Details of the Researcher

PHOTO

Akira Imatani
Section
Graduate School of Medicine
Job title
Professor
Degree
  • 博士(医学)(東北大学)

Research History 5

  • 2012/03 - Present
    東北大学 病院 消化器内科 (兼務)

  • 2012/03 - Present
    東北大学医学系研究科 保健学専攻 教授

  • 2010/10 - 2012/02
    東北大学 病院 消化器内科 講師

  • 2008/04 - 2010/08
    東北大学 医学系研究科 消化器病態学分野 助教

  • 1994/08 - 1998/01
    米国国立衛生研究所 国立がん研究所(NIH, NCI)

Education 1

  • 東北大学 医学部

    - 1989/03

Professional Memberships 6

  • 日本消化器病学会

  • 日本癌学会

  • 日本内視鏡学会

  • 日本消化管学会

  • 日本内科学会

  • 日本消化器がん検診学会

︎Show all ︎Show first 5

Research Interests 7

  • 幹細胞

  • 胃癌

  • 食道癌

  • Helicobacter pylori

  • 発癌

  • 分化制御

  • 老化

Research Areas 2

  • Life sciences / Gastroenterology /

  • Life sciences / Tumor biology /

Papers 366

  1. TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells. International-journal Peer-reviewed

    Hai The Phung, Hiroyuki Nagashima, Shuhei Kobayashi, Naoki Asano, Tomoaki Machiyama, Tsuyoshi Sakurai, Shunichi Tayama, Atsuko Asao, Akira Imatani, Takeshi Kawabe, Yuko Okuyama, Naoto Ishii, Takanori So

    ImmunoHorizons 4 (3) 129-139 2020/03/10

    DOI: 10.4049/immunohorizons.2000007  

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    TNFR-associated factor 5 (TRAF5) is a cytosolic adaptor protein and functions as an inflammatory regulator. However, the in vivo function of TRAF5 remains unclear, and how TRAF5 controls inflammatory responses in the intestine is not well understood. In this study, we found that intestinal epithelial cells from Traf5-/- mice expressed a significantly lower level of NF-κB-regulated proinflammatory genes, such as Tnf, Il6, and Cxcl1, as early as day 3 after dextran sulfate sodium (DSS) exposure when compared with wild-type mice. The intestinal barrier integrity of DSS-treated Traf5-/- mice remained intact at this early time point, and Traf5-/- mice showed decreased body weight loss and longer colon length at later time points. Surprisingly, the protein level of TRAF2, but not TRAF3, was reduced in colon tissues of Traf5-/- mice after DSS, indicating the requirement of TRAF5 for TRAF2 protein stability in the inflamed colon. Experiments with bone marrow chimeras confirmed that TRAF5 deficiency in nonhematopoietic cells caused the attenuated colitis. Our in vitro experiments demonstrated that proinflammatory cytokines significantly promoted the degradation of TRAF2 protein in Traf5-/- nonhematopoietic cells in a proteasome-dependent manner. Collectively, our data suggest a novel regulatory function of TRAF5 in supporting the proinflammatory function of TRAF2 in nonhematopoietic cells, which may be important for acute inflammatory responses in the intestine.

  2. Sox2 induces tumorigenesis and angiogenesis of early stage esophagealsquamous cell carcinoma through secretion of Suprabasin. International-journal Peer-reviewed

    Kiichi Takahashi, Naoki Asano, Akira Imatani, Yutaka Kondo, Masashi Saito, Akio Takeuchi, Xiaoyi Jin, Masahiro Saito, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    Carcinogenesis 41 (11) 1543-1552 2020/02/14

    DOI: 10.1093/carcin/bgaa014  

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    Early stage of esophageal squamous cell carcinoma (ESCC) is known to be accompanied by angiogenesis and morphological changes of microvessels. Transcription factor Sox2 is amplified in various cancers including ESCC, but the role of Sox2 in the carcinogenesis and angiogenesis has not been determined. Hence, we aimed to investigate the role of Sox2 in the early stage of ESCC. We found that the expression of Sox2 was significantly higher in early stage ESCC tissues than that in their adjacent normal tissues. We then established Sox2-inducible normal human esophageal squamous cell line (HetSox2) to investigate the role of Sox2 in esophageal carcinogenesis and angiogenesis in vitro. Sox2 overexpression led to increased cell proliferation and spheroid formation. The culture supernatant of Sox2-overexpressing HetSox2 induced migration and sprouting of endothelial cell line HUVEC. As for the mechanism, we found that the expression of secreted protein Suprabasin was directly induced by Sox2. Suprabasin enhanced proliferation of normal human esophageal squamous cells and HUVEC when added to the culture. Moreover, Suprabasin enhanced migration and sprouting of HUVEC cells, which were observed with the culture supernatant of Sox2-oversxpressing HetSox2. This angiogenic effect of Suprabasin was abolished by inhibiting AKT phosphorylation, which suggested its dependence on AKT signaling. Finally, we showed that Suprabasin expression and the density of microvessels were significantly higher in ESCC tissues with high Sox2 expression. Our study suggested that increased Sox2 expression in esophageal squamous cells induced Suprabasin expression, and as a result initiated the carcinogenesis via increased cell proliferation and angiogenesis.

  3. Notch1 directly induced CD133 expression in human diffuse type gastric cancers. International-journal Peer-reviewed

    Hidetomo Konishi, Naoki Asano, Akira Imatani, Osamu Kimura, Yutaka Kondo, Xiaoyi Jin, Takeshi Kanno, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Tomoyuki Koike, Tooru Shimosegawa

    Oncotarget 7 (35) 56598-56607 2016/08/30

    DOI: 10.18632/oncotarget.10967  

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    CD133 is considered as a stem-like cell marker in some cancers including gastric cancers, and Notch1 signaling is known to play an important role in the maintenance and differentiation of stem-like cells. We aimed to investigate whether Notch1 signaling contributes to the carcinogenesis of gastric cancers and CD133 induction. CD133 expression was detected in 51.4% of diffuse type gastric cancers while it was not detected in intestinal type gastric cancers. Similarly, only poorly-differentiated gastric cancer cell lines expressed CD133 and activated-Notch1. Inhibiting Notch1 signaling resulted in decreased CD133 expression, side population cells, cell proliferation and anchorage independent cell growth. Chromatin immunoprecipitation suggested that this Notch1 dependent regulation of CD133 was caused by direct binding of activated-Notch1 to the RBP-Jκ binding site in the 5' promoter region of CD133 gene. In addition, knocking down RBP-Jκ reduced CD133 induction in activated-Notch1 transfected cells. These findings suggested that Notch1 signaling plays an important role in the maintenance of the cancer stem-like phenotype in diffuse type gastric cancer through an RBP-Jκ dependent pathway and that inhibiting Notch1 signaling could be an effective therapy against CD133 positive diffuse type gastric cancers.

  4. Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses. International-journal Peer-reviewed

    Naoki Asano, Akira Imatani, Tomohiro Watanabe, Jun Fushiya, Yutaka Kondo, Xiaoyi Jin, Nobuyuki Ara, Kaname Uno, Katsunori Iijima, Tomoyuki Koike, Warren Strober, Tooru Shimosegawa

    Cancer research 76 (5) 1135-45 2016/03/01

    DOI: 10.1158/0008-5472.CAN-15-2272  

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    Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori-induced expression of the intestinal epithelial-specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori-induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori-infected patients to limit their risks of accumulating precancerous gastric lesions.

  5. Gender differences in oesophageal mucosal injury in a reflux oesophagitis model of rats. International-journal Peer-reviewed

    Tomohiro Masaka, Katsunori Iijima, Hiroyuki Endo, Kiyotaka Asanuma, Nobuyuki Ara, Fumitake Ishiyama, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    Gut 62 (1) 6-14 2013/01

    DOI: 10.1136/gutjnl-2011-301389  

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    OBJECTIVE: There is a strong male predominance of oesophageal adenocarcinoma, which might be related to the higher prevalence of precursor lesions such as erosive reflux oesophagitis in men compared with women. This experiment investigated the gender difference in a reflux oesophagitis model of rats and explored the potential role of oestrogen in controlling oesophageal tissue damage. DESIGN: An acid-reflux oesophagitis model was surgically produced in male and female rats, and ascorbic acid in the diet and sodium nitrite in the drinking water were administered to half of either group to provoke luminal exogenous nitric oxide (NO) as an exacerbating agent. Seven days after the surgery, the oesophagus was excised, and the injury area, myeloperoxidase activity and pro-inflammatory cytokine levels were measured. Furthermore, 17β-oestradiol was administered to ovariectomised female rats or male rats, which then underwent reflux oesophagitis surgery. RESULTS: While there was no gender difference in oesophageal damage in the baseline model, oesophageal damage was more intensively observed in males than in females in the presence of exogenous NO administration. While oesophageal damage was increased in ovariectomised rats compared with sham ovariectomised, exacerbated oesophageal damage was attenuated by the replacement of 17β-oestradiol. In addition, exacerbated oesophageal damage in male rats was suppressed by 17β-oestradiol. CONCLUSION: This is the first study showing the prominent gender difference in the severity of oesophageal tissue damage in a gastro-oesophageal reflux disease-related animal model, highlighting the critical involvement of oestrogen in controlling gastro-oesophageal reflux disease-related oesophageal epithelial injury.

  6. Gene polymorphisms of NOD1 and interleukin-8 influence the susceptibility to erosive esophagitis in Helicobacter pylori infected Japanese population. International-journal Peer-reviewed

    Tomoyuki Oikawa, Naoki Asano, Akira Imatani, Motoki Ohyauchi, Jun Fushiya, Yutaka Kondo, Yasuhiko Abe, Tomoyuki Koike, Katsunori Iijima, Tooru Shimosegawa

    Human immunology 73 (11) 1184-9 2012/11

    DOI: 10.1016/j.humimm.2012.08.004  

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    Helicobacter pylori (H. pylori) infection generally protects patients from erosive esophagitis through reduction of acid production due to gastric mucosal atrophy. However, there are H. pylori infected patients who still have erosive esophagitis. The reason for this discrepancy remains unclear. We have previously reported that polymorphisms in IL-8 promoter region influence the susceptibility of H. pylori related diseases. On the other hand, nucleotide-binding oligomerization domain 1 (NOD1) is known to play an important role in H. pylori infection. Hence, we hypothesized polymorphisms of these two molecules in H. pylori infected patients may influence the susceptibility to erosive esophagitis. Genomic DNA was extracted from 312 H. pylori infected Japanese, consisting of 110 patients with erosive esophagitis and 202 healthy controls. ND1+32656 T/GG and IL-8-251 A/T polymorphisms were genotyped by direct sequencing. ND1+32656 GG allele and IL-8-251 T/T allele increased the risk of erosive esophagitis with odds ratio (OR) of 1.9 (95% confidence interval (CI) 1.1-3.0, p=0.013) and 1.7 (95% CI 1.1-2.8, p=0.036), respectively. Combination of these two alleles increased the risk with OR of 3.2(95% CI 1.6-6.5, p=0.001). In conclusion, ND1+32656 GG and IL-8-251 T/T allele may be associated with less reactivity to H. pylori infection, and may increase the risk of erosive esophagitis even in H. pylori infected Japanese population.

  7. The role of nitric oxide in the induction of caudal-type homeobox 2 through epidermal growth factor receptor in the development of Barrett's esophagus. International-journal Peer-reviewed

    Gen Kusaka, Kaname Uno, Katsunori Iijima, Hiroyuki Endo, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    Scandinavian journal of gastroenterology 47 (10) 1148-58 2012/10

    eISSN: 1502-7708

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    OBJECTIVE: The high concentration of nitric oxide (NO) around the gastro-esophageal junction (GEJ) might play an important role in the development of Barrett's esophagus (BE), a precursor of Barrett's adenocarcimona. Although previous studies revealed that the expression of caudal-type homeobox 2 (CDX2), an important marker of BE, might be induced through Epidermal Growth Factor Receptor (EGFR), the roles of NO in this signal transduction remain unclear. MATERIAL AND METHODS: First, we investigated the expressions of EGFR, CDX2 and nitrotyrosine by immunohistochemical study for BE and squamous epithelium of human specimens. Second, we studied the effect of peroxynitrite, peroxynitrite stimulator, SIN-1, or NO donor, NOC7, on the expression of phosphorylated EGFR and CDX2 in KYSE30, an EGFR-rich human esophageal squamous cell carcinoma cell-line. Specific inhibitors for EGFR, AG1478 and small interfering RNA for EGFR (EGFR-siRNA) were employed to elucidate the role of EGFR in the induction of CDX2. RESULTS: The immunohistochemical study revealed that the expressions of EGFR, CDX2 and nitrotyrosine in BE were stronger than those in squamous epithelium with positive correlations. Exposure to peroxynitrite, SIN-1 or NOC7 induced EGFR phosphorylation and CDX2 expression in dose- and time-dependent manners. Both EGFR phosphorylation and CDX2 induction were significantly diminished by AG 1478 and EGFR-siRNA. CONCLUSIONS: We revealed for the first time that extrinsic NO might directly induce CDX2 expression through EGFR phosphorylation. We suggested that NO had an important role in the development of BE from squamous epithelium around GEJ.

  8. Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression. International-journal Peer-reviewed

    Sho Asonuma, Akira Imatani, Naoki Asano, Tomoyuki Oikawa, Hidetomo Konishi, Katsunori Iijima, Tomoyuki Koike, Shuichi Ohara, Tooru Shimosegawa

    American journal of physiology. Gastrointestinal and liver physiology 297 (2) G312-22 2009/08

    DOI: 10.1152/ajpgi.00518.2007  

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    Helicobacter pylori is a major cause of the transdifferentiation into intestinal metaplasia that may develop gastric cancer. However, the molecular pathogenesis of this transdifferentiation is poorly understood. A SRY-related HMG box protein Sox2 is an essential transcription factor of organ development in brain, lung, and stomach. Our aim of this study was to investigate the mechanism responsible for regulation of Sox2 in host Th1-dominant response to H. pylori. Sox2 protein was immunohistochemically expressed in both human oxyntic and pyloric glands with H. pylori infection, but not in intestinal metaplasia. Western immunoblotting of gastric epithelial cell lines showed that IL-4, a Th2-related cytokine, dose dependently enhanced Sox2 expression among H. pylori infection-mediated cytokines. Small changes of Sox2 expression were observed after each treatment with IFN-gamma, IL-1beta, or TNF-alpha. IL-4-mediated Sox2 induction was suppressed by the inhibition of STAT6 activation with STAT6 RNA interference, and electrophoretic mobility shift assay indicated that activation of the Sox2 promoter by IL-4 occurred through the action of STAT6. Furthermore, H. pylori and IFN-gamma inhibited the phosphorylation of STAT6, resulting in the suppression of IL-4-mediated Sox2 expression. Immunohistochemical analyses showed significantly the suppressed STAT6 activity in H. pylori-infected human gastric mucosa. Additionally, downregulation of Sox2 by knockdown experiments led to intestinal phenotype with expressions of Cdx2 and MUC2. These results suggest that H. pylori and IFN-gamma interfere with the differentiation into oxyntic and pyloric glands by the downregulation of Sox2 on IL-4/STAT6 signaling, which may contribute to the transdifferentiation into intestinal metaplasia.

