Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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胃癌の腹膜転移に対する新規の腹腔内ウイルス療法(Novel intraperitoneal virotherapy for the peritoneal metastasis of gastric cancer)

Kikuchi Satoru, Ishikawa Wataru, Ogawa Toshihiro, Kuroda Shinji, Kuwada Kazuya, Nishizaki Masahiko, Kagawa Shunsuke, Fujiwara Toshiyoshi

日本胃癌学会総会記事 91回 337 - 337 2019.2

観音開き法による食道残胃吻合を行ったLAPGとLATGとの中期および長期成績比較(Mid- and long-term comparison of LAPG with double-flap esophagogastrostomy and LATG)

Kuroda Shinji, Nishizaki Masahiko, Kikuchi Satoru, Tsumura Tomoko, Kuwada Kazuya, Kagawa Shunsuke, Fujiwara Toshiyoshi

日本胃癌学会総会記事 91回 302 - 302 2019.2

近位胃切除術後のEGJCに対するDFTを使用した弁形成食道胃吻合術(Valvutoplastic esophagogastrostomy using DFT for EGJC after proximal gastrectomy)

Nishizaki Masahiko, Kuroda Shinji, Noma Kazuhiro, Kikuchi Satoru, Kuwada Kazuya, Tanabe Shunsuke, Kagawa Shunsuke, Shirakawa Yasuhiro, Fujiwara Toshiyoshi

日本胃癌学会総会記事 91回 273 - 273 2019.2

Multicenter retrospective study to evaluate the efficacy and safety of the double-flap technique as antireflux esophagogastrostomy after proximal gastrectomy (rD-FLAP Study).

Shinji Kuroda, Yasuhiro Choda, Shinya Otsuka, Satoshi Ueyama, Norimitsu Tanaka, Atsushi Muraoka, Shinji Hato, Toshikazu Kimura, Kohji Tanakaya, Satoru Kikuchi, Shunsuke Tanabe, Kazuhiro Noma, Masahiko Nishizaki, Shunsuke Kagawa, Yasuhiro Shirakawa, Yasuaki Kamikawa, Toshiyoshi Fujiwara

Annals of gastroenterological surgery 3 ( 1 ) 96 - 103 2019.1

Language：English Publishing type：Research paper (scientific journal)

Aim: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. Methods: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. Results: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). Conclusion: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

DOI： 10.1002/ags3.12216

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外科医のトレーニング技術の継承とはカダバートレーニングにおける技術の継承

近藤喜太, 信岡大輔, 黒田新士, 前田直見, 西崎正彦, 白川靖博, 藤原俊義

日本外科学会雑誌 120 ( 1 ) 105 - 107 2019.1

【腹腔鏡下胃切除後体腔内再建のKnack & Pitfalls】腹腔鏡下噴門側胃切除術観音開き法(上川法)による再建

西崎正彦, 黒田新士, 野間和広, 菊地覚次, 白川靖博, 藤原俊義

手術 73 ( 1 ) 55 - 59 2019.1

Photoimmunotherapy for cancer-associated fibroblasts targeting fibroblast activation protein in human esophageal squamous cell carcinoma. Reviewed International journal

Shinichiro Watanabe, Kazuhiro Noma, Toshiaki Ohara, Hajime Kashima, Hiroaki Sato, Takuya Kato, Shinichi Urano, Ryoichi Katsube, Yuuri Hashimoto, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Hisataka Kobayashi, Toshiyoshi Fujiwara

Cancer biology & therapy 20 ( 9 ) 1234 - 1248 2019

Language：English Publishing type：Research paper (scientific journal)

Cancer-associated fibroblasts (CAFs) are strongly implicated in tumor progression, including in the processes of tumorigenesis, invasion, and metastasis. The targeting of CAFs using various therapeutic approaches is a novel treatment strategy; however, the efficacy of such therapies remains limited. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a novel targeted therapy employing a cell-specific mAb conjugated to a photosensitizer, has been introduced as a new type of phototherapy. In this study, we have developed a novel NIR-PIT technique to target CAFs, by focusing on fibroblast activation protein (FAP), and we evaluate the treatment efficacy in vitro and in vivo. Esophageal carcinoma cells exhibited enhanced activation of fibroblasts, with FAP over-expressed in the cytoplasm and on the cell surface. FAP-IR700-mediated PIT showed induced rapid cell death specifically for those cells in vitro and in vivo, without adverse effects. This novel therapy for CAFs, designed as local control phototherapy, was safe and showed a promising inhibitory effect on FAP+ CAFs. PIT targeting CAFs via the specific marker FAP may be a therapeutic option for CAFs in the tumor microenvironment in the future.

DOI： 10.1080/15384047.2019.1617566

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Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer. Reviewed International journal

Shuichi Sakamoto, Shunsuke Kagawa, Kazuya Kuwada, Atene Ito, Hiroki Kajioka, Yoshihiko Kakiuchi, Megumi Watanabe, Tetsuya Kagawa, Ryuichi Yoshida, Satoru Kikuchi, Shinji Kuroda, Hiroshi Tazawa, Toshiyoshi Fujiwara

Oncoimmunology 8 ( 12 ) e1671760 2019

Language：English Publishing type：Research paper (scientific journal)

A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC.

