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

【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)

【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)

【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)

【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)

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

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

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

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

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

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

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

Cysts or necrotic components in pancreatic ductal adenocarcinoma is associated with the risk of EUS-FNA/B complications including needle tract seeding. International journal

Hiroyuki Terasawa, Kazuyuki Matsumoto, Takehiro Tanaka, Takeshi Tomoda, Taiji Ogawa, Yuki Ishihara, Tatsuya Kikuchi, Taisuke Obata, Takashi Oda, Akihiro Matsumi, Kazuya Miyamoto, Kosaku Morimoto, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Motoyuki Otsuka

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2023.10

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

BACKGROUND: EUS-FNA/B for pancreatic ductal adenocarcinoma (PDAC) is generally considered to be safe; however, while the incidence is low, there are occurrences of complications. Among these complications, there are serious ones like needle tract seeding (NTS), and it is not known than which types of tumors have the risks of EUS-FNA/B complications. This study aimed to evaluate the risk of EUS-FNA/B complications in patients with PDAC, focusing on morphological features. METHODS: Overall, 442 patients who underwent EUS-FNA/B for solid pancreatic masses between January 2018 and May 2022 in four institutions were retrospectively surveyed. Finally, 361 patients histopathologically diagnosed with PDAC were analyzed. Among these patients, 79 tumors with cysts or necrotic components were compared with 282 tumors without cysts or necrotic components. The incidence and risk of EUS-FNA/B complications including NTS were evaluated. RESULTS: There were 9 (2.4 %) of total EUS-FNA/B complications and 3 (0.8 %) of NTS. The incidence of total complication rate and NTS in tumors with cysts or necrotic components were significantly higher than in those without cysts or necrotic components (total complication 6.3 % vs. 1.4 %, p = 0.026, NTS 3.7 % vs. 0 %, p = 0.01). The transgastric route of puncture (OR: 93.3, 95 % CI: 3.81-2284.23) and the existence of cysts or necrotic components (OR: 7.3, 95 % CI: 1.47-36.19) were risk factors for EUS-FNA/B complications identified by the multivariate analysis. CONCLUSIONS: We should pay attention to the risks of EUS-FNA/B complications, including NTS, when the tumor has cysts or necrotic components.

DOI： 10.1016/j.pan.2023.10.018

Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer.

Shigeru Horiguchi, Kazuyuki Matsumoto, Kosaku Morimoto, Akihiro Matsumi, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Koichiro Tsutsumi, Hironari Kato

Acta medica Okayama 77 ( 5 ) 517 - 525 2023.10

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

We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer.

DOI： 10.18926/AMO/65974

The efficacy of non-anesthesiologist-administered propofol sedation with a target-controlled infusion system during double-balloon endoscopic retrograde cholangiopancreatography. International journal

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

BMC gastroenterology 23 ( 1 ) 296 - 296 2023.9

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

BACKGROUND: The sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP. METHODS: This retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation. RESULTS: Poor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57-66.98; P = 0.015), BMI ≥ 25 kg/m2 (OR, 11.96; 95% CI, 1.67-85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01-0.58; P = 0.015) were associated factors for poor sedation. CONCLUSIONS: NAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation.

DOI： 10.1186/s12876-023-02936-8

胆膵癌ゲノムパネル検査における検査法についての検討(Investigation of test methods for pancreatobiliary cancer genomic panel test)

堀口繁, 加藤博也, 松本和幸, 大塚基之

日本癌学会総会記事 82回 828 - 828 2023.9

先天性胆道拡張症術後の肝内胆管狭窄に対し内視鏡的胆道拡張術が有効であった一例

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

日本膵・胆管合流異常研究会プロシーディングス 46 76 - 76 2023.9

成人における偽胆石形成のリスク因子の検討

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

胆道 37 ( 3 ) 690 - 690 2023.8

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, 松本和幸, 内田大輔, 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, 山崎辰洋, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

膵臓 38 ( 3 ) A345 - A345 2023.7

当院における術後膵空腸吻合部狭窄に対する内視鏡治療成績の検討

森本光作, 山崎辰洋, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 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, 堤康一郎, 加藤博也, 大塚基之

膵臓 38 ( 3 ) A337 - A337 2023.7

高齢者における膵癌術前化学療法の有効性と安全性の検討

藤井佑樹, 堀口繁, 佐藤亮介, 小幡泰介, 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, 堤康一郎, 加藤博也, 大塚基之

膵臓 38 ( 3 ) A316 - A316 2023.7

当院における術後膵空腸吻合部狭窄に対する内視鏡治療成績の検討

森本光作, 山崎辰洋, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 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, 堤康一郎, 加藤博也, 大塚基之

膵臓 38 ( 3 ) A337 - A337 2023.7

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, 松本和幸, 内田大輔, 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, 山崎辰洋, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

膵臓 38 ( 3 ) A345 - A345 2023.7

A Comparison of the Efficacy of Plastic Stent Placement Above and Across the Sphincter of Oddi for Benign Biliary Hilar Stricture.

Hitomi Himei, Hironari Kato, Yosuke Saragai, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Acta medica Okayama 77 ( 3 ) 291 - 299 2023.6

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

We investigated the efficacy and safety of endoscopic plastic stent (PS) placement for hilar benign biliary strictures (BBSs) and compared cases with PS placement above (inside stent, IS) and across (usual stent, US) the sphincter of Oddi. Patients who underwent initial endoscopic PS placement for hilar BBSs between August 2012 and December 2021 were retrospectively analyzed. Hilar BBSs in 88 patients were investigated. Clinical success was achieved in 81 of these cases (92.0%), including 38 patients in the IS group and 43 patients in the US group. Unexpected stent exchange (uSE) before the first scheduled PS exchange occurred in 18 cases (22.2%). The median time from first stent placement to uSE was 35 days. There was no significant difference in the rate and median time to uSE between the two groups. The rates of adverse events such as pancreatitis or cholangitis in the two groups did not significantly differ. However, the rate of difficult stent removal in the IS group (15.8%) was significantly higher than that in the US group (0%) (p=0.0019). US placement is preferable to IS placement for scheduled stent exchange, as it offers the same effectiveness and risk of adverse events with easier stent removal.

DOI： 10.18926/AMO/65494

悪性輸入脚症候群に対して超音波内視鏡下消化管ドレナージが有効であった1例

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

日本消化器内視鏡学会中国支部例会 130回 83 - 83 2023.6

長期経過を追えた膵Intraductal oncocytic papillary neoplasm(IOPN)の1例

藤井佑樹, 佐藤亮介, 小幡泰介, 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プログラム・抄録集 119回 67 - 67 2023.6

進行胆道癌に対するゲムシタビン・シスプラチン・S-1併用療法の治療成績についての検討

小幡泰介, 松本和幸, 佐藤亮介, 菊池達也, 織田崇志, 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, 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プログラム・抄録集 119回 65 - 65 2023.6

肝内結石に対して内視鏡用イントロデューサーEndoSheatherが有用であった1例

佐藤亮介, 藤井佑樹, 小幡泰介, 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, 堤康一郎, 堀口繁, 加藤博也, 大塚基之

日本消化器内視鏡学会中国支部例会 130回 83 - 83 2023.6

肝内結石に対して内視鏡用イントロデューサーEndoSheatherが有用であった1例

佐藤亮介, 藤井佑樹, 小幡泰介, 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, 堤康一郎, 堀口繁, 加藤博也, 大塚基之

日本消化器内視鏡学会中国支部例会 130回 83 - 83 2023.6

進行胆道癌に対するゲムシタビン・シスプラチン・S-1併用療法の治療成績についての検討

小幡泰介, 松本和幸, 佐藤亮介, 菊池達也, 織田崇志, 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, 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プログラム・抄録集 119回 65 - 65 2023.6

悪性輸入脚症候群に対して超音波内視鏡下消化管ドレナージが有効であった1例

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

日本消化器内視鏡学会中国支部例会 130回 83 - 83 2023.6

長期経過を追えた膵Intraductal oncocytic papillary neoplasm(IOPN)の1例

藤井佑樹, 佐藤亮介, 小幡泰介, 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プログラム・抄録集 119回 67 - 67 2023.6

選択的胆管seekingのためのデバイス選択

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

Gastroenterological Endoscopy 65 ( Suppl.1 ) 971 - 971 2023.4

当院の胆膵内視鏡診療における放射線量の検討

山崎辰洋, 松本和幸, 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, 堀口繁, 堤康一郎, 加藤博也

Gastroenterological Endoscopy 65 ( Suppl.1 ) 875 - 875 2023.4

当院の胆膵内視鏡診療における放射線量の検討

山崎辰洋, 松本和幸, 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, 堀口繁, 堤康一郎, 加藤博也

Gastroenterological Endoscopy 65 ( Suppl.1 ) 875 - 875 2023.4

選択的胆管seekingのためのデバイス選択

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

Gastroenterological Endoscopy 65 ( Suppl.1 ) 971 - 971 2023.4

Risk Factors for Ceftriaxone-Associated Pseudolithiasis in Adults. International journal

Akihiro Matsumi, Takeshi Tomoda, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato

Digestion 1 - 7 2023.3

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

INTRODUCTION: Ceftriaxone (CTRX) is known to occasionally cause pseudolithiasis. This condition is often observed in children; however, few studies have reported the incidence and risk factors for CTRX-associated pseudolithiasis. METHODS: In this single-center retrospective study, we investigated the incidence of and risk factors for CTRX-associated pseudolithiasis in adults. All patients underwent computed tomography to confirm pseudolithiasis before and after CTRX administration. RESULTS: The study included 523 patients. Pseudolithiasis was detected in 89 patients (17%). Data analysis showed that abdominal area-related biliary diseases at the site of infection (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.064-0.53, p = 0.0017), CTRX administration for >3 days (OR 5.0, 95% CI: 2.5-9.9, p < 0.0001), CTRX dose of 2 mg (OR 5.2, 95% CI: 2.8-9.6, p < 0.0001), fasting period >2 days (OR 3.2, 95% CI: 1.6-6.4, p = 0.0010), and estimated glomerular filtration rate <30 mL/min/1.73 m2 (OR 3.4, 95% CI: 1.6-7.5, p = 0.0022) were independent factors for pseudolithiasis. CONCLUSIONS: CTRX-associated pseudolithiasis may occur in adults and should be considered in the differential diagnosis in patients who develop abdominal pain or liver enzyme elevation after CTRX administration, particularly in patients with chronic kidney disease, in those who are fasting, in and those who receive high-dose CTRX therapy.

DOI： 10.1159/000529522

がんゲノム医療の現状と課題中四国がんゲノム中核拠点病院における胆膵癌ゲノム医療の現状について

堀口繁, 松本和幸, 加藤博也

日本消化器病学会雑誌 120 ( 臨増総会 ) A42 - A42 2023.3

膵神経内分泌腫瘍診療の進歩小病変かつ低悪性度の膵神経内分泌腫瘍に対するEUSガイド下エタノール注入療法の有用性

松本和幸, 堀口繁, 加藤博也

日本消化器病学会雑誌 120 ( 臨増総会 ) A204 - A204 2023.3

膵癌化学療法における血中自己抗体を用いた治療効果予測の可能性

松本和幸, 高木章乃夫, 高原政宏, 小幡泰介, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也

日本消化器病学会雑誌 120 ( 臨増総会 ) A292 - A292 2023.3

EUS-HGSにおけるダブルガイドワイヤー法の有用性

松三明宏, 藤井佑樹, 小幡泰介, 佐藤亮介, 織田崇志, 菊池達也, 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

日本消化器病学会雑誌 120 ( 臨増総会 ) A321 - A321 2023.3

胆嚢オルガノイドを用いた発癌モデルより同定したmiR-34a-5p補充による胆嚢癌治療の開発

織田崇志, 堤康一郎, 小幡泰介, 菊池達也, 松三明宏, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 加藤博也, 大塚基之

日本消化器病学会雑誌 120 ( 臨増総会 ) A328 - A328 2023.3

後期高齢者におけるIPMNの治療移行割合についての検討

宮本和也, 松本和幸, 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, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也, 大塚基之

日本消化器病学会雑誌 120 ( 臨増総会 ) A378 - A378 2023.3

高齢者消化器癌診療における化学療法と外科治療の現状と課題高齢者消化器癌の化学療法開始前における高齢者機能評価と治療内容・予後についての検討

河野吉泰, 稲生祥子, 堀口繁, 加藤博也, 倉岡紗樹子, 岡上昇太郎, 里見拓也, 松枝克典, 濱田健太, 岩室雅也, 川野誠司, 河原祥朗

日本消化管学会雑誌 7 ( Suppl. ) 219 - 219 2023.1

Optimal liver drainage rate for survival in patients with unresectable malignant hilar biliary obstruction using 3D-image volume analyzer. International journal

Kosaku Morimoto, Kazuyuki Matsumoto, Taisuke Obata, Takashi Oda, Kazuya Miyamoto, Akihiro Matsumi, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Motoyuki Otsuka

Therapeutic advances in gastroenterology 16 17562848231206980 - 17562848231206980 2023

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

BACKGROUND: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. OBJECTIVES: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. DESIGN: This study was a single-center retrospective cohort study. METHODS: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. RESULTS: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with <80% drainage (n = 23) (450 days versus 224 days, p = 0.0033, log-rank test). TRBO was 201 (95% CI: 155-327) days and did not differ significantly by liver drainage rate. Multivariate Cox proportional hazards regression analysis revealed >80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p < 0.0001) as significant prognostic factors. CONCLUSION: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study. TRAIL REGISTRATION: Okayama University Hospital, IRB number: 2108-011.

DOI： 10.1177/17562848231206980

Endoscopic treatment for duodenal perforation due to biliary stent dislocation: A case report and brief review of the literature. International journal

Yuki Fujii, Kazuyuki Matsumoto, Kazuya Miyamoto, Akihiro Matsumi, Kosaku Morimoto, Hiroyuki Terasawa, Tatsuhiro Yamazaki, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato

Medicine 101 ( 48 ) e31868 2022.12

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

RATIONALE: Duodenal wall perforation by a dislocated biliary stent placed for biliary structure is rare but can be life-threatening. There are few reports on the management of stent-related duodenal perforation. PATIENT CONCERNS: Three cases included in this study had undergone endoscopic retrograde cholangiopancreatography with placement of a plastic stent for biliary stricture. Two cases had symptoms (fever or abdominal pain), while other case showed no symptom after biliary stent placement. DIAGNOSES: Dislocation of plastic stents was revealed on computed tomography or endoscopic images. Two patients were diagnosed with duodenal perforation due to distal migration of long stents with a straight shape on the distal side. One patient was diagnosed with fistula formation between the intrahepatic bile duct and duodenum due to perforation of a pigtail stent. INTERVENTIONS: All cases could successfully be managed endoscopically with closure by hemoclips or stent replacement. OUTCOMES: All 3 cases were improved after endoscopic treatment without any subsequent intervention. LESSONS: Longer stents with a straight distal side are associated with a higher risk of duodenal perforation. Endoscopic management is appropriate as a first-line approach for a clinically stable patient. At the time of stent placement, we should pay attention to the length and type of stent.

DOI： 10.1097/MD.0000000000031868

【胆膵EUSのトラブルシューティング】治療的EUS EUS-guided biliary drainage(EUS-BD) 処置後の腹痛

加藤博也, 内田大輔, 松本和幸, 堀口繁, 堤康一郎

消化器内視鏡 34 ( 12 ) 2011 - 2015 2022.12

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report. International journal

Ryosuke Sato, Kazuyuki Matsumoto, Hiromitsu Kanzaki, Akihiro Matsumi, Kazuya Miyamoto, Kosaku Morimoto, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Koichiro Tsutsumi, Shigeru Horiguchi, Hironari Kato

World journal of clinical cases 10 ( 31 ) 11607 - 11616 2022.11

Language：English

BACKGROUND: Gastric linitis plastica (GLP) is a subset of gastric cancer with a poor prognosis. It is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies, and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) for GLP has been recently reported. Meanwhile, autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic syndrome. We herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with GLP. CASE SUMMARY: An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after eating. His laboratory data revealed high levels of serum carbohydrate antigen 19-9 and immunoglobulin-G4. Endoscopic examinations showed giant gastric folds and reddish mucosa; however, no epithelial changes were observed. The gastric lumen was not distensible by air inflation, suggesting GLP. Computed tomography showed the thickened gastric wall, the diffuse enlargement of the pancreas, and the peripancreatic rim, which suggested autoimmune pancreatitis (AIP) coexisting with GLP. Because the pathological findings of the endoscopic biopsy showed no malignancy, he underwent an EUS-FNB and was diagnosed with GLP. He received chemotherapy for unresectable gastric cancer due to peritoneal metastasis, after which both the gastric wall thickening and diffuse enlargement of the pancreas were improved. CONCLUSION: An EUS-FNB for GLP with a negative endoscopic biopsy is useful, and AIP may develop as a paraneoplastic syndrome.