  9. The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population Peer-reviewed

    Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T

    Gut 54 (3) 330-335 2005/03/01

    Publisher: BMJ

    DOI: 10.1136/gut.2003.033050  

    ISSN: 0017-5749

  10. Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. Peer-reviewed

    Imatani A, Callahan R

    Oncogene 19 (2) 223-231 2000/01

  11. In situ analysis of tissue dynamics and p53 expression in human gastric mucosa. Peer-reviewed

    Imatani A, Sasano H, Yabuki N, Kato K, Ohara S, Asaki S, Toyota T, Nagura H

    J Pathol. 179 (1) 39-42 1996/05

  12. Prevalence and risk factors for lymph node metastasis in duodenal neuroendocrine tumors: a systematic review and meta-analysis

    Yohei Ogata, Waku Hatta, Takeshi Kanno, Yutaka Hatayama, Masahiro Saito, Xiaoyi Jin, Tomoyuki Koike, Akira Imatani, Yuhong Yuan, Atsushi Masamune

    Journal of Gastroenterology 2025/04/03

    Publisher: Springer Science and Business Media LLC

    DOI: 10.1007/s00535-025-02247-7  

    ISSN: 0944-1174

    eISSN: 1435-5922

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    Abstract Background Although the status of lymph node metastasis (LNM) is crucial in determining treatment strategy for duodenal neuroendocrine tumors (D-NETs), robust evidence for their potential LNM risk remains lacking. This systematic review aimed to summarize the prevalence and risk factors of LNM in D-NETs. Methods This systematic review of electronic databases identified eligible case–control and cohort studies for D-NET resected either endoscopically or surgically, published from 1990 to 2023. The primary outcome was the pooled prevalence of LNM in D-NETs. Secondary outcomes included the pooled prevalence of LNM according to tumor location and functionality, as well as identifying pathological risk factors for LNM. Meta-analysis was performed. Results We identified 36 studies that involved 1,396 patients with D-NETs, including 326 with LNM. The pooled prevalence of LNM in D-NETs was 22.7% (95% confidence interval [CI] 17.3–29.2%). The prevalence was high in ampullary/peri-ampullary D-NETs and functional D-NETs (46.8 and 53.3%, respectively), whereas it was low in non-functional, non-ampullary D-NETs (NAD-NETs) (9.5%). Pathological risk factors for LNM in NAD-NETs included tumor size > 10 mm (odds ratio [OR] 7.31 [95% CI 3.28–16.31]), tumor invasion into the muscularis propria or deeper (OR 7.79 [3.65–16.61]), lymphovascular invasion (OR 5.67 [2.29–14.06]), and World Health Organization grading of G2 (OR 2.47 [1.03–5.92]). Conclusion Approximately one-fourth of the patients with D-NETs had LNM. Endoscopic resection might be acceptable for non-functional NAD-NETs with diameters of 10 mm or less, but additional surgical resection with lymphadenectomy may be recommended for cases exhibiting pathological risk factors.

  13. Type 2 and type 3 gastric neuroendocrine tumors have high risk of lymph node metastasis: Systematic review and meta‐analysis

    Yohei Ogata, Waku Hatta, Takeshi Kanno, Masahiro Saito, Xiaoyi Jin, Naoki Asano, Tomoyuki Koike, Akira Imatani, Yuhong Yuan, Atsushi Masamune

    Digestive Endoscopy 2025/04

    Publisher: Wiley

    DOI: 10.1111/den.15026  

    ISSN: 0915-5635

    eISSN: 1443-1661

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    Objectives Lymph node metastasis (LNM) is crucial in determining treatment strategies for gastric neuroendocrine tumors (gNETs). While type 3 is considered more aggressive than types 1 and 2 within the clinical subtype of gNETs, the supporting data were insufficient, due to their rarity. We aimed to study the prevalence and risk factors associated with LNM in gNETs. Methods We searched electronic databases from 1990 to 2023 to identify case–control and cohort studies regarding gNETs resected either endoscopically or surgically. The primary outcome measured was the pooled prevalence of LNM in gNETs. Secondary outcomes included categorizing the prevalence of LNM by clinical subtypes and identifying pathological risk factors associated with LNM in gNETs. Results We included 28 studies, involving 1742 patients, among whom 240 had LNM (pooled prevalence rate, 11.8%; 95% confidence interval 7.6–17.9%). The pooled prevalence rates of LNM for type 1, type 2, and type 3 gNETs were 6.0%, 38.5%, and 23.2%, respectively. Type 2 (odds ratio [95% confidence interval] 11.53 [3.46–38.49]) and type 3 (6.88 [3.79–12.49]) gNETs exhibited a higher risk for LNM compared to type 1. Pathological risk factors for LNM included tumor size >10 mm (4.18 [1.91–9.17]), tumor invasion into the muscularis propria or deeper (11.21 [3.50–35.92]), grade 2/grade 3 (5.96 [2.65–13.40]), and lymphovascular invasion (34.50 [6.70–177.51]). Conclusion We demonstrated that type 2 gNETs, as well as type 3, had a high risk of LNM. Additionally, four pathological risk factors associated with LNM were identified.

  14. Which of vonoprazan alone or intravenous proton pump inhibitor followed by vonoprazan is optimal for reducing delayed bleeding in gastric endoscopic submucosal dissection? International-journal

    Hiroko Abe, Kunio Tarasawa, Waku Hatta, Naotaro Tanno, Yutaka Hatayama, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Tomoyuki Koike, Akira Imatani, Shin Hamada, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune

    Digestion 1-19 2025/03/25

    DOI: 10.1159/000545253  

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    BACKGROUND: In gastric endoscopic submucosal dissection (ESD), both vonoprazan alone and intravenous proton pump inhibitor (PPI) followed by vonoprazan have lower delayed bleeding risk than PPI alone. This study aimed to clarify an optimal acid-suppressive method in gastric ESD. METHODS: This population-based cohort study included patients who underwent gastric ESD on only vonoprazan (vonoprazan alone group) or intravenous PPI followed by vonoprazan (intravenous PPI group) using the Diagnosis Procedure Combination database in Japan between 2014 and 2021. The primary outcome was delayed bleeding. To balance the two comparison groups, propensity score matching (PSM), based on 18 variables, was performed; subsequently, to compare the bleeding outcome, logistic regression analysis was performed. RESULTS: Of 63,952 patients, 24,710 pairs were compared following PSM. The delayed bleeding risk in the vonoprazan alone group was similar to that in the intravenous PPI group (odds ratio [OR], 1.00; 95% confidence interval, 0.93-1.08; delayed bleeding rate, 5.9% vs. 5.9%). The results were consistent in some sensitivity and subgroup analyses; however, the result was modified by the status of antithrombotic agents (p for interaction = 0.029). In additional analyses, in patients with antithrombotic agent, the vonoprazan alone group had a higher delayed bleeding risk than the intravenous PPI group (OR, 1.15). CONCLUSION: Both vonoprazan alone and intravenous PPI followed by vonoprazan might be acceptable in gastric ESD when antithrombotic agents were not administered, whereas intravenous PPI followed by vonoprazan might be favorable in patients with antithrombotic agents.

  15. Optimal direct oral anticoagulant for upper gastrointestinal endoscopic submucosal dissection.

    Yoshitaka Ono, Waku Hatta, Kunio Tarasawa, Yohei Ogata, Hiroko Abe, Isao Sato, Yutaka Hatayama, Masahiro Saito, Xiaoyi Jin, Kaname Uno, Tomoyuki Koike, Akira Imatani, Shin Hamada, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune

    Journal of gastroenterology 60 (1) 66-76 2025/01

    DOI: 10.1007/s00535-024-02171-2  

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    BACKGROUND: The patients taking direct oral anticoagulants (DOACs) are at high risk for developing ischemic stroke and delayed bleeding in upper gastrointestinal endoscopic submucosal dissection (ESD). We aimed to identify the optimal DOAC based on both adverse events in upper gastrointestinal ESD. METHODS: A retrospective population-based cohort study was conducted using the Diagnosis Procedure Combination database in Japan. We included patients on a DOAC undergoing upper gastrointestinal ESD between 2012 and 2021. The primary outcomes were ischemic stroke occurring after upper gastrointestinal ESD and delayed bleeding in gastroduodenal and esophageal ESD. Inverse probability weightings were applied to balance the four DOAC groups (dabigatran, rivaroxaban, apixaban, and edoxaban), and logistic regression analyses were performed to compare the outcomes. RESULTS: We analyzed 9729 patients on a DOAC undergoing upper gastrointestinal ESD. Ischemic stroke developed after upper gastrointestinal ESD in 1.4%, 0.7%, 0.6%, and 0.8% of patients taking dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, after weighting. Rivaroxaban and apixaban showed significantly lower risk of ischemic stroke compared with dabigatran (odds ratio, 0.15 and 0.12, respectively) in standard doses. The delayed bleeding developed after gastroduodenal ESD in 7.6%, 14.6%, 19.2%, and 17.3% of patients taking each DOAC, respectively, with the lowest risk in dabigatran, followed by rivaroxaban. A similar pattern was observed in delayed bleeding in esophageal ESD (3.2%, 5.4%, 7.5%, and 5.5% in each DOAC), but with no significant results. CONCLUSIONS: Rivaroxaban might be an optimal DOAC for upper gastrointestinal ESD showing a lower risk for both ischemic stroke and delayed bleeding.

  16. 表在型Barrett食道癌の発見契機と特徴に関する検討

    小泉 薫, 齊藤 真弘, 小池 智幸, 谷地 一真, 首藤 千博, 皆瀬 ゆみ子, 畑山 裕, 尾形 洋平, 菅野 武, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器がん検診学会雑誌 62 (Suppl大会) 744-744 2024/10

    Publisher: (一社)日本消化器がん検診学会

    ISSN: 1880-7666

    eISSN: 2185-1190

  17. DKK3の発現抑制は細胞老化の回避を介して加齢に伴う胃発癌に寄与しうる(Suppression of DKK3 may contribute to aging-related gastric carcinogenesis via suppression of cellular senescence)

    齋藤 方志, 浅野 直喜, 今谷 晃, 金 笑奕, 大塚 哲也, 正宗 淳, 今谷 晃

    日本癌学会総会記事 83回 P-2030 2024/09

    Publisher: (一社)日本癌学会

    ISSN: 0546-0476

  18. A Case of Gastric Leiomyosarcoma Completely Resected by Endoscopic Submucosal Dissection after a Precise Preoperative Diagnosis.

    Kazuma Yachi, Waku Hatta, Tomoyuki Koike, Kimiko Kayada, Naotaro Tanno, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Kaname Uno, Naoki Asano, Akira Imatani, Hirofumi Watanabe, Fumiyoshi Fujishima, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 2024/08/01

    DOI: 10.2169/internalmedicine.3645-24  

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    A 68-year-old woman was diagnosed with leiomyosarcoma (LMS) based on preoperative biopsy of the gastric body. As tumor invasion confined to the submucosa with no breaking of the submucosal layer was confirmed on endoscopic ultrasonography (EUS), the patient underwent endoscopic submucosal dissection (ESD) for gastric LMS, resulting in complete tumor resection. No apparent recurrence was observed in the 2.5 years after treatment. This is an extremely rare case of gastric LMS that underwent ESD after a precise preoperative diagnosis, with no signs of recurrence after treatment. ESD may be an acceptable option for gastric LMS when EUS findings allow this treatment method.

  19. The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers. International-journal

    Waku Hatta, Tomoyuki Koike, Naoki Asano, Yutaka Hatayama, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Kaname Uno, Akira Imatani, Atsushi Masamune

    International journal of molecular sciences 25 (14) 2024/07/18

    DOI: 10.3390/ijms25147854  

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    Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

  20. 出血性ショックをきたし血管内治療を要した食道胃粘膜下血腫の1例

    皆瀬 ゆみ子, 宇野 要, 畑山 裕, 尾形 洋平, 齊藤 真弘, 金 笑奕, 菅野 武, 八田 和久, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化器内視鏡学会東北支部例会 172回 85-85 2024/07

    Publisher: 日本消化器内視鏡学会-東北支部

  21. 術前確定診断が困難であったEBV関連リンパ球浸潤胃癌の一例

    丹野 尚太郎, 八田 和久, 畑山 裕, 尾形 洋平, 齊藤 真弘, 金 笑奕, 菅野 武, 宇野 要, 小池 智幸, 今谷 晃, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 217回 91-91 2024/07

    Publisher: 日本消化器病学会-東北支部

  22. H.pylori感染状態とディスペプシアの頻度 成人胃がん検診事業データに基づく疫学的分析

    菅野 武, 鈴木 直生, 小池 智幸, 千葉 隆士, 淺沼 清孝, 加藤 勝章, 畑山 裕, 尾形 洋平, 齊藤 真弘, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本ヘリコバクター学会学術集会プログラム・抄録集 30回 110-110 2024/06

    Publisher: (一社)日本ヘリコバクター学会

  23. Similar Effect of Vonoprazan and Oral Proton Pump Inhibitors for Preventing Rebleeding in Cases of Upper Gastrointestinal Bleeding

    Hiroko Abe, Kunio Tarasawa, Waku Hatta, Tomoyuki Koike, Isao Sato, Yoshitaka Ono, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune

    Internal Medicine 63 (7) 911-918 2024/04/01

    Publisher: Japanese Society of Internal Medicine

    DOI: 10.2169/internalmedicine.2211-23  

    ISSN: 0918-2918

    eISSN: 1349-7235

  24. 一般成人におけるディスペプシアの疫学と内視鏡所見 がん検診事業のデータから

    鈴木 直生, 菅野 武, 小池 智幸, 千葉 隆士, 淺沼 清孝, 加藤 勝章, 尾形 洋平, 齊藤 真弘, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器病学会雑誌 121 (臨増総会) A350-A350 2024/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  25. Linked Color Imaging of Barrett’s Esophageal Adenocarcinoma: Effects on Visibility

    Masahiro Saito, Tomoyuki Koike, Yuki Ohara, Yohei Ogata, Takeshi Kanno, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    Gastroenterology Insights 2024/02/05

    DOI: 10.3390/gastroent15010010  

  26. ボノプラザン投与により軽快したHypercontractile esophagusの一例

    小泉 薫, 齊藤 真弘, 小池 智幸, 谷地 一真, 首藤 千博, 皆瀬 ゆみ子, 尾形 洋平, 菅野 武, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器内視鏡学会東北支部例会 171回 95-95 2024/02

