound-guided fine needle aspiration demonstrated the presence of benign spindle cells. We performed an uncomplicated, simple, tumor enucleation through a cervical approach. Histology revealed spindle-shaped cells in a fasciculated, disarrayed pattern. Immunohistochemistry demonstrated positive staining for S-100 protein and negative staining for KIT, CD34, desmin, and α-smooth muscle actin. These findings were consistent with a benign esophageal schwannoma. CONCLUSIONS: We report our experience with esophageal schwannoma, a rare but benign diagnosis of the esophagus.

    DOI: 10.1186/s40792-017-0369-0

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  • Appropriate extent of lymphadenectomy for squamous cell carcinoma of the esophagogastric junction 査読

    Shin-ichi Kosugi, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   44   339 - 343   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Aim: To investigate the appropriate extent of lymphadenectomy for squamous cell carcinoma (SCC) of the esophagogastric junction (ECJ).
    Methods: We retrospectively reviewed the cases of 52 patients with SCC of the ECJ who underwent extended mediastinal lymphadenectomy. We assessed potential risk factors for lymph node metastasis (LNM) in the upper/middle mediastinum by conducting univariate and multivariate analyses, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value. Survival rates were calculated using the Kaplan-Meier method, and the therapeutic value index of each nodal basin dissection was calculated by multiplying the frequency of metastasis at the basin and the 5-year overall survival rate of patients with metastasis at that basin.
    Results: Twenty patients (38%) had mediastinal LNM; 13 (25%) had metastasis in the upper/middle mediastinum, and 13 (25%) had metastasis in the lower mediastinum. Tumor length (P = 0.03) and pathological nodal status (P = 0.01) were independent risk factors for upper/middle mediastinal LNM. The optimal ROC cutoff value of tumor length was 54 mm. The 5-year overall survival rate of the patients with LNM in the upper/middle mediastinum was 46%. The therapeutic value index of upper/middle mediastinal lymphadenectomy was 11.6, which was inferior to that of perigastric lymphadenectomy at 17.3, but superior to that of lower mediastinal lymphadenectomy at 5.8.
    Conclusion: An upper/middle mediastinal lymphadenectomy may be required for patients with tumors that are &gt;= 54 mm long, and in those with suspected LNM. (C) 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.ijsu.2017.07.041

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  • Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer 査読

    Yosuke Tajima, Yoshifumi Shimada, Hitoshi Kameyama, Ryoma Yagi, Takuma Okamura, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   47 ( 4 )   313 - 320   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Objective: Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer.
    Methods: This retrospective study enrolled 131 patients with stage III colorectal cancer who underwent curative resection: 72 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 59 did not (surgery-alone group). Poorly differentiated cluster was defined as a cancer cluster of &gt;= 5 cancer cells without gland-like structure, and was classified into poorly differentiated cluster G1, G2 and G3 according to the number of clusters. The benefit of 5-fluorouracil-based adjuvant chemotherapy was evaluated based on poorly differentiated cluster grade.
    Results: Thirty-nine, 40 and 52 patients were classified as poorly differentiated cluster G1, G2 and G3, respectively. Significant differences in the 5-year cumulative recurrence rate and relapse-free survival were observed between poorly differentiated cluster G1/G2 and G3 (26.7% vs. 47.5%, P = 0.010; 66.0% vs. 43.9%, P = 0.004). A comparison of cumulative recurrence rate and relapse-free survival between the chemotherapy and surgery-alone groups showed a significant benefit of adjuvant chemotherapy in poorly differentiated cluster G1/G2 patients (cumulative recurrence rate: 17.4% vs. 37.3%, P = 0.035; relapse-free survival: 79.5% vs. 51.9%, P = 0.002), but not in poorly differentiated cluster G3 patients (cumulative recurrence rate: 48.6% vs. 44.8%, P = 0.885; relapse-free survival: 51.4% vs. 32.7%, P = 0.068).
    Conclusions: In stage III colorectal cancer, poorly differentiated cluster G1/G2 predicts a significant benefit from 5-fluorouracil-based adjuvant chemotherapy, whereas poorly differentiated cluster G3 predicts a poor response to it.

    DOI: 10.1093/jjco/hyw209

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  • Surgical and long-term outcomes following oesophagectomy in oesophageal cancer patients with comorbidity 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Takaaki Hanyu, Yusuke Muneoka, Takahiro Otani, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   36 ( Pt A )   212 - 218   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Introduction: The elucidation of the clinical impact of comorbidities is important to optimize the treatment and follow-up strategy in oesophageal cancer. We aimed to clarify the surgical and long-term outcomes following oesophagectomy in oesophageal cancer patients with comorbidity.
    Methods: A total of 658 consecutive patients who underwent oesophagectomy for oesophageal cancer between 1985 and 2008 at our institution were enrolled. Based on the criteria of comorbidity as we defined it, we retrospectively reviewed and compared the surgical outcomes and survival between the comorbid (n= 251) and non-comorbid group (n=407).
    Results: Postoperative morbidity and mortality were not significantly different between the two groups. The 5-year overall survival rate of the comorbid group was significantly lower (39.3% vs. 45.2%, adjusted HR = 1.31, 95% CI: 1.07-1.62) but the 5-year disease-specific survival rate was not significantly different between the comorbid and non-comorbid groups (53.9% vs. 53.1%, adjusted HR = 1.11, 95% CI: 0.86 -1.42). The 5-year incidence rate of death from other diseases in the comorbid group was significantly higher than that in the non-comorbid group (26.7% vs. 14.8%, P &lt; 0.01). The leading cause of death from other diseases was pneumonia.
    Conclusions: Oesophagectomy in oesophageal cancer patients with comorbidity can be safely performed. However, the overall survival after oesophagectomy in these patients was unfavorable because of the high incidence of death from other diseases, especially pneumonia. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • Low fat-containing elemental formula is effective for postoperative recovery and potentially useful for preventing chyle leak during postoperative early enteral nutrition after esophagectomy. 国際誌

    Kazuki Moro, Yu Koyama, Shin-Ichi Kosugi, Takashi Ishikawa, Hiroshi Ichikawa, Takaaki Hanyu, Kohei Miura, Masayuki Nagahashi, Masato Nakajima, Kumiko Tatsuda, Junko Tsuchida, Chie Toshikawa, Mayuko Ikarashi, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    Clinical nutrition (Edinburgh, Scotland)   35 ( 6 )   1423 - 1428   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIMS: Transthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery. METHODS: A total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak. RESULTS: Patients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P < 0.01). Duration of respirator use and length of ICU stay were also significantly shorter, and TPN was used significantly less in Group LF compared to Group F (P < 0.05). Postoperative chyle leak was observed in six patients in total (8.1%); five patients in Group F and one patient in Group LF, although there was no significant difference in frequency of chyle leak per patient between Group LF and Group F. CONCLUSIONS: Early EN using low-fat elemental formula after esophagectomy with three-field lymphadenectomy was safe and valid for postoperative recovery and potentially useful in preventing chyle leak.

    DOI: 10.1016/j.clnu.2016.03.018

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  • Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery 査読

    Yusuke Muneoka, Kohei Akazawa, Takashi Ishikawa, Hiroshi Ichikawa, Atsushi Nashimoto, Hiroshi Yabusaki, Norio Tanaka, Shin-ichi Kosugi, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY   35   153 - 159   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5-year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer.
    Materials and methods: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation.
    Results: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P &lt; 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5-year RFS.
    Conclusion: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • [A Case of Simultaneous Multiple Gastric Cancers Showing Differences of Response after Neoadjuvant Chemotherapy with Docetaxel, CDDP, and S-1].

    Takeshi Sakai, Hiroshi Ichikawa, Takashi Ishikawa, Shinichi Kosugi, Takaaki Hanyu, Kenji Usui, Yusuke Muneoka, Takahiro Otani, Mariko Hishiki, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   2377 - 2379   2016年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 63-year-old man with epigastralgia was referred to our hospital and diagnosed with simultaneous multiple gastric cancers. One lesion was type 2 advanced and the other was type 0- II c early gastric cancer. CT examination revealed 4 regional lymph node metastases. Neoadjuvant chemotherapy(NAC)with docetaxel/CDDP/S-1was administered. After 2 courses of NAC, total gastrectomy with D2(-No. 10), lymphadenectomy was performed. The pathological response to NAC was judged to be Grade 3 for advanced gastric cancer and Grade 0 for early gastric cancer. The patient is alive with no evidence of disease during the 10 months after the operation.

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  • [A Case of Advanced Gastric Cancer with Portosystemic Shunt Successfully Treated with Percutaneous Transvenous Coil Embolization].

    Kenji Usui, Takaaki Hanyu, Hiroshi Ichikawa, Takashi Ishikawa, Yusuke Muneoka, Yu Sato, Yosuke Kano, Takahiro Otani, Mariko Hishiki, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Shinichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   1917 - 1919   2016年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 57-year-old man with advanced gastric cancer and multiple liver metastases was referred to our hospital. He underwent a palliative gastrectomy to treat hemorrhage, and S-1 and cisplatin therapy was administered. After 7 courses of chemotherapy, a new liver metastatic lesion and a tumor thrombus in the right portal vein appeared. Moreover, the serum level of ammonia was elevated(296 mg/dL)following a consciousness disorder. Enhanced CT revealed an inferior mesenteric vein to left renal vein shunt, which led to the diagnosis of portal systemic encephalopathy due to portosystemic shunt. Percutaneous transvenous coil embolization was performed. The serum ammonia level decreased, and the encephalopathy disappeared. As a result, he was able to continue chemotherapy.

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  • [A Case of Advanced Gastric Cancer Resected for Rebleeding after Palliative Radiotherapy for Hemostasis].

    Yusuke Muneoka, Hiroshi Ichikawa, Takashi Ishikawa, Takaaki Hanyu, Yu Sato, Yosuke Kano, Kenji Usui, Takahiro Otani, Mariko Hishiki, Kohei Miura, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Shinichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   43 ( 12 )   1936 - 1938   2016年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    We report a case of advanced gastric cancer(AGC)that was resected for rebleeding after palliative radiotherapy for hemostasis. A 74-year-old man with Stage IV gastric cancer received chemotherapy and achieved stable disease. After 23 months, he experienced continuous bleeding from the tumor due to regrowth. Palliative radiotherapy was conducted to control the bleeding, and the tumor successfully achieved hemostasis. However, 6 weeks later, the patient experienced rebleeding and developed hemostatic shock. We then performed a successful emergency gastrectomy. Bleeding negatively affects quality of life in patients with AGC and is potentially lethal. Although palliative radiotherapy for bleeding of gastric cancer is a safe and useful treatment within a short time frame in cases of rebleeding, emergency gastrectomy may be necessary. Therefore, when we select this treatment, the possibility of subsequent surgical treatment must be considered.

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  • DNA damage response and sphingolipid signaling in liver diseases.

    Masayuki Nagahashi, Yasunobu Matsuda, Kazuki Moro, Junko Tsuchida, Daiki Soma, Yuki Hirose, Takashi Kobayashi, Shin-Ichi Kosugi, Kazuaki Takabe, Masaaki Komatsu, Toshifumi Wakai

    Surgery today   46 ( 9 )   995 - 1005   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.

    DOI: 10.1007/s00595-015-1270-8

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  • Clinical Significance of Extramural Tumor Deposits in the Lateral Pelvic Lymph Node Area in Low Rectal Cancer: A Retrospective Study at Two Institutions 査読

    Ryoma Yagi, Yoshifumi Shimada, Hitoshi Kameyama, Yosuke Tajima, Takuma Okamura, Jun Sakata, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Takashi Kawasaki, Kei-ichi Honma

    ANNALS OF SURGICAL ONCOLOGY   23 ( Suppl 4 )   552 - 558   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer.
    This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses.
    Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P &lt; 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P &lt; 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001).
    The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

    DOI: 10.1245/s10434-016-5379-9

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  • Tumor Budding Detection by Immunohistochemical Staining is Not Superior to Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1 Colorectal Cancer 査読

    Takuma Okamura, Yoshifumi Shimada, Hitoshi Nogami, Hitoshi Kameyama, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai, Yoichi Ajioka

    DISEASES OF THE COLON & RECTUM   59 ( 5 )   396 - 402   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    BACKGROUND: Tumor budding is recognized as an important risk factor for lymph node metastasis in pT1 colorectal cancer. Immunohistochemical staining for cytokeratin has the potential to improve the objective diagnosis of tumor budding over detection based on hematoxylin and eosin staining. However, it remains unclear whether tumor budding detected by immunohistochemical staining is a significant predictor of lymph node metastasis in pT1 colorectal cancer.
    OBJECTIVE: The purpose of this study was to clarify the clinical significance of tumor budding detected by immunohistochemical staining in comparison with that detected by hematoxylin and eosin staining.
    DESIGN: This was a retrospective study.
    SETTINGS: The study was conducted at Niigata University Medical & Dental Hospital.
    PATIENTS: We enrolled 265 patients with pT1 colorectal cancer who underwent surgery with lymph node dissection.
    MAIN OUTCOME MEASURES: Tumor budding was evaluated by both hematoxylin and eosin and immunohistochemical staining with the use of CAM5.2 antibody. Receiver operating characteristic curve analyses were conducted to determine the optimal cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining. Univariate and multivariate analyses were performed to identify the significant factors for predicting lymph node metastasis.
    RESULTS: Receiver operating characteristic curve analyses revealed that the cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining for predicting lymph node metastases were 5 and 8. On multivariate analysis, histopathological differentiation (OR, 6.21; 95% CI, 1.16-33.33; p = 0.03) and tumor budding detected by hematoxylin and eosin staining (OR, 4.91; 95% CI, 1.64-14.66; p = 0.004) were significant predictors for lymph node metastasis; however, tumor budding detected by CAM5.2 staining was not a significant predictor.
    LIMITATIONS: This study was limited by potential selection bias because surgically resected specimens were collected instead of endoscopically resected specimens.
    CONCLUSIONS: Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.

    DOI: 10.1097/DCR.0000000000000567

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  • Successful Re-resection for Locally Recurrent Retroperitoneal Liposarcoma at Four Years After Ex Vivo Tumor Resection and Autotransplantation of the Liver: A Case Report. 国際誌

    T Kobayashi, K Miura, H Ishikawa, D Soma, Z Zhang, K Yuza, Y Hirose, K Takizawa, M Nagahashi, J Sakata, H Kameyama, S Kosugi, T Wakai

    Transplantation proceedings   48 ( 4 )   1215 - 7   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Surgical resection should be considered for isolated locally recurrent retroperitoneal liposarcomas. We experienced a case of successful re-resection for locally recurrent retroperitoneal liposarcomas 4 years after ex vivo tumor resection and autotransplantation of the liver. A 75-year-old man was admitted to our hospital. His diagnosis was local recurrence of liposarcomas. He had previously undergone ex vivo tumor resection and autologous orthotopic liver transplantation for a retroperitoneal tumor 4 years earlier. The resected tumor size was 23.5 × 15.5 × 12.5 cm. The tumor was revealed by means of histopathologic study to be a myxoid liposarcoma. Follow-up computerized tomography showed 2 recurrent tumors in the retropancreatic and para-aortic lesions. Although adhesion was severe within the operative field, we successfully performed complete en bloc re-resection of each recurrent tumor. The operative time was 250 minutes, and blood loss was 300 mL. The resected tumor sizes were 3.9 × 3.2 × 1.5 cm and 4.5 × 3.3 × 3.0 cm. The tumors were revealed by means of histopathologic study to be dedifferentiated liposarcomas. Postoperative complications included intestinal obstruction and colocutaneous fistula formation, both of which were treated surgically. The patient was discharged in an ambulatory state at 80 days after re-resection of the recurrent tumors. At the time of writing, he was alive with no evidence of recurrence, 14 months after re-resection and 62 months after primary ex vivo tumor resection. This is the first case of successful surgical re-resection for locally recurrent liposarcoma after ex vivo tumor resection and autotransplantation of the liver.

    DOI: 10.1016/j.transproceed.2016.01.026

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  • Successful Endoscopic Management of Acute Necrotic Pancreatitis and Walled Off Necrosis After Auxiliary Partial Orthotopic Living-Donor Liver Transplantation: A Case Report. 国際誌

    T Kobayashi, K Miura, H Ishikawa, D Soma, Z Zhang, K Yuza, Y Hirose, K Takizawa, M Nagahashi, J Sakata, H Kameyama, S Kosugi, T Wakai

    Transplantation proceedings   48 ( 4 )   1212 - 4   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Endoscopic management of acute necrotic pancreatitis and walled off necrosis is less invasive than surgical treatment and has become the 1st choice for treating pancreatic necrosis and abscess. We treated a case of acute necrotic pancreatitis and walled off necrosis after auxiliary partial orthotopic living-donor liver transplantation (APOLT). A 24-year-old woman was admitted to our university hospital for removal of the internal biliary stent, which had already been placed endoscopically for the treatment of biliary stricture after APOLT. She had been treated for acute liver failure by APOLT 10 years before. After we removed the internal stent with the use of an endoscopic retrograde approach, she presented with severe abdominal pain and a high fever. Her diagnosis was severe acute pancreatitis after endoscopic retrograde cholangiography (ERC). Her symptoms worsened, and she had multiple organ failure. She was transferred to the intensive care unit (ICU). Immunosuppression was discontinued because infection treatment was necessary and the native liver had already recovered sufficiently. After she had been treated for 19 days in the ICU, she recovered from her multiple organ failure. However, abdominal computerized tomography demonstrated the formation of pancreatic walled off necrosis and an abscess on the 20th day after ERC. We performed endoscopic ultrasonography-guided abscess drainage and repeated endoscopic necrosectomy. The walled off necrosis diminished gradually in size, and the symptoms disappeared. The patient was discharged on the 87th day after ERC. This is the 1st report of a case of acute necrotic pancreatitis and walled off necrosis that was successfully treated by endoscopic management after APOLT.

    DOI: 10.1016/j.transproceed.2015.12.113

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  • Study of Immune Tolerance Cases in Adult Living Donor Liver Transplantation. 国際誌

    K Miura, T Kobayashi, Z Zhang, D Soma, Y Hirose, H Ishikawa, K Takizawa, M Nagahashi, J Sakata, H Kameyama, M Minagawa, S Kosugi, Y Koyama, T Wakai

    Transplantation proceedings   48 ( 4 )   1119 - 22   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS: A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS: Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipient's child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS: In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.

    DOI: 10.1016/j.transproceed.2015.12.093

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  • Six-Year Graft Survival After Partial Pancreas Heterotopic Auto-Transplantation: A Case Report. 国際誌

    T Kobayashi, K Miura, H Ishikawa, D Soma, Z Zhang, K Yuza, Y Hirose, K Takizawa, M Nagahashi, J Sakata, H Kameyama, S-I Kosugi, T Tada, H Hirukawa, T Wakai

    Transplantation proceedings   48 ( 3 )   988 - 90   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Long-term graft survival of partial pancreas auto-transplantation after total pancreatectomy has not been clarified. The clinical implications of repeat completion pancreatectomy for locally recurrent pancreatic carcinoma in the remnant pancreas after initial pancreatectomy also have not been clarified. METHODS: We have previously reported a 61-year-old woman presenting with re-sectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreas head. We also performed distal pancreas auto-transplantation with the use of a part of the resected pancreas to preserve endocrine function. RESULTS: The patient was discharged at 20 days after surgery without any complications. She had been followed regularly in our outpatient clinic. She had been treated with S-1 as adjuvant chemotherapy; 72 months after the completion total pancreatectomy with distal partial pancreas auto-transplantation, the patient was alive without any evidence of the pancreatic carcinoma recurrence. The pancreas graft was still functioning with a blood glucose level of 112 mg/dL, HbA1C of 6.7%, and serum C-peptide of 1.2 ng/mL; and urinary C-peptide was 11.6 μg/d. CONCLUSIONS: Our patient demonstrated that repeated pancreatectomies can provide a chance for survival after a locally recurrent pancreatic carcinoma if the disease is limited to the remnant pancreas. An additional partial pancreas auto-transplantation was successfully performed to preserve endocrine function. However, the indications for pancreas auto-transplantation should be decided carefully in the context of pancreatic carcinoma recurrence.

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  • Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors.

    Tatsuo Kanda, Takashi Ishikawa, Shin-Ichi Kosugi, Kyo Ueki, Tetsuya Naito, Toshifumi Wakai, Seiichi Hirota

    International journal of clinical oncology   21 ( 2 )   295 - 301   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Patients undergoing imatinib therapy for gastrointestinal stromal tumors (GISTs) show drug resistance during treatment in the late stages. The aims of this study were to determine survival after the appearance of imatinib secondary resistance (ISR) and to identify the prognostic factors. METHODS: Eligible were patients with unresectable and metastatic GISTs who were diagnosed with ISR and/or underwent treatment for ISR in our institution between 2001 and 2012. A total of 48 patients were enrolled and overall survival was retrospectively analyzed. The Cox proportional hazards model was used to identify the independent prognostic factors. Median follow-up time was 58 months. RESULTS: As of the cutoff date, 41 of the 48 patients with ISR had died, of which 39 died of GISTs. The overall 1-, 3-, and 5-year survival rates of the 48 patients were 64.6, 32.8, and 20.4 %, respectively, and median survival time was 22 months. The favorable independent prognostic factors identified were long progression-free survival in first-line imatinib therapy (P = 0.04), small diameter of progressive disease (PD) (P = 0.02), and surgical resection of PD (P = 0.01). CONCLUSION: Surgical resection of PD in selected cases could improve prognosis in ISR patients undergoing GIST treatment.

    DOI: 10.1007/s10147-015-0903-7

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  • A Case of Minimally Invasive Apocrine Carcinoma Derived from Ductal Adenoma 査読

    Kazuki Moro, Yu Koyama, Masayuki Nagahashi, Miki Hasegawa, Chie Toshikawa, Junko Tsuchida, Takaaki Hanyu, Takashi Ishikawa, Yoshifumi Shimada, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Shinichi Kosugi, Takashi Kato, Gen Watanabe, Yoichi Ajioka, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer &amp; chemotherapy   43 ( 2 )   235 - 237   2016年2月

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    掲載種別:研究論文(学術雑誌)  

    A 63-year-old woman was found to have a mass in her right breast and visited our hospital to undergo a detailed examination. A histopathological examination by using ultrasound-guided core needle biopsy revealed ductal carcinoma in situ. A partial mastectomy with sentinel lymph node biopsy was performed for the cancer of the right breast. The postoperative histopathological examination indicated apocrine carcinoma with a predominantly intraductal component without lymph node metastasis. The discrimination between ductal adenoma and apocrine carcinoma sometimes becomes a problem in making decisions about treatment. We need to take care when making a diagnosis.

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  • Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma 査読

    Jun Sakata, Toshifumi Wakai, Yasunobu Matsuda, Taku Ohashi, Yuki Hirose, Hiroshi Ichikawa, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Yu Koyama, Kouhei Akazawa, Yoichi Ajioka

    ANNALS OF SURGICAL ONCOLOGY   23 ( 1 )   225 - 234   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma.
    A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model.
    Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or a parts per thousand yen2; P = 0.005) and the LNR (0, 0-5, or &gt; 5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes.
    The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

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  • Risk Factors and Clinical Outcomes of Recurrent Laryngeal Nerve Paralysis After Esophagectomy for Thoracic Esophageal Carcinoma 査読

    Yu Sato, Shin-ichi Kosugi, Naotaka Aizawa, Takashi Ishikawa, Yosuke Kano, Hiroshi Ichikawa, Takaaki Hanyu, Kotaro Hirashima, Takeo Bamba, Toshifumi Wakai

    WORLD JOURNAL OF SURGERY   40 ( 1 )   129 - 136   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The objectives of this study were to assess the incidence of recurrent laryngeal nerve paralysis (RLNP) using laryngoscopy after esophagectomy for thoracic esophageal carcinoma and to clarify the risk factors influencing postoperative RLNP.
    A total of 299 patients who underwent laryngoscopic examination after esophagectomy were retrospectively reviewed. Patients who were found to have postoperative RLNP were followed up every 1-3 months, with a median follow-up period of 3 months. Recovery from paralysis was also evaluated on the basis of each affected nerve. Multivariate analyses using logistic regression were used to identify independent risk factors for RLNP. Cumulative recovery rate was calculated using Kaplan-Meier method.
    A total of 178 (59.5 %) patients were diagnosed with RLNP by first laryngoscopy [bilateral in 59 (33.1 %) patients, right in 15 (8.4 %), and left in 104 (58.4 %)]. In 206 patients who underwent transthoracic and thoracoscopic esophagectomy, independent risk factors for RLNP were lymph node dissection along the right RLN (odds ratio [OR] 3.01, 95 % confidence interval [CI] 1.06-8.54, P = 0.04) and cervical anastomosis (OR 5.94, 95 % CI 1.78-19.80, P &lt; 0.01). Cumulative recovery rate from RLNP was 61.7 % at 12 months after esophagectomy with 91 nerves eventually recovering from paralysis. Median recovery time was 6 months.
    RLNP developed in 60 % of patients after esophagectomy and may be associated with lymphadenectomy around the right RLN and cervical esophageal mobilization. Although 62 % of affected nerves recovered within 12 months, great attention should be given when performing these procedures.