DOI： 10.12998/wjcc.v10.i31.11607

医原性主膵管損傷に対してEUS-PDが有効であった一例

大里俊樹, 宮本和也, 小幡泰介, 織田崇志, 菊池達也, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 堤康一郎, 加藤博也

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 118回・129回 147 - 147 2022.11

SpyGlass DSによるEHLと胆道鏡用バスケットが有用であった肝内結石の1例

松三明宏, 藤井佑樹, 松本和幸, 小幡泰介, 織田崇志, 菊池達也, 宮本和也, 森本光作, 寺澤裕之, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也

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 118回・129回 146 - 146 2022.11

Linitis plastica型胃癌の診断に超音波内視鏡ガイド下針生検が有用であった1例

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

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 118回・129回 139 - 139 2022.11

ペムブロリズマブが奏功した高頻度マイクロサテライト不安定性を有する肝内胆管癌の1例

角田太助, 藤井佑樹, 堀口繁, 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, 堤康一郎, 加藤博也

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 118回・129回 90 - 90 2022.11

アンメットメディカルニーズへの挑戦当院における膵消化管神経内分泌腫瘍に対するペプチド受容体放射性核種療法(PRRT)導入後の現状

藤井佑樹, 堀口繁, 内田大輔, 松本和幸, 加藤博也

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 118回・129回 77 - 77 2022.11

Optimization of Isolation Method for Extracellular Vesicles from Pancreatic Juice and Impact of Protease Activity. International journal

Koichiro Tsutsumi, Eijiro Ueta, Hironari Kato, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Digestive diseases and sciences 67 ( 10 ) 4797 - 4804 2022.10

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

BACKGROUNDS: Pancreatic juice (PJ) is directly associated with pancreatic lesions, including pancreatic ductal cancer and intraductal papillary mucinous neoplasm-derived cancer. Therefore, EVs secreted from these lesions into PJ can be promising biomarkers for early diagnosis. However, there are limited data from analysis of EVs in PJ samples. AIMS AND METHODS: We aimed to determine the stability of EVs in PJ collected using endoscopic naso-pancreatic drainage (ENPD) tubes as well as catheter during endoscopic retrograde cholangiography (ERCP), with or without the impact of positive protease activity, and optimize the EV isolation method. RESULTS: Size exclusion chromatography was found to be an optimal isolation method for EVs in PJ as it achieved higher recovery and purity of EVs compared with differential ultracentrifugation and polymer-based precipitation. Approximately 40% of the PJ samples collected during ERCP and more than 90% of those collected using ENPD tubes had positive protease activity. In vitro exposure to room temperature for less than 3 h was harmless to the structure of double-membrane EVs in PJ and the expression levels of TSG101, even with positive protease activity. CONCLUSIONS: We clarified the physiobiological status of EVs in PJ and optimized the EV isolation method using suitable PJ samples; these findings can be utilized to discover biomarkers for cancer diagnosis and elucidate their function.

DOI： 10.1007/s10620-021-07339-x

人工知能を用いた膵癌におけるEUS-FNAの迅速細胞診診断

藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 堤康一郎, 井上博文, 谷本太郁由, 加藤博也, 河原祥朗

日本消化器病学会雑誌 119 ( 臨増大会 ) A783 - A783 2022.10

胆道癌の新たな治療戦略(遺伝子パネル・分子標的・術前治療) 当院における肝内胆管癌のがんゲノム医療の現状について

堀口繁, 松本和幸, 加藤博也

日本消化器病学会雑誌 119 ( 臨増大会 ) A586 - A586 2022.10

A case of endoscopic retrograde cholangiopancreatography-related main pancreatic duct perforation salvaged by endoscopic ultrasonography-guided pancreatic duct drainage.

Ryosuke Sato, Kazuyuki Matsumoto, Akihiro Matsumi, Kosaku Morimoto, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Koichiro Tsutsumi, Shigeru Horiguchi, Hironari Kato

Clinical journal of gastroenterology 15 ( 6 ) 1179 - 1184 2022.9

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

We herein report a 78-year-old man who underwent endoscopic retrograde cholangiopancreatography (ERCP) to examine main pancreatic duct (MPD) stenosis. During ERCP, MPD perforation occurred due to the cytology brush maneuver. Endoscopic pancreatic stenting to bridge the perforated site failed because the MPD was bent and formed a loop. Thus, we placed the stent at the proximal perforated side. The patient developed retroperitoneal perforation and pancreatic fistula with infection, showing a worsening condition. Pancreatic duct drainage was not effective, so we performed endoscopic ultrasonography-guided pancreatic duct drainage. Subsequently, he gradually improved and was discharged 3 months after initial ERCP.

DOI： 10.1007/s12328-022-01699-1

Stent-in-stent techniqueにて抜去した胆管金属ステントの2例

松三明宏, 松本和幸, 小幡泰介, 織田崇志, 菊池達也, 宮本和也, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也

胆道 36 ( 3 ) 349 - 349 2022.9

生体肝移植後胆管狭窄に対する内視鏡治療

山崎辰洋, 松本和幸, 加藤博也, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 堀口繁, 堤康一郎

胆道 36 ( 3 ) 344 - 344 2022.9

Endoscopic ultrasonography-guided bilateral drainage with antegrade stenting in patient with malignant hilar biliary obstruction after bowel reconstruction. International journal

Ryosuke Sato, Kazuyuki Matsumoto, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Shigeru Horiguchi, Hironari Kato

Endoscopy 54 ( S 02 ) E1026-E1027 2022.8

Double guidewire technique stabilization procedure for endoscopic ultrasound-guided hepaticogastrostomy involving modifying the guidewire angle at the insertion site. International journal

Yuki Fujii, Hironari Kato, Hitomi Himei, Eijiro Ueta, Taiji Ogawa, Hiroyuki Terasawa, Tatsuhiro Yamazaki, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Surgical endoscopy 36 ( 12 ) 8981 - 8991 2022.8

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

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is often performed using a single guidewire (SGW), but the efficacy of the double guidewire (DGW) technique during endoscopic ultrasonography-guided biliary drainage has been reported. We evaluated the efficacy of the DGW technique for EUS-HGS, focusing on the guidewire angle at the insertion site. METHODS: This retrospective cohort study included consecutive patients who underwent EUS-HGS between April 2012 and March 2021. We measured the guidewire angle at the insertion site using still fluoroscopic imaging. We compared the clinical outcomes of EUS-HGS with the DGW and SGW techniques. The factors associated with successful cannula insertion, need for additional fistula dilation and adverse event rate were assessed by a logistic regression multivariable analysis. RESULTS: The DGW group showed higher technical (p = 0.020) and clinical success rates (p = 0.016) than the SGW group, which showed more adverse events (p = 0.017) than the DGW group. Successful cannula insertion was associated with a guidewire angle > 137° and an uneven double-lumen cannula. The DGW technique made the guidewire angle obtuse at the insertion site (p < 0.0001). A guidewire angle ≤ 137° (OR, 35.6; 95% CI, 1.70-744; p = 0.0045) and intrahepatic bile duct diameter of the puncture site ≤ 3.0 mm (OR, 14.4; 95% CI, 1.37-152; p = 0.0056) were risk factors for needing additional fistula dilation in a multivariate analysis, and additional dilation was a significant predictive factor for adverse events (OR, 8.3; 95% CI, 0.9-77; p = 0.026). CONCLUSIONS: The DGW technique can modify the guidewire angle at the insertion site and facilitate stent deployment with few adverse events.

DOI： 10.1007/s00464-022-09350-3

『胆膵疾患と性差』分枝型IPMNの性差による画像的特徴と長期経過の検討

宮本和也, 松本和幸, 松三明宏, 森本光作, 寺澤裕之, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也

日本高齢消化器病学会誌 25 ( 1 ) 161 - 161 2022.7

Successful removal of an uncovered metallic stent using peroral direct cholangioscopy and the stent-in-stent technique. International journal

Akihiro Matsumi, Kazuyuki Matsumoto, Tatsuhiro Yamazaki, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada

Endoscopy 2022.6

急性膵炎を契機として発見された膵頭部mixed type SCNの1例

佐藤亮介, 松三明宏, 上田英次郎, 寺澤裕之, 姫井人美, 森本光作, 小川泰司, 藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 岡田裕之

日本消化器病学会中国支部例会プログラム・抄録集 117回 89 - 89 2022.6

膵管内乳頭粘液性腫瘍由来癌との術前鑑別が困難であった限局型自己免疫性膵炎の一例

菊池達也, 藤井佑樹, 松本和幸, 松三明宏, 森本孝作, 寺澤裕之, 山崎辰洋, 堀口繁, 堤康一郎, 加藤博也

日本消化器病学会中国支部例会プログラム・抄録集 117回 92 - 92 2022.6

多発肝腫瘤を伴う胆嚢腫瘤に対してEndosheatherを用いERCP下胆嚢生検を行った1例

森本光作, 山崎辰洋, 小幡泰介, 織田崇志, 上田英次郎, 姫井人美, 松三明宏, 小川泰司, 寺澤裕之, 藤井佑樹, 松本和幸, 堀口繁, 堤康一郎, 加藤博也, 岡田裕之

日本消化器内視鏡学会中国支部例会 128回 116 - 116 2022.5

膵癌術後肝転移再発による悪性肝門部胆管閉塞に対して超音波内視鏡下両葉肝内胆管ドレナージを行った1例

佐藤亮介, 藤井佑樹, 松本和幸, 松三明宏, 森本光作, 寺澤裕之, 山崎辰洋, 堀口繁, 加藤博也

日本消化器内視鏡学会中国支部例会 128回 119 - 119 2022.5

Laminin 511-E8 Fragment Offers Superior Adhesion Properties for Gastric Cancer Cells Compared with Full-Length Laminin 511. Reviewed International journal

Masaya Iwamuro, Hidenori Shiraha, Mayu Kobashi, Shigeru Horiguchi, Hiroyuki Okada

Current issues in molecular biology 44 ( 4 ) 1539 - 1551 2022.4

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

BACKGROUND: The interaction between cancer cells and laminin (Ln) is a key event in tumor invasion and metastasis. Previously, we determined the effect of full-length Ln511 on gastric cancer cells. However, the interactions between the Ln511-E8 fragment, a truncated protein of Ln511, and gastric cancer cells have not been investigated. METHODS: We investigated the adhesion properties of gastric cancer cells to full-length Ln511 and Ln511-E8 fragments. RESULTS: The proliferation of four gastric cancer cell lines (SH-10-TC, MKN74, SC-6-JCK, and MKN45) was highest on the Ln511-E8 fragment. Further, a larger cytoplasm was observed in SH-10-TC and MKN74 cells cultured on full-length Ln511 or Ln511-E8 fragments. The percentage of adhesive cells was highest on the Ln511-E8 fragment in all four cell lines. Moreover, adhesion of the gastric cancer cells to Ln511-E8 fragment-coated plates was reduced by the Cdc42 GTPase inhibitor in a dose-dependent manner, suggesting the involvement of Cdc42 in the Ln511-E8 fragment-induced enhanced adhesion of gastric cancer cells. CONCLUSIONS: The Ln511-E8 fragment had a greater impact on the adhesion, morphology, and proliferation of gastric cancer cells than full-length laminin. Thus, the Ln511-E8 fragment is suitable for investigating the interaction between gastric cancer cells and extracellular matrices in tumor invasion and metastasis.

DOI： 10.3390/cimb44040105

Endoscopic removal of proximally migrated stents using a double-balloon enteroscope in patients with bowel reconstruction (with video). International journal

Takashi Oda, Kazuyuki Matsumoto, Eijiro Ueta, Hitomi Himei, Taiji Ogawa, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada

DEN open 2 ( 1 ) e32 2022.4

Language：English

Endoscopic migrated stent removal using a balloon-assisted enteroscope is technically difficult in patients with bowel reconstruction. We report the treatment outcomes and endoscopic removal methods for migrated stents using a double-balloon enteroscope (DBE). We retrospectively studied 12 patients with stent migration into the main pancreatic duct (MPD) or bile duct who underwent bowel reconstruction between January 2012 and June 2020. The successful removal rates in the MPD (n = 3) and the bile duct (n = 9) were 66.7% (2/3) and 88.9% (8/9), respectively. The removal techniques included the indirect method (n = 3), the direct method (n = 4), and a combination of indirect and direct methods (n = 3). The removal devices included an extraction balloon catheter (n = 7), basket catheter (n = 5), biopsy forceps (n = 3), and snare (n = 2). Stent removal using a DBE was feasible and useful as the first treatment for patients with bowel reconstruction. The choice of the direct and/or indirect method according to the situation of the migrated stent is important.

DOI： 10.1002/deo2.32

術後腸管症例におけるステント迷入に対するダブルバルン内視鏡を用いたステント抜去法

織田崇志, 松本和幸, 加藤博也, 小幡泰介, 上田英次郎, 姫井人美, 松三明宏, 森本光作, 小川泰司, 寺澤裕之, 藤井佑樹, 山崎辰洋, 堀口繁, 堤康一郎

Gastroenterological Endoscopy 64 ( Suppl.1 ) 765 - 765 2022.4

胃切後Roux-en-Y再建腸管を有する患者の総胆管結石治療におけるバルーン内視鏡下ERCPの治療戦略

小幡泰介, 堤康一郎, 加藤博也, 織田崇志, 森本光作, 姫井人美, 松三明宏, 上田英次郎, 小川泰司, 寺澤裕之, 藤井佑樹, 山崎辰洋, 松本和幸, 堀口繁, 岡田裕之

Gastroenterological Endoscopy 64 ( Suppl.1 ) 820 - 820 2022.4

胆管空腸吻合術後の肝内結石に対する直接胆道鏡の有用性の検討

松三明宏, 松本和幸, 加藤博也, 小幡泰介, 織田崇志, 上田英次郎, 姫井人美, 森本光作, 小川泰司, 寺澤裕之, 藤井佑樹, 山崎辰洋, 堀口繁, 堤康一郎, 岡田裕之

Gastroenterological Endoscopy 64 ( Suppl.1 ) 821 - 821 2022.4

Surgical resection of mixed neuroendocrine-non-neuroendocrine neoplasm in the biliary system: a report of two cases. International journal

Ayano Tamaki, Yuma Tani, Hiroki Sato, Ryuichi Yoshida, Kazuya Yasui, Shigeru Horiguchi, Takashi Kuise, Yuzo Umeda, Kazuhiro Yoshida, Tomokazu Fuji, Kenjiro Kumano, Kosei Takagi, Takahito Yagi, Toshiyoshi Fujiwara

Surgical case reports 8 ( 1 ) 38 - 38 2022.3

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

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. CASE PRESENTATION: Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. CONCLUSION: We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations.

DOI： 10.1186/s40792-022-01386-w

Study Protocol for a Trial: A Single-Arm, Open-Labeled Study Evaluating Transcatheter Arterial Embolization Plus Everolimus Combination Therapy for Patients With Liver Metastasis of Gastroenteropancreatic Neuroendocrine Tumors. International journal

Yasuto Takeuchi, Hironari Kato, Shigeru Horiguchi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki

Clinical Medicine Insights. Oncology 16 11795549221127750 - 11795549221127750 2022

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

BACKGROUND: The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study. METHODS: We design a single-arm, open-label, prospective study to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastases of GEP-NETs. The study started in June 2021 at Okayama University Hospital and is expected to enroll 18 patients over a 2-year period. DISCUSSION: This study is a prospective study investigating a new treatment method for a rare disease called GEP-NETs. We may obtain useful information that contributes to the treatment guidelines in this study. However, NET is a rare disease, and although the number of cases is statistically established, it may not be possible to accurately assess causality.TRIAL REGISTRATION NUMBER: jRCT1061210015.

DOI： 10.1177/11795549221127750

Successful endoscopic three-branch self-expandable metallic stent placement using a novel device delivery system for malignant hilar biliary stricture. International journal

Kazuyuki Matsumoto, Hironari Kato, Yuki Fujii, Tatsuhiro Yamazaki, Koichiro Tsutsumi, Shigeru Horiguchi, Hiroyuki Okada

Endoscopy 2021.12

Pancreatic actinomycosis treated by antibiotics after diagnosis using endoscopic ultrasound-guided fine-needle biopsy.

Kazuya Miyamoto, Kazuyuki Matsumoto, Kazuki Ocho, Koji Fujita, Shigeru Horiguchi, Ryuta Takenaka, Shigeatsu Fujiki

Clinical journal of gastroenterology 14 ( 6 ) 1785 - 1790 2021.12

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

A 71-year-old man who had undergone total gastrectomy, partial pancreatectomy, and splenectomy with Roux-en-Y reconstruction for gastric cancer was referred for a possible pancreatic tail tumor. Contrast-enhanced computed tomography showed mold-like, poor contrast lesion in the dilated main pancreatic duct in the pancreatic tail. Endoscopic ultrasonography revealed a slightly hyperechoic solid lesion that occupied the lumen of the main pancreatic duct. Linear calcification was observed in the lesions on both computed tomography and endoscopic ultrasonography, and endoscopic ultrasound-guided fine-needle biopsy was performed. Histopathology revealed sulfur grains and inflammatory infiltrates with no malignant findings. We also performed an anaerobic culture using fine-needle biopsy specimens, and Actinomyces meyeri was detected in the culture results. After confirming susceptibility, oral administration of amoxicillin was initiated. After 8 months of treatment, the size of the lesion slightly decreased, and the antibiotics treatment is still ongoing. This shows that such cases could be diagnosed based on histological findings and anaerobic culture using a fine-needle biopsy specimen, and unnecessary surgery may be avoided. In the case of tumors developed in the residual pancreas without typical malignant imaging findings, pancreatic actinomycosis should be considered as a differential diagnosis.

DOI： 10.1007/s12328-021-01523-2

Risk Factors for the Development of High-risk Stigmata in Branch-duct Intraductal Papillary Mucinous Neoplasms. Reviewed

Tatsuhiro Yamazaki, Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuki Fujii, Yosuke Saragai, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 60 ( 20 ) 3205 - 3211 2021.10

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

Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS [odds ratio, 14.2; 95% confidence interval (CI), 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014]. Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.