    Publisher: 日本消化器内視鏡学会-東北支部

  27. 内視鏡的粘膜下層剥離術を施行した粘膜内限局リンパ球浸潤胃癌の一例

    丹野 尚太郎, 尾形 洋平, 八田 和久, 小池 智幸, 齊藤 真弘, 金 笑奕, 菅野 武, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳, 山崎 有人, 藤島 史喜

    日本消化器内視鏡学会東北支部例会 171回 97-97 2024/02

    Publisher: 日本消化器内視鏡学会-東北支部

  28. Interactive training with a novel simulation model for upper gastrointestinal endoscopic hemostasis improves trainees’ technique and confidence

    Takeshi Kanno, Yutaro Arata, Eric Greenwald, Paul Moayyedi, Suguo Suzuki, Yutaka Hatayama, Masahiro Saito, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Yutaka Kagaya, Tomoyuki Koike, Atsushi Masamune

    Endoscopy International Open 2024/01/17

    Publisher: Georg Thieme Verlag KG

    DOI: 10.1055/a-2248-5110  

    ISSN: 2364-3722

    eISSN: 2196-9736

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    Background and study aims: Endoscopic hemostasis is a life-saving procedure for gastrointestinal bleeding; however, its training is often performed on real patients and during urgent situations that put patients at risk. Reports of simulation-based training models for endoscopic hemostasis are scarce. Herein, we developed a novel simulator called “Medical Rising STAR-Ulcer type” to practice endoscopic hemostasis with hemoclips and coagulation graspers. This study aimed to evaluate the reproducibility of the clinical difficulty of this model and the effectiveness of simulation-based training for clipping hemostasis.Patients and methods: This was a prospective educational study. Fifty gastroenterology resident doctors from Japan and Canada were recruited to participate in a simulation-based training program. The primary outcome was the success rate of clipping hemostasis. We measured differences in trainees’ subjective assessment scores and evaluated the co-occurrence network based on comments after training.Results: The hemostasis success rate of the trainees significantly increased after instruction (64% vs. 86%, p<0.05). The success rate for ulcers in the upper body of the stomach (59%), a high-difficulty site, was significantly lower than that for ulcers in the antrum, even after feedback and instruction. Trainees’ self-perceived proficiency and confidence significantly improved after simulation-based training (p<0.05). Co-occurrence network analysis showed that trainees valued a structured learning approach, acknowledged the simulator’s limitations, and recognized the need for continuous skill refinement. Conclusions: Our study demonstrates the potential of our simulation-based training model as a valuable tool for improving technical skills and confidence in trainees learning to perform endoscopic hemostasis.

  29. A novel dry simulator model for learning comprehensive endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy procedures while minimizing adverse bleeding events (with Video). International-journal

    Yutaka Hatayama, Takeshi Kanno, Tetsuya Takikawa, Ryotaro Matsumoto, Yutaro Arata, Suguo Suzuki, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Shin Miura, Waku Hatta, Shin Hamada, Kaname Uno, Kiyoshi Kume, Kazuhiro Kikuta, Naoki Asano, Akira Imatani, Tomoyuki Koike, Atsushi Masamune

    Digestion 2024/01/10

    DOI: 10.1159/000536217  

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    BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) are essential skills for endoscopic cholangio-pancreatic procedures. However, these procedures have a high incidence of adverse events, and most training is currently patient-based. Herein, we aimed to develop an ERCP/EST simulator model to address the need for safer training alternatives, especially for learners with limited ERCP experience. METHODS: The model was designed to facilitate the use of actual endoscopic devices, supporting learning objectives that align with the components of the validated Bethesda ERCP Skill Assessment Tool (BESAT). BESAT focuses on skills such as papillary alignment and maintenance of duodenoscope position, gentle and efficient cannulation, controlled sphincterotomy in the correct trajectory, and guidewire manipulation. Thirty gastroenterology trainees used the simulator between May 2022 and March 2023, and their satisfaction was assessed using a visual analog scale (VAS) and pre- and post-training questionnaires. RESULTS: The novel simulator model comprises a disposable duodenal papillary portion, suitable for incision with an electrosurgical knife, alongside washable upper gastrointestinal tract and bile duct portions, designed for repeated use. The duodenal papillary portion enabled reproduction of a realistic endoscope position and the adverse bleeding events due to improper incisions. The bile duct portion allowed for the reproduction of fluoroscopic-like images, enabling learners to practice guidewire guidance and insert other devices. After training, the median VAS score reflecting the expectation for model learning significantly increased from 69.5 (interquartile range [IQR]:55.5-76.5) to 85.5 (IQR: 78.0-92.0) (P<0.01). All participants expressed their desire for repeated simulator training sessions. CONCLUSIONS: This innovative simulator serves as a practical educational tool, particularly beneficial for novices in ERCP. It facilitates hands-on practice with actual devices, enhancing procedural fluency and understanding of precise incisions to minimize the risk of bleeding complications during EST.

  30. Porphyromonas gingivalis Lipopolysaccharide Damages Mucosal Barrier to Promote Gastritis-Associated Carcinogenesis

    Masayoshi Oriuchi, Sujae Lee, Kaname Uno, Koichiro Sudo, Keisuke Kusano, Naoki Asano, Shin Hamada, Waku Hatta, Tomoyuki Koike, Akira Imatani, Atsushi Masamune

    Digestive Diseases and Sciences 69 (1) 95-111 2023/11/09

    Publisher: Springer Science and Business Media LLC

    DOI: 10.1007/s10620-023-08142-6  

    ISSN: 0163-2116

    eISSN: 1573-2568

  31. シミュレータ学習プログラムは安全なESTの達成および自覚的習熟度の向上に寄与する 前向き教育介入研究

    畑山 裕, 菅野 武, 滝川 哲也, 松本 諒太郎, 齊藤 真弘, 金 笑奕, 三浦 晋, 八田 和久, 濱田 晋, 宇野 要, 粂 潔, 菊田 和宏, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    Gastroenterological Endoscopy 65 (Suppl.2) 2026-2026 2023/10

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  32. 胃癌細胞においてNotch1細胞膜受容体の維持は細胞老化を誘導する(Restoration of the Notch 1 receptor induces cellular senescence in gastric cancer cells)

    金 笑奕, 浅野 直喜, 今谷 晃, 齋藤 方志, 正宗 淳

    日本癌学会総会記事 82回 586-586 2023/09

    Publisher: (一社)日本癌学会

    ISSN: 0546-0476

  33. TBX3の異常発現は細胞老化の回避を介して加齢に伴う胃発癌に寄与しうる(Aberrant TBX3 induction may contribute to aging-related gastric carcinogenesis via suppression of cellular senescence)

    齋藤 方志, 浅野 直喜, 今谷 晃, 金 笑奕, 正宗 淳

    日本癌学会総会記事 82回 1808-1808 2023/09

    Publisher: (一社)日本癌学会

    ISSN: 0546-0476

  34. ステロイド嚥下療法により食道運動機能障害の改善を認めた好酸球性食道炎の一例

    谷地 一真, 齊藤 真弘, 小池 智幸, 首藤 千博, 尾形 洋平, 菅野 武, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器病学会東北支部例会・日本消化器内視鏡学会東北支部例会プログラム・抄録集 215回・170回 151-151 2023/07

    Publisher: 日本消化器病学会-東北支部

  35. 肝様腺癌を伴った胃腺癌の一例

    加宅田 公子, 菅野 武, 宇野 要, 藤島 史喜, 尾形 洋平, 齊藤 真弘, 金 笑奕, 八田 和久, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化器病学会東北支部例会・日本消化器内視鏡学会東北支部例会プログラム・抄録集 215回・170回 158-158 2023/07

    Publisher: 日本消化器病学会-東北支部

  36. 検診で発見されたBarrett食道腺癌の臨床病理学的特徴

    谷地 一真, 齊藤 真弘, 小池 智幸, 菅野 武, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器がん検診学会雑誌 61 (Suppl総会) 475-475 2023/06

    Publisher: (一社)日本消化器がん検診学会

    ISSN: 1880-7666

    eISSN: 2185-1190

  37. 検診にて発見された非機能性十二指腸NETに対してEMROにて断端陰性切除となった一例

    鈴木 直生, 八田 和久, 小池 智幸, 齊藤 真弘, 金 笑奕, 菅野 武, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器がん検診学会雑誌 61 (Suppl総会) 476-476 2023/06

    Publisher: (一社)日本消化器がん検診学会

    ISSN: 1880-7666

    eISSN: 2185-1190

  38. Role of T-box transcription factor 3 in gastric cancers. International-journal

    Naoki Asano, Akira Imatani, Akio Takeuchi, Masashi Saito, Xiao-Yi Jin, Waku Hatta, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    World journal of gastrointestinal pathophysiology 14 (2) 12-20 2023/03/22

    DOI: 10.4291/wjgp.v14.i2.12  

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    The expression of T-box transcription factor 3 (TBX3) has been identified in various cancers, including gastric cancers. Its role in breast cancers and melanomas has been intensively studied, and its contribution to the progression of cancers through suppressing senescence and promoting epithelial-mesenchymal transition has been reported. Recent reports on the role of TBX3 in gastric cancers have implied its involvement in gastric carcinogenesis. Considering its pivotal role in the initiation and progression of cancers, TBX3 could be a promising therapeutic target for gastric cancers.

  39. 十二指腸血管拡張症からの難治性出血を契機に後天性血友病を診断・治療しえた1例

    阿部 寛子, 齊藤 真弘, 宇野 要, 金 笑奕, 菅野 武, 八田 和久, 浅野 直喜, 小池 智幸, 今谷 晃, 正宗 淳, 市川 聡

    日本消化器内視鏡学会東北支部例会 169回 108-108 2023/02

    Publisher: 日本消化器内視鏡学会-東北支部

  40. Excessive supragastric belchingの1例

    首藤 千博, 小池 智幸, 伊丹 英昭, 谷地 一真, 大原 祐樹, 齊藤 真弘, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 214回 75-75 2023/02

    Publisher: 日本消化器病学会-東北支部

  41. PREDICTORS OF EARLY AND LATE MORTALITY AFTER THE TREATMENT FOR EARLY GASTRIC CANCERS

    OGATA Yohei, HATTA Waku, OHARA Yuki, KOIKE Tomoyuki, ABE Hiroko, SAITO Masahiro, JIN Xiaoyi, KANNO Takeshi, UNO Kaname, ASANO Naoki, IMATANI Akira, YAMAMURA Akihiro, TANAKA Naoki, KAMEI Takashi, UNNO Michiaki, NAKAMURA Tomohiro, NAKAYA Naoki, MASAMUNE Atsushi

    GASTROENTEROLOGICAL ENDOSCOPY 65 (2) 162-172 2023

    Publisher: Japan Gastroenterological Endoscopy Society

    DOI: 10.11280/gee.65.162  

    ISSN: 0387-1207

    eISSN: 1884-5738

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    Objectives: Although many patients with early gastric cancers (EGCs) die of non-gastric cancer-related causes, the association of the risk categories of lymph node metastasis (LNM) with all-cause mortality remains unclear. We aimed to clarify the predictors of early and late mortality, separately. Methods: Patients with endoscopic resection or gastrectomy for EGCs between 2003 and 2017 were retrospectively enrolled. We analyzed predictors for early and late mortality, including risk categories of LNM, treatment method, and nine non-cancer-related indices, separately, with a cut-off value of 3 years. Results: We enrolled 1439 patients with a median follow-up period of 79 months. The 5-year overall survival rate was 86.8%. In the multivariate Cox analysis, the most important predictors for early and late mortality were age ≥85 years (hazard ratio [HR] 2.88 and 4.54, respectively) and Eastern Cooperative Oncology Group Performance Status ≥2 (HR 3.00 and 4.19, respectively). Charlson comorbidity index ≥2 (HR 2.76 and 1.99, respectively), American Society of Anesthesiologists Physical Status ≥3 (HR 2.35 and 1.79, respectively), and C-reactive protein/albumin ratio ≥0.028 (HR 2.30 and 1.58, respectively) were also predictors for both early and late mortality. Male (HR 2.26), intermediate- (HR 2.12)/high-risk (HR 1.85) of LNM in eCura system, and sarcopenia evaluated by the psoas muscle mass index (HR 1.70) were predictors for early mortality. Conclusion: The combined assessment of multiple predictors might help to predict early and/or late mortality in patients with EGCs. The eCura system was associated with early mortality

  42. Discrepancy between Abdominal Symptoms and Endoscopic Findings in Patients with Gastro-duodenal Eosinophilia: A Case Series

    Hideyuki Sugawara, Takeshi Kanno, Masahiro Saito, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Tomoyuki Koike, Atsushi Masamune

    Internal Medicine 2023

    Publisher: Japanese Society of Internal Medicine

    DOI: 10.2169/internalmedicine.1137-22  

    ISSN: 0918-2918

    eISSN: 1349-7235

  43. The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia. International-journal

    Tomoki Okata, Kiyotaka Asanuma, Kenichiro Nakagawa, Waku Hatta, Tomoyuki Koike, Akira Imatani, Atsushi Masamune

    International journal of molecular sciences 23 (22) 2022/11/12

    DOI: 10.3390/ijms232213947  

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    An unidentified cause of functional dyspepsia (FD) is closely associated with medication resistance. Acid suppression is a traditional and preferential method for the treatment of FD, but the efficacy of this treatment varies between epigastric pain syndrome (EPS) and postprandial syndrome (PDS): it is efficient in the former but not much in the latter. Transepithelial electrical resistance (TEER), a surrogate of mucosal barrier function, was measured under pH 3 and pH 5 acidic conditions using duodenal biopsy specimens obtained from the patients with EPS and PDS and asymptomatic healthy controls. The infiltration of inflammatory cells to the duodenal mucosa was accessed by immunohistochemical analysis. The duodenal mucosal TEER in EPS patients was decreased by exposure to the acidic solution compared to that of the controls and the PDS patients. The decrease in TEER of the EPS patients was observed even under pH 5 weak acidic condition and was correlated to degree of the epigastric pain. Moreover, the duodenal mucosa of EPS patients presented an increase in mast cells and plasma cells that expressed Ig-E. Duodenal mucosal vulnerability to acid is likely to develop EPS.

  44. Wnt Signaling and Aging of the Gastrointestinal Tract

    Naoki Asano, Akio Takeuchi, Akira Imatani, Masashi Saito, Xiaoyi Jin, Waku Hatta, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    International Journal of Molecular Sciences 23 (20) 12210-12210 2022/10/13

    Publisher: MDPI AG

    DOI: 10.3390/ijms232012210  

    eISSN: 1422-0067

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    Aging is considered a risk factor for various diseases including cancers. In this aging society, there is an urgent need to clarify the molecular mechanisms involved in aging. Wnt signaling has been shown to play a crucial role in the maintenance and differentiation of tissue stem cells, and intensive studies have elucidated its pivotal role in the aging of neural and muscle stem cells. However, until recently, such studies on the gastrointestinal tract have been limited. In this review, we discuss recent advances in the study of the role of Wnt signaling in the aging of the gastrointestinal tract and aging-related carcinogenesis.

