Faculty Profiles - HORIGUCHI Shigeru

Papers - HORIGUCHI Shigeru

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Effectiveness of data-augmentation on deep learning in evaluating rapid on-site cytopathology at endoscopic ultrasound-guided fine needle aspiration. International journal

Yuki Fujii, Daisuke Uchida, Ryosuke Sato, Taisuke Obata, Matsumi Akihiro, Kazuya Miyamoto, Kosaku Morimoto, Hiroyuki Terasawa, Tatsuhiro Yamazaki, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hirofumi Inoue, Ten Cho, Takayoshi Tanimoto, Akimitsu Ohto, Yoshiro Kawahara, Motoyuki Otsuka

Scientific reports 14 ( 1 ) 22441 - 22441 2024.9

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

Rapid on-site cytopathology evaluation (ROSE) has been considered an effective method to increase the diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, ROSE is unavailable in most institutes worldwide due to the shortage of cytopathologists. To overcome this situation, we created an artificial intelligence (AI)-based system (the ROSE-AI system), which was trained with the augmented data to evaluate the slide images acquired by EUS-FNA. This study aimed to clarify the effects of such data-augmentation on establishing an effective ROSE-AI system by comparing the efficacy of various data-augmentation techniques. The ROSE-AI system was trained with increased data obtained by the various data-augmentation techniques, including geometric transformation, color space transformation, and kernel filtering. By performing five-fold cross-validation, we compared the efficacy of each data-augmentation technique on the increasing diagnostic abilities of the ROSE-AI system. We collected 4059 divided EUS-FNA slide images from 36 patients with pancreatic cancer and nine patients with non-pancreatic cancer. The diagnostic ability of the ROSE-AI system without data augmentation had a sensitivity, specificity, and accuracy of 87.5%, 79.7%, and 83.7%, respectively. While, some data-augmentation techniques decreased diagnostic ability, the ROSE-AI system trained only with the augmented data using the geometric transformation technique had the highest diagnostic accuracy (88.2%). We successfully developed a prototype ROSE-AI system with high diagnostic ability. Each data-augmentation technique may have various compatibilities with AI-mediated diagnostics, and the geometric transformation was the most effective for the ROSE-AI system.

DOI： 10.1038/s41598-024-72312-3

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【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

寺澤裕之, 堤康一郎, 原田圭, 服部直, 菊池達也, 小幡泰介, 佐藤亮介, 織田崇志, 松三明宏, 宮本和也, 藤井佑樹, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 801 - 806 2024.8

Language：Japanese Publisher：医学図書出版(株)

膵癌は予後不良な難治癌であるが,その一因として薬剤耐性があげられる。薬剤耐性のメカニズムとして,標的治療が難しいKRAS変異の存在やエピジェネティック機構などの遺伝子変異や薬物代謝の変化,転移・浸潤を促進するEMT,膵癌に特徴的な間質成分の多い腫瘍微小環境,さらにnon-coding RNAによる遺伝子発現の調整などがあり,それらが複合的に影響していると考えられている。この複雑な薬剤耐性メカニズムのさらなる解明がその克服において重要である。(著者抄録)

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【膵・胆道癌の発生・進展メカニズムを探る】胆道癌の薬剤耐性メカニズム

堤康一郎, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 857 - 862 2024.8

Language：Japanese Publisher：医学図書出版(株)

胆道癌の多くは根治切除が難しく,主に抗癌剤や分子標的薬を用いた薬物療法が行われるが,5年生存率は20%程度であり予後不良な疾患である。この一因として,癌細胞が抗腫瘍効果を有する薬剤から逃れて生存を維持しようとする機構,つまり癌の薬剤耐性保有やその獲得があげられる。これまでに胆道癌における七つの薬剤耐性メカニズム(mechanisms of chemoresistance:MOC)が報告されており,これらの複数が相互にまたは独立して関与していることが明らかとなっている。さまざまな遺伝子異常が基盤となって生じる薬剤耐性メカニズムの理解を深めることは,胆道癌に対する新規の治療戦略や治療法開発につながり,個々の患者における予後改善に寄与することが期待される。(著者抄録)

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【膵・胆道癌の発生・進展メカニズムを探る】胆道癌の薬剤耐性メカニズム

堤康一郎, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 857 - 862 2024.8

Language：Japanese Publisher：医学図書出版(株)

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【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

