Updated on 2026/07/30

写真a

 
MAEDA Keiko
 
Organization
Nagoya University Hospital Gastroenterology Lecturer of hospital
Graduate School
Graduate School of Medicine
Title
Lecturer of hospital

Degree 1

  1. 博士(医学) ( 2016.4   名古屋大学 ) 

Research Areas 2

  1. Life Science / Gastroenterology

  2. Life Science / Gastroenterology

Research History 5

  1. 名古屋大学医学部附属病院   消化器内科   病院講師

    2026.5

  2. Nagoya University   Hospital

    2022.2 - 2026.3

  3. 名古屋大学医学部附属病院

    2018.4

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    Country:Japan

  4. Nagoya University   Nagoya University Hospital Diagnostic and Therapeutic Endoscopy   Assistant Professor of Hospital

    2018.4 - 2021.1

  5. Boston Children's Hospital

    2016.6 - 2018.3

Professional Memberships 6

  1. 日本内科学会

  2. 日本炎症性腸疾患学会

  3. 日本消化器病学会

  4. 日本消化器内視鏡学会

  5. 日本生理学会

  6. 日本細菌学会

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Awards 7

  1. 女性研究者賞

    2024.11   日本消化器病学会   腸管上皮細胞を中心とした多細胞相互作用の解明と治療応用

  2. UJA(海外日本人研究者ネットワーク)特別賞

    2024.6   UJA(海外日本人研究者ネットワーク)  

  3. 学術奨励賞

    2023.6   日本女医会  

  4. 日本炎症性腸疾患学会-アッヴィ研究奨励賞

    2023.2   日本炎症性腸疾患学会  

  5. 令和4年度 医学系研究科医学奨励賞 最優秀賞

    2023.1   名古屋大学  

  6. Early career investigator award

    2018.6  

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

  7. Poster of distinction award

    2017.5  

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    Award type:International academic award (Japan or overseas)  Country:United States

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Papers 93

  1. Meflin confers antifibrotic properties to intestinal fibroblasts in inflammatory bowel disease. International journal Open Access

    Jingxi Mu, Keiko Maeda, Tadashi Iida, Shinji Mii, Nobutoshi Esaki, Yukihiro Shiraki, Yasuyuki Mizutani, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Kentaro Murate, Takashi Hirose, Kazuhiro Furukawa, Akina Oishi, Haruhiko Suzuki, Takayoshi Kishida, Goro Nakayama, Mitsuhiro Fujishiro, Hiroki Kawashima, Atsushi Enomoto

    The Journal of clinical investigation   Vol. 136 ( 13 )   2026.7

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

    Dysfunctional intestinal fibrosis is an irreversible complication of Crohn's disease (CD), The complex heterogeneity of intestinal mesenchymal cells makes it difficult to understand the pathogenesis of intestinal fibrosis. Previously, we identified Meflin as a marker of fibroblast subsets. This study aimed to explore the role of Meflin-positive fibroblasts in intestinal fibrogenesis and investigate the potential of pharmacological control of Meflin expression as a treatment for patients with CD. Our results indicated that Meflin expression was upregulated in fibroblasts at the early stage of fibrosis but was downregulated in established fibrosis in both patients with CD and two different mouse models, which are the chronic dextran sodium sulfate (DSS) model and an interleukin-10-deficient model that spontaneously develops intestinal inflammation. Meflin-deficient mice exacerbated intestinal fibrosis with dysregulated expression of non-canonical Wnt ligand WNT5A and its receptor ROR2. Pharmacologically induced Meflin expression through the administration of a synthetic retinoid reversed intestinal fibrosis in the DSS model and suppressed pro-fibrotic protein secretion in fibroblasts isolated from patients with CD. Our findings indicate that Meflin-positive fibroblasts represent a functional subpopulation that suppresses intestinal fibrosis. Augmentation of Meflin expression shows antifibrotic effects and holds promise as a therapeutic approach for intestinal fibrosis in patients with CD.

    DOI: 10.1172/JCI192804

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  2. Total biopsy via endoscopic submucosal dissection is useful for the diagnosis of neoplastic lesions in patients with ulcerative colitis. International journal

    Keisuke Oiwa, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Kentaro Murate, Yoshihisa Takada, Takashi Hirose, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Yoji Ishizu, Takuya Ishikawa, Kazuhiro Furukawa, Takashi Honda, Hiroki Kawashima

    European journal of gastroenterology & hepatology   Vol. 38 ( 5 ) page: 585 - 592   2026.5

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    OBJECTIVE: Ulcerative colitis-associated neoplasia (UCAN) and sporadic neoplasia require different treatment strategies; their differential diagnosis is based on endoscopic findings and biopsy results. However, accurate diagnosis is sometimes difficult. Similarly, it is often challenging to evaluate invasion depth. Recently, their diagnosis has become possible pathologically, following endoscopic UCAN resection. This study investigated whether endoscopic submucosal dissection (ESD) is useful as a treatment or diagnostic (total biopsy) modality for neoplastic lesions within the inflammatory region in patients with ulcerative colitis. METHODS: We retrospectively reviewed the characteristics, accuracy of endoscopic diagnosis, results of ESD, adverse events, and changes in therapeutic strategy after ESD for 27 neoplastic lesions (15 UCANs and 12 sporadic neoplasias) occurring within the inflammatory region of ulcerative colitis in patients at our institution between January 2016 and September 2023. RESULTS: UCANs had significantly more non-polypoid morphology ( P  = 0.037) and inflammation around the neoplasia ( P  = 0.010). The diagnostic accuracy for low-grade dysplasia was higher in sporadic neoplasias than in UCANs. ESD results ( en bloc resection/R0 resection) were similar between UCANs (100%/86.7%) and sporadic neoplasias (91.7%/83.3%). The incidence of intraoperative perforation and delayed bleeding was comparable. In eight lesions (29.6%), accurate pathological diagnosis via ESD prompted changes in the pre-ESD treatment strategy. Notably, surgical resection was avoided in three lesions (11.1%), including one UCAN lesion reclassified from high-grade dysplasia to low-grade dysplasia and two sporadic neoplasia lesions initially diagnosed as UCANs. CONCLUSION: ESD results of patients with ulcerative colitis were acceptable. ESD may be a useful modality for optimal treatment planning.

    DOI: 10.1097/MEG.0000000000003165

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  3. Therapeutic Efficacy of Risankizumab for Small Intestinal Lesions in Crohn's Disease: A Retrospective Study Using Double-Balloon Endoscopy. International journal

    Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Keiko Maeda, Kentaro Murate, Kazuhiro Furukawa, Takashi Hirose, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Yoji Ishizu, Takuya Ishikawa, Takashi Honda, Masanao Nakamura, Hiroki Kawashima

    Digestion     page: 1 - 9   2026.2

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

    BACKGROUND: Risankizumab (RZB), an IL-23p19 monoclonal antibody, has demonstrated clinical efficacy in Crohn's disease (CD), yet evidence regarding its effectiveness for deep small intestinal lesions remains scarce. These lesions are often underdiagnosed due to limited accessibility and subtle clinical presentation. PATIENTS AND METHODS: We retrospectively analyzed 32 patients with moderate-to-severe CD who underwent total small intestinal evaluation by double-balloon endoscopy (DBE) both before and 8-14 months after RZB initiation in clinical practice. Endoscopic disease activity was assessed using the modified Simple Endoscopic Score for Crohn's Disease (mSES-CD). Clinical response (CDAI), biomarker changes (CRP, LRG), and endoscopic outcomes were evaluated. RESULTS: Mean mSES-CD significantly decreased from 14.3 to 8.2 (P < 0.001), indicating substantial mucosal improvement, particularly in the jejunum and deep ileum. Endoscopic remission (mSES-CD < 2) was achieved in 13.3% of patients. Clinical remission (CDAI <150) occurred in 80% at week 12 and was sustained in 56% at one year. Significant biomarker improvements were observed. No progression of strictures was seen during follow-up. CONCLUSIONS: This study confirms the therapeutic efficacy of RZB for deep small intestinal involvement in CD based on comprehensive DBE assessment. The results support the clinical utility of RZB in patients with refractory small intestinal lesions, highlighting its potential to maintain one year disease control when ongoing mucosal inflammation is a concern. These findings underscore the importance of deep enteroscopic evaluation to optimize therapeutic strategies.

    DOI: 10.1159/000550396

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  4. Intestine-specific Faf2 depletion ameliorates obesity and metabolic dysfunction-associated steatotic liver disease by impairing lipid absorption Open Access

    Zhang J., Imai N., Cheng J., Sugiyama A., Kawecka H., Liu D., Suzuki M., Ohsaki Y., Yokoyama S., Yamamoto K., Ito T., Maeda K., Ishizu Y., Honda T., Ishikawa T., Woźniak M., Wake H., Cohen D.E., Kawashima H.

    International Journal of Biological Sciences   Vol. 22 ( 12 ) page: 6261 - 6280   2026

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    Publisher:International Journal of Biological Sciences  

    Fas-associated factor family member 2 (Faf2) is an endoplasmic reticulum (ER)–associated protein implicated in apolipoprotein B (ApoB) metabolism, yet its physiological role in the intestine remains unclear. To investigate this, we generated intestine-specific Faf2 knockout (Faf2-IKO) mice and fed them either a normal diet or a high-fat diet (HFD). Faf2-IKO mice exhibited reduced body weight and adiposity under both conditions, improved glucose tolerance, and protection against HFD-induced hepatic steatosis. In the intestine, Faf2 deficiency was associated with lipid droplet accumulation, intracellular retention of ApoB48, and reduced chylomicron abundance in lacteals, consistent with impaired intestinal lipoprotein handling. Faf2-IKO mice also exhibited elongation of the small intestine and villi after weaning. Despite these changes, Faf2-IKO mice showed elevated postprandial triglyceride and free fatty acid levels during lipid tolerance tests, indicating paradoxical alterations in postprandial lipid responses. Additionally, Faf2 deficiency was associated with ER dilation and increased expression of genes associated with ER-related cellular responses. Furthermore, in the livers of Faf2-IKO mice, genes that govern cholesterol homeostasis and sterol biosynthetic pathways were significantly enriched. Collectively, these findings suggest that intestinal Faf2 deficiency alters chylomicron-associated lipid handling and is associated with protection against obesity and metabolic dysfunction–associated steatotic liver disease in mice.

    DOI: 10.7150/ijbs.134379

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  5. Initial Tumor Size and Narrow-Band Image Findings Estimate Growth Speed in Duodenal Tumors. Reviewed International journal

    Takashi Hirose, Naomi Kakushima, Yoshiyuki Minami, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Kazuhiro Furukawa, Masanao Nakamura, Masato Nakaguro, Hiroki Kawashima

    Digestive diseases (Basel, Switzerland)     page: 1 - 10   2024.7

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

    INTRODUCTION: Recently, the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention. METHODS: A single-center, retrospective study was performed on the medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than 1 year by endoscopy were analyzed. The primary outcome was an analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI). RESULTS: The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter ≥10 mm at first detection (p = 0.004; odds ratio 19.5 [2.03-186.96]) and mixed type by M-NBI (p = 0.036; odds ratio 9.69 [1.05-89.88]) were identified as risk factors of tumors growing at a rate of ≥3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotypes. CONCLUSION: Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention.

    DOI: 10.1159/000540544

    PubMed

  6. Monoclonal Antibodies Against Mature Interleukin-18 Ameliorate Colitis and Repair Goblet Cell Function Reviewed International journal Open Access

    Jingxi Mu, Keiko Maeda, Ayako Ohashi, Takeshi Urano, Yuko Nariai, Hiroki Kamino, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Kentaro Murate, Kenta Yamamoto, Takashi Hirose, Kazuhiro Furukawa, Mitsuhiro Fujishiro, Hiroki Kawashima

    Digestive Diseases and Sciences   Vol. 69 ( 7 ) page: 2573 - 2585   2024.7

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s10620-024-08453-2

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  7. Artificial intelligence-based diagnostic imaging system with virtual enteroscopy and virtual unfolded views to evaluate small bowel lesions in Crohn's disease. Reviewed International journal

    Kazuhiro Furukawa, Masahiro Oda, Osamu Watanabe, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Kensaku Mori, Hiroki Kawashima

    Revista espanola de enfermedades digestivas     2024.3

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    Since even subtle mucosal changes may be depicted using virtual endoscopy created by the three-dimensional reconstruction of MDCT images, we developed a novel diagnostic imaging system that integrates and displays virtual enteroscopy, curved planar reconstruction, and a virtual unfolded view, the width of which changes with increases/decreases in the inner luminal diameter. The system is also equipped with artificial intelligence that superimposes and displays depressed areas, generates an automatic small bowel centerline that connects fragmented small bowel regions, and performs electronic cleansing. We retrospectively evaluated the diagnostic performance of this system for small bowel lesions in Crohn's disease, which were divided into two groups: endoscopically-observable and endoscopically-unobservable. Lesion detection rates for stenoses, longitudinal ulcers with a cobblestone appearance, and scars were excellent in both groups. This system, when used in combination with endoscopy, shows slight mucosal changes in areas in which an endoscope cannot reach due to strictures, thereby extending the range of observation of the small bowel. This system is a useful diagnostic modality that has the capacity to assess mucosal healing and provide extraluminal information.