    DOI: 10.1007/s00268-015-3261-8

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  • Prognostic significance of NQO1 expression in esophageal squamous cell carcinoma after preoperative chemotherapy with cisplatin and 5-fluorouracil followed by curative esophagectomy 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Yuki Hirose, Yasunobu Matsuda, Takashi Ishikawa, Takaaki Hanyu, Kenji Usui, Yusuke Muneoka, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   9 ( 7 )   7393 - 7401   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    NAD(P) H:quinone oxidoreductase-1 (NQO1) confers resistance to anticancer agents, particularly to oxidative stress inducers such as cisplatin or 5-fluorouracil in malignant tumors. Here we evaluated the association between NQO1 expression in esophageal squamous cell carcinoma (ESCC) cells and the patients' responses to preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), and we elucidated the prognostic significance of NQO1 expression in ESCC patients. We retrospectively analyzed the cases of 40 patients who underwent preoperative CF therapy followed by curative esophagectomy with lymphadenectomy. Immunohistochemistry of the surgically resected specimens was conducted using the primary monoclonal antibody against NQO1. Eighteen of the 40 patients (45%) had tumors that showed high NQO1 expression (NQO1-high group). The poorer histological response to preoperative CF therapy was dominant in the NQO1-high group compared to the NQO1-low group (72% and 45%, respectively) but the difference was not significant (P=0.09). The 3-year recurrence-free survival rate after esophagectomy in the NQO1-high group was significantly lower compared to the NQO1-low group (39% vs. 76%; P&lt;0.01). A Cox proportional hazards model revealed that high NQO1 expression was an independent unfavorable prognostic factor (HR=3.53; P=0.02) as was pN3 (HR=14.7; P&lt;0.01). The immunohistochemical evaluation of NQO1 expression has potential to predict the treatment response and prognosis in patients who undergo preoperative CF therapy followed by esophagectomy for ESCC.

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  • Clinical significance of MED12 expression in colorectal cancer

    Yoshifumi Shimada, Yosuke Tajima, Hitoshi Kameyama, Ryoma Yagi, Takuma Okamura, Yuki Hirose, Jun Sakata, Takashi Kobayashi, Yasunobu Matsuda, Yoichi Ajioka, Shin-ichi Kosugi, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   9 ( 7 )   6937 - 6944   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    MED12 is a transcriptional mediator complex subunit, which negatively regulates the transforming growth factor beta (TGF-beta) pathway. The TGF-beta pathway plays a major role in the induction of epithelial-mesenchymal transition 9EMT). MED12 loss induces activation of the TGF-beta pathway, resulting in EMT and drug resistance to epidermal growth factor receptor (EGFR)-targeted therapy. We aimed to investigate the clinical significance of MED12 loss detected by immunohistochemistry in patients with colorectal cancer (CRC). A total of 100 patients diagnosed with stage I-IV CRC were enrolled in this retrospective study. MED12 expression was evaluated immunohistochemically, and classified as either positive (>= 20%) or negative (<20%) with regard to the percentage of immunoreactive cells. The relationships between MED12 loss and clinicopathological characteristics and RAS mutation status were analyzed. Overall, 79 and 21 patients were classified as MED12 positive and MED12 negative, respectively. MED12 negativity was significantly associated with tumor budding (P = 0.034), N category (P = 0.010), and M category (P = 0.031). Among stage IV CRC patients, 18 of 31 patients had the RAS wild-type gene; 6 of these patients were MED12 negative, and were considered to have the potential for resistance to EGFR-targeted therapy despite the presence of the wild-type gene. In conclusion, MED12 loss is associated with tumor budding, nodal metastasis, and distant metastasis in patients with CRC, suggesting that MED12 loss induces activation of the TGF-beta pathway resulting in EMT. Future treatment strategies focusing on patients MED12 loss may improve the prognosis of patients with CRC.

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  • Histologic determination of primary site of perihilar cholangiocarcinoma based on microscopi'c tumor invasion of the vasculo-biliary sheaths

    Yuki Hirose, Jun Sakata, Makoto Inoue, Zhengkun Zhang, Taku Ohashi, Kohei Miura, Kazuyasu Takizawa, Hiroshi Ichikawa, Masayuki Nagahashi, Takashi Kobayashi, Shin-ichi Kosugi, Hitoshi Kameyanna, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   9 ( 2 )   627 - 638   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:E-CENTURY PUBLISHING CORP  

    This study aimed to histologically characterize microscopic tumor invasion of the vasculo-biliary sheaths in perihilar cholangiocarcinoma so as to determine the primary tumor site and to clarify clinicopathologic differences according to the primary site. A retrospective analysis was conducted of 52 patients who underwent resection for perihilar cholangiocarcinoma involving both the hepatic hilus and the liver, verified histologically. Histologic features of the vasculo-biliary sheath invasion were evaluated by double staining with hematoxylin-eosin to assess general morphology and Victoria Blue to detect the elastic fibers of the vasculo-biliary sheaths. The perihilar cholangiocarcinomas were classified into extrahepatic-type (34 patients), featuring an extrahepatic component involving the liver, and intrahepatic-type (18 patients), featuring an intrahepatic component involving the hepatic hilus. Hemihepatectomy with extrahepatic bile duct resection was the most common surgical procedure. Tumor size (p = 0.002), pN classification (p = 0.005), and pM classification (p = 0.023) were significant independent prognostic factors. The primary site was not significantly associated with survival after resection (p = 0.214), as patients with extrahepatictype tumors had a cumulative 5-year survival rate of 32%, compared with 28% for patients with intrahepatic-type tumors. Double staining with hematoxylin-eosin and Victoria Blue permits histologic discrimination between tumors of extrahepatic and intrahepatic origin, and thereby determination of the primary tumor site in clinical cases of perihilar cholangiocarcinoma. Combining extrahepatic-type and intrahepatic-type tumors under the term perihilar cholangiocarcinoma is valid clinically, as these tumors show comparable surgical outcomes with similar clinical management.

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  • Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer 査読

    Yoshifumi Shimada, Tomoki Kido, Hitoshi Kameyama, Mae Nakano, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Masayuki Nagahashi, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Toshifumi Wakai, Yoichi Ajioka

    SURGERY TODAY   45 ( 12 )   1493 - 1500   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Perineural invasion (PN) diagnosed by hematoxylin-eosin (HE) staining is an important prognostic factor after curative-intent surgery in patients with colorectal cancer. However, the clinical significance of PN diagnosed by immunohistochemistry (IHC) has not been investigated. The present study assessed the clinical significance of PN diagnosed by IHC with an anti-S100 antibody in patients with colorectal cancer.
    We retrospectively enrolled 184 consecutive patients with stage I-III colorectal cancer who had undergone curative-intent surgery. We analyzed the absence/presence of PN diagnosed by HE staining (HE-PN) compared to that diagnosed by IHC with the anti-S100 antibody (S100-PN). Potential prognostic factors were identified by univariate and multivariate analyses of the overall and relapse-free survival. The statistics were used to assess the inter-observer reproducibility.
    The incidence of HE-PN and S100-PN among the 184 patients was 60 patients (32.6 %) and 113 patients (61.4 %), respectively (P &lt; 0.001). A multivariate Cox proportional hazards regression model analysis indicated that S100-PN was an independent prognostic factor for both the overall and relapse-free survival. The value was 0.77 for S100-PN and 0.47 for HE-PN.
    PN diagnosed by IHC is an important prognostic factor in patients with colorectal cancer. An inter-observer assessment showed superior judgment reproducibility for S100-PN compared with HE-PN.

    DOI: 10.1007/s00595-014-1096-9

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  • Internal hernia after laparoscopic-assisted proximal gastrectomy with jejunal interposition for gastric cancer: a case report 国際誌

    Kotaro Hirashima, Takashi Ishikawa, Shin-ichi Kosugi, Yosuke Kano, Yu Sato, Hiroshi Ichikawa, Takaaki Hanyu, Takeo Bamba, Toshifumi Wakai

    Surgical Case Reports   1 ( 1 )   49 - 49   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Internal hernia after gastrectomy is a rare complication. It can progress rapidly to vascular disturbance, necrosis, and perforation, therefore early diagnosis and surgical treatment is essential. We present a case of internal hernia following laparoscopic-assisted proximal gastrectomy with jejunal interposition reconstruction in a 68-year-old man, who presented with acute abdominal pain and vomiting. Computed tomography showed a whirl sign, ascites, and a closed-loop formation of the small intestine. We diagnosed an internal hernia and performed emergency surgery. Laparotomy revealed chyle-like ascites and extensive small intestine with poor color. We recognized that about 20 cm of jejunum from the ligament of Treitz was strangulated behind the pedicle of the jejunum lifted during laparoscopic-assisted proximal gastrectomy. We relieved the strangulation, whereupon the color of the strangulated intestine was restored. Therefore, we did not perform intestinal resection and reconstruction. Finally, we fixed the jejunal pedicle and mesentery of the transverse colon. We report this case as there are few reported cases of internal hernia after laparoscopic-assisted proximal gastrectomy.

    DOI: 10.1186/s40792-015-0051-3

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    その他リンク: http://link.springer.com/article/10.1186/s40792-015-0051-3/fulltext.html

  • Conservative treatment of idiopathic spontaneous pneumoperitoneum in a bedridden patient: a case report 国際誌

    Ryo Tanaka, Hitoshi Kameyama, Masayuki Nagahashi, Tatsuo Kanda, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Takashi Kobayashi, Jun Sakata, Shin-ichi Kosugi, Toshifumi Wakai

    Surgical Case Reports   1 ( 1 )   69 - 69   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Idiopathic spontaneous pneumoperitoneum is a rare condition that is characterized by intraperitoneal gas for which no clear etiology has been identified. We report here a case of idiopathic spontaneous pneumoperitoneum, which was successfully managed by conservative treatment. A 77-year-old woman who was bedridden with speech disability as a sequela of brain hemorrhage presented at our hospital with a 1-day history of abdominal distention. On physical examination, she had stable vital signs and slight epigastric tenderness on deep palpation without any other signs of peritonitis. A chest radiograph and computed tomography showed that a large amount of free gas extended into the upper abdominal cavity. Esophagogastroduodenoscopy revealed no perforation of the upper gastrointestinal tract. The patient was diagnosed with idiopathic spontaneous pneumoperitoneum, and conservative treatment was selected. The abdominal distension rapidly disappeared, and the patient resumed oral intake on the 5th hospital day without deterioration of symptoms. Knowledge of this rare disease and accurate diagnosis with findings of clinical imaging might contribute towards refraining from unnecessary laparotomy.

    DOI: 10.1186/s40792-015-0073-x

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  • Prognostic significance of peritoneal lavage cytology at three cavities in patients with gastric cancer. 国際誌

    Yosuke Kano, Shin-ichi Kosugi, Takashi Ishikawa, Takahiro Otani, Yusuke Muneoka, Yu Sato, Takaaki Hanyu, Kotaro Hirashima, Takeo Bamba, Toshifumi Wakai

    Surgery   158 ( 6 )   1581 - 9   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: We sought to determine the prognostic significance of intraoperative peritoneal lavage cytology (CY) at 3 different abdominal cavities and establish the optimal treatment for gastric cancer patients with positive peritoneal cytology (CY1). METHODS: A total of 1,039 patients with primary gastric adenocarcinoma who underwent CY at 3 cavities (Douglas' pouch, left subphrenic cavity, and right subhepatic cavity) were enrolled; 116 (11%) patients had at least one positive cavity. We retrospectively analyzed the clinicopathologic characteristics and survival of these 116 patients with CY1. RESULTS: Seventeen (15%) of the patients had negative cytology at Douglas' pouch but positive cytology at one or both of the other cavities. The 116 patients' overall 2-year survival rate was 22.9%, with the median survival time of 11 months. The overall 2-year survival rates for the patients with positive cytology at 1, 2, and 3 cavities were 41.9%, 35.8%, and 15%, with median survival times of 17, 18, and 9 months, respectively (P < .01). A multivariate analysis revealed that macroscopic type 4 tumor, R2 resection, lymph node metastasis, and postoperative chemotherapy were independent prognostic factors. Among the CY1 patients with type 4 tumors, there was no substantial difference in survival between the patients who underwent R1 or R2 resection, although the statistical power of this subgroup analysis was low. CONCLUSION: CY at 3 cavities might be a useful method to decrease the false-negative rate. Palliative gastrectomy for CY1 patients with type 4 tumors is still controversial.

    DOI: 10.1016/j.surg.2015.04.004

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  • Locally Advanced Breast Cancer Treated with Halsted's Operation Because of Drug-Induced Lung Injury Caused by Neoadjuvant Chemotherapy--A Case Report

    Kazuki Moro, Masayuki Nagahashi, Junko Tsuchida, Kumiko Tatsuda, Chie Toshikawa, Miki Hasegawa, Takashi Ishikawa, Yoshifumi Shimada, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Shin ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer &amp; chemotherapy   42 ( 12 )   1803 - 1805   2015年11月

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    掲載種別:研究論文(学術雑誌)  

    A 64-year-old woman discovered a mass in her left breast and visited our hospital. A thorough examination resulted in a diagnosis of left, locally advanced breast cancer (cT4bN3, M0, cStage Ⅲc) with muscle invasion and Level Ⅲ lymph node metastases. Because of drug-induced lung disease following 4 courses of adriamycin and cyclophosphamide, the chemotherapy had to be stopped. Halsted's operation and postoperative radiotherapy (50 Gy) were performed. The patient was alive with no evidence of recurrence 9 months after surgery. Although multidisciplinary therapy is recommended in locally advanced breast cancer, chemotherapy sometimes cannot be performed due to factors such as age and physical status. Halsted's operation could be considered as a treatment of choice in patients with locally advanced breast cancer. It is important to choose the treatment strategy based on the condition of the patient.

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  • [Mesorectal Lymph Node Metastasis Arising from Rectal Invasion by an Ovarian Cancer--A Case Report].

    Toru Mizuki, Yoshifumi Shimada, Yutaka Yagi, Yosuke Tajima, Mae Nakano, Masato Nakano, Kumiko Tatsuda, Takashi Ishikawa, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Shin-ichi Kosugi, Yu Koyama, Toshifumi Wakai, Takayuki Enomoto

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2300 - 2   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 58-year-old woman presenting with abdominal distension was diagnosed with a tumor in the right ovary. A chest-abdominal-pelvic computed tomography scan revealed multiple lung metastases, multiple liver metastases, and peritoneal dissemination. Invasion of the rectum by peritoneal dissemination of the Douglas' pouch was suspected. She was diagnosed with Stage Ⅳ right ovarian cancer and was treated with preoperative chemotherapy. After chemotherapy, debulking surgery of the abdominal cavity (total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and Hartmann's procedure) was performed. Because there was swelling observed in multiple mesorectal lymph nodes, lymph node dissection was performed based on methods used for rectal cancer surgery. Postoperative histopathological examination revealed multiple mesorectal lymph node metastases arising from ovarian cancer. We suggest that mesorectal lymph node dissection be considered a part of debulking surgery for ovarian cancers that have invaded the rectum.

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  • [A Case of Rectal Carcinoma with Recurrence around the Drainage Site Complicated by Fournier's Gangrene].

    Kaoru Abe, Hitoshi Kameyama, Yoshifumi Shimada, Saki Yamada, Daiki Soma, Ryoma Yagi, Kohei Miura, Kumiko Tatsuda, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2291 - 3   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 71-year-old woman diagnosed with Fournier's gangrene caused by penetration of a rectal carcinoma was referred to our hospital. Emergency drainage and sigmoid colostomy were performed. Pathological examination of a biopsy sample showed moderately differentiated tubular adenocarcinoma. Abdominoperineal resection with bilateral salpingo-oophorectomy and hysterectomy was performed with curative intent after 4 courses of chemotherapy with S-1 and oxaliplatin. The postoperative pathological diagnosis was StageⅡ (pT4bN0M0). The patient received tegafur/uracil and Leucovorin as adjuvant chemotherapy. Seven months after the curative operation, partial pneumonectomy was performed for the recurrence of the rectal carcinoma in the right lung. Eight months after pneumonectomy, recurrent tumors were observed in the right lung and subcutaneous fat layer of the right buttock along the drainage site. The tumor in the right buttock was excised along with part of the gluteus maximus, and partial pneumonectomy was then performed. Three years and 6 months after the emergency drainage, the patient is alive with no evidence of recurrence. After drainage for rectal carcinoma complicated by Fournier's gangrene, the possibility of recurrence around the drainage site should be considered.

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  • [Three Cases of Stage Ⅳ Low Rectal Cancer with Lateral Pelvic Lymph Node Metastasis].

    Hiroshi Tamura, Yoshifumi Shimada, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Takashi Ishikawa, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Shin-ichi Kosugi, Toshifumi Wakai, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2303 - 5   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Case 1: A 61-year-old man who had a diagnosis of low rectal cancer with lateral pelvic lymph node (LPLN) metastasis and multiple liver metastases underwent low anterior resection with LPLN dissection. The initial surgery was followed by chemotherapy, and then an extended right hepatectomy with partial resection of the liver was performed. Subsequently, a lung metastasis was detected, and the lung was partially resected. The patient was alive 9 years and 6 months after the initial operation. Case 2: A 53-year-old man had a diagnosis of low rectal cancer. After 5 courses of mFOLFOX6 plus bevacizumab, he underwent low anterior resection with LPLN dissection and resection of the peritoneal metastasis. The patient was alive 6 years and 3 months after the surgery without any signs of recurrence. Case 3: A 48-year-old man had a diagnosis of low rectal cancer and multiple liver metastases. He underwent low anterior resection with LPLN dissection and right hepatic lobectomy. He subsequently showed liver and lung metastases. The patient received systemic chemotherapy, and is alive with recurrent disease. We report 3 cases of Stage Ⅳ low rectal cancer with LPLN metastasis, and propose that LPLN dissection is important as a part of R0 resection for Stage Ⅳ low rectal cancer.

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  • [A Case of Solitary Paraaortic Lymph Node Recurrence after Surgical Resection for Combined Hepatocellular and Cholangiocarcinoma].

    Yuki Hirose, Jun Sakata, Kizuki Yuza, Daiki Soma, Natsuru Sudo, Hirosuke Ishikawa, Kumiko Tatsuda, Kohei Miura, Kazuyasu Takizawa, Kabuto Takano, Masayuki Nagahashi, Takashi Kobayashi, Hitoshi Kameyama, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   1860 - 2   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 46-year-old woman underwent right hemihepatectomy, cholecystectomy, and sampling of the hilar lymph nodes for combined hepatocellular and cholangiocarcinoma. She received oral S-1 after hepatectomy. However, her serum level of carcinoembryonic antigen gradually increased, and solitary paraaortic lymph node recurrence was detected on positron emission tomography-computed tomography 12 months after hepatectomy. The patient underwent paraaortic lymph node dissection. Histologic examination revealed solitary paraaortic lymph node metastasis composed of hepatocellular carcinoma. After paraaortic lymph node dissection, she was administered sorafenib, and she remains alive and healthy with no evidence of disease 17 months after the initial resection.

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  • [Signet-Ring Cell Carcinoma of the Ampulla of Vater--Report of a Case].

    Kizuki Yuza, Jun Sakata, Daiki Soma, Takuya Ando, Yuki Hirose, Hirosuke Ishikawa, Kohei Miura, Kumiko Tatsuda, Taku Ohashi, Kazuyasu Takizawa, Masayuki Nagahashi, Hitoshi Kameyama, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   1767 - 9   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 62-year-old man presented with pruritus caused by obstructive jaundice. He was diagnosed with carcinoma of the ampulla of Vater and underwent pylorus-preserving pancreaticoduodenectomy. Histologic examination revealed signet-ring cell carcinoma without nodal metastasis. The patient underwent a partial resection of the small bowel for small bowel obstruction 38 months after the initial resection. Histologic examination disclosed signet-ring cell carcinoma at the surface of the resected small bowel, and the diagnosis of peritoneal recurrence was confirmed. He received oral S-1(100 mg/day) every other day for 14 months until bowel obstruction caused by peritoneal carcinomatosis became apparent. The patient died of the disease 58 months after the initial resection.

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  • [A Case of Radical Resection for Locally Advanced Pancreatic Cancer with Positive Peritoneal Cytology Treated with Chemoradiotherapy].

    Ryohei Sato, Kazuyasu Takizawa, Kizuki Yuza, Daiki Soma, Yuki Hirose, Yuta Morimoto, Kohei Miura, Masayuki Nagahashi, Kabuto Takano, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2385 - 7   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 54-year-old female patient was admitted with obstructive jaundice. The patient was diagnosed with locally advanced unresectable pancreatic cancer of the head with invasion to the super mesenteric artery and the third portion of the duodenum. A biliary- and gastric-enteric bypass surgery was performed, and peritoneal lavage cytology was positive during surgery. After 6 courses of gemcitabine and S-1 combination chemotherapy, the CA19-9 level was normalized and the primary tumor shrank to 79% of its original size. Diagnostic laparoscopy revealed that distant metastasis was not detected and the peritoneal lavage cytology was negative. After additional chemoradiation therapy, a pancreaticoduodenectomy was perfomed. Microscopic investigation revealed that about 60% of the cancer tissue had been replaced by fibrosis and no cancer cells were found at the surgical margin. The patient was alive with no evidence of recurrence 17 months after radical surgery.

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  • [Repeated Pancreatic Resections with Parenchymal Preservation for Pancreatic Metastases of Renal Cell Carcinoma--Report of a Case].

    Hirosuke Ishikawa, Jun Sakata, Daiki Soma, Kizuki Yuza, Takuya Ando, Yuki Hirose, Kohei Miura, Kumiko Tatsuda, Taku Ohashi, Kazuyasu Takizawa, Masayuki Nagahashi, Hitoshi Kameyama, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2254 - 5   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 51-year-old man underwent right nephrectomy for renal cell carcinoma. Six months later, a solitary metastatic tumor was detected in the pancreatic tail and he underwent distal pancreatectomy and splenectomy. One year and 6 months after the initial resection, a solitary metastatic tumor was detected in the pancreas head, and he underwent partial pancreatectomy. A solitary metastatic tumor was detected again in the remnant pancreatic body 3 years and 10 months after the initial resection. Partial resection of the distal part of the remnant pancreas was performed. The patient remains alive and well with no evidence of remnant disease 4 years after the initial resection.

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  • [A Case of Long-Term Survival Following Metastasectomies of Liver Metastasis, Lung Metastasis, and Peritoneal Dissemination of Cecal Cancer].

    Jun Yamamoto, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Saki Yamada, Ryoma Yagi, Kumiko Tatsuda, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   1597 - 9   2015年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    The patient was a 73-year-old woman. She underwent right hemicolectomy and D3 lymph node dissection for cecal cancer in June 2003. Although a peritoneal dissemination was intraoperatively noted around the primary tumor lesion, it was resected concurrently and thus R0 surgery was accomplished. Postoperative adjuvant chemotherapy was not performed. During the follow-up on an outpatient basis, a solitary left lung metastasis was found and partial left upper lobectomy of the lung was performed in December 2004. A solitary liver metastasis was identified in the liver (S3), and lateral segmentectomy of the liver was performed in June 2007. The patient was alive with no evidence of recurrence 11 years and 9 months after resection of the primary lesion and 7 years and 9 months after the hepatectomy. Long-term survival can be achieved by performing resection without residual cancer even in some cases with metachronous metastatic recurrences in multiple organs. Metastasectomy should be considered proactively when the patient is in a good general condition and R0 resection is possible.

