研究者詳細 - 垣内　慶彦

論文 - 垣内　慶彦

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An effective surgical educational system in the era of robotic surgery: "Double-Surgeon Technique" in robotic gastrectomy for minimally invasive surgery. 国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Yusuke Yoshida, Nobuhiko Kanaya, Hajime Kashima, Satoru Kikuchi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Langenbeck's archives of surgery 410 ( 1 ) 20 - 20 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Gastric cancer (GC) remains a major malignancy. Robotic gastrectomy (RG) has gained popularity due to various advantages. Despite those advantages, many hospitals lack the necessary equipment for RG and are still performing laparoscopic gastrectomy (LG) due to its established minimal invasiveness and safety. METHODS: This study assessed the effectiveness of the "Double-Surgeon Technique" (DST) for improving surgical education and proficiency with LG. The DST involves both a console-side surgeon and a patient-side surgeon working actively in RG, enhancing the skill acquisition needed for LG and potentially reducing surgical time. Assessment of this method was performed by surgical time, and cases were divided into three groups: first half (Phase 1: P1) and second half (P2) before the introduction of DST, and after the introduction of DST (P3). RESULTS: Two surgical trainees were trained using the DST. The learning curve in both reached a plateau in P2, but descended again in P3. For one trainee, surgical time for P3 was significantly reduced compared to P1 (p = 0.001) and P2 (p = 0.0027) despite the intervals between laparoscopic distal gastrectomy as the main surgeon in P3 being significantly longer than in P2 (p = 0.0094). Other surgical results in both trainees did not differ significantly. Further, no difference in induction phase results of RG were evident between surgeons and trainees with or without DST experience. CONCLUSION: Surgical education using the DST could be effective in the current context of the need for RG and LG.

DOI： 10.1007/s00423-024-03593-5

Optimization of workflow processes for sustainable paternal involvement: case study of an academic "daddy surgeon" in Japan.

Nobuhiko Kanaya, Shinji Kuroda, Yoshitaka Kondo, Yuko Takehara, Yoshihiko Kakiuchi, Hitoshi Minagi, Masaki Sakamoto, Shunsuke Kagawa, Hitomi Kataoka, Toshiyoshi Fujiwara

Surgery today 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Work-life balance is often discussed in Japan. Yet surgeons find it challenging to take paternity leave because of their demanding surgical duties and a strong sense of responsibility. One Japanese male surgeon had his first paternity experience as a research fellow in the US. When he returned to Japan, he resumed his surgical training and started a research project to become an academic surgeon. When he and his wife were expecting their second child, they discussed his paternity participation before the delivery and decided on a sustainable paternity participation plan. By coordinating his responsibilities with his co-workers, he limited his attendance at work to daytime hours only for 1 month to manage paternity duties. This adjustment did not affect the number of main and assistant operations conducted that month and effective optimization of workflow processes decreased the extra workload for other team members. His experience suggests that the optimization of workflow processes can enhance personal life, including paternity participation. (150/150).

DOI： 10.1007/s00595-024-02959-y

Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity. 国際誌

Tomoko Ohtani, Shinji Kuroda, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Kento Kumon, Masashi Hashimoto, Chiaki Yagi, Ryoma Sugimoto, Satoru Kikuchi, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara

Cancer immunology, immunotherapy : CII 74 ( 1 ) 12 - 12 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Dendritic cells (DCs) are crucial in cancer immunity, because they activate cytotoxic T cells by presenting tumor antigens. Recently, oncolytic virus therapy has been recognized as a systemic immune stimulator. We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. However, their effects on DCs remained unclear. In the present study, the aim was to elucidate the mechanisms of DC activation by OBP-702, focusing particularly on tumor-derived exosomes. Exosomes (Exo53, Exo301, or Exo702) were isolated from conditioned media of human or murine pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and PAN02) after treatment with Ad-p53, OBP-301, or OBP-702. Exo702 derived from Panc-1 and MiaPaCa-2 cells significantly upregulated CD86, CD80, CD83 (markers of DC maturation), and IFN-γ in DCs in vitro. Similarly, Exo702 derived from PAN02 cells upregulated CD86 and IFN-γ in bone marrow-derived DCs in a bilateral PAN02 subcutaneous tumor model. This DC maturation was inhibited by GW4869, an inhibitor of exosome release, and anti-CD63, an antibody targeting the exosome marker. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.

DOI： 10.1007/s00262-024-03849-5

Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report. 国際誌

Hitoshi Minagi, Nobuhiko Kanaya, Yoshitaka Kondo, Yoshihiko Kakiuchi, Shinji Kuroda, Ryohei Shoji, Hajime Kashima, Yuki Matsumi, Satoru Kikuchi, Kunitoshi Shigeyasu, Fuminori Teraishi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Surgical case reports 10 ( 1 ) 229 - 229 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement. CASE REPRESENTATION: A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital. CONCLUSIONS: Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.

DOI： 10.1186/s40792-024-02030-5

発生部位からみた肉腫の適切な外科的切除縁とは?-領域横断的な認識の統合- 後腹膜脂肪肉腫に対する外科的切除縁の最適化

近藤喜太, 金谷信彦, 庄司良平, 松三雄騎, 垣内慶彦, 重安邦俊, 菊地覚次, 黒田新士, 田辺俊介, 野間和広, 寺石文則, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 OWS3 - 2 2024年10月

NTRK融合遺伝子とERBB2 amplificationが合併したマイクロサテライト安定型大腸癌

重安邦俊, 高橋利明, 山本英喜, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本癌治療学会学術集会抄録集 62回 ICCJ3 - 6 2024年10月

術前治療後の局所進行直腸癌に対するロボット支援手術の短期～中期治療成績

寺石文則, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 2317 - 2317 2024年7月

下部消化管大腸癌集学的治療について高齢化社会における大腸癌患者の長期生存を目指した遠隔転移制御戦略

重安邦俊, 高橋利明, 楳田祐三, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 596 - 596 2024年7月

下部消化管大腸癌集学的治療について高齢化社会における大腸癌患者の長期生存を目指した遠隔転移制御戦略

重安邦俊, 高橋利明, 楳田祐三, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 596 - 596 2024年7月

術前治療後の局所進行直腸癌に対するロボット支援手術の短期～中期治療成績

寺石文則, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 2317 - 2317 2024年7月

下部消化管新規内科治療が台頭する時代の炎症性腸疾患に対する外科治療の意義手術適応クローン病患者において術前の栄養学的・免疫学的指標の改善が術後合併症を軽減する

Moriwake Kazuya, Kondo Yoshitaka, Sakamoto Masaki, Kanaya Nobuhiko, Kakiuchi Yoshihiko, Shigeyasu Kunitoshi, Kuroda Shinji, Teraishi Fuminori, Kagawa Shunsuke, Fujiwara Toshiyoshi

日本消化器外科学会総会 79回 345 - 345 2024年7月

私が目指すScientific Surgeonとその現状と未来

金谷信彦, 黒田新士, 近藤喜太, 坂本真樹, 垣内慶彦, 菊地覚次, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 668 - 668 2024年7月

上部消化管上部消化管癌に対する更なる低侵襲・機能温存治療観音開き法再建後の吻合部狭窄および狭窄症状のリスク因子分析から見えた再建手技の理想型

黒田新士, 垣内慶彦, 菊地覚次, 賀島肇, 田辺俊介, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 573 - 573 2024年7月

