Kyushu University [HARUEI OGINO (Lecturer) Faculty of Medical Sciences, Department of Hepatology and Pancreatology]

HARUEI OGINO

Last modified date：2023.04.10

Lecturer / Department of Hepatology and Pancreatology / Faculty of Medical Sciences

Papers

1.	Eikichi Ihara, Haruei Ogino, Kazumasa Muta, Shohei Hamada, Masafumi Wada, Yoshitaka Hata, Hiroko Ikeda, Xiaopeng Bai, Yosuke Minoda, Mitsuru Esaki, Yoshimasa Tanaka, Takatoshi Chinen, Yoshihiro Ogawa, The treatment effects of acotiamide in esophagogastric outflow obstruction: a prospective longitudinal observational study., Esophagus : official journal of the Japan Esophageal Society, 10.1007/s10388-021-00887-1, 2021.10, OBJECTIVES: We have found that an altered lower esophageal sphincter (LES) accommodation response is an underlying cause of esophagogastric junction outflow obstruction (EGJOO). The objective of this study was to examine the treatment effect of acotiamide, a prokinetic agent which improves impaired gastric accommodation in functional dyspepsia, in patients with EGJOO. METHODS: A prospective observational longitudinal study was conducted between October 2014 and March 2020. Acotiamide (100 mg, 3 times a day) was administered to 25 patients with EGJOO for 4 weeks. High-resolution manometry (HRM) was performed just before and after 4 weeks of treatment. RESULTS: As the primary outcome, the extent of integrated relaxation pressure (IRP) after treatment (14.6, 12.1-22.0 mmHg) was significantly lower than that before treatment (19.4, 17.1-27.4 mmHg). The extent of LES accommodation index after treatment (32.7, 21.0-40.0 mmHg) was also significantly lower than that before treatment (39.3, 31.2-50.2 mmHg). Acotiamide normalized the IRP (
2.	Yosuke Minoda, Shuzaburo Nagatomo, Nao Fujimori, Kei Nishioka, Shotaro Kakehashi, Katsuhito Teramatsu, Yu Takamatsu, Haruei Ogino, Eikichi Ihara, Usefulness of a gel immersion-assisted EUS-guided fine-needle aspiration/biopsy for ampullary lesions (with videos)., Endoscopic ultrasound, 10.4103/EUS-D-21-00043, 2021.09.
3.	Kei Nishioka, Haruei Ogino, Takatoshi Chinen, Eikichi Ihara, Yoshimasa Tanaka, Kazuhiko Nakamura, Yoshihiro Ogawa, Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease., Journal of gastroenterology, 10.1007/s00535-021-01819-7, 2021.08, BACKGROUND: Biologics against tumor necrosis factor-α (TNF) and the p40 subunit of interleukin (IL)-12 and IL-23 are increasingly used in inflammatory bowel disease (IBD) treatment. However, information on response prediction to these agents is limited. Thus, we aimed to identify factors for IBD treatment response prediction. METHODS: We conducted a retrospective study in 33 IBD subjects for anti-TNF and a prospective study of 23 IBD and 11 non-IBD subjects for ustekinumab (UST). Mucosal biopsy specimens were obtained before treatment with biologics. The expression of 18 immune-related genes encoding representative cytokines and transcription factors was analyzed by quantitative polymerase chain reaction. RESULTS: There was no difference between the treatment-resistant and -sensitive groups with regard to clinical characteristics. A higher expression of oncostatin M (OSM) and its receptor OSMR in the intestinal mucosa was most strongly associated with anti-TNF resistance, whereas lower IL23A expression was most strongly associated with UST resistance. In addition to the absolute expression levels of genes, concordant or discordant expression patterns of particular gene sets were associated with treatment sensitivity and resistance. CONCLUSIONS: The association of anti-TNF resistance and mucosal OSM and OSMR expression was consistent with the results of a previous study in a European cohort. Our observation that IBD subjects with higher mucosal IL23A expression were more likely to achieve remission by UST has not been previously reported. The response to biologics may thus be predicted in IBD patients through the analysis of mucosal gene expression levels and patterns..
4.	Yuichiro Nishihara, Haruei Ogino, Masaru Tanaka, Eikichi Ihara, Keita Fukaura, Kei Nishioka, Takatoshi Chinen, Yoshimasa Tanaka, Jiro Nakayama, Dongchon Kang, Yoshihiro Ogawa, Mucosa-associated gut microbiota reflects clinical course of ulcerative colitis., Scientific reports, 10.1038/s41598-021-92870-0, 11, 1, 13743-13743, 2021.07, This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC..
5.	Shohei Hamada, Eikichi Ihara, Kazumasa Muta, Masafumi Wada, Yoshitaka Hata, Hiroko Ikeda, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Yoshihiro Ogawa, Onigiri esophagography as a screening test for esophageal motility disorders., Journal of neurogastroenterology and motility, 10.5056/jnm20138, 2021.07, Background/Aims: No screening test for esophageal motility disorder (EMD) has been established, the objective of this study is to examine the potential usefulness of our newly developed "Onigiri esophagography" combined with an obstruction level (OL) classification system in screening for EMD. Methods: A total of 102 patients with suspected EMDs who underwent both high-resolution manometry (HRM) and Onigiri esophagography between April 2017 and January 2019 were examined. The EMD diagnosis was performed based on the Chicago classification version 3.0 by HRM. Onigiri esophagography was performed using a liquid medium (barium sulfate) followed by a solid medium, which consisted of an Onigiri (a Japanese rice ball) with barium powder. The extent of medium obstruction was assessed by the OL classification, which was defined in a stepwise fashion from OL0 (no obstruction) to OL4 (severe obstruction). Results: Thirty-two percent of the patients with OL0 (32.3%), OL1 (50.0%), OL2 (88.0%), OL3 (100.0%), and OL4 (100.0%) were diagnosed EMDs by HRM. The area under the curve, as determined by a receiver operating characteristic analysis, for the OL classification was 0.86. Using the cutoff value of OL1, the sensitivity and specificity were 87.3% and 61.3%, respectively, while using a cutoff value of OL2, the sensitivity and specificity were 73.2% and 90.3%, respectively. Conclusion: In conclusion, Onigiri esophagography combined with the OL classification system can be used as a screening test for EMDs with a cutoff value of OL1..
6.	Mitsuru Esaki, Eikichi Ihara, Norikazu Hashimoto, Shuichi Abe, Chihoko Aratono, Noriko Shiga, Yorinobu Sumida, Hiroyuki Fujii, Kazuhiro Haraguchi, Shunsuke Takahashi, Tsutomu Iwasa, Kayoko Nakano, Masafumi Wada, Shinichi Somada, Kei Nishioka, Yosuke Minoda, Haruei Ogino, Yoshihiro Ogawa, Efficacy of hybrid endoscopic submucosal dissection with SOUTEN in gastric lesions: An ex vivo porcine model basic study., World journal of gastrointestinal surgery, 10.4240/wjgs.v13.i6.563, 13, 6, 563-573, 2021.06, BACKGROUND: Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice. AIM: To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study. METHODS: Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection, perforation, procedure time/speed for both, mucosal incision, and submucosal dissection. Factors associated with difficulty in ESD including longer procedure time, incomplete resection, and perforation, were also investigated. Categorical and continuous data were analyzed using the chi-square test or Fisher's exact test and the Mann-Whitney U test, respectively. RESULTS: The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD (median: 8.3 min vs 16.2 min, P
7.	Mitsuru Esaki, Ryosuke Maehara, Shuzaburo Nagatomo, Kei Nishioka, Yosuke Minoda, Haruei Ogino, Eikichi Ihara, Application of traction-method to hybrid endoscopic submucosal dissection for gastrointestinal tumors., Endoscopy, 10.1055/a-1422-2902, 2021.04.