DOI： 10.1080/2162402X.2019.1671760

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Forefront of perioperative team medicine for esophageal cancer surgery

Yasuhiro Shirakawa, Shunsuke Tanabe, Toshiyoshi Fujiwara

Journal of Japanese Society of Gastroenterology 116 ( 2 ) 138 - 144 2019

The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer. Reviewed International journal

Kuwada K, Kagawa S, Yoshida R, Sakamoto S, Ito A, Watanabe M, Ieda T, Kuroda S, Kikuchi S, Tazawa H, Fujiwara T

Journal of experimental & clinical cancer research : CR 37 ( 1 ) 307 - 307 2018.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated. MATERIALS AND METHODS: Peritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice. RESULTS: CD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival. CONCLUSION: Intraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.

DOI： 10.1186/s13046-018-0981-2

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上腹部開腹歴を有する腹腔鏡下胃切除術における安全性の検討

津村朋子, 黒田新士, 桑田和也, 菊池覚次, 西崎正彦, 香川俊輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS115 - 5 2018.12

食道胃接合部癌に対する治療戦略食道胃接合部癌に対する胸腔鏡腹腔鏡を併用した切除再建術式の有用性

野間和広, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 田辺俊介, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) SY8 - 2 2018.12

チーム医療における人材育成のためのカダバーサージカルトレーニング

近藤喜太, 前田直見, 黒田新士, 信岡大輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS223 - 1 2018.12

巨大食道裂孔ヘルニアの噴門形成術後に発症した胃噴門部癌に対するRedo surgery

田辺俊介, 白川靖博, 西脇紀之, 松田達雄, 前田直見, 桑田和也, 菊地覚次, 黒田新士, 野間和広, 楳田祐三, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS148 - 1 2018.12

膜と層を意識した胸腔鏡下食道切除術胸腔鏡下食道癌手術における交感神経を指標とした上縦隔リンパ節郭清

白川靖博, 西脇紀之, 松田達雄, 前田直見, 田辺俊介, 野間和広, 西崎正彦, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) PD8 - 1 2018.12

taTMEを安全に導入、普及させるためのcadaver surgical trainingの役割

戸嶋俊明, 近藤喜太, 信岡大輔, 黒田新士, 前田直見, 寺石文則, 白川靖博, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS78 - 7 2018.12

Closed-LECS手技の確立と今後の可能性早期胃癌、十二指腸病変への応用

菊地覚次, 西崎正彦, 黒田新士, 桑田和也, 津村朋子, 香川俊輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) OS23 - 2 2018.12

上部胃癌に対する再建法を考える腹腔鏡下噴門側胃切除術における観音開き法再建の中長期成績

西崎正彦, 黒田新士, 菊地覚次, 桑田和也, 津村朋子, 田邊俊介, 野間和広, 香川俊輔, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) WS12 - 7 2018.12

内視鏡外科におけるCadaver教育が果たすべき役割と未来

近藤喜太, 前田直見, 黒田新士, 信岡大輔, 西崎正彦, 白川靖博, 藤原俊義

日本内視鏡外科学会雑誌 23 ( 7 ) EDS - 2 2018.12

Prognostic Factors for Pediatric Living Donor Liver Transplantation: Impact of Zero-mortality Transplant for Cholestatic Diseases.

Takahito Yagi, Kosei Takagi, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Takashi Kuise, Toshiyoshi Fujiwara

Acta medica Okayama 72 ( 6 ) 567 - 576 2018.12

Language：English Publishing type：Research paper (scientific journal)

Living donor liver transplantation (LDLT) is the final therapeutic arm for pediatric end-stage liver diseases. Toward the goal of achieving further improvement in LDLT survival, we investigated factors affecting recipient survival. We evaluated the prognostic factors of 60 pediatric recipients (< 16 years old) who underwent LDLT between 1997 and 2015. In a univariate analysis, non-cholestatic (NCS) disease, graft/recipient body weight ratio, cold and warm ischemic times, and intraoperative blood loss were significant factors impacting survival. In a multivariate analysis, NCS disease was the only significant factor worsening survival (p=0.0021). One-and 5-year survival rates for the cholestatic disease (CS, n=43) and NCS (n=17) groups were 100% vs. 70.6% and 97.4% vs. 58.8% (p=0.004, log-rank). Intergroup comparisons revealed that CS was significantly associated with operation time, cold ischemia, hepatomegaly of the native liver, and portal plasty. These data suggest that a cirrhotic, swollen, artery-dominant liver did not increase graft size-related risks despite the surgical complexity of preceding operations. The NCS group's poorer survival originated from recurrence of the primary disease and liver manifestation of systemic disease untreatable by transplantation. Improving the survival of pediatric recipients requires intensive efforts to prevent primary disease relapse and more rapid diagnoses to exclude contraindications from NCS disease.

DOI： 10.18926/AMO/56374

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Papers - FUJIWARA Toshiyoshi