A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study). 査読

Shinji Kuroda, Michihiro Ishida, Yasuhiro Choda, Atsushi Muraoka, Shinji Hato, Tetsuya Kagawa, Norimitsu Tanaka, Toshiharu Mitsuhashi, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Annals of gastroenterological surgery 8 ( 3 ) 374 - 382 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. METHODS: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. RESULTS: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). CONCLUSION: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

DOI： 10.1002/ags3.12783

「多様な外科医が活躍する社会」の実現に向けて Academic daddy surgeonを目指した一外科医の試み

金谷信彦, 黒田新士, 坂本真樹, 垣内慶彦, 近藤喜太, 竹原裕子, 香川俊輔, 藤原俊義

日本外科系連合学会誌 49 ( 3 ) 276 - 276 2024年5月

「多様な外科医が活躍する社会」の実現に向けて Academic daddy surgeonを目指した一外科医の試み

金谷信彦, 黒田新士, 坂本真樹, 垣内慶彦, 近藤喜太, 竹原裕子, 香川俊輔, 藤原俊義

日本外科系連合学会誌 49 ( 3 ) 276 - 276 2024年5月

Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus. 査読国際誌

Masashi Hashimoto, Shinji Kuroda, Nobuhiko Kanaya, Daisuke Kadowaki, Yusuke Yoshida, Masaki Sakamoto, Yuki Hamada, Ryoma Sugimoto, Chiaki Yagi, Tomoko Ohtani, Kento Kumon, Yoshihiko Kakiuchi, Kazuya Yasui, Satoru Kikuchi, Ryuichi Yoshida, Hiroshi Tazawa, Shunsuke Kagawa, Takahito Yagi, Yasuo Urata, Toshiyoshi Fujiwara

British journal of cancer 130 ( 7 ) 1187 - 1195 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

DOI： 10.1038/s41416-024-02583-0

薬物療法と手術を組み合わせた直腸癌遠隔転移症例の長期生存への取り組み

重安邦俊, 香川俊輔, 高橋利明, 梅田響, 松三雄騎, 菊地覚次, 垣内慶彦, 庄司良平, 近藤喜太, 黒田新士, 楳田祐三, 藤原俊義

日本大腸肛門病学会雑誌 77 ( 4 ) 238 - 238 2024年4月

高齢者,併存疾患を有する症例などハイリスク症例の胃癌に対するconversion手術の現況と成績年齢と全身状態から考えるStageIV胃癌に対するConversion手術の是非

垣内慶彦, 黒田新士, 金谷信彦, 賀島肇, 菊地覚次, 重安邦俊, 香川俊輔, 藤原俊義

日本外科学会定期学術集会抄録集 124回 WS - 3 2024年4月

大臀筋に浸潤した局所進行直腸癌に対してtotal neoadjuvant therapyが奏効した一例

坂本真樹, 寺石文則, 庄司良平, 金谷信彦, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 85 ( 3 ) 461 - 461 2024年3月

高齢者に対する薬物治療術前化学療法を要する高齢胃癌患者に対する治療戦略

垣内慶彦, 黒田新士, 金谷信彦, 賀島肇, 菊地覚次, 重安邦俊, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 203 - 203 2024年2月

上部胃癌に対する脾摘と脾門郭清の手技と成績脾門郭清における脾摘の有無によらない脾門アプローチの定型化

黒田新士, 垣内慶彦, 皆木仁志, 庄司良平, 金谷信彦, 賀島肇, 菊地覚次, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 184 - 184 2024年2月

Minimum invasive surgeryでの胃切除術時における手ブレ軽減の工夫

皆木仁志, 垣内慶彦, 黒田新士, 金谷信彦, 賀島肇, 菊地覚次, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 369 - 369 2024年2月

高齢者/ハイリスク患者の低侵襲手術肥満症合併胃癌患者に対するロボット支援下胃切除のリンパ節郭清効果

賀島肇, 皆木仁志, 金谷信彦, 垣内慶彦, 菊地覚次, 黒田新士, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 215 - 215 2024年2月

術後障害の評価と対策術後継続的な栄養指導による胃切除術後障害の軽減効果

菊地覚次, 半澤俊哉, 賀島肇, 庄司良平, 松三雄騎, 垣内慶彦, 黒田新士, 田辺俊介, 野間和広, 香川俊輔, 藤原俊義

日本胃癌学会総会記事 96回 175 - 175 2024年2月

Epidural versus patient-controlled intravenous analgesia on pain relief and recovery after laparoscopic gastrectomy for gastric cancer: randomized clinical trial. 査読国際誌

Satoru Kikuchi, Takashi Matsusaki, Toshiharu Mitsuhashi, Shinji Kuroda, Hajime Kashima, Nobuo Takata, Ema Mitsui, Yoshihiko Kakiuchi, Kazuhiro Noma, Yuzo Umeda, Hiroshi Morimatsu, Toshiyoshi Fujiwara

BJS open 8 ( 1 ) 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG. METHODS: In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia. RESULTS: Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event. CONCLUSIONS: PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG.Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm).

DOI： 10.1093/bjsopen/zrad161

Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy. 査読国際誌

Shunya Hanzawa, Satoru Kikuchi, Shinji Kuroda, Ryohei Shoji, Hajime Kashima, Yuki Matsumi, Ayako Takahashi, Yoshihiko Kakiuchi, Kosei Takagi, Shunsuke Tanabe, Kazuhiro Noma, Shunsuke Kagawa, Kenichi Shikata, Toshiyoshi Fujiwara

Nutrition and cancer 76 ( 6 ) 476 - 485 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

DOI： 10.1080/01635581.2024.2340782

胃癌術後1年目に局所リンパ節再発との鑑別を要した腹腔内デスモイド腫瘍の1例

片山哲也, 垣内慶彦, 黒田新士, 近藤喜太, 菊地覚次, 重安邦俊, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会雑誌 56 ( 12 ) 677 - 684 2023年12月

記述言語：日本語出版者・発行元：(一社)日本消化器外科学会

症例は44歳の男性で,胃癌に対して腹腔鏡下幽門側胃切除術,D2リンパ節郭清,Billroth-I法再建を施行し,病理組織診断はpT2N0M0 Stage IBであった.術後1年目のCTおよびPET-CTにて,#6リンパ節郭清領域にリンパ節再発を示唆する所見を認めたため腹腔鏡下腫瘤摘出術を施行し,病理組織診断でデスモイド腫瘍であった.デスモイド腫瘍は術前診断が困難であり,その発生機序の一因として手術による機械刺激が挙げられるため,胃癌術後に発生した際は再発との鑑別が困難である.再発リスクの低い症例では化学療法などを施行する前に,診断的治療を目的とした手術を行うことは有用であり,術中迅速検査などで再発が否定できるのであれば,他臓器合併切除は極力避けるべきである.胃癌術後にリンパ節再発との鑑別を要したデスモイド腫瘍の1例を経験した.(著者抄録)

炎症性腸疾患に対する低侵襲手術の新しい工夫瘻孔形成を伴うクローン病低侵襲手術の効果とバイオ製剤導入時期の腸管機能温存への影響

近藤喜太, 金谷信彦, 庄司良平, 垣内慶彦, 菊地覚次, 重安邦俊, 田辺俊介, 黒田新士, 野間和広, 寺石文則, 楳田祐三, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 28 ( 7 ) 2246 - 2246 2023年12月

