2024/02/03 更新

写真a

ウエハラ ケイ
上原 圭
Uehara Kay
所属
付属病院 消化器外科 講師
職名
講師
外部リンク

研究キーワード

  • 直腸癌

  • 大腸癌

  • 化学療法

  • 拡大手術

研究分野

  • ライフサイエンス / 消化器外科学  / 大腸癌

学歴

  • 名古屋大学   大学院医学系研究科

    2004年4月 - 2007年3月

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    国名: 日本国

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  • 名古屋大学   医学部

    1990年4月 - 1996年3月

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    国名: 日本国

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経歴

  • 日本医科大学   消化器外科   講師

    2023年4月 - 現在

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論文

  • 神経線維腫症I型に合併した巨大虫垂神経線維腫症の1例

    野中 有紀子, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 梅田 晋一, 服部 憲史, 中山 吾郎, 横山 幸浩, 江畑 智希

    日本外科系連合学会誌   48 ( 3 )   436 - 436   2023年5月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 局所進行結腸癌に対する術前化学療法の臨床経験

    田根 雄一郎, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 川勝 章司, 中山 吾郎, 服部 憲史, 梅田 晋一, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   DP - 7   2023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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  • 食道癌術後の縫合不全リスク評価システム

    杉田 静紀, 宮田 一志, 横山 幸浩, 伊神 剛, 上原 圭, 水野 隆史, 山口 淳平, 清水 大輔, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   DP - 5   2023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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  • 肛門管・直腸粘膜への進展を伴う肛門周囲Paget病に対する領域横断的手術治療戦略

    深田 浩志, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 川勝 章司, 中山 吾郎, 服部 憲史, 梅田 晋一, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   DP - 4   2023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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  • 局所再発直腸癌の最難関 側方再発への手術戦略

    上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太郎, 神原 祐一, 田根 雄一郎, 杉田 静紀, 川勝 章司, 渡辺 伸元, 砂川 真輝, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 梅田 晋一, 服部 憲史, 中山 吾郎, 伊神 剛, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   SF - 2   2023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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  • 右側結腸癌における病理学的転移陰性腫大間膜リンパ節の意義の検討

    村田 悠記, 小倉 淳司, 上原 圭, 小林 龍太朗, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 川勝 章司, 中山 吾郎, 服部 憲史, 梅田 晋一, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   SF - 2[Y]   2023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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  • 進行下部直腸癌に対する術前化学療法を基本とした治療戦略 Watch & Wait strategyを含めたresponse-guided strategyの導入経験

    小倉 淳司, 上原 圭, 村田 悠記, 小林 龍太朗, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 川勝 章司, 杉田 静紀, 梅田 晋一, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   123回   SF - 5   2023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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  • Crohn's disease-associated anorectal cancer has a poor prognosis with high local recurrence: a subanalysis of the Nationwide Japanese Study. 国際誌

    Takayuki Ogino, Tsunekazu Mizushima, Makoto Fujii, Yuki Sekido, Hidetoshi Eguchi, Riichiro Nezu, Hiroki Ikeuchi, Uchino Motoi, Kitaro Futami, Kinya Okamoto, Hisashi Nagahara, Kazuhiro Watanabe, Koji Okabayashi, Kazutaka Yamada, Hiroki Ohge, Shinji Tanaka, Yusuke Mizuuchi, Yoshiki Ohkita, Yu Sato, Hideki Ueno, Toru Kono, Michio Itabashi, Hideaki Kimura, Koya Hida, Yusuke Kinugasa, Kenichi Takahashi, Fumikazu Koyama, Tsunekazu Hanai, Kiyoshi Maeda, Toshihiro Noake, Yoshifumi Shimada, Takayuki Yamamoto, Junya Arakaki, Keiji Mastuda, Junji Okuda, Eiji Sunami, Yoshito Akagi, Kenji Kastumata, Kay Uehara, Takeshi Yamada, Shin Sasaki, Soichiro Ishihara, Yoichi Ajioka, Kenichi Sugihara

    The American journal of gastroenterology   2023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)  

    OBJECTIVES: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared to sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n=233) and sporadic CRC (n=129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer (CC) and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared to sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs. 71.17%, P<0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (HR 2.36, 95% CI: 1.54-3.62, P<0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared to sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. CONCLUSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

    DOI: 10.14309/ajg.0000000000002269

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  • Robot-assisted surgery for rectal cancer with solitary sacrococcygeal metastasis after neoadjuvant chemoradiotherapy: A case report.

    Hiroshi Saito, Masanori Kotake, Kenichi Ishibayashi, Daisuke Fujimori, Koichiro Sawada, Daisuke Yamamoto, Masahiro Oshima, Hironori Hayashi, Kaeko Oyama, Takuo Hara, Kay Uehara, Noriyuki Inaki

    Asian journal of endoscopic surgery   16 ( 3 )   563 - 566   2023年3月

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    記述言語:英語  

    An 81-year-old man was referred to our hospital for anal bleeding. Colonoscopy revealed a type 3 tumor at the upper rectum and biopsy showed adenocarcinoma. An enhanced circumferential lesion at the upper rectum and a solitary soft-tissue shadow at the fifth sacral vertebra to the coccyx were detected on abdominal magnetic resonance imaging. Fluorodeoxyglucose uptake was observed at the same sites on positron emission tomography. The patient was diagnosed with rectal cancer with isolated sacrococcygeal metastasis and was treated with neoadjuvant chemoradiotherapy followed by robotic surgery. Hartmann's operation was performed in the lithotomy position. The left internal iliac artery and vein were then divided. The internal pudendal artery and vein, the piriformis muscle, and sacrospinous ligament were also divided while preserving the lumbosacral trunk. The scheduled transection line of the sacral surface was fully exposed to prevent massive bleeding during sacrectomy. The dorsal surface of the sacrum was then exposed in the prone position and communicated with the pelvic space. The sacrum was transected at the superior margin of S3 and a specimen was extracted. Pathological findings revealed the infiltration of cancer cells in the sacrococcygeal specimen. The postoperative course was uneventful and the patient was discharged on postoperative day 13.

    DOI: 10.1111/ases.13184

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  • Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer. 国際誌

    Mikiko Takebayashi Kano, Toshio Kokuryo, Taisuke Baba, Kimitoshi Yamazaki, Junpei Yamaguchi, Masaki Sunagawa, Atsushi Ogura, Nobuyuki Watanabe, Shunsuke Onoe, Kazushi Miyata, Takashi Mizuno, Kay Uehara, Tsuyoshi Igami, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino

    Anticancer research   43 ( 3 )   1009 - 1016   2023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/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

    DOI: 10.21873/anticanres.16245

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  • Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer. 国際誌

    Kimitoshi Yamazaki, Toshio Kokuryo, Junpei Yamaguchi, Masaki Sunagawa, Atsushi Ogura, Nobuyuki Watanabe, Shunsuke Onoe, Kazushi Miyata, Takashi Mizuno, Kay Uehara, Tsuyoshi Igami, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino

    Anticancer research   43 ( 2 )   621 - 630   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/AIM: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. MATERIALS AND METHODS: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. RESULTS: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. CONCLUSION: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

    DOI: 10.21873/anticanres.16198

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  • Impact of preoperative muscle mass and quality on surgical outcomes in patients undergoing major hepatectomy for perihilar cholangiocarcinoma.

    Yuichi Asai, Junpei Yamaguchi, Takashi Mizuno, Shunsuke Onoe, Nobuyuki Watanabe, Tsuyoshi Igami, Kay Uehara, Yukihiro Yokoyama, Tomoki Ebata

    Journal of hepato-biliary-pancreatic sciences   30 ( 2 )   202 - 211   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)  

    PURPOSES: This study sought to define the impact of skeletal muscle mass and quality on postoperative outcomes in patients with perihilar cholangiocarcinoma. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma were included. The normalized total psoas area (TPA) (psoas muscle index [PMI]) and average Hounsfield units of the TPA (psoas muscle density [PMD]) were measured using preoperative computed tomography images. The cohort was dichotomized using the following indices: sex-specific lowest tertile (low PMI and low PMD) and other (normal PMI and normal PMD). Intraoperative and postoperative outcomes were compared, focusing on PMI and PMD. RESULTS: A total of 456 patients were analyzed. The intraoperative blood loss (IBL) was 21.3 ml/kg in the low PMI group and 17.2 ml/kg in the normal PMI group (P = .008). Patients in the low PMI or PMD group experienced postoperative infectious complications more frequently than those in the other groups. The median survival time was 37.8 months in the low PMI group and 54.2 months in the normal PMI group (P = .027). CONCLUSIONS: PMI and PMD were closely associated with IBL and postoperative infectious complications. Additionally, PMI impacted long-term survival. These results suggest an importance of improving muscle mass and quality before surgery.

    DOI: 10.1002/jhbp.1220

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  • 下部進行直腸癌における術前化学療法後の側方リンパ節縮小の意義の検討

    小倉 淳司, 上原 圭, 村田 悠記, 神原 祐一, 小池 佳勇, 三品 拓也, 小林 龍太郎, 宮田 一志, 水野 隆史, 山口 淳平, 國料 俊男, 梅田 晋一, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   76 ( 2 )   184 - 184   2023年2月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 免疫チェックポイント阻害薬により病理学的完全奏功が得られたMSI-High大腸癌腹壁限局播種再発・小腸間膜リンパ節転移の1例

    小林 龍太朗, 上原 圭, 小倉 淳司, 村田 悠記, 鳥居 直矢, 深田 浩志, 神原 祐一, 梅田 晋一, 服部 憲史, 中山 吾郎, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   76 ( 2 )   248 - 248   2023年2月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Current status of transanal total mesorectal excision for rectal cancer and the expanding indications of the transanal approach for extended pelvic surgeries. 国際誌

    Kay Uehara, Atsushi Ogura, Yuki Murata, Masanori Sando, Toshiki Mukai, Toshisada Aiba, Takeshi Yamamura, Masanao Nakamura

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   35 ( 2 )   243 - 254   2023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)  

    Transanal total mesorectal excision (taTME) has been rapidly accepted as a promising surgical approach to the distal rectum. The benefits include ease of access to the bottom of the deep pelvis linearly over a short distance in order to easily visualize the important anatomy. Furthermore, the distal resection margins can be secured under direct vision. Additionally, a two-team approach combining taTME with a transabdominal approach could decrease the operative time and conversion rate. Although taTME was expected to become more rapidly popularized worldwide, enthusiasm for it has stalled due to unfamiliar intraoperative complications, a lack of oncologic evidence from randomized trials, and the widespread use of robotic surgery. While international registries have reported favorable short- and medium-term outcomes from taTME, a Norwegian national study reported a high local recurrence rate of 9.5%. The characteristics of the recurrences included rapid, multifocal growth in the pelvis, which was quite different from recurrences following traditional transabdominal TME; thus, the Norwegian Colorectal Cancer Group reached a consensus for a temporary moratorium on the performance of taTME. To ensure acceptable baseline quality and patient safety, taTME should be performed by well-trained colorectal surgeons. Although the appropriate indications for taTME remain controversial, the transanal approach is extremely important as a means of goal setting in difficult TME cases and as an aid to the transabdominal approach in various types of extended pelvic surgeries. The benefits in transanal lateral lymph node dissection and pelvic exenteration are presented herein.

    DOI: 10.1111/den.14464

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  • Impact of combined resection of the internal iliac artery on loss of volume of the gluteus muscles after pelvic exenteration.

    Yuki Murata, Kay Uehara, Atsushi Ogura, Satoko Ishigaki, Toshisada Aiba, Takashi Mizuno, Toshio Kokuryo, Yukihiro Yokoyama, Hiroshi Yatsuya, Tomoki Ebata

    Surgery today   53 ( 7 )   791 - 799   2022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)  

    PURPOSE: To clarify the influence of additional internal iliac artery (IIA) resection on the loss of the gluteus muscle volume after pelvic exenteration (PE). METHODS: The subjects of this retrospective analysis were 78 patients who underwent PE with or without IIA resection (n = 44 and n = 34, respectively) between 2006 and 2018. The areas of gluteal muscles (GMs) and psoas muscles (PSMs) were calculated using CT images before and 6 months after PE, and the difference was compared. RESULTS: The volumes of the GMs and PSMs were significantly reduced after PE (P < 0.001 and P = 0.005, respectively). In the IIA resection group, the GMs were significantly reduced after surgery, but the PSMs were not. The maximum GM (Gmax) was the most atrophied among the GMs. Multivariable analysis revealed that complete IIA resection was an independent promotor of the loss of volume of the Gmax (P = 0.044). In 18 patients with unilateral IIA resection, the downsizing rate of the Gmax was significantly greater on the resected side than on the non-resected side (P = 0.008). CONCLUSIONS: The GMs and PSMs were significantly smaller after PE. Complete IIA resection reduced the Gmax area remarkably. Preservation of the superior gluteus artery is likely to help maintain Gmax size, suggesting a potential preventative measure against secondary sarcopenia.

    DOI: 10.1007/s00595-022-02635-z

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  • Minimum radial margin in pelvic exenteration for locally advanced or recurrent rectal cancer. 国際誌

    Toshisada Aiba, Kay Uehara, Yuta Tsuyuki, Atsushi Ogura, Yuki Murata, Takashi Mizuno, Junpei Yamaguchi, Toshio Kokuryo, Yukihiro Yokoyama, Tomoki Ebata

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology   48 ( 12 )   2502 - 2508   2022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)  

    PURPOSE: The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status. METHODS: Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0-1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately. RESULTS: The rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005). CONCLUSIONS: Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM.

    DOI: 10.1016/j.ejso.2022.06.015

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  • T4b大腸癌に対する腹腔鏡手術:手技の工夫と成績 cT4b大腸癌に対する腹腔鏡手術の適応と攻略法

    上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太郎, 神原 祐一, 深田 浩志, 野中 有紀子, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 杉田 静紀, 服部 憲史, 中山 吾郎, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   79 - 79   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 困難症例に対する大腸癌手術:手技の工夫と成績 他臓器浸潤結腸癌に対する腹腔鏡手術の実際と工夫

    小倉 淳司, 上原 圭, 村田 悠記, 鳥居 直矢, 小林 龍太朗, 深田 浩志, 野中 有紀子, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 中山 吾郎, 服部 憲史, 梅田 晋一, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   1875 - 1875   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 切除不能肺転移を有する直腸癌同時性切除可能肝転移に対する腹腔鏡下rescue liver resection

    水野 隆史, 小倉 淳司, 尾上 俊介, 村田 悠記, 川勝 章司, 伊神 剛, 宮田 一志, 杉田 静紀, 上原 圭, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   2508 - 2508   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 胆道解剖の変異を伴う症例に対する単孔式腹腔鏡下胆嚢摘出術における蛍光胆道鏡の有効性と限界

    伊神 剛, 上原 圭, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 小倉 淳司, 杉田 静紀, 川勝 章司, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   1365 - 1365   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • イマチニブ投与後に経肛門アプローチを併用して前方臓器温存し得た直腸巨大GISTの1例

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 砂川 真輝, 杉田 静紀, 梅田 晋一, 服部 憲史, 中山 吾郎, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   659 - 659   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 骨盤外科手術に必要な外科解剖-拡大手術、他臓器合併切除を安全に行うために- 局所進行・再発直腸癌に対する腹腔鏡下骨盤内臓全摘術の安全な導入に向けた取り組み umbilical 1stアプローチの有用性

    村田 悠記, 上原 圭, 小倉 淳司, 小林 龍太朗, 鳥居 直矢, 深田 浩志, 野中 有紀子, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 中山 吾郎, 服部 憲史, 梅田 晋一, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   908 - 908   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 進行再発直腸癌に対する腹腔鏡拡大手術:手技の工夫と成績 当科における局所再発直腸癌に対する腹腔鏡下拡大手術の治療成績

    深田 浩志, 上原 圭, 小倉 淳司, 村田 悠記, 鳥居 直矢, 小林 龍太朗, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 砂川 真輝, 杉田 静紀, 服部 憲史, 中山 吾郎, 江畑 智希

    日本内視鏡外科学会雑誌   27 ( 7 )   933 - 933   2022年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • Early volume loss of skeletal muscle after esophagectomy: a risk for late-onset postoperative pneumonia. 国際誌

    Koudai Nishimura, Kazushi Miyata, Masahide Fukaya, Yukihiro Yokoyama, Kay Uehara, Junpei Yamaguchi, Takashi Mizuno, Shunsuke Onoe, Atsushi Ogura, Tomoki Ebata

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus   35 ( 11 )   2022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)  

    Late-onset postoperative pneumonia (LOPP) after esophagectomy is poorly understood. This study was designed to clarify the features and risk factors for this event. Patients who underwent esophagectomy for esophageal cancer between 2006 and 2016 were included. LOPP was defined as radiologically proven pneumonia that occurred over 3 months after surgery, and clinically relevant late-onset postoperative pneumonia (CR-LOPP) was defined as LOPP that required administration of oxygen and antibiotics in the hospital and/or more intensive treatment. The total psoas muscle area (TPA) was measured using preoperative and postoperative (at 3 months after surgery) computed tomography scan images. Potential risk factors for CR-LOPP were investigated. Among 175 study patients, 46 (26.3%) had LOPP, 29 (16.6%) of whom exhibited CR-LOPP with a cumulative incidence of 15.6% at 3 years and 22.4% at 5 years. Four (13.8%) of these patients died of LOPP. Univariable analysis showed that clinical stage ≥III (P = 0.005), preoperative prognostic nutritional index (PNI) <45 (P = 0.035), arrhythmia (P = 0.014), postoperative hospital stay ≥40 days (P = 0.003), and percent decrease of TPA more than 5% (P < 0.001) were associated with CR-LOPP but not early onset postoperative pneumonia. Multivariable analysis revealed that clinical stage ≥III (hazard ratio [HR] 3.01, P = 0.004), postoperative hospital stay ≥40 days (HR 2.51, P = 0.015), and percent decrease of TPA >5% (HR 9.93, P < 0.001) were independent risk factors for CR-LOPP. CR-LOPP occurred in over 20% of patients at 5 years, and early postoperative loss of TPA was a potential trigger for this delayed complication.

    DOI: 10.1093/dote/doac019

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  • BRAF V600E変異陽性進行再発大腸癌の治療成績から考える転移巣切除の至適適応

    神野 孝徳, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 神原 祐一, 小林 龍太朗, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    日本癌治療学会学術集会抄録集   60回   OF - 3   2022年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • 肝門部領域胆管癌術後のComprehensive Complication Indexの至適な算出期間は?

    川勝 章司, 水野 隆史, 山口 淳平, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 伊神 剛, 上原 圭, 宮田 一志, 小倉 淳司, 村田 悠記, 國料 俊男, 横山 幸浩, 江畑 智希

    日本消化器外科学会雑誌   55 ( Suppl.2 )   241 - 241   2022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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  • 膵癌における栄養評価およびCA19-9に基づく術前予後層別化 非解剖学的バイオマーカーによるアプローチ

    尾上 俊介, 横山 幸浩, 伊神 剛, 上原 圭, 水野 隆史, 山口 淳平, 宮田 一志, 砂川 真輝, 渡辺 伸元, 小倉 淳司, 杉田 静紀, 村田 悠記, 川勝 章司

    日本消化器外科学会雑誌   55 ( Suppl.2 )   163 - 163   2022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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  • 高齢者に対する大腸がん治療の個別化を考える 術前CRP/Alb比高値と術後内臓脂肪面積減少は高齢者大腸癌患者の予後不良因子である

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本癌治療学会学術集会抄録集   60回   OWS9 - 2   2022年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌治療学会  

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  • Optimal diagnostic criteria for lateral lymph node dissection using magnetic resonance imaging: a multicenter prospective study. 国際誌

    Kazushige Kawai, Akio Shiomi, Takuya Miura, Kay Uehara, Jun Watanabe, Shinsuke Kazama, Hideki Ueno, Kazuhiro Sakamoto, Yusuke Kinugasa, Keiichi Takahashi, Koya Hida, Madoka Hamada, Soichiro Ishihara, Kenichi Sugihara

    ANZ journal of surgery   93 ( 1-2 )   206 - 213   2022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)  

    BACKGROUND: LLND in cases with suspected lateral lymph node (LLN) metastasis has been focused on as a novel treatment strategy in recent years. However, the optimal indication for LLND in rectal cancer patients has not been determined. This study aimed to establish the optimal indication for lateral lymph node dissection (LLND) in patients with rectal cancer using magnetic resonance imaging (MRI). METHODS: A total of 209 patients with rectal adenocarcinoma who underwent total mesorectal excision and LLND in 13 hospitals were prospectively registered. By matching the sizes of the harvested LNs and those in magnetic resonance imaging (MRI), the pathological outcome of each LN was confirmed one-by-one. Using parameters of the LLNs in MRI, the optimal diagnostic criteria for LLND were established. RESULTS: Of 3241 harvested LLNs, including 83 metastatic nodes, 1010 (31.1%) were visualized on MRI. Although all parameters assessed showed strong correlations with the presence of metastasis, none of these parameters could discriminate metastatic LLNs from non-metastatic nodes with sufficient sensitivity. However, by using the combination of long axis and short/long ratio in pretreatment MRI, we could establish optimal criteria for LLND. The sensitivity and specificity of the criteria for LLN metastasis were 94.3% and 40.2%, respectively. CONCLUSIONS: In conclusion, we established novel criteria for LLND in rectal cancer patients using MRI. Our criteria will be of great clinical use in determining indications for LLND.

    DOI: 10.1111/ans.18029

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  • 直腸癌術後異時性肝・肺転移に対して化学療法開始後1年7ヵ月でconversion切除し得た1例

    深田 浩志, 上原 圭, 小倉 淳司, 村田 悠記, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   75 ( 9 )   A221 - A221   2022年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 当院におけるMSI-High大腸癌に対する免疫チェックポイント阻害薬の臨床経験

    小林 龍太朗, 上原 圭, 小倉 淳司, 村田 悠記, 神原 祐一, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本大腸肛門病学会雑誌   75 ( 9 )   A149 - A149   2022年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 直腸癌術前集学的治療の成績:Watch & Waitを含めて 局所進行直腸癌に対する術前化学療法を基本とした治療戦略Tripletレジメンの臨床経験とWatch and Wait strategyの安全な導入

    小倉 淳司, 上原 圭, 村田 悠記, 鳥居 直矢, 小林 龍太朗, 深田 浩志, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   75 ( 9 )   A54 - A54   2022年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 困難な状況下でも良いストーマを造設する手技 腸管粘膜反転が困難な場合の対処法 煙突状ストーマ造設術の有用性について

    村田 悠記, 上原 圭, 小倉 淳司, 神原 祐一, 小林 龍太朗, 鳥居 直矢, 深田 浩志, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本大腸肛門病学会雑誌   75 ( 9 )   A69 - A69   2022年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Role of resection for extrahepatopulmonary metastases of colon cancer. 国際誌

    Takuya Mishina, Kay Uehara, Atsushi Ogura, Yuki Murata, Toshisada Aiba, Takashi Mizuno, Yukihiro Yokoyama, Tomoki Ebata

    Japanese journal of clinical oncology   52 ( 7 )   735 - 741   2022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: Although surgical resection for liver or lung metastases of colorectal cancer has been widely accepted, the use of this approach for extrahepatopulmonary metastases remains debatable due to the systemic nature of the disease. The aim of this study was to clarify the utility of resection along with perioperative chemotherapy for patients with extrahepatopulmonary metastases of colon cancer. METHODS: This is a retrospective single-arm study at a single institution. Forty-two patients with resectable extrahepatopulmonary metastases who underwent metastasectomy with curative intent between 2009 and 2018 at Nagoya University Hospital were retrospectively analyzed. The primary outcomes measured were overall and relapse-free survival. RESULTS: The most common metastatic site was the peritoneum (n = 31), followed by the distant lymph nodes (n = 10), ovary (n = 1) and spleen (n = 1), with overlaps. Preoperative and postoperative chemotherapies were administered to 22 and 8 patients, respectively; the remaining 14 patients received surgery alone. R0 resection was achieved in 36 patients (85.7%). The 5-year overall survival and 3-year relapse-free survival rates were 58.6% and 33.8%, respectively. In the univariate analysis, R1 resection was associated with a poor relapse-free survival rate (P = 0.02). In the multivariate analysis, the absence of perioperative chemotherapy was an independent risk factor for poor overall survival rates (P = 0.02). CONCLUSIONS: Surgical resection benefited selected patients with extrahepatopulmonary metastases with favorable long-term survival outcomes. Surgery alone without systemic chemotherapy is likely to bring poor outcome; therefore, preoperative induction might be promising to keep up with chemotherapy.