DOI： 10.2169/internalmedicine.7168-21

Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer. Reviewed International journal

Soichiro Ako, Hironari Kato, Kazuhiro Nouso, Hideaki Kinugasa, Hiroyuki Terasawa, Hiroshi Matushita, Saimon Takada, Yosuke Saragai, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Daisuke Nobuoka, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

Cancer biology & therapy 22 ( 10-12 ) 1 - 7 2021.10

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

BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

DOI： 10.1080/15384047.2021.1980312

【膵疾患に対する内視鏡診療のすべて】膵疾患に対する内視鏡治療内視鏡的膵管ステント留置術の適応と実際

加藤博也, 松本和幸, 堀口繁, 堤康一郎, 岡田裕之

消化器内視鏡 33 ( 9 ) 1437 - 1444 2021.9

Language：Japanese Publisher：(株)東京医学社

内視鏡的膵管ステント留置術(EPS)の適応となるのはおもに慢性膵炎による狭窄や膵石であるが、急性膵炎や膵癌、膵外傷など、その他の疾患に伴う膵管狭窄に対してもEPSは適応となる。また、膵炎に伴う仮性嚢胞や術後の膵液瘻にもEPSはしばしば適応となる。胆管ステントと同様、膵管ステントも近年では多くの種類が流通しており、形状、太さ、長さもさまざまで状況に応じた取捨選択が必要となる。また、EPSを行う際には、まず内視鏡的経鼻膵管ドレナージを行ってからEPSに移行する方法がある。さらに、EPSは良性の狭窄に対して行うことが多い点が、悪性疾患で適応となることが多い胆道狭窄とは異なる。そのため、ステント交換・抜去のタイミングなどドレナージのあとのマネジメントも重要である。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02312&link_issn=&doc_id=20211008090012&doc_link_id=%2Faq9syokd%2F2021%2F003309%2F013%2F1437-1444%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2021%2F003309%2F013%2F1437-1444%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Randomized trial comparing the 25G and 22G Franseen needles in endoscopic ultrasound‐guided tissue acquisition from solid pancreatic masses for adequate histological assessment Reviewed International journal

Takeshi Tomoda, Hironari Kato, Yuuki Fujii, Tatsuhiro Yamazaki, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hirofumi Inoue, Takehiro Tanaka, Toshiharu Mitsuhashi, Hiroyuki Okada

Digestive Endoscopy 2021.7

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

BACKGROUND: The effects of the Franseen needle size in endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) of solid pancreatic masses remain unclear. This study aimed to compare 25G and 22G Franseen needles in terms of adequate tissue acquisition from solid pancreatic masses. METHODS: In this single-center, crossover, randomized noninferiority trial, eligible patients underwent EUS-FNB with both 25G and 22G Franseen needles in a randomized order between November 2018 and August 2020. Tissue specimens from each pass were separately evaluated based on the cellularity scoring system. The primary outcome was the proportion of acquired specimens allowing adequate histological assessment (cellularity score ≥3). A -15% noninferiority margin was assumed. RESULTS: Data from 88 patients were analyzed, which showed malignant and benign lesions in 84 (95.5%) and four (4.5%) patients, respectively. Of the 88 specimens, 62 (70.5%) and 69 (78.4%) acquired using 25G and 22G needles, respectively, allowed adequate histological assessment. The adjusted proportion difference was -6.6% (95% confidence interval -8.8% to -4.5%), indicating noninferiority of the 25G Franseen needle (P < 0.001). The diagnostic accuracies of the 25G and 22G needles were 86.4% and 89.8%, respectively, with no significant difference (P = 0.180). Adverse events occurred in one patient. CONCLUSIONS: The 25G Franseen needle showed a noninferior adequate tissue acquisition and similar diagnostic performance compared to that of the 22G Franseen needle. However, a 15% noninferiority margin was high for clinical use; thus, further consideration is needed (Clinical Trial Registry no. UMIN000034596).

DOI： 10.1111/den.14079

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/den.14079

Efficacy of double-balloon enteroscopy-assisted endoscopic balloon dilatation combined with stent deployment for hepaticojejunostomy anastomotic stricture. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Toru Ueki, Tsuneyoshi Ogawa, Ken Hirao, Yutaka Akimoto, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 2021.7

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

BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is a significant complication of biliary reconstruction surgery. Endoscopic management of HJAS using double-balloon enteroscopy has expanded; however, retrospective reports in this setting are limited. This study aimed to evaluate the efficacy of endoscopic balloon dilatation combined with stent deployment for HJAS. METHODS: This was a single-arm prospective clinical trial involving 40 patients with treatment-naïve HJAS enrolled between March 2016 and August 2019 at four endoscopy units in Japan. For HJAS, plastic stents combined with balloon dilatation were placed for 6 months after initial stenting. The primary outcome was HJ anastomosis patency 12 months after stent removal. RESULTS: The technical success rate was 97.5% (39/40). The failed case required percutaneous transhepatic biliary drainage using the rendezvous technique. All cases achieved successful endoscopic treatment. During the treatment period, four of 40 patients (10%) ended the study protocol due to unrelated causes and were excluded from the primary analysis. Among the 36 patients, clinical success was achieved in 34 (94.4%) patients. The remaining two patients achieved HJAS resolution after an additional 3 months. All 36 patients achieved HJAS resolution. Adverse events were observed in two patients (5.0%) who developed moderate cholangitis. During a median follow-up of 21.3 months, HJAS recurrence was observed in 8.3% (3/36) with a median time to recurrence of 4.3 months and HJ anastomosis patency at 12 months was 94.4%. CONCLUSIONS: Endoscopic balloon dilatation combined with plastic stent deployment for 6 months was a safe and effective strategy for HJAS. (Clinical Trial Registry no. UMIN000020613).

DOI： 10.1111/den.14097

Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography for the Treatment of Common Bile Duct Stones in Patients with Roux-en-Y Gastrectomy: Outcomes and Factors Affecting Complete Stone Extraction. Reviewed International journal

Taisuke Obata, Koichiro Tsutsumi, Hironari Kato, Toru Ueki, Kazuya Miyamoto, Tatsuhiro Yamazaki, Akihiro Matsumi, Yuki Fujii, Kazuyuki Matsumoto, Shigeru Horiguchi, Kengo Yasugi, Tsuneyoshi Ogawa, Ryuta Takenaka, Hiroyuki Okada

Journal of clinical medicine 10 ( 15 ) 2021.7

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

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in patients with Roux-en-Y gastrectomy (RYG) remains technically challenging. METHODS: Seventy-nine RYG patients (median 79 years old) underwent short-type double-balloon enteroscopy-assisted ERCP (sDBE-ERCP) for CBD stones at three referral hospitals from 2011-2020. We retrospectively investigated the treatment outcomes and potential factors affecting complete stone extraction. RESULTS: The initial success rates of reaching the papilla of Vater, biliary cannulation, and biliary intervention, including complete stone extraction or biliary stent placement, were 92%, 81%, and 78%, respectively. Of 57 patients with attempted stone extraction, complete stone extraction was successful in 74% for the first session and ultimately in 88%. The adverse events rate was 5%. The multivariate analysis indicated that the largest CBD diameter ≥ 14 mm (odds ratio (OR), 0.04; 95% confidence interval (CI), 0.01-0.58; p = 0.018) and retroflex position (OR, 6.43; 95% CI, 1.12-36.81; p = 0.037) were independent predictive factors affecting complete stone extraction achievement. CONCLUSIONS: Therapeutic sDBE-ERCP for CBD stones in a relatively elderly RYG cohort, was effective and safe. A larger CBD diameter negatively affected complete stone extraction, but using the retroflex position may be useful for achieving complete stone clearance.

DOI： 10.3390/jcm10153314

Hemosuccus Pancreaticus Due to the Rupture of a Pseudoaneurysm That Developed in an Intraductal Papillary Mucinous Neoplasm.

Taisuke Obata, Kazuyuki Matsumoto, Hironari Kato, Tatsuhiro Yamazaki, Yuki Fujii, Takeshi Tomoda, Shigeru Horiguchi, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 60 ( 13 ) 2033 - 2038 2021.7

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

A 76-year-old woman with branch duct intraductal papillary mucinous neoplasm (IPMN) was admitted with epigastric pain and vomiting. She had received warfarin due to a history of deep vein thrombosis. A blood test showed decreased serum hemoglobin and elevated serum amylase. Contrast-enhanced computed tomography revealed acute pancreatitis and formation of a pseudoaneurysm in the IPMN. We suspected rupture of a pseudoaneurysm and performed trans-catheter angiography. Angiography showed extravasation from the posterior superior pancreaticoduodenal artery, and coil embolization was performed. It is important to be alert for the formation of pseudoaneurysm in patients with cystic neoplasms.

DOI： 10.2169/internalmedicine.6445-20

Extracellular vesicle-shuttled miRNAs as a diagnostic and prognostic biomarker and their potential roles in gallbladder cancer patients. Reviewed International journal

Eijiro Ueta, Koichiro Tsutsumi, Hironari Kato, Hiroshi Matsushita, Hidenori Shiraha, Masakuni Fujii, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Scientific reports 11 ( 1 ) 12298 - 12298 2021.6

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

Circulating microRNAs (miRNAs) in serum extracellular vesicles (EVs) are a promising biomarker in cancer. We aimed to elucidate the serum EVs miRNA biomarkers to identify patients with gallbladder cancer (GBC) and to clarify their potential roles. One hundred nineteen serum EVs from GBC and non-GBC individuals were isolated by pure-EVs-yieldable size-exclusion chromatography, and then were analyzed using a comprehensive miRNAs array and RT-qPCR-based validation. The functional roles of the identified miRNAs were also investigated using GBC cell lines. Serum EVs miR-1246 and miR-451a were significantly upregulated and downregulated, respectively in GBC patients (P = 0.005 and P = 0.001), in line with their expression levels in cancer tissue according to an in silico analysis. The combination of CEA and CA19-9 with miR-1246 showed the highest diagnostic power (AUC, 0.816; Sensitivity, 72.0%; Specificity, 90.8%), and miR-1246 was an independent prognostic marker of GBC (Hazard ratio, 3.05; P = 0.017) according to a Cox proportional hazards model. In vitro, miR-1246 promoted cell proliferation and invasion, while miR-451a inhibited cell proliferation and induced apoptosis with the targeting of MIF, PSMB8 and CDKN2D. Taken together, miR-1246 in serum EVs has potential application as a diagnostic and prognostic marker and miR-451a may be a novel therapeutic target in GBC.

DOI： 10.1038/s41598-021-91804-0

Laminin-411 and -511 Modulate the Proliferation, Adhesion, and Morphology of Gastric Cancer Cells. Reviewed International journal

Masaya Iwamuro, Hidenori Shiraha, Atsushi Oyama, Daisuke Uchida, Shigeru Horiguchi, Hiroyuki Okada

Cell biochemistry and biophysics 79 ( 2 ) 407 - 418 2021.6

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

Laminins (Ln), a type of extracellular matrix glycoprotein, are key regulators of cellular behavior. Recent work revealed that in various tumor cell lines, laminin isoforms influence specific responses, such as cell anchorage, survival, proliferation, migration, organization, and specialization. The contribution of laminin isoforms to the function of gastric cancer cells, however, remain unclear. Here, we revealed that in gastric cancer, laminin isoforms Ln411, Ln421, Ln511, and Ln521 promote cellular proliferation; Ln511 and Ln521 increase cell cytoplasmic volume; Ln511 hampers invadopodia formation in some cells, Ln511 enables prompt adhesion of cells to plates, and Ln411 and Ln511 do not alter the gastric cancer stem cell markers CD44 and Lgr5. These results indicate that Ln411 and Ln511 dynamically modulate the proliferation, adhesion, and morphology of gastric cancer cells in different ways that are independent of stem cell properties. In particular, Ln511 showed a high affinity for gastric cancer cells. Our observations broaden the possible options for controlling cancer cell progression and metastasis by modulating laminin-integrin interactions.

DOI： 10.1007/s12013-021-00972-3

Efficacy of low dose rectal diclofenac for preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: Propensity score-matched analysis. International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuuki Fujii, Yousuke Saragai, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 4 ) 656 - 662 2021.5

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

BACKGROUND: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). However, the efficacy of low dose rectal NSAIDs for preventing PEP remains controversial. METHODS: We performed a retrospective study of 301 patients with native papilla and a body weight of <50 kg who underwent ERCP between September 2010 and October 2019. After July 2016, a 25 mg dose of rectal diclofenac was routinely administered within 15 min before ERCP (NSAIDs group, n = 72) and the control group (n = 229) consisted of patients undergoing ERCP before this date without treatment. We compared the incidence of PEP between the two groups using propensity score matching. RESULTS: A total of 66 pairs of patients in each group were selected. The patients and procedural-related factors were similar in both groups. In total, 15 patients (11.4%) developed PEP: 12.1% (8/66) in the NSAIDs group and 10.6% (7/66) in the control group (Odds ratio (OR) 1.2; 95% confidence interval (CI) 0.4-3.5; P = 0.78). There was no significant difference in incidence of other adverse events related to ERCP between the two groups. CONCLUSIONS: Prophylactic administration of a 25 mg dose of rectal diclofenac did not reduce the incidence of PEP in patients with a native papilla and a body weight of <50 kg in this study and a certain dose of rectal NSAIDs, such as a 100-mg dose, should be administered regardless of body weight to prevent PEP.

DOI： 10.1111/den.13828

The Long-Term Outcomes of Endoscopic Papillectomy and Management of Cases of Incomplete Resection: A Single-Center Study. International journal

Shinichiro Muro, Hironari Kato, Akihiro Matsumi, Yuki Ishihara, Yosuke Saragai, Shuntaro Yabe, Saimon Takata, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 25 ( 5 ) 1247 - 1252 2021.5

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

BACKGROUND: Endoscopic papillectomy is increasingly performed as an alternative to surgery for early ampullary tumors. AIM: This retrospective study aimed to evaluate the long-term results of endoscopic papillectomy, the management of cases with incomplete endoscopic resection, and the long-term recurrence rates. METHODS: All 46 patients who underwent endoscopic papillectomy for ampullary tumors between November 2003 and March 2018 were retrospectively evaluated. RESULTS: The final pathological diagnoses were adenoma (n = 44) and adenocarcinoma (n = 2). Histopathological evaluations after endoscopic papillectomy revealed that complete resection was achieved in 19 patients (19/46, 41.3%). Among the 27 patients with incomplete resection, the margin was histopathologically positive in 14 patients and difficult to evaluate in 13. Additional surgery was performed for 2 of the 14 patients with positive margins. Excluding 2 patients who received additional surgery, 7 of the 25 patients with incomplete resection had recurrence, and 18 had no recurrence during the follow-up period. Ten (77%) of the 13 patients in whom the margin was difficult to evaluate had no recurrence. CONCLUSION: Approximately 80% of the patients in whom the histopathological evaluation of the resected margin was difficult had no recurrence even after approximately 5 years of follow-up. Thus, careful observation may be considered for these patients.

DOI： 10.1007/s11605-020-04532-7

Endoscopic ultrasonography findings of pancreatic parenchyma for predicting subtypes of intraductal papillary mucinous neoplasms. Reviewed International journal

Yuki Fujii, Kazuyuki Matsumoto, Hironari Kato, Tatsuhiro Yamazaki, Takeshi Tomoda, Shigeru Horiguchi, Koichiro Tsutsumi, Kenji Nishida, Takehiro Tanaka, Keiji Hanada, Hiroyuki Okada

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 21 ( 3 ) 622 - 629 2021.4

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

BACKGROUND AND AIMS: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). METHODS: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. RESULTS: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type. CONCLUSIONS: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.

DOI： 10.1016/j.pan.2021.01.026

Treatment outcomes, including risk factors of stone recurrence, for hepatolithiasis using balloon-assisted endoscopy in patients with hepaticojejunostomy (with video). Reviewed International journal

Yuki Ishihara, Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Takeshi Tomoda, Akihiro Matsumi, Kazuya Miyamoto, Tatsuhiro Yamazaki, Yosuke Saragai, Yuki Fujii, Daisuke Uchida, Shigeru Horiguchi, Hiroyuki Okada

Surgical endoscopy 35 ( 4 ) 1895 - 1902 2021.4

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

BACKGROUND AND STUDY AIMS: Endoscopic treatment outcomes for hepatolithiasis in patients with altered anatomy are not well known. The aim of this study was to evaluate the treatment outcomes of hepatolithiasis in patients with hepaticojejunostomy (HJ) using short-type double-balloon endoscopy (sDBE) and to assess the risk factors for stone recurrence. PATIENTS AND METHODS: This was a retrospective cohort study that consisted of 73 patients with hepatolithiasis who underwent bowel reconstruction with HJ at an academic center. Stone removal was performed using sDBE. After balloon-occluded cholangiography using sDBE, peroral direct cholangioscopy (PDCS) using ultraslim endoscopy was performed to check for residual stones, depending on the bowel reconstruction method. Recurrence was defined as the development of cholangitis from stones. RESULTS: The success rate of reaching the HJ site was 92% (67/73), and the complete stone removal rate was 93% (62/67) with multiple sessions (mean number 1.5 ± 0.9). The occurrence rate of procedure-related adverse events was 6.8%. Among 58 patients evaluated for stone recurrence, 13 (22%) developed recurrence during a median follow-up period of 2.7 years (interquartile range: 1.5-4.8). Multivariate analyses determined that a stone diameter ≥ 8 mm [odds ratio (OR), 5.57; 95% confidence interval (CI), 1.39-37.2; p = 0.013] and performing PDCS (OR, 0.16; 95% CI, 0.0084-0.90; p = 0.036) were significant factors for stone recurrence. CONCLUSIONS: Endoscopic treatment using sDBE for hepatolithiasis was effective and safe. PDCS might reduce the rate of stone recurrence by detecting stones that are too small to confirm on fluoroscopic images.

DOI： 10.1007/s00464-020-08139-6

Multicenter Retrospective Analysis of Chemotherapy for Advanced Pancreatic Acinar Cell Carcinoma: Potential Efficacy of Platinum- and Irinotecan-Containing Regimens. International journal

Hideaki Takahashi, Masafumi Ikeda, Satoshi Shiba, Hiroshi Imaoka, Akiko Todaka, Kazuhiko Shioji, Kei Yane, Yasushi Kojima, Satoshi Kobayashi, Akinori Asagi, Masato Ozaka, Ryoji Takada, Yoshikuni Nagashio, Shigeru Horiguchi, Akiyoshi Kasuga, Eiichiro Suzuki, Takeshi Terashima, Makoto Ueno, Chigusa Morizane, Junji Furuse

Pancreas 50 ( 1 ) 77 - 82 2021.1

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

OBJECTIVES: The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC). METHODS: Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument. RESULTS: The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not. CONCLUSIONS: Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.