減量・代謝改善手術を安全かつ有効に行うためのちょっとした工夫腹腔鏡下スリーブ状胃切除における縫合補強材を用いた大彎側切離の安全性と手術時間短縮効果

賀島肇, 菊地覚次, 香川俊輔, 皆木仁志, 庄司良平, 金谷信彦, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本内視鏡外科学会雑誌 28 ( 7 ) 408 - 408 2023年12月

Omental Abscess after Laparoscopic Proximal Gastrectomy Successfully Treated with Percutaneous Drainage. 査読

Atsunobu Sakurai, Mayu Uka, Toshihiro Iguchi, Koji Tomita, Yusuke Matsui, Yoshihiko Kakiuchi, Shinji Kuroda, Toshiyoshi Fujiwara, Takao Hiraki

Acta medica Okayama 77 ( 6 ) 665 - 669 2023年12月

記述言語：英語

We report the case details of a 65-year-old Japanese man with an omental abscess that was discovered 43 days after he underwent a laparoscopic proximal gastrectomy for gastric cancer. His chief complaint was mild abdominal pain that had persisted for several days. The abscess was diagnosed as a rare postoperative complication. We hesitated to perform a reoperation given the invasiveness of general anesthesia and surgery, plus the possibility of postoperative adhesions and because the patient's general condition was stable and he had only mild abdominal pain. Percutaneous drainage using a 10.2-F catheter was performed with the patient under conscious sedation and computed tomography-fluoroscopy guidance, with no complications. After the procedure, the size of the abscess cavity was remarkably reduced, and 23 days later the catheter was withdrawn.

DOI： 10.18926/AMO/66160

低侵襲胃癌手術における脾門リンパ節郭清-脾摘か脾温存か、適応とアプローチの実際- 低侵襲アプローチによる脾温存脾門リンパ節郭清手技の定型化とその標準術式としての可能性

黒田新士, 菊地覚次, 垣内慶彦, 賀島肇, 金谷信彦, 庄司良平, 皆木仁志, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 28 ( 7 ) 2681 - 2681 2023年12月

腹腔鏡下胃切除術の際の12mmポート挿入方向の工夫による手ブレ軽減効果

皆木仁志, 垣内慶彦, 黒田新士, 金谷信彦, 賀島肇, 菊地覚次, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 28 ( 7 ) 570 - 570 2023年12月

病理組織学的に膵浸潤を認めた壁外発育型胃GISTの1例

新田薫, 垣内慶彦, 庄司良平, 重安邦俊, 菊地覚次, 近藤喜太, 黒田新士, 寺石文則, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 84 ( 11 ) 1829 - 1829 2023年11月

Prognostic nutritional index is a prognostic factor for patients with gastric cancer and esophagogastric junction cancer undergoing proximal gastrectomy with esophagogastrostomy by the double-flap technique: A secondary analysis of the rD-FLAP study. 査読国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Yasuhiro Choda, Shinya Otsuka, Satoshi Ueyama, Norimitsu Tanaka, Atsushi Muraoka, Shinji Hato, Yasuaki Kamikawa, Toshiyoshi Fujiwara

Surgical oncology 50 101990 - 101990 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Although proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer. METHODS: The study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015. RESULTS: A total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93-6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ≥2) (p = 0.010, HR: 2.29, 95% CI: 1.22-4.30) and pathological N factor ([pN] ≥1) (p = 0.001, HR: 3.27, 95% CI: 1.66-6.46). In patients with preoperative PNI ≥45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16-5.54) was an independent poor prognostic factor, for which operation time (≥300 min) and blood loss (≥200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45. CONCLUSIONS: PNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients.

DOI： 10.1016/j.suronc.2023.101990

米国留学中に経験した出産育児と共稼ぎから見えた外科医のワークライフバランスへの提言

金谷信彦, 黒田新士, 竹原裕子, 皆木仁志, 垣内慶彦, 近藤喜太, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S65 - S65 2023年10月

肥満手術の現状と展望減量代謝改善手術(Bariatric Metabolic Surgery:BMS)チームの介入による術前減量効果と腹腔鏡下スリーブ状胃切除手術(Laparoscopic sleeve gastrectomy:LSG)による減量効果の関係

賀島肇, 菊地覚次, 香川俊輔, 皆木仁志, 庄司良平, 金谷信彦, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S184 - S184 2023年10月

胃憩室を合併した高度肥満症に対して腹腔鏡下スリーブ状胃切除を施行した1例

廣砂賢祐, 賀島肇, 菊地覚次, 香川俊輔, 庄司良平, 金谷信彦, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S332 - S332 2023年10月

胃憩室を合併した高度肥満症に対して腹腔鏡下スリーブ状胃切除を施行した1例

廣砂賢祐, 賀島肇, 菊地覚次, 香川俊輔, 庄司良平, 金谷信彦, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S332 - S332 2023年10月

肥満手術の現状と展望減量代謝改善手術(Bariatric Metabolic Surgery:BMS)チームの介入による術前減量効果と腹腔鏡下スリーブ状胃切除手術(Laparoscopic sleeve gastrectomy:LSG)による減量効果の関係

賀島肇, 菊地覚次, 香川俊輔, 皆木仁志, 庄司良平, 金谷信彦, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S184 - S184 2023年10月

米国留学中に経験した出産育児と共稼ぎから見えた外科医のワークライフバランスへの提言

金谷信彦, 黒田新士, 竹原裕子, 皆木仁志, 垣内慶彦, 近藤喜太, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S65 - S65 2023年10月

Cadaver Surgical Trainingによる解剖を基本とした手術手技獲得の重要性

近藤喜太, 垣内慶彦, 前田直見, 菊地覚次, 田辺俊介, 黒田新士, 野間和広, 楳田祐三, 白川靖博, 藤原俊義

日本臨床外科学会雑誌 84 ( 増刊 ) S95 - S95 2023年10月

Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses. 査読国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Expert opinion on therapeutic targets 1 - 10 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Exosomes are cell-derived nanovesicles involved in cell-to-cell communications. These nanovesicles are generally considered to contain important carriers of information such as DNA and RNA, and show specific tropism. AREAS COVERED: The combination of existing therapeutic agents with exosomes enhances therapeutic effects by increasing uptake into the tumor. Induction of immunogenic cell death (ICD) may also be triggered more strongly than with the drug alone. Oncolytic viruses (OVs) are even more effective as a drug in combination with exosomes. Although OVs are more likely to cause immune activity, combination with exosomes can exert synergistic effects. OVs have potent anti-tumor effects, but many limitations, such as being limited to local administration and vulnerability to attack by antibodies. Incorporation into exosomes can overcome these limitations and may allow effects against distant tumors. EXPERT OPINION: Novel therapies using exosomes are very attractive in terms of enhancing therapeutic efficacy and reducing side effects. This approach also contains elements overcoming disadvantages in OVs, which have not been used clinically until now, and may usher in a new era of cancer treatments.