    DOI: 10.17235/reed.2024.10405/2024

    PubMed

  8. Reply: Interleukin-18 Inhibition in Inflammatory Bowel Diseases: A Delicate Balance.

    Maeda K, Kawashima H

    Inflammatory bowel diseases     2024.3

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    Language:English  

    DOI: 10.1093/ibd/izae039

    PubMed

  9. Risk factors for rebleeding in gastroduodenal ulcers. International journal

    Nobuhito Ito, Kohei Funasaka, Toshihisa Fujiyoshi, Kazuki Nishida, Yusuke Satta, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takuya Ishikawa, Takeshi Yamamura, Eizaburo Ohno, Masanao Nakamura, Ryoji Miyahara, Yoji Sasaki, Jun-Ichi Haruta, Mitsuhiro Fujishiro, Hiroki Kawashima

    Irish journal of medical science   Vol. 193 ( 1 ) page: 173 - 179   2024.2

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    BACKGROUND: Rebleeding after hemostasis of the gastroduodenal ulcer (GDU) is one of the indicators associated with death among GDU patients. However, there are few studies on risk score that contribute to rebleeding after endoscopic hemostasis of bleeding peptic ulcers. AIMS: The aim of this study was to identify factors associated with rebleeding, including patient factors, after endoscopic hemostasis of bleeding gastroduodenal ulcers and to stratify the risk of rebleeding. METHODS: We retrospectively enrolled 587 consecutive patients who were treated for Forrest Ia to IIa bleeding gastroduodenal ulcers with endoscopic hemostasis at three institutions. Risk factors associated with rebleeding were assessed using univariate and multivariate logistic regression analyses. The Rebleeding Nagoya University (Rebleeding-N) scoring system was developed based on the extracted factors. The Rebleeding-N score was internally validated using bootstrap resampling methods. RESULTS: Sixty-four patients (11%) had rebleeding after hemostasis of gastroduodenal ulcers. Multivariate logistic regression analysis revealed four independent rebleeding risk factors: blood transfusion, albumin <2.5, duodenal ulcer, and diameter of the exposed vessel ≧2 mm. Patients with 4 risk factors in the Rebleeding-N score had a 54% rebleeding rate, and patients with 3 risk factors had 44% and 25% rebleeding rates. In the internal validation, the mean area under the curve of the Rebleeding-N score was 0.830 (95% CI = 0.786-0.870). CONCLUSIONS: Rebleeding after clip hemostasis of bleeding gastroduodenal ulcers was associated with blood transfusion, albumin <2.5, diameter of the exposed vessel ≧2 mm, and duodenal ulcer. The Rebleeding-N score was able to stratify the risk of rebleeding.

    DOI: 10.1007/s11845-023-03450-2

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  10. OLITIS CYSTICA PROFUNDA DIAGNOSED BY ESD

    YAMADA Kentaro, YAMAMURA Takeshi, NAKAMURA Masanao, MAEDA Keiko, SAWADA Tsunaki, ISHIKAWA Eri, KAJIKAWA Go, HASEGAWA Issei, YOKOI Takio, KAWASHIMA Hiroki

    GASTROENTEROLOGICAL ENDOSCOPY   Vol. 66 ( 3 ) page: 279 - 285   2024

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    Language:Japanese   Publisher:Japan Gastroenterological Endoscopy Society  

    <p>A 46-year-old female patient presented to our hospital for close examination and treatment after a rectal mass was observed during a CS performed at another hospital. On repeat CS, we observed a 10-mm, submucosal, tumor-like mass in the lower rectum. EUS showed a 10-mm hypoechoic tumor located in the submucosa. We performed ESD because the boring biopsy specimens showed nonspecific pathologic findings. Pathological examination of the resected lesion confirmed the diagnosis of colitis cystica profunda.</p>

    DOI: 10.11280/gee.66.279

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  11. Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing. Reviewed International journal

    Masanao Nakamura, Kentaro Murate, Keiko Maeda, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Kazuhiro Furukawa, Takashi Hirose, Kota Uetsuki, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Yoji Ishizu, Takuya Ishikawa, Takashi Honda, Hiroki Kawashima

    Digestion   Vol. 105 ( 5 ) page: 400 - 410   2024

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    INTRODUCTION: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. METHODS: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. RESULTS: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. CONCLUSION: SST expression in the mucus is considered to be an important factor associated with UC activity.

    DOI: 10.1159/000540052

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  12. A CASE OF INTRA-ABDOMINAL HAEMORRHAGE AFTER COLD SNARE POLYPECTOMY FOR COLORECTAL POLYPS Open Access

    IKEGAMI Shuji, YAMAMURA Takeshi, NAKAMURA Masanao, MAEDA Keiko, SAWADA Tsunaki, ISHIKAWA Eri, YAMASHITA Ayako, KAWAMURA Tatsuya, YOKOI Takio, KAWASHIMA Hiroki

    GASTROENTEROLOGICAL ENDOSCOPY   Vol. 66 ( 5 ) page: 1236 - 1241   2024

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    Language:Japanese   Publisher:Japan Gastroenterological Endoscopy Society  

    <p>A 51-year-old man underwent colonoscopy for endoscopic resection of polyps which were detected by CT colonography. Cold Snare Polypectomy (CSP) was performed for resection of an adenomatous polyp present in the splenic flexure. Two hours after the endoscopy, the patient experienced a sudden epigastric pain. Abdominal CT showed a mass-like thickening of the colon wall at the splenic flexure, leakage of contrast medium from the blood vessels in the wall, and hemorrhagic ascites in the abdominal cavity. The patient was diagnosed with intra-abdominal hemorrhage post a CSP procedure and underwent partial resection of the transverse colon through transverse colostomy. The surgical specimen showed a marked hematoma in the muscle layer below the site of CSP; however, no perforation was evident.</p>

    DOI: 10.11280/gee.66.1236

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  13. Monoclonal Antibody Against Mature Interleukin-18 Ameliorates Colitis in Mice and Improves Epithelial Barrier Function Reviewed International journal

    Shuji Ikegami, Keiko Maeda, Takeshi Urano, Jingxi Mu, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Kenta Yamamoto, Hisanori Muto, Akina Oishi, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

    Inflammatory Bowel Diseases   Vol. 30 ( 8 ) page: 1353 - 1366   2023.12

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    Abstract

    Background

    Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD.

    Methods

    The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed.

    Results

    Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression.

    Conclusions

    Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.

    DOI: 10.1093/ibd/izad292

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  14. Real-World Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis.

    Uchida G, Nakamura M, Yamamura T, Maeda K, Sawada T, Ishikawa E, Furukawa K, Iida T, Mizutani Y, Yamao K, Ishikawa T, Ishizu Y, Honda T, Ishigami M, Kawashima H

    Inflammatory intestinal diseases   Vol. 8 ( 2 ) page: 60 - 68   2023.10

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    Language:English   Publisher:Inflammatory Intestinal Diseases  

    Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2-8 and weeks 24-48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

    DOI: 10.1159/000531497

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  15. Clinical characteristics of Dieulafoy's lesion in the small bowel diagnosed and treated by double-balloon endoscopy. Reviewed International journal Open Access

    Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Takuya Ishikawa, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

    BMC gastroenterology   Vol. 23 ( 1 ) page: 290 - 290   2023.8

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    BACKGROUND: Obscure gastrointestinal bleeding refers to bleeding for which the source cannot be ascertained even through balloon-assisted endoscopy. In certain instances, Dieulafoy's lesion in the small bowel is presumed to be the underlying cause. AIM: This retrospective study aimed to elucidate the clinical characteristics of Dieulafoy's lesion in the small bowel as diagnosed via double-balloon endoscopy while also exploring the feasibility of predicting bleeding from Dieulafoy's lesion prior to endoscopy in cases of obscure gastrointestinal bleeding. METHODS: A comprehensive analysis of our database was conducted, identifying 38 patients who received a diagnosis of Dieulafoy's lesion and subsequently underwent treatment via double-balloon endoscopy. The clinical background, diagnosis, and treatment details of patients with Dieulafoy's lesion were carefully examined. RESULTS: The median age of the 38 patients was 72 years, and 50% of the patients were male. A total of 26 (68%) patients exhibited a high comorbidity index. The upper jejunum and lower ileum were the most frequently reported locations for the occurrence of Dieulafoy's lesion in the small bowel. The detected Dieulafoy's lesions exhibited active bleeding (n = 33) and an exposed vessel with plaque on the surface (n = 5). Rebleeding after endoscopic treatment occurred in 8 patients (21%, median period: 7 days, range: 1-366 days). We conducted an analysis to determine the definitive nature of the initial double-balloon endoscopy diagnosis. Multivariate analysis revealed that hematochezia of ≥ 2 episodes constituted the independent factor associated with ≥ 2 double-balloon endoscopy diagnoses. Additionally, we explored factors associated with rebleeding following endoscopic treatment. Although the number of hemoclips utilized displayed a likely association, multivariate analysis did not identify any independent factor associated with rebleeding. CONCLUSION: If a patient encounters multiple instances of hematochezia, promptly scheduling balloon-assisted endoscopy, equipped with optional instruments without delay is advised, after standard endoscopic evaluation with esophagogastroduodenoscopy and colonoscopy is unrevealing.

    DOI: 10.1186/s12876-023-02913-1

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  16. Protocol for measuring transcytosis and recycling of IgG in intestinal epithelial Caco-2 cells and primary human intestinal organoids Open Access

    Maeda, K; Gwilt, KB; Schmieder, SS; Zachos, NC; Lencer, WI

    STAR PROTOCOLS   Vol. 4 ( 2 )   2023.6

  17. Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study. Reviewed International journal

    Shuji Ikegami, Masanao Nakamura, Takashi Honda, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Kenta Yamamoto, Satoshi Furune, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Masatoshi Ishigami, Fumie Kinoshita, Yoshihiro Kadota, Takumi Tochio, Yoshiharu Shimomura, Yoshiki Hirooka, Hiroki Kawashima

    Alimentary pharmacology & therapeutics   Vol. 57 ( 11 ) page: 1249 - 1257   2023.6

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    BACKGROUND: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. AIMS: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. METHODS: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. RESULTS: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. DISCUSSION: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

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  18. ENDOSCOPIC TREATMENT OF DUODENAL NEUROENDOCRINE TUMORS

    Furukawa, K; Furune, S; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Nakamura, M; Kawashima, H

    GASTROINTESTINAL ENDOSCOPY   Vol. 97 ( 6 ) page: AB1211 - AB1212   2023.6

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  19. CO2 enterography in endoscopic retrograde cholangiography using double-balloon endoscopy: A randomized clinical trial. Reviewed International journal

    Kentaro Murate, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yuichi Kida, Masaya Esaki, Motonobu Hamazaki, Tadashi Iida, Yasuyuki Mizutani, Kentaro Yamao, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Fumie Kinoshita, Masahiko Ando, Hiroki Kawashima

    Journal of gastroenterology and hepatology   Vol. 38 ( 5 ) page: 761 - 767   2023.5

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    BACKGROUND AND AIM: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation. METHODS: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications. RESULTS: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication.

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  20. Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia

    Muroi, K; Kakushima, N; Furukawa, K; Furune, S; Ito, N; Hirose, T; Hida, E; Suzuki, T; Suzuki, T; Hirai, K; Shibata, H; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ohno, E; Nakamura, M; Fujishiro, M; Kawashima, H

    ESOPHAGUS   Vol. 20 ( 2 ) page: 325 - 332   2023.4

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    Background and aims: Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE). Methods: A total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10 cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups. Results: The sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005). Conclusion: This study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.

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  21. Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet. International journal Open Access

    Hisanori Muto, Takashi Honda, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Tetsuya Ishikawa, Shungo Adachi, Chikara Sato, Noriko M Tsuji, Masatoshi Ishigami, Mitsuhiro Fujishiro, Hiroki Kawashima

    Nutrients   Vol. 15 ( 6 )   2023.3

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    The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.

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  22. Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease. Reviewed International journal

    Tatsuya Kawamura, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

    Inflammatory bowel diseases   Vol. 29 ( 2 ) page: 245 - 253   2023.2

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    BACKGROUND: Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. METHODS: Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. RESULTS: Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. CONCLUSIONS: Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.

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  23. SMALL INTESTINAL GANGLIONEUROMATOSIS IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1: A CASE REPORT

    KIDA Yuichi, SAWADA Tsunaki, ISHIKAWA Eri, SAKAKIBARA Ayako, YAMAMURA Takeshi, MAEDA Keiko, ESAKI Masaya, HAMAZAKI Motonobu, MURATE Kentaro, NAKAMURA Masanao

    GASTROENTEROLOGICAL ENDOSCOPY   Vol. 65 ( 7 ) page: 1232 - 1238   2023

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    <p>A 50-year-old woman with neurofibromatosis type 1 who hospitalized for chronic diarrhea was transferred to our hospital for evaluation of small intestinal dilatation and thickening. Transoral double-balloon enteroscopy revealed jejunal dilatation and suppressed peristalsis; however, mucosal inflammation, such as ulcers or erosions were not detected. Transanal double-balloon enteroscopy detected the intestinal stenosis with inflammatory polyps and a longitudinal ulcer. Histopathological evaluation of duodenal, jejunal, and ileal specimens by biopsy revealed ganglion cells and Schwannian cells; therefore, the patient was diagnosed with ganglioneuromatosis with neurofibromatosis type 1. Small intestinal dilatation was associated with suppressed peristalsis caused by ganglioneuromatosis and was diagnosed as secondary chronic intestinal pseudo-obstruction. Abdominal distention persisted despite conservative therapy. However, she remained asymptomatic, and oral intake remained unaffected. Ganglioneuromatosis is rare; however, clinicians should be mindful that ganglioneuromatosis is an abdominal complication associated with systemic disease such as neurofibromatosis type 1 and multiple endocrine neoplasia type 2B.</p>

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  24. Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia. Reviewed International journal

    Emiko Hida, Koichi Muroi, Naomi Kakushima, Satoshi Furune, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Maeda Keiko, Takeshi Yamamura, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Mitsuhiro Fujishiro, Hiroki Kawashima

    Digestion   Vol. 104 ( 3 ) page: 202 - 211   2023

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    INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

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  25. Factors related to delayed adverse events of endoscopic submucosal dissection in the duodenum. Reviewed International journal Open Access

    Tatsuya Kawamura, Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

    Digestive diseases (Basel, Switzerland)   Vol. 41 ( 1 ) page: 80 - 88   2023

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    INTRODUCTION: Endoscopic submucosal dissection for duodenal neoplasms (D-ESD) is considered a technically demanding procedure regarding the high risk of delayed adverse events. Data regarding optimal managements of ulcers after D-ESD are lacking. METHODS: A retrospective analysis was performed on consecutive 145 cases of D-ESD for superficial non-ampullary duodenal epithelial tumors at a single referral center. Factors related to delayed adverse events and the healing process of ulcers after D-ESD were analyzed. RESULTS: Complete ulcer suture after D-ESD was performed in 128 cases (88%). Two delayed perforation occurred among cases with incomplete suture. Delayed bleeding occurred in 8 cases (6%) within three weeks. The ulcer closure rate at second-look endoscopy was significantly low among cases with delayed bleeding (12.5% vs 75%, P=0.001). The bleeding rate before second-look endoscopy was significantly high among patients who did not have complete ulcer closure after D-ESD (0.8% vs 12%, P=0.036). The ratio of lesions located in the 2nd oral-Vater was significantly low among ulcers re-opened at second-look endoscopy (38% vs 14%, P=0.044). Proton-pump inhibitors (PPI) were administered for a median of seven weeks (range 1-8 weeks). At three weeks, active ulcer stages were observed in a few cases, and healing or scarring was observed in most cases. CONCLUSIONS: Complete ulcer suture was related to decreased risk of delayed adverse events after D-ESD. From the bleeding period and healing process of D-ESD ulcers, the minimum required length of PPI may be three weeks after D-ESD.