  45. 上部消化管内視鏡治療におけるP-CABの後出血予防効果 propensity scoreを用いたデータベース解析

    阿部 寛子, 八田 和久, たら澤 邦男, 尾形 洋平, 齊藤 真弘, 菅野 武, 金 笑奕, 宇野 要, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    潰瘍 49 55-55 2022/10

    Publisher: (一社)日本潰瘍学会

    ISSN: 2189-7956

  46. 上部消化管出血患者における,ボノプラザンのPPI内服に対する再出血・死亡リスクの検討 傾向スコアを用いたDPCデータベースの解析

    阿部 寛子, 八田 和久, たら澤 邦男, 小野 義高, 尾形 洋平, 齊藤 真弘, 菅野 武, 金 笑奕, 宇野 要, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    Gastroenterological Endoscopy 64 (Suppl.2) 2069-2069 2022/10

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  47. 出血を再現した十二指腸ESTシミュレータモデルの開発

    畑山 裕, 菅野 武, 滝川 哲也, 齊藤 真弘, 金 笑奕, 三浦 晋, 八田 和久, 濱田 晋, 宇野 要, 粂 潔, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    Gastroenterological Endoscopy 64 (Suppl.2) 2138-2138 2022/10

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  48. 上部消化管内視鏡治療におけるP-CABの後出血予防効果 propensity scoreを用いたデータベース解析

    阿部 寛子, 八田 和久, たら澤 邦男, 尾形 洋平, 齊藤 真弘, 菅野 武, 金 笑奕, 宇野 要, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    潰瘍 49 55-55 2022/10

    Publisher: (一社)日本潰瘍学会

    ISSN: 2189-7956

  49. 食道発がん(腺癌、扁平上皮癌)に関する新知見と臨床へのインパクト Barrett食道腺癌の局在に関するMII-pHによる食道内逆流因子と,MNBIを用いた粘膜傷害に関する検討

    齊藤 真弘, 小池 智幸, 大原 祐樹, 谷地 一真, 首藤 千博, 伊丹 英昭, 八田 和久, 宇野 要, 今谷 晃, 正宗 淳

    日本食道学会学術集会プログラム・抄録集 76回 33-33 2022/09

    Publisher: (NPO)日本食道学会

  50. Suppressed cellular senescence mediated by T-box3 in aged gastric epithelial cells may contribute to aging-related carcinogenesis

    Akio Takeuchi, Naoki Asano, Akira Imatani, Masashi Saito, Xiaoyi Jin, Masahiro Saito, Takeshi Kanno, Waku Hatta, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    Cancer Research Communications 2022/07/14

    Publisher: American Association for Cancer Research (AACR)

    DOI: 10.1158/2767-9764.crc-22-0084  

    eISSN: 2767-9764

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    Abstract Aging is a risk factor for cancers in various organs. Recent advances in the organoid culturing system have made it viable to investigate the influence of aging utilizing these mini organs. In this study, we aimed to examine the implications of aging for gastric carcinogenesis. Gastric organoids established from aged mice grew larger, proliferated vigorously, and survived longer than that from young mice. Since Wnt/b-catenin signaling was intensified in the aged organoids and since removal of Wnt-related factors diminished their proliferation, we investigated for Wnt target gene that contributed to enhanced proliferation and discovered that the aged organoids expressed the transcription factor T-box3 (Tbx3), which has been reported to suppress cellular senescence. Indeed, cellular senescence was suppressed in the aged organoids, and this resulted from enhanced G2/M transition. As for the mechanism involved in the intensified Wnt/b-catenin signaling, we identified that Dickkopf3 (Dkk3) expression was reduced in the aged organoids due to methylation of the Dkk3 gene. Finally, the expression of TBX3 was enhanced in human atrophic gastritis and even more enhanced in human gastric cancers. In addition, its expression correlated positively with patients' age. These results indicated that the emergence of anti-senescent property in aged gastric organoids due to enhanced Tbx3 expression led to accelerated cellular proliferation and organoid formation. Since the enhanced Tbx3 expression seen in aged gastric organoids was also observed in human gastric cancer tissues, this Dkk3-Wnt-Tbx3 pathway may be involved in aging-related gastric carcinogenesis.

  51. A Case of Gastric Cancer With a Rare Spreading Pattern Into the Submucosal Layer

    Yutaka Hatayama, Takeshi Kanno, Masahiro Saito, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Tomoyuki Koike, Atsushi Masamune

    Journal of the Canadian Association of Gastroenterology 6 (4) 135-136 2022/04/08

    Publisher: Oxford University Press (OUP)

    DOI: 10.1093/jcag/gwac012  

    ISSN: 2515-2084

    eISSN: 2515-2092

  52. Recent approach for preventing complications in upper gastrointestinal endoscopic submucosal dissection

    Waku Hatta, Tomoyuki Koike, Hiroko Abe, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    DEN Open 2 (1) 2022/04

    Publisher: Wiley

    DOI: 10.1002/deo2.60  

    ISSN: 2692-4609

    eISSN: 2692-4609

  53. Parietal Cell Dysfunction: A Rare Cause of Gastric Neuroendocrine Neoplasm with Achlorhydria and Extreme Hypergastrinemia.

    Yasuaki Abe, Waku Hatta, Sho Asonuma, Tomoyuki Koike, Hiroko Abe, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Hironobu Sasano, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 61 (16) 2441-2448 2022/02/01

    DOI: 10.2169/internalmedicine.8253-21  

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    A 69-year-old woman with multiple neuroendocrine neoplasms (NENs) was referred to our hospital. Although she had extreme hypergastrinemia (11,675 pg/mL), no findings that indicated types I to III gastric NENs were found. Although gastric corpus atrophy was suspected on conventional white-light imaging, findings on magnifying endoscopy with narrow-band imaging indicated no severe atrophy. A biopsy from the background fundic gland mucosa revealed no atrophic changes, parietal cells with vacuolated cytoplasm and negative findings for H+K+-ATPase [please check this carefully]. Thus, this case was diagnosed as multiple NENs with parietal cell dysfunction. Neither progression nor metastasis has been confirmed during two-year follow-up.

  54. Decreased Expression of NRF2 Target Genes after Alcohol Exposure in the Background Esophageal Mucosa of Patients with Esophageal Squamous Cell Carcinoma

    Shusuke Toda, Waku Hatta, Kiyotaka Asanuma, Naoki Asano, Yoshitaka Ono, Hiroko Abe, Yohei Ogata, Masahiro Saito, Takeshi Kanno, Xiaoyi Jin, Kaname Uno, Tomoyuki Koike, Akira Imatani, Shin Hamada, Tomohiro Nakamura, Naoki Nakaya, Atsushi Masamune

    The Tohoku Journal of Experimental Medicine 258 (3) 195-206 2022

    Publisher: Tohoku University Medical Press

    DOI: 10.1620/tjem.2022.j077  

    ISSN: 0040-8727

    eISSN: 1349-3329

  55. Is Additional Gastrectomy Required for Elderly Patients after Endoscopic Submucosal Dissection with Endoscopic Curability C-2 for Early Gastric Cancer? International-journal

    Waku Hatta, Takuji Gotoda, Tomoyuki Koike, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    Digestion 103 (1) 83-91 2022

    DOI: 10.1159/000519514  

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    BACKGROUND: With the ongoing growth of the aged population, the number of elderly patients suffering from gastric cancer has increased in Japan. Since the frequency of lymph node metastasis (LNM) in patients after endoscopic submucosal dissection (ESD) with endoscopic curability (eCura) C-2 for early gastric cancer (EGC) is relative low, the following question can be raised: "Is additional gastrectomy required for elderly patients with such criteria for ESD?" SUMMARY: For therapeutic decision-making after ESD with eCura C-2, the risk of all-cause mortality and impaired quality of life (QoL) should thus be evaluated. Risk stratification of LNM and gastric cancer-specific mortality was established by the eCura system; however, it remains unclear how much these categories and treatment selection affect all-cause mortality. The contribution of prognostic tools for predicting all-cause mortality was noted to vary across the studies of patients with EGC; thus, further studies that investigate comprehensive geriatric assessment (CGA) may be required. Regarding the QoL, studies on elderly patients remain to be lacking. Furthermore, one of the issues with CGA and QoL tools is that they are time consuming. Key Messages: Combined evaluation of risk stratification of gastric cancer-specific mortality by the eCura system and risk of nongastric cancer-related mortality and impaired QoL may be the current optimal method to decide treatment strategy after ESD with eCura C-2 for EGC among elderly patients. A large-scale prospective study that investigates CGA domains is required to identify predictors of all-cause mortality and impaired QoL, and a more easily usable tool should be developed.

  56. Nitric oxide could promote development of Barrett's esophagus by S-nitrosylation-induced inhibition of Rho-ROCK signaling in esophageal fibroblasts. International-journal

    Taku Fujiya, Kiyotaka Asanuma, Tomoyuki Koike, Tomoki Okata, Masahiro Saito, Naoki Asano, Akira Imatani, Atsushi Masamune

    American journal of physiology. Gastrointestinal and liver physiology 322 (1) G107-G116 2022/01/01

    DOI: 10.1152/ajpgi.00124.2021  

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    Barrett's esophagus arises in the process of wound healing in distal esophageal epithelium damaged by gastroesophageal reflux disease. Differentiation of fibroblast into myofibroblasts, a smooth muscle cell-like phenotype and tissue contraction are crucial processes in wound healing. No study has evaluated mechanism by which luminal esophageal nitric oxide (NO) affect Rho-associated coiled coil-forming protein kinase (Rho-ROCK) signaling pathway, a key factor of tissue contraction, in stromal fibroblasts to develop Barrett's esophagus. Using esophageal fibroblasts, we performed collagen-based cell contraction assays and evaluated influence of Rho-ROCK signaling in the exposure to acidic bile salts and NOC-9, which is an NO donor. We found that enhanced cell contraction induced by acidic bile salts was inhibited by NO, accompanied by decrease in phosphorylated myosin light chain expression and stress fiber formation. NO directly S-nitrosylated GTP-RhoA and consequently blocked Rho-ROCK signaling. Moreover, exposure to NO and Y27632, a Rho-ROCK signaling inhibitor, decreased α-SMA expression and increased bone morphogenetic protein-4 (BMP4) expression and secretion. These findings could account for the increased expression of BMP4 in the columnar epithelial cells and stromal fibroblasts in human Barrett's esophagus. NO could impair wound contraction by blocking the Rho-ROCK signaling pathway and promote the development of Barrett's esophagus.NEW & NOTEWORTHY Barrett's esophagus is the condition where esophageal epithelium damaged by gastroesophageal reflux disease (GERD) is abnormally healed via replacing of metaplastic columnar epithelium, but very few studies have conducted focusing wound healing in the development of Barrett's esophagus. Esophageal luminal nitric oxide inhibits Rho-ROCK signaling pathway in esophageal fibroblasts, which leads to delay tissue contraction, a pivotal step in proper wound healing. Moreover, this inhibition increases tissue BMP4 expression. Impaired wound healing could be related to Barrett's esophagus.

  57. Comparison of Magnifying Endoscopy with Blue Light Imaging and Narrow Band Imaging for Determining the Invasion Depth of Superficial Esophageal Squamous Cell Carcinoma by the Japanese Esophageal Society's Intrapapillary Capillary Loop Classification. International-journal

    Waku Hatta, Tomoyuki Koike, Yohei Ogata, Yutaka Kondo, Nobuyuki Ara, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    Diagnostics (Basel, Switzerland) 11 (11) 2021/10/20

    DOI: 10.3390/diagnostics11111941  

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    Blue light imaging (BLI) and narrow-band imaging (NBI) are two modalities that enable narrow-band light observation. We aimed to compare the diagnostic ability of magnifying endoscopy with BLI (ME-BLI) and NBI (ME-NBI) for determining the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by the Japanese Esophageal Society's intrapapillary capillary loop (IPCL) classification. We enrolled 81 patients between 2014 and 2018, and the still endoscopic images for diagnosing the invasion depth at the same part in ME-BLI and ME-NBI were registered. Two blinded investigators reviewed them and diagnosed the invasion depth by the IPCL classification. Subsequently, the diagnostic yields in two modalities were compared. The overall accuracies for the invasion depth by the IPCL classification in ME-BLI and ME-NBI did not differ significantly (67.9-71.6% vs. 72.8-74.1%). In the analysis based on the invasion depth, the sensitivities and positive predictive values in tumors invading the muscularis mucosa or submucosa ≤200 µm were low (23.1-30.8% and 16.7-25.0%, respectively) in both modalities. In conclusion, the diagnostic ability for determining the invasion depth of SESCC by the IPCL classification was relatively similar in ME-BLI and ME-NBI, but diagnosis by magnifying endoscopy alone might not be satisfactory.

  58. Predictors of early and late mortality after the treatment for early gastric cancers. International-journal

    Yohei Ogata, Waku Hatta, Yuki Ohara, Tomoyuki Koike, Hiroko Abe, Masahiro Saito, Xiaoyi Jin, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Akihiro Yamamura, Naoki Tanaka, Takashi Kamei, Michiaki Unno, Tomohiro Nakamura, Naoki Nakaya, Atsushi Masamune

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 34 (4) 816-825 2021/10/18

    DOI: 10.1111/den.14172  

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    OBJECTIVES: Although many patients with early gastric cancers (EGCs) die of non-gastric cancer-related causes, the association of the risk categories of lymph node metastasis (LNM) with all-cause mortality remains unclear. We aimed to clarify the predictors of early and late mortality, separately. METHODS: Patients with endoscopic resection or gastrectomy for EGCs between 2003 and 2017 were retrospectively enrolled. We analyzed predictors for early and late mortality, including risk categories of LNM, treatment method, and nine non-cancer-related indices, separately, with a cut-off value of 3 years. RESULTS: We enrolled 1439 patients with a median follow-up period of 79 months. The 5-year overall survival rate was 86.8%. In the multivariate Cox analysis, the most important predictors for early and late mortality were age ≥85 years (hazard ratio [HR] 2.88 and 4.54, respectively) and Eastern Cooperative Oncology Group Performance Status ≥2 (HR 3.00 and 4.19, respectively). Charlson comorbidity index ≥2 (HR 2.76 and 1.99, respectively), American Society of Anesthesiologists Physical Status ≥3 (HR 2.35 and 1.79, respectively), and C-reactive protein/albumin ratio ≥0.028 (HR 2.30 and 1.58, respectively) were also predictors for both early and late mortality. Male (HR 2.26), intermediate- (HR 2.12)/high-risk (HR 1.85) of LNM in eCura system, and sarcopenia evaluated by the psoas muscle mass index (HR 1.70) were predictors for early mortality. CONCLUSION: The combined assessment of multiple predictors might help to predict early and/or late mortality in patients with EGCs. The eCura system was associated with early mortality.