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  • [Usefulness of Palliative Gastrojejunal Bypass Surgery]. 査読

    Hashimoto Y, Suzuki S, Nihei K, Ohtaki M, Sakamoto K, Yagi R, Shironomae T, Nagai Y, Mishina T, Kameyama H, Ichikawa H, Tatsuda K, Kobayashi T, Kosugi S, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   1559 - 1560   2015年11月

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  • [A Case of Long-Term Survival of a Patient with Liver Metastasis of Colon Cancer and Suspected Inferior Vena Cava Invasion]. 査読

    Otani T, Kameyama H, Kaneko K, Sato T, Suzuki S, Okada T, Aono T, Muto I, Hasegawa M, Sakata J, Kobayashi T, Minagawa M, Kosugi S, Kurosaki I, Wakai T

    Gan to kagaku ryoho. Cancer & chemotherapy   42 ( 12 )   2184 - 2186   2015年11月

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  • Stage IV下部直腸癌に対する側方リンパ節郭清とmetastasectomy

    島田 能史, 田村 博史, 八木 亮磨, 田島 陽介, 岡村 拓磨, 中野 雅人, 亀山 仁史, 永橋 昌幸, 坂田 純, 小林 孝, 小杉 伸一, 若井 俊文, 野上 仁, 丸山 聡, 瀧井 康公

    日本消化器外科学会雑誌   48 ( Suppl.2 )   148 - 148   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器外科学会  

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  • 家族性大腸腺腫症術後に発症した回腸嚢内腺腫、回腸嚢内腺癌の検討

    中野 雅人, 亀山 仁史, 島田 能史, 阿部 馨, 山田 沙季, 庭野 稔之, 岩城 孝和, 廣瀬 雄己, 八木 亮磨, 田島 陽介, 岡村 拓磨, 中野 麻恵, 永橋 昌幸, 石川 卓, 坂田 純, 小林 隆, 皆川 昌広, 小杉 伸一, 小山 諭, 若井 俊文

    日本消化器外科学会雑誌   48 ( Suppl.2 )   360 - 360   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器外科学会  

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  • A case of pneumatosis cystoides intestinalis secondary to gefitinib therapy for lung adenocarcinoma 査読

    Takuya Ando, Jun Sakata, Tomohiro Maruyama, Yuki Hirose, Yasuyuki Okabe, Kazuyasu Takizawa, Masayuki Nagahashi, Yoshifumi Shimada, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Shinichi Kosugi, Yu Koyama, Aya Ohtsubo, Satoshi Watanabe, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   42 ( 7 )   847 - 849   2015年7月

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    掲載種別:研究論文(学術雑誌)  

    Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition, characterized by subserosal or submucosal air within the bowel wall. Herein, we report a rare case of PCI secondary to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). A 71-year-old man, who had received gefitinib therapy for 2 years and 5 months for lung adenocarcinoma with metastases to the bones and brain, presented with abdominal pain, diarrhea, and vomiting. Computed tomography of the abdomen revealed intramural air in the small bowel, free air in the abdomen, and moderate ascites. A diagnosis of PCI was made, and the patient was managed conservatively by discontinuing gefitinib treatment, because his vital signs were stable and there was no sign of peritonitis. The patient&#039;s symptoms gradually improved, and follow-up CT after 1 week revealed that the initial findings had almost completely resolved. Clinicians should note that treatment with gefitinib might cause PCI.

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  • Incidence and Risk Factors for Anastomotic Stricture after Esophagectomy with Gastric Tube Reconstruction. 国際誌

    Takaaki Hanyu, Shin-Ichi Kosugi, Takashi Ishikawa, Hiroshi Ichikawa, Toshifumi Wakai

    Hepato-gastroenterology   62 ( 140 )   892 - 7   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIMS: The aim of this study was to investigate the incidence and risk factors for anastomotic stricture after esophagectomy with gastric tube reconstruction. METHODOLOGY: A total of 150 consecutive patients with esophageal cancer who underwent esophagectomy with gastric tube reconstruction were analyzed in this study. Anastomotic stricture was de fined as disturbance of the passage of a standard endo scope, with no evidence of locoregional cancer recurrence. Cumulative incidence was calculated using the Kaplan-Meier method. A total of 38 clinicopathological variables were assessed to elucidate the risk factors by univariate and multivariate analyses. RESULTS: Anastomotic stricture developed in 61 of 150 patients 41%). The cumulative incidences were 34.2% at 6 months, and 37.9% at 12 months. Fifty-seven patients (93%) developed anastomotic stricture within 12 months after esophagectomy. A low preoperative partial pressure of arterial oxygen (odds ratio, 2.23; 95% confidence interval, 1.10-4.55; p = 0.027) and the presence of postoperative complications of Grade 3 or higher (3.05; 1.04-9.00; p = 0.043) were identified as the independent risk factors. CONCLUSIONS: The incidence of anastomotic stricture after esophagectomy was high. A modification of anastomotic procedure may be necessary for patients with a low preoperative partial pressure of arterial oxygen to prevent the development of stricture.

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  • Severe cellulitis and abdominal wall emphysema following laparoscopic colonic surgery: A case report.

    Ryo Tanaka, Hitoshi Kameyama, Tadasu Chida, Tatsuo Kanda, Yosuke Kano, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Shin-Ichi Kosugi, Toshifumi Wakai

    Asian journal of endoscopic surgery   8 ( 2 )   193 - 6   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Abdominal wall emphysema is a common complication of laparoscopic surgery. This condition is usually harmless; however, if an infection occurs, it can develop into a serious condition such as necrotizing fasciitis. We report a case of a 51-year-old woman suffering from severe cellulitis that spread from an area of abdominal wall emphysema after laparoscopic surgery for sigmoid colon cancer. Recognizing this complication, early diagnosis, and prompt treatment are cornerstones for successful management of this potentially fatal disease.

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  • Prognostic analysis of submucosa-invasive gastric cancer with lymph node metastasis 査読

    Takaald Hanyu, Atsushi Matsuki, Shin-ichi Kosugi, Takashi Ishikawa, Atsushi Nashimoto, Hiroshi Yabusaki, Masaki Aizawa, Hiroshi Ichikawa, Yoshifumi Shimada, Yuki Hirose, Toshifumi Wakai

    SURGERY   157 ( 4 )   716 - 722   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    Background. The aims of this study were to identify prognostic factors of patients with submucosa-invasive (T1b) gastric cancer and to verify the validity of adjuvant chemotherapy for this disease.
    Methods. We retrospectively examined the cases of 1,236 consecutive patients in our prospectively maintained database with T1b gastric cancer who underwent gastrectomy in 1995-2012. We used 11 clinicopathologic characteristics to identify prognostic factors by univariate and multivariate analyses. We compared the survival of the 160 node-positive T1b gastric cancer patients with that of 133 patients in the same database who had node-positive muscularis propria-invasive (T2) gastric cancer and had undergone gastrectomy without adjuvant chemotherapy during the same period, as a reference cohort.
    Results. The 5-year overall survival rate was 91.4% for all 1,236 patients. Advanced age (hazard ratio [HR] 4.51; 95% confidence interval [CI] 3.26-6.24; P &lt; .01), male sex (HR 2.26; 95% CI 1.5- 3.26; P &lt; .01), and the presence of lymph node metastasis (HR 1.89; 95% CI 1.33-2.70; P &lt; .01) were independent prognostic factors. The 5-year overall survival rates were 92.5 % in node-negative patients, 84.5% in patients with 1 or 2 metastatic nodes, and 80.1% in patients with 3 or more metastatic nodes (P &lt;.01). The 5-year overall survival rates of the node-positive T1b and T2 gastric cancer patients were 83.6% and 81.2%, respectively (P = .73).
    Conclusion. The prognosis of node-positive T1b gastric cancer patients after curative gastrectomy was unsatisfactory. Adjuvant chemotherapy should be considered for these patients, especially those with 3 or more metastatic nodes.

    DOI: 10.1016/j.surg.2014.10.009

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  • Randomized study of low‐dose versus standard‐dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303) 国際誌

    Masayuki Shinoda, Nobutoshi Ando, Ken Kato, Satoshi Ishikura, Hoichi Kato, Yasuhiro Tsubosa, Keiko Minashi, Hiroshi Okabe, Yusuke Kimura, Tatsuyuki Kawano, Shin‐Ichi Kosugi, Yasushi Toh, Kenichi Nakamura, Haruhiko Fukuda

    Cancer Science   106 ( 4 )   407 - 412   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

    DOI: 10.1111/cas.12622

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.12622

  • Immune responses in patients with esophageal cancer treated with SART1 peptide-pulsed dendritic cell vaccine. 国際誌

    Miwako Narita, Tatsuo Kanda, Takashi Abe, Takayoshi Uchiyama, Minami Iwafuchi, Zhiyin Zheng, Aichun Liu, Tsutomu Kaifu, Shinichi Kosugi, Masahiro Minagawa, Kyogo Itoh, Masuhiro Takahashi

    International journal of oncology   46 ( 4 )   1699 - 709   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Patients with advanced stage of squamous cell carcinoma of esophagus have a poor prognosis with a lethal outcome. In order to explore the feasibility and effectiveness of dendritic cell (DC)-based immunotherapy for squamous cell carcinoma of esophagus, we performed a phase I/II clinical trial of monocyte-derived dendritic cells (moDCs) pulsed with SART1 peptide in seven patients with advanced stage of this disease. Although the feasibility of this therapy was definite, the effectiveness was not clearly confirmed in advanced stage of squamous cell carcinoma of esophagus. However, in vitro study revealed that moDCs generated for this therapy possessed a potent ability of inducing SART1 peptide-specific cytotoxic T lymphocytes (CTLs). In addition, these moDCs were demonstrated to be able to produce exosomes with an antigen presenting ability for inducing SART1 peptide-specific CTLs. ELISPOT assay using cryopreserved patient's lymphocytes demonstrated that IFN-γ ELISPOTs were increased after four times of SART1 peptide-pulsed moDC vaccinations compared with before the vaccination in a patient. The present study demonstrated that moDCs prepared from advanced stage of squamous cell carcinoma of esophagus possess a good immune function and in vivo immune responses (detected by ELISPOT assay) were evoked by the infusion of these moDCs. These findings suggest that DC-based immunotherapy could be one of the modalities applicable for squamous cell carcinoma of esophagus.

    DOI: 10.3892/ijo.2015.2846

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  • Three cases of esophageal carcinoma achieved a pathological complete response after neoadjuvant chemotherapy with cisplatin and 5-fluorouracil

    Hidehito Oyanagi, Hiroshi Ichikawa, Shin Ichi Kosugi, Takeo Banba, Takaaki Hanyu, Kotaro Hirashima, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   42 ( 4 )   497 - 501   2015年4月

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    掲載種別:研究論文(学術雑誌)  

    We report three cases of esophageal carcinoma all of which achieved a pathological complete response after neoadjuvant chemotherapy (NAC) with cisplatin and 5-fluorouracil (CF). All three patients were men with clinical stage II squamous cell carcinoma of the middle thoracic esophagus. We administered 2 courses of CF treatment as NAC and then performed radical esophagectomy. Pathologic examination revealed no viable tumor cells in the resected esophagus. The patients are currently alive with no evidence of disease.

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  • Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis 査読

    Hiroshi Ichikawa, Akihiko Yoshida, Tatsuo Kanda, Shin-ichi Kosugi, Takashi Ishikawa, Takaaki Hanyu, Takahiro Taguchi, Marimu Sakumoto, Hitoshi Katai, Akira Kawai, Toshifumi Wakai, Tadashi Kondo

    CANCER SCIENCE   106 ( 1 )   115 - 124   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of the small intestine (I-GIST) show more aggressive behavior than those of the stomach (S-GIST), and the molecular background of the malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for four cases each of surgically resected I-GIST and S-GIST using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GIST and 23 S-GIST. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly downregulated in I-GIST at both the protein and mRNA levels (P&lt;0.01; fold difference 2.0). Immunohistochemistry of 254 additional cases from multiple clinical facilities showed that PML-negative cases were significantly frequent in the I-GIST group (P&lt;0.001). The 5-year recurrence-free survival rate was significantly lower in the PML-negative than in the PML-positive cases (60.1% vs 91.7%; P&lt;0.001). Multivariate analysis revealed that downregulation of PML was an independent unfavorable prognostic factor (hazard ratio=2.739; P=0.001). Our study indicated that prognostication based on PML expression may have potential for optimizing the treatment strategy for GIST patients. Further validation studies of PML for clinical application, and investigation for the mechanistic significance of PML to clarify the molecular backgrounds of malignancy in GIST are warranted.

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  • Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer: Supplementary exploratory analysis of JCOG9907 査読

    Hiroya Takeuchi, Junki Mizusawa, Ken Kato, Kozo Kataoka, Hiroyasu Igaki, Tetsuya Abe, Hisayuki Matsushita, Kazuhiko Hayashi, Satoru Nakagawa, Takaki Yoshikawa, Isao Nozaki, Takeshi Iwaya, Shinichi Kosugi, Motohiro Hirao, Harushi Udagawa, Soji Ozawa, Yasuhiro Tsubosa, Kenichi Nakamura, Nobutoshi Ando, Yuko Kitagawa

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 3 )   2015年1月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/jco.2015.33.3_suppl.155

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  • A Case of Obstructive Colitis with Elevated Serum Carcinoembryonic Antigen

    Hitoshi Kameyama, Masayuki Nagahashi, Yuki Hirose, Natsuru Sudo, Yosuke Tajima, Masato Nakano, Yoshifumi Shimada, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Journal of Clinical Case Reports   5 ( 11 )   2015年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:OMICS Publishing Group  

    DOI: 10.4172/2165-7920.1000635

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  • Predictive Factors for Non-Sentinel Lymph Node Metastasis in the Case of Positive Sentinel Lymph Node Metastasis in Two or Fewer Nodes in Breast Cancer 国際誌

    Chie Toshikawa, Yu Koyama, Masayuki Nagahashi, Kumiko Tatsuda, Kazuki Moro, Junko Tsuchida, Miki Hasegawa, Toshiyuki Niwano, Naoko Manba, Mayuko Ikarashi, Hitoshi Kameyama, Takashi Kobayashi, Shin-ichi Kosugi, Toshifumi Wakai

    Journal of Clinical Medicine Research   7 ( 8 )   620 - 626   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elmer Press, Inc.  

    BACKGROUND: In breast cancer, recent clinical trials have shown that sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection results in excellent prognosis if there is sentinel lymph node (SLN) metastasis in two or fewer nodes. The aim of the present study was to investigate the association between non-SLN metastasis and clinicopathological factors in case of SLN metastasis in two or fewer nodes in breast cancer. METHODS: Patients who underwent SLNB for invasive breast cancer and were found to have positive SLN in two or fewer nodes were evaluated. The associations between non-SLN metastasis and clinicopahological factors were examined. Statistical analyses were performed using the Mann-Whitney and Chi-square tests, with statistical significance set at P < 0.05. RESULTS: A total of 358 patients were enrolled during the study period and all of these patients were female and 54 patients had SLN metastasis (15%). Positive SLN in two or fewer nodes was identified in 44 patients (81.5%). Among these patients, 17 (38.6%) were found to have non-SLN metastasis. Non-SLN metastasis was associated with invasive tumor size (P = 0.015) and lymphatic involvement (P = 0.035). Multivariate analysis showed that tumor size (P = 0.011) and lymphatic involvement (P = 0.019) remained significant independent predictors of non-SLN metastasis, and that an invasive tumor size cut-off point of 28 mm was useful for dividing patients with positive SLN in two or fewer nodes into non-SLN-positive and non-SLN-negative groups. CONCLUSIONS: Non-SLN metastasis was found in more than 30% of patients with SLN metastasis present in two or fewer nodes. Large tumor size and the presence of lymphatic involvement were significantly associated with non-SLN metastasis.

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  • Prognostic Significance of Initial Recurrence Site in Hematogenous Recurrence of Esophageal Squamous Cell Carcinoma 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Tatsuo Kanda, Takashi Ishikawa, Kazuhito Yajima, Kohei Akazawa, Tsutomu Suzuki, Toshifumi Wakai

    HEPATO-GASTROENTEROLOGY   61 ( 136 )   2241 - 2246   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Hematogenous recurrences of esophageal squamous cell carcinoma (ESCC) have dismal prognoses, but prognostic heterogeneity exists in this disease. The objectives of this study were to clarify the prognosis in this disease with regard to the initial recurrence site and to define the prognostic factors. Methodology: We retrospectively reviewed the cases of 67 consecutive patients with hematogenous recurrence in major organs after esophagectomy for ESCC of the thoracic esophagus and the esophagogastric junction. We analyzed clinicopathological characteristics, survival probability and potential prognostic factors. Results: Lung, liver, bone, and multiple-organ metastases occurred in 24, 19, 14, and 10 patients, respectively. Twenty-seven patients simultaneously had locoregional recurrence (combined recurrence). Among all 67 patients, the median disease-free interval (DFI) was 9.7 months, and the median survival time after the initial recurrence was 4.9 months. The patients with initial lung metastasis had most favorable prognosis with the median survival time of 9.8 months. A multivariate analysis identified that initial recurrence site, DFI, combined recurrence, and anticancer therapy were independent prognostic factors. Conclusions: The initial recurrence site contributes to the prognostic heterogeneity of patients with hematogenous recurrence of ESCC. The prognostic factors identified in this study are useful to optimize the management of these patients.

    DOI: 10.5754/hge13171

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  • Surgical resection after chemotherapy for advanced rectal cancer - Report of a case

    Kazuyoshi Suda, Hitoshi Kameyama, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1572 - 1574   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    Herein, we present a case of advanced rectal cancer surgically resected after chemotherapy. A 65-year-old woman presented with anal pain, and rectal cancer extending beyond the anus was diagnosed. The primary tumor was a well-differentiated adenocarcinoma with a KRAS mutation. Computed tomography revealed cancer invasion into the vagina and sacral and coccygeal bones, and cancer metastases to the bilateral inguinal lymph nodes and the left lung. Sigmoid colostomy and subcutaneous venous port insertion were performed. The patient was treated with modified oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX6) plus bevacizumab. She showed a partial response according to the Response Evaluation Criteria in Solid Tumors after 13 courses of chemotherapy. The primary tumor was then resected via posterior pelvic exenteration, bilateral inguinal lymphadenectomy, and sacral/coccygeal resection. Histological examination of the resected specimens revealed moderately differentiated adenocarcinoma with vaginal invasion. Metastasis to a right inguinal lymph node was observed. The pathological stage was ypT4bN0M1b, ypStage IV according to the tumor-node-metastasis system of the eighth edition of the Japanese Classification of Colorectal Carcinoma. The pathological response grade of the tumor after chemotherapy was determined to be Grade 1b.

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  • A case of an elderly patient who underwent single-incision laparoscopic surgery for small intestine cancer

    Yoshifumi Hashimoto, Hitoshi Kameyama, Yuki Hirose, Ryoma Yagi, Mae Nakano, You Sato, Tomoki Kido, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakano, Takashi Ishikawa, Yoshifumi Shimada, Takashi Kobayashi, Jun Sakata, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2442 - 2443   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    An 81-year-old man presented with chief complaints of abdominal pain and vomiting. Intestinal obstruction was found at the time of admission to a local hospital in October 2011. Conservative treatment provided symptomatic relief; however, he was readmitted with similar symptoms in December 2011. Small-intestinal wall thickening was detected by abdominal and pelvic computed tomography, and he was referred to our hospital. Small-bowel endoscopy revealed an elevated subcircumferential tumor in the jejunum. Biopsy revealed well to moderately differentiated adenocarcinoma diagnosed as jejunal cancer, which caused narrowing of the jejunum. Single-incision laparoscopy-assisted small-bowel resection was performed. The intraoperative findings were a tumor with inflammatory changes in the jejunum and enlarged surrounding lymph nodes. We performed regional lymph node dissection. Histopathological analysis showed moderately differentiated small-intestinal tubular adenocarcinoma and 2 of 5 lymph nodes positive for metastatic cancer cells. After an uneventful postoperative course, he was discharged on day 7. He preferred not to undergo postoperative adjuvant chemotherapy and quickly recovered his activities of daily living postoperatively. He stayed home until he developed abdominal distention resulting from peritoneal recurrence 1 year and 6 months postoperatively and died 1 month later.

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  • A case of descending colon cancer with multiple liver metastases effectively treated with capecitabine/oxaliplatin (CapeOX) and bevacizumab

    Mae Nakano, Hitoshi Kameyama, Yoshifumi Shimada, Yoshifumi Hashimoto, Mana Hosoi, Masato Nakano, Hitoshi Nogami, Takaaki Hanyu, Kazuyasu Takizawa, Takashi Ishikawa, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1785 - 1787   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    A 57-year-old woman was referred to our hospital because of descending colon cancer with multiple liver metastases. Abdominal magnetic resonance imaging (MRI) revealed 13 liver metastases across the lobes. We started combination chemotherapy with capecitabine/oxaliplatin (CapeOX) and bevacizumab. After 9 courses of the treatment, the number and size of the liver metastases were remarkably reduced on MRI. Left colectomy and partial hepatectomy were performed. Histopathological examination revealed no residual cancer cells in the colon but revealed a few cancer cells in 4 of 7 resected liver specimens. At 11 postoperative months, 1 liver metastasis reappeared, for which we performed laparoscopy-assisted partial hepatectomy. At 21 months after the second operation, the patient was well without any signs of recurrence. Thus, the combination chemotherapy with CapeOX and bevacizumab allowed for the successful resection of the tumor and metastasis in our patient who initially had unresectable colon cancer and multiple liver metastases.

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  • A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer

    Ryo Tanaka, Hitoshi Kameyama, Mae Nakano, Hiroshi Ichikawa, Takaaki Hanyu, Masato Nakano, Takashi Ishikawa, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Shin Ichi Kosugi, Masahiro Minagawa, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   2364 - 2366   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, NO, MO, Stage IA) during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

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  • Single-port laparoscopic stoma creation for fecal diversion - Experience of ten consecutive patients

    Ryoma Yagi, Hitoshi Kameyama, Mae Nakano, You Sato, Tomoki Kido, Masato Nakano, Yoshifumi Shimada, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1643 - 1644   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    Purpose: In the present study, we aimed to describe the surgical results of single-port laparoscopic stoma creation in our institution. Methods: We examined the safety of the surgical procedure and short-term results in 10 consecutive patients who underwent single-port laparoscopic stoma creation at our hospital between April 2011 and July 2013. Results: The median age of the patients was 60.5 (range, 31-75) years. Five patients were men, and 5 were women. There were 5 cases of colorectal cancer, 2 each of extramammary Paget's disease and uterine cancer, and one of perineal neurofibroma. Eight surgeries were performed for bowel obstruction or stenosis, and two surgeries were performed for other reasons. The median operative time was 59.5 (range, 40-91) min, blood loss volume was 0 (range, 0-10) mL, postoperative duration before commencement of oral intake was 2.5 (range, 1-4) days, and duration of postoperative hospital stay was 11 (range, 5-19) days. No short-term complications were noted after the surgery. Conclusion: Single-port laparoscopic stoma creation appears to be feasible in terms of safety and short-term surgical results, and may improve the quality of life of patients requiring fecal diversion.

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  • A case of long-term survival in a patient with rectal cancer with virchow lymph node metastasis, liver metastases, and lung metastases

    Hidehito Oyanagi, Hitoshi Kameyama, Hitoshi Nogami, Yoshifumi Shimada, Mae Nakano, Masato Nakano, Takashi Ishikawa, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1674 - 1676   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    A 69-year-old man with advanced rectal cancer and liver metastases was treated with 2 courses of chemotherapy with irinotecan and S-1 followed by low anterior resection and partial hepatectomy. Chemotherapy with S-1 was then administered for 22 months. However, lung metastases developed, for which partial pneumonectomy was performed. Seven months later, computed tomography (CT) revealed swelling of the left supraclavicular lymph node. Despite chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6); 5-fluorouracil, Leucovorin and irinotecan (FOLFIRI); and capecitabine plus bevacizumab, the lung metastases recurred and Virchow lymph node swelling was noted again. Accordingly, palliative therapy was administered. The patient died 3 years 1 month after Virchow lymph node resection. Herein, we describe a case of advanced rectal cancer, in which lung and Virchow lymph node metastases developed after liver metastasis. Surgical excision of the metastases resulted in long-term survival of 6 years following the first operation.

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  • Surgical curative resection after chemotherapy and portal vein embolization for multiple liver metastases of rectal cancer - Report of a case

    Shinnosuke Hotta, Hitoshi Nogami, Mae Nakano, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1794 - 1795   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    A 34-year-old woman presenting with bloody stools was diagnosed with a rectal tumor. Computed tomography (CT) revealed multiple liver masses in Couinaud segments IV, V, and VU. The lesions were diagnosed as multiple liver metastases from rectal cancer. Right trisegmentectomy of the liver was considered the optimal treatment option for curative resection; however, liver volumetric examination using CT estimated that the remnant liver volume after right trisegmentectomy would be only 24.6 % of the total liver volume. Therefore, she underwent resection of the primary lesion followed by systemic chemotherapy for multiple liver metastases. She showed a partial response, according to the Response Evaluation Criteria in Solid Tumors, after 5 courses of capecitabine/oxaliplatin plus bevacizumab. Embolization of the right branch of the portal vein was performed to increase liver volume. A subsequent liver volumetric examination with CT estimated that the remnant liver volume after right trisegmentectomy would be 38.4 % of the total liver volume. Therefore, she underwent right trisegmentectomy of the liver for curative resection of the liver metastases. She had had no signs of recurrence at 3 years and 6 months after initial surgery.