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  26. 特集 消化管内視鏡治療のリスク克服に向けて 1.待機的内視鏡治療に潜むリスクとそのマネジメント(6)大腸EMR/ESD

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 古川 和宏, 川嶋 啓揮

    臨床消化器内科   Vol. 38 ( 1 ) page: 42 - 47   2022.12

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  27. Network Analysis of Gut Microbiota Including <i>Fusobacterium</i> and Oral Origin Bacteria and Their Distribution on Tumor Surface, Normal Mucosa, and in Feces in Patients with Colorectal Cancer

    Ohashi, A; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Ishikawa, E; Yamamoto, K; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Fujishiro, M

    DIGESTION   Vol. 103 ( 6 ) page: 451 - 461   2022.12

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    Introduction: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC. Methods: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3-V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon. Results: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum. Conclusion: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC.

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  28. The effects of ustekinumab on small intestinal lesions and stenotic lesions. Reviewed Open Access

    Hirotaka Wada, Kentaro Murate, Masanao Nakamura, Kazuhiro Furukawa, Naomi Kakushima, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Goro Nakayama, Norifumi Hattori, Shinichi Umeda, Masatoshi Ishigami

    Nagoya journal of medical science   Vol. 84 ( 4 ) page: 825 - 838   2022.11

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    Crohn's disease patients suffer from symptoms originating from small bowel lesions, including strictures. As many of these patients also have a potential risk of surgery, it is important to consider various therapeutic strategies for small bowel lesions. We retrospectively analyzed the therapeutic effects of ustekinumab, interleukin-12 and -23 blocker, for small intestinal lesions and intestinal stenosis in order to contribute to the optimal management of Crohn's disease. Patients who underwent total colonoscopy or small bowel endoscopy before and after the introduction of ustekinumab were enrolled in this study. The colonoscopy findings were evaluated by the simple endoscopic score for Crohn's disease, and small bowel endoscopy findings were evaluated using the modified simple endoscopic score for Crohn's disease. Endoscopic scores were compared before and after the introduction of ustekinumab and between the responders and non-responders to ustekinumab. Responders were defined as those whose Crohn's disease activity index score at 24 weeks fell below 150 points, or those whose score decreased by more than 100 points from the pre-induction level. A total of 50 patients were enrolled in the study, and the number of responders was 35. Pre-induction simple endoscopic scores were lower for responders, but no significant difference was observed in the modified simple endoscopic scores. The total decrease in the endoscopic score was significantly higher in the responders for both the small and large intestine. Use of ustekinumab as a first-line treatment for patients with small bowel lesions or stricture-prone lesions may be a new treatment consideration in the future.

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  29. Analysis of immunologic comorbidities in ulcerative colitis patients: a tool to prevent exacerbations in ulcerative colitis cases. Reviewed Open Access

    Miguel Ricardo Rodríguez Meza, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

    Nagoya journal of medical science   Vol. 84 ( 4 ) page: 733 - 745   2022.11

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    There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn's disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient's prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44-10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.

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  30. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan. Reviewed International journal Open Access

    Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, Mitsuhiro Fujishiro

    BMC gastroenterology   Vol. 22 ( 1 ) page: 342 - 342   2022.7

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    BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene. RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

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  31. Effects of steroid use for stenosis prevention after endoscopic submucosal dissection for cervical esophageal cancer. Reviewed

    Koichi Muroi, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Nobuhito Ito, Takashi Hirose, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Kohei Funasaka, Ryoji Miyahara, Mitsuhiro Fujishiro

    International journal of clinical oncology   Vol. 27 ( 5 ) page: 940 - 947   2022.5

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    BACKGROUND AND AIM: Esophageal stenosis is a serious complication after endoscopic submucosal dissection (ESD) for thoracic esophageal cancer (TEC), and steroid has been applied for stenosis prevention. However, the rate of stenosis and effect of steroid for ESD of cervical esophageal cancer (CEC) remain unknown. The aim was to clarify the rate and managements of post-ESD stenosis for CEC. METHODS: A total of 325 lesions with 272 patients who underwent ESD for esophageal cancers were enrolled and were divided to the CEC group (43 lesions) or the TEC group (282 lesions). Patient characteristics, clinicopathological features, procedure-related outcomes of esophageal ESD, stenosis rate and clinical outcome of steroid use cases were evaluated. RESULTS: More patients in the CEC group received preventive steroid treatment compared to the TEC group (37.2% vs 14.5%, P = 0.001). The rate of post-ESD stenosis tended to be higher in the CEC group (11.6%) than in the TEC group (6.7%). For cases of 3/4 ≤ of circumference, local injection with oral steroid had lower stenosis rate than local injection only in both groups (CEC 40% vs 100%, TEC 30.7% vs 56.3%). More sessions and longer duration of dilation were needed to release the stenosis in the CEC group (20 times vs. 5 times, P = 0.015; 196 days vs. 55 days, P = 0.043). CONCLUSION: The post-ESD stenosis rate of CEC tended to be higher than that of TEC. More intensive preventive measures for post-ESD stenosis may be needed for CEC than TEC.

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  32. Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis. Reviewed International journal Open Access

    Keiko Maeda, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Akina Oishi, Shuji Ikegami, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

    Biomedicines   Vol. 10 ( 4 )   2022.4

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    The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

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  33. Diagnostic performance of endoscopic classifications for neoplastic lesions in patients with ulcerative colitis: A retrospective case-control study. Reviewed International journal Open Access

    Yuichi Kida, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yasuyuki Mizutani, Naomi Kakushima, Kazuhiro Furukawa, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Masatoshi Ishigami, Mitsuhiro Fujishiro

    World journal of gastroenterology   Vol. 28 ( 10 ) page: 1055 - 1066   2022.3

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    BACKGROUND: It is unclear whether the Japan Narrow-Band Imaging Expert Team (JNET) classification and pit pattern classification are applicable for diagnosing neoplastic lesions in patients with ulcerative colitis (UC). AIM: To clarify the diagnostic performance of these classifications for neoplastic lesions in patients with UC. METHODS: This study was conducted as a single-center, retrospective case-control study. Twenty-one lesions in 19 patients with UC-associated neoplasms (UCAN) and 23 lesions in 22 UC patients with sporadic neoplasms (SN), evaluated by magnifying image-enhanced endoscopy, were retrospectively and separately assessed by six endoscopists (three experts, three non-experts), using the JNET and pit pattern classifications. The results were compared with the pathological diagnoses to evaluate the diagnostic performance. Inter- and intra-observer agreements were calculated. RESULTS: In this study, JNET type 2A and pit pattern type III/IV were used as indicators of low-grade dysplasia, JNET type 2B and pit pattern type VI low irregularity were used as indicators of high-grade dysplasia to shallow submucosal invasive carcinoma, JNET type 3 and pit pattern type VI high irregularity/VN were used as indicators of deep submucosal invasive carcinoma. In the UCAN group, JNET type 2A and pit pattern type III/IV had a low positive predictive value (PPV; 50.0% and 40.0%, respectively); however, they had a high negative predictive value (NPV; 94.7% and 100%, respectively). Conversely, in the SN group, JNET type 2A and pit pattern type III/IV had a high PPV (100% for both) but a low NPV (63.6% and 77.8%, respectively). In both groups, JNET type 3 and pit pattern type VI-high irregularity/VN showed high specificity. The inter-observer agreement of JNET classification and pit pattern classification for UCAN among experts were 0.401 and 0.364, in the same manner for SN, 0.666 and 0.597, respectively. The intra-observer agreements of JNET classification and pit pattern classification for UCAN among experts were 0.387, 0.454, for SN, 0.803 and 0.567, respectively. CONCLUSION: The accuracy of endoscopic diagnosis using both classifications was lower for UCAN than for SN. Endoscopic diagnosis of UCAN tended to be underestimated compared with the pathological results.

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  34. Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images. Reviewed Open Access

    Keiko Hirai, Takamichi Kuwahara, Kazuhiro Furukawa, Naomi Kakushima, Satoshi Furune, Hideko Yamamoto, Takahiro Marukawa, Hiromitsu Asai, Kenichi Matsui, Yoji Sasaki, Daisuke Sakai, Koji Yamada, Takahiro Nishikawa, Daijuro Hayashi, Tomohiko Obayashi, Takuma Komiyama, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Hiroki Kawashima, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association   Vol. 25 ( 2 ) page: 382 - 391   2022.3

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    BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

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  35. Fecal incontinence and oral regurgitation during duodenal endoscopic submucosal dissection using the water pressure method. Reviewed International journal

    Yoshihisa Takada, Takashi Hirose, Kazuki Nishida, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima, Mitsuhiro Fujishiro

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   Vol. 34 ( 3 ) page: 526 - 534   2022.3

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    OBJECTIVES: Endoscopic submucosal dissection (ESD) in the duodenum is challenging. The water pressure method (WP-ESD) has been developed with a decreased rate of perforation. However, details of perioperative adverse events of WP-ESD are unknown. The purpose of this study was to clarify the frequency and related factors of fecal incontinence and oral regurgitation during WP-ESD. METHODS: A chart-based retrospective analysis was performed on 43 patients who underwent duodenal WP-ESD. The saline volume given into the body was calculated in all cases. All adverse events during WP-ESD until 6 weeks were extracted, and factors related to intraoperative fecal incontinence or oral regurgitation were analyzed. The frequency of fecal incontinence and oral regurgitation was also compared to those of 83 conventional ESD cases. RESULTS: In WP-ESD, intraoperative fecal incontinence occurred in 12 (28%), oral regurgitation in six (14%), and aspiration pneumonia in one patient. For fecal incontinence, the infusion speed (saline volume divided by resection time) around 17 mL/min was a significant factor in multivariable analysis. For oral regurgitation, only tumor size was a significant factor in univariate analysis (P = 0.027). Significant difference was observed in the frequency of fecal incontinence between WP-ESD and conventional ESD (28% vs. 0%, P < 0.001), but no difference was observed in oral regurgitation or aspiration pneumonia. CONCLUSIONS: Intraoperative fecal incontinence is a unique adverse event of WP-ESD related to the infusion speed. WP-ESD did not pose a risk for oral regurgitation, but we should be aware of the risk in large tumor cases.

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  36. 今月の主題 炎症性腸疾患の粘膜治癒を再考する 主題 Crohn病における小腸粘膜治癒評価の意義-小腸カプセル内視鏡の立場から

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 飯田 忠, 水谷 泰之, 石川 卓哉, 大野 栄三郎, 川嶋 啓揮, 藤城 光弘

    胃と腸   Vol. 57 ( 2 ) page: 183 - 189   2022.2

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    DOI: 10.11477/mf.1403202660

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  37. Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces. Reviewed International journal Open Access

    Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer

    Cell host & microbe   Vol. 30 ( 2 ) page: 216 - +   2022.2

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    Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or virus-binding initiates degradation of PARD6B. The loss of PARD6B causes the depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface, thus enabling a form of cell-autonomous host defense.

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  38. Initial experience of tofacitinib for treating refractory moderate-to-severe ulcerative colitis. Reviewed Open Access

    Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Takashi Honda, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Nagoya journal of medical science   Vol. 84 ( 1 ) page: 169 - 179   2022.2

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    Ulcerative colitis (UC) is an incurable, chronic inflammatory disease of the large bowel whose etiology and pathogenesis have not yet been comprehensively explained. Tofacitinib is a small molecule Janus kinase inhibitor that was introduced for treating refractory UC. We aimed to examine the efficacy and safety of tofacitinib for the treatment of 18 patients with UC. Continuous treatment rates were 50, 38, and 33% at 8, 24, and 52 weeks, respectively. Overall, 83.3% of these patients showed tumor necrosis factor (TNF) antibody failure status. When the effective status was defined as a Lichtiger index (LI) that decreased by 3 points or more or was less than 4 points and remission status was defined as an LI less than 4 points, the effective and remission rates (%) at 2, 8, and 16 weeks were 55.5 (10/18) and 22.2 (4/18), 38.8 (7/18) and 33.3 (6/18), and 38.8 (7/18) and 38.8 (7/18), respectively. Background characteristics of 2-week responders and non-responders were compared. C-reactive protein level in responders was significantly lower than that in non-responders, and the hemoglobin level in responders was significantly higher than that in non-responders. This study provides preliminary results of the effectiveness of tofacitinib even for TNF antibody and tacrolimus failure patients.