DOI： 10.1080/14728222.2023.2259102

共生細菌とがん免疫応答酪酸は腫瘍融解ウイルスの抗腫瘍効果を向上させる(Commensal bacteria and tumor immunity Butyrate enhances the antitumor efficacy of telomerase-specific oncolytic adenoviruses)

坂本真樹, 黒田新士, 垣内慶彦, 橋本将志, 八木千晶, 杉本龍馬, 濱田侑紀, 吉田有佑, 門脇大輔, 半澤俊哉, 菊地覚次, 香川俊輔, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 82回 1660 - 1660 2023年9月

Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma. 査読国際誌

Masashi Yoshimoto, Shunsuke Kagawa, Hiroki Kajioka, Atsuki Taniguchi, Shinji Kuroda, Satoru Kikuchi, Yoshihiko Kakiuchi, Tomohiko Yagi, Shohei Nogi, Fuminori Teraishi, Kunitoshi Shigeyasu, Ryuichi Yoshida, Yuzo Umeda, Kazuhiro Noma, Hiroshi Tazawa, Toshiyoshi Fujiwara

Cancer letters 567 216260 - 216260 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy.

DOI： 10.1016/j.canlet.2023.216260

腹腔鏡下に十二指腸前壁を開放し切除を行った十二指腸Brunner腺過誤腫の一例

加藤貴光, 垣内慶彦, 庄司良平, 近藤喜太, 黒田新士, 野間和宏, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 78回 P018 - 4 2023年7月

周術期管理チーム介入後にみえてきたフレイル高齢者大腸癌治療の課題術前機能評価を用いた新たな取り組み

寺石文則, 山田元彦, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 藤原俊義

日本消化器外科学会総会 78回 O33 - 5 2023年7月

【下部】切除不能な遠隔転移を有する局所進行大腸癌に対する集学的治療戦略大腸癌患者の長期生存を目指した遠隔転移臓器別の切除適応と化学療法レジメンの選択

重安邦俊, 高橋利明, 楳田祐三, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 78回 WS20 - 9 2023年7月

【上部】【Challenges beyond borders】高度進行胃癌に対するconversion surgeryの現状と新たな治療戦略 Stage IV因子と腫瘍マーカー変化率から見えたStage IV胃癌の予後を改善するための至適手術介入条件

垣内慶彦, 黒田新士, 菊地覚次, 重安邦俊, 賀島肇, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 78回 PD3 - 6 2023年7月

【下部】切除不能な遠隔転移を有する局所進行大腸癌に対する集学的治療戦略大腸癌患者の長期生存を目指した遠隔転移臓器別の切除適応と化学療法レジメンの選択

重安邦俊, 高橋利明, 楳田祐三, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 78回 WS20 - 9 2023年7月

周術期管理チーム介入後にみえてきたフレイル高齢者大腸癌治療の課題術前機能評価を用いた新たな取り組み

寺石文則, 山田元彦, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 藤原俊義

日本消化器外科学会総会 78回 O33 - 5 2023年7月

体脂肪分布からみた減量代謝改善手術の効果

賀島肇, 菊地覚次, 香川俊輔, 黒田新士, 垣内慶彦, 松三雄騎, 山田元彦, 野間和広, 楳田祐三, 藤原俊義

日本消化器外科学会総会 78回 O18 - 2 2023年7月

【上部】【Challenges beyond borders】高度進行胃癌に対するconversion surgeryの現状と新たな治療戦略 Stage IV因子と腫瘍マーカー変化率から見えたStage IV胃癌の予後を改善するための至適手術介入条件

垣内慶彦, 黒田新士, 菊地覚次, 重安邦俊, 賀島肇, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 78回 PD3 - 6 2023年7月

【消化器外科における各種デバイスの使い方とピットフォール】上部消化管食道・胃切除術における自動縫合器の使い方とピットフォール

田邊俊介, 垣内慶彦, 前田直見, 菊地覚次, 黒田新士, 野間和広, 藤原俊義

外科 85 ( 4 ) 345 - 350 2023年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞近年,自動縫合器を使用した臓器の切離,および再建が普及している.一方で,従来行われていた手縫い吻合と異なり,各臓器において使用の際のピットフォールが存在すると思われる.今回,当科で行っている食道および胃切除術時のサーキュラーステープラおよびリニアステープラの使い方およびそのピットフォールを説明する.

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00393&link_issn=&doc_id=20230414270006&doc_link_id=10.15106%2Fj_geka85_345&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka85_345&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

外科医療におけるサルコペニア・フレイル対策の最前線胃切除術後の認知行動療法を応用したサルコペニア予防策の効果

菊地覚次, 高田暢夫, 半澤俊哉, 賀島肇, 松三雄騎, 垣内慶彦, 黒田新士, 前田直見, 田辺俊介, 野間和広, 楳田祐三, 藤原俊義

日本外科学会定期学術集会抄録集 123回 SY - 1 2023年4月

Removing the Esophageal Stump During Reconstruction for Esophagojejunostomy in Total Gastrectomy for Gastric Cancer: the Modified Overlap Method. 査読国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Satoru Kikuchi, Hajime Kashima, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 27 ( 3 ) 643 - 645 2023年3月

A Case Report of Non-typical Annular Pancreas Diagnosed during Laparoscopic Gastric Surgery. 査読

Toshiaki Takahashi, Yoshihiko Kakiuchi, Satoru Kikuch, Shinji Kuroda, Sho Takeda, Kunitoshi Shigeyasu, Yoshitaka Kondo, Fuminori Teraishi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Acta medica Okayama 77 ( 1 ) 91 - 95 2023年2月

記述言語：英語

An annular pancreas is a rare anomaly of the pancreas, defined as pancreatic tissue that totally or partly encircles the duodenum, usually the descending portion. A 76-year-old man who was diagnosed with gastric cancer cT3N0M0 Stage IIB underwent laparoscopic distal gastrectomy with D2 lymph node dissection. Intraoperatively, the dorsal half of the duodenal bulb was seen to be half surrounded by the pancreas, and a non-typical annular pancreas was diagnosed. Because of the risk to the pancreas, it was considered impossible to perform anastomosis by a linear stapler as in the usual laparoscopic procedure. Therefore, we performed laparoscopically assisted distal gastrectomy and Billroth-I reconstruction using a circular stapler, and the surgery was completed without difficulties. His postoperative course was good despite the development of a pancreatic fistula, which was an International Study Group for Pancreas Fistula biochemical leak. Some APs can be diagnosed preoperatively, but the rarer subtypes such as ours are more difficult to visualize on imaging. In gastrectomy, it is both oncologically important and technically challenging to perform lymph node dissection around the pancreas. In this case with an especially proximal pancreas, a circular stapler was considered better suited for gastroduodenal anastomosis and required a broader field than that afforded by laparoscopy. A case of non-typical annular pancreas diagnosed during laparoscopic gastric surgery is described.