    DOI: 10.1093/jjco/hyac045

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  • Japanese multicenter prospective study investigating laparoscopic surgery for locally advanced rectal cancer with evaluation of CRM and TME quality (PRODUCT trial)

    Ichiro Takemasa, Atsushi Hamabe, Masaaki Ito, Shuichiro Matoba, Jun Watanabe, Suguru Hasegawa, Masanori Kotake, Masafumi Inomata, Kazuki Ueda, Kay Uehara, Kazuhiro Sakamoto, Masataka Ikeda, Tsunekazu Hanai, Tsuyoshi Konishi, Shigeki Yamaguchi, Daisuke Nakano, Shigeru Yamagishi, Kenji Okita, Atsushi Ochiai, Yoshiharu Sakai, Masahiko Watanabe

    Annals of Gastroenterological Surgery   6 ( 6 )   767 - 777   2022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)  

    AIM: In Japan, we have not been able to validate the results of laparoscopic surgery for locally advanced rectal cancer using the universal index "circumferential resection margin (CRM)." Previously, we established a semi-opened circular specimen processing method and validated its feasibility. In the PRODUCT trial, we aimed to assess CRM in patients with locally advanced rectal cancer who underwent laparoscopic rectal resection. METHODS: This was a multicenter, prospective, observational study. Eligible patients had histologically confirmed rectal adenocarcinoma located at or below 12 cm above the anal verge with clinical stage II or III and were scheduled for laparoscopic or robotic surgery. The primary endpoint was pathological CRM. CRM ≤1 mm was defined as positive. RESULTS: A total of 303 patients operated on between August 2018 and January 2020 were included in the primary analysis. The number of patients with clinical stage II and III was 139 and 164, respectively. Upfront surgery was performed for 213 patients and neoadjuvant therapy for 90 patients. The median CRM was 4.0 mm (IQR, 2.1-8.0 mm), and CRM was positive in 26 cases (8.6%). Univariate and multivariate analyses demonstrated that a predicted CRM from the mesorectal fascia of ≤1 mm on MRI was the significant factor for positive CRM (P = .0012 and P = .0045, respectively). CONCLUSION: This study showed the quality of laparoscopic rectal resection based on the CRM in Japan. Preoperative MRI is recommended for locally advanced rectal cancer to prevent CRM positivity.

    DOI: 10.1002/ags3.12592

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  • 術前CAR(CRP/albumin ratio)は高齢者大腸癌術後症例の予後予測因子である

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 横山 幸浩, 江畑 智希

    日本消化器外科学会総会   77回   P119 - 6   2022年7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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  • 切除可能同時性大腸癌肝転移症例に対する肝実質温存肝切除が生存率に与える影響

    村田 悠記, 水野 隆史, 上原 圭, 小倉 淳司, 宮田 一志, 山口 淳平, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    日本消化器外科学会総会   77回   P093 - 4   2022年7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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  • 遠位胆管癌における病理学的腫瘍浸潤長は術前CT検査で予測可能か?

    金森 明, 横山 幸浩, 伊神 剛, 水野 隆史, 山口 淳平, 尾上 俊介, 渡辺 伸元, 上原 圭, 宮田 一志, 江畑 智希

    日本消化器外科学会総会   77回   P142 - 2   2022年7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 proposal of drain removal criteria in hepatobiliary resection.

    Nobuyuki Watanabe, Takashi Mizuno, Junpei Yamaguchi, Yukihiro Yokoyama, Tsuyoshi Igami, Shunsuke Onoe, Kay Uehara, Masaki Sunagawa, Tomoki Ebata

    Journal of hepato-biliary-pancreatic sciences   29 ( 9 )   974 - 982   2022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: Standardized criteria for drain removal in hepatobiliary resection are lacking. Here, we evaluated the outcomes of delayed removal policy in this extended surgery. METHODS: Patients undergoing hepatectomy with biliary reconstruction between 2012 and 2018 were retrospectively reviewed. The drains were removed on postoperative day (POD) 7 when the drainage fluid was grossly serous, biochemically normal, and negative for bacterial contamination as assessed by Gram staining; additionally, no abnormal fluid collection was confirmed by computed tomography. Clinically relevant abdominal complications (CRACs), including biliary leakage, pancreatic fistula or intra-abdominal abscess, served as the primary outcome measure. RESULTS: Among 374 study patients, surgical drains were removed in 166 (44.3%) patients who met the criteria. Of these patients, 16 (9.6%) patients subsequently required additional drainage due to CRAC. Drains were retained and exchanged in 208 (55.6%) patients who did not meet the criteria. Of these, exchanged drains were soon removed in 34 patients due to no signs of CRAC. The diagnostic ability of the criteria revealed 0.916 sensitivity, 0.815 specificity, and 0.866 accuracy. CONCLUSION: The four findings on POD 7 worked well as criteria for drain removal, and these criteria may be helpful in drain management after hepatobiliary resection.

    DOI: 10.1002/jhbp.1194

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  • Management of inguinal lymph node metastases from rectal and anal canal adenocarcinoma. 国際誌

    Harunobu Sato, Kotaro Maeda, Yusuke Kinugasa, Hiroyasu Kagawa, Shunsuke Tsukamoto, Keiichi Takahashi, Hiroaki Nozawa, Yasumasa Takii, Tsuyoshi Konishi, Yoshito Akagi, Takeshi Suto, Shigeki Yamaguchi, Heita Ozawa, Koji Komori, Masayuki Ohue, Junichiro Hiro, Seiichi Shinji, Kazuhito Minami, Tomoharu Shimizu, Kazuhiro Sakamoto, Kay Uehara, Hiroshi Takahashi, Kenichi Sugihara

    Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland   24 ( 10 )   1150 - 1163   2022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)  

    AIM: The surgical treatment of inguinal lymph node (ILN) metastases secondary to anorectal adenocarcinoma remains controversial. This study aimed to clarify the surgical treatment and management of ILN metastasis according to its classification. METHODS: This retrospective, multi-centre, observational study included patients with synchronous or metachronous ILN metastases who were diagnosed with rectal or anal canal adenocarcinoma between January 1997 and December 2011. Treatment outcomes were analysed according to recurrence and prognosis. RESULTS: Among 1181 consecutively enrolled patients who received treatment for rectal or anal canal adenocarcinoma at 20 referral hospitals, 76 (6.4%) and 65 (5.5%) had synchronous and metachronous ILN metastases, respectively. Among 141 patients with ILN metastasis, differentiated carcinoma, solitary ILN metastasis and ILN dissection were identified as independent predictive factors associated with a favourable prognosis. No significant difference was found in the frequency of recurrence after ILN dissection between patients with synchronous (80.6%) or metachronous (81.0%) ILN metastases. Patients who underwent R0 resection of the primary tumour and ILN dissection had a 5-year survival rate of 41.3% after ILN dissection (34.1% and 53.1% for patients with synchronous and metachronous ILN metastases, respectively, P = 0.55). CONCLUSION: The ILN can be appropriately classified as a regional lymph node in rectal and anal canal adenocarcinoma. Moreover, aggressive ILN dissection might be effective in improving the prognosis of low rectal and anal canal adenocarcinoma with ILN metastases; thus, prophylactic ILN dissection is unnecessary.

    DOI: 10.1111/codi.16169

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  • 【肝胆膵癌におけるconversion therapy】胆道癌におけるconversion therapy 胆道癌conversion慎重な立場から 胆道癌におけるconversion therapyの現状と問題点

    高橋 大五郎, 水野 隆史, 尾上 俊介, 渡辺 伸元, 山口 淳平, 砂川 真輝, 上原 圭, 横山 幸浩, 江畑 智希

    肝胆膵   84 ( 5 )   669 - 677   2022年5月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • 腹腔鏡下直腸癌手術におけるエネルギーデバイスの選択 腹腔鏡下直腸癌手術におけるエネルギーデバイスの選択 電気メスを中心とした立場から

    上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太郎, 神原 祐一, 深田 浩志, 服部 憲史, 中山 吾郎, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本外科系連合学会誌   47 ( 3 )   413 - 413   2022年5月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 扁平上皮癌に悪性転化した仙尾部奇形腫の1例

    小林 龍太朗, 上原 圭, 小倉 淳司, 村田 悠記, 神原 祐一, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本外科系連合学会誌   47 ( 3 )   470 - 470   2022年5月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 【本邦の大腸癌治療の現状と展望-海外における標準治療と比較して】局所再発に対する治療選択と実践

    上原 圭, 小倉 淳司, 村田 悠記, 渡辺 伸元, 砂川 真輝, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    日本外科学会雑誌   123 ( 3 )   255 - 261   2022年5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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  • 【本邦の大腸癌治療の現状と展望-海外における標準治療と比較して】局所再発に対する治療選択と実践

    上原 圭, 小倉 淳司, 村田 悠記, 渡辺 伸元, 砂川 真輝, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    日本外科学会雑誌   123 ( 3 )   255 - 261   2022年5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  

    局所再発直腸癌に対する治療戦略はその病態の不均一性から治療は個々の症例に応じて選択すべきである.そのためには,手術技術を磨くことは当然のことであるが,近年発達著しい集学的治療の知識を身に着け,経験を積むことが必要不可欠である.性質上,無作為化比較試験からの情報を得ることが難しく,多くがセンター施設での経験に基づく指針ではあるが,本稿では,本邦および海外での局所再発直腸癌治療の現状と展望を述べる.(著者抄録)

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  • 【直腸癌局所再発に挑む-最新の治療戦略と手術手技】総論 局所再発直腸癌の治療方針 臓器温存手術や遠隔転移併存症例の手術適応も含めて

    村田 悠記, 上原 圭, 小倉 淳司, 杉田 静紀, 渡辺 伸元, 砂川 真輝, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    臨床外科   77 ( 5 )   514 - 519   2022年5月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>ポイント ◆局所再発直腸癌の治療ではR0切除がきわめて重要であり,R0達成のためには拡大切除を躊躇すべきでない.◆尿路機能温存のためには,少なくとも片側の骨盤神経を温存する.また膀胱後屈を避けるため,腸管再建や骨盤充填術の施行が望ましい.◆切除可能同時性遠隔転移を伴う症例も手術適応としている.ただし,切除の順序やタイミングは慎重に考慮すべきである.

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01539&link_issn=&doc_id=20220506510007&doc_link_id=10.11477%2Fmf.1407213704&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1407213704&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 高度肥満者に対する手術の工夫 高度肥満症例に対し"小さいが安全な術野"を連続させる腹腔鏡下大腸切除術

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 小林 龍太朗, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本外科系連合学会誌   47 ( 3 )   394 - 394   2022年5月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 他科と連携した骨盤内臓全摘術 骨盤部感染の低減/QOL向上を目指して

    村田 悠記, 上原 圭, 小倉 淳司, 神原 祐一, 小林 龍太朗, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本外科系連合学会誌   47 ( 3 )   421 - 421   2022年5月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • Feasibility of the semi-opened method of specimen resection for a circumferential resection margin in rectal cancer surgery: a multicenter study

    Ichiro Takemasa, Koichi Okuya, Kenji Okita, Masayuki Ishii, Masaaki Ito, Kay Uehara, Tsuyoshi Konishi, Shigeki Yamaguchi, Masafumi Inomata, Shintaro Sugita, Tadashi Hasegawa, Atsushi Ochiai, Yoshiharu Sakai, Masahiko Watanabe

    Surgery Today   2022年4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/s00595-022-02481-z

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    その他リンク: https://link.springer.com/article/10.1007/s00595-022-02481-z/fulltext.html

  • 悪性転化した仙尾部奇形腫の2例

    西村 元伸, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 神原 祐一, 小林 龍太朗, 神野 孝徳, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   DP - 8   2022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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  • 切除可能同時性肝転移症例の治療戦略 肝実質温存術式の有用性

    三品 拓也, 水野 隆史, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 神原 祐一, 西村 元伸, 小林 龍太朗, 服部 憲史, 中山 吾郎, 國料 俊男, 伊神 剛, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   SF - 7   2022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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  • 進行直腸癌に対する治療戦略【International】所進行直腸癌に対する術前化学療法におけるbevacizumabの意義の検討

    小倉 淳司, 上原 圭, 村田 悠記, 小池 佳男, 三品 拓也, 神原 祐一, 西村 元伸, 小林 龍太郎, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   PD - 1   2022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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  • 進行直腸癌に対する治療戦略【International】所進行直腸癌に対する術前化学療法におけるbevacizumabの意義の検討

    小倉 淳司, 上原 圭, 村田 悠記, 小池 佳男, 三品 拓也, 神原 祐一, 西村 元伸, 小林 龍太郎, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   PD - 1   2022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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  • 骨盤内臓全摘術後の骨盤死腔炎のリスク因子から考える対策法

    小林 龍太朗, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 三品 拓也, 神原 祐一, 西村 元伸, 服部 憲史, 中山 吾郎, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡邊 伸元, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   DP - 4   2022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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  • 悪性転化した仙尾部奇形腫の2例

    西村 元伸, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 神原 祐一, 小林 龍太朗, 神野 孝徳, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   DP - 8   2022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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  • 切除可能同時性肝転移症例の治療戦略 肝実質温存術式の有用性

    三品 拓也, 水野 隆史, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 神原 祐一, 西村 元伸, 小林 龍太朗, 服部 憲史, 中山 吾郎, 國料 俊男, 伊神 剛, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   SF - 7   2022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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  • 肝門部胆管癌の手術限界を考える 肝門部領域胆管癌肝切除における術中出血量の安全限界

    川勝 章司, 水野 隆史, 山口 淳平, 尾上 俊介, 渡辺 伸元, 伊神 剛, 上原 圭, 宮田 一志, 小倉 淳司, 國料 俊男, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   SY - 1   2022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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  • 骨盤内臓全摘術後の骨盤死腔炎のリスク因子から考える対策法

    小林 龍太朗, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 三品 拓也, 神原 祐一, 西村 元伸, 服部 憲史, 中山 吾郎, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡邊 伸元, 横山 幸浩, 江畑 智希

    日本外科学会定期学術集会抄録集   122回   DP - 4   2022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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  • 小細胞癌成分を含む胆管癌の2切除例

    南 貴之, 水野 隆史, 山口 淳平, 尾上 俊介, 渡辺 伸元, 伊神 剛, 上原 圭, 宮田 一志, 横山 幸浩, 江畑 智希

    日本消化器外科学会雑誌   55 ( 4 )   240 - 250   2022年4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  

    外科的切除後に対照的な経過を呈した胆管小細胞癌の2例を経験した.症例1は70歳の男性で,肝門部領域胆管癌に対して肝左葉尾状葉切除,肝外胆管切除を施行した.病理組織学的に乳頭腺癌と小細胞癌が混在する腺神経内分泌癌を認め,小細胞癌成分の静脈侵襲を認めた.進行度はpT2N0M0,fStage IIであった.術後にゲムシタビン単独療法を行ったが,術後4ヵ月目に多発肝再発を認め,5ヵ月目に原病死した.症例2は65歳の男性で,遠位胆管癌に対して亜全胃温存膵頭十二指腸切除を施行した.病理組織学的に神経内分泌癌(小細胞癌)を認め,進行度はpT2N1M0,fStage IIIと診断された.術後に,肺小細胞癌に準じてシスプラチン+エトポシド併用療法を4コース投与した.現在,術後8年無再発生存中である.胆管小細胞癌は根治切除後も早期再発する例が多く,肺小細胞癌に準じた薬物治療を含む集学的治療が必要である.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01117&link_issn=&doc_id=20220519490003&doc_link_id=1390010457709023488&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390010457709023488&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

  • 【ガイドラインには書いていない 大腸癌外科治療のCQ-妥当な治療と適応を見直そう】高度進行大腸癌への術前治療を分子標的薬別に考える Total neoadjuvant therapy・triplet時代における術前治療の最新エビデンス

    小倉 淳司, 上原 圭, 村田 悠記, 水野 隆史, 國料 俊男, 伊神 剛, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    臨床外科   77 ( 2 )   199 - 206   2022年2月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>ポイント ◆局所進行直腸癌に対し,術前CRTへの分子標的薬併用による局所制御・生存率への上乗せ効果は証明されていない.一方,NACやinduction chemotherapyへの分子標的薬併用による局所制御への上乗せ効果の報告は散見される.◆Stage IV・再発大腸癌では,分子標的薬を併用することで奏効率・腫瘍縮小率が上昇し,原発巣・遠隔転移巣ともR0切除やconversion手術のチャンスが増加する.◆"Cure"をめざした術前治療との併用こそが,分子標的薬の真の使いどころかもしれない.

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  • 【胆道癌治療の最前線】肝外胆管癌に対する手術術式と適応

    尾上 俊介, 水野 隆史, 渡辺 伸元, 横山 幸浩, 國料 俊男, 伊神 剛, 上原 圭, 山口 淳平, 宮田 一志, 砂川 真輝, 小倉 淳司, 江畑 智希

    外科   84 ( 2 )   136 - 141   2022年2月

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    記述言語:日本語   出版者・発行元:(株)南江堂  

    <文献概要>肝外胆管癌は,非治癒因子が存在しない限り根治切除をめざす.肝外胆管癌は肝門部領域胆管癌と遠位胆管癌に分類され,それぞれ尾状葉を伴う肝葉切除・肝外胆管切除術,膵頭十二指腸切除術(pancreaticoduodenectomy:PD)が標準術式となる.肝門部領域胆管癌に対する肝切除術式を決定する際はBismuth分類が有用である.遠位胆管癌のPDの術式は,胃切除範囲や再建法にバリエーションがあり,上腸間膜動脈周囲リンパ節郭清はリンパ節の適正評価に有用である.これら肝外胆管癌の手術適応は癌遺残度の可能性,血管浸潤,リンパ節転移などの腫瘍因子を考慮したうえで決定する.

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    その他リンク: https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00393&link_issn=&doc_id=20220128060007&doc_link_id=10.15106%2Fj_geka84_136&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka84_136&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • Stoma creation is associated with a low incidence of midline incisional hernia after colorectal surgery: the "fighting over the fascia" theory concerning the incision and stoma hole.

    Noriaki Ohara, Kay Uehara, Atsushi Ogura, Masanori Sando, Toshisada Aiba, Yuki Murata, Takashi Mizuno, Kokuryo Toshio, Yukihiro Yokoyama, Satoko Ishigaki, Yuanying Li, Hiroshi Yatsuya, Tomoki Ebata

    Surgery today   52 ( 6 )   953 - 963   2022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)  

    PURPOSE: Parastomal hernia (PH) develops more frequently than incisional hernia (IH) after colorectal surgery with stoma. This study evaluated our hypothesis that inward traction of the fascia when closing a midline incision widens the stoma hole and increases the incidence of PH. METHODS: A total of 795 patients who underwent colorectal resection between 2006 and 2016 were retrospectively analyzed. The risk classification was constructed from IH risk factors extracted from the non-stoma group. Then, the classification was extrapolated to the stoma group for predicting midline IH and PH. RESULTS: The incidence of IH was 5.3% in the stoma group and 12.5% in the non-stoma group (p = 0.005). PH developed in 19.6% of 97 patients with permanent stoma. The risk classification was able to predict PH without a significant difference but was well balanced in patients with permanent stoma; however, it failed to predict IH in the stoma group. CONCLUSION: The risk classification constructed from the non-stoma group was useful for predicting not midline IH but PH, suggesting that the stoma site was the most vulnerable for herniation. The "fighting over the fascia" theory between the midline incision and stoma hole may explain the causal relationship between the midline IH and PH.

    DOI: 10.1007/s00595-021-02434-y

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  • Direct Observation of Retinal Microvessels in Cancer Patients After Systemic Administration of Bevacizumab and Oxaliplatin. 国際誌

    Ayako Mitsuma, Yasuki Ito, Tomoya Shimokata, Chie Tanaka, Kay Uehara, Goro Nakayama, Hiroko Terasaki, Yuichi Ando

    Cancer diagnosis & prognosis   2 ( 3 )   330 - 335   2022年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIM: Antiangiogenic chemotherapy is the backbone of the various anticancer therapies. To date no practical biomarker predicting their antitumor effects and toxicity has been reported. We aimed to determine the feasibility of direct retinal observation as a practical biomarker in antiangiogenic chemotherapy. PATIENTS AND METHODS: By direct retinal observation using a nonmydriatic retinal camera, we measured retinal microvessel diameters in 10 patients with colorectal cancer before and after intravenous infusion of bevacizumab and oxaliplatin. All patients also received oral capecitabine during their therapy. RESULTS: Retinal microvessel diameters were decreased from baseline temporarily by 14.5±6.5% after infusion of bevacizumab and oxaliplatin in five patients who responded to treatment and 8.8±6.2% in the other five patients (p=0.008). CONCLUSION: Measurement of retinal microvessel diameters by direct observation appears to be feasible in patients receiving systemic chemotherapy. The decrease of retinal microvessel diameters might indicate improved tumor response to treatment with bevacizumab-containing systemic chemotherapy.

    DOI: 10.21873/cdp.10113

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  • 横行結腸・脾彎曲・下行結腸癌に対する郭清手技と治療成績 下行結腸癌 下行結腸癌に対するリンパ節郭清

    上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 神原 祐一, 西村 元伸, 小林 龍太郎, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 砂川 真輝, 杉田 静紀, 江畑 智希

    日本内視鏡外科学会雑誌   26 ( 7 )   PD16 - 1   2021年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 鏡視下での骨盤拡大手術の適応と限界 腹腔鏡下骨盤内臓全摘術の適応と限界

    上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 神原 祐一, 西村 元伸, 小林 龍太郎, 伊神 剛, 水野 隆史, 宮田 一志, 尾上 俊介, 砂川 真輝, 杉田 静紀, 江畑 智希

    日本内視鏡外科学会雑誌   26 ( 7 )   CSY17 - 2   2021年12月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 切除不能同時性肝肺転移を有する直腸癌に対してFOLFOXIRI+bevacizumab療法で奏功が得られ二期的にR0切除し得た1例

    村田 悠記, 水野 隆史, 上原 圭, 小倉 淳司, 三品 拓也, 小池 佳勇, 神原 祐一, 西村 元伸, 小林 龍太郎, 神野 孝徳, 國料 俊男, 伊神 剛, 山口 淳平, 宮田 一志, 尾上 俊介, 砂川 真輝, 渡辺 伸元, 杉田 静紀, 横山 幸浩, 江畑 智希

    日本消化器病学会東海支部例会プログラム抄録集   135回   81 - 81   2021年12月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-東海支部  

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  • 【conversion surgeryのすべて 切除不能を切除可能に!】局所進行直腸癌に対するconversion surgeryの現状と展望 術前化学療法を施行してきた立場から日本独自の治療戦略を考える

    小倉 淳司, 上原 圭, 村田 悠記, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    消化器外科   44 ( 13 )   1873 - 1885   2021年12月

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    記述言語:日本語   出版者・発行元:(株)へるす出版  

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  • 肝門部胆管癌術後,三度の右側大腸癌を切除した一例

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 鈴木 優美, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 佐藤 雄介, 服部 憲史, 中山 吾郎, 相場 利貞, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本消化器外科学会雑誌   54 ( Suppl.2 )   186 - 186   2021年11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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  • 【胆道狭窄の診断と治療】各論(治療) 肝門部領域胆管癌に対する手術適応と術式選択

    尾上 俊介, 水野 隆史, 渡辺 伸元, 横山 幸浩, 伊神 剛, 上原 圭, 山口 淳平, 砂川 真輝, 江畑 智希

    肝胆膵   83 ( 5 )   819 - 823   2021年11月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • Superiority of clinical American Joint Committee on Cancer T classification for perihilar cholangiocarcinoma.

    Mihoko Yamada, Takashi Mizuno, Junpei Yamaguchi, Yukihiro Yokoyama, Tsuyoshi Igami, Shunsuke Onoe, Nobuyuki Watanabe, Kay Uehara, Keitaro Matsuo, Tomoki Ebata

    Journal of hepato-biliary-pancreatic sciences   29 ( 7 )   768 - 777   2021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: Clinical tumor staging is essential information for making a therapeutic decision in cancer. This study aimed to identify the optimal tumor classification system for predicting resectability and survival probability in perihilar cholangiocarcinoma. METHODS: Patients who were treated for perihilar cholangiocarcinoma between 2009 and 2018 were enrolled. Local tumor extension was staged radiologically according to a diameter-based classification system in addition to the AJCC, Blumgart, and Bismuth systems. Survival and resectability were compared between T subgroups, and the discriminability of the four systems was assessed with Harrell's concordance index (C-index). RESULTS: Among 702 study patients, 559 (80.0%) underwent laparotomy, 489 (70.0%) of whom underwent resection. The resectability significantly decreased for more advanced tumors in all systems (P < .001); the AJCC system had the greatest discriminability for resectability (area under the curve 0.721). Overall survival at 5 years was 69.9% for AJCC cT1, 45.8% for cT2, 31.8% for cT3, and 15.3% for cT4 tumors (cT1 vs cT2; P = .002, cT2 vs cT3; P = .008 and cT3 vs cT4; P < .001). The AJCC system had the largest C-index of 0.627. CONCLUSIONS: The AJCC T system was the optimal classification system for predicting resectability and survival in perihilar cholangiocarcinoma.