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  39. Evaluation of ulcerative colitis activity using transabdominal ultrasound shear wave elastography. Reviewed International journal Open Access

    Kenta Yamada, Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Tadashi Iida, Eri Ishikawa, Yasuyuki Mizutani, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Naomi Kakushima, Kazuhiro Furukawa, Masanao Nakamura, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Quantitative imaging in medicine and surgery   Vol. 12 ( 1 ) page: 618 - 626   2022.1

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    BACKGROUND: Transabdominal ultrasound (US) has been reported to be effective in the evaluation of ulcerative colitis (UC). US can measure shear wave elastography (SWE) and shear wave dispersion (SWD), which may be correlated with inflammation and necrosis. We aimed to investigate the relationship between UC activity and SWE and SWD. METHODS: Patients with UC who underwent US within 2 days before or after a colonoscopy between April 2019 and March 2020 were included. SWE and SWD were measured in the sigmoid colon; the correlations of SWE and SWD with the Lichtiger index and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were investigated. We also compared SWE and SWD between patients with mucosal healing and those in the active phase according to the UCEIS. RESULTS: Twenty-six UC patients were enrolled. The median Lichtiger index, UCEIS, SWE values, and SWD values were 8 [interquartile range (IQR), 5.3-10.8], 4 (IQR, 3.3-5), 1.69 (IQR, 1.49-2.16) m/s, and 11.9 (IQR, 10.9-13.3) (m/s)/kHz, respectively. The Lichtiger index and UCEIS were negatively correlated with the SWE values (rs=-0.404 and rs=-0.506) but not with the SWD values (rs=0.004 and rs=0.002). The SWE values differed significantly between the mucosal healing and active phase groups [2.40 (IQR, 2.18-3.38) vs. 1.62 (IQR, 1.44-1.95) m/s, P=0.007], whereas the SWD values did not [13.1 (IQR, 7.05-21.6) vs. 11.9 (IQR, 11.1-13.2) (m/s)/kHz, P=0.918]. CONCLUSIONS: SWE may be useful for the evaluation of UC activity and could be a noninvasive method of assessing disease severity.

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  40. Preliminary Comparison of Endoscopic Brush and Net Catheters as the Sampling Tool to Analyze the Intestinal Mucus in the Rectum with Ulcerative Colitis Patients. International journal Open Access

    Masanao Nakamura, Keiko Maeda, Kenta Yamamoto, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami, Hiroki Kawashima

    Digestion   Vol. 103 ( 3 ) page: 232 - 243   2022

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    BACKGROUND: The pathophysiology of ulcerative colitis (UC) remains unclear, but early lesions on the colorectal mucosal surface may play an important role in its etiology. Intestinal mucus samples, including inner and outer layers, are collected by net or brush catheters, but the quality of the samples obtained by each method has not been fully investigated. OBJECTIVE: The purpose of this study was to compare the microbiome and protein content of intestinal mucus collected by net and brush catheters during colonoscopy. METHODS: Intestinal mucus samples from the lower rectum of 4 patients with UC were collected using a net catheter, a brush catheter, and intestinal fluid suction. Microbiome and protein content were analyzed using 16S rRNA gene sequencing and mass spectrometry. RESULTS: The patients demonstrated significant differences in microbiome alpha diversity (p < 0.05), but this difference was not observed between the sampling methods. Net catheter samples demonstrated higher total protein concentrations than brush catheter samples. The brush catheter group had more Lachnospira, a butyrate-producing bacterium, when compared to the net group. The brush catheter group also had more oral bacteria of Staphylococcus and Dialister in those with active phase when compared to the net group. CONCLUSIONS: Brush catheters are more likely to collect the intestinal mucus inner layer, whereas net catheters are more likely to collect larger samples that include the outer mucus layer, as well as the intestinal fluid. Two sampling methods with different types of collection of the mucosa may lead to different results among patients with mucosal vulnerabilities.

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  41. 小腸Dieulafoy病変(矢野-山本分類Type 2a)の診断と治療についての臨床的検討

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 川嶋 啓揮

    日本小腸学会学術集会プログラム・抄録集   Vol. 6 ( 0 ) page: 65 - 65   2022

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    <p>【背景】小腸Dieulafoy病変は、内視鏡観察時に自然止血されている可能性があるため確定診断と治療が遅れる傾向を有する。一方では、Dieulafoy病変の臨床的特徴を把握しておくことによって診断のタイミングや治療戦略を事前に検討できるかもしれない。本研究の目的は、当院で経験された同病変の臨床的特徴を後方視的に調査し、その最適な診断と治療につき検討することであった。</p><p>【対象・方法】対象は当院において2003年6月から2022年7月の間に小腸出血が疑われダブルバルーン内視鏡(以下DBE)を施行し、Dieulafoy病変と診断、内視鏡治療を受けた36例であった。本研究におけるDieulafoy病変の定義は、粘膜面の変化は露出血管部のみとし、付着する血栓を認める場合と露出血管からの噴出性かそれに準じる活動性出血を認める場合とした。臨床的背景、治療方法などを検討した。</p><p>【結果】男性/女性は19/17例、平均年齢は71±10歳であった。33例でなんらかの基礎疾患を有していた。抗血栓薬の使用を19例で認め、ワーファリン10例、バイアスピリン7例(重複あり)の順で多かった。累計の出血エピソードは中央値で2回(1-18回)であった。最低血中ヘモグロビン値は5.9±1.7g/dl、赤血球輸血は2例以外の全例で行われていた。症状発現からDBEまでは中央値18日(2-63日)であった。DBE時の所見について、病変部位は深部十二指腸、上部空腸、中部空腸、下部空腸、中部回腸、下部回腸で各々3、18、8、2、2,6例で認められた(重複あり)。治療はクリッピング34例、APC凝固2例であった。偶発症は再出血10例(27.7%)、急性膵炎1例であった。</p><p>【結語】小腸Dieulafoy病変は診断に苦慮し、治療までに時間と輸血処置などを多く要していた。本病変が疑われた際には早めの内視鏡検査が検討される。</p>

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  42. Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling. Reviewed Open Access

    Miguel Ricardo Rodríguez Meza, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami

    Internal medicine (Tokyo, Japan)   Vol. 61 ( 17 ) page: 2593 - 2599   2022

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    We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that CD3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

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  43. Real-world local recurrence rate after cold polypectomy in colorectal polyps less than 10 mm using propensity score matching. International journal Open Access

    Masashi Saito, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Eri Ishikawa, Yasuyuki Mizutani, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Masatoshi Ishigami, Mitsuhiro Fujishiro

    World journal of gastroenterology   Vol. 27 ( 47 ) page: 8182 - 8193   2021.12

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    BACKGROUND: Cold polypectomy (CP) is a simple and safe procedure for polyps less than 10 mm in size; however, there is concern about local recurrence following CP because of unidentified margins of excised specimens and the lack of tumor suppression effect by coagulation. Some clinical trials have evaluated local persistent recurrence; their results suggest that a higher rate of local recurrence has not been documented so far. There were few reports that observed the course over long periods of time after CP in clinical practice. AIM: To evaluate the presence of local recurrence following CP and hot polypectomy (HP) using propensity score matching. METHODS: We analyzed 275 patients who underwent polypectomy for non-pedunculated colorectal polyps less than 10 mm (959 Lesions) between October 2016 and 2017 and underwent follow-up endoscopy subsequently. We divided them into the CP group (706 Lesions), wherein CP was performed, and the HP group (253 Lesions), wherein HP was performed. Using propensity score matching, we extracted 215 Lesions in each group and evaluated the local recurrence and content of CP in the real clinic and adverse events using medical records. RESULTS: After propensity score matching, there were no significant differences in the patients' and their endoscopic background (age, use of antithrombotics, indications, size, morphology, location of polyps, and polypectomy device) between the groups. The mean duration between colorectal polypectomy and the next follow-up colonoscopy was 17.5 ± 7.1 (range, 6-39) mo in the CP group and 15.7 ± 6.0 (range, 6-35) mo in the HP group, which was significantly longer in the CP group (P = 0.005). The local recurrence rate was 0.93% in the CP group and 0.93% in the HP group, without a significant difference (P = 0.688). Additionally, no differences were observed in the macroscopic en bloc resection rate, histopathological complete resection rate, and pathological results between the groups. Adverse events did not occur in either group. CONCLUSION: Local recurrence after CP was equivalent to that following HP in clinical practice. CP is useful and safe in the treatment of non-pedunculated polyps of less than 10 mm.

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  44. 特集 Cold polypectomyの課題 4.症例からみえた課題(1)小腸ポリープに対するcold polypectomy

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 川嶋 啓揮

    臨床消化器内科   Vol. 37 ( 1 ) page: 93 - 96   2021.12

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  45. Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival. Reviewed International journal Open Access

    Kentaro Yamada, Tsunaki Sawada, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Eri Ishikawa, Tadashi Iida, Yasuyuki Mizutani, Naomi Kakushima, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Satoshi Furune, Tetsunari Hase, Kenji Yokota, Osamu Maeda, Naozumi Hashimoto, Masashi Akiyama, Yuichi Ando, Mitsuhiro Fujishiro

    World journal of gastroenterology   Vol. 27 ( 41 ) page: 7190 - 7206   2021.11

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    BACKGROUND: Despite the popularity of immune checkpoint inhibitors (ICIs) in the treatment of advanced cancer, patients often develop gastrointestinal (GI) and non-GI immune-related adverse events (irAEs). The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports. This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment. AIM: To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs. METHODS: In this single-center, retrospective, observational study, we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020. We analyzed the clinical characteristics of patients who received ICI treatment. We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer (LC) and malignant melanoma (MM). Kaplan-Meier analysis was used to compare the median overall survival (OS). Multivariate Cox proportional hazards models were used to identify prognostic factors. A P value < 0.05 was considered statistically significant. RESULTS: GI-irAEs occurred in 34 of 605 patients (5.6%) treated with an anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibody alone and in nine of 56 patients (16.1%) treated with an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies. The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies (P < 0.05). In 130 patients with MM, OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs (P = 0.035). In contrast, in 209 patients with non-small cell LC, there was no significant difference in OS between the groups. The multivariate analyses showed that a performance status of 2-3 (hazard ratio: 2.406; 95% confidence interval: 1.125-5.147; P = 0.024) was an independent predictive factor for OS in patients with MM. CONCLUSION: Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies. Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

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  46. Endocytoscopy Is Useful for the Diagnosis of Superficial Nonampullary Duodenal Epithelial Tumors. Reviewed International journal Open Access

    Takashi Hirose, Naomi Kakushima, Kazuhiro Furukawa, Satoshi Furune, Eri Ishikawa, Tsunaki Sawada, Keiko Maeda, Takeshi Yamamura, Takuya Ishikawa, Eizaburo Ohno, Masanao Nakamura, Kazuki Nishida, Takio Yokoi, Hiroki Kawashima, Mitsuhiro Fujishiro

    Digestion   Vol. 102 ( 6 ) page: 895 - 902   2021.11

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    INTRODUCTION: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. METHODS: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. RESULTS: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining. CONCLUSIONS: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.

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  47. Detection of Colorectal Neoplasms Using Linked Color Imaging: A Prospective, Randomized, Tandem Colonoscopy Trial. Reviewed International journal Open Access

    Issei Hasegawa, Takeshi Yamamura, Hiroto Suzuki, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Masanao Nakamura, Mitsuhiro Fujishiro

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association   Vol. 19 ( 8 ) page: 1708 - +   2021.8

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    BACKGROUND AND AIMS: A higher adenoma detection rate (ADR) has been shown to be related to a lower incidence and mortality of colorectal cancer. We analyzed the efficacy of linked color imaging (LCI) by assessing the detection, miss, and visibility of various featured adenomas as compared with white light imaging (WLI). METHODS: This was a prospective, randomized, tandem trial. The participants were randomly assigned to 2 groups: first observation by LCI, then second observation by WLI (LCI group); or both observations by WLI (WLI group). Suspected neoplastic lesions were resected after magnifying image-enhanced endoscopy. The primary outcome was to compare the ADR during the first observation. Secondary outcomes included evaluation of adenoma miss rate (AMR) and visibility score. RESULTS: A total of 780 patients were randomized, 700 of whom were included in the final analysis. The ADR was 69.6% and 63.2% in the LCI and WLI groups, respectively, with no significant difference. However, LCI improved the average ADR in low-detectors compared with high-detectors (76.0% vs 55.1%; P < .001). Total AMR was 20.6% in the LCI group, which was significantly lower than that in the WLI group (31.1%) (P < .001). AMR in the LCI group was significantly lower, especially for diminutive adenomas (23.4% vs 35.1%; P < .001) and nonpolypoid lesions (25.6% vs 37.9%; P < .001) compared with the WLI group. CONCLUSION: Although both methods provided a similar ADR, LCI had a lower AMR than WLI. LCI could benefit endoscopists with lower ADR, an observation that warrants additional study. (UMIN Clinical Trials Registry, Number: UMIN000026359).

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  48. Difference of efficacy for small bowel lesion in Crohn

    Sawada, T; Nakamura, M; Yamamura, T; Maeda, K; Ishikawa, E; Fujishiro, M

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 36   page: 116 - 116   2021.8

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  49. An evaluation of resectability among endoscopic treatment methods for rectal neuroendocrine tumors <10 mm. Reviewed International journal

    Kazuhiro Toriyama, Takeshi Yamamura, Masanao Nakamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Kazuhiro Furukawa, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Mitsuhiro Fujishiro

    Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology   Vol. 22 ( 2 ) page: 104 - 110   2021.6

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    BACKGROUND AND STUDY AIMS: With respect to rectal neuroendocrine tumor (NET) resection, it remains unclear which of the following methods is the most effective: conventional endoscopic mucosal resection (cEMR), EMR using a fitted cap (EMR-C), EMR with a ligation band device (EMR-L), or endoscopic submucosal dissection (ESD). Thus, in this study, we aim to retrospectively evaluate the most effective endoscopic resection for rectal NETs < 10 mm. PATIENTS AND METHODS: In total, 61 consecutive patients with primary rectal NETs < 10 mm in diameter were included in this study; they were then divided into three groups: those with cEMR; those with modified EMR (mEMR) involving EMR-C and EMR-L; and those with ESD. The primary endpoint was to evaluate the difference in the complete en bloc resection rate. The secondary endpoint was to investigate differences in procedure time and complications. RESULTS: Among the three groups, a significant difference was found in procedure time (cEMR vs ESD, P < .01; mEMR vs ESD, P < .01), en bloc resection rate (cEMR vs mEMR, P = .015), tumor size (mEMR vs ESD, P < .01), percentage of tumor diameter ≥ 5 mm (mEMR vs ESD, P < .01), and complete en bloc resection rate (cEMR vs mEMR, P = .014). Meanwhile, no significant difference was noted in terms of complication rate among the three groups. CONCLUSION: The mEMR was the most suitable resection method for rectal NETs < 10 mm with respect to the risks and benefits from procedure-related factors, such as complete en bloc resection rate, procedure time, and complication rate.