DOI： 10.18926/AMO/64368

Fabry病患者におけるサイトメガロウイルス感染による小腸穿孔の1例

中村峻輔, 菊地覚次, 垣内慶彦, 黒田新士, 野間和広, 楳田祐三, 都地友紘, 藤原俊義

日本消化器外科学会雑誌 56 ( 2 ) 87 - 93 2023年2月

記述言語：日本語出版者・発行元：(一社)日本消化器外科学会

症例は66歳の男性で,Fabry病による慢性腎不全に対して維持透析中であった.右肺癌に対して肺部分切除を施行後膿胸の増悪のため,ICUで全身管理中に小腸穿孔,汎発性腹膜炎を来し当科紹介となった.原因不明の小腸穿孔として緊急手術を施行した.術中所見では,Treitz靱帯より約200cmの部位での小腸穿孔,腸間膜側から腹腔内への穿破を認め,腹腔内汚染は著明であった.小腸を約20cm切除し,洗浄ドレナージ,回腸人工肛門造設を行った.切除標本では粘膜面に多発潰瘍を認め,その1ヶ所に穿孔を認めた.病理組織学的検査では,サイトメガロウイルス(cytomegalovirus;以下,CMVと略記)免疫染色検査で潰瘍部に一致して陽性細胞が検出され,CMV感染による小腸穿孔と診断した.CMV感染による消化管穿孔はまれであるが,免疫不全患者ではその存在を常に念頭に置く必要があり,早期診断・治療が重要である.(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01117&link_issn=&doc_id=20230308270006&doc_link_id=10.5833%2Fjjgs.2022.0036&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2022.0036&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

【こだわりの体腔内縫合・吻合術】胃外科腹腔鏡下/ロボット支援下噴門側胃切除後の観音開き法による再建

黒田新士, 菊地覚次, 垣内慶彦, 香川俊輔, 藤原俊義

手術 77 ( 2 ) 189 - 195 2023年2月

高齢者pStage III大腸癌の予後と転帰から術後化学療法について考察する

寺石文則, 成田周平, 武田正, 垣内慶彦, 重安邦俊, 矢野修也, 近藤喜太, 野間和広, 楳田祐三, 香川俊輔, 藤原俊義

日本大腸肛門病学会雑誌 76 ( 1 ) 114 - 114 2023年1月

胃癌に対する噴門側胃切除:手技の工夫と成績観音開き法(上川法)再建における吻合部狭窄ゼロを目指した手技の改変

黒田新士, 菊地覚次, 垣内慶彦, 野間和広, 楳田祐三, 寺石文則, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1848 - 1848 2022年12月

内視鏡外科手術における遠隔医療の現状と課題内視鏡外科手術におけるカダバーサージカルトレーニング遠隔手術指導シミュレーションの実際

近藤喜太, 庄司良平, 垣内慶彦, 前田直見, 菊地覚次, 重安邦俊, 黒田新士, 田辺俊介, 野間和広, 吉田龍一, 寺石文則, 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 27 ( 7 ) 1268 - 1268 2022年12月

術後再発困難症例に対する前方臓器温存のための集学的治療を併用したTaAPRの有用性

庄司良平, 近藤喜太, 垣内慶彦, 賀島肇, 松三雄騎, 寺石文則, 菊地覚次, 黒田新士, 田辺俊介, 野間和広, 吉田龍一, 楳田祐三, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 775 - 775 2022年12月

症例数の限られた地方病院での安全かつ有効な新規代謝改善手術導入の課題

賀島肇, 菊地覚次, 香川俊輔, 黒田新士, 半澤俊哉, 庄司良平, 垣内慶彦, 松三雄騎, 野間和広, 楳田祐三, 寺石文則, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 298 - 298 2022年12月

術前治療後の腹腔鏡下直腸癌手術の治療成績

寺石文則, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 1138 - 1138 2022年12月

十二指腸腫瘍の局在や特性に応じたLECSのアプローチ法や切除法の工夫と成績

菊地覚次, 西崎正彦, 黒田新士, 賀島肇, 松三雄騎, 半澤俊哉, 垣内慶彦, 田辺俊介, 野間和広, 香川俊輔, 楳田祐三, 藤原俊義

日本内視鏡外科学会雑誌 27 ( 7 ) 730 - 730 2022年12月

Involvement in the tumor-infiltrating CD8+ T cell expression by the initial disease of remnant gastric cancer. 査読国際誌

Yoshihiko Kakiuchi, Satoru Kikuchi, Shinji Kuroda, Shunsuke Kagawa, Toshiyoshi Fujiwara

World journal of surgical oncology 20 ( 1 ) 374 - 374 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Remnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC. METHODS: Between January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis. RESULTS: On univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3-13.0). In addition, tumor-infiltrating CD8+ T cells expression was higher in the benign disease group than in the malignant group (p=0.046). CONCLUSIONS: Initial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8+ T cells in RGC may involve in.

DOI： 10.1186/s12957-022-02853-2

腹腔鏡下スリーブ状胃切除(LSG)の安全な導入と普及への課題

菊地覚次, 賀島肇, 香川俊輔, 江口潤, 中司敦子, 高橋絢子, 黒田新士, 半澤俊哉, 庄司良平, 垣内慶彦, 松三雄騎, 野間和広, 楳田祐三, 和田淳, 藤原俊義

肥満研究 28 ( Suppl. ) 354 - 354 2022年11月

マジンドール(Mazindol:MZD)先行導入後に腹腔鏡下スリーブ胃切除術を行った高度肥満の2例

賀島肇, 菊地覚次, 香川俊輔, 江口潤, 中司敦子, 高橋絢子, 黒田新士, 半澤俊哉, 庄司良平, 垣内慶彦, 松三雄騎, 野間和広, 楳田祐三, 和田淳, 藤原俊義

肥満研究 28 ( Suppl. ) 352 - 352 2022年11月

OBP-702を用いたウイルス治療による膵癌の長期抗腫瘍免疫賦活効果

橋本将志, 黒田新士, 金谷信彦, 垣内慶彦, 菊地覚次, 田澤大, 香川俊輔, 浦田泰生, 藤原俊義

癌と化学療法 49 ( 10 ) 1127 - 1129 2022年10月

記述言語：日本語出版者・発行元：(株)癌と化学療法社

膵癌は予後不良な癌であり,近年話題の癌免疫療法に対しても免疫細胞の浸潤が乏しい腫瘍として知られている。また,近年術前化学療法の有効性が注目されている。我々は,腫瘍特異的に増殖する腫瘍融解アデノウイルス製剤(OBP-301)を開発し,食道癌において放射線療法+OBP-301治療の臨床試験が進行中である。臨床試験のなかで腫瘍浸潤リンパ球やPD-L1の発現増強を認め,免疫学的な治療効果も期待されている。次世代の薬剤としてOBP-301にp53遺伝子を搭載したOBP-702を開発し,膵癌に対して強力な治療効果を発揮することを確認した。今回,膵癌におけるOBP-702の有効性に関し,長期抗腫瘍免疫の指標としてCD8陽性メモリーT細胞に注目して検討した。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00296&link_issn=&doc_id=20221021370020&doc_link_id=%2Fab8gtkrc%2F2022%2F004910%2F021%2F1127-1129%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2022%2F004910%2F021%2F1127-1129%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

[Telomerase-Specific Oncolytic Adenovirus Expressing p53 Gene Stimulating CD8+ Memory T Cells in Pancreatic Cancer].

Masashi Hashimoto, Shinji Kuroda, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Satoru Kikuchi, Hiroshi Tazawa, Shunsuke Kagawa, Yasuo Urata, Toshiyoshi Fujiwara

Gan to kagaku ryoho. Cancer & chemotherapy 49 ( 10 ) 1127 - 1129 2022年10月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Pancreatic cancer has poor prognosis despite the various developed multimodal treatment strategies. Currently, neoadjuvant chemotherapy and immunotherapy have attracted substantial attention as effective treatment strategies. However, amplifying immune response with existing treatments is difficult. We developed telomerase-specific oncolytic adenoviruses (OAs), including OBP-301 that is currently tested in a clinical trial of combined anti-PD-1 antibody and p53-armed OBP- 301 variant(OBP-702). OAs have immune-modulation functions and induce CD8+ T cells into tumors by releasing immunogenic cell death markers, such as extracellular adenosine triphosphate. Here, we investigated the effectiveness of OBP- 702 in pancreatic cancer treatments, focusing on the influence on CD8+ memory T cells.