    DOI: 10.1002/jhbp.1066

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  • Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma: Comparison Between H12345'8'-B-MHV and H1234-B. 国際誌

    Shimpei Otsuka, Takashi Mizuno, Junpei Yamaguchi, Shunsuke Onoe, Nobuyuki Watanabe, Yoshie Shimoyama, Tsuyoshi Igami, Kay Uehara, Yukihiro Yokoyama, Masato Nagino, Tomoki Ebata

    Annals of surgery   277 ( 3 )   e585-e591   2021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)  

    OBJECTIVE: The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. BACKGROUND: In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). METHODS: Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. RESULTS: Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% (P = 0.432) and 24% versus 0% in advanced tumors (P = 0.011). Tumor size ≥18 mm (P = 0.041), portal vein invasion (P = 0.009), and conventional LH (P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years (P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group (P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor (P = 0.009) along with ductal margin status (P = 0.030). CONCLUSIONS: The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.

    DOI: 10.1097/SLA.0000000000005248

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  • [Ⅱ.Treatment for Recurrent Cholangiocarcinoma].

    Nobuyuki Watanabe, Yukihiro Yokoyama, Tsuyoshi Igami, Kay Uehara, Takashi Mizuno, Junpei Yamaguchi, Kazushi Miyata, Shunsuke Onoe, Atsushi Ogura, Tomoki Ebata

    Gan to kagaku ryoho. Cancer & chemotherapy   48 ( 10 )   1223 - 1226   2021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)  

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  • Liver、Pancreas、Biliary Tract Cancer 肝・胆・膵癌 再発肝胆膵がんへの新たな挑戦 II.胆管癌切除後再発への治療方針

    渡辺 伸元, 横山 幸浩, 伊神 剛, 上原 圭, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 小倉 淳司, 江畑 智希

    癌と化学療法   48 ( 10 )   1223 - 1226   2021年10月

  • 他科連携で高難度手術を克服する 他科と連携した骨盤内臓全摘術 骨盤部感染の低減/QOL向上を目指して

    村田 悠記, 上原 圭, 小倉 淳司, 三品 拓也, 小池 佳勇, 神原 祐一, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S120 - S120   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 【Stepごとに要点解説 標準術式アトラス最新版】大腸 直腸癌 骨盤内臓全摘術

    小倉 淳司, 上原 圭, 村田 悠記, 三品 拓也, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 江畑 智希

    臨床外科   76 ( 11 )   128 - 137   2021年10月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

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  • 進行直腸癌に対する集学的治療 Total Neoadjuvant Therapyを見据えた、進行直腸癌に対する術前化学療法の治療奏効予測因子の検討

    三品 拓也, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 神原 祐一, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S343 - S343   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 肝十二指腸間膜の定型的リンパ節郭清

    水野 隆史, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 伊神 剛, 山口 淳平, 砂川 正輝, 國料 敏男, 上原 圭, 宮田 一志, 小倉 淳司, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S502 - S502   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • Bismuth I型胆管癌に対する肝門部胆管高位切離 肝切除を避けるために

    尾上 俊介, 水野 隆史, 渡辺 伸元, 横山 幸浩, 國料 俊男, 伊神 剛, 上原 圭, 山口 淳平, 宮田 一志, 砂川 真輝, 小倉 淳司, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S502 - S502   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 胆道癌肝切除における門脈切除・再建

    江畑 智希, 水野 隆史, 尾上 俊介, 渡辺 伸元, 伊神 剛, 山口 淳平, 上原 圭, 宮田 一志, 砂川 真輝, 小倉 淳司, 國料 俊男, 横山 幸浩

    日本臨床外科学会雑誌   82 ( 増刊 )   S503 - S503   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 肝門部領域胆管癌における膵内胆管の切除法 PDを避ける工夫

    渡辺 伸元, 水野 隆史, 尾上 俊介, 横山 幸浩, 國料 俊男, 伊神 剛, 上原 圭, 山口 淳平, 宮田 一志, 砂川 真輝, 小倉 淳司, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S503 - S503   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 骨盤内巨大Solitary fibrous tumorの2例

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S673 - S673   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 右側肝切除におけるArantius管を指標にした肝門部血管処理

    尾上 俊介, 水野 隆史, 渡辺 伸元, 横山 幸浩, 國料 俊男, 伊神 剛, 上原 圭, 山口 淳平, 宮田 一志, 砂川 真輝, 小倉 淳司

    日本臨床外科学会雑誌   82 ( 増刊 )   S504 - S504   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 腹腔鏡下仙骨合併腫瘍切除を施行した骨盤内巨大神経鞘腫の一例

    西村 元伸, 上原 圭, 小倉 淳司, 服部 憲史, 中山 吾郎, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本臨床外科学会雑誌   82 ( 増刊 )   S932 - S932   2021年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • Outcomes of robot-assisted versus conventional laparoscopic low anterior resection in patients with rectal cancer: propensity-matched analysis of the National Clinical Database in Japan. 国際誌

    T Matsuyama, H Endo, H Yamamoto, I Takemasa, K Uehara, T Hanai, H Miyata, T Kimura, H Hasegawa, Y Kakeji, M Inomata, Y Kitagawa, Y Kinugasa

    BJS open   5 ( 5 )   2021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)  

    BACKGROUND: Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy. METHODS: This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. RESULTS: Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). CONCLUSION: These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection.

    DOI: 10.1093/bjsopen/zrab083

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  • 当科におけるBRAF V600E変異陽性大腸癌に対するBRAF阻害剤併用療法の使用経験

    神野 孝徳, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 神原 祐一, 鈴木 優美, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   74 ( 9 )   A208 - A208   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 当科における局所進行結腸癌に対する術前化学療法の臨床経験

    小倉 淳司, 上原 圭, 小池 佳勇, 村田 悠記, 神野 孝徳, 鈴木 優美, 三品 拓也, 神原 祐一, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   74 ( 9 )   A200 - A200   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 会陰部に広範に自壊した局所再発直腸粘液癌に対し、仙骨合併骨盤内臓全摘術+複数の筋皮弁再建を施行し、R0切除を達成し得た一例

    神原 祐一, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 小池 佳勇, 鈴木 優美, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   74 ( 9 )   A204 - A204   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 結腸癌腹膜播種に対する外科切除の意義

    三品 拓也, 上原 圭, 小倉 淳司, 村田 悠記, 小池 佳勇, 鈴木 優美, 神原 祐一, 西村 元伸, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   74 ( 9 )   A209 - A209   2021年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index. 国際誌

    Shoji Kawakatsu, Junpei Yamaguchi, Takashi Mizuno, Nobuyuki Watanabe, Shunsuke Onoe, Tsuyoshi Igami, Yukihiro Yokoyama, Kay Uehara, Masato Nagino, Keitaro Matsuo, Tomoki Ebata

    Annals of surgery   2021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: To visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n=27; II, n=132; IIIa, n=290; IIIb, n=4; IVa, n=21; IVb, n=1; and V, n=9). The trajectory was categorized into 3 patterns: mild (n=209), moderate (n=235), and severe (n=40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. CONCLUSIONS: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.

    DOI: 10.1097/SLA.0000000000005162

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  • The carcinoembryonic antigen ratio is a potential predictor of survival in recurrent colorectal cancer.

    Yumi Suzuki, Atsushi Ogura, Kay Uehara, Toshisada Aiba, Noriaki Ohara, Yuki Murata, Takanori Jinno, Takuya Mishina, Yusuke Sato, Norifumi Hattori, Goro Nakayama, Yasuhiro Kodera, Tomoki Ebata

    International journal of clinical oncology   26 ( 7 )   1264 - 1271   2021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 carcinoembryonic antigen (CEA) "value" itself is often useless in patients with a normal CEA level at initial presentation and those with tumor-irrelevant elevated CEA. Although the unified marker using CEA has been desirable for recurrent tumor staging as well as for primary tumor staging, little is known concerning its relationship with the survival of patients with recurrent colorectal cancer in particular. METHODS: This retrospective historical study included patients who experienced disease relapse after curative surgery for stage I-III colorectal cancer between 2006 and 2018. A total of 129 patients with recurrent disease after curative surgery for colorectal cancer were included. We focused on the CEA "ratio" (CEA-R: the ratio of the CEA level at the time of recurrence to that measured 3 months before recurrence) and aimed to evaluate the correlation between CEA-R and survival in recurrent colorectal cancer. RESULTS: Patients with a high CEA-R (≥ 2) exhibited significantly worse 2 year survival than those with a low CEA-R (< 2) (88.1% vs. 44.9%, P < 0.001), irrespective of the CEA value before primary resection. Multivariate analyses demonstrated that the CEA-R (HR; 3.270, 95% CI 1.646-6.497, P = 0.001) was a significant prognostic factor. CONCLUSION: The CEA-R is a potential marker stratifying the survival of patients with disease relapse who exhibit aggressive biology at recurrent disease foci. As a novel marker, the CEA-R would serve as a clinical guide for tailoring treatment strategies at the time of disease relapse in patients with colorectal cancer.

    DOI: 10.1007/s10147-021-01919-7

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  • Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer. 国際誌

    Atsushi Ogura, Kay Uehara, Toshisada Aiba, Masanori Sando, Aya Tanaka, Noriaki Ohara, Yuki Murata, Yusuke Sato, Norifumi Hattori, Goro Nakayama, Tomoki Ebata, Yasuhiro Kodera, Masato Nagino

    European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology   47 ( 5 )   1005 - 1011   2021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)  

    INTRODUCTION: The oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC. MATERIALS AND METHODS: We examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed. RESULTS: In the median follow-up duration after surgery of 60 months (3-120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32-28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27-27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01-6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06-29.93, P = 0.043). CONCLUSION: NAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.

    DOI: 10.1016/j.ejso.2020.10.038

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  • クローン病再手術症例に対する腹腔鏡手術の検討

    服部 憲史, 中山 吾郎, 上原 圭, 相場 利貞, 佐藤 雄介, 小倉 淳司, 神田 光郎, 田中 千恵, 山田 豪, 小池 聖彦, 藤原 道隆, 江畑 智希, 小寺 泰弘

    日本外科学会定期学術集会抄録集   121回   PS - 2   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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  • 進行再発大腸癌における3次治療以降の予後予測因子の検討

    神野 孝徳, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 7   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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  • 大腸癌術後ストマ造設症例における腹壁瘢痕および傍ストマヘルニアの因果関係

    大原 規彰, 上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 神野 孝徳, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 8   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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  • 再発大腸癌における予後予測マーカーとしてのCEA比の有用性

    鈴木 優美, 小倉 淳司, 上原 圭, 相場 利貞, 大原 規彰, 村田 悠記, 神野 孝徳, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   PS - 1   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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  • 下部直腸癌術後患者の長期腎機能へ影響を与える因子の検討

    山東 雅紀, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 川井 覚, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 5   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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  • 直腸癌同時性肝転移に対する手術治療戦略

    米川 佳彦, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   PS - 8   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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  • 頸部リンパ節転移再発に対し二次治療が著効し病理学的完全奏効を得たRAS/BRAF V600E変異型横行結腸癌の1例

    村田 悠記, 上原 圭, 相場 利貞, 小倉 淳司, 深谷 昌秀, 宮田 一志, 田中 綾, 大原 規彰, 神野 孝徳, 江畑 智希

    日本消化器外科学会雑誌   54 ( 4 )   278 - 284   2021年4月

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

    今日,進行再発大腸癌治療において遺伝子検査は必要不可欠なものとなっている.中でもBRAF V600E変異症例の予後は極めて不良と報告され,その治療選択に悩むことは少なくない.今回,オキサリプラチンベースの術後補助化学療法が終了した直後の術後9ヵ月の早期に,頸部リンパ節再発を来し,BRAF V600E変異型で予後不良が予測された症例に対し,二次治療としてのFOLFIRI+aflibercept療法が著効し,切除により病理学的完全奏効を確認した1例を経験した.術後経過観察期間は9ヵ月とまだ短いが,外来で無再発,無治療で経過観察中である.予後不良とされるBRAF V600E変異型であっても野生型と同様に一定の全身コントロールが可能であれば,転移巣切除を考慮する意義はあると考えられた.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01117&link_issn=&doc_id=20210519510007&doc_link_id=10.5833%2Fjjgs.2020.0057&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2020.0057&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 再発大腸癌における予後予測マーカーとしてのCEA比の有用性

    鈴木 優美, 小倉 淳司, 上原 圭, 相場 利貞, 大原 規彰, 村田 悠記, 神野 孝徳, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   PS - 1   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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  • 進行再発大腸癌における3次治療以降の予後予測因子の検討

    神野 孝徳, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 7   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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  • 進行再発大腸癌に対する集学的アプローチの最先端 結腸癌非肝肺転移に対する外科切除の意義

    三品 拓也, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   WS - 2   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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  • 大腸癌術後ストマ造設症例における腹壁瘢痕および傍ストマヘルニアの因果関係

    大原 規彰, 上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 神野 孝徳, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 8   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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  • 局所進行直腸癌における術前化学療法後の病理学的リンパ節転移奏功度の意義

    相場 利貞, 上原 圭, 小倉 淳司, 大原 規彰, 神野 孝徳, 鈴木 優美, 三品 拓也, 村田 悠記, 渡辺 伸元, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 深谷 昌秀, 伊神 剛, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 5   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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  • 骨盤内臓全摘術後のサルコペニア 内腸骨動脈血管処理に着目して

    村田 悠記, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 神野 孝徳, 三品 拓也, 鈴木 優美, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 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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  • The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. 国際誌

    Hiroki Kobayashi, Krystyna A Gieniec, Josephine A Wright, Tongtong Wang, Naoya Asai, Yasuyuki Mizutani, Tadashi Lida, Ryota Ando, Nobumi Suzuki, Tamsin R M Lannagan, Jia Q Ng, Akitoshi Hara, Yukihiro Shiraki, Shinji Mii, Mari Ichinose, Laura Vrbanac, Matthew J Lawrence, Tarik Sammour, Kay Uehara, Gareth Davies, Leszek Lisowski, Ian E Alexander, Yoku Hayakawa, Lisa M Butler, Andrew C W Zannettino, M Omar Din, Jeff Hasty, Alastair D Burt, Simon J Leedham, Anil K Rustgi, Siddhartha Mukherjee, Timothy C Wang, Atsushi Enomoto, Masahide Takahashi, Daniel L Worthley, Susan L Woods

    Gastroenterology   160 ( 4 )   1224 - 1239   2021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 & AIMS: Cancer-associated fibroblasts (CAFs), key constituents of the tumor microenvironment, either promote or restrain tumor growth. Attempts to therapeutically target CAFs have been hampered by our incomplete understanding of these functionally heterogeneous cells. Key growth factors in the intestinal epithelial niche, bone morphogenetic proteins (BMPs), also play a critical role in colorectal cancer (CRC) progression. However, the crucial proteins regulating stromal BMP balance and the potential application of BMP signaling to manage CRC remain largely unexplored. METHODS: Using human CRC RNA expression data, we identified CAF-specific factors involved in BMP signaling, then verified and characterized their expression in the CRC stroma by in situ hybridization. CRC tumoroids and a mouse model of CRC hepatic metastasis were used to test approaches to modify BMP signaling and treat CRC. RESULTS: We identified Grem1 and Islr as CAF-specific genes involved in BMP signaling. Functionally, GREM1 and ISLR acted to inhibit and promote BMP signaling, respectively. Grem1 and Islr marked distinct fibroblast subpopulations and were differentially regulated by transforming growth factor β and FOXL1, providing an underlying mechanism to explain fibroblast biological dichotomy. In patients with CRC, high GREM1 and ISLR expression levels were associated with poor and favorable survival, respectively. A GREM1-neutralizing antibody or fibroblast Islr overexpression reduced CRC tumoroid growth and promoted Lgr5+ intestinal stem cell differentiation. Finally, adeno-associated virus 8 (AAV8)-mediated delivery of Islr to hepatocytes increased BMP signaling and improved survival in our mouse model of hepatic metastasis. CONCLUSIONS: Stromal BMP signaling predicts and modifies CRC progression and survival, and it can be therapeutically targeted by novel AAV-directed gene delivery to the liver.

    DOI: 10.1053/j.gastro.2020.11.011

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  • 直腸がんの治療戦略-内視鏡外科をどう活かすか? 骨盤拡大手術における内視鏡外科手術での後腹膜アプローチ

    上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 松村 卓樹, 三品 拓也, 大原 規彰, 鈴木 優美, 伊神 剛, 水野 隆史, 宮田 一志, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本内視鏡外科学会雑誌   25 ( 7 )   SSY5 - 3   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • The significance of the time to arterial perfusion in intraoperative ICG angiography during colorectal surgery. 国際誌

    Toshisada Aiba, Kay Uehara, Atsushi Ogura, Aya Tanaka, Yoshihiko Yonekawa, Norifumi Hattori, Goro Nakayama, Yasuhiro Kodera, Tomoki Ebata, Masato Nagino

    Surgical endoscopy   35 ( 12 )   7227 - 7235   2021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: Intraoperative indocyanine green angiography (ICG-A) is a promising tool to confirm blood supply; however, the assessment is difficult without clear demarcation. In this study, the clinical impact of the time to arterial perfusion (TAP) on anastomotic leakage (AL) was evaluated, especially in patients without ICG demarcation. METHODS: The TAP was assessed using ICG-A during colorectal surgery in 110 patients. ICG demarcation required changing the transection line, and the TAP was measured at the new stump. The patients were divided into marginal flow (MF) and direct flow (DF) groups according to the arterial route. Delayed TAP was defined as the third quartile or slower TAP in each group. RESULTS: Sixty-six patients (60%) were classified into the MF group, including 64 patients who underwent rectal or sigmoid resection with high ligation of the inferior mesenteric artery. The cut-off value of the delayed TAP in the MF group was significantly slower than that in the DF group (30 and 22 s, respectively, p < 0.001). In the entire cohort, the transection line was changed in 2 patients, resulting in no AL. Nevertheless, AL still developed in 6 patients (5.4%), 5 of whom were in the MF group, and delayed TAP was found in 5 of 6 patients. Delayed TAP was significantly associated with AL in the MF group (p = 0.046). CONCLUSIONS: In patients without ICG demarcation, delayed TAP might be helpful for predicting the high-risk patients with AL in the MF group; however, performing diverting stoma or strictly careful observation might be a realistic reaction.

    DOI: 10.1007/s00464-020-08185-0

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  • The survival benefit of neoadjuvant chemotherapy for resectable colorectal liver metastases with high tumor burden score.

    Yoshihiko Yonekawa, Kay Uehara, Takashi Mizuno, Toshisada Aiba, Atsushi Ogura, Toshiki Mukai, Yukihiro Yokoyama, Tomoki Ebata, Yasuhiro Kodera, Masato Nagino

    International journal of clinical oncology   26 ( 1 )   126 - 134   2021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: The indications for neoadjuvant chemotherapy (NAC) in resectable colorectal liver metastases (CRLMs) remain unclear. Tumor burden score (TBS) is a prognostic tool based on tumor size and number of tumors. However, its utility in the NAC setting for initially resectable CRLM has never been investigated. METHODS: TBS is a distance from the origin on a Cartesian plane to the coordinates (x, y) = (tumor size in centimeter, number of tumors). TBS < 3 was defined as "TBS-low", whereas TBS ≥ 3 as "TBS-high". Between 2008 and 2018, 102 patients who underwent hepatectomy for resectable CRLM were retrospectively analyzed using the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: Among the TBS-low (n = 46) and TBS-high (n = 56) groups, baseline patient characteristics were mostly similar except for TBS-related parameters. NAC was more frequently administered in the TBS-high group (p = 0.038). The overall survival (OS) rates were similar between the two groups. Subgroup analysis showed that NAC was associated with non-significantly improved 5-year OS in the TBS-high group [76.1% with NAC and 54.9% without NAC (p = 0.093)]. In multivariate analysis, NAC was an independent prognostic factor for favorable OS only in the TBS-high group, while adjuvant chemotherapy (AC) was associated with improved OS only in the TBS-low group. CONCLUSION: In patients with resectable CRLM, the TBS-high population had a survival benefit from NAC, while the TBS-low population benefited from AC. TBS may serve as an indicator for patients who will benefit from NAC.

    DOI: 10.1007/s10147-020-01793-9

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  • 消化管腫瘍の新展開 進行消化管癌における集学的治療の実際と課題 局所進行直腸癌に対する術前化学療法の効果と限界

    上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 神野 孝徳, 村田 悠記, 三品 拓也, 鈴木 優美, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 小寺 泰弘, 江畑 智希

    日本消化管学会雑誌   5 ( Suppl. )   142 - 142   2021年1月

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    記述言語:日本語   出版者・発行元:(一社)日本消化管学会  

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  • The role of surgery for locally recurrent and second recurrent rectal cancer with metastatic disease. 国際誌

    Aya Tanaka, Kay Uehara, Toshisada Aiba, Atsushi Ogura, Toshiki Mukai, Yukihiro Yokoyama, Tomoki Ebata, Yasuhiro Kodera, Masato Nagino

    Surgical oncology   35   328 - 335   2020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 role of surgery for locally recurrent rectal cancer (LRRC) with resectable distant metastases or second LRRC remains unclear. This study aimed to clarify the influence of synchronous distant metastases (SDMs), a history of distant metastasis resection (HDMR), and a second LRRC on the outcome. METHODS: The long-term outcomes of 70 surgically treated patients with LRRC between 2006 and 2018 were compared by SDM (n = 10), HDMR (n = 17), and second LRRC (n = 7). RESULTS: Among the 10 patients with SDM, 4 patients underwent simultaneous resection, whereas the other 6 underwent staged resection with distant first approach. Recurrence developed in 9 patients, of which 2 patients with liver re-resection achieved long-term survival without cancer. The patients with and without SDM had equivalent 5-year overall survival rate (40.5% vs. 53.3%, p = 0.519); however, patients with SDM had a worse 3-year recurrence-free survival rate than those without SDM (10.0% vs. 37.5%, p = 0.031). Multivariate analysis showed that primary non-sphincter-preserving surgery, second LRRC, and R1 resection were independent risk factors for overall survival. Similarly, primary non-sphincter-preserving surgery, second LRRC, SDM, and R1 resection were risk factors for recurrence-free survival. CONCLUSIONS: Patients with SDM might still be suitable to undergo salvage surgery and achieve favourable overall survival. Distant metastasectomy should be performed first, followed by a sufficient interval to avoid unnecessary LRRC resection in uncurable patients. An HDMR should not be taken into consideration when making surgical plans. Surgical indication of second LRRC should be strict, especially in referred patients.

    DOI: 10.1016/j.suronc.2020.09.001

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  • Pelvic exenteration associated with future renal dysfunction.

    Masanori Sando, Kay Uehara, Yuanying Li, Toshisada Aiba, Atsushi Ogura, Tomoki Ebata, Yasuhiro Kodera, Hiroshi Yatsuya, Masato Nagino

    Surgery today   50 ( 12 )   1601 - 1609   2020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)  

    PURPOSE: This study aimed to clarify the long-term change in the renal function after pelvic exenteration (PE) and to evaluate the risk factors for any future dysfunction. METHODS: This study comprised 40 patients. A greater than 25% decline in the estimated glomerular filtration rate (eGFR) at 3 years was defined as early renal function disorder (ERFD), possibly predicting future chronic kidney disease (CKD). RESULTS: In the entire cohort, the median eGFR decreased by 23% at 3 years, and CKD developed in 50%. The patients were divided into the ERFD (n = 16) and non-ERFD (n = 24) groups. In the ERFD group, the eGFR significantly decreased by 28% during the first 1.5 years and continued to decline after that, resulting in 81.3% of patients reaching CKD, whereas it was 4% and 37.5%, respectively, in the non-ERFD group. In a growth model analysis, late urinary tract complications (UTC) and small bowel obstruction were shown to be risk factors for ERFD. CONCLUSION: Although PE was associated with a high incidence of future CKD, ERFD could predict it. Close observation of the eGFR decline over 1.5 years might be beneficial to identify ERFD patients. High-risk patients with late UTC and small bowel obstruction should, therefore, be observed carefully.