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  50. Diagnostic yield of colon capsule endoscopy for Crohn's disease lesions in the whole gastrointestinal tract Open Access

    Yamada Keisaku, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    BMC GASTROENTEROLOGY   Vol. 21 ( 1 )   2021.2

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  51. Ustekinumab is effective against small bowel lesions in Crohn's disease: two case reports. Reviewed

    Kentaro Murate, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Clinical journal of gastroenterology   Vol. 14 ( 1 ) page: 129 - 135   2021.2

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    We encountered two patients with Crohn's disease (CD) for whom induction of ustekinumab was effective for the management of small intestinal lesions with stenosis. The first symptomatic CD case was a 40-year-old female with longitudinal ulcers in the small bowel found at double-balloon endoscopy. She was in a biologic-naïve condition. Her symptoms improved immediately after ustekinumab induction. We confirmed the condition of intestinal mucosa by double-balloon endoscopy. Deep ulcers remained open at 24 weeks and were scarred at 72 weeks. The second case was a 50-year-old male who failed to respond to treatment with anti-TNFα agents. The lumen was narrow caused by circumferential ulcer, and an endoscope could not pass the site before induction. The circumferential ulcer had been healed by ustekinumab induction, and an endoscope passed through at 72 weeks. These two cases support the therapeutic efficacy of ustekinumab in alleviating small bowel lesions in CD patients.

    DOI: 10.1007/s12328-020-01242-0

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  52. Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

    Ishikawa Eri, Nakaguro Masato, Nakamura Masanao, Yamamura Takeshi, Sawada Tsunaki, Mizutani Yasuyuki, Maeda Keiko, Furukawa Kazuhiro, Shimoyama Yoshie, Kawashima Hiroki, Fujishiro Mitsuhiro

    PATHOLOGY INTERNATIONAL   Vol. 71 ( 1 ) page: 33 - 41   2021.1

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    DOI: 10.1111/pin.13048

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  53. The microbiome can predict mucosal healing in small intestine in patients with Crohn's disease. Reviewed

    Shun Hattori, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Kenta Yamamoto, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

    Journal of gastroenterology   Vol. 55 ( 12 ) page: 1138 - 1149   2020.12

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    BACKGROUND: Mucosal healing is the main treatment goal for Crohn's disease. In this situation, some patients have difficulty with endoscopic evaluation of the entire small intestine. Crohn's disease is closely associated with the gut microbiota, but the relationship between the microbiome and disease activity in the small intestine remains unclear. We examined the association between the microbiome and endoscopic findings in the small intestine and determined whether the microbiome can predict mucosal healing. METHODS: The patients with Crohn's disease who were scheduled for capsule or balloon-assisted endoscopy were included in this prospective study. Patients whose entire small intestine was evaluated were divided into two groups based on ulcerative findings. The microbiomes in the fecal samples were analyzed using 16S rRNA sequencing. RESULTS: The 38 enrolled patients were divided into the ulcer group (24) and mucosal healing group (14). The ulcer group exhibited lower α diversity. Six genera, namely Faecalibacterium (P = 0.008), Lachnospira (P = 0.009), Paraprevotella (P = 0.01), Dialister (P = 0.012), Streptococcus (P = 0.025), and Clostridium (P = 0.028) were enriched in the mucosal healing group. A predictive score for mucosal healing was defined using these six genera. The area under the curve was 0.795 and the sensitivity and specificity for predicting mucosal healing were 0.643 and 0.917, respectively. CONCLUSIONS: Fecal microbiome is corelated with disease activity in the entire small intestine in Crohn's disease patients. The predictive score proposed by microbiota characteristics was a potential biomarker for mucosal healing in the small intestine.

    DOI: 10.1007/s00535-020-01728-1

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  54. Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms Open Access

    Esaki Masaya, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Suzuki Hiroto, Kuno Takeshi, Yamada Kentaro, Hasegawa Issei, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Hirooka Yoshiki, Fujishiro Mitsuhiro

    DIGESTION     2020.11

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  55. Accuracy of carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography using double-balloon endoscopy Open Access

    Niwa Yoshiki, Nakamura Masanao, Kawashima Hiroki, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

    WORLD JOURNAL OF GASTROENTEROLOGY   Vol. 26 ( 42 ) page: 6669 - 6678   2020.11

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    DOI: 10.3748/wjg.v26.i42.6669

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  56. Endoscopic Activity and Serum TNF-alpha Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn's Disease Patients

    Murate Kentaro, Maeda Keiko, Nakamura Masanao, Sugiyama Daisuke, Wada Hirotaka, Yamamura Takeshi, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Miyahara Ryoji, Ishigami Masatoshi, Nishikawa Hiroyoshi, Fujishiro Mitsuhiro

    INFLAMMATORY BOWEL DISEASES   Vol. 26 ( 11 ) page: 1669 - 1681   2020.11

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    DOI: 10.1093/ibd/izaa086

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  57. Mutation analysis of gastrointestinal stromal tumors using RNA obtained via endoscopic ultrasound-guided fine-needle aspiration Open Access

    Funasaka Kohei, Miyahara Ryoji, Furukawa Kazuhiro, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Kawashima Hiroki, Hirooka Yoshiki, Ohmiya Naoki, Fujishiro Mitsuhiro

    TRANSLATIONAL ONCOLOGY   Vol. 13 ( 11 )   2020.11

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  58. New modality for the quantitative evaluation of tissue elasticity using a forward-viewing radial-array echoendoscope for colorectal neoplasms

    Esaki Masaya, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Furukawa Kazuhiro, Kawashima Hiroki, Hirooka Yoshiki, Fujishiro Mitsuhiro

    INTERNATIONAL JOURNAL OF COLORECTAL DISEASE     2020.10

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    DOI: 10.1007/s00384-020-03790-w

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  59. A forward-viewing radial-array echoendoscope is useful for diagnosing the depth of colorectal neoplasia invasion

    Kuno Takeshi, Yamamura Takeshi, Nakamura Masanao, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Esaki Masaya, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Fujishiro Mitsuhiro

    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES     2020.9

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    DOI: 10.1007/s00464-020-07936-3

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  60. 診断に苦慮した広範囲胆管癌の1例

    芳川 昌功, 川嶋 啓揮, 大野 栄三郎, 石川 卓哉, 小屋 敏也, 田中 浩敬, 酒井 大輔, 飯田 忠, 西尾 亮, 鈴木 博貴, 植月 康太, 八鹿 潤, 山田 健太, 澤田 つな騎, 前田 啓子, 山村 健史, 古川 和宏, 舩坂 好平, 中村 正直, 宮原 良二, 廣岡 芳樹

    肝胆膵治療研究会誌   Vol. 16 ( 1 ) page: 93 - 93   2020.9

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  61. 表在型食道扁平上皮癌におけるLinked Color Imagingで観察される色情報と深達度および血管径との相関に関する検討 Open Access

    小林 健一, 宮原 良二, 舩坂 好平, 古川 和宏, 澤田 つな騎, 前田 啓子, 山村 健史, 石川 卓也, 大野 栄三郎, 中村 正直, 川嶋 啓揮, 中黒 匡人, 奥村 結希, 廣岡 芳樹, 藤城 光弘

    Gastroenterological Endoscopy   Vol. 62 ( 9 ) page: 1624 - 1633   2020.9

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    【背景】食道扁平上皮癌の治療方針決定に正確な深達度診断が重要であるが,MM/SM1の正診率は低く解決すべき課題となっている.本研究の目的はLED光源を用いたLCIにおける食道表在癌に対する色と深達度の関連性について検討することである.【方法】表在型食道癌と診断された病変に対し白色光につづいてLCIで観察を行った.色合いの評価についてはCIE-L*a*b*空間を用いて色値を算出し,深達度ごとの癌部と非癌部の色差を算出した.血管径およびintrapapillary capillary loopの分岐角を病理的に算出し,色合いとの相関を検討した.【結果】48症例52病変が登録された.深達度別の正常と病変部の色差において,MM/SM1以深群ではEP/LPM群に比べて有意に色差が大きかった(P=0.025).血管径はb*値と弱い正の相関を認めた(相関係数=0.302,P=0.033).【結論】LED光源を用いたLCI観察は,表在型食道癌における深達度診断の向上に有用である可能性があるが,その有用性を示すのにはさらなる検討が必要である.(著者抄録)

    DOI: 10.11280/gee.62.1624

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  62. 特集 クローン病小腸狭窄病変に対する内視鏡的バルーン拡張術─基本からピットフォールまで Ⅱ.クローン病小腸狭窄病変に対するバルーン拡張術(4)クローン病におけるバルーン拡張術のコツ a.ダブルバルーン内視鏡の立場から

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 石川 恵里, 古川 和宏, 角嶋  直美, 藤城 光弘

    INTESTINE   Vol. 24 ( 3 ) page: 197 - 202   2020.8

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    DOI: 10.19020/int.0000000486

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  63. 特集 分子標的時代のIBD 診療 -IBD の寛解導入,寛解維持の実践 3.IBD 治療における寛解導入と寛解維持に関するトピック(5)UC 関連腫瘍の早期診断と治療

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 喜田 裕一, 古川 和宏, 川嶋 啓揮, 藤城 光弘

    臨床消化器内科   Vol. 35 ( 10 ) page: 1267 - 1273   2020.8

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    DOI: 10.19020/cg.0000001325

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  64. Subjective Symptoms in Patients with Eosinophilic Esophagitis Are Related to Esophageal Wall Thickness and Esophageal Body Pressure.

    Muroi K, Kakushima N, Furukawa K, Ishikawa E, Sawada T, Ishikawa T, Maeda K, Yamamura T, Ohno E, Nakamura M, Kawashima H, Funasaka K, Miyahara R, Fujishiro M

    Digestive diseases and sciences     2020.8

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    DOI: 10.1007/s10620-020-06527-5

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  65. Use of Immunostaining for the diagnosis of Lymphovascular invasion in superficial Barrett's esophageal adenocarcinoma. Reviewed International journal Open Access

    Hosono I, Miyahara R, Furukawa K, Funasaka K, Sawada T, Maeda K, Yamamura T, Ishikawa T, Ohno E, Nakamura M, Kawashima H, Yokoi T, Tsukamoto T, Hirooka Y, Fujishiro M

    BMC gastroenterology   Vol. 20 ( 1 ) page: 175 - 175   2020.6

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    BACKGROUND: The prevalence of Barrett's esophageal adenocarcinoma (BEA) is increasing in Japan. Accurate assessment of lymphovascular invasion (LVI) after endoscopic resection or surgery is essential in evaluating treatment response. This study aimed to assess the usefulness of immunostaining in determining the extent of LVI in superficial BEA. METHODS: We retrospectively included 41 patients who underwent endoscopic resection or surgery between January 2007 and July 2018. In all cases, 3-μm serial sections from paraffin-embedded resected specimens were used for hematoxylin and eosin (H-E) staining and immunostaining for D2-40 and CD31. Two specialized gastrointestinal pathologists (T.Y. and T.T.), blinded to clinical information, independently evaluated the extent of LVI from these specimens. The LVI-positivity rate was evaluated with respect to the depth of invasion, changes in the positivity rate on immunostaining, pathological characteristics of patients with LVI, lymph node metastasis or relapse, and course after treatment. RESULTS: H-E staining alone identified LVI in 7 patients (positivity rate: 17.1%). Depths of invasion were categorized based on extension to the submucosa (SM) or deeper. On immunostaining for D2-40 and CD31, additional positivity was detected in 2 patients with SM1 and 1 SM3, respectively; LVI was detected in 10 patients (positivity rate: 24.4%). LVI-positivity rates with invasion of the superficial muscularis mucosa (SMM)/lamina propria mucosa (LPM)/deep muscularis mucosa (DMM), SM 1, 2, and 3 were 0, 75, 28.6, and 55.6%, respectively. CONCLUSIONS: Combined H-E staining and immunostaining is useful in diagnosing LVI in superficial BEA, particularly in endoscopically resected specimens.

    DOI: 10.1186/s12876-020-01319-7

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  66. Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice.

    Nishikawa T, Maeda K, Nakamura M, Yamamura T, Sawada T, Mizutani Y, Ito T, Ishikawa T, Furukawa K, Ohno E, Miyahara R, Kawashima H, Honda T, Ishigami M, Yamamoto T, Matsumoto S, Hotta Y, Fujishiro M

    Digestive diseases and sciences     2020.6

  67. Clinical Factors Associated with Missing Colorectal Polyp on Colon Capsule Endoscopy

    Yamada Keisaku, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Miyahara Ryoji, Kawashima Hiroki, Hotta Naoki, Hirooka Yoshiki

    DIGESTION   Vol. 101 ( 3 ) page: 316-322   2020.5

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    DOI: 10.1159/000498942

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  68. Double-balloon endoscopic retrograde cholangiopancreatography for patients who underwent liver operation: A retrospective study. Open Access

    Nishio R, Kawashima H, Nakamura M, Ohno E, Ishikawa T, Yamamura T, Maeda K, Sawada T, Tanaka H, Sakai D, Miyahara R, Ishigami M, Hirooka Y, Fujishiro M

    World journal of gastroenterology   Vol. 26 ( 10 ) page: 1056 - 1066   2020.3

  69. Usefulness of Endoscopic Ultrasound Elastography Combined With the Strain Ratio in the Estimation of Treatment Effect in Autoimmune Pancreatitis. Reviewed International journal Open Access

    Ishikawa T, Kawashima H, Ohno E, Tanaka H, Maeda K, Sawada T, Yamamura T, Furukawa K, Nakamura M, Miyahara R, Ishigami M, Fujishiro M

    Pancreas   Vol. 49 ( 2 ) page: E21 - E22   2020.2

  70. Color information from linked color imaging is associated with invasion depth and vascular diameter in superficial esophageal squamous cell carcinoma

    Kobayashi Kenichi, Miyahara Ryoji, Funasaka Kohei, Furukawa Kazuhiro, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Kawashima Hiroki, Nakaguro Masato, Okumura Yuki, Hirooka Yoshiki, Fujishiro Mitsuhiro

    DIGESTIVE ENDOSCOPY   Vol. 32 ( 1 ) page: 65 - 73   2020.1

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    DOI: 10.1111/den.13469

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  71. Comparison of high-resolution manometry in patients complaining of dysphagia among patients with or without diabetes mellitus Open Access

    Muroi K.

