研究者詳細 - 藤原　俊義

論文 - 藤原　俊義

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胃癌治療における栄養治療戦略患者教育プログラムが胃癌術後の体および骨格筋量の変化に及ぼす影響(Effect of patient education protocol on body weight and skeletal muscle reduction after gastrectomy)

高田暢夫, 菊地覚次, 黒田新士, 垣内慶彦, 田辺俊介, 西崎正彦, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 93回 216 - 216 2021年3月

Minimally invasive approach for gastric SMT depending on the characteristics of tumor(和訳中)

Kikuchi Satoru, Nishizaki Masahiko, Kuroda Shinji, Takata Nobuhiko, Takeda Sho, Kakiuchi Yoshihiko, Sugimoto Ryoma, Kagawa Shunsuke, Shirakawa Yasuhiro, Fujiwara Toshiyoshi

日本内視鏡外科学会雑誌 25 ( 7 ) OS55 - 6 2021年3月

胃癌に対する内視鏡外科手術手技の工夫(Present position and future possibility of the double-flap reconstruction after proximal gastrectomy)

Kuroda Shinji, Nishizaki Masahiko, Choda Yasuhiro, Ishida Michihiro, Muraoka Atsushi, Tanaka Norimitsu, Hato Shinji, Kikuchi Satoru, Takata Nobuo, Kakiuchi Yoshihiko, Tanabe Shunsuke, Noma Kazuhiro, Kagawa Shunsuke, Shirakawa Yasuhiro, Kamikawa Yasuaki, Fujiwara Toshiyoshi

日本内視鏡外科学会雑誌 25 ( 7 ) WS33 - 7 2021年3月

進行・再発胃癌に対するNivolumabの実臨床での治療成績(Clinical Outcome of Nivolumab for Advanced or Recurrent Gastric Cancer)

香川俊輔, 黒田新士, 菊地覚次, 西崎正彦, 野間和広, 田辺俊介, 重安邦俊, 前田直見, 垣内慶彦, 武田正, 近藤喜太, 矢野修也, 寺石文則, 藤原俊義

日本胃癌学会総会記事 93回 284 - 284 2021年3月

術前療法が直腸癌鏡視下手術に与える短期、長期治療成績の検討

武田正, 畑七々子, 高橋一剛, 小松泰浩, 三村直毅, 垣内慶彦, 重安邦俊, 菊地覚次, 矢野修也, 近藤喜太, 黒田新士, 寺石文則, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 25 ( 7 ) DP77 - 3 2021年3月

岡山大学における消化器外科領域鏡視下カダバートレーニングの現状と未来

近藤喜太, 前田直見, 黒田新士, 楳田祐三, 矢野修也, 菊地覚次, 田辺俊介, 野間和広, 寺石文則, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 25 ( 7 ) SP9 - 1 2021年3月

カダバーサージカルトレーニングにおける遠隔手術指導の実際

近藤喜太, 前田直見, 菊地覚次, 矢野修也, 黒田新士, 野間和弘, 寺石文則, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 25 ( 7 ) BSP4 - 4 2021年3月

Surgical training model and safe implementation of robotic pancreatoduodenectomy in Japan: a technical note. 国際誌

Kosei Takagi, Yuzo Umeda, Ryuichi Yoshida, Takahito Yagi, Toshiyoshi Fujiwara, Amer H Zureikat, Melissa E Hogg, Bas Groot Koerkamp

World journal of surgical oncology 19 ( 1 ) 55 - 55 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Growing evidence for the advantages of robotic pancreatoduodenectomy (RPD) has been demonstrated internationally. However, there has been no structured training program for RPD in Japan. Herein, we present the surgical training model of RPD and a standardized protocol for surgical technique. METHODS: The surgical training model and surgical technique were standardized in order to implement RPD safely, based on the Dutch training system collaborated with the University of Pittsburgh Medical Center. RESULTS: The surgical training model included various trainings such as basic robotic training, simulation training, biotissue training, and a surgical video review. Furthermore, a standardized protocol on the surgical technique was established to understand the tips, tricks, and pitfalls of RPD. CONCLUSIONS: Safe implementation of RPD can be achieved through the completion of a structured training program and learning surgical technique. A nationwide structured training system should be developed to implement the program safely in Japan.

DOI： 10.1186/s12957-021-02167-9

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Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis. 国際誌

Hiroki Kajioka, Shunsuke Kagawa, Atene Ito, Masashi Yoshimoto, Shuichi Sakamoto, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Yuzo Umeda, Kazuhiro Noma, Hiroshi Tazawa, Toshiyoshi Fujiwara

Cancer letters 497 1 - 13 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.