    DOI: 10.1007/s00595-020-02036-0

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  • 各領域におけるロボット支援手術 当院でのダヴィンチシステムを用いた食道手術の現状

    宮田 一志, 深谷 昌秀, 石井 健太, 西村 廣大, 鳥居 直矢, 江畑 智希, 横山 幸浩, 伊神 剛, 上原 圭, 水野 隆史, 山口 淳平, 尾上 俊介, 相場 利貞, 渡辺 伸元, 梛野 正人

    日本外科系連合学会誌   45 ( 5 )   538 - 538   2020年12月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 食道癌ハイリスク症例に対する二期分割手術の短期成績

    深谷 昌秀, 宮田 一志, 石井 健太, 西村 廣大, 米川 佳彦, 江畑 智希, 横山 幸浩, 伊神 剛, 上原 圭, 梛野 正人

    日本食道学会学術集会プログラム・抄録集   74回   163 - 163   2020年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本食道学会  

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  • What is the impact of systemic chemotherapy for lateral lymph nodes in patients with locally advanced low rectal cancer? 国際誌

    Atsushi Ogura, Kay Uehara, Toshisada Aiba, Norifumi Hattori, Goro Nakayama, Osamu Maeda, Yuichi Ando, Yasuhiro Kodera, Tomoki Ebata, Masato Nagino

    International journal of colorectal disease   35 ( 11 )   2073 - 2080   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)  

    PURPOSE: Systemic chemotherapy (SC) before surgery is a potential treatment to improve survival in patients with advanced rectal cancer. However, the impact of SC on lateral lymph nodes (LLNs) remains unclear. METHODS: A total of 78 patients with stage II/III low rectal cancer, who received 3-month oxaliplatin-based SC followed by LLN dissection (LLND) in principle, were analysed retrospectively. "Total lateral lymph node metastases (tLLNMs)" was defined as having either pathological LLNMs (pLLNMs) or lateral local recurrences (LLRs). Patients with the maximum short-axis size of LLNs ≥ 7 mm were classified into the swollen group (n = 21). RESULTS: In the total cohort, tLLNMs included 6 pLLNMs (7.7%) and 2 LLRs (2.6%). In the non-swollen group, no patients had pLLNMs, but one had LLR (1.8%). In the swollen group, pLLNMs and LLRs were detected in 6 (28.6%) and 1 (4.8%), respectively. The swollen group was an independent risk factor for tLLNMs (P < 0.001), leading to the significantly worse 5-year relapse-free survival (RFS) of 52.4% than the others. CONCLUSION: For patients without swollen LLNs, SC could allow for omission both of lateral irradiation and LLND. For patients with swollen LLNs, the lateral local control was favourable after SC and LLND without chemoradiotherapy (CRT); however, oxaliplatin-based SC might be insufficient to improve survival, requiring more intensive chemotherapy. CRT should be indicated according to the other risk factors of central local recurrence, although the swollen LLNs should be removed.

    DOI: 10.1007/s00384-020-03690-z

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  • 大腸 症例(悪性)

    村田 悠記, 上原 圭, 相場 利貞, 小倉 淳司, 山東 雅紀, 田中 綾, 大原 規彰, 神野 孝徳, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 江畑 智希, 小寺 泰弘, 梛野 正人

    日本消化器外科学会雑誌   53 ( Suppl.2 )   210 - 210   2020年11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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  • 【大腸癌術前治療up-to-date】大腸癌術前化学療法のup-to-date

    上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 10 )   417 - 423   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

    本邦での遠隔転移を伴わない局所進行大腸癌の標準治療は手術+術後補助化学療法であるものの,その治療成績が満足できるものとはいい難い.一方,近年の著しい薬物療法の進歩を背景に,術前化学療法(NAC)は日常臨床の中で徐々に普及しているが,その長期成績は明らかでない.直腸癌に対する術前化学療法(NAC)は欧米では放射線化学療法(CRT)を省略することになり,高リスク症例では受け入れられ難い.しかし,術前治療を一般的に行って来なかった本邦では,NACは単に術後補助化学療法の前倒しであり,可能な施設に限りがあるCRTと比較して,多くの施設で受け入れられやすい.NACはCRTと比較して局所効果はやや劣るものの,生存率は遜色ない.今後は,リスク分類により個別化治療を提供していく必要がある.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01146&link_issn=&doc_id=20201202370004&doc_link_id=10.3862%2Fjcoloproctology.73.417&url=https%3A%2F%2Fdoi.org%2F10.3862%2Fjcoloproctology.73.417&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • 高齢大腸癌患者に対する外科治療の成績

    相場 利貞, 上原 圭, 小倉 淳司, 山東 雅紀, 田中 綾, 大原 規彰, 神野 孝徳, 村田 悠記, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 江畑 智希, 小寺 泰弘, 梛野 正人

    日本消化器病学会雑誌   117 ( 臨増大会 )   A717 - A717   2020年10月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 局所進行・再発直腸癌に対する安全な手術手技 局所再発直腸癌の最難関"Sacroiliac recurrence"に対する挑戦と安全な手術手技

    小倉 淳司, 上原 圭, 相場 利貞, 田中 綾, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本臨床外科学会雑誌   81 ( 増刊 )   262 - 262   2020年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • Chemotherapy-free intervalを得るため積極的に手術適応としたBRAF V600E変異型盲腸癌腹膜播種再発の1例

    神野 孝徳, 上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 9 )   A185 - A185   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 直腸癌に対する術前治療の現状と展望 下部進行直腸癌に対するpatient-adopted strategyを目指した当科の術前治療と成績

    小倉 淳司, 上原 圭, 相場 利貞, 田中 綾, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 9 )   A52 - A52   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 骨盤内臓全摘術の手術手技と成績 骨盤内臓全摘術の基本と応用

    上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 9 )   A68 - A68   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Importance of the neoadjuvant rectal (NAR) score to the outcome of neoadjuvant chemotherapy alone for locally advanced rectal cancer.

    Toshiki Mukai, Keisuke Uehara, Toshisada Aiba, Atsushi Ogura, Toyonori Tsuzuki, Aya Tanaka, Masanori Sando, Noriyuki Ohara, Yusuke Sato, Norifumi Hattori, Goro Nakayama, Yasuhiro Kodera, Masato Nagino

    Surgery today   50 ( 8 )   912 - 919   2020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)  

    PURPOSE: The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. However, its effectiveness after neoadjuvant chemotherapy (NAC) alone has not been fully investigated. METHODS: We analyzed data retrospectively on 61 patients with rectal cancer, who received NAC followed by surgical resection between 2010 and 2015, and evaluated the impact of the NAR score on survival. RESULTS: The median NAR score was 14.9. Of the 61 patients, 13, 35, and 13 were classified as having NAR-low (< 8), NAR-intermediate (8-16), and NAR-high (> 16) scores, respectively. The median observation period was 49.0 months. According to the NAR score, the 3-year DFS in the NAR-low group was 100%, which was significantly better than that in the NAR-intermediate (64.8%, p = 0.041), and NAR-high (61.5%, p = 0.018) groups. When the NAR-intermediate and NAR-high groups were investigated as a single high-risk group, the 3-year DFS of the patients who received adjuvant chemotherapy was 88.7%, which was significantly better than that of the patients who did not receive adjuvant chemotherapy (53.3%, p = 0.042). CONCLUSIONS: The NAR score may predict the DFS and could serve as a favorable indicator of adjuvant chemotherapy after NAC alone.

    DOI: 10.1007/s00595-020-01964-1

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  • Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan. 国際誌

    Hiroya Taniguchi, Keisuke Uehara, Goro Nakayama, Hiroshi Nakayama, Toshisada Aiba, Norifumi Hattori, Masato Kataoka, Yasuyuki Nakano, Yoshihisa Kawase, Osamu Okochi, Hiroshi Matsuoka, Setsuo Utsunomiya, Eiji Sakamoto, Yoshinori Mori, Shinichi Umeda, Toshio Shikano, Koji Komori, Masahiro Tajika, Shigenori Kadowaki, Kei Muro, Yasushi Yatabe

    Translational oncology   13 ( 7 )   100786 - 100786   2020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: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAFV600E, BRAFnon-V600E, and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAFV600E and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC.

    DOI: 10.1016/j.tranon.2020.100786

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  • International consensus on natural orifice specimen extraction surgery (NOSES) for gastric cancer (2019). 国際誌

    Xu Guan, Zheng Liu, Amjad Parvaiz, Antonio Longo, Avanish Saklani, Ali A Shafik, Jian-Chun Cai, Charles Ternent, Lin Chen, Cuneyt Kayaalp, Fatih Sumer, Fernanda Nogueira, Feng Gao, Fang-Hai Han, Qing-Si He, Ho-Kyung Chun, Chang-Ming Huang, Hai-Yang Huang, Rui Huang, Zhi-Wei Jiang, Jim S Khan, Joaquim Manuel da, Costa Pereira, Joseph W Nunoo-Mensah, Jung Tack Son, Liang Kang, Keisuke Uehara, Ping Lan, Le-Ping Li, Han Liang, Bing-Rong Liu, Juan Liu, Dan Ma, Ming-Yin Shen, Mohammad Rashidul Islam, Narimantas Evaldas Samalavicius, Kai Pan, Petr Tsarkov, Xin-Yu Qin, Ricardo Escalante, Sergey Efetov, Seung Kyu Jeong, Suk-Hwan Lee, Dong-Hui Sun, Li Sun, Tatiana Garmanova, Yan-Tao Tian, Gui-Yu Wang, Guo-Jun Wang, Guo-Rong Wang, Xiao-Qiang Wang, William Tzu-Liang Chen, Woo Yong Lee, Su Yan, Zu-Li Yang, Gang Yu, Pei-Wu Yu, Dan Zhao, Yun-Shi Zhong, Jian-Ping Wang, Xi-Shan Wang

    Gastroenterology report   8 ( 1 )   5 - 10   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)  

    At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.

    DOI: 10.1093/gastro/goz067

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  • Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer.

    Yojiro Hashiguchi, Kei Muro, Yutaka Saito, Yoshinori Ito, Yoichi Ajioka, Tetsuya Hamaguchi, Kiyoshi Hasegawa, Kinichi Hotta, Hideyuki Ishida, Megumi Ishiguro, Soichiro Ishihara, Yukihide Kanemitsu, Yusuke Kinugasa, Keiko Murofushi, Takako Eguchi Nakajima, Shiro Oka, Toshiaki Tanaka, Hiroya Taniguchi, Akihito Tsuji, Keisuke Uehara, Hideki Ueno, Takeharu Yamanaka, Kentaro Yamazaki, Masahiro Yoshida, Takayuki Yoshino, Michio Itabashi, Kentaro Sakamaki, Keiji Sano, Yasuhiro Shimada, Shinji Tanaka, Hiroyuki Uetake, Shigeki Yamaguchi, Naohiko Yamaguchi, Hirotoshi Kobayashi, Keiji Matsuda, Kenjiro Kotake, Kenichi Sugihara

    International journal of clinical oncology   25 ( 1 )   1 - 42   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)  

    The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

    DOI: 10.1007/s10147-019-01485-z

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  • Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II).

    Norifumi Hattori, Goro Nakayama, Keisuke Uehara, Toshisada Aiba, Kiyoshi Ishigure, Eiji Sakamoto, Yuichiro Tojima, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Masahiko Koike, Michitaka Fujiwara, Masato Nagino, Yasuhiro Kodera

    International journal of clinical oncology   25 ( 1 )   118 - 125   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)  

    OBJECTIVE: This multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer. METHODS: Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1-14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety. RESULTS: A total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57-86%) and 96% (95% CI 80-99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively. CONCLUSION: CapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

    DOI: 10.1007/s10147-019-01546-3

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  • Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. 国際誌

    Atsushi Ogura, Tsuyoshi Konishi, Geerard L Beets, Chris Cunningham, Julio Garcia-Aguilar, Henrik Iversen, Shigeo Toda, In Kyu Lee, Hong Xiang Lee, Keisuke Uehara, Peter Lee, Hein Putter, Cornelis J H van de Velde, Harm J T Rutten, Jurriaan B Tuynman, Miranda Kusters

    JAMA surgery   154 ( 9 )   e192172   2019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)  

    Importance: Previously, it was shown in patients with low rectal cancer that a short-axis (SA) lateral node size of 7 mm or greater on primary magnetic resonance imaging (MRI) resulted in a high lateral local recurrence (LLR) rate after chemoradiotherapy or radiotherapy ([C]RT) with total mesorectal excision (TME) and that this risk was lowered by a lateral lymph node dissection (LLND). The role of restaging MRI after (C)RT with regard to LLR risk and which specific patients might benefit from an LLND is not fully understood. Objective: To determine the factors on primary and restaging MRI that are associated with LLR in low rectal cancer after (C)RT and to formulate specific guidelines on which patients might benefit from an LLND. Design, Setting, and Participants: In this retrospective, multicenter, pooled cohort study, patients who underwent surgery for cT3 or cT4 low rectal cancer with a curative intent from 12 centers in 7 countries from January 2009 to December 2013 were included. All patients' MRIs were rereviewed according to a standardized protocol, with specific attention to lateral nodal features. The original cohort included 1216 patients. For this study, patients who underwent (C)RT and had a restaging MRI were selected, leaving 741 for analyses across 10 institutions, including 651 who underwent (C)RT with TME and 90 who underwent (C)RT with TME and LLND. Main Outcomes and Measures: The main purpose was to identify the factors on primary and restaging MRI associated with LLR after (C)RT with TME. Whether high-risk patients might benefit in terms of LLR reduction from an LLND was also studied. Results: Of the 741 included patients, 480 (64.8%) were male, and the mean (SD) age was 60.4 (12.0) years. An SA lateral node size of 7 mm or greater on primary MRI resulted in a 5-year LLR rate of 17.9% after (C)RT with TME. At 3 years, there were no LLRs in 28 patients (29.2%) with lateral nodes that were 4 mm or less on restaging MRI. Nodes that were 7 mm or greater on primary MRI and greater than 4 mm on restaging MRI in the internal iliac compartment resulted in a 5-year LLR rate of 52.3%, significantly higher compared with nodes in the obturator compartment of that size (9.5%; hazard ratio, 5.8; 95% CI, 1.6-21.3; P = .003). Compared with (C)RT with TME alone, treatment with (C)RT with TME and LLND in these unresponsive internal nodes resulted in a significantly lower LLR rate of 8.7% (hazard ratio, 6.2; 95% CI, 1.4-28.5; P = .007). Conclusions and Relevance: Restaging MRI is important in clinical decision making in lateral nodal disease. In patients with shrinkage of lateral nodes from an SA node size of 7 mm or greater on primary MRI to an SA node size of 4 mm or less on restaging MRI, which occurs in about 30% of cases, LLND can be avoided. However, persistently enlarged nodes in the internal iliac compartment indicate an extremely high risk of LLR, and an LLND lowered LLR in these cases.

    DOI: 10.1001/jamasurg.2019.2172

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  • Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial). 国際誌

    Keisaku Kondo, Satoshi Matsusaka, Soichiro Ishihara, Hisanaga Horie, Keisuke Uehara, Masahiko Oguchi, Keiko Murafushi, Masashi Ueno, Nobuyuki Mizunuma, Taiju Shimbo, Daiki Kato, Junji Okuda, Yojiro Hashiguchi, Masanori Nakazawa, Eiji Sunami, Kazushige Kawai, Hideomi Yamashita, Tohru Okada, Yuichi Ishikawa, Masashi Fujii, Toshifusa Nakajima

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology   134   199 - 203   2019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)  

    PURPOSE: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study. PATIENTS AND METHODS: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m2/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity. RESULTS: Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively. CONCLUSIONS: The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.

    DOI: 10.1016/j.radonc.2019.02.006

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  • Neoadjuvant CAPOX and bevacizumab alone for locally advanced rectal cancer: long-term results from the N-SOG 03 trial.

    Akihiro Tomida, Keisuke Uehara, Kazuhiro Hiramatsu, Atsuyuki Maeda, Eiji Sakamoto, Yoshito Okada, Yasuhiro Kurumiya, Goro Nakayama, Masanao Nakamura, Toshisada Aiba, Masato Nagino

    International journal of clinical oncology   24 ( 4 )   403 - 410   2019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: Neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains an experimental treatment, and the efficacy in terms of long-term outcome has not been fully elucidated. The N-SOG 03 trial examined the safety and efficacy of neoadjuvant CAPOX and bevacizumab (Bev) without radiotherapy in patients with poor-risk LARC. METHODS: Thirty-two patients with MRI-defined LARC received neoadjuvant CAPOX and Bev followed by curative resection between 2010 and 2011. The overall survival (OS), progression-free survival (PFS), and local-relapse rate (LRR) were calculated using the Kaplan-Meier method, and the risk factors were evaluated by multivariate analysis using the Cox proportional hazard models. This trial is registered with UMIN, number 000003507. RESULTS: In the entire cohort, the 5-year OS was 81.3%. Because of disease progression during chemotherapy, 3 patients ultimately did not undergo curative surgery. As a result, 29 patients underwent R0/1 resection. Among these 29 patients, the 5-year OS, PFS, and LRR were 89.7%, 72.4% and 13.9%, respectively. In multivariate analysis, cT4b tumor was an independent poor prognostic factor for OS and LRR, and ypT4b tumor and absence of N down-staging were independent poor prognostic factors for PFS. CONCLUSIONS: Patients with cT4b tumor were not suitable for NAC alone. However, the long-term outcomes of the other patients were satisfactory, and NAC alone might be an option for treatment of LARC. N down-staging was likely to bring favorable PFS, even in patients with cStage III.

    DOI: 10.1007/s10147-018-1372-6

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  • International consensus on natural orifice specimen extraction surgery (NOSES) for colorectal cancer. 国際誌

    Xu Guan, Zheng Liu, Antonio Longo, Jian-Chun Cai, William Tzu-Liang Chen, Lu-Chuan Chen, Ho-Kyung Chun, Joaquim Manuel da Costa Pereira, Sergey Efetov, Ricardo Escalante, Qing-Si He, Jun-Hong Hu, Cuneyt Kayaalp, Seon-Hahn Kim, Jim S Khan, Li-Jen Kuo, Atsushi Nishimura, Fernanda Nogueira, Junji Okuda, Avanish Saklani, Ali A Shafik, Ming-Yin Shen, Jung-Tack Son, Jun-Min Song, Dong-Hui Sun, Keisuke Uehara, Gui-Yu Wang, Ye Wei, Zhi-Guo Xiong, Hong-Liang Yao, Gang Yu, Shao-Jun Yu, Hai-Tao Zhou, Suk-Hwan Lee, Petr V Tsarkov, Chuan-Gang Fu, Xi-Shan Wang

    Gastroenterology report   7 ( 1 )   24 - 31   2019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)  

    In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.

    DOI: 10.1093/gastro/goy055

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  • Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. 国際誌

    Atsushi Ogura, Tsuyoshi Konishi, Chris Cunningham, Julio Garcia-Aguilar, Henrik Iversen, Shigeo Toda, In Kyu Lee, Hong Xiang Lee, Keisuke Uehara, Peter Lee, Hein Putter, Cornelis J H van de Velde, Geerard L Beets, Harm J T Rutten, Miranda Kusters

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology   37 ( 1 )   33 - 43   2019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)  

    PURPOSE: Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs. PATIENTS AND METHODS: Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features. RESULTS: On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042). CONCLUSION: LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.

    DOI: 10.1200/JCO.18.00032

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  • Short-term outcomes of robotic-assisted laparoscopic rectal surgery: A pilot study during the introductory period at a local municipal hospital.

    Toshisada Aiba, Keisuke Uehara, Taro Aoba, Kazuhiro Hiramatsu, Takehito Kato, Masato Nagino

    Journal of the anus, rectum and colon   3 ( 1 )   27 - 35   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The aim of this pilot study was to confirm the safety and feasibility of the induction of robotic-assisted laparoscopic rectal surgery (RRS) at a local municipal hospital. A municipal hospital does not indicate a small hospital. The most significant difference between a municipal hospital and a center or university hospital is that most surgeons in a municipal hospital are general surgeons. METHODS: The first 30 patients who underwent RRS at the municipal hospital were enrolled between April 2015 and June 2016. All surgeries were performed by a single trained surgeon using the da VinciⓇ Si surgical system. The primary endpoint was the incidence of postoperative major complications. RESULTS: Of the study patients, 29 had adenocarcinoma and 1 had ulcerative colitis. The surgical procedures included anterior resection (n = 22), intersphincteric resection (n = 2), abdominoperineal resection (n = 4), Hartmann's procedure (n = 1), and total coloproctectomy (n = 1). There were no intraoperative complications and conversion cases. The median operative time and blood loss were 283.5 min and 9 ml, respectively. The incidence rate of postoperative major complications was 10%, which included anastomotic leakage in 2 patients and ileus in 1 patient. Postoperative urinary dysfunction did not occur in any patient. Complete resection was achieved for all patients. CONCLUSIONS: We demonstrated that the induction of RRS was safe and feasible, even at a local municipal hospital, given that the surgeons had the sufficient skills and experience in both laparoscopic and colorectal surgery. *The study protocol was registered at the University Hospital Medical Information Network (UMIN000017022).

    DOI: 10.23922/jarc.2017-039

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  • Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy.

    Taihei Oshiro, Keisuke Uehara, Toshisada Aiba, Toshiki Mukai, Tomoki Ebata, Masato Nagino

    International journal of clinical oncology   23 ( 4 )   681 - 688   2018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)  

    PURPOSE: Our sincere hope is to establish the predictive factors of neoadjuvant chemotherapy (NAC) response and provide patients with greater certainty regarding treatment outcomes. The aim of this study was to assess the response to NAC and survival in patients with locally advanced rectal cancer (LARC) according to their RAS/BRAF mutation status. METHODS: Data on 57 patients with LARC who received NAC between 2009 and 2016 were analyzed retrospectively. The patients were classified into two groups based on their mutation status: wild-type in both RAS and BRAF (WT) or mutant-type in either RAS or BRAF (MT). RESULTS: Twenty-three patients were classified as WT, and the remaining 34 patients were MT. Histological response to NAC was similar in both groups. In responders, the 3-year relapse-free survival (RFS) was better compared with the non-responders (92 and 66%, respectively). In the WT group, the 3-year RFS was 95% which was significantly better than that in the MT group (59%, p = 0.011). The MT group was further subdivided into the following 2 groups by the pathological response; the MT responders (n = 10) and MT non-responders (n = 24). The 3-year RFS was 50% in the MT non-responders, which was significantly worse compared to that in the remaining patients (92%, p = 0.001). CONCLUSION: RAS/BRAF mutations did not affect the response to NAC. However, the RFS was likely to be poor for those in the MT group who did not achieve favorable pathological response. In contrast, the RFS was favorable in the WT group regardless of the pathological response.

    DOI: 10.1007/s10147-018-1253-z

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  • Pre-exposure to Fluorouracil Increased Trifluridine Incorporation and Enhanced its Anti-tumor Effect for Colorectal Cancer. 国際誌

    Taisuke Baba, Toshio Kokuryo, Junpei Yamaguchi, Yukihiro Yokoyama, Keisuke Uehara, Tomoki Ebata, Masato Nagino

    Anticancer research   38 ( 3 )   1427 - 1434   2018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/AIM: Trifluridine/tipiracil (FTD/TPI) is used for metastatic colorectal cancer, that is refractory to 5-fluorouracil (5-FU)-based therapies. However, the impact of pre-exposure to 5-FU on the anti-cancer effect of FTD, which is a key component of FTD/TPI, is unclear. MATERIALS AND METHODS: The incorporation into DNA and anti-cancer activity of FTD were analyzed in several cancer cell lines under response to FTD treatment with or without 5-FU pre-exposure. The volumes of tumors in xenografted nude mice were examined among groups that were either untreated or treated with S-1, FTD/TPI or FTD/TPI with pre-exposure to S-1. RESULTS: Pre-exposure to 5-FU significantly increased FTD incorporation into DNA and enhanced its anti-cancer effect for viability and proliferation of cancer cells. In the xenograft nude mouse model, the tumor volumes in the FTD/TPI-treated and S-1-pre-exposed group were lower than those in the FTD/TPI-only-treated group. Although both FTD dose and exposure time in the FTD/TPI-treated and S-1-pre-exposed mice were smaller than those in the FTD/TPI-only-treated mice, the incorporated FTD in the tumors in the former group was 86.5% of that in the latter group. CONCLUSION: Pre-exposure to 5-FU enhanced the incorporation into DNA and the anti-cancer effect of FTD in the context of colorectal cancer. Our data indicate the potential for a new sequential therapy using S-1 and FTD/TPI to improve prognosis of colorectal cancer.