8.	Kazumasa Muta, Eikichi Ihara, Shohei Hamada, Hiroko Ikeda, Masafumi Wada, Yoshitaka Hata, Xiaopeng Bai, Yuichiro Nishihara, Yoshimasa Tanaka, Haruei Ogino, Yoshihiro Ogawa, Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows., Scientific reports, 10.1038/s41598-021-87052-x, 11, 1, 7898-7898, 2021.04, The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice..
9.	Hiroaki Okuno, Haruei Ogino, Eikichi Ihara, Kei Nishioka, Yoshimasa Tanaka, Takatoshi Chinen, Motoyuki Kohjima, Takamasa Oono, Masatake Tanaka, Takeshi Goya, Nao Fujimori, Yoichiro Iboshi, Takuji Gotoda, Yoshihiro Ogawa, Discriminant equation using mucosally expressed cytokines and transcription factor for making definite diagnosis of inflammatory bowel disease unclassified., BMC gastroenterology, 10.1186/s12876-021-01656-1, 21, 1, 73-73, 2021.02, BACKGROUND: The pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC. METHODS: A total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis. RESULTS: Through discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively. CONCLUSIONS: The discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC..
10.	Yosuke Minoda, Eikichi Ihara, Keishi Komori, Haruei Ogino, Yoshihiro Otsuka, Takatoshi Chinen, Yasuo Tsuda, Koji Ando, Hidetaka Yamamoto, Yoshihiro Ogawa, Efficacy of endoscopic ultrasound with artificial intelligence for the diagnosis of gastrointestinal stromal tumors., Journal of gastroenterology, 10.1007/s00535-020-01725-4, 55, 12, 1119-1126, 2020.12, BACKGROUND: Although endoscopic ultrasound (EUS) is reported to be suitable for determining the layer from which subepithelial lesions (SELs) originate, it is difficult to distinguish gastrointestinal stromal tumor (GIST) from non-GIST using only EUS images. If artificial intelligence (AI) can be used for the diagnosis of SELs, it should provide several benefits, including objectivity, simplicity, and quickness. In this pilot study, we propose an AI diagnostic system for SELs and evaluate its efficacy. METHODS: Thirty sets each of EUS images with SELs ≥ 20 mm or
11.	Haruei Ogino, Keita Fukaura, Yoichiro Iboshi, Yousuke Nagamatsu, Hiroaki Okuno, Kei Nishioka, Yuichiro Nishihara, Yoshimasa Tanaka, Takatoshi Chinen, Eikich Ihara, Yoshihiro Ogawa, Role of the IL-23-T-bet/GATA3 Axis for the Pathogenesis of Ulcerative Colitis., Inflammation, 10.1007/s10753-020-01358-y, 2020.10, Ulcerative colitis (UC) has been considered a Th2- and Th17-related disease. However, anti-IL-12/23 p40 antibody, which blocks Th1 and Th17 cell induction and maintenance, has shown efficacy in treating UC, suggesting that UC might not be a prototypical Th2 and Th17 cell-mediated autoimmune disease. To verify how the immune responses in UC patients interact with each other, we analyzed the cytokine expression and transcription factors involved in the Th1, Th2, and Th17 responses. The mucosal expression of 19 cytokines and transcription factors related to Th1, Th2, and Th17 cells, as well as Tregs, were measured by quantitative polymerase chain reaction using endoscopic biopsy specimens from inflamed colons of UC patients. A correlation analysis between the cytokines and transcription factors was conducted. The characteristic cytokine profile in UC patients has two immune response clusters: Th17-related responses and Th1-/Th2-related responses. IL-23 showed a weaker association with Th17 cell-related cytokines and transcription factor RORC and a much stronger correlation with T-bet and GATA3. In the high-IL-23-expression group, the rate of chronic continuous type was higher and the remission rate lower than in the low-IL-23-expression group. IL-23 may be a very important cytokine for evaluating the UC disease condition, as the expression of IL-23 is associated with certain clinical characteristics of UC patients. A unique association between IL-23 and T-bet/GATA3 might play a key role in the pathogenesis of UC..
12.	Mitsuru Esaki, Kazuhiro Haraguchi, Kazuya Akahoshi, Naru Tomoeda, Akira Aso, Soichi Itaba, Haruei Ogino, Yusuke Kitagawa, Hiroyuki Fujii, Kazuhiko Nakamura, Masaru Kubokawa, Naohiko Harada, Yosuke Minoda, Sho Suzuki, Eikichi Ihara, Yoshihiro Ogawa, Endoscopic mucosal resection vs endoscopic submucosal dissection for superficial non-ampullary duodenal tumors., World journal of gastrointestinal oncology, 10.4251/wjgo.v12.i8.918, 12, 8, 918-930, 2020.08, BACKGROUND: The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) is controversial. AIM: To compare the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs. METHODS: We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs, which included eight hospitals in Fukuoka, Japan, between April 2001 and October 2017. A total of 142 patients with SNADETs treated with EMR or ESD were analyzed. Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups. We analyzed the treatment outcomes, including the rates of en bloc/complete resection, procedure time, adverse event rate, hospital stay, and local or metastatic recurrence. RESULTS: Twenty-eight pairs of patients were created. The characteristics of patients between the two groups were similar after matching. The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group [median procedure time (interquartile range): 6 (3-10.75) min vs 87.5 (68.5-136.5) min, P
13.	Hiroaki Okuno, Haruei Ogino, Eikichi Ihara, Kei Nishioka, Yoichiro Iboshi, Takatoshi Chinen, Toshiaki Ochiai, Hirotada Akiho, Kazuhiko Nakamura, Takuji Gotoda, Yoshihiro Ogawa, Interleukin-1β as a Predictor of Glucocorticoid Response in Ulcerative Colitis., Digestion, 10.1159/000507435, 1-11, 2020.05, BACKGROUND/AIM: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1β could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1β could predict the response to GC in patients with UC. METHODS: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1β, GC receptor α (GRα), GRβ, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1β levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRβ, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1β. CONCLUSIONS: Mucosally expressed IL-1β can be used as a predictor of GC response in patients with UC..
14.	Yosuke Minoda, Eikichi Ihara, Haruei Ogino, Keishi Komori, Yoshihiro Otsuka, Hiroko Ikeda, Mitsuru Esaki, Takatoshi Chinen, Takahiro Matsuguchi, Shunsuke Takahashi, Noriko Shiga, Rie Yoshimura, Yoshihiro Ogawa, The Efficacy and Safety of a Promising Single-Channel Endoscopic Closure Technique for Endoscopic Treatment-Related Artificial Ulcers: A Pilot Study., Gastrointestinal tumors, 10.1159/000503994, 7, 1-2, 21-29, 2020.04, Background/Aims: It is important to appropriately manage patients with procedure-related artificial mucosal ulcers or procedure-related complications. Many endoscopic closure techniques have been reported; however, they often require the use of special devices. We developed a single-channel endoscopic closure technique (SCCT) that can be performed with conventional devices. In the present study, we describe the technique and evaluate its efficacy. Methods: Twenty-five consecutive patients who underwent endoscopic treatment and whose artificial ulcer was closed using the SCCT were enrolled in this study. The technical success rate, number of clips for closure, procedure time, complication rate on the day of the procedure, clinical success rates on days 1 and 5, and incidence of severe stenosis of the gastrointestinal (GI) tract at 2 months after the procedure were evaluated. Results: The median ulcer diameter was 20 mm. The tumor locations were the stomach (n = 19), jejunum (n = 1), and colon (n = 5). The technical success rate was 100% (25/25), and the rate of incomplete closure was 0% (0/25). Eight clips were needed on average. The median procedure time was 18 min (range 5-49 min). The complication rate was 0% (25/25). The clinical success rates on days 1 and 5 were 100% (19/19) and 100% (9/9), respectively. No patients presented stenosis as a late complication at 2 months after the procedure (0/25). Conclusion: The SCCT could be applied in the treatment of artificial ulcers in several parts of the GI tract with a high clinical success rate and no complications. The SCCT appears to be a good option for closing artificial mucosal ulcers..