  59. 40年に及ぶ疫学的評価による本邦における食道胃接合部腺癌、食道腺癌の増加

    畑山 裕, 菅野 武, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 金村 政輝, 正宗 淳

    日本消化器病学会雑誌 118 (臨増大会) A738-A738 2021/10

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  60. 食道腫瘍に対する内視鏡診療の最前線 食道ESDにおけるP-CABの後出血抑制効果 propensity scoreを用いたデータベース解析

    阿部 寛子, 八田 和久, たら澤 邦男, 尾形 洋平, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    日本食道学会学術集会プログラム・抄録集 75回 10-10 2021/09

    Publisher: (NPO)日本食道学会

  61. GERDの診断・病態・治療の最新の知見 Postprandial HRIMにおける胃食道逆流の検討

    伊丹 英昭, 中川 健一郎, 齊藤 真弘, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本食道学会学術集会プログラム・抄録集 75回 15-15 2021/09

    Publisher: (NPO)日本食道学会

  62. 表在型Barrett食道腺癌に対するLCIの視認性に関する検討

    大原 祐樹, 齊藤 真弘, 小池 智幸, 阿部 寛子, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本食道学会学術集会プログラム・抄録集 75回 132-132 2021/09

    Publisher: (NPO)日本食道学会

  63. A rare case of penetration related to ischemic duodenitis after ventricular assist device implantation for dilated cardiomyopathy.

    Hiroko Abe, Kaname Uno, Naoki Tanaka, Masamichi Mizuma, Waku Hatta, Naoki Asano, Tomoyuki Koike, Akira Imatani, Michiaki Unno, Atsushi Masamune

    Clinical journal of gastroenterology 14 (4) 1186-1190 2021/08

    DOI: 10.1007/s12328-021-01346-1  

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    A 66-year-old man with a history of diabetes and dilated cardiomyopathy underwent the implantation of a ventricular assist device (VAD) at the age of 62. He suffered from epigastralgia for a month and then visited our hospital with complaints of severe epigastralgia and hematemesis. A physical examination revealed abdominal distension without rigidity. Laboratory data showed severe systemic inflammation, multiple organ failure, and disseminated intravascular coagulation. Computed tomography showed multifocal thickness of the gastroduodenal wall with surrounding panniculitis, gas in a portal vein and a perigastric vein. Emergency esophago-gastro duodenoscopy (EGD) demonstrated a large erosion in the antrum of the stomach, and penetration surrounded by circumferentially ischemic mucosa in the second and third portions of the duodenum. Based on informed consent, conservative therapy was performed, and his condition improved enabling the start of oral intake on the 37th hospital day. However, 7 days later, there was a relapse of epigastralgia after a meal. Gastrointestinal series and EGD revealed a 10-mm-long pinhole-like stricture at the site. After laparoscopic gastro-jejunal bypass surgery, he has remained in a good condition for 2 years. We demonstrated a rare case of penetration due to severe ischemic duodenitis 4 years after VAD implantation.

  64. Prevention of delayed bleeding with vonoprazan in upper gastrointestinal endoscopic treatment.

    Hiroko Abe, Waku Hatta, Yohei Ogata, Tomoyuki Koike, Masahiro Saito, Xiaoyi Jin, Kenichiro Nakagawa, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Tomohiro Nakamura, Naoki Nakaya, Kunio Tarasawa, Kenji Fujimori, Kiyohide Fushimi, Atsushi Masamune

    Journal of gastroenterology 56 (7) 640-650 2021/07

    DOI: 10.1007/s00535-021-01781-4  

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    BACKGROUND: Delayed bleeding is the major adverse event in upper gastrointestinal endoscopic treatment (UGET). We aimed to investigate the efficacy of vonoprazan, which is the novel strong antisecretory agent, to reduce the risk for delayed bleeding in comparison with proton pump inhibitors (PPIs) in UGET. METHODS: This retrospective population-based cohort study used the Diagnosis Procedure Combination database in Japan. We included patients on vonoprazan or PPI in UGET between 2014 and 2019. The primary outcome was delayed bleeding. We conducted propensity score matching to balance the comparison groups, and logistic regression analyses to compare the bleeding outcomes. RESULTS: We enrolled 124,422 patients, in which 34,822 and 89,600 were prescribed with vonoprazan and PPI, respectively. After propensity score matching, the risk for delayed bleeding was lower in vonoprazan than in PPI (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.71-0.80), consistent with sensitivity analysis results. In the subgroup analyses of seven UGET procedures, vonoprazan was significantly advantageous in esophageal endoscopic submucosal dissection (E-ESD) (OR, 0.71; 95% CI, 0.54-0.94) and gastroduodenal endoscopic submucosal dissection (GD-ESD) (OR, 0.70; 95% CI, 0.65-0.75), although correction for multiple testing of the outcome data removed the significance in E-ESD. These results were also consistent with sensitivity analysis results. In the five other procedures, no significant advantage was found. CONCLUSIONS: This nationwide study found that, compared with PPI, vonoprazan can reduce delayed bleeding with approximately 30% in GD-ESD. Vonoprazan has the possibility to become a new treatment method for preventing delayed bleeding in this procedure.

  65. A Rare Case of Localized Esophageal Amyloidosis.

    Taku Fujiya, Waku Hatta, Tomoyuki Koike, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Kenichiro Nakagawa, Takeshi Kanno, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Nagaaki Katoh, Tsuneaki Yoshinaga, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 60 (10) 1529-1532 2021/05/15

    DOI: 10.2169/internalmedicine.6321-20  

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    A 72-year-old man without any symptoms was referred to our hospital. Esophagogastroduodenoscopy revealed an elevated esophageal lesion that was covered with normal mucosa. The examination of biopsy specimens from the lesion revealed amyloid light-chain (AL) (λ) type amyloid deposits, but there were no amyloid deposits elsewhere in the gastrointestinal tract. Further examinations did not indicate systemic amyloidosis. Thus, this case was diagnosed as a localized esophageal amyloidosis. As the clinical outcome of localized amyloidosis is favorable, this case was scheduled for close follow-up. Localized amyloidosis should be considered in the differential diagnosis of esophageal submucosal tumors.

  66. 新規内視鏡シミュレーターを用いた、消化管止血術学習プログラムによる教育介入研究

    畑山 裕, 菅野 武, 齊藤 真弘, 中川 健一郎, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A329-A329 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  67. Helicobacter pylori感染による分化制御遺伝子Notch1の発現抑制を介した胃粘膜萎縮機序の解明

    金 笑奕, 浅野 直喜, 今谷 晃, 齋藤 方志, 竹内 章夫, 斉藤 真弘, 中川 健一郎, 菅野 武, 八田 和久, 宇野 要, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A330-A330 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  68. 歯周病菌リポ多糖類刺激によるピロリ菌除菌療法後の胃粘膜バリア傷害の検討

    織内 優好, 宇野 要, 李 秀載, 齊藤 真弘, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 浅野 直喜, 小池 智幸, 今谷 晃, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A332-A332 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  69. Barrett食道腺癌の周在性に関する食道内逆流因子と基線値の検討

    大原 祐樹, 齊藤 真弘, 小池 智幸, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A345-A345 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  70. 新規内視鏡シミュレーターを用いた、消化管止血術学習プログラムによる教育介入研究

    畑山 裕, 菅野 武, 齊藤 真弘, 中川 健一郎, 金 笑奕, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A329-A329 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  71. Helicobacter pylori感染による分化制御遺伝子Notch1の発現抑制を介した胃粘膜萎縮機序の解明

    金 笑奕, 浅野 直喜, 今谷 晃, 齋藤 方志, 竹内 章夫, 斉藤 真弘, 中川 健一郎, 菅野 武, 八田 和久, 宇野 要, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A330-A330 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  72. 歯周病菌リポ多糖類刺激によるピロリ菌除菌療法後の胃粘膜バリア傷害の検討

    織内 優好, 宇野 要, 李 秀載, 齊藤 真弘, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 浅野 直喜, 小池 智幸, 今谷 晃, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A332-A332 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  73. Barrett食道腺癌の周在性に関する食道内逆流因子と基線値の検討

    大原 祐樹, 齊藤 真弘, 小池 智幸, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化器病学会雑誌 118 (臨増総会) A345-A345 2021/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  74. 胃十二指腸ESDにおけるP-CABの後出血予防効果 propensity scoreを用いたデータベース解析

    阿部 寛子, 八田 和久, たら澤 邦男, 尾形 洋平, 齊藤 真弘, 菅野 武, 金 笑奕, 中川 健一郎, 宇野 要, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 210回 45-45 2021/02

    Publisher: 日本消化器病学会-東北支部

  75. 胃十二指腸ESDにおけるP-CABの後出血予防効果 propensity scoreを用いたデータベース解析

    阿部 寛子, 八田 和久, たら澤 邦男, 尾形 洋平, 齊藤 真弘, 菅野 武, 金 笑奕, 中川 健一郎, 宇野 要, 小池 智幸, 今谷 晃, 藤森 研司, 伏見 清秀, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 210回 45-45 2021/02

    Publisher: 日本消化器病学会-東北支部

  76. 【Barrett食道腺癌の内視鏡診断と治療2021】Barrett食道腺癌のsurveillance LSBEを中心に

    小池 智幸, 齊藤 真弘, 大原 祐樹, 伊丹 英昭, 外田 修裕, 竹内 章夫, 大方 智樹, 李 秀載, 中川 健一郎, 金 笑奕, 菅野 武, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    胃と腸 56 (2) 163-173 2021/02

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  77. Linked-color Imaging May Help Improve the Visibility of Superficial Barrett's Esophageal Adenocarcinoma by Increasing the Color Difference.

    Masahiro Saito, Tomoyuki Koike, Yuki Ohara, Kenichiro Nakagawa, Takeshi Kanno, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 60 (21) 3351-3358 2021

    DOI: 10.2169/internalmedicine.6674-20  

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    Objective Linked-color imaging (LCI), a new technology for image-enhanced endoscopy, emphasizes the color of the mucosa, and its practicality in the detection of early gastric and colon cancers has been reported. However, whether or not LCI is useful for the diagnosis of Barrett's adenocarcinoma (BA) has been unclear. In this study, we explored whether or not LCI enhances the color difference between a BA lesion and the surrounding mucosa. Methods Twenty-one lesions from 20 consecutive patients with superficial BA who underwent endoscopic submucosal dissection between November 2014 and September 2017 were retrospectively examined. The color differences (ΔE*) between the inside and outside of the lesion were evaluated retrospectively using white-light imaging (WLI), blue-light imaging (BLI), and LCI objectively, based on a Commission Internationale de l'Eclairage (CIE) lab color system. Furthermore, we compared the morphology, color, and circumferential location of the lesion. Results The median values of the color difference (ΔE*) in WLI and BLI were 9.1 and 5.8, respectively, and no difference was observed. In LCI, the median color difference was 17.6, which was higher than that of WLI and BLI. Regardless of the morphology, color, and circumferential location of BA lesions, the color difference was larger in LCI than in WLI. Conclusion LCI increases the color difference between the BA and the surrounding Barrett's mucosa.

  78. 好酸球性食道炎・GERD診療の最前線 当科のPPI抵抗性GERD患者におけるsupragastric belchingの占める割合に関する検討

    伊丹 英昭, 中川 健一郎, 大原 祐樹, 齊藤 真弘, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化管学会雑誌 5 (Suppl.) 202-202 2021/01

    Publisher: (一社)日本消化管学会

    ISSN: 2433-3840

  79. 逆流性食道炎に対するVonoprazanの維持療法中に出現した腺窩上皮型胃癌の1例

    齊藤 真弘, 小池 智幸, 藤島 史喜, 中川 健一郎, 管野 武, 金 笑変, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化管学会雑誌 5 (Suppl.) 285-285 2021/01

    Publisher: (一社)日本消化管学会

    ISSN: 2433-3840

  80. Predictors of Early and Late Mortality after Endoscopic Resection for Esophageal Squamous Cell Carcinoma.

    Yohei Ogata, Waku Hatta, Tomoyuki Koike, Masahiro Saito, Xiaoyi Jin, Kenichiro Nakagawa, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Tomohiro Nakamura, Naoki Nakaya, Atsushi Masamune

    The Tohoku journal of experimental medicine 253 (1) 29-39 2021/01

    DOI: 10.1620/tjem.253.29  

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    In esophageal squamous cell carcinoma (ESCC) comprising 90% of cases with esophageal cancer, endoscopic resection (ER) is recommended for patients with negligible risk of ESCC-related mortality. In fact, a main cause of death in patients underwent ER is not ESCC. We thus aimed to clarify the predictors for early and late mortality among patients underwent ER of ESCC between 2005 and 2018 at our institution. In this retrospective cohort study, we investigated the prognosis and predictors of early and late mortality with the cut-off value of 3 years. We enrolled 407 patients with a median 69 months follow-up. The 5-year overall survival and disease-specific survival, an indicator of ESCC-related mortality, were 83.4% and 98.4%, respectively. In multivariate Cox analyses, Eastern Cooperative Oncology Group performance status (ECOG-PS), consisting of six grades by a patient's level of activity, ≥ 2 was a predictor for early and late morality [hazard ratio (HR), 7.21 (P = 0.007) and 15.62 (P = 0.021), respectively]. Charlson comorbidity index (CCI), which is an index for predicting mortality by comorbid conditions, ≥ 2 was also a predictor for both mortality [HR, 2.97 (P = 0.017) and 1.90 (P = 0.019), respectively]. However, age was a predictor only for late mortality [HR, 3.08 (P = 0.010) in 80-84 years and 8.38 (P < 0.001) in ≥ 85 years]. Considering the predictive ability for early mortality, we propose that ECOG-PS and/or CCI are better indices compared with age in deciding treatment strategy after ER for ESCC.

  81. 食道胃接合部癌の治療戦略 内視鏡診断から外科治療まで(領域横断的セッション) 表在型Barrett食道腺癌の内視鏡的特徴と治療に関する検討

    齊藤 真弘, 小池 智幸, 大原 祐樹, 阿部 泰明, 中川 健一郎, 八田 和久, 淺沼 清孝, 宇野 要, 今谷 晃, 正宗 淳

    日本食道学会学術集会プログラム・抄録集 74回 41-41 2020/12

    Publisher: (NPO)日本食道学会

  82. 食道扁平上皮癌における分化制御遺伝子Sox2の発現増強による発癌・血管新生機序の解明

    高橋 貴一, 浅野 直喜, 今谷 晃, 金 笑奕, 竹内 章夫, 齋藤 方志, 齊藤 真弘, 中川 健一郎, 菅野 武, 八田 和久, 宇野 要, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 117 (臨増大会) A692-A692 2020/10

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  83. 食道扁平上皮癌における分化制御遺伝子Sox2の発現増強による発癌・血管新生機序の解明

    高橋 貴一, 浅野 直喜, 今谷 晃, 金 笑奕, 竹内 章夫, 齋藤 方志, 齊藤 真弘, 中川 健一郎, 菅野 武, 八田 和久, 宇野 要, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 117 (臨増大会) A692-A692 2020/10

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  84. Localized Gastric Amyloidosis that Displayed Morphological Changes over 10 Years of Observation. Peer-reviewed

    Yasushi Takahashi, Waku Hatta, Tomoyuki Koike, Yohei Ogata, Taku Fujiya, Masahiro Saito, Xiaoyi Jin, Kenichiro Nakagawa, Takeshi Kanno, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Nagaaki Katoh, Tsuneaki Yoshinaga, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 60 (4) 539-543 2020/09/30

    DOI: 10.2169/internalmedicine.5031-20  

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    We herein report an extremely rare case of localized gastric amyloidosis (LGA) with morphological changes during the follow-up. A 71-year-old woman who had a depressed lesion with central elevation in the gastric lower body was diagnosed with LGA. Esophagogastroduodenoscopy at 10 years after the initial examination showed that the lesion had grown and changed morphologically, exhibiting a submucosal tumor-like appearance. Since the lesion was confined to the submucosa, the patient underwent endoscopic submucosal dissection. The final pathological diagnosis was amyloid light-chain (AL)-type LGA. This case may provide useful information regarding the natural history of AL-type LGA.