Prognostic risk factors for postoperative long-term outcomes in elderly stage IA gastric cancer patients. 査読国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Satoru Kikuchi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Journal of gastrointestinal oncology 13 ( 5 ) 2178 - 2185 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The number of gastric cancer (GC) patients with other diseases is increasing due to the aging of the population. In particular, in stage IA GC patients who have multiple diseases, surgical indications should be considered after identifying prognostic factors. We therefore investigated prognostic factors for stage IA GC in the elderly. METHODS: Patient characteristics were collected and analyzed retrospectively for elderly patients with stage IA GC who underwent curative surgical treatment at Okayama University Hospital between 2010 and 2015, and an elderly group (EG; 75-79 years old) and very elderly group (VEG; ≥80 years old) were compared. RESULTS: Fifty-three patient in the EG and 31 patients in the VEG were compared. No factors associated with clinicopathological characteristics or surgical or postoperative short-term outcomes differed significantly between groups. Although no factors in the EG appeared significantly associated with poor overall survival (OS), severe comorbidity [Charlson Comorbidity Index (CCI) ≥2; P=0.019], open gastrectomy (P=0.012), high volume of blood loss (≥300 mL; P=0.013) and long postoperative hospital stay (≥14 days; P=0.041) were significantly associated with poor OS. Furthermore, only CCI ≥2 [hazard ratio (HR) =9.2; 95% confidence interval (CI): 1.2-68.9; P=0.032] was an independent prognostic factor associated with poor OS. Five-year OS was 88.9% for CCI 0/1 patients and 62.3% for CCI ≥2 patients, representing very impressive results. CONCLUSIONS: CCI ≥2 is an important prognostic factor in clinical decisions in stage IA GC patients ≥2, so careful determination of surgical indications is desirable.

DOI： 10.21037/jgo-22-527

がん治療におけるサルコペニアとフレイルの意義患者参加型継続的栄養指導による胃癌術後のサルコペニア予防効果

菊地覚次, 高田暢夫, 黒田新士, 田辺俊介, 前田直見, 賀島肇, 垣内慶彦, 野間和広, 香川俊輔, 高橋絢子, 楳田祐三, 四方賢一, 藤原俊義

日本癌治療学会学術集会抄録集 60回 WS19 - 2 2022年10月

当施設における大腸憩室炎に対する手術治療成績

寺石文則, 垣内慶彦, 重安邦俊, 近藤喜太, 黒田新士, 野間和広, 香川俊輔, 藤原俊義

日本消化器外科学会雑誌 55 ( Suppl.2 ) 255 - 255 2022年10月

外科医不足に対してCadaver Surgical Trainingが果たす役割

近藤喜太, 庄司良平, 垣内慶彦, 黒田新士, 前田直見, 田辺俊介, 菊地覚次, 寺石文則, 香川俊輔, 藤原俊義

日本臨床外科学会雑誌 83 ( 増刊 ) S32 - S32 2022年10月

血清エクソソームE1A-DNAはテロメラーゼ特異的腫瘍融解アデノウイルスの治療効果予測バイオマーカーとして有用である(Exosomal E1A-DNA in serum as a predictive biomarker of telomerase-specific oncolytic adenovirus)

八木千晶, 黒田新士, 吉田有佑, 坂本真樹, 濱田侑紀, 杉本龍馬, 橋本将志, 垣内慶彦, 菊地覚次, 香川俊輔, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 81回 E - 3068 2022年9月

p53搭載テロメラーゼ特異的腫瘍融解アデノウイルスの抗腫瘍効果予測スコアリングシステム(Scoring system to predict antitumor effects of p53-armed telomerase-specific oncolytic adenovirus)

杉本龍馬, 黒田新士, 吉田有佑, 坂本真樹, 濱田侑紀, 八木千晶, 橋本将志, 垣内慶彦, 菊地覚次, 香川俊輔, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 81回 P - 3347 2022年9月

血清エクソソームE1A-DNAはテロメラーゼ特異的腫瘍融解アデノウイルスの治療効果予測バイオマーカーとして有用である(Exosomal E1A-DNA in serum as a predictive biomarker of telomerase-specific oncolytic adenovirus)

八木千晶, 黒田新士, 吉田有佑, 坂本真樹, 濱田侑紀, 杉本龍馬, 橋本将志, 垣内慶彦, 菊地覚次, 香川俊輔, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 81回 E - 3068 2022年9月

p53搭載テロメラーゼ特異的腫瘍融解アデノウイルスの抗腫瘍効果予測スコアリングシステム(Scoring system to predict antitumor effects of p53-armed telomerase-specific oncolytic adenovirus)

杉本龍馬, 黒田新士, 吉田有佑, 坂本真樹, 濱田侑紀, 八木千晶, 橋本将志, 垣内慶彦, 菊地覚次, 香川俊輔, 田澤大, 浦田泰生, 藤原俊義

日本癌学会総会記事 81回 P - 3347 2022年9月

高度肥満症に対する減量・代謝改善手術の効果と安全性

香川俊輔, 菊地覚次, 黒田新士, 武田正, 垣内慶彦, 寺石文則, 近藤喜太, 重安邦俊, 楳田祐三, 藤原俊義

日本消化器外科学会総会 77回 P276 - 6 2022年7月

H.pylori未感染胃粘膜を背景に発生したリンパ節転移を伴う低分化型進行胃癌の一例

倉岡紗樹子, 川野誠司, 小橋真由, 岡上昇太郎, 里見拓也, 稲生祥子, 濱田健太, 河野吉泰, 神崎洋光, 岩室雅也, 河原祥朗, 岡田裕之, 垣内慶彦, 黒田新士, 藤原俊義, 田中健大, 池田宣聖

日本消化器病学会中国支部例会プログラム・抄録集 117回 75 - 75 2022年6月

Surgical technique of suprapancreatic D2 lymphadenectomy focusing on the posterior hepatic plexus for advanced gastric cancer. 査読国際誌

Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Sho Takeda, Satoru Kikuchi, Kazuhiro Noma, Ryuichi Yoshida, Yuzo Umeda, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Langenbeck's archives of surgery 407 ( 2 ) 871 - 877 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Although D2 lymphadenectomy is currently considered a standard procedure for advanced gastric cancer (GC) worldwide, there is room for discussion about the appropriate range of suprapancreatic D2 lymphadenectomy. Focusing on the posterior hepatic plexus (PHP), which is not well recognized, we developed a surgical technique of suprapancreatic D2 lymphadenectomy, which we have called PHP-D2, and its short-term and long-term efficacies were evaluated in comparison with non-PHP-D2. METHODS: GC patients who underwent distal gastrectomy with D2 lymphadenectomy between July 2006 and May 2013 were enrolled, from which patients who had peritoneal metastasis and/or were peritoneal cytology-positive during surgery were excluded. Their medical records were retrospectively reviewed. RESULTS: Ninety-two patients (non-PHP-D2: 48, PHP-D2: 44) were enrolled. Shorter operation time (330 min vs 275 min, p < 0.0001) and less blood loss (290 mL vs 125 mL, p < 0.0001) were observed in PHP-D2, and no pancreatic fistulas were observed in PHP-D2. More lymph nodes of #11p (1 vs 1.5, p = 0.0328) and #12a lymph nodes (0 vs 1, p = 0.0034) were retrieved in PHP-D2, with no significant differences in #8a and #9 lymph nodes. Lymphatic recurrence was significantly less in PHP-D2 (p = 0.0166), and univariate and multivariate analyses showed that non-PHP-D2 was a significant risk factor for lymphatic recurrence (p = 0.0158), although there were no significant differences between non-PHP-D2 and PHP-D2 in 5-year overall survival and 5-year relapse-free survival. CONCLUSION: PHP-D2 was a safe and feasible procedure that had the potential to reduce lymphatic recurrence, and it can be a standard procedure of D2 lymphadenectomy for advanced GC.