15.	Yosuke Minoda, Takatoshi Chinen, Takashi Osoegawa, Soichi Itaba, Kazuhiro Haraguchi, Hirotada Akiho, Akira Aso, Yorinobu Sumida, Keishi Komori, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa, Superiority of mucosal incision-assisted biopsy over ultrasound-guided fine needle aspiration biopsy in diagnosing small gastric subepithelial lesions: a propensity score matching analysis., BMC gastroenterology, 10.1186/s12876-020-1170-2, 20, 1, 19-19, 2020.01, BACKGROUND: Gastric subepithelial lesions, including gastrointestinal stromal tumors, are often found during routine gastroscopy. While endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has been the gold standard for diagnosing gastric subepithelial lesions, alternative open biopsy procedures, such as mucosal incision-assisted biopsy (MIAB) has been reported useful. The aim of this study is to evaluate the efficacy of MIAB for the diagnosis of gastric SELs compared with EUS-FNAB. METHODS: We retrospectively analyzed medical records of 177 consecutive patients with gastric SELs who underwent either MIAB or EUS-FNAB at five hospitals in Japan between January 2010 and January 2018. Diagnostic yield, procedural time, and adverse event rates for the two procedures were evaluated before and after propensity-score matching. RESULTS: No major procedure-related adverse events were observed in either group. Both procedures yielded highly-accurate diagnoses once large enough samples were obtained; however, such successful sampling was more often accomplished by MIAB than by EUS-FNAB, especially for small SELs. As a result, MIAB provided better diagnostic yields for SELs smaller than 20-mm diameter. The diagnostic yields of both procedures were comparable for SELs larger than 20-mm diameter; however, MIAB required significantly longer procedural time (approximately 13 min) compared with EUS-FNAB. CONCLUSIONS: Although MIAB required longer procedural time, it outperformed EUS-FNAB when diagnosing gastric SELs smaller than 20-mm diameter..
16.	Shohei Hamada, Eikichi Ihara, Hiroko Ikeda, Kazumasa Muta, Haruei Ogino, Takatoshi Chinen, Yoshimasa Tanaka, Yoshihiro Ogawa, Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease., Digestion, 10.1159/000503340, 102, 2, 1-8, 2019.10, INTRODUCTION: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. METHODS: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. RESULTS: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17% respectively) and vonoprazan groups (0, 0, 10, 49, and 41% respectively; p
17.	Xiaopeng Bai, Eikichi Ihara, Yoshihihro Otsuka, Shinichi Tsuruta, Katsuya Hirano, Yoshimasa Tanaka, Haruei Ogino, Mayumi Hirano, Takatoshi Chinen, Hirotada Akiho, Kazuhiko Nakamura, Yoshinao Oda, Yoshihiro Ogawa, Involvement of different receptor subtypes in prostaglandin E2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body, European Journal of Pharmacology, 10.1016/j.ejphar.2019.172405, 857, 2019.08, Prostaglandin E₂ (PGE₂) plays a role in the pathogenesis of gastro-esophageal reflux disease (GERD). There are 4 subtypes of PGE₂, PGE₂ receptor 1, 2, 3 and 4 (EP 1–4). In GERD patents, PGE₂, EP2 and EP4 are upregulated. However, the effects of PGE2 on esophageal motility remain elusive. We examined how PGE₂ regulates motility in the porcine circular smooth muscle of the lower esophageal sphincter (LES), and the circular and longitudinal smooth muscle of the esophagus body in organ bath. PGE₂ induced tonic relaxation in the LES and circular smooth muscle, but transient contraction in longitudinal smooth muscle. The relaxation of the LES and circular smooth muscle was similar in pattern and mechanism, but was much larger in the LES. The relaxation was completely blocked by a voltage-gated K⁺ channel blocker or 40 mM K⁺ depolarization, indicating the involvement of K⁺ channel. Longitudinal smooth muscle contraction was completely blocked by an L-type Ca²⁺ channel blocker, showing the contribution of Ca²⁺ movement. The involvement of the EP receptor in motility was examined with selective receptor agonists and antagonists. Activation of EP2 and EP4 caused relaxation in the LES and circular smooth muscle. Compatible with PGE₂, EP2 and EP4 agonists caused more significant relaxation in the LES than in circular smooth muscle. EP1 contributed to the longitudinal smooth muscle contraction. The different effects of PGE₂ in the LES, circular and longitudinal smooth muscle contributes to esophageal motility, their impairment might increase the amount and frequency of esophageal reflux..
18.	Keita Fukaura, Yoichiro Iboshi, Haruei Ogino, Eikichi Ihara, Kazuhiko Nakamura, Yuichiro Nishihara, Kei Nishioka, Takatoshi Chinen, Tsutomu Iwasa, Akira Aso, Ayako Goto, Kazuhiro Haraguchi, Hirotada Akiho, Naohiko Harada, Yoshihiro Ogawa, Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients With Quiescent Ulcerative Colitis, Inflammatory bowel diseases, 10.1093/ibd/izy395, 25, 6, 1019-1027, 2019.05, BACKGROUND: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. METHODS: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. RESULTS: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). CONCLUSIONS: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care..
19.	Takashi Osoegawa, Yosuke Minoda, Eikichi Ihara, Keishi Komori, Aso Akira, Ayako Goto, Soichi Itaba, Haruei Ogino, Kazuhiko Nakamura, Naohiko Harada, Kosuke Makihara, Shinichi Tsuruta, Hidetaka Yamamoto, Yoshihiro Ogawa, Mucosal incision-assisted biopsy versus endoscopic ultrasound-guided fine-needle aspiration with a rapid on-site evaluation for gastric subepithelial lesions A randomized cross-over study, Digestive Endoscopy, 10.1111/den.13367, 31, 4, 413-421, 2019.01, Objectives: This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. Methods: This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. Results: A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3% vs 70.8%, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). Conclusions: The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern..