  85. A Case of the Development of Foveolar-type Gastric Adenocarcinoma during Maintenance Therapy of Vonoprazan for Reflux Esophagitis. Peer-reviewed

    Masahiro Saito, Tomoyuki Koike, Yasuaki Abe, Kenichiro Nakagawa, Takeshi Kanno, Xiaoyi Jin, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 60 (3) 391-396 2020/08/29

    DOI: 10.2169/internalmedicine.5431-20  

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    We herein report the first case of foveolar-type gastric adenocarcinoma that developed after the initiation of vonoprazan (VPZ). A 51-year-old man had heartburn at the first visit and reflux esophagitis endoscopically, so he started taking VPZ. An approximately 5-mm-sized reddish polyp with a raspberry-like morphology was detected at the anterior wall of the upper body of the stomach 156 weeks after starting maintenance therapy with VPZ 10 mg/day. It was diagnosed as foveolar-type gastric adenocarcinoma based on a biopsy. Another approximately 4-mm-sized foveolar-type gastric adenocarcinoma was also detected at the posterior wall of the middle body of the stomach.

  86. Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease. International-journal Peer-reviewed

    Kazuaki Norita, Kiyotaka Asanuma, Tomoyuki Koike, Tomoki Okata, Taku Fujiya, Yasuaki Abe, Kenichiro Nakagawa, Waku Hatta, Kaname Uno, Tomohiro Nakamura, Naoki Nakaya, Naoki Asano, Akira Imatani, Tooru Shimosegawa, Atsushi Masamune

    Digestion 102 (3) 1-11 2020/08/12

    DOI: 10.1159/000508661  

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    BACKGROUND AND OBJECTIVE: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients' mucosal integrity of the proximal esophagus. METHODS: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis. RESULTS: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1β mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules. CONCLUSIONS: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.

  87. A rare case of gastric squamous-cell carcinoma metastasized from the cervix. Peer-reviewed

    Masayoshi Oriuchi, Kaname Uno, Fumiyoshi Fujishima, Akio Takeuchi, Sujae Lee, Waku Hatta, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atushi Masamune

    Clinical journal of gastroenterology 13 (6) 1062-1065 2020/07/25

    DOI: 10.1007/s12328-020-01191-8  

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    Gastric squamous-cell carcinoma (SqCC) metastasized form the cervix is rarely detected in endoscopic examination, although cervical carcinoma is the second most common in gynecologic malignancy. A 59-year-old female visited a clinic for anorexia, and an esophago-gastro-duodenoscopy (EGD) revealed multiple submucosal tumors (SMTs) of the stomach. After she was referred, an image-enhanced endoscopy enhanced multiple SMTs with white spots, whose findings were irregular micro-vascular patterns in the mucosa with irregular/absent micro-surface pattern. We took endoscopic biopsies, whose histological diagnoses were SqCC in the layer of the lamina propria under normal epithelium. Positron emission tomography-CT, CT and magnetic resonance imaging revealed an irregularly enhanced mass of the cervix, the irregularly thickening wall of the stomach and peritoneal nodules. Palliative care alone was administered based on poor condition associated with the Stage IV cervical carcinoma. In this case, endoscopic detection of gastric SqCC might provide a tip to make final diagnosis of primary site of cervical SqCC. The numbers of endoscopic examination become increasing, so further deep awareness of such patterns of metastasis in cervical cancer are required.

  88. 食道胃接合部内腔で発生する高濃度一酸化窒素は創傷治癒におけるRho-ROCK経路を阻害しBarrett食道発生を促進させる

    藤谷 拓, 淺沼 清孝, 八田 和久, 宇野 要, 浅野 直喜, 今谷 晃, 小池 智幸, 正宗 淳

    日本消化器病学会雑誌 117 (臨増総会) A228-A228 2020/07

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  89. Correction: TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells. International-journal

    Hai The Phung, Hiroyuki Nagashima, Shuhei Kobayashi, Naoki Asano, Tomoaki Machiyama, Tsuyoshi Sakurai, Shunichi Tayama, Atsuko Asao, Akira Imatani, Takeshi Kawabe, Yuko Okuyama, Naoto Ishii, Takanori So

    ImmunoHorizons 4 (4) 216-216 2020/04/23

    DOI: 10.4049/immunohorizons.2000022  

  90. The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease. International-journal Peer-reviewed

    Yasuaki Abe, Tomoyuki Koike, Masahiro Saito, Tomoki Okata, Kenichiro Nakagawa, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune

    Digestion 102 (3) 1-9 2020/02/14

    DOI: 10.1159/000506152  

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    INTRODUCTION: Weakly acidic reflux has been reported to be the major cause of symptoms in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) undergoing PPI treatment. We previously reported that reflux at pH 4-5 was the main factor that induced symptoms in such patients. The present study aimed to elucidate the symptom-ameliorating effect of vonoprazan (VPZ) by evaluating the change in the pH value of the refluxate using multichannel intraluminal impedance and pH (MII-pH) monitoring. METHODS: We retrospectively evaluated the records of MII-pH monitoring in 29 symptom index (SI) and/or symptom association probability (SAP)-positive patients with PPI-refractory NERD. After switching to VPZ 20 mg/day, we performed MII-pH monitoring again. We assessed the change in the score of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the pH value of the refluxate, and the percent times of intragastric pH <4 or <5 before and after switching. We divided the patients into the following 2 groups according to the FSSG score after switching: effective and noneffective groups. RESULTS: Among of the 29 SI/SAP-positive patients, 16 underwent switching to VPZ. Furthermore, of these 16 patients, 10 underwent MII-pH monitoring again after switching. The FSSG score decreased, the pH value of the refluxate increased, and the percent times of intragastric pH <4 or <5 reduced after switching when compared with the findings before switching. In the effective group, both the proportion of reflux at pH <4 and that of reflux at pH 4-5 decreased while taking VPZ when compared with the findings while taking double-dose PPI. In the noneffective group, the proportion of reflux at pH <4 decreased but that of reflux at pH 4-5 increased and that of reflux at pH <5 did not change overall while taking VPZ. In addition, the percent times of intragastric pH <5 values were low in the effective group. CONCLUSION: Symptom suppression appears to be inadequate in patients with persistent reflux at pH 4-5 even with VPZ 20 mg/day. Strong acid suppressive therapy with VPZ to increase the pH value of the refluxate to ≥5 is useful for symptom improvement.

  91. Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease. International-journal Peer-reviewed

    Yasuaki Abe, Tomoyuki Koike, Masahiro Saito, Tomoki Okata, Kazuaki Norita, Hiroki Kikuchi, Kenichiro Nakagawa, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Tooru Shimosegawa, Atsushi Masamune

    Digestion 101 (4) 375-381 2020

    DOI: 10.1159/000500133  

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    BACKGROUND AND OBJECTIVES: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. METHODS: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4-5, 5-6, and 6-7. RESULTS: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4-5 (19%) was much higher than in that of pH 5-6 (11%) and pH 6-7 (12%). In the reflux at pH 4-5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5-6 and pH 6-7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. CONCLUSION: Reflux at pH <5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.

  92. Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016. Peer-reviewed

    Masamune A, Kikuta K, Hamada S, Tsuji I, Takeyama Y, Shimosegawa T, Okazaki K, Collaborators. Collaborators, Kanno A, Sano T, Uchida K, Ikeura T, Fujimori N, Nakai Y, Kamisawa T, Kubota K, Motoya M, Shimizu K, Ushijima T, Fukasawa M, Naitoh I, Ueno M, Okuwaki K, Uza N, Asada M, Mukai T, Kudo Y, Uetsuki K, Mitoro A, Watanabe H, Terai S, Hayashi K, Imamura Y, Haba S, Hara K, Fujisawa T, Iwasaki E, Okumura F, Kawaji Y, Kitano M, Nishino T, Nagahama M, Hirano A, Aruga Y, Yamamoto S, Inui K, Kubota Y, Takahashi K, Sakagami J, Kobayashi T, Miraki T, Watanabe T, Sato H, Takeda Y, Satoh M, Kobashigawa K, Chiba M, Tamura T, Sawada N, Mizukami K, Sekine M, Unno J, Ishizawa T, Funayama H, Hatayama K, Miyakawa H, Sakai T, Kuwatani M, Toki M, To

    Journal of Gastroenterology 55 (4) 462-470 2019/12

    DOI: 10.1007/s00535-019-01658-7  

    ISSN: 0944-1174

    eISSN: 1435-5922

  93. Continuous liquid-suction catheter attachment for endoscope reduces volume of liquid reflux to the mouth in esophageal endoscopic submucosal dissection. International-journal Peer-reviewed

    Waku Hatta, Tomoyuki Koike, Hideki Okata, Takashi Hanzawa, Masahiro Saito, Yutaka Kondo, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Katsunori Iijima, Tomohiro Nakamura, Naoki Nakaya, Atsushi Masamune

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 31 (5) 527-534 2019/09

    DOI: 10.1111/den.13392  

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    BACKGROUND AND AIM: Pooling of liquid in the esophageal lumen can worsen the field of vision and cause liquid reflux to the mouth, which leads to aspiration pneumonia, in esophageal endoscopic submucosal dissection (ESD). We developed a continuous liquid-suction catheter attachment for the endoscope (CLCA) that has multiple tiny holes and can suction the liquid without causing mucosal injury. Thus, we aim to show the efficacy of CLCA in esophageal ESD. METHODS: This was a single-blinded, randomized controlled trial involving patients with superficial esophageal cancer. The enrolled patients were randomly assigned to the conventional ESD (C-ESD) or ESD with CLCA (CLCA-ESD) groups. Primary endpoint was volume of liquid reflux to the mouth during the ESD procedure. Secondary endpoints were incidence of aspiration pneumonia and procedure time. RESULTS: Fifty patients were enrolled in this trial. Volume of liquid reflux to the mouth was significantly lower in the CLCA-ESD group than in the C-ESD group (mean: 10 vs 73 mL, P = 0.010). Furthermore, the incidence of aspiration pneumonia on computed tomography (CT) scan between the two groups was also significantly different (4.0% vs 32.0%, P = 0.023), although no significant difference was observed through chest radiography. In addition, procedure time tended to be shorter in the CLCA-ESD group (P = 0.054). CONCLUSION: This study first showed that use of CLCA in esophageal ESD reduced the volume of liquid reflux to the mouth and contributed to decreased incidence of aspiration pneumonia on CT scan (UMIN000018167).

  94. A Primary Barrett's Adenocarcinoma with a Squamous Cell Carcinoma Component. Peer-reviewed

    Akio Takeuchi, Waku Hatta, Tomoyuki Koike, Masahiro Saito, Xiaoyi Jin, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Atsushi Masamune

    Internal medicine (Tokyo, Japan) 58 (17) 2467-2472 2019/09/01

    DOI: 10.2169/internalmedicine.2722-19  

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    The present report describes an extremely rare case of Barrett's adenocarcinoma (BAC) with a squamous cell carcinoma (SCC) component. A 55-year-old man was diagnosed with esophageal adenocarcinoma on Barrett's esophagus. The patient underwent endoscopic submucosal dissection, but the pathology revealed deep submucosal invasive, moderately differentiated tubular adenocarcinoma and focal SCC with vascular invasion. In addition, morphological transition between adenocarcinoma and SCC components was confirmed. The patient underwent additional surgery, which revealed lymph node metastasis, and then received S-1 adjuvant chemotherapy. Based on the pathological findings, the transdifferentiation process may have a role in the histogenesis of this tumor.

  95. Strong Intra-Esophageal Reflux May Contribute to the Development of Barrett's Adenocarcinoma and Affect the Localization. International-journal Peer-reviewed

    Masahiro Saito, Tomoyuki Koike, Kenichiro Nakagawa, Yasuaki Abe, Kazuaki Norita, Hiroki Kikuchi, Takeshi Kanno, Waku Hatta, Nobuyuki Ara, Kaname Uno, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Tooru Shimosegawa, Atsushi Masamune

    Digestion 101 (6) 1-9 2019/08/14

    DOI: 10.1159/000502377  

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    BACKGROUND: There has been no study that has directly measured the esophageal reflux factors in Barrett's adenocarcinoma (BA) using 24-h multichannel intraluminal impedance-pH monitoring (24-h MII-pH). We aimed to clarify the esophageal reflux factors in Barrett's esophagus (BE) and BA and the factors that determine the location of BA with 24-h MII-pH. METHODS: We performed 24-h MII-pH in 26 patients with superficial BA treated endoscopically (BA group) and 13 patients with BE (BE group) and examined the esophageal reflux factors (esophageal acid exposure time [AET], bolus exposure (acid, weakly acid, and alkaline), and number of reflux episodes. In the BA group, there were 16 cases in which the lesions were localized in an area in contact with the esophagogastric junction (EGJ; EGJ group), and 10 cases in which the lesions were proximal to the BE and separated from the EGJ (non-EGJ group). RESULTS: Total reflux in the bolus exposure in the BA group showed higher values compared to that in the BE group. The total of acid and weakly acid reflux of bolus exposure was significantly higher in the BA group than that in the BE group. The BA group also had greater numbers of total reflux episodes than the BE group. As for the cancer locations in BE, the cases in which the lesions were located proximally and separated from the EGJ had more AET and total reflux and acid reflux indicated by bolus exposure compared to the lesions adjacent to the EGJ. CONCLUSIONS: Stronger gastro-esophageal reflux appeared to be an important factor in the development of adenocarcinoma from BE. In addition, the cancer location in BE may be related to the intensity of esophageal reflux.