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  • A case of long-term survival after lateral pelvic lymph node dissection for recurrence as skip metastasis of rectal cancer

    Kazuyoshi Suda, Hitoshi Kameyama, Hitoshi Nogami, Yoshifumi Shimada, Takaaki Hanyu, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1620 - 1621   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    Herein, we present a case of long-term survival after lateral pelvic lymph node dissection for recurrence in the form of skip metastasis of rectal cancer. A 63-year-old man underwent abdominoperineal resection without lateral pelvic lymph node dissection for advanced lower rectal cancer. The histological diagnosis was type 2, 85×50 mm, tub1, pT4a, ly0, v1, pPM0, pDM0 and pN0, pStage II (Japanese Classification of Colorectal Carcinoma, 8th edition). Six months after surgery, enhanced computed tomography showed right obturator lymph node metastasis. We performed lateral pelvic lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma in the right obturator lymph node. The lymph node metastasis was diagnosed as a skip metastasis of the rectal cancer. The patient has had no recurrence for 9 years after resection of the lateral pelvic lymph node.

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  • A case of curatively resected, locally advanced ascending colon cancer with ileal conduit invasion

    Hitoshi Kameyama, Yoshifumi Shimada, Hitoshi Nogami, Mae Nakano, Masato Nakano, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin Ichi Kosugi, Yu Koyama, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 12 )   1677 - 1679   2014年11月

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    掲載種別:研究論文(学術雑誌)  

    A 71-year-old man was referred to our hospital because of repeated bowel obstruction. He had previously undergone cystectomy with ileal conduit urinary diversion for the treatment of bladder cancer at the age of 28 years. Computed tomography revealed a mass in the ascending colon. Ileostomy was initially performed because of poor general condition that improved with postoperative nutrition management. Enema findings revealed ascending colon cancer and we therefore decided to perform curative surgery. Intraoperative findings revealed that the ascending colon cancer had invaded the ileal conduit. However, it was confirmed that the ureter-ileal conduit anastomosis and the mesentery of the ileal conduit could be preserved. We performed right colectomy and partial resection of the ileal conduit with curative intent. The pathological stage was pT4bpN0cM0, pStage II. There were no signs of recurrence 15 months after curative surgery.

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  • どこまで膵臓は残せるのか 膵体部温存手術における自験例での検討

    皆川 昌広, 滝沢 一泰, 高野 可赴, 坂田 純, 小林 隆, 小杉 伸一, 小山 諭, 若井 俊文

    日本消化器外科学会雑誌   47 ( Suppl.2 )   269 - 269   2014年10月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器外科学会  

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  • 胃癌ESD後追加外科切除症例の検討

    田中 亮, 小杉 伸一, 市川 寛, 羽入 隆晃, 石川 卓, 橋本 哲, 竹内 学, 小林 正明, 坂田 純, 小林 隆, 皆川 昌広, 小山 諭, 若井 俊文

    日本消化器外科学会雑誌   47 ( Suppl.2 )   148 - 148   2014年10月

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    記述言語:日本語   出版者・発行元:(一社)日本消化器外科学会  

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  • A case of a large liposarcoma of the chest

    Koji Toge, Yu Koyama, Kumiko Tatsuta, Miki Hasegawa, Eiko Sakata, Takashi Kobayashi, Masahiro Minagawa, Shinichi Kosugi, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   41 ( 8 )   1037 - 1040   2014年8月

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    掲載種別:研究論文(学術雑誌)  

    A 49-year-old woman with a growing tumor of the left anterior chest wall was admitted to our hospital. This patient was diagnosed with a malignant well-differentiated tumor by needle biopsy and underwent surgery involving wide resection of the tumor, associated excision of the major pectoralis muscle, and part of the mammary tissue and skin. The tumor measured 14.2X 17.8 cm and weighed 1,220 g. Histopathologically, the tumor was confirmed to be a dedifferentiated liposarcoma, and local recurrence and metastasis often occurs in spite of complete surgical resection. However, no local recurrence or metastasis has been detected 2 months post-surgery. The main anatomic sites of liposarcomas are the retroperitoneum and lower extremities; only 19 liposarcoma cases of the anterior chest wall have been reported in Japan.

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  • Conservative treatment of esophageal perforation related to a peptic ulcer with pyloric stenosis

    Ryo Tanaka, Shin-ichi Kosugi, Daisuke Sato, Hiroshi Hirukawa, Tetsuya Tada, Hiroshi Ichikawa, Takaaki Hanyu, Takashi Ishikawa, Takashi Kobayashi, Toshifumi Wakai

    Clinical Journal of Gastroenterology   7 ( 4 )   295 - 298   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    We report a case of esophageal perforation (Boerhaave syndrome) caused by vomiting related to a duodenal ulcer with pyloric stenosis. A 45-year-old male presented with left chest pain and dyspnea after forceful vomiting. Chest radiography and computed tomography (CT) revealed a massive left pleural effusion and left tension pneumothorax. Abdominal CT revealed pyloric stenosis with a remarkably dilated stomach. Tube thoracostomy and nasogastric suction were immediately performed and we selected conservative treatment based on the following factors-a stable general condition without sepsis, early diagnosis, and good drainage. Esophagogastroduodenoscopy on hospital day 9 demonstrated a healing ulcer in the lower esophagus and pyloric stenosis. We performed distal gastrectomy as elective surgery for pyloric stenosis due to a duodenal ulcer on hospital day 30. In summary, an esophageal perforation with contamination spreading to the thoracic cavity was successfully treated with conservative treatment.

    DOI: 10.1007/s12328-014-0493-3

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    その他リンク: http://link.springer.com/article/10.1007/s12328-014-0493-3/fulltext.html

  • Proteomic and meta-transcriptomic study on lymph node metastasis in gastric cancer

    Hiroshi Ichikawa, Tatsuo Kanda, Shin-ichi Kosugi, Yasuyuki Kawachi, Toshifumi Wakai, Tadashi Kondo

    EuPA Open Proteomics   3   183 - 194   2014年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.euprot.2014.03.001

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  • Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer. 国際誌

    S Hirabayashi, S Kosugi, Y Isobe, A Nashimoto, I Oda, K Hayashi, I Miyashiro, S Tsujitani, Y Kodera, Y Seto, H Furukawa, H Ono, S Tanabe, M Kaminishi, S Nunobe, T Fukagawa, R Matsuo, T Nagai, H Katai, T Wakai, K Akazawa

    Annals of oncology : official journal of the European Society for Medical Oncology   25 ( 6 )   1179 - 84   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

    DOI: 10.1093/annonc/mdu125

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  • Prognostic factors and causes of death in patients cured of esophageal cancer. 国際誌

    Tomoyuki Kakuta, Shin-Ichi Kosugi, Tatsuo Kanda, Takashi Ishikawa, Takaaki Hanyu, Tsutomu Suzuki, Toshifumi Wakai

    Annals of surgical oncology   21 ( 5 )   1749 - 55   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The number of patients cured of esophageal cancer after esophagectomy is gradually increasing owing to advances in surgical techniques, perioperative management, and adjuvant therapies. This study assessed the clinical course and sought to identify the prognostic factors of these patients. METHODS: A series of 220 consecutive patients who underwent esophagectomy and survived for more than 5 years with no relapse were enrolled. Survival analysis was performed using 25 variables including patient characteristics and operative and perioperative factors. Potential prognostic factors were identified by univariate and multivariate analyses, and the development of other primary cancers and the causes of death were retrospectively reviewed. RESULTS: The overall 10-, 15-, and 20-year survival rates were 71.6, 50.1, and 32.2 %, respectively, with a median survival time of 180 months (range, 61-315 months). The negative independent prognostic factors identified were age at surgery [hazard ratio (HR), 1.05; P < .01], being male (HR, 2.62; P = .02), pulmonary comorbidities (HR, 2.03; P = .02), synchronous presence of other cancers (HR, 2.35; P < .01), colonic/jejunal interposition (HR, 1.76; P = .03), perioperative blood transfusion (HR, 1.92; P = .02), development of pulmonary complications (HR, 1.71; P = .02), and adjuvant radiotherapy (HR, 2.13; P = .01). Pulmonary diseases and other primary cancers were found to be the most common causes of death. CONCLUSIONS: Careful follow-up including the surveillance of other primary cancers is required for long-term survivors of esophageal cancer after esophagectomy.

    DOI: 10.1245/s10434-014-3499-7

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  • Laparoscope-assisted Hassab's operation for esophagogastric varices after living donor liver transplantation: a case report. 国際誌

    T Kobayashi, K Miura, H Ishikawa, H Oya, Y Sato, M Minagawa, J Sakata, K Takano, K Takizawa, H Nogami, S-I Kosugi, T Wakai

    Transplantation proceedings   46 ( 3 )   986 - 8   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This is the first successful report of a laparoscope-assisted Hassab's operation for esophagogastric varices after living donor liver transplantation (LDLT). A 35-year-old man underwent LDLT using a right lobe graft as an aid for primary sclerosing cholangitis (PSC) in 2005. Follow-up endoscopic and computed tomography (CT) examinations showed esophagogastric varices with splenomegaly in 2009 that increased (esophageal varices [EV]: locus superior [Ls], moderator enlarged, beady varices [F2], medium in number and intermediate between localized and circumferential red color signs [RC2]; gastric varices [GV]: extension from the cardiac orifice to the fornix [Lg-cf], moderator enlarged, beady varices [F2], absent red color signs [RC0]). A portal venous flow to the esophagogastric varices through a large left gastric vein was also confirmed. Preoperative Child-Pugh was grade B and score was 9. Because these esophagogastric varices had a high risk of variceal bleeding, we proceeded with a laparoscope-assisted Hassab's operation. Operative time was 464 minutes. Blood loss was 1660 mL. A graft liver biopsy was also performed and recurrence of PSC was confirmed histologically. It was suggested that portal hypertension and esophagogastric varices were caused by recurrence of PSC. Postoperative complications were massive ascites and enteritis. Both of them were treated successfully. This patient was discharged on postoperative day 43. Follow-up endoscopic study showed improvement in the esophagogastric varices (esophageal varices [EV]: locus superior [Ls], no varicose appearance [F0], absent red color signs [RC0], gastric varices [GV]: adjacent to the cardiac orifice [Lg-c], no varicose appearance [F0], absent red color signs [RC0]) at 6 months after the operation. We also confirmed the improvement of esophagogastric varices by serial examinations of CT.

    DOI: 10.1016/j.transproceed.2013.10.047

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  • Amplification of Genomic DNA for Decoy Receptor 3 Predicts Post-Resection Disease Recurrence in Breast Cancer Patients. 国際誌

    Chizuko Kanbayashi, Yu Koyama, Hiroshi Ichikawa, Eiko Sakata, Miki Hasegawa, Chie Toshikawa, Naoko Manba, Mayuko Ikarashi, Takashi Kobayashi, Masahiro Minagawa, Shin-Ichi Kosugi, Toshifumi Wakai

    World journal of oncology   5 ( 1 )   14 - 23   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, shows inhibitory effects on Fas-mediated apoptosis. Currently, data are lacking on the correlation between DcR3 and the recurrence of breast cancer. The authors examined DcR3 mRNA expression and genomic amplification in breast cancer, and investigated the effect of DcR3 gene amplification on prognosis of patients. Methods: A total of 95 patients formed the basis of the current retrospective study. DcR3 mRNA expression in breast cancer tissues was examined by RNase protection assay and in situ hybridization. DcR3 gene amplification was examined by quantitative polymerase chain reaction. The correlation between DcR3 gene amplification status and clinicopathological factors was examined and also the relationship between DcR3-Amp and relapse and survival. Results: The relative copy numbers of DcR3 genomic DNA correlated significantly with the levels of DcR3 mRNA expression (ρ = 0.755, P = 0.0067). In addition, lymphatic invasion correlated significantly with DcR3 gene amplification (P = 0.012). However, there was no correlation between the remaining clinicopathological factors and DcR3 gene amplification. In the univariate analysis, the recurrence-free survival (RFS) rate of patients who were positive for DcR3 gene amplification was significantly lower than that of patients who were negative for DcR3 gene amplification (P = 0.0271). Multivariate analysis showed that DcR3 gene amplification (P = 0.028) and disease stage (P < 0.001) remained significant independent predictors of RFS. Conclusions: DcR3 gene amplification was significantly correlated with lymphatic invasion, and also DcR3 gene amplification predicts recurrence after resection, which may be an important prognostic factor in breast cancer patients.

    DOI: 10.14740/wjon764w

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  • Is early enteral nutrition initiated within 24 hours better for the postoperative course in esophageal cancer surgery? 国際誌

    Naoko Manba, Yu Koyama, Shin-Ichi Kosugi, Takashi Ishikawa, Hiroshi Ichikawa, Masahiro Minagawa, Takashi Kobayashi, Toshifumi Wakai

    Journal of clinical medicine research   6 ( 1 )   53 - 8   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Early enteral nutrition within 24 h after surgery has become a recommended procedure. In the present study, we retrospectively examined whether initiating EN within 24 h after esophagectomy improves the postoperative course. METHODS: Among 103 patients who underwent thoracic esophagectomy for esophageal cancer, we enrolled the cases in which EN was initiated within 72 h after surgery. The patients were divided into two groups: EN started within 24 h (Group D1) and EN started at 24 - 72 h (Group D2-3). Clinical factors including days for first fecal passage, dose of postoperative albumin infusion, difference in serum albumin between pre- and postoperation, incidence of postoperative infection, and use of total parenteral nutrition were compared. Statistical analyses were performed by the Mann-Whitney U test and Chi square test, with significance defined as P < 0.05. RESULTS: There was no significant difference between the groups in clinical factors. While pneumonia was significantly more frequent in Group D1 than in Group D2-3 (P = 0.0308), the frequency of infectious complications was comparable between the groups. CONCLUSION: Initiating EN within 24 h showed no advantage for the postoperative course in esophageal cancer, and thus EN should be scheduled within 24 - 72 h, based on the patient condition.

    DOI: 10.4021/jocmr1665w

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  • [Urgent gastrectomy in a patient who developed perforated gastric cancer during preoperative chemotherapy with S-1 plus cisplatin].

    Yasuyuki Okabe, Kazuhito Yajima, Takashi Ishikawa, Shin-ichi Kosugi, Kaoru Sakamoto, Yu Sato, Tatsuo Kanda, Toshifumi Wakai

    Gan to kagaku ryoho. Cancer & chemotherapy   41 ( 1 )   95 - 8   2014年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 66 -year-old man presenting with a chief complaint of upper abdominal pain was diagnosed as having an advanced adenocarcinoma, type 2, of the lower third of the stomach after endoscopy was performed. An abdominal computed tomography( CT)scan revealed 4 lymph node metastases at the infrapyloric nodes(station No. 6)and the nodes around the proximal splenic artery(station No. 11p)and the abdominal aorta(station No. 16a2). The clinical stage was determined to be T3(SS)N2M1(LYM), Stage IV. Gastrectomy with D2 plus para-aortic node dissection was scheduled after 2 courses of S-1 plus cisplatin(CDDP)with curative intent. On day 14 after starting S-1 therapy, the patient complained of severe abdominal pain and peritoneal irritation of acute onset. Because the abdominal CT scan showed a large amount of intra-abdominal free air, we performed an urgent laparotomy with a tentative diagnosis of perforation of the gastric cancer. On laparotomy, we found a perforated malignant ulcer, 5 cm in maximum diameter, in the lesser curvature of the stomach; therefore, distal gastrectomy with D1 plus lymphadenectomy and reconstruction using the Roux-en-Y method were performed. At the end of the surgery, a macroscopic residual tumor remained in the para-aortic lymph node. The postoperative course was uneventful, and the patient was discharged on day 23 after surgery. In the present case, despite the performance of urgent gastrectomy while the patient was receiving strong chemotherapy, perioperative management was successful, with no serious postoperative complication or adverse events as a result of the chemotherapy.

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  • Intrathoracic esophagojejunostomy using OrVil™ for gastric adenocarcinoma involving the esophagus 国際誌

    Kazuhito Yajima, Tatsuo Kanda, Shin-Ichi Kosugi, Yosuke Kano, Takashi Ishikawa, Hiroshi Ichikawa, Takaaki Hanyu, Toshifumi Wakai

    World Journal of Gastrointestinal Surgery   6 ( 12 )   235 - 235   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Baishideng Publishing Group Inc.  

    AIM: To demonstrate a new surgical technique of lower mediastinal lymphadenectomy and intrathoracic anastomosis of esophagojejunostomy using OrVil™. METHODS: After a total median phrenotomy, the supradiaphragmatic and lower thoracic paraesophageal lymph nodes were transhiatally dissected. The esophagus was cut off using a liner stapler and OrVil™was inserted. Finally, end-to-side esophagojejunostomy was created by using a circular stapler. From July 2009, we adopted this surgical technique for five patients with gastric cancer involving the lower esophagus. RESULTS: The median operation time was 314 min (range; 210-367 min), and median blood loss was 210 mL (range; 100-838 mL). The median numbers of dissected lower mediastinal nodes were 3 (range; 1-10). None of the patients had postoperative complications including anastomotic leakage and stenosis. The median hospital stay was 16 d (range: 15-20 d). The median length of esophageal involvement was 14 mm (range: 6-48 mm) and that of the resected esophagus was 40 mm (range: 35-55 mm); all resected specimens had tumor-free margins. CONCLUSION: This surgical technique is easy and safe intrathoracic anastomosis for the patients with gastric adenocarcinoma involving the lower esophagus.

    DOI: 10.4240/wjgs.v6.i12.235

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  • Aquaporin 8 mRNA expression after intestinal resection in rat

    Yu Koyama, Hitoshi Kameyama, Jun Sakata, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Tadashi Yamamoto, Kohei Akazawa, Toshifumi Wakai

    Open Journal of Gastroenterology   04 ( 02 )   62 - 68   2014年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/ojgas.2014.42011

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  • Treatment for perforated gastric ulcer: a multi-institutional retrospective review. 国際誌

    Ryo Tanaka, Shin-ichi Kosugi, Kaoru Sakamoto, Kazuhito Yajima, Takashi Ishikawa, Tatsuo Kanda, Toshifumi Wakai

    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract   17 ( 12 )   2074 - 81   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The optimal treatment for patients with perforated gastric ulcer (PGU) remains controversial. This study therefore investigated the treatment status for this disease in clinical practice. METHODS: We retrospectively reviewed 183 patients with PGU from 1998 to 2007 across 15 institutions, and analyzed patient characteristics and short- and long-term outcomes according to treatments received. RESULTS: Of the 183 patients, 57 who were treated conservatively had less abdominal tenderness, lower levels of serum C-reactive protein, and shorter time to presentation than the 126 patients who underwent emergency surgery. There was no significant difference in baseline characteristics between the 41 successful patients and 16 failed patients in the conservative treatment group; however, the latter had a longer average hospital stay. Eighty-three of the emergency surgery patients who underwent gastrectomy had longer surgical times, greater blood loss, and shorter time to resumption of diet than the 57 patients undergoing stomach-preserving surgery; however, there was no significant difference in postoperative complications and hospital stay between these groups. Of 91 patients who received stomach-preserving treatment, only three had treatment failure in the long-term follow-up period. CONCLUSION: Strictly selected patients should be initially considered for conservative treatment. The short-term outcomes of stomach-preserving surgery are comparable to gastrectomy; however, further evaluation of the long-term outcomes of stomach-preserving treatment is required.

    DOI: 10.1007/s11605-013-2362-7

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  • Cervical lymph node dissection for clinically submucosal carcinoma of the thoracic esophagus. 国際誌

    Shin-ichi Kosugi, Yoshihiko Kawaguchi, Tatsuo Kanda, Takashi Ishikawa, Kaoru Sakamoto, Hidenori Akaike, Hideki Fujii, Toshifumi Wakai

    Annals of surgical oncology   20 ( 12 )   4016 - 21   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The purposes of this study were to clarify the risk factors for supraclavicular lymph node (SCLN) metastasis and the survival benefit from cervical lymph node (LN) dissections in patients with clinically submucosal (cT1b) carcinoma of the thoracic esophagus. METHODS: A total of 86 patients with this disease who underwent esophagectomy with 3-field lymph node dissection were retrospectively reviewed. Multivariate logistic regression and Cox proportional hazard model were used to identify the independent risk factors for SCLN metastasis and prognostic factors, respectively. An index calculated by multiplying the frequency of metastasis at nodal basin and the 5-year overall survival rate of patients with metastasis at that basin were used to assess the therapeutic outcomes. RESULTS: A total of 40 patients (47%) were found to have pathological LN metastasis. Also, 13 patients (15%) had cervical LN metastasis: 6 and 7 with carcinoma of the upper and mid-thoracic esophagus, respectively. SCLN metastasis was found in 6 patients (7%); however, there was no independent risk factor for SCLN metastasis. The 5-year overall survival rate was 72.5%. Cervical LN metastasis was an independent prognostic factor (p = .04; odds ratio 2.55; 95% confidence interval 1.03-6.31); however, there was no significant difference in survival between patients with SCLN metastasis and those without (p = .06). The calculated index of estimated benefit from cervical LN dissections was 6.9, following upper mediastinal LN of 15.6 and perigastric LN of 8.3. CONCLUSIONS: We could not identify risk factors to predict SCLN metastasis. Cervical LN dissection should not be omitted in patients with cT1b carcinoma, especially of the upper and mid-thoracic esophagus.

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  • Is Early Enteral Nutrition Better for Postoperative Course in Esophageal Cancer Patients? 査読

    Kazuaki Kobayashi, Yu Koyama, Shin-ichi Kosugi, Takashi Ishikawa, Kaoru Sakamoto, Hiroshi Ichikawa, Toshifumi Wakai

    NUTRIENTS   5 ( 9 )   3461 - 3469   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p &lt; 0.05. Group E showed fewer days for the first fecal passage (p &lt; 0.01), lesser dose of postoperative albumin infusion (p &lt; 0.01), less use of TPN (p &lt; 0.01), and shorter duration of SIRS (p &lt; 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation.

    DOI: 10.3390/nu5093461

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  • Laser microdissection and two-dimensional difference gel electrophoresis reveal the role of a novel macrophage-capping protein in lymph node metastasis in gastric cancer. 国際誌

    Hiroshi Ichikawa, Tatsuo Kanda, Shin-Ichi Kosugi, Yasuyuki Kawachi, Hiroki Sasaki, Toshifumi Wakai, Tadashi Kondo

    Journal of proteome research   12 ( 8 )   3780 - 91   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer.

    DOI: 10.1021/pr400439m

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  • Risk factors influencing the pleural drainage volume after transthoracic oesophagectomy. 国際誌

    Shin-ichi Kosugi, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Kaoru Sakamoto

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   43 ( 6 )   1116 - 20   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The objective of this study was to clarify the factors influencing pleural drainage volume after transthoracic oesophagectomy and to determine criteria for the selection of patients who would benefit from the early removal of chest drains. METHODS: Clinicopathological characteristics of 155 patients who underwent transthoracic oesophagectomy were prospectively collected, and the daily drainage volume of each patient was retrospectively reviewed. Potential risk factors were compared between the high-output group (n = 39) and low-output group (n = 116), which were dichotomized using the 75th percentile of total pleural drainage volume of the total study population. Multivariate logistic regression analyses were used to identify independent risk factors. RESULTS: The median duration of drainage was 10 days, with a median total drainage volume of 2258 ml. Of 27 potential risk factors influencing the drainage volume, creatinine clearance (P = 0.04), operative approach (P = 0.03) and thoracic duct removal (P = 0.01) were significantly associated with the total pleural drainage volume. The removal of the thoracic duct (P = 0.02; odds ratio, 4.02; 95% confidence interval 1.20-13.41) and lower creatinine clearance (P = 0.04; odds ratio, 1.02; 95% confidence interval 1.00-1.04) was independent risk factors for increased pleural drainage volume after transthoracic oesophagectomy. CONCLUSIONS: The early removal of chest drains may be possible in patients without these risk factors.

    DOI: 10.1093/ejcts/ezs556

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  • Two-step laparoscopic surgery for a patient with synchronous double cancer of the colon and stomach accompanied by severe chronic obstructive pulmonary disease. 国際誌

    Kazuhito Yajima, Shin-Ichi Kosugi, Yosuke Kano, Takaaki Hanyu, Hiroshi Ichikawa, Takashi Ishikawa, Hitoshi Nogami, Toshifumi Wakai

    Case reports in surgery   2013   246515 - 246515   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Laparoscopic treatment strategies for synchronous intra-abdominal malignancies have not yet been standardized. We report a successful case of two-step laparoscopic surgery for synchronous double cancer of the colon and stomach accompanied by severe chronic obstructive pulmonary disease (COPD). A 66-year-old man with COPD was diagnosed as having advanced colon cancer and early gastric cancer. On admission, he could not go upstairs (Grade III according to the Hugh-Jones classification) and his forced expiratory volume in 1 second was 600 mL (35.9%). The patient initially underwent laparoscopy-assisted sigmoidectomy with D3 lymphadenectomy, followed by laparoscopy-assisted distal gastrectomy with D1 lymphadenectomy 68 days later. The patient's each postoperative course was uneventful with no pulmonary complications, and the patient was discharged 9 and 11 days after the first and second operations, respectively. The present case demonstrates that two-step laparoscopic surgery may be a safe and feasible surgical procedure for high-risk patients with synchronous intra-abdominal malignancies.