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  • Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer.

    Toshiaki Watanabe, Kei Muro, Yoichi Ajioka, Yojiro Hashiguchi, Yoshinori Ito, Yutaka Saito, Tetsuya Hamaguchi, Hideyuki Ishida, Megumi Ishiguro, Soichiro Ishihara, Yukihide Kanemitsu, Hiroshi Kawano, Yusuke Kinugasa, Norihiro Kokudo, Keiko Murofushi, Takako Nakajima, Shiro Oka, Yoshiharu Sakai, Akihito Tsuji, Keisuke Uehara, Hideki Ueno, Kentaro Yamazaki, Masahiro Yoshida, Takayuki Yoshino, Narikazu Boku, Takahiro Fujimori, Michio Itabashi, Nobuo Koinuma, Takayuki Morita, Genichi Nishimura, Yuh Sakata, Yasuhiro Shimada, Keiichi Takahashi, Shinji Tanaka, Osamu Tsuruta, Toshiharu Yamaguchi, Naohiko Yamaguchi, Toshiaki Tanaka, Kenjiro Kotake, Kenichi Sugihara

    International journal of clinical oncology   23 ( 1 )   1 - 34   2018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)  

    Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

    DOI: 10.1007/s10147-017-1101-6

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  • Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (Translated Version).

    Hideyuki Ishida, Tatsuro Yamaguchi, Kohji Tanakaya, Kiwamu Akagi, Yasuhiro Inoue, Kensuke Kumamoto, Hideki Shimodaira, Shigeki Sekine, Toshiaki Tanaka, Akiko Chino, Naohiro Tomita, Takeshi Nakajima, Hirotoshi Hasegawa, Takao Hinoi, Akira Hirasawa, Yasuyuki Miyakura, Yoshie Murakami, Kei Muro, Yoichi Ajioka, Yojiro Hashiguchi, Yoshinori Ito, Yutaka Saito, Tetsuya Hamaguchi, Megumi Ishiguro, Soichiro Ishihara, Yukihide Kanemitsu, Hiroshi Kawano, Yusuke Kinugasa, Norihiro Kokudo, Keiko Murofushi, Takako Nakajima, Shiro Oka, Yoshiharu Sakai, Akihiko Tsuji, Keisuke Uehara, Hideki Ueno, Kentaro Yamazaki, Masahiro Yoshida, Takayuki Yoshino, Narikazu Boku, Takahiro Fujimori, Michio Itabashi, Nobuo Koinuma, Takayuki Morita, Genichi Nishimura, Yuh Sakata, Yasuhiro Shimada, Keiichi Takahashi, Shinji Tanaka, Osamu Tsuruta, Toshiharu Yamaguchi, Kenichi Sugihara, Toshiaki Watanabe

    Journal of the anus, rectum and colon   2 ( Suppl I )   S1-S51   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non-polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

    DOI: 10.23922/jarc.2017-028

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  • Outcomes of stage IV patients with colorectal cancer treated in a single institution: What is the key to the long-term survival?

    Toshiki Mukai, Keisuke Uehara, Toshisada Aiba, Hayato Nakamura, Tomoki Ebata, Masato Nagino

    Journal of the anus, rectum and colon   2 ( 1 )   16 - 24   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The purpose of this study is to summarize our short- and long-term treatment results for stage IV colorectal cancer (CRC) and to clarify the factors predicting the favorable long-term survival. METHODS: Between January 2008 and December 2015, 149 consecutive patients with stage IV CRC underwent initial treatment at Nagoya University Hospital. Their clinical and pathological characteristics, the treatment methods used, and the outcomes were retrospectively analyzed. RESULTS: The median observation period was 23 months. All of the primary and metastatic lesions were technically resectable in 74 patients; however, the remaining 75 were judged as initially unresectable. R0/1 resection during the treatment course was achieved in 74 patients (50%). For the cohort as a whole, the 5-year overall survival (OS) rate was 35%. The 5-year OS rate in the R0/1 resection group was 57%, which was significantly better than that of the non-R0/1 resection group (6%, p < 0.001). In the R0/1 resection group, perioperative chemotherapy significantly improved the outcome (5-year OS; 62% vs. 0%, p = 0.03). In the non-R0/1 resection group, primary tumor resection was associated with a significantly higher favorable prognosis (3-year OS; 20.4% vs. 0%, p = 0.026). Moreover, the additional use of molecular targeted drugs significantly improved the survival. In multivariate analysis, the differentiated histologic type, R0/1 resection, and parallel use of molecular targeted drugs remained independent factors of a favorable outcome. CONCLUSIONS: The present study suggested that aggressive curative resection with perioperative chemotherapy might improve survival and that primary tumor resection might improve the outcome in the non-R0/1 group.

    DOI: 10.23922/jarc.2017-021

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  • Is There Any Reason to Still Consider Lateral Lymph Node Dissection in Rectal Cancer? Rationale and Technique. 国際誌

    Miranda Kusters, Keisuke Uehara, Cornelis J H van de Velde, Yoshihiro Moriya

    Clinics in colon and rectal surgery   30 ( 5 )   346 - 356   2017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)  

    Nodal dissemination in locally advanced rectal cancer occurs mainly in two directions: upward and lateral. Lateral node involvement has been demonstrated; however, lateral lymph node dissection (LLND) is not routinely performed in Western countries and the focus is more on neoadjuvant treatment regimens. The main reasons for this are the high morbidity associated with the operation and the uncertain oncological benefit. There is, however, recent evidence that in selected cases, neoadjuvant treatment combined with total mesorectal excision only might not be sufficient. In this article, the historical developments in the East and the West, the current evidence regarding lateral nodal disease, and the surgical steps in the LLND are discussed.

    DOI: 10.1055/s-0037-1606112

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  • Local control of sphincter-preserving procedures and abdominoperineal resection for locally advanced low rectal cancer: Propensity score matched analysis.

    Ryosuke Okamura, Koya Hida, Tomohiro Yamaguchi, Tomonori Akagi, Tsuyoshi Konishi, Michio Yamamoto, Mitsuyoshi Ota, Shuichiro Matoba, Hiroyuki Bando, Saori Goto, Yoshiharu Sakai, Masahiko Watanabe, Kazuteru Watanabe, Koki Otsuka, Ichiro Takemasa, Keitaro Tanaka, Masataka Ikeda, Chu Matsuda, Meiki Fukuda, Junichi Hasegawa, Shintaro Akamoto, Manabu Shiozawa, Atsushi Tsuruta, Takashi Akiyoshi, Takeshi Kato, Shunsuke Tsukamoto, Masaaki Ito, Masaki Naito, Akiyoshi Kanazawa, Takao Takahashi, Takashi Ueki, Yuri Hayashi, Satoshi Morita, Takashi Yamaguchi, Masayoshi Nakanishi, Hirotoshi Hasegawa, Ken Okamoto, Fuminori Teraishi, Yasuo Sumi, Jo Tashiro, Toshimasa Yatsuoka, Yoji Nishimura, Kenji Okita, Takaya Kobatake, Hisanaga Horie, Yasuyuki Miyakura, Hisashi Ro, Kunihiko Nagakari, Eiji Hidaka, Takehiro Umemoto, Hideaki Nishigori, Kohei Murata, Fuminori Wakayama, Ryoji Makizumi, Shoichi Fujii, Eiji Sunami, Hirotoshi Kobayashi, Ryosuke Nakagawa, Toshiyuki Enomoto, Shinobu Ohnuma, Jun Higashijima, Heita Ozawa, Keigo Ashida, Fumihiko Fujita, Keisuke Uehara, Satoshi Maruyama, Masato Ohyama, Seiichiro Yamamoto, Takao Hinoi, Masanori Yoshimitsu, Masazumi Okajima, Shu Tanimura, Masayasu Kawasaki, Yoshihito Ide, Shoichi Hazama, Jun Watanabe, Daisuke Inagaki, Akihiro Toyokawa

    Annals of gastroenterological surgery   1 ( 3 )   199 - 207   2017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)  

    Sphincter-preserving procedures (SPPs) for surgical treatment of low-lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II-III rectal cancer between 2010 and 2011. Patients with tumors 2-5 cm from the anal verge and clinical stage T3-4 were eligible. Primary outcome was 3-year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77-1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3-year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42-1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

    DOI: 10.1002/ags3.12032

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  • Phase II trial of neoadjuvant chemotherapy with S-1 and oxaliplatin plus bevacizumab for colorectal liver metastasis (N-SOG 05 trial). 国際誌

    Toshiki Mukai, Keisuke Uehara, Hidenari Goto, Kazuhiro Hiramatsu, Satoshi Kobayashi, Eiji Sakamoto, Atsuyuki Maeda, Eiji Takeuchi, Yoshito Okada, Tomoki Ebata, Masato Nagino

    Japanese journal of clinical oncology   47 ( 7 )   597 - 603   2017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)  

    Purpose: This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM). Methods: Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%. Results: Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint. Conclusions: NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.

    DOI: 10.1093/jjco/hyx048

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  • Perineal alveolar soft part sarcoma treated by laparoscopy-assisted total pelvic exenteration combined with pubic resection.

    Toshisada Aiba, Keisuke Uehara, Satoshi Tsukushi, Yasushi Yoshino, Tomoki Ebata, Yukihiro Yokoyama, Tsuyoshi Igami, Gen Sugawara, Masato Nagino

    Asian journal of endoscopic surgery   10 ( 2 )   198 - 201   2017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 20-year-old woman with a perineal alveolar soft part sarcoma was referred to our hospital. MRI showed that an irregular oval tumor occupied the perineum. The tumor was contiguous to the vagina, rectum, levator muscle, and pubis and was diagnosed as alveolar soft part sarcoma by transvaginal biopsy. Laparoscopy-assisted total pelvic exenteration combined with a pubic resection was performed, and an R0 resection with a wide margin was achieved. It is well known that only R0 resection improves the outcome of patients with localized alveolar soft part sarcoma. In this case, the perineal manipulation was difficult because the tumor was huge and had a rich blood flow. Massive bleeding occurred during the perineal manipulation. However, we kept the operative field dry thanks to minimal intraoperative blood loss during the laparoscopic phase. The laparoscopic approach might be advantageous for such a demanding surgical procedure for tumors in the distal pelvis and perineum.

    DOI: 10.1111/ases.12342

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  • The efficacy and safety of CapeOX plus bevacizumab therapy followed by capecitabine plus bevacizumab maintenance therapy in patients with metastatic colorectal cancer: a multi-center, single-arm, phase II study (CCOG-0902). 国際誌

    Goro Nakayama, Kiyoshi Ishigure, Hiroyuki Yokoyama, Keisuke Uehara, Hiroshi Kojima, Akiharu Ishiyama, Naomi Hayashi, Nao Takano, Norifumi Hattori, Daisuke Kobayashi, Chie Tanaka, Masamichi Hayashi, Mitsuro Kanda, Suguru Yamada, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Tsutomu Fujii, Kenta Murotani, Yuichi Ando, Yasuhiro Kodera

    BMC cancer   17 ( 1 )   243 - 243   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)  

    BACKGROUND: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. RESULTS: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0-14.8) and 30.6 months (95% CI, 27.6-33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. CONCLUSIONS: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network in 15 March 2010 ( UMIN000006478 ).

    DOI: 10.1186/s12885-017-3245-1

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  • TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion. 国際誌

    Kenji Kurita, Masao Maeda, Mohammed A Mansour, Toshio Kokuryo, Keisuke Uehara, Yukihiro Yokoyama, Masato Nagino, Michinari Hamaguchi, Takeshi Senga

    Oncology letters   12 ( 6 )   5240 - 5246   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)  

    Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues. The depletion of TRIP13 in CRC cells suppressed cell proliferation, migration and invasion. To determine whether the catalytic activity of TRIP13 was critical for cancer progression, an inactive mutant of TRIP13 was expressed in CRC cells. The invasion of cancer cells that expressed the mutant TRIP13 was significantly reduced compared with that of the wild type TRIP13-expressing cancer cells. These results indicate that TRIP13 could be a potential target for CRC treatment.

    DOI: 10.3892/ol.2016.5332

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  • A case of advanced intrahepatic cholangiocarcinoma accidentally, but successfully, treated with capecitabine plus oxaliplatin (CAPOX) therapy combined with bevacizumab: a case report. 国際誌

    Masahito Uji, Takashi Mizuno, Tomoki Ebata, Gen Sugawara, Tsuyoshi Igami, Keisuke Uehara, Masato Nagino

    Surgical case reports   2 ( 1 )   63 - 63   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)  

    Although surgical resection is the only way to cure biliary tract cancer (BTC), most BTCs are unresectable by the time they are diagnosed. Chemotherapy is usually used to treat unresectable BTC, but its impact on survival is small. Here, we report the case of a 70-year-old woman with a locally advanced intrahepatic cholangiocarcinoma that was initially diagnosed as an unresectable liver metastasis from colon cancer that had invaded all of the major hepatic veins. However, the tumor was noticeably reduced after treatment with CAPOX plus bevacizumab, which is an uncommon therapy for BTC. The tumor was finally resected by inferior right hepatic vein-preserving left hepatic trisectionectomy combined with a resection of the right hepatic vein after a right hepatic vein embolization.

    DOI: 10.1186/s40792-016-0191-0

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  • The effects of bevacizumab on intestinal anastomotic healing in rabbits.

    Hayato Nakamura, Yukihiro Yokoyama, Keisuke Uehara, Toshio Kokuryo, Junpei Yamaguchi, Toyonori Tsuzuki, Masato Nagino

    Surgery today   46 ( 12 )   1456 - 1463   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)  

    PURPOSES: The aim of this study was to investigate the effects of the preoperative administration of BV on the healing process of intestinal anastomosis in a rabbit model. METHODS: Twenty male white rabbits were randomly divided into two groups. The control group received saline 1 week before surgery, and the BV group received intravenous BV 1 week before surgery. Each rabbit underwent an enteroenterostomy and a colocolostomy. On postoperative day 7, the bursting pressures of the anastomoses, CD31 and α-smooth muscle actin (α-SMA) staining by immunohistochemistry, the gene expression of α-SMA, and collagen deposition using Picrosirius Red at the site of anastomosis were evaluated. RESULTS: The bursting pressure of small bowel anastomoses was significantly lower in the BV group than in the control group (control 184 ± 10 mmHg vs. BV 140 ± 9 mmHg; p = 0.004). The microvessel counts in the anastomotic tissue were significantly lower in the BV group than in the control group in both the small bowel (p = 0.023) and colon (p = 0.008). The expression of α-SMA, and the degree of collagen deposition decreased in the anastomotic tissue in the BV group compared with the control group. CONCLUSION: The preoperative use of BV may therefore negatively affect the rigidity of intestinal anastomosis.

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  • Modified two-dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer. 国際誌

    Goro Nakayama, Tsutomu Fujii, Kenta Murotani, Keisuke Uehara, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yuichi Ando, Yasuhiro Kodera

    Cancer science   107 ( 10 )   1492 - 1498   2016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)  

    The identification of surrogate markers for long-term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two-dimensional response (2-DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study group consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin-based chemotherapy plus bevacizumab. Two-dimensional response was defined as an area enclosed by coordinate points, including early tumor shrinkage at 8 weeks, depth of response at nadir, and 20% increase over nadir at progression. Each variable was weighted by its contribution rate to OS. The model was developed and internally validated in the learning cohort, and the performance of this model was externally verified in the validation cohort. Spearman correlation coefficients for 2-DR and OS in the learning and validation cohorts were 0.593 and 0.661, respectively. The C-indexes in predicting OS were 0.724 (95% confidence interval, 0.623-0.815) in the learning cohort and 0.762 (95% confidence interval, 0.651-0.873) in the validation cohort. Overall survival was significantly longer in patients with high 2-DR values than in patients with low 2-DR values in both the learning (37.0 vs. 24.1 months, P < 0.001) and validation (41.2 vs. 20.4 months, P < 0.001) cohorts. In contrast, differences in early tumor shrinkage and depth of response were not statistically significant. Multivariate analyses showed that 2-DR was an independent prognostic factor for OS.

    DOI: 10.1111/cas.13023

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  • The feasibility of laparoscopic extended pelvic surgery for rectal cancer.

    Hayato Nakamura, Keisuke Uehara, Atsuki Arimoto, Takehiro Kato, Tomoki Ebata, Masato Nagino

    Surgery today   46 ( 8 )   950 - 6   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)  

    PURPOSE: The present study aimed to assess the safety and feasibility of laparoscopic extended pelvic surgery for primary or recurrent rectal cancer. METHODS: The data on 77 patients, who underwent extended pelvic surgery between February 2008 and June 2014, were retrospectively analyzed. The patients were divided, based on their treatment history, into an open surgery (OS) group (n = 41) and a laparoscopic surgery (LS) group (n = 36). RESULTS: The operative time in the LS group was significantly longer than that in the OS group (766 vs. 561 min; p < 0.001). In contrast, the LS group was associated with a significantly lower volume of intraoperative blood loss (195 vs. 923 ml; p < 0.001), fluid balance (5.38 vs. 8.23 ml/kg/h; p < 0.001) and rate of complications (40.0 vs. 68.3 %; p = 0.035), and a significantly shorter postoperative hospital stay. The postoperative levels of colloid osmotic pressure and albumin were significantly higher in the LS group. CONCLUSION: The operative time of the LS group was longer than that of the OS group; however, the LS group experienced less blood loss and fewer complications. Moreover, LS was associated with a reduction in intraoperative infusions and a reduced fluid balance, which maintained homeostasis.

    DOI: 10.1007/s00595-015-1267-3

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  • Prediction of Early Recurrence After Curative Resection of Colorectal Liver Metastasis and Subsequent S-1 Chemotherapy. 国際誌

    Kohei Yamauchi, Toshio Kokuryo, Yukihiro Yokoyama, Keisuke Uehara, Junpei Yamaguchi, Masato Nagino

    Anticancer research   36 ( 5 )   2175 - 9   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: S-1, an oral 5-fluorouracil (5-FU)-based medicine that combines tegafur, gimeracil and oteracil potassium is commonly used as an adjuvant chemotherapeutic drug for the treatment of colorectal cancer. PATIENTS AND METHODS: We enrolled 53 patients who underwent curative resection for colorectal cancer and liver metastasis (synchronous, n=24; metachronous, n=29). The subsequent adjuvant chemotherapy with oral S-1 administration was initiated within 56 days after liver resection. Recurrence was evaluated by imaging studies, that were performed during the first year after liver resection. Of the 53 patients, 25 who did not recur within 1 year were defined as being in the no-recurrence (NREC) group and the remaining 18 patients were defined as being in the early-recurrence (EREC) group. There were no significant differences in gene expression profiling for drug resistance and metabolism between the NREC group and the EREC group. RESULTS: In synchronous liver metastasis, there was no significant difference in early recurrence between serum carcinoembryonic antigen (CEA) ≤5 ng/ml and serum CEA >5 ng/ml (8/24 vs. 16/24, respectively). In metachronous liver metastasis, the early recurrence rate was significantly higher in patients with CEA >5 ng/ml compared to patients with CEA ≤5 ng/ml (15/29 vs. 14/29, p=0.05). The expression of cytochrome P450 2C19 (CYP2C19) and ATP-binding cassette, sub-family B member 1 (ABCB1) were significantly lower in the EREC group (6/15) compared to the NREC group (9/15) in colorectal cancer with metachronous liver metastasis and with serum CEA >5 ng/ml. CONCLUSION: Although the exact reason for down-regulation of these genes in the group with poor prognosis is unknown, the information obtained in this study may be useful in clinical practice for colorectal cancer.

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  • Growth rate of chemotherapy-naïve lung metastasis from colorectal cancer could be a predictor of early relapse after lung resection.

    Koji Kawaguchi, Keisuke Uehara, Goro Nakayama, Takayuki Fukui, Koichi Fukumoto, Shota Nakamura, Kohei Yokoi

    International journal of clinical oncology   21 ( 2 )   329 - 334   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)  

    PURPOSE: The aim of this study was to elucidate a potential risk factor for early relapse after pulmonary metastasectomy of colorectal cancer and to propose an optimal treatment strategy for lung metastasis with an aggressive nature. METHODS: Seventy patients who underwent pulmonary metastasectomy for diachronically measurable pulmonary lesions were retrospectively analyzed. We calculated the tumor doubling time (TDT) as the growth rate of lung metastasis and divided the study population into two groups: Rapid (TDT ≤ 100 days) and Slow (TDT > 100 days). RESULTS: The patients consisted of 47 males and 23 females, with a mean age of 63 years. Forty-two patients had a relapse after pulmonary metastasectomy with a median follow-up duration of 24 months. There was a significant difference in relapse-free survival between the Rapid and Slow groups (p = 0.047). Using a multivariate analysis, no preoperative chemotherapy and a high level of serum carcinoembryonic antigen were proven to be significant risk factors for relapse after metastasectomy. Meanwhile, multivariate analyses among 37 patients without preoperative chemotherapy indicated that TDT was the sole significant factor for relapse-free survival. In addition, eight of nine patients with relapse within 12 months were placed into the Rapid group. CONCLUSIONS: Although this was a preliminary study with a small number of patients, it suggested that lung metastases demonstrating a TDT of 100 days or less have a high risk of early relapse after metastasectomy.

    DOI: 10.1007/s10147-015-0889-1

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  • Neoadjuvant treatment for locally advanced rectal cancer: a systematic review.

    Keisuke Uehara, Masato Nagino

    Surgery today   46 ( 2 )   161 - 8   2016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)  

    We reviewed the history and the current status of neoadjuvant treatment for locally advanced rectal cancer (LARC) in Western countries and Japan. The introduction of total mesorectal excision (TME) and preoperative radiotherapy (RT) were treatment revolutions that resulted in improved local control after curative resection for rectal cancer. However, local relapses still occur, even in the era of TME, and remain a cause of recurrence worldwide. The high rate of distant metastasis after curative resection remains a problem. Furthermore, the introduction of newly developed cytotoxic agents into the LARC treatment strategy continues to be an ongoing challenge. Shifting part of an adjuvant chemotherapy (CTx) regimen to the preoperative period is a promising strategy. Currently, various novel methods, such as induction CTx, consolidation CTx, concomitant administration with RT, and neoadjuvant CTx without RT, have been attempted worldwide. Although some strategies have shown favorable short-term outcomes, the long-term efficacy of the treatments needs be evaluated. At the same time, we must investigate clinical and/or molecular biomarkers to predict the therapeutic effects of each treatment, which is the fastest route to providing ideal personalized therapy for patients with LARC.

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  • The value of preoperative screening colonoscopies in patients with biliary tract cancer.

    Keita Itatsu, Yukihiro Yokoyama, Tomoki Ebata, Tsuyoshi Igami, Gen Sugawara, Keisuke Uehara, Takashi Mizuno, Masahiko Ando, Hidemi Goto, Masato Nagino

    Journal of gastroenterology   51 ( 2 )   138 - 43   2016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 purpose of this study was to evaluate the value of preoperative screening colonoscopies in patients with biliary tract cancer. METHODS: A total of 544 patients with biliary tract cancer who underwent preoperative screening colonoscopies between January 2005 and December 2012 were retrospectively analyzed. RESULTS: Synchronous colorectal neoplasia was detected in 199 patients (36.7 %), with adenocarcinomas detected in 21 (3.9 %) patients, carcinoids in two (0.4 %) patients, and adenomas in 176 (32.4 %) patients. Of those with adenomas, 32 patients were diagnosed with advanced adenomas, defined as adenomas with a maximum diameter of >1 cm, villous histology, or high-grade dysplasia because these characteristics implied the risk of malignant transformation. Fifty-five (10.1 %) of the patients with colorectal neoplasia required resection (11 surgical and 44 endoscopic resections). There were no major adverse events related to the resection. Univariate and multivariate analyses revealed that smoking status [ex-smoker + current smoker vs. non-smoker: odds ratio (OR) 2.32; 95 % confidence interval (CI) 1.30-4.21] and advanced age (≥70 vs. ≤69 years: OR 2.22; 95 % CI 1.24-3.91) were independent risk factors of having a colorectal neoplasia that required resection. CONCLUSIONS: In patients with biliary tract cancer, preoperative screening colonoscopy was feasible and provided valuable clinical information. Synchronous colorectal neoplasia was detected in a substantial number of patients. Preoperative screening colonoscopies should be considered especially in high-risk patients such as smokers and elderly patients.