DOI： 10.1097/MPA.0000000000001718

Effectiveness of Menghini-Type Needles for Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Masses. Reviewed International journal

Sho Mizukawa, Hironari Kato, Kazuyuki Matsumoto, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hirofumi Inoue, Noriyuki Tanaka, Hiroyuki Okada

Digestive diseases and sciences 66 ( 9 ) 3171 - 3178 2020.10

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

BACKGROUND: Cutting needles are thought to be effective as biopsy needles. A few types of cutting needles are available for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and the Menghini-type needle is an end-type cutting needle. AIMS: A prospective randomized controlled trial was conducted to compare the results of EUS-FNA using a Menghini-type needle (needle M) versus a conventional needle (needle S). METHODS: The main eligibility criteria were as follows: patients with a pancreatic mass referred for EUS-FNA, ≥ 20 years old, and a performance status < 4. The primary outcome was the sample quality. The secondary outcomes were factors associated with the sample quality, diagnostic accuracy, and adverse events. RESULTS: A total of 97 patients were enrolled in this study. The sample quality for total puncture with needle M (92.8%) was significantly higher than that with needle S (81.4%) (p = 0.0305). The tumor size (p = 0.033) and type of needle (p = 0.031) were significant factors associated with adequate tissue collection in univariate and multivariate analyses (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.12-6.54; p = 0.027 for tumor size, and OR 2.93; 95% CI 1.23-8.21; p = 0.0153 for type of needle). The diagnostic accuracy of each needle was 88.7% (86/97) with needle M and 73.2% (71/97) with needle S. Adverse events occurred in 2 of the 97 patients (0.02%). CONCLUSION: A Menghini-type needle was able to obtain core tissue for histology more effectively than a conventional aspiration needle. TRIAL REGISTRATION NUMBERS: UMIN registration number of 000020668.

DOI： 10.1007/s10620-020-06628-1

Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration. International journal

Kazuyuki Matsumoto, Hironari Kato, Kazuhiro Nouso, Soichiro Ako, Hideaki Kinugasa, Shigeru Horiguchi, Yosuke Saragai, Saimon Takada, Shuntaro Yabe, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Hiroyuki Okada

Digestive diseases and sciences 65 ( 10 ) 2907 - 2913 2020.10

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

BACKGROUND AND AIMS: The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence. METHODS: Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR). RESULTS: The median needle puncture number used to obtain adequate pathological samples was two (range 1-6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively. CONCLUSIONS: KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.

DOI： 10.1007/s10620-019-06006-6

The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm. International journal

Kazuya Miyamoto, Kazuyuki Matsumoto, Hironari Kato, Ryuichi Yoshida, Yuzo Umeda, Hirohumi Inoue, Takehiro Tanaka, Akihiro Matsumi, Yosuke Saragai, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Takeshi Tomoda, Shigeru Horiguchi, Takahito Yagi, Hiroyuki Okada

BMC gastroenterology 20 ( 1 ) 319 - 319 2020.9

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

BACKGROUND: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. METHODS: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. RESULTS: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). CONCLUSIONS: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

DOI： 10.1186/s12876-020-01465-y

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection. International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Takeshi Tomoda, Akihiro Matsumi, Yuki Ishihara, Yosuke Saragai, Saimon Takada, Shinichiro Muro, Daisuke Uchida, Hiroyuki Okada

Gut and liver 14 ( 5 ) 652 - 658 2020.9

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

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution.

DOI： 10.5009/gnl19200

当院における肝門部領域良性胆道狭窄に対するInside stentの有用性の検討

皿谷洋祐, 加藤博也, 上田英次郎, 松三明宏, 宮本和也, 藤井佑樹, 山崎辰洋, 内田大輔, 友田健, 堀口繁, 堤康一郎, 岡田裕之

胆道 34 ( 3 ) 582 - 582 2020.8

EUSガイド下エタノール注入療法を施行したインスリノーマの1例

松本和幸, 加藤博也, 稲垣兼一, 宮本和也, 山崎辰洋, 藤井祐樹, 内田大輔, 友田健, 堀口繁, 岡田裕之

膵臓 35 ( 3 ) A449 - A449 2020.7

Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma. Reviewed

Atsushi Oyama, Daisuke Uchida, Hidenori Shiraha, Hiroaki Sawahara, Ryo Kato, Masaya Iwamuro, Shigeru Horiguchi, Hiroyuki Okada

Acta medica Okayama 74 ( 3 ) 237 - 243 2020.6

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

The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC.

DOI： 10.18926/AMO/59957

Correction to: Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuuki Fujii, Yousuke Saragai, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Surgical endoscopy 35 ( 1 ) 239 - 240 2020.2

Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuuki Fujii, Yousuke Saragai, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Surgical endoscopy 35 ( 1 ) 232 - 238 2020.1

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

BACKGROUND: To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. METHODS: A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. RESULTS: The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5-43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. CONCLUSION: Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy.

DOI： 10.1007/s00464-020-07385-y

Single-session esophagogastroduodenoscopy and endoscopic ultrasound using a forward-viewing radial scan ultrasonic endoscope. International journal

Daisuke Uchida, Hironari Kato, Kazuyuki Matsumoto, Yuki Ishihara, Akihiro Matsumi, Yosuke Saragai, Saimon Takada, Shuntaro Yabe, Shinichiro Muro, Takeshi Tomoda, Shigeru Horiguchi, Hiroyuki Okada

BMC gastroenterology 19 ( 1 ) 220 - 220 2019.12

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

BACKGROUND: Endoscopic ultrasound is useful for obtaining high-resolution images of pancreaticobiliary diseases, but is not readily available for physical checkups. In this study, we evaluated the safety and efficacy of single-session esophagogastroduodenoscopy and endoscopic ultrasound in the detection of upper-gastrointestinal and pancreaticobiliary diseases using a forward-viewing radial scan ultrasonic endoscope. METHODS: A total of 148 patients who were scheduled for upper-gastrointestinal screening using an endoscope were prospectively included. All patients were examined by EUS in combination with EGD using a forward-viewing radial scan ultrasonic endoscope. The primary endpoint was the safety of the procedures. The secondary endpoints were the prevalence of diseases, the basal imaging capability of EUS, the procedure time, total dose of propofol, and the correlation between background factors and the prevalence of pancreatic disease. The imaging capability at each region was scored as 0 (invisible) to 2 (sufficient visualization to evaluate the organs). RESULTS: Intraoperative hypotension occurred as an adverse event of intravenous anesthesia in one patient. There were 82 pancreaticobiliary findings and 165 upper-gastrointestinal findings (malignancy not included). Follicular lymphoma of the intra-abdominal lymph nodes was detected in one patient. The mean imaging scores of each section were 1.95 (pancreatic head and papilla), 2.0 (pancreatic body), 1.99 (pancreatic tail), and 1.89 (common bile duct and gallbladder). Age, history of diabetes mellitus, and smoking history were significantly associated with the prevalence of pancreatic diseases. CONCLUSION: The simultaneous performance of EGD and EUS using a new ultrasonic endoscope is tolerable and safe for upper-gastrointestinal and pancreaticobiliary screening.

DOI： 10.1186/s12876-019-1141-7

The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer.

Kazuyuki Matsumoto, Toshiaki Ohara, Masayoshi Fujisawa, Akinobu Takaki, Masahiro Takahara, Noriyuki Tanaka, Hironari Kato, Shigeru Horiguchi, Ryuichi Yoshida, Yuzo Umeda, Soichiro Fushimi, Takahito Yagi, Akihiro Matsukawa, Hiroyuki Okada

Journal of gastroenterology 54 ( 11 ) 1019 - 1028 2019.11

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

BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens.

DOI： 10.1007/s00535-019-01586-6

Contrast-enhanced harmonic endoscopic ultrasound using time-intensity curve analysis predicts pathological grade of pancreatic neuroendocrine neoplasm.

Saimon Takada, Hironari Kato, Yosuke Saragai, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Noriyuki Tanaka, Hiroyuki Okada

Journal of medical ultrasonics (2001) 46 ( 4 ) 449 - 458 2019.10

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

PURPOSE: Histological grading is important for the treatment algorithm in pancreatic neuroendocrine neoplasms (PNEN). The present study examined the efficacy of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and time-intensity curve (TIC) analysis of PNEN diagnosis and grading. METHODS: TIC analysis was performed in 30 patients using data obtained from CH-EUS, and a histopathological diagnosis was made via EUS-guided fine-needle aspiration or surgical resection. The TIC parameters were analyzed by dividing them into G1/G2 and G3/NEC groups. Then, patients were classified into non-aggressive and aggressive groups and evaluated. RESULTS: Twenty-six patients were classified as G1/G2, and four as G3/NEC. From the TIC analysis, five parameters were obtained (I: echo intensity change, II: time for peak enhancement, III: speed of contrast, IV: decrease rate for enhancement, and V: enhancement ratio for node/pancreatic parenchyma). Three of these parameters (I, IV, and V) showed high diagnostic performance. Using the cutoff value obtained from the receiver-operating characteristic (ROC) analysis, the correct diagnostic rates of parameters I, IV, and V were 96.7%, 100%, and 100%, respectively, between G1/G2 and G3/NEC. A total of 21 patients were classified into the non-aggressive group, and nine into the aggressive group. Using the cutoff value obtained from the ROC analysis, the accurate diagnostic rates of I, IV, and V were 86.7%, 86.7%, and 88.5%, respectively, between the non-aggressive and aggressive groups. CONCLUSION: CH-EUS and TIC analysis showed high diagnostic accuracy for grade diagnosis of PNEN. Quantitative perfusion analysis is useful to predict PNEN grade diagnosis preoperatively.

DOI： 10.1007/s10396-019-00967-x

Potential Factors Affecting Results of Short-Type Double-Balloon Endoscope-Assisted Endoscopic Retrograde Cholangiopancreatography. Reviewed International journal

Daisuke Uchida, Koichiro Tsutsumi, Hironari Kato, Akihiro Matsumi, Yosuke Saragai, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Digestive diseases and sciences 65 ( 5 ) 1460 - 1470 2019.9

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

BACKGROUND: Short-type double-balloon endoscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) has been developed as an alternative approach for cases with a surgically altered gastrointestinal anatomy. However, this technique is sometimes technically challenging and carries a risk of severe adverse events. AIMS: To evaluate the factors affecting the technical success rate and adverse events of DBE-ERCP. METHODS: A total of 319 patients (805 procedures) with a surgically altered gastrointestinal anatomy underwent short DBE-ERCP. The factors affecting the technical success rate and adverse events, and the learning curve of the trainees were retrospectively evaluated. RESULTS: The technical success rate of all procedures was 90.7%. Adverse events occurred in 44 (5.5%) procedures. A multivariate analysis indicated that Roux-en-Y reconstruction and first-time short DBE-ERCP were factors affecting the technical failure and adverse event rates, while the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction was a non-risk factor for adverse events. The trainee caseload did not affect the technical success or adverse event rates significantly; however, trainees tended to perform cases involving the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction. The success rate of scope insertion increased according to experience; however, the overall success rate did not differ to a statistically significant extent. CONCLUSION: Short DBE-ERCP was useful and safe for managing cases with a surgically altered anatomy; however, trainees should concentrate on accumulating experience with easy cases, such as those with the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction or a history of DBE-ERCP.

DOI： 10.1007/s10620-019-05857-3

Successful removal of impacted large bile duct stones using electrohydraulic lithotripsy with an ultraslim endoscope after Billroth II gastrectomy. International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Daisuke Uchida, Takeshi Tomoda, Shinichiro Muro, Hiroyuki Okada

Endoscopy 51 ( 9 ) E265-E266 2019.9

Diagnostic Ability of Convex-Arrayed Endoscopic Ultrasonography for Major Vascular Invasion in Pancreatic Cancer. International journal

Yuki Fujii, Kazuyuki Matsumoto, Hironari Kato, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Shigeru Horiguchi, Noriyuki Tanaka, Hiroyuki Okada

Clinical endoscopy 52 ( 5 ) 479 - 485 2019.9

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

BACKGROUND/AIMS: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. METHODS: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels. RESULTS: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0-742] µm vs. 2,833 [1,076-5,694] µm, p=0.012) and arteries (623 [0-854] µm vs. 3,097 [1,396-6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed. CONCLUSION: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.

DOI： 10.5946/ce.2018.163

A "Back Light System" for Identification of Sites for Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Solid Pancreatic Masses: A Prospective, Randomized Study with a Crossover Design. Reviewed International journal

Ryo Harada, Hironari Kato, Soichiro Fushimi, Hirofumi Inoue, Daisuke Uchida, Yutaka Akimoto, Takeshi Tomoda, Kazuyuki Matsumoto, Yasuhiro Noma, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Clinical endoscopy 52 ( 4 ) 334 - 339 2019.7

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

BACKGROUND/AIMS: We applied a back light system (BLS) with a magnifying glass to improve the ability to assess the adequacy of specimen sampling using endosonography. We conducted this study to evaluate the efficacy of the BLS in sampling of specimens by endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses. METHODS: This was a prospective, randomized, crossover, single-center clinical trial. An endosonographer evaluated adequacy on gross visual inspection and identified whitish specimen sampling sites with and without the BLS according to a randomization sequence in the first and second passes with a 25-G needle. On cytological evaluation, the presence of well-defined pancreatic ductal epithelium was evaluated by a cytopathologist who was blinded to any clinical information. RESULTS: A total of 80 consecutive patients were eligible during the study period. Adequacy was observed for 52 specimens (65%) with the BLS and 54 (68%) without the BLS (p=0.88). In assessment of specimen adequacy on gross examination, only fair agreement was observed both with and without BLS (kappa score 0.40 and 0.29, respectively). CONCLUSION: The BLS did not influence the ability to identify specimen sampling sites or reliable assessment of specimen site adequacy using gross visual inspection.

DOI： 10.5946/ce.2019.004

Comparison Between Endoscopic Biliary Stenting Combined with Balloon Dilation and Balloon Dilation Alone for the Treatment of Benign Hepaticojejunostomy Anastomotic Stricture. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Yousuke Saragai, Sho Mizukawa, Shuntaro Yabe, Saimon Takata, Shinichiro Muro, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Ken Hirao, Tsuneyoshi Ogawa, Hiroyuki Okada

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 24 ( 6 ) 1352 - 1358 2019.6

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

BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is an important complication of biliary reconstructive surgery but has no standard treatment. We aimed to evaluate the outcomes of endoscopic treatment for benign HJAS and identify the risk factors for its recurrence. METHODS: This study retrospectively analyzed 176 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for HJAS between April 2008 and March 2016. The outcome of endoscopic biliary stenting combined with balloon dilation (EBS group) and balloon dilation alone (balloon group) was evaluated. RESULTS: The scope was successfully inserted into the HJ site in 93.8% patients (165/176), and 139 patients underwent endoscopic treatment after HJAS was confirmed. Successful biliary drainage was achieved in 137 patients by using ERCP and rendezvous procedures. Among these, 103 patients were included in balloon group and 34 patients were in EBS group. HJAS was resolved in 132 patients; five died from recurrence of primary disease. The 1 (3)-year bile duct patency rates in the balloon and EBS groups were 62.5% (46.6%) and 89.4% (84.7%), respectively (p = 0.015). Univariate analysis showed that balloon dilation (p = 0.009) and early HJAS formation (time from surgery to ERCP < 1 year) (p = 0.02) were risk factors for HJAS recurrence. In the multivariate analysis, balloon dilatation was identified as independent risk factors for HJAS recurrence. CONCLUSIONS: Balloon dilation without stent deployment and early HJAS formation are risk factors for HJAS recurrence after endoscopic treatment. Stent deployment might be recommended for definite resolution of HJAS.

DOI： 10.1007/s11605-019-04297-8

Biliary cannulation technique with ultraslim endoscope for a patient with Billroth II gastrectomy. International journal

Yosuke Saragai, Daisuke Uchida, Hironari Kato, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Endoscopy 51 ( 2 ) E38-E39 2019.2

Utility of liquid biopsy using urine in patients with pancreatic ductal adenocarcinoma. International journal

Hiroyuki Terasawa, Hideaki Kinugasa, Soichiro Ako, Mami Hirai, Hiroshi Matsushita, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hironari Kato, Kazuhiro Nouso, Hiroyuki Okada

Cancer biology & therapy 20 ( 10 ) 1348 - 1353 2019

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

In recent years, liquid biopsy for blood and body fluid in cancer patients has attracted attention. However, there have been few reports of liquid biopsy focusing on urine of pancreatic ductal adenocarcinoma (PDAC). In 56 patients with PDAC, DNA was extracted from urine and plasma prior to treatment, and KRAS mutations were analyzed with droplet digital PCR to examine the mutation detection rate. Our study showed that KRAS mutations were found in 27 cases (48%) in urine and 27 cases (48%) in plasma. The detection rate of urine KRAS mutations varied by renal functions. The rates were 70% (14/20) and 36% (13/36) in the creatinine clearance rate (CCr) < 70 mL/min group and in the CCr ≥ 70 mL/min group, respectively (P = .024). Whereas, no influence of the CCr was observed in the detection rates of plasma KRAS mutations. The rates were 50% (10/20) and 47% (17/36) in cases with the CCr < 70 mL/min group and the CCr ≥ 70 mL/min group, respectively. Although the sample size was small, this study clearly indicated a new possibility of less invasive urine liquid biopsy in PDAC patients.