    Digestion     2020

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    DOI: 10.1159/000510081

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  72. A Prospective Study of Factors Associated with Abdominal Pain in Patients during Unsedated Colonoscopy Using a Magnifying Endoscope. Open Access

    Suzuki H, Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa T, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

    Internal medicine (Tokyo, Japan)   Vol. 59 ( 15 ) page: 1795 - 1801   2020

  73. A Case of Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis. Open Access

    Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa E, Ohashi A, Kajikawa G, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

    Internal medicine (Tokyo, Japan)   Vol. 59 ( 23 ) page: 3009 - 3014   2020

  74. 単発性小腸Peutz-Jeghers型ポリープに関する臨床的検討

    鳥山 和浩, 中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 石川 恵里, 梶川 豪, 村手 健太郎, 喜田 裕一, 江崎 正哉, 濱崎 元伸, 角嶋 直美, 古川 和宏, 藤城 光弘

    日本小腸学会学術集会プログラム・抄録集   Vol. 4 ( 0 ) page: 39 - 39   2020

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    <p>【背景】Peutz-Jeghers症候群(PJS)は食道を除く全消化管において上皮の過形成と粘膜筋板のポリープ内への樹枝状増生を特徴とする過誤腫性ポリポーシスと皮膚、粘膜の色素斑を特徴とする常染色体優性遺伝性疾患である。一方、家族歴や皮膚、粘膜の色素沈着を伴わない単発性のPeutz-Jeghers型ポリープ(PJP)を認めることがあるが、その臨床的特徴に関する報告は少ないのが現状である。</p><p>【目的】単発性小腸PJPにおける臨床的特徴を明らかにする。</p><p>【対象】2007年4月から2020年5月までに当院で内視鏡治療を施行し、病理組織学的にPJPと診断された単発性小腸PJP16症例。</p><p>【結果】レトロスペクティブにカルテ、内視鏡画像をレビューした。性別は男性10例、女性6例、診断時年齢中央値(範囲)は61(18-82)歳。診断契機は貧血7例、黒色便5例、腹痛1例、イレウス症状1例、他疾患精査時の偶発的発見が2例。原発部位は空腸14例、回腸2例で、腫瘍径中央値(範囲)は25(4-35)mm。切除したPJP全病変で病変内に悪性腫瘍の併存は認めなかった。癌の既往歴を有したのは6例(前立腺癌2例、舌癌1例、大腸癌1例、胃癌1例、子宮体癌1例)。観察期間中央値(範囲)は4.6(0.1-53.7)ヶ月で再発並びに関連死は認めなかった。</p><p>【考察】単発性小腸PJPにおいては診断時の年齢が高く、発見契機としては出血関連症状が多く、病変部位は空腸に多い特徴があった。</p><p>【結語】当院で経験した単発性小腸PJPの臨床的特徴を検討した。今後更なる症例の蓄積が必要である。</p>

    DOI: 10.32264/shocho.4.0_39

    CiNii Research

  75. Specific members of gut microbiota predict mucosal healing in Crohn's disease

    Hattori S., Nakamura M., Yamamura T., Maeda K., Sawada T., Mizutani Y., Yamamoto K., Pu L. Zorron Cheng Tao, Honda T., Ishikawa T., Furukawa K., Ohno E., Miyahara R., Kawashima H., Fujishiro M.

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 34   page: 152 - 152   2019.9

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  76. Objective evaluation of the therapeutic effect of ustekinumab on Crohn's disease

    Yamamura, T; Nakamura, M; Murate, K; Maeda, K; Sawada, T; Mizutani, Y; Nishikawa, T; Hattori, S; Yamamoto, K; Pu, LZCT; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Fujishiro, M

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 34   page: 145 - 145   2019.9

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  77. Roles of the mesenchymal stromal/stem cell marker meflin in cardiac tissue repair and the development of diastolic dysfunction Open Access

    Hara A.

    Circulation Research   Vol. 125 ( 4 ) page: 414 - 430   2019.8

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    Publisher:Circulation Research  

    DOI: 10.1161/CIRCRESAHA.119.314806

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  78. USEFULNESS OF THE FORWARD-VIEWING RADIAL-ARRAY ECHOENDOSCOPE IN THE DIAGNOSIS OF INVASION DEPTH OF COLORECTAL NEOPLASIA Reviewed International journal

    Kuno, T; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Mizutani, Y; Suzuki, H; Esaki, M; Ishikawa, T; Furukawa, K; Ohno, E; Kawashima, H; Miyahara, R; Hirooka, Y

    GASTROINTESTINAL ENDOSCOPY   Vol. 89 ( 6 ) page: AB324 - AB324   2019.6

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    DOI: 10.1016/j.gie.2019.03.427

    Web of Science

  79. ダブルバルーン小腸内視鏡を用いた硬化療法にて治療効果を得た小腸多発血管腫の1例 Open Access

    山田 啓策, 山村 健史, 中村 正直, 澤田 つな騎, 水谷 泰之, 前田 啓子, 古川 和宏, 宮原 良二, 横井 太紀雄, 廣岡 芳樹

    Gastroenterological Endoscopy   Vol. 61 ( 6 ) page: 1231 - 1236   2019.6

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    Language:Japanese   Publisher:(一社)日本消化器内視鏡学会  

    70歳代男性。1ヵ月間持続する黒色便にて当科紹介となった。上下部消化管内視鏡検査では、明らかな出血源を認めなかった。小腸出血を疑いカプセル内視鏡検査を施行したところ、全小腸にわたり多発する隆起性病変を認めた。ダブルバルーン小腸内視鏡検査を行いジャンボバイオプシー目的の内視鏡的粘膜切除術(Endoscopic mucosal resection:EMR)にて海綿状血管腫と診断した。後日多発する血管腫に対してpolidocanol(Aethoxysklerol)による硬化療法を行った。4日後の内視鏡観察では、血管腫は縮小を認め、以後黒色便も消失した。小腸に多発する血管腫に対して内視鏡的硬化療法が有用であった1例を経験したので報告する。(著者抄録)

    DOI: 10.11280/gee.61.1231

    Open Access

  80. CLINICAL SIGNIFICANCE OF THE PATENCY OF GASTROINTESTINAL TRACT IN CROHN'S DISEASE EVALUATED BY PATENCY CAPSULE

    Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Kuno, T; Yamada, K; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Hirooka, Y

    GASTROINTESTINAL ENDOSCOPY   Vol. 89 ( 6 ) page: AB333 - AB333   2019.6

  81. FACTORS RELATED TO MISSED COLORECTAL POLYPS ON COLON CAPSULE ENDOSCOPY IN CLINICAL PRACTICE

    Yamada, K; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Niwa, Y; Ishikawa, E; Otsuka, H; Suzuki, H; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Hotta, N; Pu, LZCT; Hirooka, Y

    GASTROINTESTINAL ENDOSCOPY   Vol. 89 ( 6 ) page: AB155 - AB155   2019.6

  82. 今月の主題 知っておきたい小腸疾患 主題 小腸の非腫瘍性疾患-小腸リンパ管拡張症

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 丹羽 慶樹, 石川 恵里, 大塚 裕之, 鈴木 悠土, 西川 貴広, 石田 哲也, 久野 剛史, 服部 峻, 山田 啓策, 廣岡 芳樹, 藤城 光弘

    胃と腸   Vol. 54 ( 4 ) page: 532 - 536   2019.4

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    Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1403201630

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  83. Utility of linked color imaging for endoscopic diagnosis of early gastric cancer. Reviewed International journal Open Access

    Fujiyoshi T, Miyahara R, Funasaka K, Furukawa K, Sawada T, Maeda K, Yamamura T, Ishikawa T, Ohno E, Nakamura M, Kawashima H, Nakaguro M, Nakatochi M, Hirooka Y

    World journal of gastroenterology   Vol. 25 ( 10 ) page: 1248 - 1258   2019.3

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    BACKGROUND: Linked color imaging (LCI) is a method of endoscopic imaging that emphasizes slight differences in red mucosal color. AIM: To evaluate LCI in diagnostic endoscopy of early gastric cancer and to compare LCI and pathological findings. METHODS: Endoscopic images were obtained for 39 patients (43 lesions) with early gastric cancer. Three endoscopists evaluated lesion recognition with white light imaging (WLI) and LCI. Color values in Commission Internationale de l'Eclairage (CIE) 1976 L*a*b* color space were used to calculate the color difference (ΔE) between cancer lesions and non-cancer areas. After endoscopic submucosal dissection, blood vessel density in the surface layer of the gastric epithelium was evaluated pathologically. The identical region of interest was selected for analyses of endoscopic images (WLI and LCI) and pathological analyses. RESULTS: LCI was superior for lesion recognition (P < 0.0001), and ΔE between cancer and non-cancer areas was significantly greater with LCI than WLI (29.4 vs 18.6, P < 0.0001). Blood vessel density was significantly higher in cancer lesions (5.96% vs 4.15%, P = 0.0004). An a* cut-off of ≥ 24 in CIE 1976 L*a*b* color space identified a cancer lesion using LCI with sensitivity of 76.7%, specificity of 93.0%, and accuracy of 84.9%. CONCLUSION: LCI is more effective for recognition of early gastric cancer compared to WLI as a result of improved visualization of changes in redness. Surface blood vessel density was significantly higher in cancer lesions, and this result is consistent with LCI image analysis.

    DOI: 10.3748/wjg.v25.i10.1248

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  84. A case of multiple hemangiomas of the small intestine treated by sclerotherapy using double-balloon enteroscopy

    Yamada K.

    Gastroenterological Endoscopy   Vol. 61 ( 6 ) page: 1231 - 1236   2019

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    Publisher:Gastroenterological Endoscopy  

    DOI: 10.11280/gee.61.1231

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  85. Lewis Score on Capsule Endoscopy as a Predictor of the Risk for Crohn's Disease-Related Emergency Hospitalization and Clinical Relapse in Patients with Small Bowel Crohn's Disease Open Access

    Nishikawa Takahiro, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Miyahara Ryoji, Kawashima Hiroki, Hirooka Yoshiki

    GASTROENTEROLOGY RESEARCH AND PRACTICE   Vol. 2019   page: 4274257   2019

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

    DOI: 10.1155/2019/4274257

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  86. 腸リンパ管拡張症の診断と治療

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 藤城 光弘

    日本小腸学会学術集会プログラム・抄録集   Vol. 3 ( 0 ) page: 34_2 - 34_2   2019

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    Language:Japanese   Publisher:日本小腸学会  

    <p>【背景・目的】 小腸内視鏡診断の進歩により腸リンパ管拡張症(Intestinal lymphangiectasia:IL)を含む蛋白漏出性腸症の小腸精査が可能になった。本研究の目的はILの臨床経過を後ろ向きに評価し、その特徴を明らかにしたうえでより良い治療法を模索することであった。</p><p>【対象と方法】 対象は2003年6月から2019年6月までにILと診断された17例(男性9例、女性8例、発症年齢は中央値37歳、0-75歳)であった。ILの診断は蛋白漏出性腸症と診断され且つ内視鏡下生検もしくは剖検にて病理学的に腸リンパ管拡張を認めたもので、他疾患が否定的であったものとした。白色絨毛、散布性白点を有する白色絨毛群(WV)と、異常なしもしくは軽度絨毛腫大、ケルクリング襞腫大を認める非白色絨毛群(NWV)に分けて臨床成績を比較検討した。</p><p>【結果】 WV、NWVは10例、7例であった。平均血清アルブミン値(g/dl)はWV:NWV = 2.0:1.2でNWVにおいて有意に低かった(P = 0.0061)。平均<i>α</i>1アンチトリプシンクリアランスはWV:NWV = 132:284(P = 0.0509)であった。ステロイド治療への反応はWV:NWV = 2/7:6/6 例でみられた。平均観察期間48箇月において1例のILが影響した死亡例を経験したが、重篤な真菌感染症によるものであった。</p><p>【結論】 NWV群は蛋白漏出は多いがステロイドへの反応がWV群よりも良好であった。治療のゴールドスタンダードは存在せず可能な可能で効果があるものを続けることが現状であった。</p>

    DOI: 10.32264/shocho.3.0_34_2

    CiNii Research

  87. Validity of Capsule Endoscopy in Monitoring Therapeutic Interventions in Patients with Crohn's Disease. Reviewed International journal Open Access

    Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Ryoji Miyahara, Anastasios Koulaouzidis, Yoshiki Hirooka

    Journal of clinical medicine   Vol. 7 ( 10 )   2018.10

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    Mucosal healing in Crohn's disease (CD) can be evaluated by capsule endoscopy (CE). However, only a few studies have utilized CE to demonstrate the therapeutic effect of medical treatment. We sought to evaluate the validity of using CE to monitor the effect of medical treatment in patients with CD. One hundred (n = 100) patients with CD were enrolled. All patients had a gastrointestinal (GI) tract patency check prior to CE. Patients with baseline CE Lewis score (LS) ≤ 135 were included in the non-active CD group and ended the study. In those with LS > 135 (active CD group), additional treatment was administered, regardless of symptoms, as per the treating clinician's advice. Patients of the active CD group underwent follow-up CE assessment 6 months later. Out of 92 patients with confirmed GI patency who underwent CE, 40 (43.4%) had CE findings of active inflammation. Of 29 patients with LS > 135 who received additional medications and underwent follow-up CE, improvement of the LS was noted in 23 (79.3%) patients. Eleven patients were asymptomatic but received additional medications; 8 (72.7%) had improvement of the LS. This study demonstrated that additional treatment even for patients with CD in clinical remission and active small-bowel inflammation on CE can reduce mucosal damage.