20.	Yosuke Minoda, Haruei Ogino, Takatoshi Chinen, Eikichi Ihara, Kazuhiro Haraguchi, Hirotada Akiho, Nobuyoshi Takizawa, Akira Aso, Yosuke Tomita, Mitsuru Esaki, Keishi Komori, Yoshihiro Otsuka, Tsutomu Iwasa, Yoshihiro Ogawa, Objective validity of the Japan Narrow-Band Imaging Expert Team classification system for the differential diagnosis of colorectal polyps, Digestive Endoscopy, 10.1111/den.13393, 31, 5, 544-551, 2019.01, Background and Aim: The Japan Narrow-Band Imaging (NBI) Expert Team (JNET) classification is a recently proposed NBI magnifying endoscopy-based classification system for colorectal tumors. Although the usefulness of this system has been reported by JNET experts, its objective validity remains unclear. We tested its validity and usefulness for the diagnosis of colorectal polyps by including colonoscopy experts and non-experts as test participants. Methods: Forty NBI images of polyps of various JNET types were shown to 22 doctors (11 experts and 11 non-gastrointestinal [GI] trainees) who had not examined the patients. The doctors diagnosed the polyps based solely on the surface and vessel patterns in the magnified images and the JNET classification system. Concordance rates of their diagnoses with the pathological findings of the polyps were determined, and the results for experts and non-GI trainees were compared. Results: Both for colonoscopy experts and non-GI trainees, the JNET classification system was particularly useful for classifying polyps as benign or malignant. Although the accuracy rates for classifying polyps into each JNET type varied among colonoscopy experts, those who were familiar with the JNET classification system were able to diagnose polyps with approximately 90% accuracy. Common mistakes were attributable to misunderstandings of the wording in the JNET classification chart and lack of proper training. Conclusion: The JNET classification system is a practical approach for the diagnosis of colorectal polyps. Training is required even for experienced colonoscopists to adopt the system properly. Common pitfalls must be shared among colonoscopists to improve the accuracy of the diagnosis..
21.	Keishi Komori, Eikichi Ihara, Yosuke Minoda, Haruei Ogino, Taisuke Sasaki, Minako Fujiwara, Yoshinao Oda, Yoshihiro Ogawa, The Altered Mucosal Barrier Function in the Duodenum Plays a Role in the Pathogenesis of Functional Dyspepsia, Digestive Diseases and Sciences, 10.1007/s10620-019-5470-8, 64, 11, 3228-3239, 2019.01, Background: An altered gastrointestinal barrier function is reportedly associated with the pathogenesis of functional dyspepsia (FD); however, the pathogenesis of FD has not yet been fully elucidated. Aims: The objective of the present study was to determine whether the mucosal barrier function is impaired in patients with FD and to investigate the mechanisms underlying FD. Methods: The present study included patients with FD (FD group, n = 24), non-FD patients with abdominal symptoms (symptomatic control group, n = 14), and patients with no abdominal symptoms (asymptomatic control group, n = 20). The groups were compared regarding the mucosal electrical impedance (MI) values of the stomach and duodenum, which were measured using a tissue conductance meter during esophagogastroduodenoscopy. Results: There were no significant differences between the three groups in the MI of the stomach. In contrast, the duodenal MI of the FD group (17.8 ± 4.3 Ω) was significantly lower than those of the symptomatic control group (27.2 ± 6.4 Ω, p
22.	Yasuyo Hayashi, Mitsuru Esaki, Sho Suzuki, Eikichi Ihara, Azusa Yokoyama, Seiichiro Sakisaka, Taizo Hosokawa, Yoshimasa Tanaka, Takahiro Mizutani, Shinichi Tsuruta, Aya Iwao, Shun Yamakawa, Akira Irie, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Hirotada Akiho, Yoshihiro Ogawa, Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms, World Journal of Gastrointestinal Oncology, 10.4251/wjgo.v10.i12.487, 10, 12, 487-495, 2018.12, AIM To compare the outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms using Clutch Cutter (ESD-C) or other knives (ESD-O). METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer (scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding. RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C (median; 49 min) than for ESD-O (median; 88.5 min) (P
23.	Keita Fukaura, Eikichi Ihara, Haruei Ogino, Yoichiro Iboshi, Kazumasa Muta, Bai Xiaopeng, Shohei Hamada, Yoshitaka Hata, tsutomu iwasa, Akira Aso, Kazuhiko Nakamura, Yoshihiro Ogawa, Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function, Digestion, 10.1159/000487708, 98, 2, 95-103, 2018.08, Background and Aim: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans. Methods: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry. Results: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0-15.8, n = 10) than in normal esophageal motility (13.3, 12.8-14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0-14.1, n = 10) and normal esophageal motility (13.3, 12.8-14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure. Conclusions: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs..
24.	Mitsuru Esaki, Sho Suzuki, Yasuyo Hayashi, Azusa Yokoyama, Shuichi Abe, Taizo Hosokawa, Shinichi Tsuruta, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Hirotada Akiho, Eikichi Ihara, Yoshihiro Ogawa, Propensity score-matching analysis to compare clinical outcomes of endoscopic submucosal dissection for early gastric cancer in the postoperative and non-operative stomachs, BMC Gastroenterology, 10.1186/s12876-018-0855-2, 18, 1, 125-125, 2018.08, Background: Endoscopic submucosal dissection (ESD) of the postoperative stomach (ESD-P) for early gastric cancer (EGC) is considered a technically difficult procedure. However, it is difficult to compare the outcomes of ESD-P and ESD of the non-operative stomach (ESD-N) because their baseline characteristics are different. Therefore, we aimed to compare the technical outcomes of ESD-P with those of ESD-N using a propensity score-matching analysis to compensate for the differences. Methods: The chart records of 1046 patients with EGC who were treated with ESD between January 2004 and July 2016 at Kitakyushu Municipal Medical Center in Japan were reviewed in this retrospective study. Multivariate analyses and propensity score-matching were performed for age, sex, lesion location, lesion size, tumor invasion, tumor size, ulcer (scar), and operator skill. The primary outcome was procedure time. Secondary outcomes were percentages of en bloc, complete, and curative resections, and percentages of adverse events, which were evaluated between the two groups. Results: Forty-one patients were in the ESD-P group and 1005 patients were in the ESD-N group. Propensity score-matching created 41 matched pairs. According to the adjusted comparisons, ESD-P required a significantly longer procedure time (85 min vs 51 min, p
25.	tsutomu iwasa, Ryu Nakadate, Shinya Onogi, Yasuharu Okamoto, Jumpei Arata, Susumu Oguri, Haruei Ogino, Eikichi Ihara, Kenoki Ouchida, Tomohiko Akahoshi, Tetsuo Ikeda, Yoshihiro Ogawa, Makoto Hashizume, A new robotic-assisted flexible endoscope with single-hand control endoscopic submucosal dissection in the ex vivo porcine stomach, Surgical Endoscopy, 10.1007/s00464-018-6188-y, 32, 7, 3386-3392, 2018.07, Background: Difficulties in endoscopic operations and therapeutic procedures seem to occur due to the complexity of operating the endoscope dial as well as difficulty in performing synchronized movements with both hands. We developed a prototype robotic-assisted flexible endoscope that can be controlled with a single hand in order to simplify the operation of the endoscope. The aim of this study was to confirm the operability of the robotic-assisted flexible endoscope (RAFE) by performing endoscopic submucosal dissection (ESD). Methods: Study 1: ESD was performed manually or with RAFE by an expert endoscopist in ex vivo porcine stomachs; six operations manually and six were performed with RAFE. The procedure time per unit circumferential length/area was calculated, and the results were statistically analyzed. Study 2: We evaluated how smoothly a non-endoscopist can move a RAFE compared to a manual endoscope by assessing the designated movement of the endoscope. Results: Study 1: En bloc resection was achieved by ESD using the RAFE. The procedure time was gradually shortened with increasing experience, and the procedure time of ESD performed with the RAFE was not significantly different from that of ESD performed with a manual endoscope. Study 2: The time for the designated movement of the endoscope was significantly shorter with a RAFE than that with a manual endoscope as for a non-endoscopist. Conclusions: The RAFE that we developed enabled an expert endoscopist to perform the ESD procedure without any problems and allowed a non-endoscopist to control the endoscope more easily and quickly than a manual endoscope. The RAFE is expected to undergo further development..