DOI： 10.1016/j.canlet.2020.10.015

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Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation. 国際誌

Atene Ito, Shunsuke Kagawa, Shuichi Sakamoto, Kazuya Kuwada, Hiroki Kajioka, Masashi Yoshimoto, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara

BMC cancer 21 ( 1 ) 102 - 102 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated. METHODS: The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored. RESULTS: Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein. CONCLUSION: EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment.

DOI： 10.1186/s12885-021-07816-6

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Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer. 国際誌

Ryoichi Katsube, Kazuhiro Noma, Toshiaki Ohara, Noriyuki Nishiwaki, Teruki Kobayashi, Satoshi Komoto, Hiroaki Sato, Hajime Kashima, Takuya Kato, Satoru Kikuchi, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Hisataka Kobayashi, Toshiyoshi Fujiwara

Scientific reports 11 ( 1 ) 1693 - 1693 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

DOI： 10.1038/s41598-021-81465-4

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Real-Time Fluorescence Image-Guided Oncolytic Virotherapy for Precise Cancer Treatment. 国際誌

Shuya Yano, Hiroshi Tazawa, Hiroyuki Kishimoto, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M Hoffman

International journal of molecular sciences 22 ( 2 ) 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) promoter; therefore, they conditionally replicate preferentially in cancer cells. Fluorescence imaging enables visualization of invasion and metastasis in vivo at the subcellular level; including molecular dynamics of cancer cells, resulting in greater precision therapy. In the present review, we focused on fluorescence imaging applications to develop precision targeting for oncolytic virotherapy. Cell-cycle imaging with the fluorescence ubiquitination cell cycle indicator (FUCCI) demonstrated that combination therapy of an oncolytic adenovirus and a cytotoxic agent could precisely target quiescent, chemoresistant cancer stem cells (CSCs) based on decoying the cancer cells to cycle to S-phase by viral treatment, thereby rendering them chemosensitive. Non-invasive fluorescence imaging demonstrated that complete tumor resection with a precise margin, preservation of function, and prevention of distant metastasis, was achieved with fluorescence-guided surgery (FGS) with a GFP-reporter adenovirus. A combination of fluorescence imaging and laser ablation using a KillerRed-protein reporter adenovirus resulted in effective photodynamic cancer therapy (PDT). Thus, imaging technology and the designer oncolytic adenoviruses may have clinical potential for precise cancer targeting by indicating the optimal time for administering therapeutic agents; accurate surgical guidance for complete resection of tumors; and precise targeted cancer-specific photosensitization.

DOI： 10.3390/ijms22020879

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Prognostic Utility of the Glasgow Prognostic Score for the Long-Term Outcomes After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Study. 国際誌

Kenta Sui, Takehiro Okabayashi, Yuzo Umeda, Masahiro Oishi, Toru Kojima, Daisuke Sato, Yoshikatsu Endo, Tetsuya Ota, Katsuyoshi Hioki, Masaru Inagaki, Tadakazu Matsuda, Ryuji Hirai, Masashi Kimura, Takahito Yagi, Toshiyoshi Fujiwara

World journal of surgery 45 ( 1 ) 279 - 290 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The usefulness of the modified Glasgow prognostic score (GPS) as a prognostic tool remains unclear for patients undergoing curative surgery for intrahepatic cholangiocarcinoma (ICC). Therefore, this study investigated the prognostic usefulness of the GPS for patients who underwent ICC surgery. METHOD: All ICC patients who had a curative-intent hepatectomy at 17 institutions between 2000 and 2016 were included. The correlation was assessed between the preoperative GPS and the baseline characteristics of the patients, histopathological parameters, surgical parameters, and the postresection overall survival (OS). RESULT: There were 273 patients who met the eligibility criteria between the years 2000 and 2016. The postoperative OS rates at 1, 3, and 5 years were 83.8%, 56.3%, and 41.5%, respectively (median OS, 47.7 months). A multivariate analysis revealed the factors that were associated with a worse OS, which included an increased GPS (hazard ratio = 1.62; 95% confidence interval [CI]: 1.01-2.53; P = 0.03), an elevated carcinoembryonic antigen level (hazard ratio = 1.60; 95% CI: 1.06-2.41; P = 0.02), an elevated carbohydrate antigen 19-9 level (hazard ratio = 1.55; 95% CI: 1.05-2.30; P = 0.03), undifferentiated carcinoma (hazard ratio = 2.41; 95% CI: 1.56-3.67; P < 0.01), and positive metastasis to the lymph nodes (hazard ratio = 2.54; 95% CI: 1.76-3.67; P < 0.01). In ICC patients after a hepatectomy, an elevated GPS was associated with poorer OS, even if the tumour factors that affected GPS were eliminated by propensity-score matching. CONCLUSION: Preoperative GPS can be useful to predict the postoperative outcomes of ICC patients. Therefore, this relatively simple and inexpensive scoring system can be utilized to further refine patient stratification as well as to predict survival.