    DOI: 10.3390/jcm7100311

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  88. クローン病小腸術後患者に対するエレンタールの使用効果と内視鏡診断

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 石川 卓哉, 古川 和宏, 舩坂 好平, 大野 栄三郎, 川嶋 啓揮, 宮原 良二, 廣岡 芳樹

    Biomedical Research on Trace Elements   Vol. 29 ( 1 ) page: 50 - 51   2018.6

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  89. Identification of Meflin as a Potential marker for mesenchymal stromal cells Reviewed Open Access

    Maeda K, Enomoto A, Hara A, Asai N, Kobayashi T, Horinouchi A, Maruyama S, Ishikawa Y, Nishiyama T, Kiyoi H, Kato T, Ando K, Weng L, Mii S, Asai M, Mizutani Y, Watanabe O, Hirooka Y, Goto H, Takahashi M

    Scientific Reports     2016.2

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    DOI: 10.1038/srep22288

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  90. Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis Reviewed Open Access

    Miyake N, Ando T, Ishiguro K, Maeda O, Watanabe O, Hirayama Y, Maeda K, Morise K, Matsushita M, Furukawa K, Funasaka K, Nakamura M, Miyahara R, Ohmiya N, Goto H.

    World J Gastroenterol     2015.1

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    DOI: 10.3748/wjg.v21.i1.254

  91. Usefulness of Helicobacter pylori eradication for precancerous lesions of the gastric remnant Reviewed Open Access

    Sakakibara M, Ando T, Ishiguro K, Maeda O, Watanabe O, Hirayama Y, Morise K, Maeda K, Matsushita M, Furukawa K, Funasaka K, Nakamura M, Miyahara R, Goto H

    J Gastroenterol Hepatol     2014.12

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    DOI: 10.1111/jgh.12772

  92. Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis. Reviewed

    Mimura S, Ando T, Ishiguro K, Maeda O, Watanabe O, Ujihara M, Hirayama Y, Morise K, Maeda K, Matsushita M, Funasaka K, Nakamura M, Miyahara R, Ozaki N, Goto H.

    Scand J Gastroenterol     2013.10

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

    DOI: 10.3109/00365521.2013.832366

  93. Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer. Reviewed Open Access

    An J, Enomoto A, Weng L, Kato T, Iwakoshi A, Ushida K, Maeda K, Ishida-Takagishi M, Ishii G, Ming S, Sun T, Takahashi M

    J Cancer Res Clin Oncol     2013.3

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

    DOI: 10.1007/s00432-012-1328-6

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MISC 37

  1. 【十二指腸・小腸疾患アトラス】その他 血管性病変 小腸多発血管腫

    河村 達哉, 山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 横井 太紀雄, 川嶋 啓揮

    消化器内視鏡   Vol. 36 ( 4 ) page: 652 - 653   2024.4

  2. 【十二指腸・小腸疾患アトラス】腫瘍,腫瘍様病変 リンパ増殖性病変 MALT lymphoma

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 村手 健太郎, 古川 和宏, 廣瀬 崇, 川嶋 啓揮

    消化器内視鏡   Vol. 36 ( 4 ) page: 480 - 481   2024.4

  3. 【十二指腸・小腸疾患アトラス】炎症性疾患 自己免疫疾患・膠原病・血管炎など 腸リンパ管拡張症

    山下 彩子, 中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 村手 健太郎, 加留部 謙之輔, 川嶋 啓揮

    消化器内視鏡   Vol. 36 ( 4 ) page: 622 - 623   2024.4

  4. 最先端医療の今 潰瘍性大腸炎患者の腸粘液解析

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 村手 健太郎, 川嶋 啓揮

    Medical Science Digest   Vol. 50 ( 3 ) page: 156 - 157   2024.3

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  5. 特集 IBD診療-ますます増えた薬剤の選択とさらなる進化の展望 1.治療薬の使い分けの総論と各論(4)中等症UCにおけるバイオ製剤/JAK阻害薬の使い分け-抗IL-23抗体も含めて

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 川嶋 啓揮

    臨床消化器内科   Vol. 39 ( 2 ) page: 140 - 146   2024.1

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    Publisher:日本メディカルセンター  

    DOI: 10.19020/cg.0000002926

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  6. 【IBD診療-ますます増えた薬剤の選択とさらなる進化の展望】治療薬の使い分けの総論と各論 中等症UCにおけるバイオ製剤/JAK阻害薬の使い分け-抗IL-23抗体も含めて

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 川嶋 啓揮

    臨床消化器内科   Vol. 39 ( 2 ) page: 140 - 146   2024.1

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  7. 【小腸画像診断のトピックス】バルーン内視鏡:ダブルバルーン内視鏡を中心に 腫瘍性疾患と炎症性疾患に対する診断法の有用性と限界

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 村手 健太郎, 長谷川 一成, 池上 脩二, 山下 彩子, 河村 達哉, 大岩 恵祐, 八田 勇輔, 平松 美緒, 廣瀬 崇, 古川 和宏, 川嶋 啓揮

    胃と腸   Vol. 58 ( 11 ) page: 1462 - 1469   2023.11

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  8. 小腸内視鏡下生検により診断した神経線維腫症1型に合併した腸管diffuse ganglioneuromatosisの1例

    喜田 裕一, 澤田 つな騎, 石川 恵里, 榊原 綾子, 山村 健史, 前田 啓子, 江崎 正哉, 濱崎 元伸, 村手 健太郎, 中村 正直

    Gastroenterological Endoscopy   Vol. 65 ( 7 ) page: 1232 - 1238   2023.7

  9. 【消化管内視鏡治療のリスク克服に向けて】待機的内視鏡治療に潜むリスクとそのマネジメント 大腸EMR/ESD

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 古川 和宏, 川嶋 啓揮

    臨床消化器内科   Vol. 38 ( 1 ) page: 42 - 47   2022.12

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  10. 腸管上皮細胞は、病原体の接着を認識し、エンドソームの機能調節を介して、侵入を阻害する

    前田啓子, Wayne I Lencer

    実験医学     2022.8

  11. 【小腸疾患-診断・治療の最新動向-】血行障害・血管性病変 血管性病変 動静脈奇形

    山村 健史, 澤田 つな騎, 石川 恵里, 前田 啓子, 中村 正直

    日本臨床   Vol. 80 ( 増刊7 小腸疾患 ) page: 305 - 311   2022.7

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    Language:Japanese   Publisher:(株)日本臨床社  

  12. 【転移性消化管腫瘍】転移性小腸腫瘍の画像診断・形態学的特徴

    山田 健太朗, 山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 飯田 忠, 水谷 泰之, 山雄 健太郎, 石川 卓哉, 古川 和宏, 大野 栄三郎, 川嶋 啓揮

    胃と腸   Vol. 57 ( 8 ) page: 1018 - 1026   2022.7

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    Language:Japanese   Publisher:(株)医学書院  

  13. 消化器疾患診療に必要なバイオマーカー開発のための研究 潰瘍性大腸炎の内視鏡的活動性と粘膜治癒を反映するバイオマーカーの同定

    前田 啓子, 中村 正直, 石上 雅敏

    日本消化器病学会雑誌   Vol. 119 ( 臨増総会 ) page: A170 - A170   2022.3

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    Language:Japanese   Publisher:(一財)日本消化器病学会  

  14. 【炎症性腸疾患の粘膜治癒を再考する】Crohn病における小腸粘膜治癒評価の意義 小腸カプセル内視鏡の立場から

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 飯田 忠, 水谷 泰之, 石川 卓哉, 大野 栄三郎, 川嶋 啓揮, 藤城 光弘

    胃と腸   Vol. 57 ( 2 ) page: 183 - 189   2022.2

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  15. 特集 小腸内視鏡が変えた疾患マネージメント 小腸疾患に対するアプローチ

    中村 正直, 大宮 直木, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里

    消化器内視鏡   Vol. 33 ( 12 ) page: 1792 - 1798   2021.12

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    Publisher:(株)東京医学社  

    DOI: 10.24479/j02312.2022082023

    CiNii Research

  16. 【Cold polypectomyの課題】症例からみえた課題 小腸ポリープに対するcold polypectomy

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 川嶋 啓揮

    臨床消化器内科   Vol. 37 ( 1 ) page: 93 - 96   2021.12

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    Language:Japanese   Publisher:(株)日本メディカルセンター  

  17. 【小腸内視鏡が変えた疾患マネージメント】小腸疾患に対するアプローチ

    中村 正直, 大宮 直木, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里

    消化器内視鏡   Vol. 33 ( 12 ) page: 1792 - 1798   2021.12

  18. 【クローン病診療の診断から治療をマスターする】クローン病の活動性はどのように評価するのか? 内視鏡検査と検査のタイミング

    喜田 裕一, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 中村 正直

    消化器・肝臓内科   Vol. 10 ( 4 ) page: 429 - 435   2021.10

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  19. 【消化管がん検診・スクリーニングの手引き】(第VI章)下部消化管の検診でしばしば遭遇する腫瘍性疾患 大腸ポリープ

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 川嶋 啓揮, 藤城 光弘

    臨床消化器内科   Vol. 36 ( 8 ) page: 1022 - 1028   2021.7

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    Language:Japanese   Publisher:(株)日本メディカルセンター  

  20. 【潰瘍性大腸炎診療の診断から治療をマスターする】潰瘍性大腸炎の活動性はどのように評価するのか? 内視鏡検査と検査のタイミング

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 石川 恵里, 角嶋 直美, 古川 和宏, 藤城 光弘

    消化器・肝臓内科   Vol. 9 ( 1 ) page: 31 - 35   2021.1

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    Language:Japanese   Publisher:(有)科学評論社  

  21. 【クローン病小腸狭窄病変に対する内視鏡的バルーン拡張術-基本からピットフォールまで】クローン病小腸狭窄病変に対するバルーン拡張術 クローン病におけるバルーン拡張術のコツ a.ダブルバルーン内視鏡の立場から

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 石川 恵里, 古川 和宏, 角嶋 直美, 藤城 光弘

    Intestine   Vol. 24 ( 3 ) page: 197 - 202   2020.8

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    Language:Japanese   Publisher:(株)日本メディカルセンター  

  22. 【分子標的時代のIBD診療-IBDの寛解導入,寛解維持の実践】IBD治療における寛解導入と寛解維持に関するトピック UC関連腫瘍の早期診断と治療

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 石川 恵里, 喜田 裕一, 古川 和宏, 川嶋 啓揮, 藤城 光弘

    臨床消化器内科   Vol. 35 ( 10 ) page: 1267 - 1273   2020.8

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  23. Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis Reviewed

    Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa E, Ohashi A, Kajikawa G, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

    Internal medicine (Tokyo, Japan)     2020.7

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    Language:English  

    DOI: 10.2169/internalmedicine.5302-20

    PubMed

  24. 【消化器疾患とステント治療】胃・十二指腸狭窄に対するステント治療

    鈴木 智彦, 鈴木 孝弘, 森 裕, 石川 卓哉, 古川 和宏, 石川 恵里, 澤田 つな騎, 前田 啓子, 山村 健史, 大野 栄三郎, 中村 正直, 川嶋 啓揮, 藤城 光弘

    消化器・肝臓内科   Vol. 8 ( 1 ) page: 18 - 25   2020.7

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  25. Use of Immunostaining for the diagnosis of Lymphovascular invasion in superficial Barrett's esophageal adenocarcinoma. Reviewed

    Hosono I, Miyahara R, Furukawa K, Funasaka K, Sawada T, Maeda K, Yamamura T, Ishikawa T, Ohno E, Nakamura M, Kawashima H, Yokoi T, Tsukamoto T, Hirooka Y, Fujishiro M

    BMC gastroenterology   Vol. 20 ( 1 ) page: 175   2020.6

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    Language:English  

    DOI: 10.1186/s12876-020-01319-7

    PubMed

  26. Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice Reviewed

    Nishikawa T, Maeda K, Nakamura M, Yamamura T, Sawada T, Mizutani Y, Ito T, Ishikawa T, Furukawa K, Ohno E, Miyahara R, Kawashima H, Honda T, Ishigami M, Yamamoto T, Matsumoto S, Hotta Y, Fujishiro M

    Digestive diseases and sciences     2020.6

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    DOI: 10.1007/s10620-020-06359-3

    PubMed

  27. Endoscopic Activity and Serum TNF-α Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn’s Disease Patients Reviewed

    Murate K, Maeda K, Nakamura M, Sugiyama D, Wada H, Yamamura T, Sawada T, Mizutani Y, Ishikawa T, Furukawa K, Ohno E, Honda T, Kawashima H, Miyahara R, Ishigami M, Nishikawa H, Fujishiro M

    Inflammatory bowel diseases     2020.5

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    Language:English  

    DOI: 10.1093/ibd/izaa086

    PubMed

  28. Double-balloon endoscopic retrograde cholangiopancreatography for patients who underwent liver operation: A retrospective study Reviewed

    Nishio R, Kawashima H, Nakamura M, Ohno E, Ishikawa T, Yamamura T, Maeda K, Sawada T, Tanaka H, Sakai D, Miyahara R, Ishigami M, Hirooka Y, Fujishiro M

    World journal of gastroenterology   Vol. 26 ( 10 ) page: 1056-1066   2020.3

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    DOI: 10.3748/wjg.v26.i10.1056

    PubMed

  29. Usefulness of Endoscopic Ultrasound Elastography Combined With the Strain Ratio in the Estimation of Treatment Effect in Autoimmune Pancreatitis Reviewed

    Ishikawa T, Kawashima H, Ohno E, Tanaka H, Maeda K, Sawada T, Yamamura T, Furukawa K, Nakamura M, Miyahara R, Ishigami M, Fujishiro M

    Pancreas   Vol. 49 ( 2 ) page: e21-e22   2020.2

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    Language:English  

    DOI: 10.1097/MPA.0000000000001481

    PubMed

  30. Color information from linked color imaging is associated with invasion depth and vascular diameter in superficial esophageal squamous cell carcinoma Reviewed

    Kobayashi K, Miyahara R, Funasaka K, Furukawa K, Sawada T, Maeda K, Yamamura T, Ishikawa T, Ohno E, Nakamura M, Kawashima H, Nakaguro M, Okumura Y, Hirooka Y, Fujishiro M