  96. Difficult Preoperative Diagnosis of Lymphoepithelioma-Like Carcinoma of the Esophagus. International-journal Peer-reviewed

    Tomoki Okata, Kaname Uno, Fumiyoshi Fujishima, Masahiro Saito, Xiaoyi Jin, Waku Hatta, Kiyotaka Asanuma, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune

    ACG case reports journal 6 (8) e00163 2019/08

    DOI: 10.14309/crj.0000000000000163  

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    A 60-year-old man with a medical history of diabetes, liver cirrhosis, and distal gastrectomy was referred for further examination of a 10-mm pale-colored submucosal tumor around 40 cm from the incisors. Narrow band imaging-magnifying endoscopy revealed the lesion covered by smooth epithelium with irregular microvascular architecture in a sparse distribution. Endosonography showed an irregular-shaped hypoechoic lesion in the submucosa. With no evidence of metastases, we performed en bloc endoscopic submucosal dissection, whose specimen revealed esophageal lymphoepithelioma-like carcinoma invading up to 500 μm in the submucosa, a rare disease entity. Despite no additional treatment, he was alive without recurrence for longer than 88 months.

  97. Is Additional Surgery Always Sufficient for Preventing Recurrence After Endoscopic Submucosal Dissection with Curability C-2 for Early Gastric Cancer? International-journal Peer-reviewed

    Hatta W, Gotoda T, Oyama T, Kawata N, Takahashi A, Oka S, Hoteya S, Nakagawa M, Hirano M, Esaki M, Matsuda M, Ohnita K, Shimoda R, Yoshida M, Dohi O, Takada J, Tanaka K, Yamada S, Tsuji T, Ito H, Aoyagi H, Nakamura T, Nakaya N, Shimosegawa T, Masamune A

    Annals of surgical oncology 26 (11) 3636-3643 2019/07

    DOI: 10.1245/s10434-019-07579-2  

    ISSN: 1068-9265

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    BACKGROUND: When a lesion does not meet the curative criteria of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), referred to as non-curative resection or curability C-2 in the guidelines, an additional surgery is the standard therapy because of the risk of lymph node metastasis (LNM). OBJECTIVE: This study aimed to identify high-risk patients for recurrence after additional surgery for curability C-2 ESD of EGC. METHODS: This multicenter retrospective cohort study enrolled 1064 patients who underwent additional surgery after curability C-2 ESD for EGC. We evaluated the recurrence rate and the risk factors for recurrence after additional surgery in these patients. RESULTS: The 5-year recurrence rate after additional surgery was 1.3%. Multivariate Cox analysis revealed that the independent risk factors for recurrence after additional surgery were LNM (hazard ratio [HR] 32.47; p < 0.001) and vascular invasion (HR 4.75; p = 0.014). Moreover, patients with both LNM and vascular invasion had a high rate of recurrence after additional surgery (24.6% in 5 years), with a high HR (119.32) compared with those with neither LNM nor vascular invasion. Among patients with no vascular invasion, a high rate of recurrence was observed in those with N2/N3 disease according to the American Joint Committee on Cancer TNM staging system (27.3% in 5 years), in contrast with no recurrence in those with N1 disease. CONCLUSIONS: Patients with both LNM (N1-N3) and vascular invasion, as well as those with N2/N3 disease but no vascular invasion, would be candidates for adjuvant chemotherapy after additional surgery for curability C-2 ESD of EGC.

  98. Branched chain amino acids are associated with the heterogeneity of the area of lipid droplets in hepatocytes of patients with non-alcoholic fatty liver disease. International-journal Peer-reviewed

    Kakazu E, Sano A, Morosawa T, Inoue J, Ninomiya M, Iwata T, Nakamura T, Takai S, Sawada S, Katagiri H, Shimosegawa T, Masamune A

    Hepatology research : the official journal of the Japan Society of Hepatology 49 (8) 860-871 2019/04

    DOI: 10.1111/hepr.13346  

    ISSN: 1386-6346

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    AIM: Macrovesicular steatosis around the central vein (zone 3) is one of the pathological features of non-alcoholic fatty liver disease or steatohepatitis (NAFLD/NASH). The aim of this study is to elucidate precisely the association between the area of lipid droplets (LDs) and the plasma metabolic parameters in patients with NAFLD/NASH. METHODS: Eighty patients with NAFLD/NASH diagnosed by needle biopsy were enrolled. The LDs around zone 3 were counted automatically by image processing software, the total area of LDs (TLDs), the maximum area of LDs (MAXLDs), the average area of LDs (AVELDs) and the heterogeneity by the coefficient of variation (CV [%]) were quantified. The correlations between these values and plasma metabolic parameters were analyzed. We evaluated the association between branched chain amino acids (BCAAs) and the heterogeneity of LDs in hepatocytes in vitro and in vivo. RESULTS: The MAXLDs was significantly correlated with more metabolic parameters than AVELDs and TLDs. The level of BCAAs was independently associated with the CV among the metabolic parameters. In early stage NAFLD, aspartate and alanine aminotransferase were significantly higher in the high CV group than in the low CV group. The high concentration of BCAAs increased the CV of LDs in hepatocytes accompanied by the expression of phosphor-p70 S6 kinase and sterol regulatory element-binding protein 1 in vitro. A high BCAA diet induced high heterogeneity of LDs around zone 3 in ob/ob mice. CONCLUSIONS: The levels of BCAAs were associated with the LD heterogeneity of hepatocytes around zone 3 in patients with NAFLD/NASH.

  99. Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan. International-journal Peer-reviewed

    Yasuda H, Kataoka K, Takeyama Y, Takeda K, Ito T, Mayumi T, Isaji S, Mine T, Kitagawa M, Kiriyama S, Sakagami J, Masamune A, Inui K, Hirano K, Akashi R, Yokoe M, Sogame Y, Okazaki K, Morioka C, Kihara Y, Kawa S, Tanaka M, Andoh A, Kimura W, Nishimori I, Furuse J, Yokota I, Shimosegawa T

    World journal of gastroenterology 25 (1) 107-117 2019/01

    DOI: 10.3748/wjg.v25.i1.107  

    ISSN: 1007-9327

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    BACKGROUND: Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM: To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS: Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS: A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION: We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

  100. Age Affects Clinical Management after Noncurative Endoscopic Submucosal Dissection for Early Gastric Cancer. International-journal Peer-reviewed

    Esaki M, Hatta W, Shimosegawa T, Oyama T, Kawata N, Takahashi A, Oka S, Hoteya S, Nakagawa M, Hirano M, Matsuda M, Ohnita K, Shimoda R, Yoshida M, Dohi O, Takada J, Tanaka K, Yamada S, Tsuji T, Ito H, Aoyagi H, Gotoda T

    Dig Dis 37 (6) 423-433 2019

    DOI: 10.1159/000499538  

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    BACKGROUND: Additional surgery is recommended after noncurative endoscopic submucosal dissection (ESD) for early gastric cancer due to the risk of lymph node metastasis. However, age may affect the clinical management of these patients. OBJECTIVES: The aim of our retrospective multicenter study was to clarify whether age affects decision-making after noncurative ESD and if the decision affects long-term outcomes. METHODS: Age was classified as follows: non-elderly, <70 years (n = 811); elderly, 70-79 years (n= 760); and super-elderly, ≥80 years (n = 398). Age associations with the selection for additional surgery were evaluated using logistic regression analysis. Long-term outcomes were also evaluated in each age group. RESULTS: Age was inversely related to the rate of additional surgery, which ranged from 70.0% in the non-elderly group to 20.1% in the super-elderly group (p < 0.001). On multivariate analysis, age <70 years (versus age ≥80 years) was associated with the -selection of additional surgery (OR 18.6). Overall survival (OS) in patients who underwent additional surgery was -significantly higher in the non-elderly and elderly groups (p< 0.001), whereas the difference was not significant in the super-elderly group (p = 0.23). CONCLUSIONS: Despite the fact that almost 80% of super-elderly patients did not undergo additional surgery, the difference of OS between patients with and without additional surgery was not significant only in patients ≥80 years. Therefore, establishment of criteria for selecting treatment methods after noncurative ESD in elderly patients is required.

  101. Long-term prognosis of Japanese patients with biologic-naïve Crohn's disease treated with anti-tumor necrosis factor-α antibodies. International-journal Peer-reviewed

    Rintaro Moroi, Katsuya Endo, Katsutoshi Yamamoto, Takeo Naito, Motoyuki Onodera, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Yoichi Kakuta, Atsushi Masamune, Yoshitaka Kinouchi, Tooru Shimosegawa

    Intestinal research 17 (1) 94-106 2019/01

    DOI: 10.5217/ir.2018.00048  

    ISSN: 1598-9100

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    BACKGROUND/AIMS: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn's disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. METHODS: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. RESULTS: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels <2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. CONCLUSIONS: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.

  102. Prospective study of early chronic pancreatitis diagnosed based on the Japanese diagnostic criteria. Peer-reviewed

    Masamune A, Nabeshima T, Kikuta K, Hamada S, Nakano E, Kume K, Kanno A, Sato A, Tachibana Y, Inatomi O, Yamamoto S, Ikeura T, Futagami S, Taguchi M, Hanada K, Shimizu K, Kageoka M, Saito T, Eguchi T, Kubota K, Takenaka M, Mima A, Irisawa A, Ito T, Andoh A, Inui K, Takeyama Y, Yamaue H, Okazaki K, Shimosegawa T

    J Gastroenterol 54 (10) 928-935 2019/01

    Publisher: シュプリンガー・ジャパン(株)

    ISSN: 0944-1174

    eISSN: 1435-5922

  103. Endoscopic Findings of Esophageal Adenosquamous Carcinoma Diagnosed by Endoscopic Mucosal Resection. Peer-reviewed

    Endo H, Koike T, Hatta W, Asanuma K, Uno K, Asano N, Imatani A, Watanabe M, Kato K, Masamune A

    Case reports in gastroenterology 13 (1) 144-152 2019/01

    DOI: 10.1159/000499182  

  104. Recurrence patterns and outcomes of salvage surgery in cases of non-curative endoscopic submucosal dissection without additional radical surgery for early gastric cancer International-journal Peer-reviewed

    Kohei Takizawa, Waku Hatta, Takuji Gotoda, Noboru Kawata, Masahiro Nakagawa, Akiko Takahashi, Mitsuru Esaki, Akira Mitoro, Shinya Yamada, Keiko Tanaka, Mitsuru Matsuda, Jun Takada, Shiro Oka, Hirotaka Ito, Ken Ohnita, Ryo Shimoda, Shu Hoteya, Tsuneo Oyama, Tooru Shimosegawa

    Digestion 99 (1) 52-58 2018/12/01

    DOI: 10.1159/000494413  

    ISSN: 0012-2823

    eISSN: 1421-9867

  105. Different risk factors between early and late cancer recurrences in patients without additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer. International-journal Peer-reviewed

    Yamada S, Hatta W, Shimosegawa T, Takizawa K, Oyama T, Kawata N, Takahashi A, Oka S, Hoteya S, Nakagawa M, Hirano M, Esaki M, Matsuda M, Nakaya N, Gotoda T

    Gastrointestinal endoscopy 89 (5) 950-960 2018/11

    DOI: 10.1016/j.gie.2018.11.015  

    ISSN: 0016-5107

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    BACKGROUND AND AIMS: Cancer recurrence is observed in some patients without additional radical surgery after endoscopic submucosal dissection (ESD) that does not fulfill the curability criteria for early gastric cancer (EGC), categorized as "noncurative resection" or "curability C-2" in the guidelines. However, time to cancer recurrence is different in such patients. Thus, we aimed to identify the risk factors of early and late cancer recurrences in these patients. METHODS: Between 2000 and 2011, this multicenter study analyzed 905 patients who were followed up without additional radical surgery after ESD for EGC categorized as curability C-2. We evaluated the risk factors for early and late cancer recurrences, separately, after ESD. The cut-off value was defined at 2 years. RESULTS: Time to cancer recurrence in the enrolled patients showed a bimodal pattern, and the 5-year cancer recurrence rate was 3.2%. Multivariate Cox analyses revealed that lymphatic invasion (hazard ratio [HR], 8.56; P = .003) was the sole independent risk factor for early cancer recurrence. Regarding late cancer recurrence, vascular invasion (HR, 4.50; P = .039) was an independent risk factor, and lymphatic invasion tended to be a risk factor (HR, 3.63; P = .069). CONCLUSIONS: This multicenter study with a large cohort demonstrated that lymphatic invasion is mainly associated with early cancer recurrence; however, vascular invasion was a risk factor only for late recurrence in patients without additional treatment after ESD for EGC categorized as curability C-2. This finding may contribute to decision making for treatment strategies after ESD, especially for patients with a relatively short life expectancy.

  106. The Use of Higher Dose Steroids Increases the Risk of Rebleeding After Endoscopic Hemostasis for Peptic Ulcer Bleeding. International-journal Peer-reviewed

    Yutaka Kondo, Waku Hatta, Tomoyuki Koike, Yasushi Takahashi, Masahiro Saito, Takeshi Kanno, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Atsushi Masamune

    Digestive diseases and sciences 63 (11) 3033-3040 2018/11

    DOI: 10.1007/s10620-018-5209-y  

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    BACKGROUND: Previous studies have shown that several factors such as hemodynamic instability at admission are risk factors for rebleeding of peptic ulcer bleeding. However, whether steroid use increases the risk of rebleeding remains elusive. AIMS: This study aimed to clarify the risk factors for rebleeding after endoscopic hemostasis for peptic ulcer bleeding. METHODS: A total of 185 patients who underwent endoscopic hemostasis for peptic ulcer bleeding at our institution between 2005 and 2017 were retrospectively analyzed. We evaluated factors, including comorbid conditions, in-hospital onset, and steroid use, associated with rebleeding by logistic regression analysis. In addition, we investigated the association between the dose of steroids and rebleeding. RESULTS: The rebleeding rate after endoscopic hemostasis for peptic ulcer bleeding was 14.6%. In the multivariate analysis, the independent risk factors for rebleeding were steroid use (odds ratio 4.56, p = 0.015), multiple ulcers (4.43, p = 0.005), number of comorbidities ≥ 3 3.18, p = 0.026), hemodynamic instability (3.06, p = 0.039), and number of comorbidities ≥ 3 (2.93, p = 0.047). Furthermore, the use of higher dose steroids (≥ 20 mg per day in prednisolone; 10.55, p = 0.002), but not lower dose (< 20 mg per day in prednisolone), was an independent risk factor for rebleeding in the multivariate analysis. The relationship between steroid use and rebleeding was observed in a dose-dependent manner (p for trend = 0.002). CONCLUSIONS: This study first revealed that using higher dose steroids was an independent risk factor for rebleeding after endoscopic hemostasis for peptic ulcer bleeding, with a dose-response relation.