DOI： 10.1007/s00423-022-02437-4

進行・再発胃癌患者に対するNivolumabの実臨床での治療成績の検討(Clinical outcomes of nivolumab in patients with advanced or recurrent gastric cancer)

香川俊輔, 黒田新士, 菊地覚次, 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, 寺石文則, 藤原俊義

日本胃癌学会総会記事 94回 425 - 425 2022年3月

腹腔鏡下スリーブ状胃切除術導入から4年間での治療成績

香川俊輔, 菊地覚次, 黒田新士, 垣内慶彦, 武田正, 江口潤, 中司敦子, 山口哲志, 和田淳, 藤原俊義

肥満研究 27 ( Suppl. ) 358 - 358 2022年3月

進行・再発胃癌患者に対するNivolumabの実臨床での治療成績の検討(Clinical outcomes of nivolumab in patients with advanced or recurrent gastric cancer)

香川俊輔, 黒田新士, 菊地覚次, 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, 寺石文則, 藤原俊義

日本胃癌学会総会記事 94回 425 - 425 2022年3月

Association between Advanced T Stage and Thick Rectus Abdominis Muscle and Outlet Obstruction and High-Output Stoma after Ileostomy in Patients with Rectal Cancer 査読

Yasuhiro Komatsu, Kunitoshi Shigeyasu, Sho Takeda, Yoshiko Mori, Kazutaka Takahashi, Nanako Hata, Kokichi Miyamoto, Hibiki Umeda, Yoshihiko Kakiuchi, Satoru Kikuchi, Shuya Yano, Shinji Kuroda, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

International Surgery 106 ( 3 ) 102 - 111 2022年

掲載種別：研究論文（学術雑誌）

Objective: This study aimed to identify factors associated with outlet obstruction and high-output stoma (HOS) after ileostomy creation. Summary of background data: Ileostomy creation is effective in preventing leakage among patients undergoing low anterior resection for rectal cancer. However, major complications such as outlet obstruction and HOS can occur after surgery. Moreover, these complications cannot be prevented. Methods: This retrospective study included 34 patients with rectal cancer who underwent low anterior resection and ileostomy creation at Okayama University Hospital from January 2015 to December 2018. Then, the risk factors associated with outlet obstruction and HOS were analyzed. Results: Of 34 patients, 7 (21%) experienced outlet obstruction. In a multivariate logistic regression analysis, advanced T stage (P ¼ 0.10), ileostomy with a short horizontal diameter (P ¼ 0.01), and thick rectus abdominis (RA) muscle (P ¼ 0.0005) were considered independent risk factors for outlet obstruction. There was a significant correlation between outlet obstruction and HOS (P ¼ 0.03). Meanwhile, the independent risk factors of HOS were advanced T stage (P ¼ 0.03) and thick RA muscle (P ¼ 0.04). Conclusions: Thick RA muscle and advanced T stage were the common risk factors of outlet obstruction and HOS. Therefore, in high-risk patients, these complications can be prevented by choosing an appropriate ileostomy location according to RA muscle thickness and by preventing tubing into the ileostomy.

DOI： 10.9738/INTSURG-D-21-00012.1

Accreditation as a qualified surgeon improves surgical outcomes in laparoscopic distal gastrectomy. 査読

Satoru Kikuchi, Tetsuya Kagawa, Shinji Kuroda, Masahiko Nishizaki, Nobuo Takata, Kazuya Kuwada, Ryohei Shoji, Yoshihiko Kakiuchi, Toshiharu Mitsuhashi, Yuzo Umeda, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara

Surgery today 51 ( 12 ) 1978 - 1984 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS. METHODS: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period). RESULTS: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p < 0.001; 20.5 vs. 59.8 ml, p = 0.024, respectively). Furthermore, the major complication rate was significantly lower in the QS period than in the non-QS period (0 vs. 10.6%, p = 0.044). CONCLUSIONS: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.

DOI： 10.1007/s00595-021-02309-2

Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles. 査読国際誌

Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Chiaki Yagi, Ryoma Sugimoto, Yuki Hamada, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara

Molecular therapy : the journal of the American Society of Gene Therapy 29 ( 10 ) 2920 - 2930 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. Here, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.

DOI： 10.1016/j.ymthe.2021.05.015

Intracorporeal semi-hand-sewn Billroth I reconstruction in total laparoscopic distal gastrectomy. 査読

Satoru Kikuchi, Shinji Kuroda, Masahiko Nishizaki, Kazuya Kuwada, Nobuo Takata, Yoshihiko Kakiuchi, Shuya Yano, Kazuhiro Noma, Shunsuke Kagawa, Toshiyoshi Fujiwara

Asian journal of endoscopic surgery 14 ( 3 ) 640 - 643 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Intracorporeal Billroth I (B-I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi-hand-sewn (SHS) B-I reconstruction. MATERIALS AND SURGICAL TECHNIQUE: After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B-I anastomosis. All the transection line of the duodenum and one-third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand-sewn technique. DISCUSSION: SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra-abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32-63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.

DOI： 10.1111/ases.12887

SMAD4 Germline Pathogenic Variant-Related Gastric Juvenile Polyposis with Adenocarcinoma Treated with Laparoscopic Total Gastrectomy: A Case Report. 査読国際誌

Yuya Sakurai, Satoru Kikuchi, Kunitoshi Shigeyasu, Yoshihiko Kakiuchi, Takehiro Tanaka, Hibiki Umeda, Masaki Sakamoto, Sho Takeda, Shuya Yano, Mashu Futagawa, Fumino Kato, Reimi Sogawa, Hideki Yamamoto, Shinji Kuroda, Yoshitaka Kondo, Fuminori Teraishi, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Akira Hirasawa, Toshiyoshi Fujiwara

The American journal of case reports 22 e932241 2021年6月

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

BACKGROUND Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases. CASE REPORT A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing. CONCLUSIONS JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/AJCR.932241

Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study. 査読国際誌

Shinji Kuroda, Satoru Kikuchi, Yoshihiko Kakiuchi, Megumi Watanabe, Kazuya Kuwada, Tomoko Tsumura, Masahiko Nishizaki, Shunsuke Kagawa, Shiro Hinotsu, Toshiyoshi Fujiwara

International journal of surgery (London, England) 89 105946 - 105946 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin's unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk. METHODS: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1-4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2. RESULTS: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68). CONCLUSIONS: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery.

DOI： 10.1016/j.ijsu.2021.105946

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody. 査読国際誌

Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Toshiaki Morihiro, Tetsushi Kubota, Katsuyuki Aoyama, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Hiroyuki Mizuguchi, Yasuo Urata, Toshiyoshi Fujiwara

Molecular therapy : the journal of the American Society of Gene Therapy 28 ( 3 ) 794 - 804 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.