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   Vol. 32 ( 1 ) page: 65-73   2020.1

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    Language:English  

    DOI: 10.1111/den.13469

    PubMed

  31. A Prospective Study of Factors Associated with Abdominal Pain in Patients during Unsedated Colonoscopy Using a Magnifying Endoscope Reviewed

    Suzuki H, Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa T, Furukawa K, Ohno E, Honda T, Kawashima H, Ishigami M, Fujishiro M

    Internal medicine (Tokyo, Japan)   Vol. 59 ( 15 ) page: 1795-1801   2020

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    Language:English  

    DOI: 10.2169/internalmedicine.4267-19

    PubMed

  32. Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction Reviewed

    Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A

    Circulation research   Vol. 125 ( 4 ) page: 414-430   2019.8

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    Language:English  

    DOI: 10.1161/CIRCRESAHA.119.314806

    PubMed

  33. 【消化管疾患と緊急内視鏡】消化器疾患における緊急内視鏡の果たす役割

    古根 聡, 古川 和宏, 宮原 良二, 伊藤 隆徳, 澤田 つな騎, 前田 啓子, 山村 健史, 石川 卓哉, 石津 洋二, 大野 栄三郎, 中村 正直, 本多 隆, 石上 雅敏, 川嶋 啓揮, 藤城 光弘

    消化器・肝臓内科   Vol. 6 ( 1 ) page: 1 - 6   2019.7

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  34. 【原因不明消化管出血(OGIB)】緊急カプセル内視鏡・バルーン内視鏡を可能にする体制作りと実際の運用

    山村 健史, 中村 正直, 前田 啓子, 澤田 つな騎, 古川 和宏, 宮原 良二, 川嶋 啓揮, 藤城 光弘

    Intestine   Vol. 23 ( 4 ) page: 351 - 356   2019.7

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    Language:Japanese   Publisher:(株)日本メディカルセンター  

    <文献概要>小腸疾患の内視鏡診断はバルーン内視鏡(balloon-assisted endoscopy;BAE)や小腸カプセル内視鏡(small bowel capsule endoscopy;SBCE)など検査デバイスの発展により,飛躍的に向上した.それに伴い原因不明の消化管出血であるOGIB(obscure gastrointestinal bleeding)に関する論文も多く報告されるようになり,その全貌が明らかになってきている.かつて外科的手術や血管内放射線治療が必要とされた小腸出血は,内視鏡的に止血が可能になっており,患者への侵襲も少なく済むようになった.本邦では2015年にOBIGにおける診断アルゴリズムも提唱され,診断や治療方針の参考にされている.実際の診断時には,検査時期や病変の種類が病変発見成功の鍵を握っているが,現状ではその体制や運用の方法は各施設に委ねられている.今後,OGIBの診療を広めていくためには,検査の運用や体制作りも非常に重要になってくる.本稿では当院におけるOGIB時のBAEやSBCEの検査体制や運用方法について記載する.

  35. 【知っておきたい小腸疾患】小腸の非腫瘍性疾患 小腸リンパ管拡張症

    中村 正直, 山村 健史, 前田 啓子, 澤田 つな騎, 水谷 泰之, 丹羽 慶樹, 石川 恵里, 大塚 裕之, 鈴木 悠土, 西川 貴広, 石田 哲也, 久野 剛史, 服部 峻, 山田 啓策, 廣岡 芳樹, 藤城 光弘

    胃と腸   Vol. 54 ( 4 ) page: 532 - 536   2019.4

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  36. Hepatic portal venous gas following colonoscopy in a patient with Crohn's disease. Reviewed

    Ujihara M, Ando T, Ishiguro K, Maeda O, Watanabe O, Hirayama Y, Maeda K, Morise K, Matsushita M, Funasaka K, Nakamura M, Miyahara R, Ohmiya N, Goto H

    Nagoya journal of medical science   Vol. 75 ( 3-4 ) page: 273-8   2013.8

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    PubMed

  37. Importance of appropriate pharmaceutical management in pregnant women with ulcerative colitis. Reviewed

    Ujihara M, Ando T, Ishiguro K, Maeda O, Watanabe O, Hirayama Y, Morise K, Maeda K, Matsushita M, Miyahara R, Ohmiya N, Nishio Y, Yamaguchi T, Haruta J, Ina K, Goto H

    BMC research notes   Vol. 6   page: 210   2013.5

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    DOI: 10.1186/1756-0500-6-210

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Presentations 11

  1. PARD6Bによる腸管上皮細胞の新たな防御機構の同定

    前田啓子, 中村正直, 藤城光弘

    消化器病学会総会 

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    Event date: 2019.5

    Language:English   Presentation type:Symposium, workshop panel (public)  

    Venue:石川県   Country:Japan  

  2. Innate Host Defense at Mucosal Surfaces by Rapid Degradation of Pard6B and Apkc to Deplete the Apical Endosome International conference

    Keiko Maeda, Nicholas Zachos, and Wayne I Lencer

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    Event date: 2018.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  3. Only the PARD6B Paralogue of the PARD6 Polarity Protein Family Regulates the Apical Endosomal Compartment of Canine MDCK Epithelial Cells International conference

    Keiko Maeda, Wayne I Lencer

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    Event date: 2017.5

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  4. クローン病におけるustekinumabの治療効果および予後予測因子の検討

    村手健太郎、前田啓子、藤代光弘

    日本消化器病学会総会  2021.4 

  5. 潰瘍性大腸炎の内視鏡的活動性と粘膜治癒を反映するバイオマーカーの同定

    前田啓子, 中村正直, 藤代光弘

    日本消化器病学会総会  2022.4.22 

  6. Monoclonal antibody against neoepitope of caspase-cleaved mature interleukin-18 ameliorates colitis and improve barrier function

    Keiko Maeda, Masanao Nakamura, Masatoshi Ishigami

    Digestive Disease Week 2023  2023.5.8 

  7. 女性医師の多様な働き方とキャリアプラン

    前田啓子

    日本消化器病学会総会  2022.4.22 

  8. 炎症性腸疾患に対する新規インフラマソーム標的治療法の開発

    池上修二, 前田啓子, 藤代光弘

    日本消化器関連学会週間(JDDW)  2021.11.27 

  9. 腸管上皮細胞の感染防御機構の解明 Invited

    前田啓子

    第29回premium lecture  2023.1.19 

  10. 腸管上皮細胞の腸内細菌叢に対する認識機構の解明と炎症性腸疾患における機能解析

    前田啓子, 中村正直, 川嶋啓揮

    消化器病学会週間  2023.10.30 

  11. 腸管上皮細胞の腸内細菌叢に対する認識機構の解明と炎症性腸疾患における機能解析 Invited

    前田啓子

    第12回 Fukui gastroenterological frontier  2024.4.26 

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Research Project for Joint Research, Competitive Funding, etc. 8

  1. 腸管上皮細胞の防御機構の解明と治療応用

    2023.4 - 2025.3

    日本女医会 

  2. 腸管上皮細胞の抗原認識機構の解明と炎症性腸疾患への治療応用

    2023.4 - 2025.3

    日本炎症性腸疾患学会 

  3. 炎症性腸疾患の多様化を見据えた新規インフラマソーム標的治療法の開発

    2021.4 - 2022.3

    国立研究開発法人 日本医療研究開発機構  国立研究開発法人 日本医療研究開発機構 

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    Authorship:Principal investigator 

  4. 腸管上皮細胞の抗原認識機構の解明

    愛知健康増進財団 

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    Authorship:Principal investigator 

  5. 腸管上皮細胞の抗原認識機構の解明と治療応用

    日東学術振興財団 

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  6. 腸管上皮細胞の防御機構の解明と治療応用

    武田科学振興財団 

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  7. Disentangling underlying mechanism of cross-talk between the gut-brain axis to influence brain behavior functionality

    国立研究開発法人 日本医療研究開発機構 

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  8. 新しい動物モデルを用いた炎症性腸疾患の病態解明と 新規治療法の探索

    公益財団法人豊秋奨学会 

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    Authorship:Principal investigator 

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KAKENHI (Grants-in-Aid for Scientific Research) 10

  1. 細胞自律性機構による腸疾患の統合理解とその制御

    2025 - 2032

    科学技術振興機構  戦略的な研究開発の推進 創発的研究支援事業 

    前田 啓子

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    腸内細菌叢の異常は、様々な疾患の発症や進展に深く関与しますが、その直接的な制御による治療法の確立には多くの課題が残されています。私たちは、腸上皮細胞が外来異物を認識し、自らの機能を調節することで腸内環境を正常に保つという細胞自律性機構を見出しました。本研究では、この機構を基盤として腸内細菌叢の制御メカニズムおよび腸内環境の維持機構を解明し、腸疾患の統合理解につなげます。

  2. Elucidation of the cell-autonomous host defense at mucosal ssurfaces in rotavirus infection

    2024.9 - 2026.3

    国立研究開発法人 日本医療研究開発機構 

  3. 腸管上皮細胞の防御機構の解明と治療応用

    2024.9 - 2026.3

    豊秋奨学会 

  4. 新たな炎症性腸疾患動物モデルの解析による、その病態解明と治療法の開発

    Grant number:24K11129  2024.4 - 2027.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    前田 啓子, 川嶋 啓揮, 中村 正直, 村手 健太郎

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    申請者らは、炎症性腸疾患(IBD)関連遺伝子変異が報告されているParファミリーに着目し、その中のPARD6Bを介して、腸管上皮細胞が病原体の侵入を抑止するという新たな防御機構を世界に先駆けて見出した。加えて、新規に作製した腸管上皮細胞特異的PARD6B欠損マウスが自然腸炎を発症し、その病態がIBDに類似することを見出した。本研究では、①腸管上皮細胞特異的PARD6B欠損マウスが起こす自然腸炎の解析、②ヒト腸管オルガノイドや申請者らのIBDデータベースを用いたヒトPARD6Bの機能解析、③PARD6Bの発現を上昇させる新規化合物の探索を行い、IBDの治療開発を目指す。
    近年、炎症性腸疾患(IBD)患者の急増とともに難治例が増加し、新たな病態解明と治療法の確立が急務となっている。その病態には粘膜免疫の破綻、腸内細菌叢の関与とともに、腸管上皮細胞の防御機構の重要性が認識されてきている。申請者らは、IBD関連遺伝子変異が報告されているParファミリーに着目し、その中のPARD6Bを介して、腸管上皮細胞が病原体の侵入を抑止するという新たな防御機構を世界に先駆けて見出した。加えて、新規に作製した腸管上皮細胞特異的PARD6B欠損マウスが自然腸炎を発症し、その病態がIBDに類似することを見出した。本研究では、①腸管上皮細胞特異的PARD6B欠損マウスが起こす自然腸炎の解析、②ヒト腸管オルガノイドや申請者らのIBDデータベースを用いたヒトPARD6Bの機能解析を行う。
    本年度は、腸管上皮細胞特異的PARD6B欠損マウスを中心に自然腸炎を起こす機序を解析した。シングルセルRNAseqのデータから、PARD6Bは杯細胞とPaneth細胞に高発現しており、これらの細胞の形態や機能異常を認めた。腸管上皮細胞を採取し、コントロールマウスとノックアウトマウスでRNA-seqを施行しており、発現が異なる複数の遺伝子に着目をし、解析を進める予定である。複数の抗生剤カクテルの投与にて腸内細菌叢を除去すると自然腸炎の発症は認められないため、腸内細菌叢に関連した免疫細胞の活性化が予想される。そのため、腸内細菌叢や免疫細胞との関連解析も進めている。ヒト臨床検体において、発現解析を行い、IBD患者では健常人と比較して、発現や局在が異なることを見出した。ヒト、マウスに共通する機序の解析を行う予定である。
    ノックアウトマウスの解析は計画通りに進んでおり、RNA-seqで同定した複数の分子に着目をしてさらに解析を進める予定である。ヒト臨床検体を用いた解析も進めており、マウス、ヒトに共通した表現型を認めている。
    PARD6Bが高発現している杯細胞やPaneth細胞に着目をして解析を進める予定である。マウス、ヒト腸管オルガノイドを用いた解析も予定している。さらには、腸内細菌叢やその代謝産物、免疫細胞との相互作用も解析する予定である。

  5. Role of somatostatin as a neurotransmitter in the regulation of mucosal inflammation in ulcerative colitis.

    Grant number:24K11149  2024.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Coinvestigator(s) 

  6. 腸管上皮細胞の防御機構の解明

    2023.12 - 2025.12

    愛知健康増進財団 

  7. 腸管上皮細胞の抗原認識機構の解明

    2023.4 - 2025.4

    アッヴィー日本炎症性腸疾患学会 

  8. 腸管上皮細胞の機能解明と炎症性腸疾患への治療応用

    2023.4 - 2024.4

    日本女医会 

  9. Novel Inflammasome-Targeted Therapies for Diverse Inflammatory Bowel Diseases

    Grant number:21K15920  2021.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    MAEDA Keiko

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    We focused on interleukin-18 (IL-18), which is highly expressed in patients with refractory inflammatory bowel disease (IBD), and produced a specific monoclonal antibody targeting active IL-18. abnormalities, improved intestinal epithelial barrier function, and improved colitis (Mu, Maeda et al., DDS 2024, Maeda et al., IBD 2024). In addition, compared to previous anti-IL-18 antibodies, this antibody showed a superior inhibitory effect on intestinal inflammation. Furthermore, this antibody was also found to have an inhibitory effect on fibrosis progression.

  10. 腸管上皮細胞の抗原認識機構の解明と炎症性腸疾患への治療応用

    日東学術振興財団 

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Industrial property rights 2

  1. 炎症性腸疾患の活動性バイオマーカーの同定

    前田啓子, 中村正直, 石上雅敏

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    Application no:特願2022-036955  Date applied:2022.1

  2. 間葉系幹細胞とペリサイトの新規マーカーの同定

    榎本篤、前田啓子、高橋雅英

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    Application no:2015153712  Date applied:2015

    Country of applicant:Domestic