胆と膵 45 ( 8 ) 801 - 806 2024.8

Language：Japanese Publisher：医学図書出版(株)

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後期高齢者におけるIPMNの治療移行割合及び長期経過についての検討

宮本和也, 松本和幸, 服部直, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 内田大輔, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

膵臓 39 ( 3 ) A425 - A425 2024.7

Virtual indigo carmine chromoendoscopy images: A novel modality for peroral cholangioscopy using artificial intelligence technology (with video). International journal

Ryosuke Sato, Kazuyuki Matsumoto, Hideaki Kinugasa, Masahiro Tomiya, Takayoshi Tanimoto, Akimitsu Ohto, Kei Harada, Nao Hattori, Taisuke Obata, Akihiro Matsumi, Kazuya Miyamoto, Kosaku Morimoto, Hiroyuki Terasawa, Yuki Fujii, Daisuke Uchida, Koichiro Tsutsumi, Shigeru Horiguchi, Hironari Kato, Yoshiro Kawahara, Motoyuki Otsuka

Gastrointestinal endoscopy 2024.6

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

BACKGROUND AND AIMS: Accurately diagnosing biliary strictures is crucial for surgical decisions, and although peroral cholangioscopy (POCS) aids in visual diagnosis, diagnosing malignancies or determining lesion margins via this route remains challenging. Indigo carmine is commonly used to evaluate lesions during gastrointestinal endoscopy. We aimed to establish the utility of virtual indigo carmine chromoendoscopy (VICI) converted from POCS images using artificial intelligence. METHODS: This single-center, retrospective study analyzed 40 patients with biliary strictures who underwent POCS using white light imaging (WLI) and narrow-band imaging (NBI). A "cycle-consistent adversarial network" (CycleGAN) was used to convert the WLI into VICI of POCS images. Three experienced endoscopists evaluated WLI, NBI, and VICI via POCS in all patients. The primary outcome was the visualization quality of surface structures, surface microvessels, and lesion margins. The secondary outcome was diagnostic accuracy. RESULTS: VICI showed superior visualization of the surface structures and lesion margins compared with WLI (P<0.001) and NBI (P<0.001). The diagnostic accuracies were 72.5%, 87.5%, and 90.0% in WLI alone, WLI and VICI simultaneously, and WLI and NBI simultaneously, respectively. WLI and VICI simultaneously tended to result in higher accuracy than WLI alone (P=0.083) and the results were not significantly different from WLI and NBI simultaneously (P=0.65). CONCLUSIONS: VICI in POCS proved valuable for visualizing surface structures and lesion margins and contributed to higher diagnostic accuracy comparable to NBI. In addition to NBI, VICI may be a novel supportive modality for POCS.

DOI： 10.1016/j.gie.2024.06.013

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Detection of residual stones by peroral direct cholangioscopy in patients with intrahepatic stones after hepaticojejunostomy: A prospective study (with video). International journal

Kazuyuki Matsumoto, Hironari Kato, Akihiro Matsumi, Kazuya Miyamoto, Kosaku Morimoto, Yuki Fujii, Ryosuke Sato, Nao Hattori, Taisuke Obata, Hiroyuki Terasawa, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Motoyuki Otsuka

Gastrointestinal endoscopy 2024.4

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

BACKGROUND AND AIMS: The difficulty of radiographic confirmation of the presence of stones remains a challenge in the treatment of intrahepatic bile duct (IHBD) stones in patients after hepaticojejunostomy (HJ). Peroral direct cholangioscopy (PDCS) enables direct observation of the bile duct and is useful for detecting and removing residual stones; however, its effectiveness is not clearly established in this clinical context. METHODS: This single-center, single-arm, prospective study included 44 patients with IHBD who underwent bowel reconstruction with HJ during the study period. Stone removal was performed by short-type double-balloon enteroscopy (DBE). Following balloon-occluded cholangiography, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS. The primary endpoint was the rate of residual stones detected by PDCS. Secondary endpoints were success rate of PDCS, residual stone removal with PDCS, procedure time for PDCS, procedure-related adverse events, and stone recurrence rate. RESULTS: PDCS was successful in 39/44 patients (89%), among whom residual stones were detected in 16 (41%) (95% CI: 28%-54%). Twelve patients (75%) had residual stones <5 mm. Stone removal was successful in 15 (94%) patients and median procedure time for PDCS was 16 (IQR: 10-26) min. The rate of procedure-related adverse events was 7% (3/44), all of which improved with conservative treatment. During median follow-up of 2.1 years (IQR: 1.4-3.3), the overall probability of recurrence-free status at 1, 2, and 3 years was 100%, 92%, and 86%, respectively. CONCLUSIONS: PDCS is a safe and effective procedure for complete stone removal in patients with IHBD stones after HJ.