26.	Yosuke Minoda, Keishi Komori, Ryoko Naruo, tsutomu iwasa, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa, Recovery technique using a double scope to rescue failed primary endoscopic ligation, Endoscopy, 10.1055/a-0631-7760, 50, 9, E244-E245, 2018.06.
27.	Xiaopeng Bai, Eikichi Ihara, Katsuya Hirano, Yoshimasa Tanaka, Kayoko Nakano, Satomi Kita, Takahiro Iwamoto, Haruei Ogino, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura, Yoshihiro Ogawa, Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na⁺/Ca²⁺ Exchanger, CMGH, 10.1016/j.jcmgh.2017.11.004, 5, 3, 209-221, 2018.03, Background and Aims: Hydrogen sulfide (H₂S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H₂S to LES contractility was investigated by examining the effects of inhibitors of H₂S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca²⁺]_i and inversely correlated with the extracellular Na⁺ concentration ([Na⁺]_o) (25-137.4 mM), indicating involvement of an Na⁺/Ca²⁺ exchanger. The reduction in the basal [Ca²⁺]_i level by AOA was significantly augmented in the antral smooth muscle sheets of Na⁺/Ca²⁺ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H₂S regulates the LES myogenic tone by maintaining the basal [Ca²⁺]_i via Na⁺/Ca²⁺ exchanger. H₂S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia..
28.	Esaki M, Suzuki S, Hayashi Y, Yokoyama A, Abe S, Hosokawa T, Ogino H, Akiho H, Ihara E, Ogawa Y., Splash M-knife versus Flush Knife BT in the technical outcomes of endoscopic submucosal dissection for early gastric cancer: a propensity score matching analysis., BMC gastroenterology, 10.1186/s12876-018-0763-5, 18, 1, 35-35, 2018.02, Abstract BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer. A new multi-functional ESD device was developed to achieve complete ESD with a single device. A metal plate attached to its distal sheath achieves better hemostasis during the procedure than the other needle-knife device, Flush Knife BT®, that has been conventionally used. The aim of this study was to compare the technical outcomes of ESD for early gastric cancer using the Splash M-Knife® with those using the Flush Knife BT. METHODS: We conducted a retrospective review of the case records of 149 patients with early gastric cancer treated with ESD using the needle-type ESD knives between January 2012 and August 2016 at Kitakyushu Municipal Medical Center. Lesions treated with ESD using the Splash M-knife (ESD-M) and the Flush Knife BT (ESD-F) were compared. Multivariate analyses and propensity score matching were used to compensate for the differences in age, gender, underlying disease, antithrombotic drug use, lesion location, lesion position, macroscopic type, tumor size, presence of ulceration, operator level and types of electrosurgical unit used. The primary endpoint was the requirement to use hemostatic forceps in the two groups. The secondary endpoints of procedure time, en bloc and complete resection rates, and adverse events rates were evaluated for the two groups. RESULTS: There were 73 patients in the ESD-M group, and 76 patients in the ESD-F group. Propensity score matching analysis created 45 matched pairs. Adjusted comparisons between the two groups showed a significantly lower usage rate of hemostatic forceps in the ESD-M group than in the ESD-F group (6.7% vs 84.4%, p CONCLUSIONS: ESD-M appeared to reduce the usage of hemostatic forceps during ESD for early gastric cancer without increasing the adverse effects. Thus, it may contribute to a reduction in the total ESD cost..
29.	Mitsuru Esaki, Sho Suzuki, Yasuyo Hayashi, Azusa Yokoyama, Shuichi Abe, Taizo Hosokawa, Haruei Ogino, Hirotada Akiho, Eikichi Ihara, Yoshihiro Ogawa, Splash M-knife versus Flush Knife BT in the technical outcomes of endoscopic submucosal dissection for early gastric cancer A propensity score matching analysis, BMC Gastroenterology, 10.1186/s12876-018-0763-5, 18, 1, 35-35, 2018.02, Background: Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer. A new multi-functional ESD device was developed to achieve complete ESD with a single device. A metal plate attached to its distal sheath achieves better hemostasis during the procedure than the other needle-knife device, Flush Knife BT®, that has been conventionally used. The aim of this study was to compare the technical outcomes of ESD for early gastric cancer using the Splash M-Knife® with those using the Flush Knife BT. Methods: We conducted a retrospective review of the case records of 149 patients with early gastric cancer treated with ESD using the needle-type ESD knives between January 2012 and August 2016 at Kitakyushu Municipal Medical Center. Lesions treated with ESD using the Splash M-knife (ESD-M) and the Flush Knife BT (ESD-F) were compared. Multivariate analyses and propensity score matching were used to compensate for the differences in age, gender, underlying disease, antithrombotic drug use, lesion location, lesion position, macroscopic type, tumor size, presence of ulceration, operator level and types of electrosurgical unit used. The primary endpoint was the requirement to use hemostatic forceps in the two groups. The secondary endpoints of procedure time, en bloc and complete resection rates, and adverse events rates were evaluated for the two groups. Results: There were 73 patients in the ESD-M group, and 76 patients in the ESD-F group. Propensity score matching analysis created 45 matched pairs. Adjusted comparisons between the two groups showed a significantly lower usage rate of hemostatic forceps in the ESD-M group than in the ESD-F group (6.7% vs 84.4%, p
30.	Kazumasa Muta, Eikichi Ihara, Yusuke Kitagawa, Shohei Hamada, Keita Fukaura, tsutomu iwasa, Akira Aso, Haruei Ogino, Kazuhiko Nakamura, Yoshihiro Ogawa, A case of non-cardiac chest pain caused by esophageal motility disorder observed on esophageal high-resolution manometry, Journal of Japanese Society of Gastroenterology, 10.11405/nisshoshi.115.401, 115, 4, 401-408, 2018.01, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University A 20-year-old man was referred to our hospital with dysphagia and chest pain. Heart disease was denied. No abnormality was observed in upper esophagogastroduodenoscopy and fluoroscopy; furthermore, no gastric acid-related symptoms were observed on combined esophageal multichannel intraluminal impedance and pH monitoring. Esophageal high-resolution manometry (HRM) performed by liquid swallow revealed normal peristalsis; however, HRM performed while the patient was taking solid meals showed abnormal contraction, and the patient simultaneously complained of chest pain. Therefore, we diagnosed this case as non-cardiac chest pain due to esophageal motility disorder..
31.	Bai X, Ihara E, Hirano K, Tanaka Y, Nakano K, Kita S, Iwamoto T, Ogino H, Hirano M, Oda Y, Nakamura K, Ogawa Y., Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger., Cell Mol Gastroenterol Hepatol., 2017.11, Abstract BACKGROUND AND AIMS: Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. METHODS: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. RESULTS: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp-induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. CONCLUSIONS: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia.
32.	Yoichiro Iboshi, Kazuhiko Nakamura, Keita Fukaura, tsutomu iwasa, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Naohiko Harada, Makoto Nakamuta, Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis, Journal of gastroenterology, 10.1007/s00535-016-1221-1, 52, 3, 315-326, 2017.03, Background: T helper (T_h) and regulatory T (T_reg) cell-related cytokines are implicated in inflammatory bowel diseases, including ulcerative colitis (UC). While these cytokines are generally upregulated in inflamed mucosae, the key cytokine profile explaining disease severity has not been determined. Methods: The Rachmilewitz endoscopic index (REI) was assessed in 61 UC patients undergoing colonoscopy. Biopsies obtained from inflamed (REI 3–12) and noninflamed (REI 0–2) areas were analyzed by quantitative PCR for expression of mRNAs encoding cytokines and transcription factors related to Th1 (TNF-α, IFN-γ, IL-12p35, IL-12p40, and T-bet), Th2 (IL-4, IL-13, IL-33, and GATA3), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23p19, IL-6, and RORC), Th9 (IL-9, IRF4, and PU.1), and Treg (TGF-β and Foxp3). Expression patterns associated with higher REI were determined by univariate and multivariate analyses. Results: Despite general upregulation, none of these mRNAs showed univariate correlation with REI in inflamed samples. Multiple regression analysis, however, found that joint expression of IL-17A, IL-17F, IL-21, RORC, and TGF-β was significantly predictive of REI (P 2 = 0.380), with major individual contributions by IL-17A (P h/T_reg-related genes..