DOI： 10.1080/15384047.2019.1638685

Efficacy and safety of chemotherapy after endoscopic double stenting for malignant duodenal and biliary obstructions in patients with advanced pancreatic cancer: a single-institution retrospective analysis. Reviewed International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Koichiro Tsutsumi, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Hiroyuki Okada

BMC gastroenterology 18 ( 1 ) 157 - 157 2018.10

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

BACKGROUND: Advanced pancreatic cancer is accompanied not only by bile duct obstruction, but also occasionally by duodenal obstruction. With new advances in chemotherapy and improvement in the management of stent dysfunction, the life expectancy of patients with pancreatic cancer has increased. This study aimed to evaluate the efficacy and safety of chemotherapy for advanced pancreatic cancer, as well as to analyze the prognostic factors, following endoscopic double stenting. METHODS: This retrospective study was conducted from January 1, 2007 to October 31, 2015 at an academic center. Fifty consecutive patients with pancreatic cancer who had undergone endoscopic double stenting, comprising duodenal and biliary stenting, were analyzed. We reviewed the patients records and analyzed the data of stent dysfunction rates after double stenting, reintervention for stent dysfunction, chemotherapy after double stenting, adverse events associated with chemotherapy after double stenting, survival times following double stenting, and overall survival times. The hospital's institutional review board for human research approved this study. RESULTS: The overall survival time and the survival time following double stenting were 10.9 months (IQR 6.0-18.4 months) and 2.4 months (IQR 1.4-5.2 months), respectively. After double stenting, duodenal stent dysfunction occurred in 6 patients (12%), and biliary stent dysfunction occurred in 12 patients (24%), respectively. All patients who experienced stent dysfunction underwent endoscopic reintervention, and all of the procedures were successful. Twenty-one (42%) patients were treated with chemotherapy post double stenting; 9 patients received chemotherapy as a first-line treatment, 9 as a second-line treatment, and 3 as a third-line treatment. During chemotherapy, 8 (38%) patients had grade 3-4 adverse events, which were manageable. Chemotherapy post double stenting (OR, 0.19; 95% CI, 0.059-0.60; P = .0051), reintervention for biliary stent dysfunction (OR, 0.21; 95% CI, 0.081-0.50; P = .0002), and performance status (< 2) (OR, 0.28; 95% CI, 0.098-0.71; P = .0064) were significant prognostic factors after double stenting. CONCLUSIONS: Systemic chemotherapy was manageable, even in patients with double stenting. Chemotherapy after double stenting and appropriate reintervention for stent obstructions potentially prolonged the survival of patients with advance pancreatic cancer.

DOI： 10.1186/s12876-018-0886-8

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy. International journal

Hitoshi Shibuya, Susumu Hijioka, Yasunari Sakamoto, Tetsuhide Ito, Keijiro Ueda, Izumi Komoto, Noritoshi Kobayashi, Atsushi Kudo, Hiroaki Yasuda, Hayato Miyake, Junichi Arita, Sho Kiritani, Masafumi Ikeda, Hiroshi Imaoka, Makoto Ueno, Satoshi Kobayashi, Mitsuhiro Furuta, Yoshikuni Nagashio, Gou Murohisa, Taku Aoki, Shigemi Matsumoto, Masayo Motoya, Nobuaki Azemoto, Jun Itakura, Shigeru Horiguchi, Tatsuji Yogi, Tetsuro Kawagoe, Youichi Miyaoka, Fumito Imamura, Michio Senju, Hitoshi Arioka, Kazuo Hara, Masayuki Imamura, Takuji Okusaka

Cancer chemotherapy and pharmacology 82 ( 4 ) 661 - 668 2018.10

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

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

DOI： 10.1007/s00280-018-3656-y

Dipeptide γ-secretase inhibitor treatment enhances the anti-tumor effects of cisplatin against gastric cancer by suppressing cancer stem cell properties. Reviewed International journal

Ryo Kato, Masaya Iwamuro, Hidenori Shiraha, Shigeru Horiguchi, Emi Tanaka, Ken Matsumoto, Atsushi Ohyama, Hiroaki Sawahara, Teruya Nagahara, Daisuke Uchida, Koichiro Tsutsumi, Hiroyuki Okada

Oncology letters 16 ( 4 ) 5426 - 5432 2018.10

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

The γ-secretase inhibitor blocks Notch activity by preventing its cleavage at the cell surface. In the present study, the effect of the γ-secretase inhibitor on the viability of gastric cancer cells when administered in combination with cisplatin was investigated, with particular focus on CD44highLgr-5high cancer cells. The four gastric cancer cell lines, MKN45, MKN74, SC-6-JCK and SH-10-TC, were used for the experiments. In the MTT assay, treatment with 25 µM dipeptide γ-secretase inhibitor (DAPT) alone did not affect cell proliferation in any of the four cell lines. Gastric cancer cells subjected to combination treatment with DAPT and cisplatin exhibited decreased viability when compared with those treated with cisplatin alone. Flow cytometry was performed to evaluate the expression of cluster of differentiation (CD)-44 and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr-5), two cancer stem cell markers in gastric cancers. Treatment with cisplatin alone significantly increased the proportion of CD44highLgr-5high cells. However, the addition of DAPT to cisplatin reduced the CD44highLgr-5high fraction, suggesting that DAPT reduced the number of gastric cancer cells. In conclusion, the present study demonstrated the synergistic effects of DAPT in combination with cisplatin by decreasing the survival of gastric cancer cells. In addition, combination treatment with DAPT reduced the number of CD44highLgr-5high cells, which are thought to exhibit cancer stem cell properties. These results highlight the therapeutic potential of DAPT in gastric cancer treatment.

DOI： 10.3892/ol.2018.9301

Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Reviewed International journal

Satoshi Kobayashi, Takeshi Terashima, Satoshi Shiba, Yukio Yoshida, Ikuhiro Yamada, Shouta Iwadou, Shigeru Horiguchi, Hideaki Takahashi, Eiichiro Suzuki, Michihisa Moriguchi, Kunihiro Tsuji, Taiga Otsuka, Akinori Asagi, Yasushi Kojima, Ryoji Takada, Chigusa Morizane, Nobumasa Mizuno, Masafumi Ikeda, Makoto Ueno, Junji Furuse

Cancer science 109 ( 8 ) 2549 - 2557 2018.8

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

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log-rank test determined the significance of each prognostic factor. Elevated alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First-line chemotherapy included platinum-containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression-free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child-Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum-containing regimens (HR: 15.83 [95% CI: 2.25-111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second-line therapy. In conclusion, the platinum-containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

DOI： 10.1111/cas.13656

The intra-conduit release method is useful for avoiding migration of metallic stents during EUS-guided hepaticogastrostomy (with video). Reviewed

Daisuke Uchida, Hirofumi Kawamoto, Hironari Kato, Daisuke Goto, Takeshi Tomoda, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Journal of medical ultrasonics (2001) 45 ( 3 ) 399 - 403 2018.7

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

PURPOSE: Although EUS-guided hepaticogastrostomy (EUS-HGS) with a covered self-expandable metal stent (SEMS) is a useful procedure, it is associated with severe adverse events, including stent migration. We, therefore, developed an intra-conduit release method, and investigated whether the technique yields a safer and more stable procedure. METHODS: The intra-conduit release method is a procedure to release the SEMS in the working channel conduit of the scope for anchoring between the liver and stomach to avoid stent migration. Forty-three patients who underwent EUS-HGS at two high-volume centers in Japan were enrolled in this retrospective study, and the safety and usefulness of this method were evaluated retrospectively. RESULTS: The intra-conduit release method was applied in 36 cases. The technical success rate of EUS-HGS with the intra-conduit release method was significantly higher in comparison with the conventional method. Additionally, the rate of early adverse events was significantly lower than that for the conventional method. CONCLUSION: The intra-conduit release method during EUS-HGS is useful for a stable procedure that avoids early adverse events.

DOI： 10.1007/s10396-017-0846-x

Efficacy of endoscopic treatment using double-balloon enteroscopy for postoperative bile leakage in patients with hepaticojejunostomy. Reviewed International journal

Kazuyuki Matsumoto, Koichiro Tsutsumi, Hironari Kato, Shigeru Horiguchi, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Hiroyuki Okada

Endoscopy international open 6 ( 2 ) E211-E216 2018.2

急性膵炎後fluid collectionに対する超音波内視鏡下嚢胞ドレナージの治療成績

松三明宏, 松本和幸, 加藤博也, 内田大輔, 室信一郎, 友田健, 堀口繁, 岡田裕之

日本内科学会雑誌 107 ( Suppl. ) 233 - 233 2018.2

Endoscopic balloon dilatation for benign hepaticojejunostomy anastomotic stricture using short double-balloon enteroscopy in patients with a prior Whipple's procedure: a retrospective study. Reviewed International journal

Sho Mizukawa, Koichiro Tsutsumi, Hironari Kato, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Takeshi Tomoda, Shigeru Horiguchi, Hiroyuki Okada

BMC gastroenterology 18 ( 1 ) 14 - 14 2018.1

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

BACKGROUND: Endoscopic retrograde cholangiography using a short double-balloon endoscope (DB-ERC) is a promising minimally-invasive method for accessing hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy. We aimed to evaluate the immediate and long-term outcomes of balloon dilatation for benign HJ anastomotic stricture (HJAS) in patients who had previously undergone Whipple's procedure using a DB-ERC. METHODS: We conducted a retrospective analysis of 46 patients who underwent balloon dilatation alone with a DB-ERC for benign HJAS between November 2008 and November 2014. The median follow-up duration was 3.5 (interquartile range [IQR], 1.9-5.1) years. RESULTS: The technical and clinical success rates were 100%, and adverse events occurred in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5-10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent HJAS at a median of 1.2 (IQR, 0.6-2.9) years after balloon dilatation. The cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%, respectively. In univariate analysis, early stricture formation (< 1 year) was a risk factor for recurrent stenosis, although no statistically significant risk factors were observed in multivariate analysis. CONCLUSIONS: Endoscopic balloon dilatation with DB-ERC for benign HJAS is effective and safe, having good immediate technical success and few adverse events. Further improvements to this procedure are needed to prevent recurrent HJAS.

DOI： 10.1186/s12876-018-0742-x

Endoscopic Ultrasound-Guided Hepaticogastrostomy Is Effective for Repeated Recurrent Cholangitis after Surgery: Two Case Reports. International journal

Akihiro Matsumi, Hironari Kato, Yousuke Saragai, Sho Mizukawa, Saimon Takada, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Masaya Iwamuro, Shigeru Horiguchi, Yoshiro Kawahara, Hiroyuki Okada

Case reports in gastrointestinal medicine 2018 7201967 - 7201967 2018

Language：English

We report the cases of two patients who underwent endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) using metallic stents (MS) for recurrent cholangitis due to benign biliary stenosis. The patients had repeatedly undergone double-balloon endoscopy and anastomotic stenosis. Thus, EUS-HGS was performed. The procedures were successful, and placement of a covered metallic stent (C-MS) relieved cholangitis. The occurrence of cholangitis was subsequently considerably reduced. For patients with postoperative recurrent cholangitis, EUS-HGS with MS should be considered because of its efficacy and safety.

DOI： 10.1155/2018/7201967

Usefulness of a Cannula with a Flexible Tip (Swing Tip) for Managing Severe Biliary Stricture. International journal

Daisuke Uchida, Hironari Kato, Yosuke Saragai, Saimon Takada, Shinichiro Muro, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Canadian journal of gastroenterology & hepatology 2018 7125714 - 7125714 2018

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

Background and Aims: Biliary stenting for the treatment of biliary stricture is the most common indication of ERCP, but the procedure is sometimes unsuccessful because of severe strictures. The Swing Tip is useful for passing through severe strictures because it has a manually operable tip. The efficacy of using a Swing Tip was retrospectively evaluated. Methods: The 2353 patients who underwent ERCP for biliary stenting at our facility between January 2012 and July 2018 were enrolled. In all patients, procedures were begun using tapered tip-catheters, and Swing Tips were used if the procedure was found to be difficult with other devices. The indication for switching to the Swing Tip and the technical success rate were retrospectively evaluated. Results: A total of 99 patients (4.2%) underwent ERCP using the Swing Tip, including 49 patients for the selection of biliary branches and 50 for exchanging guidewires for rigid ones. In these patients, biliary stenting was successful in 22 patients (44.9%) and 45 patients (90%), respectively. The other 32 patients with failed endoscopic biliary drainage were treated via alternative approaches, such as percutaneous procedures, surgeries, or conservative treatments. There were no adverse events associated with the Swing Tip. Conclusion: The Swing Tip was technically feasible especially for exchanging guidewires during ERCP. Percutaneous procedures or surgical treatments can be avoided by using the Swing Tip. Ethical Statements: This study was approved by the institutional review board of Okayama University. All subjects provided informed consent. The study was registered in the UMIN protocol registration system (identification number UMIN 000033692).

DOI： 10.1155/2018/7125714

Indications for Endoscopic Ultrasound-Guided Pancreatic Drainage: For Benign or Malignant Cases? International journal

Daisuke Uchida, Hironari Kato, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Canadian journal of gastroenterology & hepatology 2018 8216109 - 8216109 2018

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

Background and Aims: Recurrent pancreatitis associated with pancreatic strictures requires treatment with endoscopic retrograde pancreatography (ERP), but it is sometimes technically unsuccessful. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) was developed as an alternative to a surgical approach after failed ERP; however, the indications for EUS-PD are unclear. In this study, we evaluated the outcomes of EUS-PD and established the indications for EUS-PD. Methods: A total of 15 patients had indications for EUS-PD for recurrent pancreatitis due to pancreatic strictures. There were eight patients with benign pancreatic strictures and seven with malignant pancreatic strictures. The success rate, adverse events, and long-term outcomes were evaluated. Results: The technical success rates of benign and malignant strictures were 75% (6/8) and 100% (7/7), respectively, and clinical success was achieved in 100% (6/6) and 87.5% of cases (6/7), respectively. Rendezvous procedures were performed in two patients with benign strictures. The adverse event (AE) rate was 26.7% (4/15) and included cases of peritonitis, bleeding, and stent migration. Reinterventions were performed in three patients with benign strictures and two with malignant strictures. Conclusions: EUS-PD was an appropriate treatment for not only benign strictures but also malignant strictures with recurrent pancreatitis after failed ERP. However, the AE rate was high, and reinterventions were required in some cases during long-term follow-up. The indications for EUS-PD should be considered carefully, and careful follow-up is needed.

DOI： 10.1155/2018/8216109

Comparison of two fluoroscopic images to ensure efficient scope insertion for biliary intervention in patients with Roux-en-Y hepaticojejunostomy. Reviewed International journal

Koichiro Tsutsumi, Hironari Kato, Ken Hirao, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Takeshi Tomoda, Shigeru Horiguchi, Shuntaro Yabe, Hiroyuki Seki, Yasuhiro Noma, Naoki Yamamoto, Ryo Harada, Tsuneyoshi Ogawa, Hiroyuki Okada

Endoscopy 49 ( 12 ) 1256 - 1261 2017.12

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

Background and study aims No standard procedure for endoscopic retrograde cholangiopancreatography is available for patients with Roux-en-Y hepaticojejunostomy (RYHJ) with side-to-end hepaticojejunostomy. We therefore explored methods of efficient scope insertion at a hepaticojejunostomy site. Patients and methods Patients with suspected biliary disease were prospectively enrolled. Based on two fluoroscopic images obtained on scope insertion into each lumen of a two-pronged Roux-en-Y anastomosis, we selected the lumen in which the distal end of the scope progressed toward the patient's liver or head. The accuracy of this method for selecting the correct lumen leading to the hepaticojejunostomy site was investigated. Results Of the 33 included patients, successful insertion to the hepaticojejunostomy site was achieved in 32 (97 %), 26 (81 %) of whom had undergone the imaging method. The accuracy of the method was 88 % (23/26). The time required for insertion between the anastomotic site and the hepaticojejunostomy site was shorter when the lumen selection had been correct (13 minutes [7 - 30] (n = 23) vs. 18 minutes [8 - 28] (n = 9); P = 0.95). Conclusion This method based on two fluoroscopic images was useful for achieving efficient scope insertion in patients with RYHJ.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000014183).

DOI： 10.1055/s-0043-117406

Usefulness of a newly designed plastic stent for endoscopic re-intervention in patients with malignant hilar biliary obstruction. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Hirofumi Kawamoto, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Endoscopy 49 ( 11 ) 1087 - 1091 2017.11

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

Background and study aims We designed a new 7-Fr plastic stent for treating self-expandable metal stent (SEMS) obstruction in patients with malignant hilar biliary obstruction (MHBO) via endoscopic re-intervention with the stent-in-stent (SIS) method and evaluated its efficacy. Patients and methods A total of 33 consecutive patients who underwent endoscopic re-intervention for metal stent obstruction after multi-branched SEMS placement were enrolled. The initial SEMSs were placed in two or three biliary branches in 14 and 19 patients, respectively. We retrospectively evaluated the technical and clinical success, and adverse events. Technical success was defined as successful plastic stent placement into all target branches through the lumen of the SEMS. Results The technical success rates were 85.7 % (12/14) and 78.9 % (15/19) in patients who underwent two- or three-branched biliary drainage, respectively. The clinical success rate was 100 % in the 27 patients in whom technical success was achieved. We achieved successful plastic stent placement in more than two branches, using the new plastic stent combined with a conventional plastic stent, in 97.0 % (32/33). Conclusions This new plastic stent was technically feasible for treating stent obstruction via re-intervention with SIS methods.