DOI： 10.1016/j.gie.2024.04.014

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結節を有するIPMNの良悪性診断における新規TIC解析プログラムを用いた造影EUSの有用性

宮本和也, 内田大輔, 服部直, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

Gastroenterological Endoscopy 66 ( Suppl.1 ) 977 - 977 2024.4

MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer. International journal

Takashi Oda, Koichiro Tsutsumi, Taisuke Obata, Eijiro Ueta, Tatsuya Kikuchi, Soichiro Ako, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Hironari Kato, Hiroyuki Okada, Ryota Chijimatsu, Motoyuki Otsuka

Molecular therapy. Oncology 32 ( 1 ) 200765 - 200765 2024.3

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

Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

DOI： 10.1016/j.omton.2024.200765

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経口胆道鏡検査におけるAIを用いた色素内視鏡画像への疑似変換

佐藤亮介, 松本和幸, 冨谷昌弘, 谷本太郁由, 大戸彰三, 原田圭, 服部直, 小幡泰介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 内田大輔, 衣笠秀明, 堤康一郎, 堀口繁, 加藤博也, 河原祥朗, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A356 - A356 2024.3

膵癌の分子異常と個別化治療切除不能進行膵癌治療において生殖細胞BRCA病的変異は体細胞CGP結果によらず白金製剤治療効果予測因子となる

堀口繁, 加藤博也, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堤康一郎, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A87 - A87 2024.3

神経内分泌腫瘍の新しい治療戦略膵消化管神経内分泌腫瘍肝転移に対するPRRTの治療効果予測因子についての検討

堀口繁, 加藤博也, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堤康一郎, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A108 - A108 2024.3

経口胆道鏡検査におけるAIを用いた色素内視鏡画像への疑似変換

日本消化器病学会雑誌 121 ( 臨増総会 ) A356 - A356 2024.3

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway. International journal

Taisuke Obata, Koichiro Tsutsumi, Eijiro Ueta, Takashi Oda, Tatsuya Kikuchi, Soichiro Ako, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Hironari Kato, Hiroyuki Okada, Motoyuki Otsuka

Molecular therapy. Nucleic acids 34 102054 - 102054 2023.12

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

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.

DOI： 10.1016/j.omtn.2023.102054

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Successful removal of a proximally migrated pancreatic stent using a novel device delivery system. International journal

Akihiro Matsumi, Kazuyuki Matsumoto, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Motoyuki Otsuka

Endoscopy 55 ( S 01 ) E641-E642 2023.12

Usefulness of red dichromatic imagining for peroral cholangioscopy. International journal

Kazuyuki Matsumoto, Yuki Fujii, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato

Endoscopy 55 ( S 01 ) E264-E265 2023.12

Usefulness of the artificial intelligence-mediated virtual chromoendoscopy in peroral cholangioscopy. International journal

Ryosuke Sato, Kazuyuki Matsumoto, Hideaki Kinugasa, Daisuke Uchida, Shigeru Horiguchi, Hironari Kato, Motoyuki Otsuka

Endoscopy 55 ( S 01 ) E971-E972 2023.12

ロボット支援下膵頭十二指腸切除術後の捻転を伴う輸入脚症候群に対して内視鏡的整復を行った1例

原田圭, 藤井佑樹, 小幡泰介, 佐藤亮介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 山崎辰洋, 内田大輔, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

日本消化器病学会中国支部例会・日本消化器内視鏡学会中国支部例会プログラム・抄録集 120回・131回 112 - 112 2023.11

膵神経内分泌腫瘍の治療中にうっ血性左側結腸炎を発症した1例

佐藤亮介, 堀口繁, 小幡泰介, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 内田大輔, 松本和幸, 堤康一郎, 加藤博也, 大塚基之

日本消化器病学会中国支部例会・日本消化器内視鏡学会中国支部例会プログラム・抄録集 120回・131回 84 - 84 2023.11

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Papers - HORIGUCHI Shigeru