    DOI: 10.1007/s00535-015-1092-x

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  • SATB1 and SATB2 play opposing roles in c-Myc expression and progression of colorectal cancer. 国際誌

    Mohammed A Mansour, Toshinori Hyodo, Khondker Ayesha Akter, Toshio Kokuryo, Keisuke Uehara, Masato Nagino, Takeshi Senga

    Oncotarget   7 ( 4 )   4993 - 5006   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)  

    Special AT-rich sequence-binding protein 1 and 2 (SATB1/2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB2 acts as a tumor suppressor in laryngeal squamous cell carcinoma and colon cancer, whereas SATB1 promotes the progression of numerous types of cancers. In this study, we examined the effects of SATB1 and SATB2 on the malignant characteristics of colorectal cancer cells. SATB1 and SATB2 expression were negatively correlated in colorectal cancer specimens. SATB1 expression was increased, whereas SATB2 expression was reduced, in colorectal cancer tissues compared to control tissues. Exogenous expression of SATB2 in colorectal cancer cells suppressed cell proliferation, colony formation and tumor proliferation in mice. c-Myc was reduced by SATB2 expression, and exogenous expression of c-Myc in SATB2-expressing cells restored proliferation, colony formation and in vivo tumor growth of colorectal cancer cells. We also showed that c-Myc reduction by SATB2 was mediated by the inactivation of ERK5. In contrast, SATB1 promoted c-Myc expression. The expression of SATB1 in colorectal cancer tissues was positively correlated with c-Myc expression, and SATB1 knockdown reduced c-Myc expression in colorectal cancer cells. Finally, we showed that SATB1 knockdown in colorectal cancer cells suppressed cell proliferation, colony formation and cell invasion. Our results reveal interesting features of how the structural homologs SATB1 and SATB2 exert opposing functions in colorectal tumorigenesis.

    DOI: 10.18632/oncotarget.6651

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  • Initial experience of laparoscopic pelvic exenteration and comparison with conventional open surgery. 国際誌

    Keisuke Uehara, Hayato Nakamura, Yasushi Yoshino, Atsuki Arimoto, Takehiro Kato, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino

    Surgical endoscopy   30 ( 1 )   132 - 8   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)  

    BACKGROUND: Generalization of laparoscopic pelvic surgery has brought about profound knowledge of the pelvic anatomy and has encouraged expansion of indications for laparoscopic surgery to extended pelvic surgery. Pelvic exenteration (PE) is still a demanding surgical procedure and remains an essential technique for pelvic surgery although minimally invasive and function-preserving surgery is in the mainstream of surgical treatment. However, the techniques of laparoscopic PE (LPE) have been rarely explained nor has its feasibility been fully evaluated. The aim of this study was to describe important technical points and to assess the feasibility of LPE for pelvic malignancies. METHODS: Data on 67 patients with pelvic malignancies, who underwent PE between June 2006 and August 2014, were analyzed retrospectively. LPE has been indicated since 2013. Patients were divided into the LPE group (n = 9) and the conventional open PE (OPE) group (n = 58). RESULTS: Operative time in the LPE and OPE groups was similar (935 vs. 883 min, p = 0.398). Intraoperative blood loss in the LPE group was significantly less than that in the OPE group (830 vs. 2769 ml, p = 0.003). Pathological R0 resection rate was similar in both groups (77.8 vs. 75.9%). Overall incidence of any complication and major complications were much lower in the LPE group (66.7 and 0%) compared to the OPE group (89.7 and 32.8%), although not statistically significant (p = 0.094 and 0.053, respectively). Postoperative hospital stay was significantly shorter in the LPE group than in the OPE group (27 vs. 43 days, p = 0.003). CONCLUSIONS: We confirmed that LPE for pelvic malignancies resulted in less blood loss, a lower complication rate, and shorter postoperative hospital stay compared to OPE. LPE performed by an experienced pelvic surgeon was safe and efficient, and might be a promising option for carefully selected patients.

    DOI: 10.1007/s00464-015-4172-3

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  • Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer.

    Atsuki Arimoto, Keisuke Uehara, Toyonori Tsuzuki, Toshisada Aiba, Tomoki Ebata, Masato Nagino

    International journal of clinical oncology   20 ( 5 )   935 - 42   2015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: The role of bevacizumab (Bev) in neoadjuvant chemotherapy (NAC) without radiotherapy for rectal cancer has not been fully discussed. The purpose of this study is to assess the clinicopathological benefit of Bev in NAC for rectal cancer and to investigate its influence on microvessel status in cancerous tissue. METHODS: Data on 47 patients with rectal cancer, who received NAC with or without Bev between August 2008 and November 2012, were analyzed retrospectively. The objective response was evaluated using the maximum tumor diameter. Tumor regression grade 3/4 was classified as a pathological response. RESULTS: Thirty-one patients (66 %) received NAC that included Bev and the other 16 patients were treated without Bev. The objective response rate was significantly higher in the Bev group than in the non-Bev group (64.5 vs. 25.0 %, p = 0.015). The rate of pathological response was much higher in the Bev group (41.9 %) than in the non-Bev group (12.5 %), but did not reach significant difference (p = 0.052). Microvessel density (MVD) in the resected cancerous tissue was significantly lower in the Bev group than in the non-Bev group. CONCLUSIONS: We have confirmed that objective and pathological responses were better in patients treated with NAC that included Bev than in those who received NAC without Bev. Additionally, MVD in tumor tissues was inhibited in the patients treated with Bev. To investigate the impact of Bev in NAC on long-term survival, further follow-up is required.

    DOI: 10.1007/s10147-015-0818-3

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  • A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial). 国際誌

    Satoshi Matsusaka, Soichiro Ishihara, Keisaku Kondo, Hisanaga Horie, Keisuke Uehara, Masahiko Oguchi, Keiko Murofushi, Masashi Ueno, Nobuyuki Mizunuma, Taiju Shimbo, Daiki Kato, Junji Okuda, Yojiro Hashiguchi, Masanori Nakazawa, Eiji Sunami, Kazushige Kawai, Hideomi Yamashita, Tohru Okada, Yuichi Ishikawa, Toshifusa Nakajima, Toshiaki Watanabe

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology   116 ( 2 )   209 - 13   2015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)  

    PURPOSE: This study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherapy (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). PATIENTS AND METHODS: This was a multicenter phase II study in patients with histologically proven clinical stage T3 or T4 (any N, M0) LARC. Patients preoperatively received oral S-1 (80 mg/m(2)/day on days 1-5, 8-12, 22-27, and 29-33) and infusional oxaliplatin (60 mg/m(2) days on 1, 8, 22, and 29) plus radiotherapy (50.4 Gy), with a chemotherapy gap in the third week of radiotherapy. Pathological complete response (pCR) was the primary endpoint. Secondary endpoints included toxicity, compliance, R0 resection rate, and downstaging rate. RESULTS: A total of 45 patients were enrolled at six centers in Japan. All 45 patients received CRT, and 44 underwent operation. A pCR was achieved in 12 (27.3%) of the 44 patients who underwent surgery. Near-total tumor regression was confirmed in 47.7%. There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. R0 resection was achieved in 95.5% of the patients. CONCLUSION: Preoperative CRT with S-1 plus oxaliplatin had a high pCR rate and a favorable toxicity profile.

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  • Phase II multicenter study of adjuvant S-1 for colorectal liver metastasis: survival analysis of N-SOG 01 trial. 国際誌

    Takehiro Kato, Keisuke Uehara, Atsuyuki Maeda, Eiji Sakamoto, Kazuhiro Hiramatsu, Eiji Takeuchi, Hidenari Goto, Yuichiro Tojima, Hiroshi Yatsuya, Masato Nagino

    Cancer chemotherapy and pharmacology   75 ( 6 )   1281 - 8   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)  

    PURPOSE: We previously showed that S-1 after curative resection of colorectal liver metastasis had acceptable toxicity and a high rate of completion of therapy in a prospective phase II trial. We here reported the primary endpoint of disease-free survival (DFS). METHODS: Between October 2008 and August 2010, 60 patients were eligible for this study and received S-1 for 28 days followed by a 2-week rest period. Treatment was started within 8 weeks after surgery and repeated for eight cycles. RESULTS: Median follow-up was 41 months. Among 60 patients, 45 had solitary metastasis, and the median maximum tumor diameter was 2.6 cm. The 3-year DFS and overall survival were 47.4 and 80.0 %, respectively. Recurrences developed in 31 patients, with the remnant liver the most common site (19 patients). Multivariate analysis showed that positive lymph node metastasis around the primary site (p = 0.013) and early liver metastasis (synchronous disease or metachronous disease within 12 months) (p = 0.041) were independent poor prognostic factors for DFS. Patients having both risk factors had a significantly worse DFS than those without these risk factors (p < 0.001). Early liver metastasis was an independent indicator of early recurrence within 1 year. CONCLUSIONS: S-1 after curative liver resection yielded promising survival in patients with a low tumor burden. Outcome in patients having both positive lymph node metastasis around the primary site and early liver metastasis was much worse than in patients without these conditions; therefore, they might warrant more aggressive therapy.

    DOI: 10.1007/s00280-015-2752-5

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  • SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling. 国際誌

    Mohammed A Mansour, Toshinori Hyodo, Satoko Ito, Kenji Kurita, Toshio Kokuryo, Keisuke Uehara, Masato Nagino, Masahide Takahashi, Michinari Hamaguchi, Takeshi Senga

    The FEBS journal   282 ( 8 )   1394 - 405   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)  

    Special AT-rich sequence binding protein 2 (SATB2) is an evolutionarily conserved transcription factor that has multiple roles in neuronal development, osteoblast differentiation, and craniofacial patterning. SATB2 binds to the nuclear matrix attachment region, and regulates the expression of diverse sets of genes by altering chromatin structure. Recent studies have reported that high expression of SATB2 is associated with favorable prognosis in colorectal and laryngeal cancer; however, it remains uncertain whether SATB2 has tumor-suppressive functions in cancer cells. In this study, we examined the effects of SATB2 expression on the malignant characteristics of colorectal cancer cells. Expression of SATB2 repressed the proliferation of cancer cells in vitro and in vivo, and also suppressed their migration and invasion. Extracellular signal-regulated kinase 5 (ERK5) is a mitogen-activated protein kinase that is associated with an aggressive phenotype in various types of cancer. SATB2 expression reduced the activity of ERK5, and constitutive activation of ERK5 restored the proliferation, anchorage-independent growth, migration and invasion of SATB2-expressing cells. Our results demonstrate the existence of a novel regulatory mechanism of SATB2-mediated tumor suppression via ERK5 inactivation.

    DOI: 10.1111/febs.13227

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  • A phase I dose escalation study of oxaliplatin plus oral S-1 and pelvic radiation in patients with locally advanced rectal cancer (SHOGUN trial). 国際誌

    Soichiro Ishihara, Satoshi Matsusaka, Keisaku Kondo, Hisanaga Horie, Keisuke Uehara, Masahiko Oguchi, Keiko Murofushi, Masashi Ueno, Nobuyuki Mizunuma, Taijyu Shinbo, Daiki Kato, Junji Okuda, Yojiro Hashiguchi, Masanori Nakazawa, Eiji Sunami, Kazushige Kawai, Hideomi Yamashita, Tohru Okada, Yuichi Ishikawa, Toshifusa Nakajima, Toshiaki Watanabe

    Radiation oncology (London, England)   10   24 - 24   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)  

    BACKGROUND: The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer. METHODS: Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained. RESULTS: Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses. CONCLUSIONS: The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).

    DOI: 10.1186/s13014-015-0333-8

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  • Clinical Significance of Para-Aortic Lymph Node Dissection for Advanced or Metastatic Colorectal Cancer in the Current Era of Modern Chemotherapy. 国際誌

    Atsuki Arimoto, Keisuke Uehara, Takehiro Kato, Hayato Nakamura, Tadahiro Kamiya, Masato Nagino

    Digestive surgery   32 ( 6 )   439 - 44   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIMS: Surgical resection is not generally indicated for para-aortic lymph node (PALN) metastasis from colorectal cancer. However, the clinical significance of PALN dissection (PALND) in the current era of modern chemotherapy has not been fully discussed. METHODS: Between November 2006 and February 2013, 14 patients underwent PALND for colorectal cancer and were proven as having pathological PALN metastasis. The median follow-up was 33.2 months. RESULTS: Primary location was the right-colon in 2 patients, and the left-colon or rectum in 12 patients. The timing of metastasis was metachronous in 5 patients and synchronous in 9 patients. Eleven patients (79%) received perioperative aggressive modern chemotherapy. Neoadjuvant chemotherapy with targeted drugs was introduced in 9 patients (64%) and 6 patients received adjuvant chemotherapy. Recurrence after PALND occurred in 12 patients (86%). The most common site was the lung in 6 patients (43%). The 1- and 3-year disease-free survivals were 39.3 and 7.9%, respectively. The 3-year overall survival were 41.2%. CONCLUSION: The recurrence rate after PALND for strictly selected patients was quite high even in the current era of modern chemotherapy. However, some patients achieved long-term survival or could be cured. Therefore, we should re-evaluate the efficacy of PALND in a larger prospective study.

    DOI: 10.1159/000439547

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  • Cowden syndrome complicated by a gastrointestinal stromal tumor. 国際誌

    Masanao Nakamura, Yoshiki Hirooka, Takeshi Yamamura, Koji Yamada, Asuka Nagura, Toru Yoshimura, Naoki Ohmiya, Keisuke Uehara, Yuichiro Yoshioka, Masato Nagino, Hidemi Goto

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   26 ( 5 )   673 - 5   2014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)  

    To our knowledge, this is the first report of Cowden syndrome complicated by a gastrointestinal stromal tumor (GIST) of the small bowel. A 42-year-old female patient was found to have an abdominal mass that was diagnosed as the cause of anemia and was surgically extracted. The surgical specimen was found to be a GIST. During the same period, the patient underwent an endoscopic examination of the entire gastrointestinal tract. She was also diagnosed as having Cowden syndrome based on gastrointestinal polyps and skin, thyroid and breast lesions. Cowden syndrome is associated with germline mutations in the tumorsuppressor gene PTEN. PTEN expression may be essential to tumor growth and is a predictive biomarker of the prognosis of both diseases. The present report of such a case is expected to further the analysis of Cowden syndrome.

    DOI: 10.1111/den.12167

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  • Postoperative complications following neoadjuvant bevacizumab treatment for advanced colorectal cancer.

    Yuichiro Yoshioka, Keisuke Uehara, Tomoki Ebata, Yukihiro Yokoyama, Ayako Mitsuma, Yuichi Ando, Masato Nagino

    Surgery today   44 ( 7 )   1300 - 6   2014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)  

    PURPOSES: Attempts have been made to use bevacizumab (BEV) in an adjuvant or neoadjuvant setting. However, BEV is known to cause various adverse events, and the safety of neoadjuvant BEV has not yet been fully evaluated. This study assessed the postoperative complications in patients receiving neoadjuvant BEV for colorectal cancer. METHODS: The data for 78 patients with resectable advanced or metastatic colorectal cancer who received neoadjuvant BEV followed by surgical resection were retrospectively analyzed. RESULTS: The median interval between the last BEV dose and surgery was 9 weeks. The most common postoperative complication was pelvic sepsis, which occurred in 11 patients (14 %). A biliary fistula developed in four of 23 patients who underwent liver resection. Anastomotic leakage occurred in six of 24 patients with a colorectal anastomosis, four of whom required re-laparotomy. In a univariate analysis, male gender and a greater intraoperative blood loss were associated with postoperative complications of any grade. Colorectal anastomosis was a risk factor for major complications. In a multivariate analysis, intraoperative blood loss was an independent risk factor for postoperative complications of any grade (HR 6.338; P = 0.003). With regard to major postoperative complications, colorectal primary anastomosis was the only independent predictive risk factor (HR 8.285; P = 0.013). CONCLUSIONS: In patients with colorectal cancer who underwent elective surgery after BEV treatment, the interval between BEV and surgery was not a risk factor for postoperative complications (based on a median interval of 9 weeks). Colorectal primary anastomosis was the only independent risk factor for major postoperative complications.

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  • MRI and FDG-PET for assessment of response to neoadjuvant chemotherapy in locally advanced rectal cancer. 国際誌

    Toshisada Aiba, Keisuke Uehara, Takashi Nihashi, Toyonori Tsuzuki, Hiroshi Yatsuya, Yuichiro Yoshioka, Katsuhiko Kato, Masato Nagino

    Annals of surgical oncology   21 ( 6 )   1801 - 8   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: The purpose of this study was to assess the value of magnetic resonance imaging (MRI) and additional (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC). METHODS: Data on 40 patients with LARC, who were treated with NAC and underwent MRI and FDG-PET/CT before and after NAC, were analyzed retrospectively. Surgery was performed at a median of 6 weeks after NAC and the images were compared with the histological findings. The tumor regression grade 3/4 was classified as a responder. RESULTS: Sixteen patients were pathological responders. Receiver operating characteristic (ROC) analysis revealed that MRI total volume after NAC (MRI-TV2) and ΔMRI-TV had the highest performance to assess responders (area under the ROC curve [AUC] 0.849 and AUC 0.853, respectively). The reduction rate of the maximum standardized uptake value (ΔSUVmax) was also an informative factor (AUC 0.719). There seems no added value of adding FDG-PET/CT to MRI-TV2 and ΔMRI-TV in assessment of NAC responders judging from changes in AUC (AUC of ΔSUVmax and MRI-TV2 was 0.844, and AUC of ΔSUVmax and ΔMRI-TV was 0.846). CONCLUSIONS: MRI-TV2 and ΔMRI-TV were the most accurate factors to assess pathological response to NAC. Although ΔSUVmax by itself was also informative, the addition of FDG-PET/CT to MRI did not improve performance. Patients with LARC who were treated by induction chemotherapy should receive an MRI examination before and after NAC to assess treatment response. A more than 70 % volume reduction shown by MRI volumetry may justify the omission of subsequent radiotherapy.

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  • The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer. 国際誌

    Goro Nakayama, Chie Tanaka, Keisuke Uehara, Naoki Mashita, Naomi Hayashi, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Yuich Ando, Yasuhiro Kodera

    Cancer chemotherapy and pharmacology   73 ( 4 )   847 - 55   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)  

    PURPOSE: This study was designed to evaluate (1) the impact of relative dose intensity (RDI) on tumor response and survival outcomes and (2) the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC). METHODS: Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and schedule modification, the effects of dose index (DI) and time index (TI) on outcomes were evaluated. RESULTS: The median RDIs of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80 and 79 %, respectively. Higher RDI of irinotecan in FOLFIRI was associated with significant improvements in RR (65 vs. 6 %, p < 0.01), DCR (100 vs. 59 %, p < 0.01), PFS (9.9 vs. 5.6 months, p < 0.01) and OS (26.7 vs. 12.9 months, p = 0.01) and was the only independent factor associated with PFS [hazard ratio (HR) 8.48, p < 0.01). Higher RDI of oxaliplatin in FOLFOX was significantly associated with DCR (65 vs. 6 %, p < 0.01), and higher TI of oxaliplatin was the only independent factor associated with PFS (HR 2.74, p = 0.04). CONCLUSION: RDIs of irinotecan and oxaliplatin affected clinical outcomes. Dose reductions in irinotecan, as indicated by DI, and time delays in oxaliplatin, as indicated by TI, were the only independent prognostic factors predicting PFS in patients receiving FOLFIRI and FOLFOX6, respectively.

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  • Extraluminal GI stromal tumor of the jejunum diagnosed by EUS at double-balloon endoscopy. 国際誌

    Masanao Nakamura, Naoki Ohmiya, Yoshiki Hirooka, Hiroki Kawashima, Takeshi Yamamura, Makoto Ishihara, Koji Yamada, Asuka Nagura, Toru Yoshimura, Ryoji Miyahara, Kohei Funasaka, Akihiro Itoh, Eizaburo Ohno, Takafumi Ando, Osamu Watanabe, Keisuke Uehara, Yuichiro Yoshioka, Masato Nagino, Hidemi Goto

    Gastrointestinal endoscopy   79 ( 2 )   335 - 6   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)  

    DOI: 10.1016/j.gie.2013.09.016

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  • Adenocarcinoma arising from sacrococcygeal mature teratoma in an adult female: report of a case. 国際誌

    Naoki Matsumoto, Keisuke Uehara, Masataka Ando, Junki Arimoto, Takehiro Kato, Hayato Nakamura, Tomoki Ebata, Yukihiro Yokoyama, Masato Nagino

    Frontiers in oncology   4   117 - 117   2014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 a case of adenocarcinoma arising from a sacrococcygeal mature teratoma in an adult female. A 62-year-old female was diagnosed with a presacral tumor 10 years ago. Pelvic computed tomography (CT) demonstrated a presacral heterogeneous tumor, containing multiloculated cystic area and enhanced solid component with calcification. Percutaneous needle biopsy for the solid component of the tumor identified an adenocarcinoma and the patient was diagnosed as having a sacrococcygeal teratoma with malignant transformation. Abdomino-sacral rectal resection with sacral amputation at the upper edge of the S5 was performed. The pathological diagnosis was adenocarcinoma derived from a mature teratoma. The tumor cells had infiltrated the rectal wall. After 7 months, a follow-up CT demonstrated swelling of the right inguinal lymph nodes and a right inguinal lymphadenectomy was performed. Pathological examination showed metastatic lymph nodes. The patient is doing well 21 months after the second surgery, with no signs of recurrence.

    DOI: 10.3389/fonc.2014.00117

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  • Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. 国際誌

    Keisuke Uehara, Kazuhiro Hiramatsu, Atsuyuki Maeda, Eiji Sakamoto, Masaya Inoue, Satoshi Kobayashi, Yuichiro Tojima, Yuichiro Yoshioka, Goro Nakayama, Hiroshi Yatsuya, Naoki Ohmiya, Hidemi Goto, Masato Nagino

    Japanese journal of clinical oncology   43 ( 10 )   964 - 71   2013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)  

    OBJECTIVE: This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. METHODS: Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. RESULTS: Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. CONCLUSIONS: Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).

    DOI: 10.1093/jjco/hyt115

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  • Combination therapy with single incision laparoscopic surgery and double-balloon endoscopy for small intestinal bleeding: report of three cases.

    Keisuke Uehara, Yuichiro Yoshioka, Tomoki Ebata, Yukihiro Yokoyama, Masanao Nakamura, Naoki Ohmiya, Hidemi Goto, Masato Nagino

    Surgery today   43 ( 9 )   1062 - 5   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)  

    The clinical introduction of double-balloon endoscopy (DBE) has brought about a revolution in the diagnosis and the treatment of diseases of the small intestine. DBE allows not only direct observation of the entire small intestine, but also interventional therapies, tissue sampling and India ink marking (tattooing). Single incision laparoscopic surgery (SILS) was developed from conventional laparoscopic surgery to further reduce the degree of invasiveness. SILS requires only one umbilical incision, thus resulting in almost scarless surgery. This report presents three cases of small intestinal bleeding successfully treated by SILS following tattooing under DBE. The average operative time was 67 min and average blood loss was 5 ml. All patients immediately recovered without any complications. SILS, in conjunction with presurgical tattooing by DBE for small intestinal bleeding is considered to be an ideal approach in terms of minimal surgical trauma and aesthetics.

    DOI: 10.1007/s00595-012-0299-1

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  • Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer. 国際誌

    Tomoyo Oguri, Ayako Mitsuma, Megumi Inada-Inoue, Sachi Morita, Takashi Shibata, Tomoya Shimokata, Mihoko Sugishita, Goro Nakayama, Keisuke Uehara, Yoshinori Hasegawa, Yuichi Ando

    International journal of clinical pharmacology and therapeutics   51 ( 6 )   475 - 81   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)  

    OBJECTIVE: Pharmacogenomic associations between severe oxaliplatininduced chronic peripheral neurotoxicity (OXCPN) (Grade 2 lasting for > 7 days or Grade 3) and 9 single nucleotide polymorphisms (SNPs) in 8 genes (TAC1, FOXC1, ITGA1, ACYP2, DLEU7, BTG4, CAMK2N1, and FARS2) were reported by the genomewide association study (GWAS) in Korean patients. The present study was designed to explore reliable predictors of OXCPN and thereby improve the management of metastatic colorectal cancer (CRC). METHODS: We retrospectively investigated pharmacogenomic characteristics of OXCPN in 70 Japanese patients with CRC who received oxaliplatin-based chemotherapy and updated the results of our previous analysis of ERCC1 (C118T, rs11615 and C8092A, rs3212986) and GSTP1 (Ile105Val, rs1695) polymorphisms. RESULTS: Univariate analysis suggested potential associations of severe OXCPN with rs843748 in ACYP2 and rs17140129 in FARS2, as well as with the absence of diabetes mellitus (DM) (p = 0.056, 0.072, and 0.029, respectively). There was no association between severe OXCPN and any of the 7 other SNPs. Multiple logistic regression analysis showed that an increased risk of severe OXCPN was related to rs17140129 and the absence of DM (p = 0.034 and 0.030, respectively). On updated analysis, polymorphisms of ERCC1 (C118T, rs11615) and rs10486003 in TAC1 were associated with time to the onset of Grade 1 OXCPN (p = 0.024 and 0.049, respectively). CONCLUSIONS: Severe OXCPN is significantly related to rs17140129, found in the GWAS of Korean patients, in Japanese patients. Patients without DM are more likely to have OXCPN. The association between ERCC1 polymorphism and time to the onset of OXCPN was significant on updated analysis.