DOI： 10.1055/s-0043-116215

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma Reviewed

Hiroaki Sawahara, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Ryo Kato, Atsushi Oyama, Teruya Nagahara, Masaya Iwamuro, Shigeru Horiguchi, Koichiro Tsutsumi, Mari Mandai, Tetsushige Mimura, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Masami Watanabe, Masakiyo Sakaguchi, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 10 ) 1769 - 1777 2017.10

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

Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

DOI： 10.1111/jgh.13757

Endoscopic gallbladder stenting using a rendezvous technique for cholecystitis after metal stent placement in a patient with malignant hilar biliary stricture. Reviewed International journal

Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada

Endoscopy 49 ( 9 ) E204-E205 2017.9

分枝型IPMNの手術適応について国際診療ガイドラインの見直しも含めて

室信一郎, 加藤博也, 水川翔, 内田大輔, 秋元悠, 友田健, 松本和幸, 堀口繁, 山本直樹, 堤康一郎, 岡田裕之

Gastroenterological Endoscopy 59 ( Suppl.2 ) 2183 - 2183 2017.9

Techniques for scope insertion by utilizing the "suture line on the jejunojejunostomy" in balloon enteroscopeassisted ercp in patients with surgically altered anatomies

Koichiro Tsutsumi, Hironari Kato, Shigeru Horiguchi, Kazuyuki Matsumoto, Takeshi Tomoda, Daisuke Uchida, Yutaka Akimoto, Shinichiro Muro, Sho Mizukawa, Hiroyuki Okada

Gastroenterological Endoscopy 59 ( 8 ) 1644 - 1652 2017.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Gastroenterological Endoscopy Society

The development of the balloon enteroscope has facilitated the performance of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for pancreatobiliary diseases in patients with surgically altered anatomies. However, no standard procedure has been established. Therefore, scope insertion to the target site (papilla of Vater or bilioenteric anastomosis) in patients with complicated reconstruction (e.g., pancreatoduodenectomy with modified Child method, Billroth reconstruction with gastrectomy, and Roux-en-Y reconstruction with or without gastrectomy) is performed through trial and error. Our scope insertion technique is to utilize the "suture line on the jejunojejunostomy" as a marker for identifying the correct route to the target site. Between January 2013 and March 2016, the total success rate of reaching the target site was 95.6% (347/363) at our institution. Accurate identification of the route to the target site will contribute to reduction of endoscopist's stress, a shorter scope insertion time, and the development of safe procedures for the patients.

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitrate as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis. Reviewed

Takeshi Tomoda, Hironari Kato, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Acta medica Okayama 71 ( 4 ) 357 - 362 2017.8

Language：English

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography(ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitrate might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitrate for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitrate can prevent PEP.

DOI： 10.18926/AMO/55314

ENDOSCOPIC MANAGEMENT of OCCLUDED METALLIC STENTS DEPLOYED for MALIGNANT HILAR BILIARY STRICTURE

Hironari Kato, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Gastroenterological Endoscopy 59 ( 7 ) 1524 - 1531 2017.7

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Gastroenterological Endoscopy Society

Endoscopic management of occluded metallic stents deployed for malignant hilar biliary stricture is technically demanding. Understanding the characteristics of devices such as guidewires, catheters, and stents, and handling these devices skillfully are essential for successful management. The passage of catheters and plastic stents (PS) through the mesh of metallic stents (MS) is the most difficult of all procedures for multiple occluded MS that had been deployed by the stentin-stent method, and requires precise and careful maneuvering of the endoscope and other devices. The order of PS deployment into the occluded MS is also important. The order of PS deployment has to be same as that of the previous MS deployment. Skilled techniques of not only endoscopists but also their assistants are necessary for the successful management of multiple occluded MS deployed at the hilar portion. Therefore, it is important for endoscopists to become skilled in maneuvering guidewires in daily examinations.

Long-term outcomes and risk factors of biliary stent dysfunction after endoscopic double stenting for malignant biliary and duodenal obstructions. Reviewed International journal

Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Sho Mizukawa, Syuntaro Yabe, Hiroyuki Seki, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Kenji Kuwaki, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 29 ( 5 ) 617 - 625 2017.7

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

BACKGROUND AND AIM: Few reports describe the endoscopic double-stenting procedure for malignant biliary and duodenal obstructions. We evaluated the clinical outcomes from double stenting, and analyzed the risk factors for biliary stent dysfunction following double stenting. METHODS: Eighty-one patients who underwent endoscopic double stenting for malignant biliary and duodenal obstructions were retrospectively analyzed. We determined the stent dysfunction rate and the biliary stent dysfunction risk factors, and analyzed the endoscopic reintervention results. RESULTS: Overall survival time and survival time following double stenting were 365 (38-1673) days and 73 (20-954) days, respectively. After double stenting, the 3-month and 6-month duodenal stent dysfunction rates were 14% and 41%, respectively. Reintervention technical success rate was 100% (10/10), and mean gastric outlet obstruction scoring system scores improved from 0.7 to 2.4 points (P < 0.001). The 3-month and 6-month biliary stent dysfunction rates were 26% and 41%, respectively. The reintervention technical and clinical success rates were 95% (20/21) and 81% (17/21), respectively. Risk factors for biliary stent dysfunction following double stenting were events associated with duodenal stent dysfunction (odds ratio [OR], 11.1; 95% confidence interval [CI], 2.09-87.4; P = 0.0044) and the biliary stent end's location (OR, 6.93; 95% CI, 1.37-40.2; P = 0.0019). CONCLUSIONS: Some patients had stent dysfunction irrespective of the survival period after double stenting. Endoscopic reintervention was technically feasible and clinically effective even after double stenting. Duodenal stent dysfunction and biliary stent end's location were risk factors for biliary stent dysfunction.

DOI： 10.1111/den.12830

Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery. Reviewed International journal

Shuntaro Yabe, Hironari Kato, Sho Mizukawa, Yutaka Akimoto, Daisuke Uchida, Hiroyuki Seki, Takeshi Tomoda, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 29 ( 3 ) 353 - 361 2017.5

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

BACKGROUND AND AIM: Endoscopic procedures are used as first-line treatment for bile leak after hepatobiliary surgery. Advances have been made in endoscopic techniques and devices, but few reports have described the effectiveness of endoscopic procedures and the management principles based on severity of bile leak. We evaluated the effectiveness of an endoscopic procedure for the treatment of bile leak after hepatobiliary surgery. METHODS: Fifty-eight patients underwent an endoscopic procedure for suspected bile leak after hepatobiliary surgery; the presence of bile leak on endoscopic retrograde cholangiopancreatography (ERCP) was evaluated retrospectively. Two groups were created based on bile leak severity at ERCP. We defined success as follows: technical, successful placement of the plastic stent at the intended bile duct; clinical, improvement in symptoms of bile leak; and eventual, disappearance of bile leak at ERCP. We evaluated several factors that influenced the success of the endoscopic procedure and the differences between bile leak severity. RESULTS: Success rates were as follows: technical, 90%; clinical, 79%; and eventual, 71%. Median interval between first endoscopic procedure and achievement of eventual success was 135 days (IQR, 86-257 days). Bile leak severity was the only independent factor associated with eventual success (P = 0.01). CONCLUSIONS: Endoscopic therapy is safe and effective for postoperative bile leak. Bile leak severity is the most important factor influencing successful endoscopic therapy.

DOI： 10.1111/den.12798

超音波内視鏡を用いた膵疾患診療基本から応用まで閉塞性膵炎に対するEUS下膵管ドレナージの有用性に関する検討

友田健, 加藤博也, 水川翔, 室信一郎, 秋元悠, 内田大輔, 松本和幸, 堀口繁, 堤康一郎

膵臓 32 ( 3 ) 330 - 330 2017.5

急性膵炎の後期合併症に対する手術・インターベンション治療の現状と課題急性膵炎後fluid collectionに対する超音波内視鏡下嚢胞ドレナージ術の現状

内田大輔, 加藤博也, 水川翔, 室信一郎, 秋元悠, 友田健, 松本和幸, 堀口繁, 堤康一郎, 岡田裕之

膵臓 32 ( 3 ) 448 - 448 2017.5

Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm. International journal

Shigeru Horiguchi, Hironari Kato, Hidenori Shiraha, Koichiro Tsutsumi, Naoki Yamamoto, Kazuyuki Matsumoto, Takeshi Tomoda, Daisuke Uchida, Yutaka Akimoto, Syou Mizukawa, Takehiro Tanaka, Koichi Ichimura, Akinobu Takaki, Takahito Yagi, Hiroyuki Okada

Journal of gastroenterology and hepatology 32 ( 4 ) 925 - 931 2017.4

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

BACKGROUND AND AIM: Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. METHODS: In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. RESULTS: By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074). CONCLUSIONS: Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

DOI： 10.1111/jgh.13594

Suitable Liquid Biopsy Samples for Detecting Kras Mutations in Patients with Pancreatic Cancer Reviewed

Soichiro Ako, Kazuhiro Nouso, Hideaki Kinugasa, Chihiro Dohi, Hiroshi Matsushita, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada

Gastroenterology 152 ( 5 ) S490 2017.4

当院におけるEUS下胆道ドレナージの現状

内田大輔, 加藤博也, 岡田裕之, 水川翔, 室信一郎, 秋元悠, 友田健, 松本和幸, 堀口繁, 堤康一郎

Gastroenterological Endoscopy 59 ( Suppl.1 ) 994 - 994 2017.4

経乳頭的に留置した胆管・膵管ステントの迷入症例の検討

室信一郎, 加藤博也, 水川翔, 秋元悠, 内田大輔, 友田健, 松本和幸, 堀口繁, 堤康一郎, 岡田裕之

Gastroenterological Endoscopy 59 ( Suppl.1 ) 1091 - 1091 2017.4

Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue Reviewed

Soichiro Ako, Kazuhiro Nouso, Hideaki Kinugasa, Chihiro Dohi, Hiroshi Matushita, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada

PANCREATOLOGY 17 ( 2 ) 285 - 290 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background/Objectives: The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR).
Methods: DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR.
Results: The amount of DNA isolated from the serum was much higher than that from plasma (1.0-to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01).
Conclusions: Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.pan.2016.12.011

A comparative evaluation of treatment methods for bile duct stones after hepaticojejunostomy between percutaneous transhepatic cholangioscopy and peroral, short double-balloon enteroscopy Reviewed

Koichiro Tsutsumi, Hironari Kato, Shuntaro Yabe, Sho Mizukawa, Hiroyuki Seki, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Hirofumi Kawamoto, Hiroyuki Okada

THERAPEUTIC ADVANCES IN GASTROENTEROLOGY 10 ( 1 ) 54 - 67 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS LTD

Background: Bile duct stones after hepaticojejunostomy are considered a troublesome adverse event. Although percutaneous transhepatic procedures using a cholangioscopy is performed to treat these bile duct stones, a peroral endoscopic procedure using a short, double-balloon enteroscope (sDBE) is an alternative. This study aimed to compare the immediate and long-term outcomes of both treatments for bile duct stones in patients who underwent prior hepaticojejunostomy.
Methods: Between October 2001 and May 2013, 40 consecutive patients were treated for bile duct stones after hepaticojejunostomy at a tertiary care hospital. Initial success with biliary access, biliary intervention-related technical success, clinical success, adverse events, hospitalization duration, and stone-free survival were retrospectively evaluated.
Results: The initial success rates for biliary access were 100% (8/8) with percutaneous transhepatic cholangioscopy (PTCS) and 91% (29/32) with sDBE. In three patients in whom biliary access during initial sDBE failed, successful access with subsequent PTCS was achieved, and biliary intervention-related technical success and clinical success were eventually achieved in all 40 patients. The rate of adverse events was significantly lower with sDBE than with PTCS (10% versus 45%; p = 0.025). The median hospitalization duration for complete stone clearance was significantly shorter with sDBE than with PTCS (10 versus 35 days; p < 0.001). During the median 7.2 year or 3.1 year follow up, the probabilities of being stone-free at 1, 2, and 3 years were 100%, 73%, and 64% for PTCS and 85%, 65%, and 59% for sDBE, respectively (p = 0.919).
Conclusions: sDBE was useful, with few adverse events and short hospitalization; therefore, experienced endoscopists can consider it as first-line treatment for bile duct stones in patients with prior hepaticojejunostomy.

DOI： 10.1177/1756283X16674633

Outcomes of management for biliary stricture after living donor liver transplantation with hepaticojejunostomy using short-type double-balloon enteroscopy. Reviewed International journal

Takeshi Tomoda, Koichiro Tsutsumi, Hironari Kato, Sho Mizukawa, Syuntaro Yabe, Yutaka Akimoto, Hiroyuki Seki, Daisuke Uchida, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Hiroyuki Okada

Surgical endoscopy 30 ( 12 ) 5338 - 5344 2016.12

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

BACKGROUND AND AIMS: To evaluate the outcomes of management for biliary stricture (BS) after living donor liver transplantation (LDLT) using short-type double-balloon enteroscopy. METHODS: This study retrospectively evaluated 20 patients who underwent endoscopic retrograde cholangiography using short-type double-balloon enteroscopy (sDB-ERC) upon suspicion of BS after LDLT with hepaticojejunal (HJ) reconstruction at Okayama University Hospital. RESULTS: Scope insertion to the HJ site and sDB-ERC succeeded in 85 % (17/20) and 82.4 % (14/17) of patients, respectively. Of 14 patients who required treatment for BS, 11 were successfully treated using sDB-ERC, and 3 were successfully treated using sDB-ERC and rendezvous procedures. Adverse events occurred in 2.9 % of all sessions (2/68). After resolution of BS, 7 patients (50 %) experienced a recurrence. Of these, 6 (85.7 %) were treated with only balloon dilation, and 1 (14.3 %) was treated with both balloon dilation and stent deployment (P = 0.029). CONCLUSIONS: sDB-ERC is a useful procedure for diagnosis and treatment for BS after LDLT with HJ reconstruction. Balloon dilation combined with stent deployment might be recommended for definite resolution of BS.

膵癌との鑑別を要した膵内副脾の一例

堤康一郎, 加藤博也, 堀口繁, 山本直樹, 友田健, 松本和幸, 秋元悠, 内田大輔, 室信一郎, 岡田裕之

超音波医学 43 ( 6 ) 777 - 777 2016.11

A Multicenter, Prospective, Randomized Controlled Trial Evaluating the Efficacy of Rectal Diclofenac and Sublingual Nitroglycerin as a Combined Prophylactic Treatment for Post-ERCP Pancreatitis Reviewed

Takeshi Tomoda, Hironari Kato, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

ACTA MEDICA OKAYAMA 70 ( 5 ) 405 - 408 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP). A preliminary research suggested that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) with nitroglycerin might reduce the incidence of post-ERCP pancreatitis (PEP) more effectively than NSAIDs alone. We conduct a two-arm, multicenter, prospective, randomized, superiority trial to evaluate the additional effect of nitroglycerin for prevention of PEP. A total of 900 patients randomly receive 50 mg diclofenac suppository either alone or with 5 mg isosorbide dinitrate sublingual tablet. The primary endpoint is the occurrence of PEP. This study will clarify whether NSAIDs plus nitroglycerin can prevent PEP.

A Prospective Randomized Controlled Study Comparing EUS Sonopsy CY(R) and 22-gauge Biopsy Needles for Endoscopic Ultrasound-guided Fine-Needle Aspiration of Solid Pancreatic Mass Lesions. Reviewed

Sho Mizukawa, Hironari Kato, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada, Hirofumi Inoue, Noriyuki Tanaka

Acta medica Okayama 70 ( 5 ) 417 - 420 2016.10

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

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure for precise histological diagnosis of pancreas tumors, but it is sometimes difficult to obtain adequate specimens. EUS Sonopsy CY® is a newly designed needle with original features. This randomized study will compare the tissue collection rate of EUS Sonopsy CY® to that of a conventional needle in EUS-FNA. The major eligibility criteria are as follows: Patients with a pancreatic mass referred for EUSFNA; age 20 years, and performance status＜4. The primary outcome is the tissue collection rate. This study will elucidate the efficacy of EUS Sonopsy CY®.

術後胆汁漏に対する内視鏡的胆管ドレナージ術の有用性の検討

矢部俊太郎, 加藤博也, 水川翔, 秋元悠, 内田大輔, 關博之, 友田健, 松本和幸, 山本直樹, 堀口繁, 堤康一郎

Gastroenterological Endoscopy 58 ( Suppl.2 ) 1934 - 1934 2016.10

ERCP関連処置合併症に対するcovered self-expandable metallic stentの有用性

水川翔, 加藤博也, 矢部俊太郎, 秋元悠, 關博之, 内田大輔, 友田健, 松本和幸, 堀口繁, 山本直樹, 堤康一郎, 岡田裕之

Gastroenterological Endoscopy 58 ( Suppl.2 ) 1930 - 1930 2016.10

Efficacy and Safety of Endoscopic Ultrasound-guided Ethanol Ablation Therapy for Pancreatic Neuroendocrine Tumors. Reviewed

Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Sho Mizukawa, Syuntaro Yabe, Hiroyuki Seki, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Hiroyuki Okada

Acta medica Okayama 70 ( 4 ) 313 - 6 2016.8

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

Recently, endoscopic ultrasonography (EUS)-guided ethanol ablation for small pancreatic neuroendocrine tumors (p-NETs) has been reported. However, the efficacy and safety of the technique remain unclear. We have launched a prospective pilot study of EUS-guided ethanol ablation for p-NETs. The major eligibility criteria are the presence of a pathologically diagnosed grade (G) 1 or G2 p-NET, a tumor size of 2cm, and being a poor candidate for surgery. A total of 5 patients will be treated. The primary endpoint will be the complete ablation rate at 1 month after treatment.

Diagnosing Pancreatic Tumors Using Contrast-enhanced Harmonic Endoscopic Ultrasonography with Sonazoid. Reviewed

Naoki Yamamoto, Hironari Kato, Sho Mizukawa, Shinichiro Muro, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Acta medica Okayama 70 ( 4 ) 323 - 5 2016.8

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

Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with contrast agent enabled us to assess the hemodynamics closely, despite limited data in pancreatic tumors. We have initiated a prospective, single arm, and non-randomized study to clarify the accuracy and safety of CH-EUS with Sonazoid and time-intensity curve (TIC) analysis for diagnosing benign or malignant pancreatic tumors. A total of 200 patients will undergo CH-EUS and TIC analysis. Receiver operating characteristic (ROC) analysis will be used to determine the optimal parameter cutoff values for TIC analysis. This will clarify whether CH-EUS and TIC can further improve the diagnosis of pancreatic tumors over conventional EUS.