33.	Kazuhiko Nakamura, Eikichi Ihara, Hirotada Akiho, Kazuya Akahoshi, Naohiko Harada, Toshiaki Ochiai, Norimoto Nakamura, Haruei Ogino, tsutomu iwasa, Akira Aso, Yoichiro Iboshi, Ryoichi Takayanagi, Limited effect of rebamipide in addition to proton pump inhibitor (PPI) in the treatment of post-endoscopic submucosal dissection gastric ulcers A randomized controlled trial comparing ppi plus rebamipide combination therapy with PPI monotherapy, Gut and Liver, 10.5009/gnl15486, 10, 6, 2016.11, Background/Aims: The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods: In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results: The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions: Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435)..
34.	Hirotada Akiho, Azusa Yokoyama, Shuichi Abe, Yuichi Nakazono, Masatoshi Murakami, Yoshihiro Otsuka, Kyoko Fukawa, Mitsuru Esaki, Yusuke Niina, Haruei Ogino, Promising biological therapies for ulcerative colitis: A review of the literature., World journal of gastrointestinal pathophysiology, 10.4291/wjgp.v6.i4.219, 6, 4, 219-27, 2015.11, Ulcerative colitis (UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants (including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab (anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab (another anti-TNF-α agent), tofacitinib (a Janus kinase inhibitor), and vedolizumab and etrolizumab (integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC..
35.	Kazuhiko Nakamura, Kazuya Akahoshi, Toshiaki Ochiai, Keishi Komori, Kazuhiro Haraguchi, Munehiro Tanaka, Norimoto Nakamura, Yoshimasa Tanaka, Kana Kakigao, Haruei Ogino, Eikichi Ihara, Hirotada Akiho, Yasuaki Motomura, Teppei Kabemura, Naohiko Harada, Yoshiharu Chijiiwa, Tetsuhide Ito, Ryoichi Takayanagi, Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy, Gut and Liver, 10.5009/gnl.2012.6.4.423, 6, 4, 423-426, 2012.10, Background/Aims: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. Results: The patients in the AT group were significantly older than those in the C group (p
36.	tsutomu iwasa, Haruei Ogino, Kazuhiko Nakamura, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Feeding administration of daikenchuto suppresses colitis induced by naive CD4⁺ T cell transfer into SCID mice, Digestive Diseases and Sciences, 10.1007/s10620-012-2218-0, 57, 10, 2571-2579, 2012.10, Background and Aims Daikenchuto, a traditional Japanese herbal medicine, suppresses bacterial translocation by improvement of gastrointestinal motility and blood flow. As Daikenchuto reportedly reduces gastrointestinal inflammatory activity by these mechanisms, we analyzed whether Daikenchuto suppresses experimental colitis and reduces inflammatory cytokine expression in a mouse model. Methods Colitis was induced by transfer of naive CD4⁺ T cells of BALB/c mice into SCID mice, and mice were given either control or 2.7 % Daikenchuto-containing feed. We investigated body weight, clinical symptoms, histological changes, and Th1- and Th17-cytokine expression. Cytokine mRNA expression was analyzed using real-time RT-PCR. The ratio of IL-17+ and IFN-c+ CD4⁺ T cells were analyzed by flow cytometry. Results Daikenchuto delayed the development of colitis and significantly reduced the histological inflammation scores. Analyses of cytokine mRNA revealed that Th17 cytokines were significantly decreased in colons of mice that received Daikenchuto. Absolute numbers of IL-17+ or IFN-c+ CD4⁺ T cells per colon were less in mice receiving Daikenchuto than in mice that received control feed, as both groups received naive CD4⁺ T cells to induce colitis. Conclusions We demonstrated that feeding administration of Daikenchuto suppresses colitis induced by naive CD4⁺ T cell transfer into SCID mice. Daikenchuto may show clinical benefit in the treatment of human inflammatory bowel disease and further studies are warranted..
37.	Haruei Ogino, Kazuhiko Nakamura, tsutomu iwasa, Eikichi Ihara, Hirotada Akiho, Yasuaki Motomura, Kazuya Akahoshi, Hisato Igarashi, Masaki Kato, Kazuhiro Kotoh, Tetsuhide Ito, Ryoichi Takayanagi, Regulatory T cells expanded by rapamycin in vitro suppress colitis in an experimental mouse model, Journal of Gastroenterology, 10.1007/s00535-011-0502-y, 47, 4, 366-376, 2012.04, Background: To provide rapid immunosuppression without side effects, we analyzed whether rapamycin alone, and regulatory T cells (Tregs) expanded ex vivo by rapamycin, suppressed colitis in a mouse model. Methods: Severe combined immunodeficiency (SCID) mice reconstituted with naive CD4⁺ T cells were treated with or without intraperitoneal rapamycin. Body weight was evaluated. CD4⁺ T cells were cultured inthe presence of rapamycin for three 7-day rounds of stimulation. The ratio of Tregs to CD4⁺T cells was analyzed by flow cytometry. NaiveCD4⁺T cells were transferred into SCID mice with CD4⁺ T cells expanded in the presence or absence of rapamycin. Clinical symptoms of colitis, histological changes, and cytokine expression were investigated. Results: Systemic rapamycin partially prevented the development of colonic inflammation in a transfer model of colitis, but decreased body weight in control mice. With rapamycin, stimulated CD4 ⁺T cells expanded eightfold in 3 weeks in vitro, and the proportion of Tregs increased to about 40%. Without rapamycin, CD4⁺T cells expanded 20-fold in 3 weeks, but the proportion of Tregs remained at about 15%. CD4⁺ T cells expanded with rapamycin prevented the development of colitis in a naïve CD4⁺ T-cell transfer model, in association with the down regulation of Th1 and Th17 responses. Conclusions: We demonstrated, for the first time, that CD4⁺ T cells expanded with rapamycin in vitro suppressed colitis. Therefore, rapamycin-expanded Treg transfer therapy is expected to be efficacious for inflammatory bowel disease..