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  • Serum Intestinal Fatty Acid Binding Protein in Patients with Small Bowel Obstruction

    Kaoru Sakamoto, Tatsuo Kanda, Takeo Bamba, Hiroyuki Funaoka, Shin-ichi Kosugi, Kazuhito Yajima, Takashi Ishikawa

    Surgical Science   04 ( 06 )   302 - 307   2013年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Research Publishing, Inc.  

    DOI: 10.4236/ss.2013.46059

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  • WallFlex™ Duodenal Stent Placement in a Gastric Cancer Patient with Malignant Stenosis of a Roux-en-Y Gastrojejunostomy following Distal Gastrectomy. 国際誌

    Tomoyuki Kakuta, Kazuhito Yajima, Seiji Kayama, Yoshihiro Tsuno, Keita Saito, Takashi Ishikawa, Shin-Ichi Kosugi, Tatsuo Kanda

    Case reports in oncology   5 ( 3 )   554 - 60   2012年9月

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    記述言語:英語  

    A 69-year-old Japanese woman with a history of distal gastrectomy with a Roux-en-Y reconstruction for advanced gastric cancer was admitted to our hospital complaining of severe dysphagia. On admission, the patient was only able to take liquids, and a firm, fist-sized tumor was palpable in her left upper abdomen. An endoscopic examination disclosed stenosis of the jejunal limb of the gastrojejunostomy. Abdominal computed tomography revealed that a recurrent tumor, 5.0 cm in diameter, was compressing the jejunal limb of the gastrojejunostomy. A knitted nitinol self-expandable metallic stent (WallFlex™ duodenal stent) was placed endoscopically at the stenotic jejunum from the gastrojejunostomy. The time required for stenting and total endoscopic manipulation was 12 and 35 minutes, respectively. No stent-related complications were observed. The patient could resume oral ingestion 1 day after endoscopic stenting and was discharged on the fifth day after treatment. She survived for 201 days after stenting. She continued oral ingestion for 194 days and stayed at home for 165 days. The WallFlex duodenal stent allows safe endoscopic stenting, even in cases of malignant stenosis of a gastrojejunostomy following distal gastrectomy. This stenting device will extend the indications for endoscopic palliation of gastric cancer patients with gastric outlet stenosis.

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  • Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study.

    Tatsuo Kanda, Kazuhito Yajima, Shin-Ichi Kosugi, Takashi Ishikawa, Yoichi Ajioka, Katsuyoshi Hatakeyama

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   15 ( 3 )   235 - 44   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Current advances in chemotherapy provide opportunities for stage IV gastric cancer patients with distant metastasis to undergo potentially curable resection. There are, however, few data on gastrectomy as a secondary surgery aimed at rendering such patients cancer-free. METHODS: We investigated stage IV gastric cancer patients who underwent surgery with curative intent after S-1-based chemotherapy between 2000 and 2008. Twenty-eight patients from 12 hospitals were enrolled in this study. Factors indicating that the tumors were incurable included clinical stage T4 in 9 patients, para-aortic node metastasis in 15, peritoneal metastasis in 7, and liver metastasis in 4. RESULTS: Of the 28 laparotomy patients, 26 underwent complete resection with no residual tumor, obtaining a complete resection rate of 92.9%. There were no in-hospital deaths or reoperations. In four patients, the primary tumor showed pathological complete response. The 1-, 3-, and 5-year overall survival rates after secondary gastrectomy were 82.1, 45.9, and 34.4%, respectively, with a median survival time of 29 months. Univariate analysis revealed histological tumor length, clinical depth of tumor invasion, number of metastatic nodes, pathological depth of tumor invasion, and pathological response to be the factors influencing patient survival after secondary surgery. On multivariate analysis, histological tumor length (5.0 cm or larger) was the only significant prognostic factor (relative risk 3.23, P = 0.028). CONCLUSIONS: Secondary gastrectomy following S-1-based chemotherapy was a safe and effective treatment for stage IV gastric cancer. Primary tumor size is an indicator for the appropriate selection of patients for this treatment.

    DOI: 10.1007/s10120-011-0100-y

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  • Prospective observational study of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors: long-term follow-up and second malignancy. 国際誌

    Tatsuo Kanda, Takashi Ishikawa, Seiichi Hirota, Kazuhito Yajima, Shin-ichi Kosugi, Manabu Ohashi, Satoshi Suzuki, Yasuoki Mashima, Yoichi Ajioka, Katsuyoshi Hatakeyama

    Japanese journal of clinical oncology   42 ( 7 )   578 - 85   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Limited data are available concerning long-term results of imatinib therapy in patients with advanced gastrointestinal stromal tumors. We aimed to clarify the long-term outcomes of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors. METHODS: A prospective, observational study of imatinib therapy for unresectable and metastatic gastrointestinal stromal tumors was conducted in our institution. Imatinib was initiated at a dose of 400 mg daily and continued until disease progression. Safety, efficacy and long-term tolerability and survival were evaluated in an intent-to-treat population. The median follow-up period in this study was 68 months. RESULTS: Seventy patients were enrolled between December 2001 and December 2009. Treatment-related Grade 3/4 adverse events occurred in 49 patients (70.0%). Although 14 patients required adverse effect management with hospitalization, only 5 patients (7.1%) withdrew from the treatment owing to imatinib intolerance. The tumor response and clinical benefit rates were 61.4 and 85.7%, respectively. Thirty-seven patients (52.9%) maintained the treatment at 400 mg daily imatinib, whereas 33 patients (47.1%) had their dose reduced to 300 mg daily or less. The overall survival rate at 5 years was 60.9% and the median survival time was 70 months. The median progression-free survival time of all the 70 enrolled patients was 30 months. Seven patients (10.0%) suffered from second malignancies, including three patients with genitourinary carcinomas. CONCLUSIONS: Despite the need for dose reduction, the long-term results of imatinib therapy for advanced gastrointestinal stromal tumors were good in Japanese patients. Physicians should pay attention to the occurrence of second malignancies during imatinib therapy for gastrointestinal stromal tumor patients.

    DOI: 10.1093/jjco/hys056

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  • Clinicopathological Characteristics and Prognosis of Patients With Esophageal Carcinoma Invading Adjacent Structures Found During Esophagectomy 査読

    Shin-Ichi Kosugi, Hiroshi Ichikawa, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Katsuyoshi Hatakeyama

    JOURNAL OF SURGICAL ONCOLOGY   105 ( 8 )   767 - 772   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Objectives: A treatment strategy for patients with esophageal carcinoma invading adjacent structures found during esophagectomy (surgical T4; sT4) has not been established and the role of esophagectomy remains controversial. The aims of this study were to assess the clinicopathological characteristics and to clarify the prognostic factors of patients who underwent esophagectomy for sT4 tumors.
    Methods: A consecutive series of 76 patients who were found to have sT4 tumors was reviewed retrospectively. T4 tumors were divided into two groups according to the invaded structures. Cox's multivariate proportional hazard model was used to identify prognostic factors.
    Results: Complete tumor clearance with combined resection was performed in 12 patients (16%). Overall 1-, 3-, and 5-year survival rates were 40.8%, 9.2%, and 7.9%, respectively. There was no significant relationship between survival and invaded structure type or residual tumor status. Postoperative therapy was selected as an independent prognostic factor.
    Conclusions: The complete resection rate was low and the prognosis of patients with sT4 tumors was poor. Subclassification according to the invaded structures was not a prognostic factor in this study. Postoperative therapy may improve survival in sT4 patients and should be considered irrespective of residual tumor status after esophagectomy. J. Surg. Oncol. 2012;105:767-772. (C) 2012 Wiley Periodicals, Inc.

    DOI: 10.1002/jso.22092

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  • Reexpansion Pulmonary Edema following Laparoscopy-Assisted Distal Gastrectomy for a Patient with Early Gastric Cancer: A Case Report. 国際誌

    Kazuhito Yajima, Tatsuo Kanda, Ryo Tanaka, Yu Sato, Takashi Ishikawa, Shin-Ichi Kosugi, Tadayuki Honda, Katsuyoshi Hatakeyama

    Case reports in surgery   2012   863163 - 863163   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report here a case of reexpansion pulmonary edema following laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer. A 57-year-old Japanese woman with no preoperative comorbidity was diagnosed with early gastric cancer. The patient underwent LADG using the pneumoperitoneum method. During surgery, the patient was unintentionally subjected to single-lung ventilation for approximately 247 minutes due to intratracheal tube dislocation. One hour after surgery, she developed severe dyspnea and produced a large amount of pink frothy sputum. Chest radiography results showed diffuse ground-glass attenuation and alveolar consolidation in both lungs without cardiomegaly. A diagnosis of pulmonary edema was made, and the patient was immediately intubated and received ventilatory support with high positive end-expiratory pressure. The patient gradually recovered and was weaned from the ventilatory support on the third postoperative day. This case shows that single-lung ventilation may be a risk factor for reexpansion pulmonary edema during laparoscopic surgery with pneumoperitoneum.

    DOI: 10.1155/2012/863163

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  • Community-acquired pneumonia during long-term follow-up of patients after radical esophagectomy for esophageal cancer: analysis of incidence and associated risk factors. 国際誌

    Takaaki Hanyu, Tatsuo Kanda, Kazuhito Yajima, Yoshinari Tanabe, Shintaro Komukai, Shin-Ichi Kosugi, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    World journal of surgery   35 ( 11 )   2454 - 62   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: There are no data concerning the occurrence of community-acquired pneumonia (CAP) in esophageal cancer patients during long-term follow-up after radical esophagectomy. The aims of the present study were to determine the incidence of CAP in esophageal cancer patients who underwent radical esophagectomy and to identify the risk factors. METHODS: A total of 186 consecutive patients who underwent radical esophagectomy for thoracic esophageal carcinoma in our hospital between 1991 and 2000 were enrolled in this study. Data on the occurrence of CAP were retrospectively collected from medical records, follow-up files, and telephone interviews with patients. The cumulative incidence of CAP was calculated by the Kaplan-Meier method, and the risk factors for CAP were determined by univariate and multivariate analyses. The median follow-up time was 77 months (range 12-216 months). RESULTS: Sixty patients suffered from CAP during the follow-up period. The cumulative incidence was 25.8% at 5 years and 38.4% at 10 years. Multivariate analysis revealed the following as the significant risk factors for CAP: presence of lymph node metastasis (Hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.55-4.50; P < 0.001), colonic interposition (HR, 2.87; 95% CI, 1.41-5.82; P = 0.004), obstructive lung disease (HR, 1.95; 95% CI, 1.11-3.42; P = 0.021), and preoperative hypoalbuminemia (HR, 2.08; 95% CI, 1.20-3.60; P = 0.009). CONCLUSIONS: There is a high incidence of CAP in esophageal cancer patients after esophagectomy. Positive nodal metastasis, colonic interposition, obstructive lung disease, and preoperative hypoalbuminemia are risk factors for this long-term postoperative morbidity.

    DOI: 10.1007/s00268-011-1226-0

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  • Risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with three-field lymph node dissection. 国際誌

    Shin-Ichi Kosugi, Tatsuo Kanda, Kazuhito Yajima, Takashi Ishikawa, Katsuyoshi Hatakeyama

    Annals of surgical oncology   18 ( 10 )   2961 - 7   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Extended radical esophagectomy with three-field lymph node dissection (3-FLD) has offered significant survival benefit, but some patients still suffer from early recurrence and die within 1 year after surgery. The purpose of this study was to identify the risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with 3-FLD. METHODS: A consecutive series of 276 patients who underwent extended radical esophagectomy with 3-FLD was retrospectively reviewed. Excluding patients who underwent incomplete resection or died of other diseases within 1 year, we compared the clinicopathological characteristics between 203 patients who survived more than 1 year (1-year survival group) and 27 who died of cancer recurrence within 1 year (early-death group) by univariate and multivariate analysis. RESULTS: Sixty-six patients (32.5%) had recurrent disease in the 1-year survival group. Hematogenous recurrences were more frequent in the early-death group than in the 1-year survival group (41% vs. 26%, respectively, p = 0.0481). There was a significant difference in nodal status, number of metastatic nodes, pathological stage, vessel invasion, and intramural metastasis, and there was borderline significance in the difference of depth of invasion and histological type between the two groups by univariate analysis. Multivariate analysis demonstrated that intramural metastasis was an independent risk factor. CONCLUSIONS: Patients with intramural metastasis have a significant risk of early death even after extended radical esophagectomy with 3-FLD; however, it remains unknown whether surgical intervention can play a significant role for these patients.

    DOI: 10.1245/s10434-011-1712-5

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  • Secondary resistance to imatinib mesylate 70 months after initiation of therapy in a patient with a metastatic gastric gastrointestinal stromal tumor.

    Kumiko Tatsuda, Tatsuo Kanda, Takashi Ishikawa, Seiichi Hirota, Ken Nishikura, Kazuhito Yajima, Shin-Ichi Kosugi, Katsuyoshi Hatakeyama

    Clinical journal of gastroenterology   4 ( 4 )   218 - 222   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It is unknown how long the risk of developing secondary resistance to imatinib persists in patients with gastrointestinal stromal tumors (GISTs). Here we report a case of a patient with a metastatic gastric GIST who developed secondary resistance to imatinib 70 months after initiation of imatinib therapy. A 62-year-old woman with a gastric GIST underwent total gastrectomy with pancreaticosplenectomy. Immunohistochemistry revealed a KIT-positive GIST. The mitotic index of the tumor was 13/50 high-power fields, indicating a high-risk malignancy. After surgery, the patient developed a solitary liver metastasis and underwent right hepatic lobectomy. Four months later, a metastatic tumor was found at the left adrenal gland, and imatinib therapy was initiated in December 2004. Imatinib therapy led to marked tumor shrinkage and complete clinical remission in the patient. However, in October 2010, computed tomography scans revealed a peritoneal metastasis in the ileocecal area. The tumor progression was clinically determined to be due to the development of secondary resistance to imatinib, and the patient's treatment was switched to sunitinib. This case illustrates secondary resistance to imatinib can develop even after a sustained and marked treatment response. Long-term therapy and close monitoring are recommended for the management of patients with metastatic GISTs.

    DOI: 10.1007/s12328-011-0234-9

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  • [Treatment strategy for marginally resectable GIST].

    Tatsuo Kanda, Takashi Ishikawa, Toshiro Ozaki, Kazuhito Yajima, Shinichi Kosugi, Katsuyoshi Hatakeyama

    Gan to kagaku ryoho. Cancer & chemotherapy   38 ( 8 )   1266 - 70   2011年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Gastrointestinalstromaltumors (GIST)are occasionally found as large abdominal tumors at presentation. However, the best treatment approach for such large and marginally resectable GISTs remains unclear. The survival of patients with clinically malignant GISTs or GISTs with incomplete resection was as short as 1-2 years. Imatinib, a KIT kinase inhibitor, shows promise as a preoperative treatment for marginally resectable GIST, because it exhibits potent antitumor activity for unresectable and metastatic GISTs. Data obtained from imatinib therapy for advanced GISTs indicate that preoperative treatment with 400 mg of imatinib daily for 6-12 months is recommended, although no standard regimen has been established so far. Positron emission tomography is useful for the early assessment of the efficacy of preoperative imatinib treatment, a critical step for the management of patients with marginally resectable GIST. Two case studies have shown the safety and strong antitumor activity of preoperative imatinib treatment and concluded that treatment contributed to reducing surgical morbidity. However, a multicenter phase II trial conducted in the United States has shown that complete resection was not sufficiently achieved in patients who underwent preoperative imatinib treatment: complete resection rates were 77% for primary cases and 58% for metastatic cases, whereas the treatment was not associated with severe postoperative complications. The clinical guidelines for GIST in Japan regard preoperative imatinib treatment for marginally resectable GIST as an experimental treatment. More clinical evidence is required before making preoperative imatinib treatment the standard treatment for marginally resectable GIST.

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  • [Sunitinib as a second-line therapy for imatinib-resistant gastrointestinal stromal tumors].

    Takashi Ishikawa, Tatsuo Kanda, Shinichi Kosugi, Kazuhito Yajima, Katsuyoshi Hatakeyama

    Gan to kagaku ryoho. Cancer & chemotherapy   38 ( 6 )   916 - 21   2011年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Gastrointestinal stromal tumor(GIST)is one ofthe representative diseases for which molecularly targeted therapy is very effective. Imatinib mesylate, a tyrosine kinase inhibitor of KIT and platelet-derived growth factor receptor(PDGFR), has dramatically improved the prognosis ofpatients with advanced, recurrent, and/or metastatic GISTs. Although the rate of response to imatinib therapy is high, the emergence ofimatinib -resistant tumors and the second-line therapy following imatinib therapy have become new clinical problems. Sunitinib malate, a multi-targeted tyrosine kinase inhibitor that shows activity against KIT and other receptor tyrosine kinases, including PDGFR and vascular endothelial growth factor receptor, is the only treatment for imatinib-resistant GISTs that is covered by national health insurance in Japan as ofthis writing. Several clinical trials that evaluated sunitinib as potential second-line therapy in Western countries and Japan found a clinical benefit rate of2 4 to 39% and a median time to progression of7 months. However, it is necessary to adequately manage the adverse events of sunitinib therapy in order to receive the full benefits of the therapy, because various severe adverse events, particularly thrombocytopenia and hand-foot syndrome in Japanese GIST patients, frequently lead to poor tolerability. Further investigation is required to find an appropriate regimen for Japanese GIST patients.

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  • Pedunculated gastric tube interposition in an esophageal cancer patient with prepyloric adenocarcinoma. 国際誌

    Tatsuo Kanda, Yu Sato, Kazuhito Yajima, Shin-Ichi Kosugi, Atsushi Matsuki, Takashi Ishikawa, Takeo Bamba, Hajime Umezu, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    World journal of gastrointestinal oncology   3 ( 5 )   75 - 8   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gastric carcinoma is one of the malignancies that are most frequently associated with esophageal carcinoma. We describe herein our device for advanced esophageal cancer associated with early gastric cancer in the antrum. A 57-year-old man presenting with dysphagia and upper abdominal pain was admitted to our hospital. Preoperative examinations revealed locally advanced squamous cell carcinoma (SCC) of the middle thoracic esophagus (T3N0M0 Stage IIA) and mucosal signet-ring cell carcinoma of the gastric antrum (T1N0M0 Stage IA). Although the gastric tumor appeared to be an intramucosal carcinoma, its margin was obscure, so endoscopic en-bloc resection was considered inadequate. We chose surgical resection of the gastric tumor as well as the esophageal SCC after neoadjuvant chemotherapy with 5-fluorouracil and cisplatin for advanced esophageal cancer. Following transthoracic esophagectomy with three-field lymph node dissection, the gastric carcinoma was removed by gastric antrectomy, which preserved the right gastroepiploic vessels, and a pedunculated short gastric tube was used as the esophageal substitute. Twenty-eight months after the surgery, the patient is well with no evidence of cancer recurrence. Because it minimizes surgical stress and organ sacrifice, gastric tube interposition is a potentially useful technique for esophageal cancer associated with localized early gastric cancer.

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  • [An update on surgical treatment for gastrointestinal stromal tumor].

    Takashi Ishikawa, Tatsuo Kanda, Shin-Ichi Kosugi, Kazuhito Yajima, Katsuyoshi Hatakeyama

    Gan to kagaku ryoho. Cancer & chemotherapy   38 ( 5 )   722 - 7   2011年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Complete surgical resection is the treatment of choice for primary gastrointestinal stromal tumor (GIST), even with current advances in molecular targeting therapy with imatinib and sunitinib. In recent years, function-preserving and minimally invasive surgeries have also been performed as treatment strategies for submucosal tumors, including GISTs that are clinically diagnosed as low-risk. It is crucial, however, not to compromise radicality when indicating these procedures. On the other hand, a multidisciplinary treatment, including surgical resection, is necessary even for the treatment of advanced or metastatic/ recurrent GISTs in which the treatment of choice is imatinib therapy. Furthermore, surgical treatment is expected to be effective for resectable liver metastases, secondary resistance to imatinib, or residual tumors responding to imatinib. In this regard, surgical resection as a multidisciplinary treatment is considered to have gained recognition as an important option. However, sufficient evidence is lacking, and thus, the results of ongoing clinical trials are highly anticipated. For the surgical treatment of GIST, it is important to select patients carefully based on objective data to obtain maximum therapeutic effects.

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  • Phase II Study of Weekly Paclitaxel Following Fixed Three Cycles of S-1-based Chemotherapy for Advanced Gastric Cancer

    Manabu Ohashi, Tatsuo Kanda, Takashi Kobayashi, Masaki Hirota, Morihito Hayami, Kazuhito Yajima, Atsushi Matsuki, Shin-ichi Kosugi, Katsuyoshi Hatakeyama

    HEPATO-GASTROENTEROLOGY   58 ( 106 )   652 - 658   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Awareness of the clinical importance of second-line chemotherapy for incurable gastric cancer has been increasing. To assess the clinical validity of the new concept that second-line chemotherapy following predetermined cycles of first-line chemotherapy would improve survival, we conducted a phase II study.Methodology: Patients with pathologically proven incurable gastric adenocarcinoma and adequate organ functions were enrolled. S-1 or S-1 plus cisplatin was administered as first-line chemotherapy. The number of cycles of S-1-based chemotherapy was determined to be three as a maximum unless there was disease progression. The treatment was followed by weekly administration of paclitaxel. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and safety.Results: Thirty-seven patients were eligible for enrollment. Twenty-eight patients (76%) underwent the second-line chemotherapy with paclitaxel after completion of S-1-based chemotherapy or disease progression. Treatment-related grade 3 or 4 toxicity was noted in 14 patients during S-1-based chemotherapy, and in 6 patients during paclitaxel treatment. The median survival time was 455 days and the median progression-free survival was 229 days.Conclusions: Sequential set chemotherapy with three cycles of S-1-based chemotherapy followed by weekly paclitaxel is feasible. The survival results are equivalent to those of other current regimens using S-1.

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  • Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma. 国際誌

    Hiroshi Ichikawa, Shin-ichi Kosugi, Satoru Nakagawa, Tatsuo Kanda, Masanori Tsuchida, Teruaki Koike, Otsuo Tanaka, Katsuyoshi Hatakeyama

    Surgery   149 ( 2 )   164 - 70   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The clinical significance of operative treatment for metachronous pulmonary metastasis from esophageal carcinoma is unclear. METHODS: We retrospectively reviewed 23 consecutive patients who underwent operative resection for metachronous pulmonary metastasis from esophageal carcinoma from 1991 to 2008. Patient baseline characteristics, survival probability, and prognostic factors were analyzed. The median follow-up period was 31 months for surviving patients. RESULTS: There were 19 men and 4 women, with a median age of 66 years at the time of pulmonary resection. The median disease-free interval was 15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a maximum number of 4. The median operative time and blood loss were 94.5 minutes and 18 mL, respectively. The median length of postoperative stay was 12.5 days. The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7 months. Univariate analysis revealed that an extrapulmonary metastasis as the initial recurrence site was an unfavorable prognostic factor (P = .0411). Multivariate analyses, however, did not identify the initial recurrence site as an independent prognostic factor (P = .0542). CONCLUSION: Operative resection for metachronous pulmonary metastasis from esophageal carcinoma is an acceptable treatment. This study of a limited number of patients may have created a constitutional selection bias. An antecedent extrapulmonary metastasis was found to be an unfavorable prognostic factor.

    DOI: 10.1016/j.surg.2010.07.047

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  • Endobronchial metastasis from adenocarcinoma of gastric cardia 7 years after potentially curable resection. 国際誌

    Takaaki Hanyu, Tatsuo Kanda, Atsushi Matsuki, Go Hasegawa, Kazuhito Yajima, Masanori Tsuchida, Shin-Ichi Kosugi, Makoto Naito, Katsuyoshi Hatakeyama

    World journal of gastrointestinal surgery   2 ( 8 )   270 - 4   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Endobronchial metastasis (EBM) is a rare form of metastasis from extrapulmonary malignant tumors, although there are few reports of EBM from gastric cancer specifically. We report the case of a 51-year-old woman who had undergone gastrectomy for advanced gastric cancer seven years previously but was diagnosed with a solitary lung tumor by follow-up computed tomography. On diagnosis of primary lung cancer, she underwent pulmonary lobectomy, but immunohistochemical examination confirmed the resected tumor to be an EBM from the gastric cancer. Six months later, she was diagnosed with peritoneal metastases and underwent chemotherapy with gastric cancer regimen. She is still alive at 33 mo after the lobectomy. Generally, the prognosis for EBM is poor although multidisciplinary treatment can lead to long-term survival. Precise diagnosis on the basis of detailed pathological and immunohistochemical evaluation can contribute to deciding the most effective treatment and improving prognosis.