    DOI: 10.5414/CP201851

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  • Synchronous rectal and esophageal cancer treated with chemotherapy followed by two-stage resection. 国際誌

    Setsuo Utsunomiya, Keisuke Uehara, Takuya Kurimoto, Ken Hirose, Masahide Fukaya, Yu Takahashi, Yoshiro Taguchi, Keita Itatsu, Masato Nagino

    World journal of clinical cases   1 ( 2 )   87 - 91   2013年5月

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    記述言語:英語  

    We report a case of 61-year-old male who had synchronous advanced rectal cancer involving the urinary bladder massively associated with multiple liver metastases, and esophageal cancer successfully treated by neoadjuvant chemotherapy followed by two-stage resection. Although complete resection of each of the lesions was considered possible by performing anterior pelvic exenteration, liver resection, and esophagectomy, it might be impossible for the patient to endure the stress of all of these operative procedures at once. Therefore, we planned to perform staged treatment with prioritizing consideration. First, we instituted chemotherapy with the FOLFOX (oxaliplatin + fluorouracil + leucovorin) plus cetuximab regimen, which could adequately control both rectal and esophageal cancer. After 6 cycles of chemotherapy, high anterior resection combined with cystoprostatectomy and lateral segmentectomy plus partial hepatectomy was performed followed by staged esophagectomy with three-field lymph node dissection. It was possible to use oxaliplatin and cetuximab safely as neoadjuvant therapy not only for advanced rectal cancer but for esophageal cancer, and it was effective.

    DOI: 10.12998/wjcc.v1.i2.87

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  • Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer. 国際誌

    Sachi Morita, Keisuke Uehara, Goro Nakayama, Takashi Shibata, Tomoyo Oguri, Megumi Inada-Inoue, Tomoya Shimokata, Mihoko Sugishita, Ayako Mitsuma, Yuichi Ando

    Cancer chemotherapy and pharmacology   71 ( 2 )   405 - 11   2013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)  

    PURPOSE: Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy. METHODS: We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure. RESULTS: The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension. CONCLUSIONS: This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.

    DOI: 10.1007/s00280-012-2028-2

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  • Phase II trial of adjuvant chemotherapy with S-1 for colorectal liver metastasis. 国際誌

    Keisuke Uehara, Atsuyuki Maeda, Eiji Sakamoto, Kazuhiro Hiramatsu, Eiji Takeuchi, Kenji Sakaguchi, Yuichiro Tojima, Yu Takahashi, Tomoki Ebata, Masato Nagino

    Annals of surgical oncology   20 ( 2 )   475 - 81   2013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: This phase II trial was designed to evaluate the safety and efficacy of adjuvant chemotherapy with S-1 in patients with curatively resected liver metastasis from colorectal cancer. Results of an interim analysis of safety and short-term outcomes are reported. METHODS: Patients who underwent curative resection of liver metastasis from colorectal cancer received S-1 monotherapy (on days 1-28, followed by 14 days' rest, 8 cycles) as adjuvant chemotherapy. RESULTS: Among 62 patients enrolled between October 2008 and August 2010, a total of 60 patients were eligible for analysis. The most frequent grade 3 or higher hematologic toxicity involved neutropenia in three patients (5.0 %). Nonhematologic toxicities of grade 3 or higher were fatigue in 6.7 % of patients. Grade 4 enteritis occurred in one patient, but resolved promptly after withdrawal of S-1 therapy. The completion rate of the eight scheduled cycles of chemotherapy was 58.3 %. The most common reasons for withdrawal of treatment was the detection of early relapse in 16 patients (64 %). When the 16 patients who had recurrence during adjuvant treatment were excluded from analysis, 79.5 % of the remaining 44 patients completed the scheduled treatment. Early recurrence within 1 year after curative liver resection occurred in 21 patients (35 %). The most common site was the remnant liver in 14 patients. CONCLUSIONS: Orally administered S-1 after curative liver resection has an acceptable toxicity profile and a high rate of completion of the therapy. S-1 can be safely used and might be a viable treatment option in an adjuvant setting.

    DOI: 10.1245/s10434-012-2665-z

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  • Optimal schedule of adjuvant chemotherapy with S-1 for stage III colon cancer: study protocol for a randomized controlled trial. 国際誌

    Kenichi Yoshimura, Keisuke Uehara, Yuichiro Tojima, Satoru Kawai, Yasuji Mokuno, Atsuyuki Maeda, Takanori Kyokane, Satoshi Kobayashi, Yuichiro Yoshioka, Masato Nagino

    Trials   14   17 - 17   2013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: Although, in Western countries, oxaliplatin-based regimens have been established as a gold standard treatment for patients with stage III or high risk stage II colon cancer after curative resection, in Japan fluorouracil-based regimens have been widely accepted and recommended in the guidelines for adjuvant settings in patients with stage III colon cancer. S-1, an oral preparation evolved from uracil and tegafur, has equivalent efficacy to uracil and tegafur/leucovorin for treating patients with advanced colorectal cancer and might be a suitable regimen in an adjuvant setting. However, the completion rate of the standard six-week cycle of the S-1 regimen is poor and the establishment of an optimal treatment schedule is critical. Therefore, we will conduct a multicenter randomized phase II trial to compare six-week and three-week cycles to establish the optimal schedule of S-1 adjuvant therapy for patients with stage III colon cancer after curative resection. METHODS/DESIGN: The study is an open-label, multicenter randomized phase II trial. The primary endpoint of this study is three-year disease-free survival rate. Secondary endpoints are the completion rate of the treatment, relative dose intensity, overall survival, disease-free survival, and incidence of adverse events. The sample size was 200, determined with a significance level of 0.20, power of 0.80, and non-inferiority margin of a 10% absolute difference in the primary endpoint. DISCUSSION: Although S-1 has not been approved yet as a standard treatment of colon cancer in an adjuvant setting, it is a promising option. Moreover, in Japan S-1 is a standard treatment for patients with stage II/III gastric cancer after curative resection and a promising option for patients with colorectal liver metastases in an adjuvant setting. However, a six-week cycle of treatment is not considered to be the best schedule, and some clinicians use a modified schedule, such as a three-week cycle to keep a sufficient dose intensity with few adverse events. Therefore, it will be useful to determine whether a three-week cycle has an equal or greater efficacy and tolerance to side-effects compared with the standard six-week cycle schedule, and thus may be the most suitable treatment schedule for S-1 treatment. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000006750.

    DOI: 10.1186/1745-6215-14-17

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  • The efficacy and safety of bevacizumab beyond first progression in patients treated with first-line mFOLFOX6 followed by second-line FOLFIRI in advanced colorectal cancer: a multicenter, single-arm, phase II trial (CCOG-0801). 国際誌

    Goro Nakayama, Keisuke Uehara, Kiyoshi Ishigure, Hiroyuki Yokoyama, Akiharu Ishiyama, Takehiko Eguchi, Kenji Tsuboi, Norifumi Ohashi, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yuich Ando, Yasuhiro Kodera

    Cancer chemotherapy and pharmacology   70 ( 4 )   575 - 81   2012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)  

    PURPOSE: The aim of this study was to evaluate the efficacy and safety of the planned continuation of bevacizumab beyond first progression (BBP) in Japanese patients with metastatic colorectal cancer (mCRC). METHODS: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. Secondary endpoints of the study were overall survival (OS), survival beyond first progression (SBP), progression-free survival (PFS), response rate (RR), disease control rate (DCR), and safety. RESULTS: In the first-line setting, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7 %, DCR of 89.4 %, and median PFS of 13.1 months (95 % CI, 8.7-17.5 months). Thirty-one patients went on to receive a second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6 %, DCR of 62.1 %, and median PFS of 7.3 months (95 % CI, 5.0-9.6 months). Median 2nd PFS was 18.0 months (95 % CI, 13.7-22.3 months). The median OS and SBP were 30.8 months (95 % CI, 27.6-34.0 months) and 19.6 months (95 % CI, 13.5-25.7 months), respectively. No critical events associated with bevacizumab were observed during the second-line therapy. CONCLUSION: The planned continuation of bevacizumab during a second-line treatment, BBP strategy, is feasible for the Japanese mCRC patients.

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  • Locally recurrent rectal cancer successfully treated by total pelvic exenteration with combined ischiopubic rami resection: report of a case. 国際誌

    Keisuke Uehara, Yuichiro Yoshioka, Yoshiro Taguchi, Tsuyoshi Igami, Tomoki Ebata, Yukihiro Yokoyama, Gen Sugawara, Satoshi Tsukushi, Yoshihiro Nishida, Yasushi Yoshino, Masato Nagino

    Japanese journal of clinical oncology   42 ( 1 )   58 - 62   2012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)  

    A combined ischiopubic rami resection is extremely rare in the field of gastroenterologic surgery. We report a case of a locally recurrent rectal cancer that was successfully treated by total pelvic exenteration with combined ischiopubic rami resection. A 58-year-old male with locally recurrent rectal cancer and liver metastases was referred to our hospital. Computed tomography and magnetic resonance imaging showed a perineal tumor, which had invaded the prostate, urethra, and obturator internus muscle, and two liver metastases. Because the perineal tumor was very close to the dorsal vein complex and the pubic symphysis, it was considered difficult to approach and divide the dorsal vein complex, and still retain oncologic safety. To achieve R0 resection, total pelvic exenteration with ischiopubic rami resection, total emasculation and partial liver resection were performed. Pathological examination revealed that surgical margins were negative for cancer cells. Although reconstruction of the pelvic ring was not performed, his ambulatory function had recovered to an almost normal status at 6 months after the operation.

    DOI: 10.1093/jjco/hyr169

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  • Rectal duplication cyst successfully treated by laparoscopic total mesorectal excision using the prolapsing technique.

    K Akahane, K Uehara, Y Yoshioka, F Koide, T Ebata, Y Yokoyama, T Igami, G Sugawara, Y Takahashi, M Fukaya, K Itatsu, M Nakamura, H Goto, M Nagino

    Asian journal of endoscopic surgery   4 ( 4 )   174 - 7   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)  

    Congenital alimentary tract duplication is a rare disease. It most frequently occurs in the ileum, with the rectum being the rarest site. Herein, we report a 38-year-old woman who was referred to our hospital because of severe anal pain. On digital examination, a smooth, round, rubbery mass was palpable; it was located 5 cm from the anal verge in the posterior rectal wall. A CT scan demonstrated a 5-cm cystic lesion located anterior to the sacrum that was displacing the rectum anteriorly. Spontaneous remission of the tumor was evident; however, after 5 months of follow-up, the patient experienced the same severe anal pain. MRI demonstrated a recurrent cystic lesion. To prevent further complications and to confirm or deny malignancy, laparoscopic total mesorectal excision using the prolapsing technique was performed. Pathologically, the cystic lesion was diagnosed as a rectal duplication cyst. This is the first report of a rectal duplication cyst successfully treated by laparoscopic total mesorectal excision.

    DOI: 10.1111/j.1758-5910.2011.00097.x

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  • Conversion chemotherapy using cetuximab plus FOLFIRI followed by bevacizumab plus mFOLFOX6 in patients with unresectable liver metastases from colorectal cancer. 国際誌

    Keisuke Uehara, Seiji Ishiguro, Kazuhiro Hiramatsu, Hideki Nishio, Eiji Takeuchi, Daisuke Takahari, Yuichiro Yoshioka, Yu Takahashi, Tomoki Ebata, Kenichi Yoshimura, Kei Muro, Masato Nagino

    Japanese journal of clinical oncology   41 ( 10 )   1229 - 32   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)  

    Recently, in patients with unresectable colorectal liver metastasis, liver resection sometimes becomes possible by intensive systemic chemotherapy, i.e. conversion therapy. However, among cases that do not respond well to first-line chemotherapy, it is rare that second-line chemotherapy results in a marked response allowing liver resection. We consider that the liver resection rate may be increased by initiating second-line treatment at an earlier stage before progression subsequent to first-line chemotherapy. We are conducting a multicentre Phase II study to evaluate the efficacy and safety of sequential chemotherapy using six cycles of cetuximab plus FOLFIRI (5-fluorouracil, folinic acid and irinotecan) followed by six cycles of bevacizumab plus FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) as conversion chemotherapy. The primary endpoint is the liver resection rate during the bevacizumab + FOLFOX phase. Fifty patients are required for this study.

    DOI: 10.1093/jjco/hyr115

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  • Phase II trial of neoadjuvant chemotherapy with XELOX plus bevacizumab for locally advanced rectal cancer. 国際誌

    Keisuke Uehara, Seiji Ishiguro, Eiji Sakamoto, Atsuyuki Maeda, Masaya Inoue, Yuichiro Tojima, Satoshi Kobayashi, Naoki Omiya, Naoki Ishizuka, Akimasa Nakao, Hidemi Goto, Masato Nagino

    Japanese journal of clinical oncology   41 ( 8 )   1041 - 4   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)  

    In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. On the other hand, in Japan, treatment results without radiotherapy are by no means inferior; therefore, extrapolation of results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative treatment with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy using XELOX plus bevacizumab without radiotherapy in patients with locally advanced rectal cancer. The primary endpoint of the study is treatment compliance. Secondary endpoints are overall survival, disease-free survival, local recurrence-free survival, objective response rate, R0 resection rate and adverse events. Thirty patients are required for this study.

    DOI: 10.1093/jjco/hyr084

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  • A left hepatectomy and caudate lobectomy combined resection of the ventral segment of the right anterior sector for hilar cholangiocarcinoma--the efficacy of PVE (portal vein embolization) in identifying the hepatic subsegment: report of a case.

    Tsuyoshi Igami, Yukihiro Yokoyama, Hideki Nishio, Tomoki Ebata, Gen Sugawara, Yoshiki Senda, Koji Oda, Tetsuya Abe, Keisuke Uehara, Masato Nagino

    Surgery today   39 ( 7 )   628 - 32   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This report presents a case of a left hepatectomy and a caudate lobectomy combined resection of the ventral segment of the right anterior sector for hilar cholangiocarcinoma using percutaneous transhepatic portal vein embolization (PVE). The patient was a 44-year-old man admitted to a local hospital with obstructive jaundice. He was diagnosed to have hilar cholangiocarcinoma and was referred to the hospital for further treatment. Cholangiography revealed stenosis of the left hepatic duct and the hilar bile ducts. The dorsal branch of the right anterior sector joined the right posterior branch and the tumor did not invade to the confluence of these branches. Arteriography and portography reconstructed by multidetector-raw computed tomography revealed the ventral branches of the right anterior sector, which separately diverged from the other right anterior branches. It was therefore necessary to perform a left hepatectomy and caudate lobectomy combined resection of the ventral segment of the right anterior sector to completely remove the tumor. Portal vein embolization was thus performed on the left portal vein and the ventral branches of the right anterior sector. Intraoperatively, when the hepatic artery was temporally clamped, the demarcation between the ventral segment and the dorsal segment of the right anterior sector could be clearly visualized. The planned surgery was performed safely. This case demonstrates that the utilization of PVE is useful for a difficult and intricate hepatectomy, which requires an accurate identification of a hepatic subsegment.

    DOI: 10.1007/s00595-008-3902-8

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  • Clinicopathological significance of fibrous tissue around fixed recurrent rectal cancer in the pelvis. 国際誌

    K Uehara, T Shimoda, Y Nakanishi, H Taniguchi, T Akasu, S Fujita, S Yamamoto, Y Moriya

    The British journal of surgery   94 ( 12 )   1530 - 5   2007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: Fibrous tissue around a locally recurrent rectal tumour is an interesting histological feature, but its clinicopathological significance has not been investigated. METHODS: This retrospective study examined clinicopathological findings in 48 patients who underwent curative total pelvic exenteration with distal sacrectomy (TPES) between 1992 and 2004. Data were analysed with respect to fibrosis around the recurrent tumour, categorized into one of three groups: no fibrosis (f0), partial fibrosis (f1) or circumferential fibrosis (f2). RESULTS: Ten, 17 and 21 patients had f0, f1 and f2 fibrosis respectively, with 5-year survival of none, four and eight patients respectively. The overall survival of patients with circumferential fibrosis was significantly better than that in patients with no fibrosis (P = 0.003). Univariable analysis showed that a high level of sacrectomy (P = 0.036), absence of lymphatic invasion (P = 0.031) and circumferential fibrosis (P = 0.039) were significantly associated with better overall survival. In multivariable analysis, circumferential fibrosis (P = 0.031) and low serum carcinoembryonic antigen levels (P = 0.044) were independent factors for a favourable outcome. CONCLUSION: The outcome of patients with locally recurrent rectal cancer after curative TPES appears to be better when circumferential fibrosis is present around the tumour.

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  • Clinicopathological significance of microscopic abscess formation at the invasive margin of advanced low rectal cancer. 国際誌

    K Uehara, Y Nakanishi, T Shimoda, H Taniguchi, T Akasu, Y Moriya

    The British journal of surgery   94 ( 2 )   239 - 43   2007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 aim of this study was to evaluate the clinicopathological significance of microscopic abscess formation (MAF) at the invasive front of advanced low rectal cancer. METHODS: The clinicopathological features of 226 consecutive patients with low rectal cancer, who underwent curative resection between May 1997 and December 2002, were analysed. RESULTS: Fifty-seven (25.2 per cent) of the 226 tumours had MAF and 169 (74.8 per cent) did not. Patients with tumours showing MAF were more likely to have extended surgery than those without MAF: 47 versus 31.4 per cent respectively underwent non-sphincter-preserving surgery (P=0.029) and 82 versus 60.9 per cent underwent lateral lymph node dissection (P=0.003). The incidence of lymph node metastases was lower in patients with MAF (30 versus 53.3 per cent; P=0.002). Univariable analysis of disease-free survival revealed that depth of invasion (P<0.001), lymph node status (P<0.001), histological type (P=0.035), lymphatic invasion (P<0.001), venous invasion (P<0.001), perineural invasion (P<0.001), focal dedifferentiation (P<0.001) and MAF (P<0.001) were significant prognostic factors. Multivariable analysis showed that lymph node status (P<0.001), perineural invasion (P=0.002), venous invasion (P=0.033) and MAF (P=0.012) remained independent prognostic factors. CONCLUSION: MAF may reflect indolent tumour behaviour and a more favourable outcome in patients with advanced low rectal cancer.

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  • Impact of upward lymph node dissection on survival rates in advanced lower rectal carcinoma. 国際誌

    Keisuke Uehara, Seiichiro Yamamoto, Shin Fujita, Takayuki Akasu, Yoshihiro Moriya

    Digestive surgery   24 ( 5 )   375 - 81   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIMS: This study investigated appropriate level of upward lymph node (LN) dissection in advanced lower rectal carcinoma. METHODS: A total of 285 consecutive patients with stage II/III lower rectal carcinoma were analyzed. LN dissection was classified as follows: division of the root of the superior rectal artery (UD2), division of the root of the inferior mesenteric artery (UD3) and UD3 with para-aortic LN dissection (UD4). RESULTS: LN metastases at the root of the inferior mesenteric artery were found in 4 patients. Their prognoses were worse than those of the other stage III patients (p = 0.011). On the other hand, LN metastases along the superior rectal artery were discovered in 14 patients, whose 5-year overall survival rate was 61.2%. By removing the LNs either UD2 or UD3/4, a similar survival rate was achieved in stage III patients with LN metastases along the superior rectal artery. CONCLUSION: Survival of a minority with metastatic LNs at the root of the inferior mesenteric artery was poor. Additionally, survival is no worse in patients with positive LN along the superior rectal artery as long as these positive nodes are resected by either UD2 or UD3/4. Low ligation is adequate for advanced lower rectal carcinoma.

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  • Intrabiliary polypoid growth of liver metastasis from colonic adenocarcinoma with minimal invasion of the liver parenchyma.

    Keisuke Uehara, Hiroshi Hasegawa, Seiji Ogiso, Eiji Sakamoto, Tsuyoshi Igami, Syusaku Ohira, Toshiharu Mori

    Journal of gastroenterology   39 ( 1 )   72 - 5   2004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)  

    Liver metastases from colorectal cancer easily invade the Glisson's triad and sometimes have intrabiliary tumor growth. This behavior is by no means rare, and causes the cut end of the Glisson's triad to be positive for cancer. We report here a 72-year-old Japanese man with a medical history of ascending colon cancer in whom enhanced computed tomography (CT) showed a low-density mass in the caudate lobe of the liver and dilatation of the peripheral intrahepatic bile duct. He underwent right hemihepatectomy and caudate lobectomy. The resected specimen showed a polypoid tumor in the bile duct lumen, with minimal invasion of the liver parenchyma; the tumor was similar to cholangio-carcinoma. Histological findings proved it to be well-differentiated adenocarcinoma. Immunochemically, the tumor cells were positive for cytokeratin (CK) 20, but negative for CK7, and we finally diagnosed him with intrabiliary polypoid growth of liver metastasis from colonic cancer. For complete surgical resection, it is very important to diagnose intrabiliary tumor growth. However, we could not diagnose it preoperatively in spite of the CT detecting an intrabiliary polypoid tumor, because the CT revealed no extrabiliary tumors in the liver parenchyma. We have to pay attention to the fact that CT rarely demonstrates only intrabiliary growth without extrabiliary tumors.

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  • Skip lymph node metastases from a small hepatocellular carcinoma with difficulty in preoperative diagnosis. 国際誌

    Keisuke Uehara, Hiroshi Hasegawa, Seiji Ogiso, Eiji Sakamoto, Syusaku Ohira, Tsuyoshi Igami, Toshiharu Mori

    Journal of gastroenterology and hepatology   18 ( 3 )   345 - 9   2003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)  

    Recent autopsy studies have clarified the frequency of lymph node (LN) metastases from hepatocellular carcinoma (HCC). However, LN metastases commonly occur in advanced and poorly differentiated HCC and are very rare in small HCC. We encountered a patient with skip LN metastases from a small HCC, 10 mm in diameter. An intra-abdominal tumor adjoining the duodenum was detected by follow-up ultrasonography for viral hepatitis C. Computed tomography showed, in addition to the tumor bordering the duodenum, a small low-density area of the liver (S6), 2 cm in diameter, and a swelling of LN adjacent to the common hepatic artery. Upper gastrointestinal rentogenography revealed a compression of the duodenal second portion without irregularity of the mucosa. Our pre-operative diagnosis was duodenal gastrointestinal stromal tumor with LN metastasis and HCC or liver metastasis. However, laparotomy proved them to be LN metastases from a small HCC and partial hepatectomy and LN dissection were performed. The patient is doing well 22 months after surgery with no signs of recurrence. In the cases of HCC with LN metastases, the prognosis is generally very poor. However, in small HCC, the clinical characteristics are not fully evaluated. In treatment, we have to keep LN metastases, particularly skip LN metastases, in mind, even in cases of small HCC.

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  • [A Case of the Cyst of the Gallbladder].