38.	Kazuhiko Nakamura, Tetsuhide Ito, Kazuhiro Kotoh, Eikichi Ihara, Haruei Ogino, Tsutomu Iwasa, Yoshimasa Tanaka, Yoichiro Iboshi, Ryoichi Takayanagi, Hepatopancreatobiliary manifestations of inflammatory bowel disease, Clinical Journal of Gastroenterology, 10.1007/s12328-011-0282-1, 5, 1, 1-8, 2012.02, Inflammatory bowel disease (IBD) is frequently associated with extraintestinal manifestations such as hepatopancreatobiliary manifestations (HPBMs), which include primary sclerosing cholangitis (PSC), pancreatitis, and cholelithiasis. PSC is correlated with IBD, particularly ulcerative colitis (UC); 70-80% of PSC patients in Western countries and 20-30% in Japan have comorbid UC. Therefore, patients diagnosed with PSC should be screened for UC by total colonoscopy. While symptoms of PSC-associated UC are usually milder than PSC-negative UC, these patients have a higher risk of colorectal cancer, particularly in the proximal colon. Therefore, regular colonoscopy surveillance is required regardless of UC symptoms. Administration of 5-aminosalicylic acid or ursodeoxycholic acid may prevent colorectal cancer and cholangiocarcinoma. While PSC is diagnosed by diffuse multifocal strictures on cholangiography, it must be carefully differentiated from immunoglobulin G4 (IgG4)-associated cholangitis, which shows a similar cholangiogram but requires different treatment. When PSC is suspected despite a normal cholangiogram, the patient may have small-duct PSC, which requires a liver biopsy. IBD patients have a high incidence of acute and chronic pancreatitis. Most cases are induced by cholelithiasis or medication, although some patients may have autoimmune pancreatitis (AIP), most commonly type 2 without elevation of serum IgG4. AIP should be accurately identified based on characteristic image findings, because AIP responds well to corticosteroids. Crohn's disease is frequently associated with gallstones, and several risk factors are indicated. HPBMs may influence the management of IBD, therefore, accurate diagnosis and an appropriate therapeutic strategy are important, as treatment depends upon the type of HPBM..
39.	Kenji Kanayama, Kazuhiko Nakamura, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Th1 responses are more susceptible to infliximab-mediated immunosuppression than Th17 responses, Digestive Diseases and Sciences, 10.1007/s10620-011-1780-1, 56, 12, 3525-3533, 2011.12, Background Treatment with infliximab, a chimeric antitumor necrosis factor (TNF)-α antibody, is highly efficient in patients with inflammatory bowel disease (IBD). It neutralizes soluble TNF-α and induces the apoptosis of transmembrane TNF-α-positive macrophages and T cells in the gut. Recently, T helper (Th)17, as well as Th1, responses have been implicated in the pathogenesis of IBD. Aims To clarify the effects of infliximab on Th1 and Th17 responses in vitro. Methods Naive CD4 ⁺ T cells isolated from the peripheral blood of healthy volunteers were stimulated under Th1- or Th17-inducing conditions in the presence of 10 μg/ml of infliximab or control immunoglobulin (Ig)G1. The concentrations of interferon (IFN)-c, interleukin (IL)-17, and TNF-α in the culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Th1 and Th17 cells were immunostained with infliximab or control IgG1 and transmembrane TNF-α-positive cells were analyzed by flow cytometry. Annexin V staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays were conducted in order to analyze the percentage of apoptotic cells. Results Both Th1 and Th17 cells expressed soluble and transmembrane TNF-α abundantly. Although infliximab suppressed IFN-γ secretion by Th1 cells and IL-17 secretion by Th17 cells, the level of the former was more profound than the latter. Infliximab increased annexin V- and TUNEL-positive apoptotic cells under Th1-inducing conditions, but not under Th17-inducing conditions. Conclusions Infliximab suppressed Th1 and Th17 differentiation in vitro; however, IFN-γ production by Th1 cells was more profoundly suppressed than IL-17 secretion by Th17 cells. Th1 responses were more susceptible to infliximab-mediated apoptosis than Th17 responses. Our results clarify a new mechanism of action of infliximab..
40.	Soichi Itaba, Yorinobu Sumida, Akira Aso, Yoichiro Iboshi, Tsutomu Iwasa, Haruei Ogino, Hisato Igarashi, Hirotada Akiho, Kazuhiko Nakamura, Tetsuhide Ito, Ryoichi Takayanagi, Endoscopic ultrasound-guided transmural drainage of inflammatory peripancreatic fluid collections with a wire-guided triple-lumen needle knife, Digestive Endoscopy, 10.1111/j.1443-1661.2010.01089.x, 23, 3, 269, 2011.07.
41.	Haruei Ogino, Kazuhiko Nakamura, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, CD4+CD25+ regulatory T cells suppress Th17-responses in an experimental colitis model, Digestive Diseases and Sciences, 10.1007/s10620-010-1286-2, 56, 2, 376-386, 2011.02, Background: After the recent discovery of Th17 cells, it was proposed that Th17 responses are involved in the pathogenesis of inflammatory bowel diseases (IBD). CD4⁺CD25⁺ regulatory T cells (Treg) are considered to be an attractive tool for the treatment of IBD. Here, we investigated whether Treg are capable of suppressing Th17-mediated colitis. Methods: Naive CD4 ⁺ T cells were transferred into SCID mice with or without Treg. In some experiments, Treg were transferred into recipient mice with established colitis. Mice treated with Treg were injected with an anti-transforming growth factor (TGF)-β mAb or control IgG. Clinical symptoms of colitis, histological changes and cytokine expressions were investigated. Results: SCID mice transferred with naive CD4⁺ T cells developed chronic colitis with significant increases in Th1 and Th17 cytokine expressions in the colon. When Treg were co-transferred with naive CD4⁺ T cells, development of colitis was prevented, and Th17 cytokine expressions were markedly reduced. Similarly, when Treg were transferred into mice with established colitis, the colitis was significantly ameliorated in association with dramatic reductions in Th17 cytokine expressions. Injection of anti-TGF-β mAb abolished the Treg-mediated suppression with significant elevations in Th17 cytokine productions. Conclusion: This adoptive transfer model of colitis was associated with augmented Th1 and Th17 responses, and Treg were capable of suppressing colonic inflammation by downregulating Th17 responses as well as Th1 responses via TGF-β. Consequently, Treg transfer therapy is expected to be efficacious for IBD even if Th17 is involved in the pathogenesis..
42.	Soichi Itaba, Yoichiro Iboshi, Kazuhiko Nakamura, Haruei Ogino, Yorinobu Sumida, Akira Aso, Shigetaka Yoshinaga, Hirotada Akiho, Hisato Igarashi, Masaki Kato, Kazuhiro Kotoh, Tetsuhide Ito, Ryoichi Takayanagi, Low-frequency of bacteremia after endoscopic submucosal dissection of the stomach., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/j.1443-1661.2010.01066.x, 23, 1, 69-72, 2011.01, Mainstream therapy for early gastric cancer in Japan has now shifted from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection (ESD). Although bacteremia is reported as being infrequent and transient in gastric EMR, there are no reports of it being investigated in gastric ESD. This study aimed to determine the frequency of bacteremia in gastric ESD. A prospective study, in 46 consecutive patients who underwent gastric ESD, investigated the frequency of bacteremia before and after the procedure. Results: The median time for the total ESD procedure was 105min (range 30-400). The median volume of the submucosal injection was 80ml (range 20-260). The mean size of the resected specimen was 40±9.7mm. Blood cultures obtained before ESD were positive in 4.4% (2/45) of cases. Bacillus subtilis and Bacillus spp. were the isolated microorganisms. Blood cultures obtained 10min after ESD were positive in 4.3% (2/46) of cases; with the same microorganisms being isolated. Blood cultures obtained 3h after ESD were all negative. No signs of sepsis were seen in the two patients with a positive blood culture 10min after ESD. The frequency of bacteremia after gastric ESD was low and transient. ESD for gastric lesions is thought to have a low risk of infectious complications; therefore, prophylactic administration of antibiotics may not be warranted..
43.	T. Iwasa, K. Nakamura, Haruei Ogino, Y. Iboshi, A. Aso, Eikichi Ihara, R. Takayanagi, Reply to Hagiwara, Endoscopy, 10.1055/s-0030-1256699, 43, 10, 2011.01.