術後再建腸管を有する膵胆道疾患に対する新たなダブルバルーン内視鏡(EI-580BT)の有用性に関する検討

友田健, 堤康一郎, 水川翔, 室信一郎, 内田大輔, 秋元悠, 松本和幸, 山本直樹, 堀口繁, 加藤博也, 岡田裕之

胆道 30 ( 3 ) 527 - 527 2016.8

Biliary Anastomotic Stricture After Adult Living Donor Liver Transplantation With Duct-to-Duct Reconstruction: Outcome After Endoscopic Treatment Including Rendezvous Procedure. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Sho Mizukawa, Syuntaro Yabe, Yutaka Akimoto, Hiroyuki Seki, Daisuke Uchida, Kazuyuki Matsumoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Transplantation 100 ( 7 ) 1500 - 6 2016.7

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

BACKGROUND: To evaluate the outcomes and investigate the factors associated with restricture after endoscopic treatment. METHODS: Between April 2001 and July 2014, 98 patients experienced biliary anastomotic stricture (BAS) after living donor liver transplantation (LDLT) with duct-to-duct reconstruction, and all were first referred to Okayama University Hospital for endoscopic stent deployment. When deployment was unsuccessful, a percutaneous transhepatic procedure was used. Treatment outcomes, including stricture resolution, BAS recurrence, and risk factors of BAS recurrence, were evaluated retrospectively. RESULTS: Successful stent deployment was achieved in 90 of 98 patients (91.8%) by both procedures. Among the 90 patients, stricture resolution was eventually observed in 72. The median number of endoscopic retrograde cholangiographies performed was 5. After a median follow-up period of 48.8 months from stent removal, BAS recurrence that required intervention occurred in 22 patients (30.6%). In multivariate analysis, portal vein stenosis after LDLT was associated with BAS recurrence after endoscopic treatment (P = 0.03). Among the 22 patients who required reintervention, 16 (73%) had their stents removed, and recurrence after retreatment occurred in 3 patients (18.8%). CONCLUSIONS: Endoscopic treatment is a useful procedure for the treatment for BAS after LDLT with duct-to-duct reconstruction. Portal vein stenosis may be one of the risks associated with the recurrence of BAS.

DOI： 10.1097/TP.0000000000001187

Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells Reviewed

Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Hiroaki Sawahara, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 ( 6 ) 1154 - 1159 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

DOI： 10.1111/jgh.13259

Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma Reviewed

Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

ONCOLOGY REPORTS 35 ( 5 ) 2576 - 2582 2016.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC.

DOI： 10.3892/or.2016.4681

Effectiveness of peroral direct cholangioscopy using an ultraslim endoscope for the treatment of hepatolithiasis in patients with hepaticojejunostomy (with video). Reviewed International journal

Kazuyuki Matsumoto, Koichiro Tsutsumi, Hironari Kato, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Yasuhiro Noma, Shigeru Horiguchi, Hiroyuki Okada, Kazuhide Yamamoto

Surgical endoscopy 30 ( 3 ) 1249 - 54 2016.3

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

BACKGROUND: Hepatolithiasis is a postoperative complication of hepaticojejunostomy (HJ) performed for various pancreatobiliary diseases. Hepatolithiasis can cause repeated cholangitis. Complete stone removal and bile stasis elimination are therefore necessary. Here, we evaluated the effectiveness of peroral direct cholangioscopy (PDCS) using an ultraslim endoscope for treating hepatolithiasis in HJ patients. METHODS: We studied 14 patients with hepatolithiasis who underwent bowel reconstruction with HJ between April 2012 and May 2014. Diagnostic and therapeutic endoscopic retrograde cholangiography using a short double-balloon enteroscope (DBE) was initially performed. Following stone removal, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS. RESULTS: The success rate of PDCS procedure was 85.7% (12/14). In 5 of 12 (41.7%) patients with successful PDCS, the residual stones were detected and removed completely using a 5-Fr basket catheter and suction after normal saline irrigation. In the remaining 7 (58.3%) patients, no residual stone was detected. The median procedure time was 14 min (range 8-36) with no serious postoperative complications. The median follow-up time after PDCS was 21 months (range 5-26), and only 1 patient (8.3%) had IHBD stone recurrence with an anastomotic stricture. CONCLUSIONS: PDCS using an ultraslim endoscope appears to be useful for detecting and removing residual stones following hepatolithiasis treatment using a DBE. The combined use of a DBE and PDCS may reduce the risk of hepatolithiasis recurrence in HJ patients.

DOI： 10.1007/s00464-015-4323-6

Alteration of serum N-glycan profile in patients with autoimmune pancreatitis Reviewed

Takeshi Tomoda, Kazuhiro Nouso, Hironari Kato, Koji Miyahara, Chihiro Dohi, Yuki Morimoto, Hideaki Kinugasa, Yutaka Akimoto, Kazuyuki Matsumoto, Naoki Yamamoto, Yasuhiro Noma, Shigeru Horiguchi, Koichiro Tsutsumi, Maho Amano, Shin-Ichiro Nishimura, Kazuhide Yamamoto

PANCREATOLOGY 16 ( 1 ) 44 - 51 2016.1

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

Objectives: The aims of this study were to determine the change in whole-serum N-glycan profile in autoimmune pancreatitis (AIP) patients and to investigate its clinical utility.
Methods: We collected serum from 21 AIP patients before any treatment, and from 60 healthy volunteers (HLTs). Serum glycan profile was measured by comprehensive and quantitative high-throughput glycome analysis.
Results: Of the 53 glycans detected, 14 were differentially expressed in AIP patients. Pathway analysis demonstrated that agalactosyl and monogalactosyl bi-antennary glycans were elevated in AIP patients. Among the 14 glycans, #3410, #3510, and #4510 showed high area under receiver operating characteristic (AUROC) values (0.955, 0.964, and 0.968 respectively) for the diagnosis of AIP. These three glycans were mainly bound to immunoglobulin G; however, their serum levels were significantly higher, even in AIP patients who showed lower serum IgG4 levels, than in HLTs.
Conclusions: We demonstrated, for the first time, whole-serum glycan profiles of AIP patients and showed that the levels of glycans #3410, #3510, and #4510 were increased in AIP patients. These glycans might be valuable biomarkers of AIR Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

DOI： 10.1016/j.pan.2015.11.002

Contrast-enhanced harmonic endoscopic ultrasonography with time-intensity curve analysis for intraductal papillary mucinous neoplasms of the pancreas. Reviewed International journal

Naoki Yamamoto, Hironari Kato, Takeshi Tomoda, Kazuyuki Matsumoto, Ichiro Sakakihara, Yasuhiro Noma, Shigeru Horiguchi, Ryo Harada, Koichiro Tsutsumi, Keisuke Hori, Takehiro Tanaka, Hiroyuki Okada, Kazuh de Yamamoto

Endoscopy 48 ( 1 ) 26 - 34 2016.1

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

BACKGROUND AND STUDY AIMS: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. PATIENTS AND METHODS: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. RESULTS: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). CONCLUSIONS: CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.

DOI： 10.1055/s-0034-1393563

Pancreatic Hepatoid Carcinoma Mimicking a Solid Pseudopapillary Neoplasm: A Challenging Case on Endoscopic Ultrasound-guided Fine-needle Aspiration Reviewed

Yutaka Akimoto, Hironari Kato, Kazuyuki Matsumoto, Ryo Harada, Shinsuke Oda, Soichiro Fushimi, Shou Mizukawa, Shuntaro Yabe, Daisuke Uchida, Hiroyuki Seki, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Takahito Yagi, Hiroyuki Okada

INTERNAL MEDICINE 55 ( 17 ) 2405 - 2411 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

A 59-year-old man was admitted to our hospital for treatment of a 45 mm pancreatic mass found during a medical examination. Endoscopic ultrasound-guided fine-needle aspiration cytology showed polygonal cells with pseudopapillary structures. The tumor cells were positive for nuclear/cytoplasmic beta-catenin and CD10, and negative for chromogranin A. After a tentative diagnosis of a solid pseudopapillary neoplasm, middle pancreatectomy was performed. Histologically, polygonal cells with abundant eosinophilic cytoplasm formed in the trabeculae and were immunohistochemically positive for HepPar1 and protein induced by vitamin K absence or antagonist-II. The tumor was finally diagnosed to be pancreatic hepatoid carcinoma. No recurrence occurred for 12 months, even without adjuvant chemotherapy.

DOI： 10.2169/internalmedicine.55.6741

Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model. Reviewed International journal

Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Soichiro Fushimi, Masaya Iwamuro, Shinsuke Oda, Sho Mizukawa, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Shigeru Horiguchi, Hiroyuki Okada

Ecancermedicalscience 10 663 - 663 2016

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

BACKGROUND: Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma. METHODS: Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven. RESULTS: Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively. CONCLUSIONS: Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.

DOI： 10.3332/ecancer.2016.663

[Radical surgery after successful chemotherapy in a case of primary small cell carcinoma of the liver]. Reviewed

Yutaka Akimoto, Koichiro Tsutsumi, Hironari Kato, Hidenori Hata, Hiroyuki Sakae, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Yasuhiro Noma, Naoki Yamamoto, Shigeru Horiguchi, Ryo Harada, Hiroyuki Okada, Hiroyuki Yanai, Takahito Yagi, Kazuhide Yamamoto

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 112 ( 11 ) 2024 - 34 2015.11

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

A 52-year-old woman was admitted to our hospital with right upper quadrant pain with gallbladder wall thickening and multiple liver tumors. Endoscopic ultrasound-guided biopsy revealed small cell carcinomas of both the gallbladder and liver. After 10 cycles of chemotherapy with etoposide and cisplatin, marked shrinkage of the tumors was evident on computed tomography. The patient subsequently underwent hepatectomy and resection of the extrahepatic bile duct and gallbladder with curative intent. Although no viable tumor cells were found in the resected specimens, we confirmed phagocytosis of tumor cells killed by chemotherapy in the resected liver specimen. Therefore, we suspected that the patient had primary small cell carcinoma of the liver that had been successfully treated. This is a rare case of primary small cell carcinoma of the liver that showed pathological complete response to chemotherapy with etoposide and cisplatin.

DOI： 10.11405/nisshoshi.112.2024

当院における生体肝移植後の胆管狭窄に対する内視鏡治療

友田健, 加藤博也, 内田大輔, 秋元悠, 松本和幸, 山本直樹, 堀口繁, 堤康一郎, 高木章乃夫, 岡田裕之, 八木孝仁

移植 50 ( 4-5 ) 481 - 481 2015.10

Hepatic stellate cells promote upregulation of epithelial cell adhesion molecule and epithelial-mesenchymal transition in hepatic cancer cells Reviewed

Teruya Nagahara, Hidenori Shiraha, Hiroaki Sawahara, Daisuke Uchida, Yasuto Takeuchi, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

ONCOLOGY REPORTS 34 ( 3 ) 1169 - 1177 2015.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Microenvironment plays an important role in epithelial-mesenchymal transition (EMT) and sternness of cells in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) is known as a tumor stemness marker of HCC. To investigate the relationship between microenvironment and sternness, we performed an in vitro co-culture assay. Four HCC cell lines (HepG2, Hep3B, HuH-7 and PLC/PRF/5) were co-cultured with the TWNT-1 immortalized hepatic stellate cells (HSCs), which create a microenvironment with HCC. Cell proliferation ability was analyzed by flow cytometry (FCM) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while migration ability was assessed by a wound healing assay. Expression of EpCAM was analyzed by immunoblotting and FCM. HCC cell lines were co-cultured with TWNT-1 treated with small interfering RNA (siRNA) for TGF-beta and HB-EGF; we then analyzed proliferation, migration ability and protein expression using the methods described above. Proliferation ability was unchanged in HCC cell lines co-cultured with TWNT-1. Migration ability was increased in HCC cell lines (HepG2, Hep3B, HuH-7 and PLC/PRF/5) directly (216.2 +/- 67.0, 61.0 +/- 22.0, 124.0 +/- 66.2 and 51.5 +/- 40.3%) and indirectly (102.5 +/- 22.0, 84.6 +/- 30.9, 86.1 +/- 25.7 and 73.9 +/- 29.7%) co-cultured with TWNT-1 compared with the HCC uni-culture. Immunoblot analysis revealed increased EpCAM expression in the HCC cell lines co-cultured with TWNT-1. Flow cytometry revealed that the population of E-cadherin(-)/N-cadherin(+) and EpCAM-positive cells increased and accordingly, EMT and stemness in the HCC cell line were activated. These results were similar in the directly and indirectly co-cultured samples, indicating that humoral factors were at play. Conversely, HCC cell lines co-cultured with siRNA-treated TWNT-1 showed decreased migration ability, a decreased population of EpCAM-positive and E-cadherin(-)/N-cadherin(+) cells. Taken together, humoral factors secreted from TWNT-1 promote upregulation of EpCAM and EMT in hepatic cancer cells.

DOI： 10.3892/or.2015.4126

Walled-off necrosisに対するstep-up approachによる内視鏡的治療成績

秋元悠, 加藤博也, 松本和幸, 内田大輔, 友田健, 山本直樹, 堀口繁, 堤康一郎, 岡田裕之

Gastroenterological Endoscopy 57 ( Suppl.2 ) 2209 - 2209 2015.9

当院におけるmodified FOLFIRINOXの治療成績についての検討

堀口繁, 加藤博也, 水川翔, 矢部俊太郎, 關博之, 秋元悠, 内田大輔, 友田健, 松本和幸, 山本直樹, 堤康一郎, 那須淳一郎, 岡田裕之, 山本和秀

日本消化器病学会雑誌 112 ( 臨増大会 ) A899 - A899 2015.9

デバイス突破を目的としたSoehendra stent retrieverを用いた拡張術

松本和幸, 加藤博也, 堤康一郎, 秋元悠, 内田大輔, 友田健, 山本直樹, 堀口繁, 岡田裕之

Gastroenterological Endoscopy 57 ( Suppl.2 ) 2200 - 2200 2015.9

Endoscopic ultrasonography-guided transjejunal drainage for postoperative pancreatic fistula using forward-viewing echoendoscope. Reviewed

Takeshi Tomoda, Hironari Kato, Yutaka Akimoto, Kazuyuki Matsumoto, Naoki Yamamoto, Yasuhiro Noma, Ryo Harada, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Clinical journal of gastroenterology 8 ( 4 ) 228 - 31 2015.8

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

There are few reports on endoscopic ultrasonography (EUS)-guided transjejunal drainage. Here, we report a case with postoperative pancreatic fistula treated by endoscopic transjejunal drainage using a forward-viewing (FV) echoendoscope. A 69-year-old woman who had undergone pancreaticoduodenectomy was admitted because of pancreatic fistula. Placement of plastic stents into the pancreatic duct using a double-balloon enteroscope and EUS-guided transgastric drainage failed. We attempted EUS-guided transjejunal drainage using an FV echoendoscope that can advance through the acute-angled intestinal tract safely, and drainage was performed. There were no complications, and follow-up computed tomography showed complete resolution.

DOI： 10.1007/s12328-015-0580-0

胆管空腸吻合術後の肝内結石治療における細径内視鏡を用いた経口直接胆道鏡の有用性

松本和幸, 堤康一郎, 加藤博也, 秋元悠, 内田大輔, 友田健, 山本直樹, 堀口繁, 八木孝仁, 岡田裕之

胆道 29 ( 3 ) 503 - 503 2015.8

Efficacy of Endoscopic Over 3-branched Partial Stent-in-Stent Drainage Using Self-expandable Metallic Stents in Patients With Unresectable Hilar Biliary Carcinoma. Reviewed International journal

Daisuke Uchida, Hironari Kato, Shinichiro Muro, Yasuhiro Noma, Naoki Yamamoto, Shigeru Horiguchi, Ryo Harada, Koichiro Tsutsumi, Hirofumi Kawamoto, Hiroyuki Okada, Kazuhide Yamamoto

Journal of clinical gastroenterology 49 ( 6 ) 529 - 36 2015.7

Language：English

BACKGROUND: The treatment of biliary stricture is crucially important for continuing stable chemotherapy for unresectable biliary carcinoma; however, there is no consensus regarding the use of hilar biliary drainage. In this study, we examined the efficacy of endoscopic over 3-branched biliary drainage using self-expandable metallic stents (SEMSs) in patients with unresectable malignant hilar biliary stricture (HBS). METHODS: A total of 77 patients with unresectable HBS treated with a SEMS and chemotherapy were retrospectively reviewed. There were 59 patients with cholangiocarcinoma and 18 patients with gallbladder carcinoma. The patients were divided into 2 groups (4- or 3-branched group and 2- or 1-branched group) and compared with respect to the duration of stent patency and overall survival. RESULTS: A comparison of the patients' baseline characteristics showed no significant differences between the 4- or 3-branched group and the 2- or 1-branched group. Neither the duration of patency nor survival time exhibited significant differences between the 2 groups, although, among the patients achieving disease control , the duration of patency period and survival time of the 4- or 3-branched group were significantly higher than those observed in the 2- or 1-branched group (P=0.0231 and 0.0466). CONCLUSIONS: The use of endoscopic over 3-branched biliary drainage with a SEMS may improve the duration of patency in patients with HBS.