    DOI: 10.4240/wjgs.v2.i8.270

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  • Purulent spondylitis related to anastomotic fistula after esophageal cancer surgery. 国際誌

    Tomoyuki Kakuta, Shin-ichi Kosugi, Tatsuo Kanda, Katsuyoshi Hatakeyama

    Interactive cardiovascular and thoracic surgery   11 ( 2 )   204 - 6   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 73-year-old man underwent neoadjuvant chemotherapy followed by transhiatal esophagectomy with gastric tube reconstruction for advanced esophageal cancer with palliative intent. Cervical esophagogastrostomy with circular-stapled end-to-side anastomosis was performed; however, anastomotic fistula developed. Fever, severe pain in the nape of the neck and numbness of the left hand were noted after drainage by wide opening of cervicotomy and the administration of empiric antibiotics. Magnetic resonance imaging revealed high signal intensity between the inferior C5 vertebral body and the intervertebral disc on T2-weighted images, and some areas were contrast-enhanced, suggesting purulent spondylodiscitis. Because methicillin-resistant Staphylococcus aureus was detected by bacterial culture from the drained pus, sensitive antibiotics were given, and those symptoms improved rapidly without sequelae.

    DOI: 10.1510/icvts.2010.235515

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  • Surveillance and treatment for second primary cancer in the gastric tube after radical esophagectomy. 国際誌

    Takeo Bamba, Shin-ichi Kosugi, Manabu Takeuchi, Masaaki Kobayashi, Tatsuo Kanda, Atsushi Matsuki, Katsuyoshi Hatakeyama

    Surgical endoscopy   24 ( 6 )   1310 - 7   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Recent improvement in the survival of patients after esophagectomy for esophageal cancer has led to increasing occurrence of second primary cancer in the pulled-up stomach as gastric tube cancer (GTC). However, a treatment strategy for GTC including surveillance has not been established. The aims of this study are to clarify the incidence and clinicopathological characteristics of GTC and to assess the treatment results of endoscopic resection. METHODS: Twenty-five patients with 29 GTC lesions treated between 1989 and 2007 were analyzed retrospectively. RESULTS: The median interval between esophagectomy and GTC detection was 86 months, and the 10-year cumulative incidence rate of GTC was 8.6%. Of 18 asymptomatic GTCs, 17 lesions (94.4%) were detected by periodic endoscopy and 15 (88.2%) of them were treated endoscopically. Of all 29 GTCs, endoscopic submucosal dissection (ESD) was performed in 10 GTCs with a completely curative resection rate of 90%, which was significantly higher than that of 7 GTCs treated with endoscopic mucosal resection (EMR) (14.3%, P = 0.004). In these 17 GTCs, no cancer recurrence developed during a median follow-up period of 24 months, and the 3-year survival rate was 80.8%. CONCLUSIONS: For patients after esophagectomy with gastric pull-up, long-term follow-up including periodic endoscopy is necessary to detect a potentially curable GTC. ESD is a feasible and safe procedure for GTC, with oncologically favorable features.

    DOI: 10.1007/s00464-009-0766-y

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  • Urgent surgery for intraperitoneal bleeding from GIST during imatinib therapy.

    Takehiko Enomoto, Tatsuo Kanda, Kazuhito Yajima, Seiichi Hirota, Atsushi Matsuki, Shin-Ichi Kosugi, Takashi Kato, Yoichi Ajioka, Katsuyoshi Hatakeyama

    Clinical journal of gastroenterology   3 ( 2 )   73 - 7   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The rupture or bleeding of a gastrointestinal stromal tumor (GIST) is a life-threatening adverse event that can happen during imatinib therapy, but few such cases have been reported in the medical literature. Here, we report a case of intraperitoneal bleeding from GIST during imatinib therapy. A 75-year-old man was diagnosed with a large GIST with liver metastasis and admitted to our hospital for abdominal pain on the 13th day of imatinib therapy. The pain disappeared after 7 days of hospitalization; however, the patient complained of diffuse abdominal pain 5 days after discharge. He presented with muscular guarding, and abdominal-pelvic CT demonstrated dense ascites. The tentative diagnosis was peritoneal hemorrhage from GIST, and urgent laparotomy was performed. During the laparotomy, we noted hemoperitoneum of approximately 500 ml; we resected a bulky metastatic tumor on the greater omentum and a primary tumor on the jejunum. The patient took imatinib (400 mg daily) from the ninth postoperative day and underwent monthly checkups for 9 months after the surgery. When GIST patients complain of sudden and severe abdominal pain during imatinib therapy, bleeding from GIST should be considered as a possible adverse effect of imatinib.

    DOI: 10.1007/s12328-010-0143-3

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  • Surgical resection of gastrointestinal stromal tumor of esophagus following preoperative imatinib treatment: A case report

    Sato, H., K, a, T., Hirota, S., Bamba, T., Sakamoto, K., Kosugi, S.-I., Matsuki, A., Mashima, Y., Watanabe, G., Hatakeyama, K.

    Esophagus   7 ( 1 )   65 - 69   2010年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s10388-009-0217-9

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  • A case of metastatic esophageal tumor from breast cancer

    Kaoru Sakamoto, Shin-ichi Kosugi, Yu Koyama, Tatsuo Kanda, Atsushi Matsuki, Katsuyoshi Hatakeyama

    Esophagus   7 ( 1 )   53 - 57   2010年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    A 58-year-old woman was admitted to our hospital with the complaint of dysphagia that had developed 37 months after initiation of treatment for breast cancer. Endoscopy revealed severe stenosis 32 cm from the incisors through which the endoscope could not pass. No mucosal irregularities were observed, and biopsies of the stenotic lesion were negative for malignancy. Computed tomography showed wall thickening of the midthoracic esophagus and left pleural effusion, which had increased metabolic activity as detected by 18F-fluorodeoxyglucose positron emission tomography. Cytological examination of the pleural effusion showed adenocarcinoma compatible with metastasis from a prior lobular carcinoma of the breast. Vinorelbine effectively relieved her symptoms, and the disease stabilized for approximately 1 year. However, she died 16 months after the diagnosis of metastatic esophageal tumor from the preceding breast cancer. © Japan Esophageal Society and Springer 2010.

    DOI: 10.1007/s10388-009-0216-x

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  • Local differences in electrogastrographic indices associated with total gastrectomy, total colectomy, distal gastrectomy and colonic replacement.

    Shinji Homma, Yasuo Kobayashi, Shinichi Kosugi, Manabu Ohashi, Tatsuo Kanda, Katsuyoshi Hatakeyama

    Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi   46 ( 5 )   235 - 48   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The electrogastrographic indices of spectral frequency, instability factor (IF), power amplitude, and power content (%) were compared between control subjects (C), and subjects following either total gastrectomy (TG), total colectomy (TC), distal gastrectomy (DG) or colonic replacement surgery (CR). In the fasting state, both the spectral frequency and IF of the epigastric 3-cycle per minute (cpm) group of the TC subjects were significantly lower than those indices in C, TG, DG, and CR subjects. In contrast, the power amplitude and power content of the epigastric 3-cpm group of both TG and DG subjects were significantly lower than those of C and TC subjects. The original epigastric waves of TG had remarkably high amplitudes. Furthermore, the absolute power of the epigastric 3-cpm of the TC subjects was 10 times higher than that in either the C or TG subjects. These results may be partially explained by the assumption that the recorded epigastric electrogastrography (EGG) is mainly contributed to by the 3-cpm myoelectric activity of the stomach and colon, while the infraumbilical EGG is mainly contributed to by the 3-cpm myoelectric activity of the colon. Topographic EGG maps visually supported these assumptions.

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  • An esophageal squamous cell carcinoma patient with high serum granulocyte-colony stimulating factor level: Report of a case

    Tanabe, T., K, a, T., Ishihara, N., Kosugi, S.-I., Matsuki, A., Watanabe, G., Sasamoto, R., Hatakeyama, K.

    Esophagus   6 ( 4 )   253 - 258   2009年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s10388-009-0206-z

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  • Gastric cancer surgery for patients with liver cirrhosis. 国際誌

    Yoshiyuki Ikeda, Tatsuo Kanda, Shin-Ichi Kosugi, Kazuhito Yajima, Atsushi Matsuki, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    World journal of gastrointestinal surgery   1 ( 1 )   49 - 55   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: To elucidate the influence of liver cirrhosis (LC) on the prognosis of patients with gastric cancer (GC). METHODS: Of the 1347 GC patients who underwent curative gastrectomy for GC between January 1984 and June 2007, 25 patients (21 men and 4 women with a median age of 67 years; range 54-77 years) with LC were enrolled in this study. Using the Child-Pugh classification, 15 patients were evaluated as grade A and 10 patients as grade B. No grade C patient underwent gastrectomy in this series. Clinical outcomes, including postoperative morbidity and survival, were retrospectively analyzed based on medical records and surgical files. RESULTS: There was no significant difference in operative blood loss and perioperative blood transfusion between the two groups. The most common postoperative complication was intractable ascites, which was the single postoperative morbidity noted more frequently in grade B patients (40.0%) than in grade A patients (6.7%) with statistical significance (P = 0.041). Operative mortality due to hepatic failure was seen in one grade A patient. Three patients had hepatocellular carcinoma (HCC) at presentation and two patients developed HCC after surgery. Overall 5-year survival rate was 58.9% in patients with early GC and 33.3% in patients with advanced GC (P = 0.230). GC-specific 5-year survival rate of early GC patients was 90.0% while that of advanced GC patients was 58.3% (P = 0.010). Four patients with early GC died of uncontrolled HCC, of which two were synchronous and two metachronous. CONCLUSION: The risk of postoperative intractable ascites is high, particularly in grade B patients. Early detection and complete control of HCC is vital to improve a patient's prognosis.

    DOI: 10.4240/wjgs.v1.i1.49

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  • Retrospective review of surgery and definitive chemoradiotherapy in patients with squamous cell carcinoma of the thoracic esophagus aged 75 years or older. 国際誌

    Shin-Ichi Kosugi, Ryuta Sasamoto, Tatsuo Kanda, Atsushi Matsuki, Katsuyoshi Hatakeyama

    Japanese journal of clinical oncology   39 ( 6 )   360 - 6   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The aim of this study was to review the treatment outcomes of surgery and definitive chemoradiotherapy (CRT) in elderly patients with squamous cell carcinoma of the thoracic esophagus. METHODS: A total of 64 patients aged 75 or older were retrospectively reviewed; 40 were treated with surgery and 24 with CRT. The CRT group included eight patients with unresectable disease and four patients medically unfit for surgery. Surgery included esophagectomy with lymphadenectomy and CRT consisted of 60-70 Gy of radiation concurrent with 5-fluorouracil alone or combined with cisplatin. Short- and long-term outcomes and survival of each modality were assessed. RESULTS: In the surgery group, 33 patients (82.5%) had co-morbid conditions. Complete resection rate was 90.0%. An overall post-operative complication rate was 65.0% and in-hospital mortality was seen in three patients (7.5%). In the CRT group, complete response rate was 41.7%. Leukopenia was most common Grade 3 hematological toxicity. Treatment-related deaths caused by acute toxicities occurred in three patients (12.5%), whereas those caused by late toxicities in four (16.7%). For cStage I disease in the surgery group, the overall 1-, 3- and 5-year survival rate were 90.9%, 63.6% and 54.5%, respectively, with a median survival time of 78.7 months. For cStages II-IV, the median survival time of the surgery and the CRT group was 18.7 and 12.8 months, respectively. CONCLUSIONS: The short- and long-term outcomes of surgery for the elderly seemed acceptable; however, definitive CRT may be a promising treatment modality. Further investigation may alter the sphere of influence in the field of esophageal cancer treatment in the elderly.

    DOI: 10.1093/jjco/hyp030

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  • Risk factors of reflux esophagitis in the cervical remnant following esophagectomy with gastric tube reconstruction. 国際誌

    Kazuhito Yajima, Shin-Ichi Kosugi, Tatsuo Kanda, Atsushi Matsuki, Katsuyoshi Hatakeyama

    World journal of surgery   33 ( 2 )   284 - 9   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The risk factors and suitable treatment of reflux esophagitis (RE) of the cervical remnant in patients undergoing radical esophagectomy remain unclear. The aim of this study was to evaluate the risk factors in patients with RE in the cervical remnant. METHODS: We retrospectively examined 141 consecutive patients who underwent esophagectomy and reconstruction with gastric tubing. RE was diagnosed by upper gastrointestinal endoscopy and graded according to the Los Angeles Classification. Statistically, 11 potential risk factors of RE were evaluated. The postoperative follow-up time ranged from 18 to 204 months (median 60 months). RESULTS: Among a total of 141 patients, 48 (34%) had RE in the cervical remnant, with 14 (29%) cases categorized as grade B, nine (19%) as grade C, and 25 (52%) as grade D. The cumulative incidence of RE in the cervical remnant was 24% at 5 years after surgery and 60% at 10 years, respectively. Pyloroplasty and bile reflux were identified as independent risk factors of RE in the cervical remnant by univariate and multivariate analyses. CONCLUSIONS: The results of this study show a high incidence and high grade of RE in the cervical remnant after esophagectomy. Routine endoscopic examination and suitable medication is required for the control of RE in the cervical remnant together with surgical procedures to avoid bile reflux.

    DOI: 10.1007/s00268-008-9856-6

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  • Schwannoma of the esophagus: a case exhibiting high 18F-fluorodeoxyglucose uptake in positron emission tomography imaging. 国際誌

    A Matsuki, S Kosugi, T Kanda, S Komukai, M Ohashi, H Umezu, Y Mashima, T Suzuki, K Hatakeyama

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus   22 ( 4 )   E6-E10   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Esophageal schwannoma is rare and it is difficult preoperatively to confirm a definitive diagnosis, even using current imaging techniques. We present a case of a benign esophageal schwannoma that was surgically excised and confirmed by immunohistochemical staining. Conventional radiological studies, including barium meal, computed tomography and endoscopic examination had shown a solid submucosal tumor of the upper thoracic esophagus but had been unable to confirm the diagnosis. Positron emission tomography was carried out to evaluate the malignant potential and showed a high uptake of 18F-fluorodeoxyglucose (FDG) into the tumor in both the early and delayed phase, suggesting that the tumor was a potentially malignant tumor such as a gastrointestinal stromal tumor. This is the first reported case of esophageal schwannoma that indicated a high FDG uptake. Although consensus has not been reached regarding the precise mechanism of FDG accumulation in schwannomas, we discuss our clinicopathological findings and review other studies of the subject.

    DOI: 10.1111/j.1442-2050.2007.00712.x

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  • Gastric tube interposition for corrosive esophagitis associated with pyloric stenosis.

    Atsushi Matsuki, Tatsuo Kanda, Shin-ichi Kosugi, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    Surgery today   39 ( 3 )   261 - 4   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Corrosive esophagitis, caused by swallowing corrosive acid or alkali, results in cicatricial stricture of the esophagus. The stricture is often accompanied by pyloric stenosis because strong acids act synergistically with gastric juice. Resection of both the esophagus and stomach is usually necessary, and the colon or jejunum is used as an esophageal substitute. We describe how we successfully treated corrosive esophagitis associated with pyloric stenosis, by performing gastric tube interposition for the esophageal reconstruction. After resecting the injured distal part of the stomach, we pulled the pedunculated gastric tube up to the cervix after anastomosis to the jejunal limb in a Roux-en-Y fashion. This reconstruction procedure prevented excessive organ sacrifice and was minimally invasive. Thus, esophageal reconstruction by interposition using a pedunculated gastric tube can be used effectively to treat corrosive esophagitis associated with pyloric stenosis.

    DOI: 10.1007/s00595-008-3834-3

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  • Successful treatment for a benign esophagorespiratory fistula with perioperative nutritional management and multistep esophageal bypass operation: a case report

    Takeo Bamba, Shin-ichi Kosugi, Tatsuo Kanda, Yu Koyama, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    Esophagus   5 ( 2 )   93 - 97   2008年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    A 49-year-old man was referred to our hospital for treatment of an esophagorespiratory fistula following 5-year airway stenting for stenosis of tracheal anastomosis. In consideration of the prior polysurgery and the patient's poor general status and malnutrition, we selected multistep esophageal bypass combined with feeding enterostomy for nutritional support. Respiratory symptoms and pneumonia were rapidly improved by esophageal transection and decompression via a catheter esophagostomy. Nutritional status was also improved by enteral nutrition via a catheter gastrostomy. Four months after the esophageal transection, we conducted an esophageal bypass using an ileocolonic conduit because the right gastroepiploic artery had been used for omental reinforcement of tracheal anastomosis. The patient had no postoperative complications and was discharged 53 days after the bypass surgery. Multistep esophageal bypass including feeding enterostomy for perioperative nutritional management is a safe and useful alternative to direct closure for a critically ill patient with an esophagorespiratory fistula who is at high risk for operative mortality. © 2008 Japan Esophageal Soceity and Springer.

    DOI: 10.1007/s10388-008-0148-x

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  • Postoperative reorganization of gastric pacemaker activity in patients after an extended period following distal gastrectomy.

    Shinji Homma, Yasuo Kobayashi, Shinichi Kosugi, Manabu Ohashi, Tatsuo Kanda, Haruhiko Okamoto, Katsuyoshi Hatakeyama

    Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi   44 ( 3-4 )   113 - 22   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We recorded and analyzed electrogastrograms (EGGs) from 12 patients following distal gastrectomy. The EGGs were recorded from between 3 and 262 months post-operatively. Gastric electrical activity, which showed a distinct repeating pattern with a frequency of 3 cycles per minute (cpm), was easily recognizable in subjects who were recorded 16-20 years postoperatively, but was not clearly evident in EGG running spectra of subjects with a shorter postoperative period. Although the postprandial instability factor of the 3-cpm components (standard deviation of mean spectral frequency of peak 3-cpm group/mean of the 3-cpm spectral frequency) of the epigastric and supraumbilical EGGs showed a significant negative linear correlation with postoperative months, no such correlation was seen in the postprandial to fasting power ratio (postprandial power / fasting power) of the 3-cpm activity component. Therefore, we hypothesized that the disorganized pacemaker activity of the remnant stomach following distal gastrectomy can be reorganized to work as a synchronized unit over a long postoperative recovery period of from 15 to 20 years. A greater degree of epigastric and supraumbilical fasting 6-cpm power seemed to result in a worse quality of life (QOL). Similarly, a larger ratio of the supraumbilical postprandial to fasting power ratio of the 6-cpm activity seemed to result in a worse QOL. In contrast a larger ratio of the infaraumbilical postprandial to fasting power content of the 6-cpm activity seemed to result in a better QOL.

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  • Gastrojejunostomy as induction treatment for S-1-based chemotherapy in patients with incurable gastric cancer.

    Manabu Ohashi, Tatsuo Kanda, Masaki Hirota, Takashi Kobayashi, Kazuhito Yajima, Shin-ichi Kosugi, Katsuyoshi Hatakeyama

    Surgery today   38 ( 12 )   1102 - 7   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: The development of new generation anticancer agents, including the oral drug, S-1, may alter the clinical importance of gastrojejunostomy in the treatment of incurable gastric cancer. We reviewed a series of patients who underwent gastrojejunostomy for this reason between 2002 and 2005. METHODS: Fourteen patients underwent gastrojejunostomy followed by S-1-based chemotherapy for incurable gastric cancer with obstruction or stenosis of the gastric outlet at Niigata University Medical and Dental Hospital and two affiliated hospitals. The safety of gastrojejunostomy, outcome of palliation, and survival time were analyzed retrospectively. We compared the survival times with those of patients who underwent palliative gastrectomy or exploratory laparotomy between 1987 and 2001. RESULTS: The median operative time and blood loss were 153 min and 66 ml, respectively. There were no major complications. The median starting time for chemotherapy after gastrojejunostomy was 15.5 days. All patients were discharged after gastrojejunostomy, and the median postoperative home stay ratio was 68%. The median survival time after gastrojejunostomy was 354 days, which was significantly longer than that of patients who underwent palliative gastrectomy or exploratory laparotomy. CONCLUSION: Gastrojejunostomy for incurable gastric cancer contributes not only to improving quality of life (QOL), but to prolonging survival through the induction and maintenance of S-1-based chemotherapy.

    DOI: 10.1007/s00595-007-3749-4

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  • Extranodal spreading of esophageal squamous cell carcinoma: clinicopathological characteristics and prognostic impact. 国際誌

    Tadashi Tanabe, Tatsuo Kanda, Shin-Ichi Kosugi, Yoshiyuki Ikeda, Shigeto Makino, Shintaro Komukai, Manabu Ohashi, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    World journal of surgery   31 ( 11 )   2192 - 8   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Microscopic cancer spreading to extranodal connective tissues (extranodal spreading: ENS) is occasionally found in resected specimens from patients with esophageal squamous cell carcinoma (SCC), but the prognostic impact of ENS remains unclear. The aims of this study were to elucidate the prognostic impact of ENS to help determine the most suitable management for the patients with ENS. METHODS: We histologically re-evaluated 7,349 lymph nodes obtained from 171 patients with SCC of the thoracic esophagus who underwent potentially curable resection between 1992 and 2003. We defined ENS as microscopic penetration of tumor cells from metastatic lymph nodes or tumor cell dissemination into extranodal connective tissues. RESULTS: Extranodal spreading was found in 37 (21.6%) patients, and it had a significant relationship with diameter and depth of the tumor, lymphatic and venous invasion, intramural metastasis, and number of metastatic nodes. Patients who were ENS positive were at higher risk of recurrence, and their overall survival rate was lower than that for ENS-negative patients. Furthermore, recurrent risk was higher and overall survival rate was lower in ENS-positive patients than in ENS-negative patients when they had 1-3 metastatic nodes, but recurrent risk and overall survival rate of the patients with 4 or more metastatic nodes were very similar in ENS-positive and ENS-negative patients. CONCLUSIONS: The present findings suggest that in SCC of the thoracic esophagus, the presence of ENS increases recurrent risk and reduces the overall survival of the patients with 1-3 metastatic nodes. Patients showing ENS should be managed in the same way as patients with 4 or more metastatic nodes.

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  • Multiple carcinoids in the duodenum, pancreas and stomach accompanied with type A gastritis: a case report. 国際誌

    Takeo Bamba, Shinichi Kosugi, Tatsuo Kanda, Toshihiro Tsubono, Yasuo Sakai, Nobuyuki Musha, Noriko Ishihara, Katsuyoshi Hatakeyama

    World journal of gastroenterology   13 ( 15 )   2247 - 9   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.

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  • Gastric carcinosarcoma presenting as a huge epigastric mass.

    Yoshiyuki Ikeda, Shin-Ichi Kosugi, Ken Nishikura, Manabu Ohashi, Tatsuo Kanda, Takashi Kobayashi, Katsuyoshi Hatakeyama

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   10 ( 1 )   63 - 8   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gastric carcinosarcoma often presents with an elevated lesion or increased thickness of the stomach wall. Histological diagnosis is achieved using conventional hematoxylin and eosin staining to confirm the coexistence of both epithelial and mesenchymal elements. We report a case of gastric carcinosarcoma presenting as a large mass in the epigastric region. Specimens obtained by endoscopic biopsy and surgical excision showed diffuse proliferation of atypical cells in sheet formation. No mucus production or glandular structures were apparent, but immunoreactivity for both epithelial and mesenchymal markers was noted. These findings led to a definitive diagnosis of gastric carcinosarcoma. Immunohistochemical analysis is useful for the early diagnosis and treatment of gastric carcinosarcoma.

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  • Radio-guided sentinel node mapping in patients with superficial esophageal carcinoma: feasibility study. 国際誌

    Shin-Ichi Kosugi, Satoru Nakagawa, Tatsuo Kanda, Ikuo Odano, Kazuhito Yajima, Koji Kaneko, Manabu Ohashi, Katsuyoshi Hatakeyama

    Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy   16 ( 3 )   181 - 6   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The aim of this study was to assess whether the sentinel node concept could be applicable to clinically early carcinoma of the esophagus. We studied ten consecutive cT1N0 patients who underwent radical esophagectomy with regional lymph node dissection. On the day before surgery, 99m-Tc tin colloid was injected endoscopically around the primary tumor. Lymphoscintigraphy was also performed about three hours after injection. Immediately after surgery, the radioactivity of all dissected lymph nodes was measured with a hand-held gamma probe. The radioactivity and the metastatic status assessed by routine histopathologic examination were compared. A total of six patients had hot spots detected by lymphoscintigraphy, of which the detection rate was 60% (6 of 10). The ex vivo hot node detection rate was 90% (9 of 10). Three patients were found to have metastatic nodes. In one patient, sentinel node mapping failed to identify any hot spot or hot node. In the other two patients, the metastatic nodes did not correspond to hot nodes. The accuracy of hot node status was 77.8% (7 of 9), and the false-negative rate was 100% (2 of 2). The present study showed that radio-guided sentinel node detection is insufficiently reliable at present due to the high false-negative rate and low accuracy.