44.	T. Iwasa, K. Nakamura, Haruei Ogino, S. Itaba, H. Akiho, R. Okamoto, Y. Iboshi, A. Aso, H. Murao, K. Kanayama, T. Ito, R. Takayanagi, Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis, Endoscopy, 10.1055/s-0030-1255931, 43, 1, 70-72, 2011, Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers..
45.	Haruei Ogino, Tadashi Misawa, Toshifumi Nasu, Yuuji Ihara, Shigeru Kubo, Yojiro Sadamoto, Naohiko Harada, Kazuhiko Nakamura, A case of advanced gastric cancer effectively treated by TS-1 for 4 years, Gan to kagaku ryoho. Cancer & chemotherapy, 32, 6, 833-836, 2005.01, The patient was a 66-year-old man who had advanced gastric cancer with metastasis to liver and lymph nodes. He received daily oral administration of 100 mg of TS-1 for 28 days followed by 14 days rest as one treatment course. After 2 coures, regression of the primary lesion and reduction in size of the liver and lymph metastases were observed..
46.	Haruei Ogino, Shigeru Kubo, Tadashi Misawa, Toshifumi Nasu, Yuuji Ihara, Yojiro Sasamoto, Naohiko Harada, A case of the passage of a stripped colonic mucosa, Gastroenterological Endoscopy, 47, 1, 22-27, 2005.01, A 77 year old woman was admitted to our hospital with anal bleeding. Colonoscopy revealed the polypoid mucosa in the sigmoid colon. Contrast medium enema revealed the flapping stripped mucosa easily pushed back to the descending colon by air pressure with diffuse circular ulceration of lower descending colon. The patient had taken warfarin potassium^R for the anticoagulation therapy until the onset. The medication of warfarin was stopped and the conservative treatment with total parenteral nutrition was performed. Because healing tendency was confirmed by colonoscopy, anticoagulation therapy was started again. However the medication caused recurrent anal bleeding ten days later. So anticoagulation therapy with warfarin potassium was substituted for the antiplatelet therapy with aspirin. After 3 months, the ulcer was healed over with little stenosis. The passage of a stripped colonic mucosa have been rarely reported. In our case, this ulceration seemed to be caused not by ischemic colitis but by mucosal dissection due to submucosal hematoma, because colonoscopy revealed discreat regular margined ulcer without inflammation on the anal side of the ulcer lesion. Therefore, the passage of a colonic mucosa might have occurred from submucosal hematoma due to bleeding tendency by warfarin potassium..
47.	T. Mizutani, H. Akiho, W. I. Khan, H. Murao, Haruei Ogino, K. Kanayama, K. Nakamura, R. Takayanagi, Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy, Neurogastroenterology and Motility, 10.1111/j.1365-2982.2009.01396.x, 22, 2, 2010.02, Background Inflammatory bowel disease (IBD) patients in remission often experience irritable bowel syndrome (IBS)-like symptoms. We investigated the mechanism for intestinal muscle hypercontractility seen in T-cell-induced enteropathy in recovery phase. Methods BALB/c mice were treated with an anti-CD3 antibody (100 μg per mouse) and euthanized at varying days post-treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF-α) and serotonin (5-HT)-expressing enterochromaffin cell numbers in the small intestine. The role of 5-HT in anti-CD3 antibody-induced intestinal muscle function in recovery phase was assessed by inhibiting 5-HT synthesis using 4-chloro-DL-phenylalanine (PCPA). Key Results Small intestinal tissue damage was observed from 24 h after the anti-CD3 antibody injection, but had resolved by day 5. Carbachol-induced smooth muscle cell contractility was significantly increased from 4 h after injection, and this muscle hypercontractility was evident in recovery phase (at day 7). Th2 cytokines (IL-4, IL-13) were significantly increased from 4 h to day 7. 5-HT-expressing cells in the intestine were increased from day 1 to day 7. The 5-HT synthesis inhibitor PCPA decreased the anti-CD3 antibody-induced muscle hypercontractility in recovery phase. Conclusions & Inferences Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5-HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase..
48.	N. Higuchi, Y. Sumida, K. Nakamura, S. Itaba, S. Yoshinaga, T. Mizutani, K. Honda, K. Taki, H. Murao, Haruei Ogino, K. Kanayama, H. Akiho, A. Goto, Y. Segawa, T. Yao, R. Takayanagi, Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas A case series, Endoscopy, 10.1055/s-0028-1119467, 41, 2, 175-178, 2009.02, In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and ¹⁸F- fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and ¹⁸F-FDG- PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and ¹⁸F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma..
49.	Haruei Ogino, Toshiaki Ochiai, Norimoto Nakamura, Daisuke Yoshimura, Teppei Kabemura, Tetsuya Kusumoto, Hiroshi Matsuura, Akihiko Nakashima, Kuniomi Honda, Kazuhiko Nakamura, Duplication cyst of the small intestine found by double-balloon endoscopy A case report, World Journal of Gastroenterology, 10.3748/wjg.14.3924, 14, 24, 3924-3926, 2008.10, A 35-year-old man was admitted due to bloody stool and anemia. The bleeding source could not be detected by esophagogastroduodenoscopy or colonoscopy. Double balloon endoscopy (DBE) revealed a diverticulum-like hole in which coagula stuck in the ileum at 1 meter on the oral side from the ileocecal valve. The adjacent mucosa just to the oral side of the hole was elevated like a submucosal tumor. The lesion was considered the source of bleeding and removed surgically. It was determined to be a cyst with an ileal structure on the mesenteric aspect accompanying gastric mucosa. The diagnosis was a duplication cyst of the ileum, which is a rare entity that can cause gastrointestinal bleeding. In the present case, DBE was used to find the hemorrhagic duplication cyst in the ileum..
50.	Masahiro Matsumoto, Rie Yoshimura, Hirotada Akiho, Naomi Higuchi, Kunihisa Kobayashi, Noriaki Matsui, Kentaro Taki, Hiroyuki Murao, Haruei Ogino, Kenji Kanayama, Yorinobu Sumida, Takahiro Mizutani, Kuniomi Honda, Shigetaka Yoshinaga, Soichi Itaba, Hiromi Muta, Naohiko Harada, Kazuhiko Nakamura, Ryoichi Takayanagi, Gastric emptying in diabetic patients by the ¹³ C-octanoic acid breath test Role of insulin in gastric motility, Journal of gastroenterology, 10.1007/s00535-007-2031-2, 42, 6, 469-474, 2007.06, Background: Impairment of gastric emptying is well recognized in patients with diabetes mellitus (DM), especially long-standing insulin-dependent diabetes mellitus (IDDM). The aim of this study was to evaluate the cause of delayed gastric emptying in DM patients. Methods: In 16 controls, 16 non-insulin-dependent diabetes mellitus (NIDDM) patients and 23 IDDM patients, gastric emptying was studied using the ¹³ C octanoic acid breath test. Breath samples were taken before a test meal labeled with 100mg of ¹³ C octanoic acid, and at 15-min intervals over a 300-min period postprandially. Results: In all DM patients, the gastric emptying coefficient was lower than that in the controls (P ¹³ CO ₂ excretion compared with the controls, but IDDM patients showed more delayed gastric emptying than NIDDM patients (P ¹³ C octanoic acid breath test is useful for evaluating DM patients with delayed gastric emptying..
51.	T. Terashima, K. Hiramatsu, A. Shimatani, M. Matsuda, Haruei Ogino, Y. Satomura, Y. Noda, An esophageal ulcer mimicking advanced esophageal cancer in a patient on alendronate sodium treatment for osteoporosis., Endoscopy, 10.1055/s-2006-944671, 38 Suppl 2, 2006.01.

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