DOI： 10.1007/s00268-020-05797-4

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【消化器・一般外科領域の手術教育を考える】総論手術教育における手術記録の活用法

楳田祐三, 杭瀬崇, 吉田龍一, 吉田一博, 藤原俊義, 八木孝仁

手術 75 ( 1 ) 43 - 53 2021年1月

【徹底解説術後後遺症をいかに防ぐか-コツとポイント】胃癌ダンピング症候群その病態と機能温存手術による予防のポイント

菊地覚次, 黒田新士, 藤原俊義

臨床外科 76 ( 1 ) 38 - 42 2021年1月

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 ◆胃切除後障害の代表的な一つであるダンピング症候群予防は,胃切除後のQOL向上において重要である.◆ダンピング症候群を予防する機能温存手術の適応や手術手技のコツを正しく理解する.◆管理栄養士などの医療スタッフと連携したチーム医療体制の構築と患者教育が重要である.

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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=20210108600008&doc_link_id=10.11477%2Fmf.1407213236&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1407213236&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

Microanatomy-based standardization of left upper mediastinal lymph node dissection in thoracoscopic esophagectomy in the prone position. 国際誌

Yasuhiro Shirakawa, Kazuhiro Noma, Naoaki Maeda, Shunsuke Tanabe, Kazufumi Sakurama, Toshiyoshi Fujiwara

Surgical endoscopy 35 ( 1 ) 349 - 357 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although thoracoscopic esophagectomy in the prone position (TEPP) has become a standard procedure for esophageal cancer surgery, upper mediastinal lymph node dissection (UMLND) on the left side remains an issue. We have recently developed a new standardized approach to left UMLND in TEPP based on the microanatomy of the membranes and layers with the aim of achieving quick and safe surgery. The purpose of this study was to establish and evaluate our new standardized procedure in left UMLND. PATIENTS AND METHODS: Patients were divided into 2 groups: a pre-standardization group (n = 100) and a post-standardization group (n = 100). Eventually, 83 paired cases were matched using propensity score matching. In our new standardized procedure, left UMLND was performed while focusing on the visceral sheath, vascular sheath, and the fusion layer between them using a magnified view. RESULTS: The thoracoscopic operative time was significantly shorter (P < 0.001) in the post-standardization group [n = 83; 209.0 (176.0-235.0) min] than in the pre-standardization group [n = 83; 235.5 (202.8-264.5) min]. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the two groups. There was a tendency for the total postoperative morbidity to decrease in the post-standardization group. Furthermore, the left recurrent laryngeal nerve palsy rate was significantly lower in the post-standardization group (18.1% to 8.7%, P = 0.015). CONCLUSION: Microanatomy-based standardization contributes to safe and efficient left UMLND.

DOI： 10.1007/s00464-020-07407-9

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外科系新専門医制度のあるべきグランドデザイン地域枠医師に対する外科専門研修のあり方充実した地域医療の実現を目指して

黒田新士, 吉田龍一, 池田宏国, 岡崎幹生, 大澤晋, 小谷恭弘, 山根正修, 杉本誠一郎, 菊地覚次, 安井和也, 野田卓男, 笠原真悟, 豊岡伸一, 土井原博義, 藤原俊義

日本外科学会雑誌 122 ( 1 ) 83 - 85 2021年1月

外科系新専門医制度のあるべきグランドデザイン地域枠医師に対する外科専門研修のあり方充実した地域医療の実現を目指して査読

日本外科学会雑誌 122 ( 1 ) 83 - 85 2021年1月

がん関連線維芽細胞由来IL-6制御による免疫応答の効率化バイオマーカーとしてのIL-6の可能性

西脇紀之, 野間和広, 大原利章, 河崎健人, 赤井正明, 小林照貴, 加藤卓也, 前田直見, 菊地覚次, 田辺俊介, 田澤大, 白川靖博, 藤原俊義

日本分子腫瘍マーカー研究会誌 36 32 - 33 2021年

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. 国際誌

Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

PloS one 16 ( 4 ) e0250643 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

DOI： 10.1371/journal.pone.0250643

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