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  • Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: report of a case. 国際誌

    Shin Ichi Kosugi, Tatsuo Kanda, Tadashi Nishimaki, Satoru Nakagawa, Kazuhito Yajima, Manabu Ohashi, Katsuyoshi Hatakeyama

    World journal of gastroenterology   12 ( 25 )   4101 - 3   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed. Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 mo was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.

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  • Gallstone ileus with cholecystoduodenal fistula presenting massive upper gastrointestinal hemorrhage. 国際誌

    Shin-Ichi Kosugi, Tatsuo Tani, Isao Kurosaki, Katsuyoshi Hatakeyama

    Journal of gastroenterology and hepatology   21 ( 3 )   624 - 5   2006年3月

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    記述言語:英語  

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  • Adenocarcinoma arising from heterotopic gastric mucosa in the stomach. 国際誌

    Shin-Ichi Kosugi, Tatsuo Kanda, Katsuyoshi Hatakeyama

    Journal of gastroenterology and hepatology   21 ( 2 )   483 - 4   2006年2月

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    記述言語:英語  

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  • [Safety and efficacy of hypotonic CDDP intraperitoneal administration for gastric cancer with peritoneal dissemination].

    Takeo Bamba, Tatsuo Kanda, Manabu Ohashi, Takaaki Hanyu, Kaoru Sakamoto, Takashi Ishikawa, Kazuhito Yajima, Shigeto Makino, Tadashi Tanabe, Shin-ichi Kosugi, Katsuyoshi Hatakeyama

    Gan to kagaku ryoho. Cancer & chemotherapy   32 ( 11 )   1695 - 7   2005年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    We examined safety and efficacy of hypotonic CDDP intraperitoneal administration followed by systemic chemotherapy using MTX/5-FU and UFT. Between 1998 and 2004, seven patients who had histologically proven gastric adenocarcinoma with peritoneal metastases underwent palliative gastrectomy at Niigata University Medical Hospital. For residual peritoneal tumors, 100 mg/body of CDDP diluted with distilled water was intraperitoneally administered to the patients before closure of abdominal wall and was drained 30 to 60 minutes after administration. During the postoperative period, a patient suffered from intraperitoneal abscess and another patient had a renal dysfunction with an increasing level of serum Cr (2.1 mg/dl). As adverse effects of the following systemic chemotherapy, three patients had grade 3 anemia and one had grade 3 leukopenia. The median time to progression was 109 days and the median survival time was 248 days. Although intraperitoneal CDDP administration is safe to be carried out intraoperatively, the effect on survival is not better than new anticancer drugs, such as TS-1 and paclitaxel.

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  • Efficacy and toxicity of fluorouracil, doxorubicin, and cisplatin/nedaplatin treatment as neoadjuvant chemotherapy for advanced esophageal carcinoma. 国際誌

    Shin-Ichi Kosugi, Tatsuo Kanda, Satoru Nakagawa, Manabu Ohashi, Tadashi Nishimaki, Katsuyoshi Hatakeyama

    Scandinavian journal of gastroenterology   40 ( 8 )   886 - 92   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Patients with advanced esophageal carcinoma including clinical T4 tumor, extensive lymph node metastasis, or intramural metastasis have a dismal prognosis, despite recent multimodality treatments. The aim of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy using fluorouracil, doxorubicin, and cisplatin or nedaplatin (FAP/N) in these patients. MATERIAL AND METHODS: Twenty-six patients were enrolled in this study. The first 9 patients received 600 mg/m2 fluorouracil on days 1-7 and days 29-35, and 30 mg/m2 doxorubicin and 60 mg/m2 cisplatin on days 1 and 29 (FAP). The next 17 patients received modified FAP, in which 50 mg/m2 nedaplatin was given instead of cisplatin (FAN). RESULTS: Grade 3 or 4 toxicities developed in 6 patients (23.1%) during chemotherapy, but there was no discontinuation of treatment. The clinical response rate was 46.2%. Twenty-one patients (80.8%) underwent esophagectomy, and R0 resection was achieved in 16 patients (61.5%). The 1-year survival rates of 26 patients, 21 patients with resectable tumor, 16 with R0 resection, and 12 clinical responders, were 31.3%, 32.1%, 33.3%, and 45.5%, respectively, each with a median survival time of 9 months. The median progression-free survival time of 26 patients was 6 months; in 16 patients with R0 resection progression-free survival was 6.5 months. There was no correlation between the recurrence pattern and tumor spread before treatment. CONCLUSIONS: FAP/N was found to have acceptable toxicities and the ability to control locoregional tumors, but made little contribution to patient survival. The efficacy of this treatment for patients with advanced esophageal carcinoma, however, may not yet be apparent.

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  • Safety and efficacy of chemotherapy using TS-1 followed by paclitaxel for advanced or recurrent gastric cancer with peritoneal dissemination

    Ohashi, M., K, a, T., Yajima, K., Banba, T., Tanabe, T., Kosugi, S., Hatakeyama, K.

    Gan to kagaku ryoho. Cancer \& chemotherapy.   32 ( 11 )   2005年

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    掲載種別:研究論文(学術雑誌)  

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  • An esophageal cancer case unresectable due to tuberculous fibrosing mediastinitis : report of a case

    KANDA T

    Esophagus   1 ( 3 )   131 - 134   2004年9月

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  • Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19-9, and squamous cell carcinoma antigen levels in esophageal cancer patients. 国際誌

    Shin-ichi Kosugi, Tadashi Nishimaki, Tatsuo Kanda, Satoru Nakagawa, Manabu Ohashi, Katsuyoshi Hatakeyama

    World journal of surgery   28 ( 7 )   680 - 5   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and squamous cell carcinoma (SCC) antigen levels were assessed to determine if their levels are useful for staging esophageal cancer preoperatively and for predicting patient survival after esophagectomy. Hence their seropositivity was investigated for a correlation with resectability, clinicopathologic parameters of tumor progression, and treatment outcomes in patients with unresectable esophageal cancer ( n = 63) and those undergoing esophagectomy for resectable disease ( n = 267). Abnormal elevation of serum SCC antigen levels showed a significant correlation with resectability ( p< 0.0001), depth of tumor invasion ( p < 0.0001), lymph node status ( p = 0.0015), TNM stage ( p < 0.0001), lymphatic invasion ( p = 0.0019), blood vessel invasion ( p = 0.0079), and poor survival after esophagectomy ( p = 0.0061). A significant relation ( p = 0.0145) was found between elevated serum CEA levels and distant metastasis, whereas the seropositivity of CA 19-9 showed no association with resectability, tumor progression, or patient survival. These results indicate that abnormal elevation of serum SCC antigen is a useful predictor of advanced esophageal cancer associated with poor survival after esophagectomy.

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  • Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. 国際誌

    Satoru Nakagawa, Tatsuo Kanda, Shin-ichi Kosugi, Manabu Ohashi, Tsutomu Suzuki, Katsuyoshi Hatakeyama

    Journal of the American College of Surgeons   198 ( 2 )   205 - 11   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Extended radical esophagectomy with three-field lymphadenectomy for patients with thoracic esophageal cancer has been shown to be effective. But even if this operation is performed, some patients still experience relapse of the disease. The purpose of this study was to clarify the pattern and timing of recurrence after extended radical esophagectomy. STUDY DESIGN: Recurrence of esophageal squamous cell carcinoma was examined in 171 of 174 patients who underwent extended radical esophagectomy with three-field lymphadenectomy. Recurrence patterns were classified as locoregional (at the site of the primary tumor, the anastomotic site, or the lymph nodes), hematogenous, and other (pleura or site of gastrostomy). Factors associated with recurrence were identified using univariate and multivariate statistical methods for survival analysis. RESULTS: The overall 5-year survival rate was 55.6%. Recurrence was recognized in 74 patients (43.3%). The median disease-free interval until recurrence was 11 months. Thirty patients (17.5%) developed a locoregional recurrence, and 24 (14.0%) developed a hematogenous recurrence. Five patients (2.9%) developed both recurrences simultaneously and were classified as hematogenous recurrences. Of 30 patients with cervical lymph node metastasis, recurrent disease was recognized in 19 patients (63.3%). In multivariate analysis of 160 patients, the depth of invasion and pM-lym (cervical or celiac lymph node metastasis) were significant factors for locoregional recurrence; the depth of invasion and number of lymph node metastases at operation were significant factors for hematogenous recurrence. Survival time for patients with hematogenous recurrence (median 16 months) was significantly shorter than that of patients with locoregional recurrence (median 25.5 months). CONCLUSIONS: Locoregional recurrence is associated mainly with the extent of the local tumor and lymph node metastasis; hematogenous recurrence is not only associated with tumor stage but also with the tumor's oncologic behavior.

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  • Self-expandable metallic stents for palliation of malignant esophageal obstruction: special reference to quality of life and survival of patients. 国際誌

    K Yajima, T Kanda, S Nakagawa, K Kaneko, S Kosugi, M Ohashi, K Hatakeyama

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus   17 ( 1 )   71 - 5   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    SUMMARY. Self-expandable metallic stents (EMS) provide a common option for malignant esophageal stenosis because of the low complication rate and high dysphagia improvement rate. However, there are few studies on the functional duration of EMS and the extent of improvement of the quality of life. We retrospectively analyzed 18 patients who received EMSs in our division from 1996 to 2002. The median duration of possible food intake and the median survival period were 94.5 and 108 days. The median duration of domiciliary treatment was 56 days. Six of the 18 patients were not discharged from hospital after EMS insertion. The Karnofsky index was found to be a significant determinant of the feasibility of domiciliary treatment. One-third of the patients are incapable of obtaining the benefits of the palliative therapy. EMS deployment should be prudently selected for patients exhibiting low performance status.

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  • Indication of hepatic resection for metastatic liver tumors from gastric cancer

    Ohashi, M., K, a, T., Muneoka, K., Ikeda, Y., Yajima, K., Tanabe, T., Kosugi, S., Nakagawa, S., Hatakeyama, K.

    Gan to kagaku ryoho. Cancer \& chemotherapy   31 ( 11 )   2004年

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    掲載種別:研究論文(学術雑誌)  

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  • Hepatocellular carcinoma and splenic artery aneurysm arising in a patient with Budd-Chiari syndrome: A case report

    Kitami, C.-E., Kurosaki, I., Yokoyama, N., Kosugi, S., Hatakeyama, K., Tsukada, K.

    Japanese Journal of Gastroenterological Surgery   37 ( 11 )   2004年

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    掲載種別:研究論文(学術雑誌)  

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  • Eosinophilic colitis accompanied by Tolosa-Hunt syndrome: report of a case.

    Shin-ichi Kosugi, Kazutoshi Date, Masahiro Minagawa, Hiroyuki Ishikawa, Katsuyoshi Hatakeyama, Kazuhiko Endo, Yoshihiko Kimura

    Journal of gastroenterology   38 ( 6 )   613 - 4   2003年

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    記述言語:英語  

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  • Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus. 国際誌

    S Nakagawa, T Nishimaki, S Kosugi, M Ohashi, T Kanda, K Hatakeyama

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus   16 ( 1 )   4 - 8   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.

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  • Outcomes and prognostic factors after surgical resection of hypopharyngeal and cervical esophageal carcinomas

    T Nishimaki, T Kanda, S Nakagawa, S Kosugi, T Tanabe, K Hatakeyama

    INTERNATIONAL SURGERY   87 ( 1 )   38 - 44   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT COLLEGE OF SURGEONS  

    Carcinomas of the hypopharynx and the cervical esophagus carry poor prognosis regardless of any treatment modality. To improve long-term survival, prognostic factors for overall survival after surgical resection of these tumors were investigated. Clinical and pathological data from 52 patients undergoing surgical resection for hypopharyngeal (n = 20) and cervical esophageal (n = 32) cancers were reviewed to assess treatment outcomes and prognostic factors. The in-hospital mortality and morbidity rates were 13.5% and 50%, respectively. The 5-year survival rate of the 52 patients was 31.2%. The depth of tumor invasion, quality of tumor clearance, gender of the patients, postoperative complications, and intramural metastasis were revealed by the univariate analysis to be significant prognostic factors. The first four of these factors were specified by the multivariate analysis as independent prognostic factors for overall survival. Complete clearance of loco-regional disease and prevention of postoperative complications are of particular importance for the improvement of long-term survival in patients with these cancers.

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  • Mucus outflow from the appendiceal orifice due to an appendiceal mucocele. 国際誌

    M Minagawa, H Ishikawa, K Date, S Kosugi, K Hatakeyama, K Endo, K Kimura, F Fukuda

    Gastrointestinal endoscopy   53 ( 4 )   493 - 493   2001年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Allelic loss mapping and physical delineation of a region harboring a thymic lymphoma suppressor gene on mouse chromosome 16. 国際誌

    A Matsuki, H Kosugi-Okano, Y Ochiai, Kosugi Si, T Miyazawa, Wakabayashi Yi, K Hatakeyama, O Niwa, R Kominami

    Biochemical and biophysical research communications   282 ( 1 )   16 - 20   2001年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Our previous mapping of allelic loss in gamma-ray induced thymic lymphomas in F(1) hybrid and backcross mice between BALB/c and MSM strains identified three regions with high frequencies of allelic loss which probably harbor a tumor suppressor gene. One region, Tlsr7, exists near the D16 Mit122 locus on chromosome 16. This study has further localized Tlsr7 by constructing a physical map and scanning a total of 587 thymic lymphomas. The map consists of 13 overlapping BAC clones and isolation of BAC-derived polymorphic probes leads to fine mapping of allelic losses. Eleven lymphomas show informative breakpoints of allelic loss regions relative to the flanking markers on the map. Pulsed-field gel electrophoresis of NotI digests of the clones shows that the commonly lost region is localized within an approximately 300 kb interval near D16Mit192. This map is invaluable to facilitate the identification of genes in the Tlsr7 region.

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  • Homozygous deletions and point mutations of the Ikaros gene in gamma-ray-induced mouse thymic lymphomas. 国際誌

    H Okano, Y Saito, T Miyazawa, T Shinbo, D Chou, S Kosugi, Y Takahashi, S Odani, O Niwa, R Kominami

    Oncogene   18 ( 48 )   6677 - 83   1999年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Our previous genome-wide analysis of allelic loss for thymic lymphomas that were induced by gamma-irradiation in F1 hybrid mice between BALB/c and MSM strains suggested the centromeric region on chromosome 11 as a site harboring a tumor suppressor gene. Interestingly, to this region the mouse Ikaros gene was mapped which was postulated to participate in oncogenic process from the study of Ikaros knockout mice. Here we show fine allelic loss mapping in the vicinity of Ikaros in 191 lymphomas, indicating that the critical region of allelic loss was centered at the Ikaros locus. PCR analysis revealed that nine lymphomas failed to give PCR-amplification for either of two exon primer pairs, indicative of homozygous deletion. Six and five mutations were detected in the N-terminal zinc finger domain and the activation domain of Ikaros, respectively, and six of the eleven were frameshift or nonsense mutations that resulted in truncation of Ikaros protein. The results strongly suggest a direct role for Ikaros in development of mouse thymic lymphomas. This provides the experimental basis for further analysis of Ikaros mutations in human cancer.

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  • Accumulation of aberrant Y chromosomes in gamma-ray-induced thymic lymphomas lacking p53. 国際誌

    D Chou, J Matsuki, Y Saitou, S I Kosugi, T Shinbo, F Gejyo, O Niwa, R Kominami

    Molecular carcinogenesis   26 ( 3 )   157 - 62   1999年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Male F(1) hybrids between MSM mice carrying a deficient p53 allele and BALB/c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtained, 46 of which developed in mice carrying the deficient p53 allele. Because the Y chromosome contributes little to cellular function, the stability of the Y chromosome in the tumors was assessed by polymerase chain reaction by examining three genes: Smcy and Sry on the short arm and Sts in the pseudoautosomal region of the long arm of the Y chromosome. Twenty-one lymphomas had lost one or two genes, probably as a result of mitotic recombination or interstitial deletion, whereas no lymphomas had lost all three genes. The p53 status of the lymphomas was determined by genotyping and allelic loss analysis; 34 had retained two wild-type p53 alleles, suggesting normal function; 34 had lost both alleles, indicating loss of function; and the other 12 had at least one wild-type p53 allele, so their p53 status was unclear. Compilation of these data revealed that changes in the Y chromosome were detected in only two of the 34 lymphomas retaining functional p53 but in 18 of the 34 lymphomas lacking p53 function, suggesting that p53 deficiency leads to an increase in the accumulation of radiation-induced aberrant chromosomes. This is consistent with our previous result from analysis of the inactive X chromosome. In contrast, a decrease in the fidelity of mitotic transmission in p53-deficient lymphomas was not noted for the Y chromosome.

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  • Allelic loss mapping and physical delineation of a region harboring a putative thymic lymphoma suppressor gene on mouse chromosome 12. 国際誌

    T Shinbo, A Matsuki, Y Matsumoto, S Kosugi, Y Takahashi, O Niwa, R Kominami

    Oncogene   18 ( 28 )   4131 - 6   1999年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Our previous allelic loss analysis of gamma-ray induced thymic lymphomas in F1 hybrid and backcross mice between BALB/c and MSM strains mapped the Tlsr4 region exhibiting a high frequency of allelic loss (62%) to a 2.9 cM interval between the markers D12Mit53 and D12Mit279 on mouse chromosome 12. To narrow further the interval harboring a putative tumor suppressor gene, a high-density scan has been carried out for informative 361 thymic lymphomas. Construction of a physical map of Tlsr4 with 3 YAC and 15 BAC clones and isolation of YAC- and BAC-derived polymorphic probes lead to fine allelic loss mapping. Three successive polymorphic sites within one BAC exhibit the retention of both alleles in seven, one and four lymphomas, suggesting that a common region of allelic loss for Tlsr4 exists within the BAC region. Pulsed-field gel electrophoresis of NotI digests of this and other clones determines that the commonly lost region is a 35 kb interval with a NotI site. NotI sites are frequently associated with coding regions, and our preliminary sequencing has identified ESTs in the region. Thus, the present study facilitates the identification of genes in the Tlsr4 region that would lead to isolation of a novel tumor suppressor gene.

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  • Mutations in the p53 and scid genes do not cooperate in lymphomagenesis in doubly heterozygous mice. 国際誌

    S Kosugi, T Miyazawa, D Chou, Y Saito, T Shinbo, A Matsuki, H Okano, C Miyaji, H Watanabe, K Hatakeyama, O Niwa, R Kominami

    Biochemical and biophysical research communications   255 ( 1 )   99 - 103   1999年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Analysis of double mutant mice of the p53 and scid genes, which have a combination of cell cycle checkpoint/apoptosis and DNA repair defects, shows that the latter defect synergistically enhances lymphoma development with loss of the former function. These mice lack the ability to eliminate lymphocytes predisposed to neoplastic transformation resulting from faulty antigen receptor gene rearrangement. Here we examine the cooperativity in double heterozygotes of p53 and scid in which normal development of lymphocytes is not impaired. MSM mice carrying a p53-knockout allele were crossed with BALB/c mice heterozygous for the scid locus and 129 offspring were obtained. They were subjected to gamma-ray irradiation, 84 thymic lymphomas being generated. The tumors and host mice were genotyped of p53 and scid. Among 42 mice developing p53-deficient lymphomas, scid/+ and +/+ genotypes did not provide difference in onset and latency. Besides, allelic loss of the Scid gene occurred at a high frequency in those lymphomas but the loss exhibited no allelic bias. The results suggest that the scid/+ genotype is not a modifier of loss of p53 function in the double heterozygotes.

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  • Accumulation of recombinant chromosomes and low fidelity of transmission of chromosome X DNA markers in gamma-ray-induced lymphomas lacking p53. 国際誌

    N Koide, Y Matsumoto, S Kosugi, D Chou, K Sakai, K Hatakeyama, O Niwa, R Kominami

    Molecular carcinogenesis   24 ( 1 )   57 - 63   1999年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    F1 offspring of male MSM male mice with a p53-deficient (knockout) allele and normal female BALB/c mice were backcrossed with MSM mice to produce N2 mice. Female F1 and N2 mice were irradiated with gamma-radiation, and thymic lymphomas were obtained from 69 F1 and 82 N2 mice heterozygous for X chromosome markers. Of these 151 mice, 91 carried a p53-deficient allele. These lymphomas were analyzed for allelic loss by using four marker loci distributed on X chromosome to assess the stability of the inactive X chromosome, which contributes little to cellular functions. Twenty lymphomas showed allelic loss of all four loci, suggesting loss of a whole inactive X chromosome due to mitotic nondisjunction, whereas 24 lost only a part of an X chromosome, as a result of somatic recombination. The p53 status of the lymphomas was determined by genotyping and allelic loss analysis: 53 had retained two wild-type p53 alleles, suggesting normal function; 69 had lost both alleles, indicating loss of function; and the remaining 29 had at least one wild-type p53 allele, so their p53 status was unclear. Compilation of these two data revealed one nondisjunction-type change and five recombination-type mutations on X chromosome in 53 lymphomas retaining functional p53. In contrast, 14 and 16 of these alterations, respectively, were observed in 69 lymphomas lacking p53 function. These results suggest that p53 loss significantly increases the accumulation of recombinant chromosomes and decreases the fidelity of mitotic chromosome transmission of the X chromosome in gamma-ray-induced lymphomas.

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  • Rational extent of lymphadenectomy based on the anatomic characteristics of lymph node metastasis in potentially curable esophageal cancer

    Nishimaki, T., Suzuki, T., K, a, T., Hayashi, T., Kosugi, S.-I., Watanabe, N., Komukai, S., Hatakeyama, K.

    Japanese Journal of Gastroenterological Surgery   32 ( 10 )   1999年

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    掲載種別:研究論文(学術雑誌)  

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  • Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation. 国際誌

    S Suzuki, S Kosugi, S Kuwabara, K Ueki, Y Oka, T Nishimaki, K Aizawa, T Suzuki, J Soga, K Hatakeyama

    Journal of experimental & clinical cancer research : CR   17 ( 2 )   187 - 91   1998年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

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  • Allelic loss analysis of gamma-ray-induced mouse thymic lymphomas: two candidate tumor suppressor gene loci on chromosomes 12 and 16. 国際誌

    Y Matsumoto, S Kosugi, T Shinbo, D Chou, M Ohashi, Y Wakabayashi, K Sakai, M Okumoto, N Mori, S Aizawa, O Niwa, R Kominami

    Oncogene   16 ( 21 )   2747 - 54   1998年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A total of 429 gamma-ray-induced thymic lymphomas were obtained from F1 and backcross mice between BALB/c and MSM strains, about a half of which carried a p53-deficient allele. A genome-wide allelic loss analysis has revealed two loci exhibiting frequent allelic losses but no allelic preference, one is localized within a 2.9 cM region between D12Mit53 and D12Mit279 loci on chromosome 12, and the other is near the D16Mit122/D16Mit162 loci on chromosome 16. The frequency of allelic loss in the D12Mit279 region is 62% and does not differ in tumors between the presence and absence of the p53-deficient allele. In contrast, the loss frequency of D16Mit122 is raised by the existence of p53-deficient allele: 62% for p63(-/+) and 13% for p53(+/+), suggesting co-operative function of the two losses. The D12Mit279 and D16Mit122 regions probably harbor different types of tumor suppressor gene that play key roles in lymphoma development.

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  • Telomerase activity and metastasis: expansion of cells having higher telomerase activity within culture lines and tumor tissues.

    Y Saito, S Kosugi, T Suda, Y Wakabayashi, Y Mishima, K Hatakeyama, R Kominami

    Japanese journal of cancer research : Gann   88 ( 8 )   732 - 7   1997年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Tumor cells with metastatic potential may have a high telomerase activity that augments telomeric DNA repeats, allowing the cells to escape from the inhibition of cell proliferation due to shortened telomeres. We examined the expression level of telomerase activity using the telomeric repeat amplification protocol among a series of cell lines obtained by repeated transplantation of a mouse fibrosarcoma. The lines could be grouped into three; one has no metastatic potential, and the other two show metastatic abilities after intravenous or subcutaneous injection. Comparison of their telomerase activity indicated that more malignant lines had higher activity. A similar relation was seen in metastatic nodules formed through clonal expansion from the heterogeneous population of inoculated cells; clonality was monitored in terms of variable patterns of subtelomeric repeats. The results suggest that a high level of telomerase activity may not be requisite for metastasis, but may confer a propensity to dominate in a tumor tissue.