    Toshiharu Mori, Hiroshi Hasegawa, Seiji Ogiso, Eiji Sakamoto, Hiroaki Shibahara, Tsuyoshi Igami, Shusaku Ohira, Keisuke Uehara, Toyonori Tsuzuki

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology   99 ( 6 )   631 - 4   2002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)  

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▼全件表示

MISC

  • 直腸癌に対する根治的腹腔鏡下手術術後の局所再発における危険因子の検討 術者の技術認定の有無が危険因子となるか

    崎村 祐介, 伴登 宏行, 肥田 侯矢, 福岡 達成, 船越 徹, 寺石 文則, 上原 圭, 井上 雄志, 鈴木 伸明, 市川 伸樹, 武富 紹信, 内藤 剛

    日本外科学会定期学術集会抄録集   123回   SF - 3   2023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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  • 【知っておくべき!最新の大腸外科局所解剖】結腸脾彎曲の外科解剖

    相場 利貞, 上原 圭, 小倉 淳司, 村田 悠記, 砂川 真輝, 渡辺 伸元, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 伊神 剛, 國料 俊男, 横山 幸浩, 江畑 智希

    消化器外科   44 ( 9 )   1409 - 1415   2021年8月

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    記述言語:日本語   出版者・発行元:(株)へるす出版  

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  • 切除可能同時性肝転移を有する大腸癌に対する周術期化学療法の有効性の検討

    三品 拓也, 上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 鈴木 優美, 神原 祐一, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本消化器外科学会総会   76回   P010 - 3   2021年7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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  • 側方リンパ節転移陽性直腸癌に対する治療戦略 側方リンパ節転移陽性直腸癌に対する治療戦略 術前化学療法の経験からの提言

    小倉 淳司, 上原 圭, 相場 利貞, 村田 悠記, 鈴木 優美, 三品 拓也, 神原 祐一, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本消化器外科学会総会   76回   PD4 - 7   2021年7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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  • 左側大腸癌の大動脈周囲リンパ節郭清の長期成績

    松村 卓樹, 上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 三品 拓也, 横山 幸浩, 小寺 泰弘, 佐野 力, 江畑 智希

    日本消化器外科学会総会   76回   P031 - 3   2021年7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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  • Paget病に対する会陰部薄筋皮弁再建後の肛門管癌に対し腹直筋皮弁再建を伴う腹腔鏡下骨盤内臓全摘術を行った1例

    鈴木 優美, 上原 圭, 相場 利貞, 小倉 淳司, 横山 幸浩, 角田 伸行, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 江畑 智希

    日本臨床外科学会雑誌   82 ( 5 )   1031 - 1031   2021年5月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 【側方リンパ節郭清のすべて-開腹からロボット手術まで】手技の実際 経肛門的アプローチによる側方リンパ節郭清

    相場 利貞, 上原 圭, 小倉 淳司, 村田 悠記, 三品 拓也, 横山 幸浩, 國料 俊男, 伊神 剛, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 江畑 智希

    臨床外科   76 ( 5 )   596 - 602   2021年5月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>ポイント ◆経肛門的アプローチでの側方リンパ節郭清(taLPLD)は,転移頻度の高い骨盤深部領域の郭清を目の前で,かつ解剖学的構造物に対して良好な鉗子の刺入角度で施行できる.◆しかし,本法で展開される経肛門視点の術野は独特であり,十分慣れ親しんでおく必要がある.◆また,taLPLDは,プラットフォームに対して極端に側方に位置する領域に対して単孔式腹腔鏡下手術の技術を使って行う手技であるため,技術的には決して容易ではない.

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01539&link_issn=&doc_id=20210428590013&doc_link_id=10.11477%2Fmf.1407213349&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1407213349&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 【令和時代における「尾状葉」のすべて】尾状葉の解剖 肝尾状葉の胆管枝

    江畑 智希, 水野 隆史, 尾上 俊介, 渡辺 伸元, 山口 淳平, 伊神 剛, 上原 圭, 宮田 一志, 小倉 淳司, 横山 幸浩

    肝胆膵   82 ( 5 )   661 - 667   2021年5月

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    記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • 直腸癌同時性肝転移に対する手術治療戦略

    米川 佳彦, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   PS - 8   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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  • 【専門医必携 新外科手術書-新しい手術手技のエッセンス】大腸 剥離層を意識した腹腔鏡下低位前方切除術の手術手技

    小倉 淳司, 上原 圭, 相場 利貞, 村田 悠記, 江畑 智希

    外科   83 ( 5 )   506 - 512   2021年4月

  • 進行再発大腸癌に対する集学的アプローチの最先端 結腸癌非肝肺転移に対する外科切除の意義

    三品 拓也, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 神野 孝徳, 鈴木 優美, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   WS - 2   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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  • 局所進行直腸癌における術前化学療法後の病理学的リンパ節転移奏功度の意義

    相場 利貞, 上原 圭, 小倉 淳司, 大原 規彰, 神野 孝徳, 鈴木 優美, 三品 拓也, 村田 悠記, 渡辺 伸元, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 深谷 昌秀, 伊神 剛, 服部 憲史, 中山 吾郎, 横山 幸浩, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 5   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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  • 下部直腸癌術後患者の長期腎機能へ影響を与える因子の検討

    山東 雅紀, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 村田 悠記, 三品 拓也, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 川井 覚, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 5   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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  • 骨盤内臓全摘術後のサルコペニア 内腸骨動脈血管処理に着目して

    村田 悠記, 上原 圭, 相場 利貞, 小倉 淳司, 大原 規彰, 神野 孝徳, 三品 拓也, 鈴木 優美, 服部 憲史, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 江畑 智希

    日本外科学会定期学術集会抄録集   121回   SF - 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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  • 当科における痔瘻癌の治療経験

    稲垣 公太, 中山 吾郎, 服部 憲史, 上原 圭, 相場 利貞, 佐藤 雄介, 小倉 淳司, 山田 豪, 小池 聖彦, 藤原 道隆, 江畑 智希, 小寺 泰弘

    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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  • 直腸癌に対するロボット支援下腹腔鏡下手術の現状と展望およびエビデンス ロボット支援下直腸癌手術の長期成績

    相場 利貞, 上原 圭, 青葉 太郎, 平松 和洋, 加藤 岳人, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 横山 幸浩, 江畑 智希

    日本内視鏡外科学会雑誌   25 ( 7 )   SY18 - 2   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 直腸がんの治療戦略-内視鏡外科をどう活かすか? 骨盤拡大手術における内視鏡外科手術での後腹膜アプローチ

    上原 圭, 相場 利貞, 小倉 淳司, 村田 悠記, 松村 卓樹, 三品 拓也, 大原 規彰, 鈴木 優美, 伊神 剛, 水野 隆史, 宮田 一志, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本内視鏡外科学会雑誌   25 ( 7 )   SSY5 - 3   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本内視鏡外科学会  

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  • 【胆膵領域の臨床試験Up to date〜これを読めば世界が見える】胆管癌切除後再発予防をめざした術後補助療法

    江畑 智希, 水野 隆史, 横山 幸浩, 國料 俊男, 伊神 剛, 山口 淳平, 尾上 俊介, 深谷 昌秀, 上原 圭, 宮田 一志, 相場 利貞, 渡辺 伸元, 小倉 淳司

    胆と膵   42 ( 1 )   81 - 85   2021年1月

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    記述言語:日本語   出版者・発行元:医学図書出版(株)  

    胆道癌の切除後の生存率は不良であり、とくに進行例に対する手術単独の効果には限界がある。このため集学的治療が必要で、そのなかでも切除後の補助化学療法に関する臨床試験の結果が重要である。最近、重要な第III相試験の結果が公開された。第一は、本邦のBCAT試験である。Gemcitabineと切除単独を比較したが、その有効性は認めなかった。第二はフランスで行われたPRODIGE-12試験で、GEMOXの切除単独群に対する有効性は認めなかった。第三は、Capecitabineの有効性を検証する英国BILCAP試験である。ITT解析では有意差を認めなかったものの、per protocol解析で有意差を認めた。これらの結果から、欧米諸国ではCapecitabineが胆道癌の術後補助化学療法として推奨されるに至った。一方、本邦では胆道癌に対して保険収載されていないため、本方針を日常診療で用いることはできない。(著者抄録)

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  • 結腸左半切除術のコツとピットフォール

    上原 圭, 相場 利貞, 小倉 淳司, 山東 雅紀, 田中 綾, 大原 規彰, 村田 悠記, 神野 孝徳, 佐藤 雄介, 服部 憲史, 中山 吾郎, 渡辺 伸元, 尾上 俊介, 宮田 一志, 山口 淳平, 水野 隆史, 深谷 昌秀, 伊神 剛, 國料 俊男, 横山 幸浩

    日本外科系連合学会誌   45 ( 5 )   495 - 495   2020年12月

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    記述言語:日本語   出版者・発行元:日本外科系連合学会  

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  • 肝臓 集学的治療

    米川 佳彦, 上原 圭, 相場 利貞, 小倉 淳司, 山東 雅紀, 田中 綾, 大原 規彰, 村田 悠記, 神野 孝徳, 佐藤 雄介, 服部 憲史, 中山 吾郎, 横山 幸浩, 國料 俊男, 伊神 剛, 深谷 昌秀, 水野 隆史, 江畑 智希, 小寺 泰弘, 梛野 正人

    日本消化器外科学会雑誌   53 ( Suppl.2 )   254 - 254   2020年11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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  • 肝門部領域胆管癌の術式選択と治療成績 肝門部領域胆管癌に対する左三区域切除と治療成績

    水野 隆史, 尾上 俊介, 渡辺 伸元, 横山 幸浩, 伊神 剛, 山口 淳平, 深谷 昌秀, 上原 圭, 宮田 一志, 相場 利貞, 小倉 淳司

    日本臨床外科学会雑誌   81 ( 増刊 )   230 - 230   2020年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 切除可能大腸癌肝転移症例における早期再発リスク因子の検討

    米川 佳彦, 上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 神野 孝徳, 三品 拓也, 鈴木 優美, 中山 吾郎, 横山 幸浩, 伊神 剛, 深谷 昌秀, 小寺 泰弘, 江畑 智希

    日本臨床外科学会雑誌   81 ( 増刊 )   325 - 325   2020年10月

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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  • 高度肥満症例に対し"小さいが安全な術野"を連続させる腹腔鏡下大腸切除術

    村田 悠記, 上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 神野 孝徳, 鈴木 優美, 三品 拓也, 深谷 昌秀, 伊神 剛, 國料 俊男, 横山 幸浩, 小寺 泰弘, 江畑 智希

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    記述言語:日本語   出版者・発行元:日本臨床外科学会  

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    神野 孝徳, 上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 深谷 昌秀, 伊神 剛, 國料 俊男, 横山 幸浩, 小寺 泰弘, 江畑 智希

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    日本外科感染症学会雑誌   17 ( 5 )   430 - 430   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 傍仙骨会陰アプローチにて切除しえた坐骨直腸窩平滑筋肉腫の1例

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 骨盤内臓全摘術の手術手技と成績 骨盤内臓全摘術の基本と応用

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    日本大腸肛門病学会雑誌   73 ( 9 )   A68 - A68   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 直腸癌に対する術前治療の現状と展望 下部進行直腸癌に対するpatient-adopted strategyを目指した当科の術前治療と成績

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    日本大腸肛門病学会雑誌   73 ( 9 )   A52 - A52   2020年9月

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  • 傍仙骨会陰アプローチにて切除しえた坐骨直腸窩平滑筋肉腫の1例

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    日本大腸肛門病学会雑誌   73 ( 9 )   A112 - A112   2020年9月

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    日本大腸肛門病学会雑誌   73 ( 9 )   A143 - A143   2020年9月

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  • 大腸癌手術の精度とCMEとTMEの意義 直腸癌他臓器合併切除標本の環状切開処理によるCRMの意義

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    日本大腸肛門病学会雑誌   73 ( 9 )   A41 - A41   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • Chemotherapy-free intervalを得るため積極的に手術適応としたBRAF V600E変異型盲腸癌腹膜播種再発の1例

    神野 孝徳, 上原 圭, 相場 利貞, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 9 )   A185 - A185   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 大腸癌手術の精度とCMEとTMEの意義 直腸癌他臓器合併切除標本の環状切開処理によるCRMの意義

    相場 利貞, 上原 圭, 小倉 淳司, 田中 綾, 大原 規彰, 村田 悠記, 鈴木 優美, 三品 拓也, 佐藤 雄介, 服部 憲史, 中山 吾郎, 小寺 泰弘, 江畑 智希

    日本大腸肛門病学会雑誌   73 ( 9 )   A41 - A41   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 大腸癌局所再発に対する外科治療【International】局所再発直腸癌の外科治療 遠隔転移の有無や既往は手術適応に影響するか(Surgical treatment for locally recurrent rectal cancer: Does the presence or history of distant metastasis affect surgical indications?)

    上原 圭, 相場 利貞, 小倉 淳司, 山東 雅紀, 田中 綾, 大原 規範, 佐藤 雄介, 服部 憲史, 中山 吾郎, 江畑 智希, 横山 幸浩, 伊神 剛, 深谷 昌秀, 水野 隆史, 山口 淳平, 宮田 一志, 尾上 俊介, 渡辺 伸元, 小寺 泰弘, 梛野 正人

    日本外科学会定期学術集会抄録集   120回   WS - 5   2020年8月

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  • 【T4b大腸癌に対する腹腔鏡下手術 安全・確実に病変を取り除くために!】尿管・膀胱浸潤 尿管・膀胱浸潤を伴う大腸癌に対する手術

    相場 利貞, 上原 圭, 小倉 淳司, 田中 綾, 大原 規彰, 神野 孝徳, 三品 拓也, 鈴木 優美, 村田 悠記, 横山 幸浩, 江畑 智希

    消化器外科   43 ( 8 )   1223 - 1230   2020年7月

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    記述言語:日本語   出版者・発行元:(株)へるす出版  

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  • Impact of UGT1A1 genotype on overall survival in Japanese advanced colorectal cancer patients treated by irinotecan-based regimens.

    Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Katsunori Shinozaki, Kanehisa Fukumoto, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Miyuki Arai, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata

    JOURNAL OF CLINICAL ONCOLOGY   34 ( 15 )   2016年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2016.34.15_suppl.3571

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  • Impact of UGT1A1 genotype on prognosis in Japanese advanced colorectal cancer patients treated by irinotecan-based regimens.

    Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Katsunori Shinozaki, Kanehisa Fukumoto, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata

    JOURNAL OF CLINICAL ONCOLOGY   33 ( 15 )   2015年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • An internally and externally validated nomogram to predict severe neutropenia in Japanese patients (pts) with advanced colorectal cancer (aCRC) treated with irinotecan (IR1)-based regimens.

    Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Hideaki Miyauchi, Sotaro Sadahiro, Ken-ichi Fujita, Toshikazu Moriwaki, Masato Nakamura, Takehiro Takahashi, Akihito Tsuji, Katsunori Shinozaki, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1200/jco.2014.32.15_suppl.3543

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  • Response to the first-line FOLFOX plus bevacizumab (BEV) therapy to predict responses to the subsequent therapies and survival in the BEV beyond progression (BBP) strategy for metastatic colorectal cancer: A retrospective analysis of CCOG-0801 study

    Goro Nakayama, Keisuke Uehara, Naomi Hayashi, Chie Tanaka, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara, Yuichi Ando, Yasuhiro Kodera

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 3 )   2014年1月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • Prospective analysis of UGT1A1 genotyping for predicting toxicities in advanced colorectal cancer (aCRC) treated with irinotecan (IRI)-based regimens: Interim safety analysis of a Japanese observational study.

    Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Sotaro Sadahiro, Hideaki Miyauchi, Katsunori Shinozaki, Takuya Miyagaki, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata

    JOURNAL OF CLINICAL ONCOLOGY   31 ( 15 )   2013年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.

    Naomi Hayashi, Goro Nakayama, Kiyoshi Ishigure, Hiroyuki Yokoyama, Toyohisa Yaguchi, Hiroshi Kojima, Kenji Tsuboi, Akihiro Ito, Tomohiro Deguchi, Masanori Sekiya, Chie Tanaka, Keisuke Uehara, Yuichi Ando, Yasuhiro Kodera

    JOURNAL OF CLINICAL ONCOLOGY   31 ( 15 )   2013年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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▼全件表示

共同研究・競争的資金等の研究課題

  • 血中循環腫瘍細胞の生着および非対称分裂・自己組織化に対する癌転移抑制法の開発

    研究課題/領域番号:19K09142  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    相場 利貞, 梛野 正人, 江畑 智希, 横山 幸浩, 國料 俊男, 山口 淳平, 上原 圭介

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

    本研究の目的は単一細胞解析によるCTC (circulating tumor cells)の生着メカニズムの解明、生着した癌細胞の非対称分裂と自己組織化のメカニズムの解明により、これまでと異なるコンセプトの新規癌転移抑制法を開発することである。
    ヒト由来癌細胞を単離した後、ローテーションによる細胞凝集・自己組織化した癌細胞集合体を作製した。細胞凝集・自己組織化した癌細胞集合体の培養は通常の細胞培養と可能であった。細胞凝集・自己組織化した癌細胞集合体に蛍光標識したsiRNAの導入し、導入効率を検討した。単離した場合と比較して効率は低くかったが可能であった。また増殖抑制効果のあるsiRNAを導入し、遺伝子発現の抑制および増殖抑制を検討した。遺伝子抑制されており、増殖抑制も可能であった。
    細胞凝集・自己組織化した癌細胞集合体をマウス腹腔内へ投与した場合、腹腔内洗浄液からのMACSシステムでの癌細胞を単離ができない。ヒト膵癌由来細胞株KLM1のマウス腹腔内への投与後、腹腔内洗浄液から癌細胞を単離せずに培養を行ない、増殖能を検討した。その結果、腹腔内洗浄液から単離せずに培養した癌細胞は、単離した場合より細胞増殖が上昇しており、腹腔内投与しなかったKLM1と比較しても細胞増殖が上昇していた。
    単離せずに培養した場合、癌細胞以外のマウス由来細胞が混入する。混入したマウス由来細胞を鑑別するために、蛍光標識した癌細胞を用いた。蛍光標識した癌細胞の腹腔内投与24時間後に、蛍光標識したsiRNAを腹腔内に投与し、その48時間後に細胞の回収を行い、単離をせずに培養を行なった。腹腔内洗浄液から単離せずに培養した癌細胞では、腹腔内投与しなかったKLM1と比較して増殖抑制効果が減弱していた。この結果より、癌細胞に腹腔内投与による修飾が付加されたと考えられた。

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  • Dual Source CTを用いた進行直腸癌の術前マネージメントシステムの確立

    研究課題/領域番号:16K10275  2016年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    石垣 聡子, 二橋 尚志, 上原 圭介

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    術前化学療法を施行した局所進行直腸癌症例を対象に、治療開始前にperfusion CTを施行し、血流量、血液量、平均通過時間、permeabilityの4項目のパラメータを定量解析した。
    症例を術前化学療法の応答群と非応答群の2群、再発・無再発群の2群に分類し、治療効果予測・予後予測が可能であるか検討を行った。
    治療応答群で有意差をもって血流量が多く、permeabilityが高い、また平均通過時間は治療応答群で長いという結果であった。無再発群では、有意差をもってpermeabilityが高く、平均通過時間は短いという結果であった。

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  • TLR7を標的にした新規癌治療法における作用機序の解明

    研究課題/領域番号:16K10531  2016年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    上原 圭介, 梛野 正人, 横山 幸浩, 國料 俊男, 山口 淳平

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

    ヒト癌細胞株に対してTLR7アゴニストであるイミキモドは増殖能、細胞死誘導能、運動能、浸潤能の抑制効果を認め、投与12時間後にはearly apoptosisを認めた。イミキモド投与により小胞体ストレスのマーカーであるBiP(immunoglobulin heavy chain-binding protein)の発現が亢進しており、アポトーシスの原因として小胞体ストレスが考えられた。しかし、別な小胞体ストレスのマーカーであるPERK(PKR-like ER kinase)の発現は変化していなかった。更なる研究は必要であるが、TLR7の機能阻害による抗腫瘍効果の新たな作用機序を解明した。

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  • TLR7アプタマーによる内因性Denger Signalの制御と新規治療法の開発

    研究課題/領域番号:25462049  2013年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    上原 圭介, 梛野 正人, 横山 幸浩, 國料 俊男, 吉岡 裕一郎

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

    胆管癌症例、膵癌症例においてTLR7とTLR ファミリーであるTLR3、TLR4、TLR5、TLR6、TLR9に関して臨床病理学的に検討を行ない、TLR7は胆管癌症例、膵癌症例において癌組織で高発現していた。TLR7 以外のTLR ファミリーTLR3、 TLR4、 TLR5、 TLR6も癌組織で有意に高発現していた。胆管癌細胞株、膵癌細胞株においてTLR7のアゴニストは増殖抑制効果を示した。担癌動物モデルの検討によりTLR7のアゴニストが抗腫瘍効果を有していることを明らかにした。本研究によりTLR7を標的にした新規治療法開発の可能性が示唆された。

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  • 化学療法関連肝障害の外科手術への影響とその病態生理の解明

    研究課題/領域番号:24591970  2012年4月 - 2014年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    吉岡 裕一郎, 梛野 正人, 横山 幸浩, 國料 俊男, 上原 圭介

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    配分額:5330000円 ( 直接経費:4100000円 、 間接経費:1230000円 )

    化学療法関連肝障害モデルとしてラットへOxaliplatinを1mg/kgから5mg/kgの濃度で週2回、2週間、4週間、8週間投与を行った。血液生化学検査では、AST、ALT、ALP、T.Bilに優位差を認めなかった。 Oxaliplatinを3mg/kg 以上の投与により体重減少を認め、Oxaliplatinの5mg/kg、週2回、4週間投与時のヒアルロン酸値に有意な上昇を認めた。急性期では肝臓は発赤しており、肝組織への免疫細胞の浸潤を認めた。晩期ではネクローシス様になっており繊維化もすすんでおり早期肝障害と晩期合併症の肝障害発症機序が異なると考えられた。このラット肝障害モデルに対して分岐鎖アミノ酸(BCAA)の連日投与を行った。分岐鎖アミノ酸(BCAA)によりヒアルロン酸の上昇が抑制されており、肝障害の軽減傾向が見られた。Oxaliplatinによる肝障害の原因が肝臓の内皮傷害または微小循環傷害と考えられたため、内皮傷害をおこすモノクロタリンを用いた肝障害モデルを用いて分岐鎖アミノ酸(BCAA)の効果についても検討した。モノクロタリンによる肝障害モデルにおいても分岐鎖アミノ酸(BCAA)の連日投与によりヒアルロン酸の上昇を抑制した。分岐鎖アミノ酸(BCAA)の肝障害に対する有効性が示唆された。
    またヒト肝臓標本における化学療法関連遺伝子の遺伝子解析を行ない、予後に関連する遺伝子群を同定した。

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  • 大腸癌microscopic abscessにおける免疫誘導の解明とその臨床応用

    研究課題/領域番号:22591483  2010年 - 2012年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    上原 圭介, 梛野 正人, 横山 幸浩, 國料 俊男, 石黒 成治

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

    microscopic abscessを有する大腸癌4症例と有しない大腸癌5症例の遺伝子解析ではToll-like receptor 7 (TLR7) を含む11の遺伝子の発現がmicroscopic abscessを有する症例で亢進していた。TLR7の下流にあるMyeloid differentiationfactor 88 (MyD88)の発現は、microscopic abscessを有する症例で有意に低下しており、microscopic abscessを有する症例の予後とMyD88の関連性が考えられた。一方でTLR7とMyD88の発現は一致していず、TLR7以外のMyD88にシグナルを伝達するTLRの関与が示唆された。

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  • 複数の癌特異的遺伝子を標的にした分子標的治療の開発

    研究課題/領域番号:20591624  2008年 - 2010年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    國料 俊男, 梛野 正人, 横山 幸浩, 上原 圭介

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    癌の病態は単一遺伝子によるものではなく、異なる複数の遺伝子の同時発現により複雑な病態として作り出されている。効果的な癌分子標的治療法の開発には単一遺伝子ではなく、機能の異なる複数の癌特異的遺伝子を遺伝子群として標的にすることが重要である。本研究では癌特異的遺伝子Nek2(NIMA related kinase 2)、FAK(Focal adhesion kinase)、TLK1(Tousled like kinase 1)を標的とした癌分子標的治療法に関する研究と抗癌剤の併用に関する研究を行った。Nek2とFAK、Nek2とTLK1のsiRNAによる同時抑制では、各遺伝子の抑制に相加効果を認め、増殖抑制能、アポトーシス誘導能に関しても相加効果を認めた。
    Nek2 siRNAとCDDP併用投与は、Nek2 siRNAまたはCDDP単独投与と比較して、有意な増殖抑制効果を認めた。Nek2 siRNAとCDDP併用投与群の遺伝子解析によりBCL2L1、APAF-1(apoptotic protease activating factor 1)の亢進、FOSとJUNの減弱を認めた。TLK1 siRNAとCDDPの併用投与は、TLK1 siRNAまたはCDDP単独投与と比較してアポトーシス誘導能の増強を認めた。担癌動物モデルにおいてもNek2 siRNAとCDDP併用投与群は単独投与群より有意な増殖抑制効果を認め、siRNAと抗癌剤の併用は相加作用ではあったが、有効であった。
    本研究により癌特異的遺伝子を標的にしたsiRNAと抗癌剤の併用による新規治療法の可能性が示唆された。

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