DOI： 10.1016/j.ymthe.2020.01.003

Short-term and long-term comparisons of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy by the double-flap technique and laparoscopy-assisted total gastrectomy for proximal gastric cancer. 査読国際誌

Tomoko Tsumura, Shinji Kuroda, Masahiko Nishizaki, Satoru Kikuchi, Yoshihiko Kakiuchi, Nobuo Takata, Atene Ito, Megumi Watanabe, Kazuya Kuwada, Shunsuke Kagawa, Toshiyoshi Fujiwara

PloS one 15 ( 11 ) e0242223 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although proximal gastrectomy (PG) is a recognized surgical procedure for early proximal gastric cancer, total gastrectomy (TG) is sometimes selected due to concern about severe gastroesophageal reflux. Esophagogastrostomy by the double-flap technique (DFT) is an anti-reflux reconstruction after PG, and its short-term effectiveness has been reported. However, little is known about the long-term effects on nutritional status and quality of life (QOL). METHODS: Gastric cancer patients who underwent laparoscopy-assisted PG (LAPG) with DFT or laparoscopy-assisted TG (LATG) between April 2011 and March 2014 were retrospectively analyzed. Body weight (BW), body mass index (BMI), and prognostic nutritional index (PNI) were reviewed to assess nutritional status, and the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 was used to assess QOL. RESULTS: A total of 36 patients (LATG: 17, LAPG: 19) were enrolled. Four of 17 LATG patients (24%) were diagnosed with Stage ≥II after surgery, and half received S-1 adjuvant chemotherapy. BW and PNI were better maintained in LAPG than in LATG patients until 1-year follow-up. Seven of 16 LATG patients (44%) were categorized as "underweight (BMI<18.5 kg/m2)" at 1-year follow-up, compared to three of 18 LAPG patients (17%; p = 0.0836). The PGSAS-45 showed no significant difference in all QOL categories except for decreased BW (p = 0.0132). Multivariate analysis showed that LATG was the only potential risk factor for severe BW loss (odds ratio: 3.03, p = 0.0722). CONCLUSIONS: LAPG with DFT was superior to LATG in postoperative nutritional maintenance, and can be the first option for early proximal gastric cancer.

DOI： 10.1371/journal.pone.0242223

PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. 査読国際誌

Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Yoshihiko Kakiuchi, Tetsushi Kubota, Katsuyuki Aoyama, Takehiro Tanaka, Satoru Kikuchi, Takeshi Nagasaka, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Scientific reports 9 ( 1 ) 4633 - 4633 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

DOI： 10.1038/s41598-019-41177-2

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer. 査読国際誌

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年

記述言語：英語掲載種別：研究論文（学術雑誌）

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

HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer. 査読国際誌

Tetsushi Kubota, Shinji Kuroda, Nobuhiko Kanaya, Toshiaki Morihiro, Katsuyuki Aoyama, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Nanomedicine : nanotechnology, biology, and medicine 14 ( 6 ) 1919 - 1929 2018年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

An issue of concern is that no current HER2-targeted therapeutic agent is effective against Trastuzumab (Tmab)-resistant gastric cancer. Gold nanoparticles (AuNPs) are promising drug carriers with unique characteristics of a large surface area available for attachment of materials such as antibodies. Here, we created HER2-targeted AuNPs (T-AuNPs) and examined their therapeutic efficacy and cytotoxic mechanisms using HER2-postive Tmab-resistant (MKN7) or Tmab-sensitive (NCI-N87) gastric cancer cell lines. In vitro, T-AuNPs showed stronger cytotoxic effects than controls against MKN7 and NCI-N87 cells although Tmab had no effect on MKN7 cells. Autophagy played an important role in T-AuNP cytotoxic mechanisms, which was considered to be driven by internalization of T-AuNPs. Finally, T-AuNPs displayed potent antitumor effects against NCI-N87 and MKN7 subcutaneous tumors in in vivo mouse models. In conclusion, HER2-targeted AuNPs with conjugated Tmab is a promising strategy for the development of novel therapeutic agents to overcome Tmab resistance in gastric cancer.

DOI： 10.1016/j.nano.2018.05.019

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system. 査読国際誌

Katsuyuki Aoyama, Shinji Kuroda, Toshiaki Morihiro, Nobuhiko Kanaya, Tetsushi Kubota, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Scientific reports 7 ( 1 ) 14177 - 14177 2017年10月

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

Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40-50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.

DOI： 10.1038/s41598-017-14717-x

A small intestine volvulus caused by strangulation of a mesenteric lipoma: a case report. 査読国際誌

Yoshihiko Kakiuchi, Hiroaki Mashima, Naoto Hori, Hirotoshi Takashima

Journal of medical case reports 11 ( 1 ) 68 - 68 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BioMed Central Ltd.

BACKGROUND: An emergency department encounters a variety of cases, including rare cases of the strangulation of a mesenteric lipoma by the greater omentum band. CASE PRESENTATION: A 67-year-old Japanese man presented with nausea, vomiting, and upper abdominal pain. There were no abnormalities detected by routine blood tests other than a slight rise in his white cell count. A contrast-enhanced computed tomography scan of his abdomen revealed a dilated intestine, a small intestine volvulus, and a well-capsulated homogeneous mass. He was suspected of having a small intestine volvulus that was affected by a mesenteric lipoma; therefore, single-port laparoscopic surgery was performed. Laparoscopy revealed a small intestine volvulus secondary to the strangulation of a mesenteric lipoma. The band and tumor were removed. He had no postoperative complications and was discharged on postoperative day 6. CONCLUSIONS: Although this case was an emergency, it showed that single-port laparoscopic surgery can be a safe, useful, and efficacious procedure.

DOI： 10.1186/s13256-017-1232-4

食道胃接合部へ達する胃大型GISTに対して腹腔鏡下胃局所切除術を施行した1例査読

垣内慶彦, 真島宏聡, 堀直人, 高嶌寛年, 西崎正彦

日鏡外会誌 22 ( 4 ) 531 - 637 2017年

[A Patient with Gastric Cancer with Peritoneal Dissemination Who Survived for Five Years after Sequential Chemotherapy with S-1 Followed by Paclitaxel].

Shinichi Urano, Yoshihiko Kakiuchi, Hirotoshi Takashima

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 2 ) 251 - 4 2016年2月

記述言語：日本語掲載種別：研究論文（学術雑誌）

A 76-year-old man complained of hematemesis and melena, and consulted the doctor. An endoscopic examination revealed type 3 advanced gastric cancer and a gastric ulcer with a visible vessel. We performed total gastrectomy with peritoneal metastasis dissection. After surgery, he received sequential chemotherapy with S-1 followed by paclitaxel. He continued the adjuvant chemotherapy without severe adverse events. He was treated successfully in spite of risk factors such as old age and postoperative body weight loss. We report herein a rare case of gastric cancer with peritoneal dissemination who achieved 5- year survival after surgery along with the literature review.

腹部大動脈瘤ステントグラフト内挿術後に腹腔鏡補助下高位前方切除術を施行した直腸癌の1例査読

垣内慶彦, 高嶌寛年

日鏡外会誌 21 229 - 233 2016年

完全内臓逆位に発症した十二指腸癌に対して膵頭十二指腸切除術を行った1例査読

垣内慶彦, 児島亨, 仁熊健文, 三村哲重

日本外科系連合学会誌 39 ( 4 ) 718 - 722 2014年

手術にて救命した重症偽膜性腸炎の2例査読

垣内慶彦, 新田泰樹, 赤在義浩

日本臨床外科学会雑誌 74 ( 11 ) 3057 - 3062 2013年

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