DOI： 10.1097/MCG.0000000000000213

ERCP using a short double-balloon enteroscope in patients with prior pancreatoduodenectomy: higher maneuverability supplied by the efferent-limb route. Reviewed International journal

Koichiro Tsutsumi, Hironari Kato, Shinichiro Muro, Naoki Yamamoto, Yasuhiro Noma, Shigeru Horiguchi, Ryo Harada, Hiroyuki Okada, Kazuhide Yamamoto

Surgical endoscopy 29 ( 7 ) 1944 - 51 2015.7

Language：English

BACKGROUND: In endoscopic retrograde cholangiopancreatography (ERCP) for patients who have undergone a pancreatoduodenectomy (PD) with a Braun anastomosis, two different approaches are available: the afferent-limb route and the efferent-limb route. This study was to clarify the usefulness of a short double-balloon enteroscope (DBE) in ERCP for prior-PD patients, and to reveal which route was optimal for ERCP. METHODS: Seventy-two consecutive patients with a prior PD underwent diagnostic or therapeutic ERCP using the DBE. This retrospective study evaluated the outcome of the ERCP and assessed the shape of the DBE by fluoroscopic imaging to compare the maneuverability of the two routes. RESULTS: In 71 patients (99%) the bilioenteric anastomosis was reached and cholangiography was performed. Treatment was required in 59 patients (83%) and was performed successfully in all. Complications occurred in two patients (3%) with cholangitis. In three patients, the afferent-limb route had to be changed to the efferent-limb route in the procedure. A gentler arc-shaped angulation of the DBE was induced using the efferent-limb route compared to the afferent-limb route (128° (n = 42) vs. 113° (n = 15); p = 0.037), and that was also revealed in 11 patients (15%) who underwent repeated ERCP by each route (123° vs. 96°; p = 0.003). CONCLUSIONS: The short DBE facilitates ERCP in prior-PD patients. Particularly, ERCP using the efferent-limb route can achieve a maneuverable procedure without unnecessary stress, such as scope insertion to the sharp-angled afferent limb and the handling of various accessories through the narrow scope channel with a sense of resistance.

DOI： 10.1007/s00464-014-3889-8

Successful biliary drainage using a metal stent through the gastric stoma Reviewed

Kazuyuki Matsumoto, Hironari Kato, Koichiro Tsutsumi, Yutaka Akimoto, Daisuke Uchida, Takeshi Tomoda, Naoki Yamamoto, Yasuhiro Noma, Shigeru Horiguchi, Hiroyuki Okada, Kazuhide Yamamoto

WORLD JOURNAL OF GASTROENTEROLOGY 21 ( 24 ) 7594 - 7597 2015.6

Language：English Publishing type：Research paper (scientific journal) Publisher：BAISHIDENG PUBLISHING GROUP INC

We report a case of biliary drainage for malignant stricture using a metal stent with an ultrathin endoscope through the gastric stoma. A 78-year-old female was referred to our hospital for jaundice and fever. She had undergone percutaneous endoscopic gastrostomy (PEG) for esophageal obstruction after radiation therapy for cancer of the pharynx. Abdominal contrast-enhanced computed tomography showed a 3-cm enhanced mass in the middle bile duct and dilatation of the intrahepatic bile duct. We initially performed endoscopic retrograde cholangiopancreatography (ERCP) with a trans-oral approach. However, neither the side-viewing endoscope nor the ultrathin endoscope passed through the esophageal orifice. Thus, we eventually performed ERCP via the PEG stoma using an ultrathin endoscope. We performed biliary drainage with a 6F introducer self-expanding metal stent. The cytology findings obtained by brush cytology showed malignancy. Her laboratory results were restored to normal levels after drainage and no complication occurred.

DOI： 10.3748/wjg.v21.i24.7594

膵疾患の分子病態 Basics and Applications 網羅的糖鎖解析によるIPMNの悪性度診断能の検討

秋元悠, 能祖一裕, 加藤博也, 宮原孝治, 内田大輔, 友田健, 松本和幸, 野間康宏, 山本直樹, 堀口繁, 堤康一郎, 岡田裕之, 山本和秀

膵臓 30 ( 3 ) 268 - 268 2015.5

PNETの集学的治療当院及び関連病院におけるPNET治療についての検討

堀口繁, 加藤博也, 秋元悠, 内田大輔, 松本和幸, 友田健, 野間康宏, 山本直樹, 堤康一郎, 伏見聡一郎, 藤井雅邦, 植木亨, 八木孝仁, 山本和秀

膵臓 30 ( 3 ) 320 - 320 2015.5

胆管空腸吻合術後の肝内結石治療に対するDB-ERCPの有用性と工夫

堤康一郎, 加藤博也, 内田大輔, 秋元悠, 友田健, 松本和幸, 野間康宏, 山本直樹, 堀口繁, 岡田裕之, 山本和秀

Gastroenterological Endoscopy 57 ( Suppl.1 ) 765 - 765 2015.4

巨大結石に対するEPLBDの有用性及び安全性の検討超高齢者に対してもEPLBDは安全に施行可能か?

友田健, 加藤博也, 秋元悠, 内田大輔, 松本和幸, 野間康宏, 山本直樹, 堀口繁, 堤康一郎, 岡田裕之, 山本和秀

Gastroenterological Endoscopy 57 ( Suppl.1 ) 740 - 740 2015.4

Double-balloon enteroscopy for choledochojejunal anastomotic stenosis after hepato-biliary-pancreatic operation. Reviewed International journal

Ichiro Sakakihara, Hironari Kato, Shinichiro Muro, Yasuhiro Noma, Naoki Yamamoto, Ryo Harada, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada, Kazuhide Yamamoto, Hiroshi Sadamori, Takahito Yagi

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 27 ( 1 ) 146 - 54 2015.1

Language：English

BACKGROUND AND AIM: There have been few reports on the success rate of balloon dilation and stent deployment using endoscopic retrograde cholangiopancreatography by double-balloon enteroscopy (DBE-ERCP) or on the follow-up period after stent removal in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. The present study was designed to evaluate the usefulness of DBE-ERCP in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. METHODS: Forty-four patients with stenosis of choledochojejunal anastomosis underwent DBE-ERCP at Okayama University Hospital between April 2008 and January 2012 (107 procedures). Rates of reaching choledochojejunal anastomosis, stent deployment, and restenosis after stent removal were retrospectively evaluated. RESULTS: Insertion of DBE into the choledochojejunal anastomotic site succeeded in 38 of 44 patients (86.4%), and anastomotic dilation and stent deployment succeeded in 36 of 44 patients (81.8%). In 32 of 44 patients (72.7%), their anastomotic stenoses were improved, and they achieved stent removal. After stent removal, restenosis of choledochojejunal anastomosis was detected in seven of 32 patients; however, the resolution of restenosis was achieved in all seven of those patients. CONCLUSION: Dilation of choledochojejunal anastomosis combined with stent deployment using DBE-ERCP seems to be a viable first-line treatment for patients with stenosis of choledochojejunal anastomosis.

DOI： 10.1111/den.12332

The efficacy and safety of single-session endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography for evaluation of pancreatic masses. Reviewed International journal

Yasuhiro Noma, Hirofumi Kawamoto, Hironari Kato, Masaya Iwamuro, Ken Hirao, Masakuni Fujii, Koichiro Tsutsumi, Shigeru Horiguchi, Naoki Yamamoto, Ichiro Sakakihara, Takeshi Tomoda, Kazuyuki Matsumoto, Hiroyuki Okada, Kazuhide Yamamoto

Hepato-gastroenterology 61 ( 134 ) 1775 - 9 2014.9

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

BACKGROUND/AIMS: There have been limited studies evaluating single-session EUS-FNA and ERCP for evaluation of pancreatic masses. The aim of this study was to determine the safety of single-session EUS-FNA and ERCP, and to compare the diagnostic accuracies of cytodiagnosis by EUS-FNA, ERCP, and their combination. METHODOLOGY: A total of 100 patients with pancreatic masses were prospectively enrolled. All patients underwent single-session EUS-FNA and ERCP. The main outcome measurement was frequency of post-procedural complications. Another measurement was diagnostic accuracy of cytodiagnosis by EUS-FNA, ERCP, and their combination. RESULTS: Procedure-related pancreatitis occurred in 10 patients, but all patients were conservatively managed. Cytodiagnosis by EUS-FNA was significantly superior to ERCP in accuracy. In patients with a pancreatic head mass, 3 cases of false negative EUS-FNA were positive on ERCP. The combination procedures improved accuracy compared with EUS-FNA alone. By contrast, in the subgroup of the pancreatic body or tail mass, the combination of EUS-FNA and ERCP did not improve cytodiagnosis compared to that with EUS-FNA alone. CONCLUSIONS: Single-session EUS-FNA and ERCP appears to be as safe as performing each procedure separately. EUS-FNA should be considered the principal procedure for cytodiagnosis. ERCP has only a complementary role in patients with pancreatic head mass.

An expanded training program for endosonographers improved self-diagnosed accuracy of endoscopic ultrasound-guided fine-needle aspiration cytology of the pancreas. Reviewed International journal

Ryo Harada, Hironari Kato, Soichiro Fushimi, Masaya Iwamuro, Hirofumi Inoue, Shinichiro Muro, Ichiro Sakakihara, Yasuhiro Noma, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada, Kazuhide Yamamoto

Scandinavian journal of gastroenterology 49 ( 9 ) 1119 - 23 2014.9

Language：English

OBJECTIVE: Rapid on-site evaluation (ROSE) of cytologic adequacy improves the diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). However, on-site advice from a cytotechnologist or cytopathologist is not always available during EUS-FNA. To enhance endosonographers' ability to assess the adequacy of EUS-FNA specimens, we designed an intensive, 2-h interactive training program. The aim of this study was to determine the usefulness of the program. METHODS: Four cytological pictures were selected by a trained cytotechnologist and board-certified cytopathologist from each of the seven patients who underwent EUS-FNA for pancreatic mass in Okayama University Hospital. In total, 28 pictures were used in this study. Twenty endosonographers and 14 cytologists with different levels of EUS-FNA experience evaluated cytological pictures independently before and after the training program. RESULTS: Endosonographers' skill in evaluating the adequacy of EUS-FNA specimens was significantly improved after the completion of the training program (p < 0.001). In contrast, almost all cytologists correctly judged the adequacy of the specimens before taking the training program. CONCLUSIONS: This intensive, 2-h interactive training program is useful for endosonographers and capable of improving ROSE of EUS-FNA specimens.

DOI： 10.3109/00365521.2014.915051

Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer Reviewed

Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Takahito Yagi, Hiromi Kumon, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 29 ( 5 ) 973 - 983 2014.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

DOI： 10.1111/jgh.12501

Loss of runt-related transcription factor 3 induces gemcitabine resistance in pancreatic cancer Reviewed

Shigeru Horiguchi, Hidenori Shiraha, Teruya Nagahara, Jyunnro Kataoka, Masaya Iwamuro, Minoru Matsubara, Shinichi Nishina, Hironari Kato, Akinobu Takaki, Kazuhiro Nouso, Takehiro Tanaka, Koichi Ichimura, Takahito Yagi, Kazuhide Yamamoto

Molecular Oncology 7 ( 4 ) 840 - 849 2013

Language：English Publishing type：Research paper (scientific journal) Publisher：John Wiley and Sons Ltd

Background &amp
Aim: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer. Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000mg/m2 gemcitabine after the surgery. The pancreatic cancer cell lines PANC-1, MIAPaCa-2, BxPC-3, SUIT-2, and KLM-1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay. Results: Patients with RUNX3-positive and RUNX3-negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3-negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3-positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3-negative cells. Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. © 2013 Federation of European Biochemical Societies.

DOI： 10.1016/j.molonc.2013.04.004

Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma Reviewed

Shigetomi Tanaka, Hidenori Shiraha, Yutaka Nakanishi, Shin-Ichi Nishina, Minoru Matsubara, Shigeru Horiguchi, Nobuyuki Takaoka, Masaya Iwamuro, Junro Kataoka, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

INTERNATIONAL JOURNAL OF CANCER 131 ( 11 ) 2537 - 2546 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

DOI： 10.1002/ijc.27575

Diagnostic usefulness of precise examinations with intraductal ultrasonography, peroral cholangioscopy and laparoscopy of immunoglobulin G4-related sclerosing cholangitis. Reviewed International journal

Shigeru Horiguchi, Fusao Ikeda, Hidenori Shiraha, Naoki Yamamoto, Ichiro Sakakihara, Yasuhiro Noma, Koichiro Tsutsumi, Hironari Kato, Hiroaki Hagihara, Tetsuya Yasunaka, Shinichiro Nakamura, Haruhiko Kobashi, Hirofumi Kawamoto, Kazuhide Yamamoto

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 24 ( 5 ) 370 - 3 2012.9

Language：English

Herein, a case of immunoglobulin G4 (IgG4)-related sclerosing cholangitis is reported. IgG4 was diagnosed based on observations from peroral cholangioscopy and laparoscopy, and these methods are proposed for definitive and precise diagnosis of this disease. A 76-year-old male patient with inguinal Paget's disease had intrahepatic bile duct dilatations detected with computed tomography at his periodic check-up. Magnetic resonance cholangiography showed stenosis of the upper common bile duct and poststenotic dilatation of left intrahepatic bile ducts. The portal tract and bilateral intrahepatic bile ducts were surrounded by a low-density area, facing a tumor-like lesion at segment 2. Cytological examinations of the stenotic and dilated lesions revealed no cellular atypia. Histological examination of the tumor showed normal liver tissue with infiltration of lymphocytes, indicating an inflammatory pseudotumor. Peroral cholangioscopy excluded the possibility of biliary cancer and indicated that the stenotic legion was of submucosal, not mucosal, origin. Laparoscopic observations showed discoloration with wide yellowish-white lobular markings and wide depressed lesions at segments 2 and 7. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. Serum IgG4 levels were elevated. From these findings, the patient was diagnosed with IgG4-related sclerosing cholangitis. After treatment with prednisolone, blood liver enzymes and IgG4 rapidly normalized, bile duct dilatations improved, and the hepatic pseudotumor disappeared. The cholangitis did not recur. In this case, biliary cancer was ruled out by observation with peroral cholangioscopy, and the spread of cholangitis in the liver periphery was verified with laparoscopy; this information could not be obtained with other modalities.

DOI： 10.1111/j.1443-1661.2012.01300.x

Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling Reviewed

Shin-Ichi Nishina, Hidenori Shiraha, Yutaka Nakanishi, Shigetomi Tanaka, Minoru Matsubara, Nobuyuki Takaoka, Masayuki Uemura, Shigeru Horiguchi, Junro Kataoka, Masaya Iwamuro, Takahito Yagi, Kazuhide Yamamoto

ONCOLOGY REPORTS 26 ( 3 ) 523 - 531 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene that is downregulated in various cancers. In the present study, we analyzed the regulatory function of RUNX3 on Jagged-1 (JAG1) expression and cancer stem cell (CSC) signaling in hepatocellular carcinoma (HCC). Eleven HCC cell lines and 30 human HCC tissues were used. RUNX3 and JAG1 expression levels were analyzed by immunoblotting and immunohistochemistry. Ectopic RUNX3 expression was induced by introducing RUNX3 cDNA into the RUNX3-negative HCC cell line Hep3B and Huh7 cells. Furthermore endogenous RUNX3 expression was knocked down by RUNX3 siRNA in SK-Hep-1 cells. In order to analyze JAG1 transcriptional regulation, we conducted reporter assays, chromatin immunoprecipitation (ChIP) assays and electrophoretic mobility shift assays (EMSAs). Tumorigenicity was analyzed using a SCID mouse liver injection model. An inverse correlation was observed between RUNX3 expression and JAG1 expression in most HCC cell lines and tissues. Restoring RUNX3 expression decreased the expression of JAG1 in Hep3B and Huh7 cells, whereas JAG1 expression was upregulated in RUNX3 siRNA-treated SK-Hep-1 cells. Reporter assays, ChIP assays and EMSAs revealed that RUNX3 directly bound to the transcriptional regulatory region of JAG1 and suppressed JAG1 transcription. Moreover, RUNX3 restoration downregulated CSCs by suppressing JAG1-mediated Notch signaling. The tumorigenic capacity of RUNX3-expressing Hep3B cells was lower compared to that of control Hep3B cells. RUNX3 expression suppressed JAG1 expression and resulted in downregulation of tumorigenesis by suppression of JAG1-mediated CSCs.

DOI： 10.3892/or.2011.1336

Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis Reviewed

Yutaka Nakanishi, Hidenori Shiraha, Shin-ichi Nishina, Shigetomi Tanaka, Minoru Matsubara, Shigeru Horiguchi, Masaya Iwamuro, Nobuyuki Takaoka, Masayuki Uemura, Kenji Kuwaki, Hiroaki Hagihara, Junichi Toshimori, Hideki Ohnishi, Akinobu Takaki, Shinichiro Nakamura, Yoshiyuki Kobayashi, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto

BMC CANCER 11 3 2011.1

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC).
Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis.
Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation.
Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

DOI： 10.1186/1471-2407-11-3

Single-pattern convergence of K-ras mutation correlates with surgical indication of intraductal papillary mucinous neoplasms. Reviewed International journal

Osamu Mizuno, Hirofumi Kawamoto, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Masakuni Fujii, Hironari Kato, Ken Hirao, Naoko Kurihara, Etsuji Ishida, Tsuneyoshi Ogawa, Hiroyuki Okada, Kazuhide Yamamoto

Pancreas 39 ( 5 ) 617 - 21 2010.7

Language：English

OBJECTIVES: One or more patterns of 6 K-ras mutations are detected in cells from the pancreatic juice of patients with intraductal papillary mucinous neoplasms (IPMNs). We investigated whether these mutations are associated with malignant progression. METHODS: Between January 2002 and December 2007, 53 patients with IPMN were subjected to collection of pure pancreatic juice to evaluate K-ras mutation. According to the histological and radiological findings, the IPMNs were classified into 4 groups: carcinoma group, adenoma group, high-risk group, and low-risk group. We retrospectively investigated the mutation with these groups. RESULTS: In patients with a positive K-ras mutation, a single pattern of K-ras mutation was observed in 80% (8/10) of the carcinoma group, in 71% (5/7) of the adenoma group, in 40% (2/5) of the high-risk group, and in 38% (8/21) of the low-risk group. The rate of a single pattern of K-ras mutation decreased in a stepwise order (P = 0.017). The incidence of a single pattern of K-ras mutation was significantly higher in the patients who received surgical therapy (75%, 12/16) than in those who did not (38%, 10/26; P = 0.033). CONCLUSIONS: The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of IPMNs.

DOI： 10.1097/MPA.0b013e3181c75d9b

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