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  • Genetic and physical delineation of the region of the mouse deafness mutation shaker-2. 国際誌

    Y Wakabayashi, Y Kikkawa, Y Matsumoto, T Shinbo, S Kosugi, D Chou, M Furuya, K Jishage, T Noda, H Yonekawa, R Kominami

    Biochemical and biophysical research communications   234 ( 1 )   107 - 10   1997年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A total of 951 backcross progeny have been obtained from a backcross segregating for the mouse deafness mutation, shaker-2(sh-2). Linkage analysis provides a detailed genetic map in the vicinity of sh-2 which comprises 40 backcross mice identified as recombinant within a 4 cM region. This allows construction of a contig consisting of 21 BAC clones across an approximately 700-kb region of sh-2. This covers the entire nonrecombinant region of sh-2 and is therefore useful to facilitate the identification of genes in the sh-2 region.

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共同研究・競争的資金等の研究

  • 食道癌術前化学療法の治療効果予測を目指したNQO1遺伝子多型の臨床的意義の解明

    研究課題/領域番号:22K08840

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    石川 卓, 宗岡 悠介, 赤澤 宏平, 廣瀬 雄己, 若井 俊文, 市川 寛, 小杉 伸一, 加納 陽介, 須貝 美佳

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 放射線画像・遺伝子解析を統合した食道癌術前治療後の癌遺残形式予測モデルの開発

    研究課題/領域番号:22K08866

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    宗岡 悠介, 若井 俊文, 羽入 隆晃, 市川 寛, 石川 卓, 臼井 賢司, 小杉 伸一, 加納 陽介, 島田 能史

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • HER2陽性胃癌における遺伝子異常の包括的評価と臨床的意義の解明

    研究課題/領域番号:19K09117

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    臼井 賢司, 奥田 修二郎, 島田 能史, 永橋 昌幸, 若井 俊文, 羽入 隆晃, 市川 寛, 石川 卓, 小杉 伸一

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究の目的は、「胃癌における癌遺伝子解析パネルを用いたERBB2 遺伝子異常評価の精度、および併存する遺伝子異常の臨床的意義を明らかにすることで、抗HER2療法を基軸とした胃癌薬物治療発展への足がかりとすること」である。本年度は、癌遺伝子パネルによるERBB2増幅とHER2発現の関係を明らかにすることを目的に実験を行った。胃癌切除検体130例の原発巣におけるHER2発現を臨床検査(HER2検査)に準じて免疫組織化学(IHC)やFISHで評価した。IHCにはヒストファイン HER2キット(MONO)ユニバーサルキット(ニチレイバイオサイエンス)を、FISHにはパスビジョンHER-2 DNAプローブキット(PathVysion;Abbott Molecular)用いた。IHCで3+、またはIHC2+でFISH陽性(HER2/CEP17比≧2.0)をHER2陽性と定義した。同一症例のERBB2増幅を癌遺伝子パネルで解析し、コピー数≧2.5倍を増幅と定義した。全例でIHCやFISHと癌遺伝子パネルは同一のホルマリン固定後パラフィン包埋(FFPE)ブロックを用いた。35例は癌遺伝子パネルとは異なるFFPEブロックを用いたHER2検査も臨床的に行われていた。
    130例中HER2陽性は16例(12.3%)であった。また、ERBB2増幅は11例(8.5%)に認められた。10例はHER2陽性かつERBB2増幅、113例はHER2陰性かつERBB2非増幅であり、HER2検査としての癌遺伝子パネルの精度は94.6%であった。癌遺伝子パネルに用いたFFPEブロックと異なる検体を用いたHER2検査の結果を検討したところ、癌遺伝子パネルの精度は80.0%と低下した。
    癌遺伝子パネルによるHER2検査の精度は高く、胃癌における抗HER2療法適応症例の選択に有用である可能性が示唆された。

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  • NOTCHシグナルを介した食道癌化学療法奏効性の分子機構の解明

    研究課題/領域番号:19K09212

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    市川 寛, 島田 能史, 永橋 昌幸, 羽入 隆晃, 石川 卓, 小杉 伸一, 加納 陽介

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    本研究の目的は、「食道癌におけるNOTCHシグナル異常の臨床的意義を明らかにすることで、食道癌化学療法奏効性の背景にある分子機構解明のための科学的基盤を確立すること」である。本年度は、食道癌術前化学療法症例の遺伝子解析、TCGAデータを用いたNOTCH関連遺伝子の変異状況の調査を行った。
    術前ドセタキセル+シスプラチン+5-FU療法を施行された8例を対象とした。癌遺伝子パネルにより435の癌関連遺伝子の異常を評価し、組織学的効果との関連を検討した。TP53変異を7例(88%)、CDKN2A欠失を3例(38%)、NFE2L2変異・NOCTH1変異・PIK3R1欠失・CDKN2B欠失・CCND1増幅をそれぞれ2例(25%)、PIK3CA変異・PTEN変異・NOTCH3変異・TGFBR2変異・KMT2D変異・EGFR増幅・VEGFR2増幅・RB1欠失・BIRC2増幅・BIRC3増幅をそれぞれ1例(13%)に認めた。化学療法奏効群4例中3例(75%)にNOTCH1またはNOTCH3の機能欠失型変異を認めた。さらにTCGAデータでは、全89症例中24例(27%)にNOTCH1・NOTCH2・NOTCH3・NOTCH4に何らかの変異を認めた。またNOTCHのtruncating mutationは10例(11%)に認められた。NOTCH変異と全生存に有意な関連は認められなかった。しかし、NOTCH1・3 truncation mutation陽性群の全生存期間中央値は11か月、陰性群は28か月と有意な差を認めた(P = 0.01)
    結論:NOTCH1・3の機能欠失型変異は術前化学療法の奏功性に関与している。一方、NOTCH1・3の機能欠失型変異陽性例の予後は不良であり、術前化学療法群における治療効果と予後に関してさらなる検証が必要である。

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  • 胃癌マイクロサテライト不安定性評価の検証と薬物治療における臨床的意義の解明

    研究課題/領域番号:19K09165

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    羽入 隆晃, 奥田 修二郎, 永橋 昌幸, 市川 寛, 石川 卓, 小杉 伸一, 加納 陽介

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究の目的は、「胃癌における癌遺伝子解析パネルを用いたMSI 解析の精度、およびその臨床的意義を明らかにすることで、MSI を基軸とした胃癌薬物治療発展への足がかりとすること」である。本年度は、癌遺伝子パネルによるMSI解析結果と、ミスマッチ修復遺伝子発現の相関とMSI解析の精度を明らかにすることを目的に実験を行った。
    癌遺伝子パネルによる遺伝子解析を施行した胃癌切除検体27例(MSI-high: 13例、MSI-low/MSS: 14例)を対象とした。原発巣におけるミスマッチ修復(MMR)タンパク質(MLH1, PMS2, MSH2, MSH6)発現を免疫組織化学(IHC)で評価した。MSI-highの13例中、10例でMLH1及びPMS2のlossを、2例でPMS2のlossを認め、1例でMMRタンパク質発現が全て保たれていた。MSI-low/MSSの14例では、全例でMMRタンパク質発現が保たれていた。MSI-high胃癌抽出において、MLH1及びPMS2のIHCによるMMR遺伝子異常評価の感度は92%、特異度は100%であった。
    また、MSI-highの13例を対象として、臨床検査であるマイクロサテライト不安定性(MSI)検査(BAT25、BAT26、NR21、NR24、MONO27 の5マーカー)を施行した。13例全てで5マーカーにMSI陽性を認め、MSI-highと判定された。
    癌遺伝子パネルで同定されたMSI-high胃癌では、従来の報告通りMLH1またはPMS2発現の欠失が多く認められる。癌遺伝子パネルによるMSI評価の精度は高く、胃癌におけるPembrolizumab療法適応症例の選択に有用である可能性が示唆された。

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  • 胃癌DNA二重鎖損傷修復機構破綻の包括的評価と臨床的意義の解明

    研究課題/領域番号:18K08698

    2018年4月 - 2021年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    堅田 朋大, 若井 俊文, 市川 寛, 島田 能史, 永橋 昌幸, 羽入 隆晃, 小杉 伸一, 廣瀬 雄己

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    本研究の目的は、「胃癌における癌遺伝子解析パネルを用いたhomologous recombination (HR)関連遺伝子異常の評価、およびその臨床的意義を明らかにすることで、HR関連遺伝子異常を基軸とした胃癌薬物治療の発展への足がかりとすること」である。
    これまでの研究から、癌遺伝子パネルによるHR関連遺伝子異常と抗γH2AX抗体による免疫組織化学により評価された胃癌DNA二本鎖修復機構の破綻とを比較したが、統計学的な関連は認められなかった。しかし、HR関連遺伝子異常を認める症例では白金系抗癌剤の治療効果が高く、再発後の予後が良好であることが示された。
    本年度は、癌遺伝子パネルの解析によるMutational signatureと白金系抗癌剤の治療効果との関連を検討した。RECISTによる最良効果がPDの症例をnon-Responder、それ以外をResponderと定義して比較した。Signature 1/3/5/6/22/othersはResponder群で34%/31%/0%/12%/10%/12%、non-Responder群で28%/23%/9%/27%/7%/6%であり、Mutational signatureの分布に有意な差を認めた(P < 0.01)。
    Signature 3は白金系抗癌剤の治療効果と関連していることが報告されている。本検討でもResponder群はnon-Responder群と比較してSignature3の割合が高く、胃癌においてもSignature 3が白金系抗癌剤の奏功性と関連している可能性が示唆された。

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  • 消化器外科手術後の包括的嚥下機能評価に関する研究

    研究課題/領域番号:17K00813

    2017年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小杉 伸一, 石川 卓, 羽入 隆晃, 市川 寛, 相澤 直孝, 真柄 仁

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    消化器外科手術前後の嚥下機能を包括的に評価し機能障害に関連する因子を探索するために,手術前後に6つの摂食嚥下機能評価を行った.解析の結果,発声持続時間と舌圧が術後有意に低下していた.発声持続時間および舌圧の変化と年齢に負の相関があった.発声持続時間の変化は術前発声持続時間,手術時間と正の相関があった.同様に,舌圧の変化は術前舌圧と正の相関があった.その他の臨床病理学的因子との間に関連はなかった.サブ解析の結果,発声持続時間と舌圧の変化は嚥下機能障害と直接関連しない可能性があり,一般的な消化器外科手術では摂食嚥下障害は起こりにくいと考えられた.

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  • 胃癌におけるBRCA1/2遺伝子変異解析およびタンパク質発現とその臨床的意義

    研究課題/領域番号:17K10580

    2017年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    滝沢 一泰, 若井 俊文, 羽入 隆晃, 市川 寛, 田澤 立之, 中田 光, 小杉 伸一

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    BRCA1/2遺伝子異常を始めとしたDNA二本鎖損傷修復機構の異常は、放射線や抗癌剤の治療効果に関与すると考えられる。また、BRCA1/2は遺伝性乳癌卵巣癌症候群の原因遺伝子である。我々は、胃癌におけるBRCA1/2遺伝子変異の臨床的意義を明らかにすることを目的に研究を行った。
    胃癌腫瘍組織にBRCA2変異を認める症例の予後は良好であり、BRCA2変異は胃癌の予後良好な因子であることが明らかになった。また、BRCA1/2胚細胞性変異陽性例ではプラチナ系抗癌剤の治療効果が高い可能性や、この遺伝子変異が胃癌の家族集積性に関与する可能性が示唆された。

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  • 胃癌におけるアクチビン受容体変異による新規シグナル伝達機構の解明及び臨床的意義

    研究課題/領域番号:17K10579

    2017年4月 - 2020年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    油座 築, 永橋 昌幸, 若井 俊文, 羽入 隆晃, 市川 寛, 小杉 伸一

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    胃癌124症例を対象に次世代シークエンサーを用いて遺伝子解析を行った.8%(10例)にアクチビン2型受容体(ACVR2A)遺伝子変異を認め,全てMSI症例だった.ACVR2A遺伝子変異群の術後5年全生存率は90%であり,ACVR2A遺伝子変異の無い群の57%に比べて有意に高かった.さらに,ACVR2A遺伝子をノックアウトした胃癌細胞株を作成し実験を行った.ACVR2Aノックアウト細胞は,mock細胞に比べてその増殖能,遊走能,浸潤能が有意に低下していた.

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  • 食道癌のリンパ行性進展に関与する脂質メディエーター分子機構の解明および臨床的意義

    研究課題/領域番号:16K10491

    2016年4月 - 2019年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    市川 寛, 永橋 昌幸, 若井 俊文, 羽入 隆晃, 小杉 伸一, 宗岡 悠介, 中野 雅人, 田中 花菜, 須藤 翔, 崎村 健司, 阿部 学

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    食道癌92症例の手術検体を対象に、活性型のリン酸化SphK1(pSphK1)とSphK1の腫瘍組織における発現を免疫組織化学で評価した。pSphK1高発現群では病理学的なリンパ節転移陽性、リンパ管侵襲陽性、壁内転移陽性の頻度が高かった。さらに、pSphK1高発現群の術後5年全生存割合は50.8%であり、低発現群の67.3%と比較して有意に低かった。一方、SphK1発現とリンパ行性進展や術後生存期間との有意な関連は認められなかった。pSphK1発現は食道癌のリンパ行性進展や患者の不良な予後と関連している。

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  • 胃癌の浸潤・転移能に関与する脂質メディエーター分子制御機構の解明および臨床的意義

    研究課題/領域番号:15K10087

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    羽入 隆晃, 永橋 昌幸, 若井 俊文, 石川 卓, 小杉 伸一, 小林 隆, 高部 和明, サラ スピーゲル

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    「胃癌細胞内でスフィンゴシンキナーゼ1型(SphK1)および産生されるスフィンゴシン-1-リン酸(S1P)が胃癌の進行・リンパ管浸潤に寄与している」という仮説をたて、胃癌外科切除例に対し、免疫組織化学検査および質量分析によりSphK1・S1Pと臨床病理学的因子および予後との関連を解析した。
    SphK1発現は胃癌進行度、特にびまん浸潤型およびリンパ管侵襲陽性と関連していることを発見し、更に生存率においてもSphK1陽性群は陰性群に比べて予後不良であった。また組織中のS1P濃度はSphK1発現との相関を認めており、胃癌の進行においてSphK1およびS1Pが重要な役割を果たしていることが示唆された。

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  • 周術期の脂肪乳剤投与による血清カルニチン動態およびL-カルニチン製剤投与の効果

    研究課題/領域番号:15K10047

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小山 諭, 諸 和樹, 永橋 昌幸, 若井 俊文, 三浦 宏平, 小杉 伸一, 小林 隆, 小松 雅明

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    静脈栄養においても、経腸栄養においても基本的に不可欠な主要栄養素の1つである脂質を有効に利用できれば手術後の侵襲下においても患者の回復に役立つ。手術後静脈栄養の際、脂肪乳剤に加えL-カルニチンを投与することにより第3~7病日での炎症反応物質であるCRPが有意に低下することより、術後の炎症反応からの離脱に有用な可能性を示した。
    また、経腸栄養においては、食道癌術後経腸栄養開始の際に低脂質含有栄養剤を使用することにより、術後回復が有意に早く進み、また、術後合併上の1つである乳び胸の予防に有用である可能性を示した。

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  • 胆道癌・膵癌の転移能に関与する脂質メディエーター分子制御機構の解明および臨床応用

    研究課題/領域番号:15H04927

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    若井 俊文, 永橋 昌幸, 松田 康伸, 小林 隆, 五十嵐 道弘, 坂田 純, 味岡 洋一, 小杉 伸一, 小松 雅明, サラ スピーゲル, フィリイプ ハイレモン, 高部 和明

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    配分額:16640000円 ( 直接経費:12800000円 、 間接経費:3840000円 )

    本発明者らは、腫瘍微小環境において癌細胞を貪食する間質液中のスフィンゴシン-1-リン酸レベルを測定する方法を開発し、腫瘍間質液中に高レベルのスフィンゴシン-1-リン酸が存在すると報告した。 重要なことに、スフィンゴシン-1-リン酸は、腫瘍微小環境における癌細胞および免疫細胞および血管/リンパ内皮細胞などの非癌成分から分泌され得る。 我々は、腫瘍微小環境における癌細胞と非癌細胞との間の相互作用におけるスフィンゴシン-1-リン酸の役割を解明し、癌患者のための標的化されたスフィンゴシン-1-リン酸シグナル伝達の将来の可能性について議論する。

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  • メタボローム解析による乳癌代謝動態に関与する脂質メディエーター分子機構の解明

    研究課題/領域番号:15K15471

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 挑戦的萌芽研究

    研究種目:挑戦的萌芽研究

    提供機関:日本学術振興会

    永橋 昌幸, 西條 康夫, 小山 諭, 小杉 伸一, 小林 隆

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    配分額:3640000円 ( 直接経費:2800000円 、 間接経費:840000円 )

    スフィンゴシンキナーゼ(SphK1およびSphK2)によって産生されるスフィンゴシン-1-リン酸(S1P)は、多面的な生理活性脂質メディエーターである。S1Pの癌細胞特異的代謝調節における役割について研究を行った。SphK1およびSphK2ノックアウト乳癌細胞の代謝物プロファイルは、解糖経路およびTCAサイクル等において有意な変化を認めた。今回の結果は、S1Pとスフィンゴシンキナーゼが癌特異的代謝において重要な役割を果たすことを示唆している。

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  • 大腸癌薬物療法抵抗性の分子機構における転写メディエーターMED12異常発現の解明

    研究課題/領域番号:15K10130

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    島田 能史, 坂田 純, 味岡 洋一, 亀山 仁史, 小杉 伸一, 小林 隆, 若井 俊文

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    転写メディエーターサブユニットであるMediator complex subunit 12(MED12)は,癌の発育進展に関与するMitogen-activated protein kinase経路および上皮間葉転換(EMT)関連遺伝子発現を抑制的に制御している.大腸癌100例を対象に,免疫組織化学染色を用いてMED12発現を評価すると,陽性が79例(79%),陰性が21例(21%)あった.MED12発現陰性症例では,簇出,リンパ節転移,遠隔転移が有意に多かった.本研究により,大腸癌の遠隔転移の機序として,MED12発現低下によるEMTが関与している可能性が示唆された.

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  • 消化管間質腫瘍の発生部位と予後に関わる遺伝子の解析

    研究課題/領域番号:26461970

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    石川 卓, 若井 俊文, 羽入 隆晃, 小杉 伸一, 小山 諭, 亀山 仁史, 市川 寛

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    小腸原発の消化管間質腫瘍(GIST)は胃原発GISTと比較して予後不良であり、自律的細胞増殖と腫瘍化に関与することが知られているDNPH遺伝子の関与に着目した。小腸GISTが臨床学的に悪性度の高いことを確認し、切除標本を用いてDNPH1の発現を検討した。DNPH1は胃原発、小腸原発のいずれのGISTにおいても発現が認められ、原発臓器の違いによる差異を見出すことはできなかったが、DNPH1の発現が腫瘍の発育に寄与していることが示唆された。

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  • 膵癌におけるBudding cancer cellの新たな生物学的評価法の確立

    研究課題/領域番号:26462056

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    滝沢 一泰, 若井 俊文, 皆川 昌広, 高野 可赴, 小林 隆, 亀山 仁史, 小杉 伸一

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    膵癌おける簇出の評価において、HE染色よりAE1/AE3免疫染色での評価の方が簇出検出個数が有意に増加した(7.8±0.5 vs 15.3±1.0, P < 0.001)。また、AE1/AE3およびKi-67の2重染色では、高簇出Ki-67陽性群は有意に予後不良であった(P < 0.001)。簇出の形質発現について、Ki-67発現およびTUNEL法によるアポトーシス検出を確認すると、Ki-67陽性症例は73%でTUNEL陽性症例はわずか7%であり、簇出でのアポトーシスは減少していた。簇出は大部分がE-Cadherin陽性、ビメンチン陰性で、本研究においては簇出での上皮間質転換は示されなかった。

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  • 膵癌における光線力学診断を応用した化学療法効果予測法の開発

    研究課題/領域番号:26462055

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    皆川 昌広, 若井 俊文, 坂田 純, 滝沢 一泰, 高野 可赴, 小林 隆, 小杉 伸一

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    術前5-ALA投与によって膵癌の標本を蛍光させることができる.15名の膵癌患者において,5-ALA投与における切除標本の確認をおこなった.蛍光パターンを3つのタイプ(カテゴリー0:蛍光なし,カテゴリー1:点状また部分的経口,カテゴリー2:全体的な蛍光)に分類した.カテゴリー0および1群,カテゴリー2群の2群にわけてカプランメイヤー法にて比較するとカテゴリー2群のほうがカテゴリー0および1群にくらべ有意に生存率が高かった.膵癌細胞株にてALA蛍光性とGemcitabineの奏効率をみてみると,ALA蛍光性があるものはGemcitabineの奏効率が高かった.

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  • 蛍光免疫組織化学を用いた大腸pSM癌における簇出の生物学的評価及びその意義

    研究課題/領域番号:26462007

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    野上 仁, 島田 能史, 若井 俊文, 味岡 洋一, 小林 隆, 小杉 伸一, 永橋 昌幸

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    本研究の目的は,「CAM5.2免疫染色における簇出評価の判定基準を立案すること」,および「HE染色およびCAM5.2免疫染色を用いて判定した簇出個数とリンパ節転移との関連を解析し,どちらがリンパ節転移予測の有用性が高いか明らかにすること」であった.
    本研究より,CAM5.2免疫染色における簇出評価の判定基準は,対物20倍1視野に8個以上の簇出が認められることと算出された.また,HE染色を用いて評価した簇出が,リンパ節転移予測の有用性が高いと結論付けられた.

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  • p62-Keap1-Nrf2 pathwayによる大腸癌抗癌剤耐性機序の解明

    研究課題/領域番号:26462006

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    亀山 仁史, 小松 雅明, 若井 俊文, 味岡 洋一, 西條 康夫, 松田 康伸, 小山 諭, 廣瀬 雄己, 小杉 伸一, 小林 隆, 永橋 昌幸

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    p62-Keap1-Nrf2経路はNQO1等の抗酸化ストレス蛋白を誘導している。NQO1は癌細胞においては抗癌剤耐性に関与することが知られている。本研究の目的は進行大腸癌におけるNQO1発現と予後の関連を明らかにすることである。KRAS野生型大腸癌において、NQO1陰性例はNQO1陽性例に比べ、病勢制御率が有意に良好であった。さらに、NQO1陰性例は無増悪再発期間、全生存期間も有意に良好であった。KRAS野生型進行大腸癌において、腫瘍におけるNQO1発現検索は、化学療法の効果または予後に関する有効な予測因子となる可能性がある。

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  • 食道癌術前補助化学療法抵抗性の分子機構における酸化ストレス系シグナル異常の解明

    研究課題/領域番号:26461971

    2014年4月 - 2017年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小杉 伸一, 小松 雅明, 若井 俊文, 石川 卓, 羽入 隆晃, 小山 諭, 廣瀬 雄己, 市川 寛

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    食道癌における化学療法抵抗性の分子機構を酸化ストレス系シグナルの観点から解明を試みた.酸化ストレス系の下流に位置する分子であるNQO1の腫瘍組織内発現は病理学的治療効果との関連はなかったが,独立した予後不良因子であった.またNQO1発現を調節するNrf2発現との間に有意な相関関係は認められなかった.一方,非腫瘍性扁平上皮のNQO1発現は臨床的治療効果と相関し,発現陰性は独立した予後良好因子であった.非腫瘍性扁平上皮のNQO1発現は,治療抵抗性や予後の予測に有用なバイオマーカーになりうる.

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  • 血中微小癌細胞の再発因子としての有用性の検証:食道癌における多施設前向き臨床研究

    研究課題/領域番号:17591381

    2005年 - 2008年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    神田 達夫, 小杉 伸一, 小山 諭, 河内 保之, 薮崎 裕, 片柳 憲雄, 大橋 学, 山口 敏和, 大橋 学

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    配分額:3870000円 ( 直接経費:3600000円 、 間接経費:270000円 )

    2006 年7 月から新潟県内4 医療施設において切除可能胸部食道扁平上皮癌患者を対象に臨床試験が開始された。血中微小癌細胞の同定はPCR 法による癌特異蛋白(CEA、SCC)mRNA の検出によった。2007 年8 月までに20 名の患者の分析が行われたが、有意な癌特異蛋白mRNA が検出された患者はおらず、試験は途中中止となった。PCR 法による血中微小癌細胞分析を臨床検査として一般化するには、いまだ課題が多い。

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  • Endoscopic surgery in upper gastrointestinal tract

    2005年

    制度名:The Other Research Programs

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    資金種別:競争的資金

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  • 上部消化管における鏡視下手術

    2005年

    制度名:その他の研究制度

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    資金種別:競争的資金

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  • Clinicopathological analysis of esophageal carcinoma

    2001年

    制度名:The Other Research Programs

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    資金種別:競争的資金

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  • 食道癌の臨床病理学的解析

    2001年

    制度名:その他の研究制度

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    資金種別:競争的資金

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