  107. Pancreatic Acinar Cell Carcinoma with Multiple Liver Metastases Effectively Treated by S-1 Chemotherapy. Peer-reviewed

    Yoshida N, Kanno A, Masamune A, Nabeshima T, Hongo S, Miura S, Takikawa T, Hamada S, Kikuta K, Kume K, Ueno M, Shimosegawa T

    Internal medicine (Tokyo, Japan) 57 (24) 3529-3535 2018/08

    DOI: 10.2169/internalmedicine.0294-17  

    ISSN: 0918-2918

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    A 79-year-old woman was referred for pancreatic tail cancer with multiple liver metastases. The pancreatic tail tumor was diagnosed as acinar cell carcinoma (ACC) histologically by endoscopic ultrasound-guided fine-needle aspiration. Because of multiple liver metastases, S-1 chemotherapy was administered, resulting in a partial response to chemotherapy one year later. After approximately three years, liver atrophy and esophageal varices developed. We suspected S-1 as the cause of the liver cirrhosis. S-1 cessation minimized ascites and improved the esophageal varices. Although S-1 can potentially treat ACC, we should be watchful for liver cirrhosis caused by its long-term administration.

  108. A new manometry device for evaluating the sphincter of Oddi using a fiber-optic pressure sensor. Peer-reviewed

    Hanzawa T, Matsunaga T, Koike T, Kanno A, Masamune A, Iijima K, Shimosegawa T, Haga Y

    Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 27 (4) 226-232 2018/08

    DOI: 10.1080/13645706.2017.1412701  

    ISSN: 1364-5706

  109. Leptin Aggravates Reflux Esophagitis by Increasing Tissue Levels of Macrophage Migration Inhibitory Factor in Rats. Peer-reviewed

    Tsugihiro Murata, Kiyotaka Asanuma, Nobuyuki Ara, Katsunori Iijima, Waku Hatta, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 245 (1) 45-53 2018/05

    DOI: 10.1620/tjem.245.45  

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    Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). We therefore investigated the mechanism whereby leptin aggravates reflux esophagitis, by focusing on esophageal tissue levels of MIF and CD3+ T lymphocytes, both of which are crucial for the reflux-induced epithelial damage. Esophageal inflammation was surgically induced in male Wistar rats by ligating the forestomach and narrowing the duodenum to facilitate gastroesophageal reflux, followed by administration of leptin or vehicle with an osmotic pump system for 1 week. We demonstrated that the administration of leptin exacerbated the reflux esophagitis with the apparent infiltration of CD3+ T lymphocytes and caused the significant increase in the esophageal tissue levels of MIF. Moreover, the leptin caused increases in the esophageal tissue levels of TNF-α, IL-1β and IL-6, downstream targets of MIF. Importantly, the increases in these pro-inflammatory cytokines were accompanied by increased protein levels of phospho-STAT3 and phospho-AKT, pivotal molecules of leptin signaling pathways. In conclusion, through enhancing the MIF-induced inflammatory signaling, leptin could contribute to the development of gastroesophageal reflux disease.

  110. Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake. Peer-reviewed

    Okata H, Hatta W, Iijima K, Asanuma K, Tsuruya A, Asano N, Koike T, Hamada S, Nakayama T, Masamune A, Shimosegawa T

    The Tohoku journal of experimental medicine 244 (4) 317-325 2018/04

    DOI: 10.1620/tjem.244.317  

    ISSN: 0040-8727

  111. Effective and less invasive diagnostic strategy for gastrointestinal GVHD. International-journal Peer-reviewed

    Endo K, Fujishima F, Kuroha M, Moroi R, Onodera M, Naito T, Kanazawa Y, Kimura T, Shiga H, Kakuta Y, Kinouchi Y, Shimosegawa T

    Endoscopy international open 6 (3) E281-E291 2018/03

    DOI: 10.1055/s-0043-122226  

    ISSN: 2364-3722

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    Background and study aims:  Rectosigmoidoscopy with biopsy has been regarded to be a useful procedure to diagnose gastrointestinal graft-versus-host disease (GVHD). However, little is known about the specific colonoscopic features of gastrointestinal GVHD. In this study, we focused on the 4 unique colonoscopic findings - orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect - which are possible specific findings of gastrointestinal GVHD. We aimed to estimate the usefulness of these four unique colonoscopic findings in the rectosigmoid portion to diagnose gastrointestinal GVHD. Patients and methods:  Seventy patients who were histologically diagnosed with gastrointestinal GVHD at our institute were retrospectively enrolled. Colonoscopic findings were reviewed, focusing on the four characteristic findings. The percentage of the positive cases for the characteristic findings was calculated. The final scoping portion and the number of cases showing any of the four characteristic findings in the rectosigmoid portion were also evaluated. The relationships between biopsy sites and the histological findings were also evaluated. Results:  Orange peel appearance was observed in 66 cases (94.3 %). Spotty redness was observed in 45 cases (64.3 %). Small mucosal sloughing was observed in 49 cases (70.0 %). Diffuse mucosal defect was observed in six cases (8.6 %). The number of cases that were concurrently positive for one, two, and three findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively. Fifty-eight cases (82.9 %) were investigated up to the rectosigmoid portion, and 12 (17.1 %) were investigated beyond the sigmoid colon. All of the cases showed at least 1 of the 4 characteristics in the rectosigmoid portion. The percentage of crypt apoptosis in the biopsy specimen from orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect were 87.5 %, 83.3 %, 87.2 %, and 88.9 %, respectively. Conclusion:  Orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect are the characteristic colonoscopic findings useful for diagnosis of gastrointestinal GVHD. These findings are frequently observed in the rectosigmoid portion. The histological detection rates for crypt cell apoptosis from these findings are high. Identifying the four characteristic findings on rectosigmoidoscopy and taking biopsies from these areas could be essential for the diagnostic strategy for gastrointestinal GVHD.

  112. Estrogen-Dependent Nrf2 Expression Protects Against Reflux-Induced Esophagitis. International-journal Peer-reviewed

    Yudai Torihata, Kiyotaka Asanuma, Katsunori Iijima, Tetsuhiko Mikami, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa

    Digestive diseases and sciences 63 (2) 345-355 2018/02

    DOI: 10.1007/s10620-017-4885-3  

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    BACKGROUND: Gastroesophageal reflux disease is more common in males than in females. The enhanced antioxidative capacity of estrogen in females might account for the gender difference. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in the host defense mechanism against oxidative stress. AIMS: This study aimed to clarify the role of Nrf2 in reflux-induced esophageal inflammation, focusing on the gender difference and nitric oxide. METHODS: Gastroesophageal reflux was surgically induced in male and female rats. Nitrite and ascorbic acid were administered for 1 week to provoke nitric oxide in the esophageal lumen. Male rats with gastroesophageal reflux were supplemented with 17β-estradiol or tert-butylhydroquinone, an Nrf2-inducing reagent. Esophageal squamous cell carcinoma KYSE30 cells were treated with 17β-estradiol. Nrf2 expression was examined by Western blotting and quantitative real-time PCR. Antioxidant gene expression profiles were examined by a PCR array. RESULTS: In the presence of nitric oxide, reflux-induced esophageal damage was less evident, whereas esophageal expression of Nrf2 and its target genes such as Nqo1 was more evident in female or male rats supplemented with 17β-estradiol than in male rats. 17β-Estradiol increased nuclear Nrf2 expression in KYSE30 cells. tert-Butylhydroquinone increased tissue Nqo1 mRNA expression, leading to a reduction in reflux-induced esophageal damage. CONCLUSIONS: Estrogen-dependent Nrf2 expression might contribute to protection against the development of gastroesophageal reflux disease in females.

  113. The Role of an Undifferentiated Component in Submucosal Invasion and Submucosal Invasion Depth After Endoscopic Submucosal Dissection for Early Gastric Cancer. International-journal Peer-reviewed

    Miyahara K, Hatta W, Nakagawa M, Oyama T, Kawata N, Takahashi A, Yoshifuku Y, Hoteya S, Hirano M, Esaki M, Matsuda M, Ohnita K, Shimoda R, Yoshida M, Dohi O, Takada J, Tanaka K, Yamada S, Tsuji T, Ito H, Aoyagi H, Shimosegawa T

    Digestion 98 (3) 161-168 2018

    DOI: 10.1159/000488529  

    ISSN: 0012-2823

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    BACKGROUND/AIMS: The role of an undifferentiated component in submucosal invasion and submucosal invasion depth (SID) for lymph node metastasis (LNM) of early gastric cancer (EGC) with deep submucosal invasion (SID ≥500 μm from the muscularis mucosa) after endoscopic submucosal dissection (ESD) has not been fully understood. This study aimed to clarify the risk factors (RFs), including these factors, for LNM in such patients. METHODS: We enrolled 513 patients who underwent radical surgery after ESD for EGC with deep submucosal invasion. We evaluated RFs for LNM, including an undifferentiated component in submucosal invasion and the SID, which was subdivided into 500-999, 1,000-1,499, 1,500-1,999, and ≥2,000 µm. RESULTS: LNM was detected in 7.6% of patients. Multivariate analysis revealed that an undifferentiated component in submucosal invasion (OR 2.22), in addition to tumor size >30 mm (OR 2.51) and lymphatic invasion (OR 3.07), were the independent RFs for LNM. However, the SID was not significantly associated with LNM. CONCLUSION: An undifferentiated component in submucosal invasion was one of the RFs for LNM, in contrast to SID, in patients who underwent ESD for EGC with deep submucosal invasion. This insight would be helpful in managing such patients.

  114. The slow progressive nature of duodenal neuroendocrine tumor: a case report of long-term observation over 14 years. Peer-reviewed

    Kiichi Takahashi, Waku Hatta, Tomoyuki Koike, Takeshi Kanno, Nobuyuki Ara, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Hironobu Sasano, Tooru Shimosegawa

    Clinical journal of gastroenterology 10 (5) 469-473 2017/10

    DOI: 10.1007/s12328-017-0758-8  

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    The number of duodenal neuroendocrine tumors has recently increased, but their natural history has not been well characterized. Here we report the case of a 59-year-old female undergoing complete resection by endoscopic mucosal resection after monitoring endoscopic morphologic changes and the size increment of a duodenal neuroendocrine tumor over the longest follow-up duration. An elevated lesion was initially detected on the duodenal bulb. Endoscopic biopsy from this lesion was performed three times during the follow-up, but all of the specimens simply demonstrated the presence of gastric metaplasia. Thereafter, in the esophagogastroduodenoscopy performed 14 years after the initial examination, a slight depression was detected in the center of the lesion together with an incremental change of its size. The histopathologic diagnosis of neuroendocrine tumor was made by deeper tissue sampling, and the patient subsequently underwent endoscopic mucosal resection for this tumor and was finally diagnosed with a G1 duodenal neuroendocrine tumor with pT2 cN0, cM0, stage IIa in the TNM classification. This is the first case demonstrating the slowly progressive nature of such a tumor with the longest follow-up of a duodenal neuroendocrine tumor ever reported, which could provide important information regarding the natural history and management of such tumors.

  115. Factors Associated With Metachronous Gastric Cancer Development After Endoscopic Submucosal Dissection for Early Gastric Cancer. International-journal

    Reiko Ami, Waku Hatta, Katsunori Iijima, Tomoyuki Koike, Hideki Ohkata, Yutaka Kondo, Nobuyuki Ara, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Journal of clinical gastroenterology 51 (6) 494-499 2017/07

    DOI: 10.1097/MCG.0000000000000620  

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    GOALS: To clarify the factors associated with metachronous gastric cancer development after endoscopic submucosal dissection (ESD) for early gastric cancer. BACKGROUND: Patients who undergo ESD for early gastric cancer have an appreciable risk of developing metachronous gastric cancer. However, there have been few reports on the association between life style and the development of such cancer. STUDY: Patients with early gastric cancer who underwent ESD at our institution between 2003 and 2012 were enrolled. Metachronous gastric cancer was defined as secondary gastric cancer detected >1 year after initial ESD. Factors, including age, gender, body mass index, eradication of Helicobacter pylori, cigarette smoking, drinking, and continuous use of a proton pump inhibitor, associated with metachronous gastric cancer development were evaluated by Cox proportional hazard regression analysis. RESULTS: A total of 539 patients with a mean 53.6-month follow-up period were analyzed. The 5-year cumulative incidence of secondary gastric cancer was 13.0%. Multivariate analysis exhibited that age of 60 years and above [hazard ratio (95% confidence interval)=4.05 (1.23-13.4)] and cigarette smoking [2.12 (1.19-3.78)] were independent risk factors for metachronous gastric cancer development. Furthermore, ≥20 pack-years of smoking [1.51 (1.03-2.24)] was a significant risk factor with a dose-response relationship (P for trend=0.042). There was no significant association between Helicobacter pylori eradication and metachronous gastric cancer development. CONCLUSIONS: This is the first study to demonstrate the detailed association between cigarette smoking and metachronous gastric cancer development.

  116. non-H.pylori、non-NSAID潰瘍(ストレス潰瘍)

    菅野 武, 飯島 克則, 小池 智幸, 八田 和久, 荒 誠之, 淺沼 清孝, 浅野 直喜, 今谷 晃, 下瀬川 徹

    日本ヘリコバクター学会誌 19 (1) 8-11 2017/05

    Publisher: (一社)日本ヘリコバクター学会

    ISSN: 2187-8005

  117. 十二指腸非乳頭部NETの内視鏡的特徴 多施設共同研究における胃NETとの比較より

    八田 和久, 小池 智幸, 淺沼 清孝, 菅野 武, 荒 誠之, 浅野 直喜, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 59 (Suppl.1) 963-963 2017/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  118. Plasma Kallikrein-Dependent Transforming Growth Factor-beta Activation in Patients With Chronic Pancreatitis and Pancreatic Cancer Peer-reviewed

    Ryutaro Teraoka, Mitsuko Hara, Kazuhiro Kikuta, Yoshiki Hirooka, Yutaka Furutani, Tooru Shimosegawa, Atsushi Masamune, Soichi Kojima

    PANCREAS 46 (3) E20-E22 2017/03

    DOI: 10.1097/MPA.0000000000000736  

    ISSN: 0885-3177

    eISSN: 1536-4828

  119. The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter. Peer-reviewed

    Hatta W, Koike T, Iijima K, Asanuma K, Asano N, Musha H, Inomata Y, Sano T, Endo H, Ikehata A, Horii T, Ohyauchi M, Yokosawa S, Kasajima A, Fujishima F, Sasano H, Nakaya N, Nakamura T, Shimosegawa T

    Digestion 95 (3) 201-209 2017/03

    DOI: 10.1159/000459619  

    ISSN: 0012-2823

  120. Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis International-journal Peer-reviewed

    Atsushi Masamune, Isao Nishimori, Kazuhiro Kikuta, Ichiro Tsuji, Nobumasa Mizuno, Tatsuo Iiyama, Atsushi Kanno, Yuichi Tachibana, Tetsuhide Ito, Terumi Kamisawa, Kazushige Uchida, Hideaki Hamano, Hiroaki Yasuda, Junichi Sakagami, Akira Mitoro, Masashi Taguchi, Yasuyuki Kihara, Hiroyuki Sugimoto, Yoshiki Hirooka, Satoshi Yamamoto, Kazuo Inui, Osamu Inatomi, Akira Andoh, Kazuyuki Nakahara, Hiroyuki Miyakawa, Shin Hamada, Shigeyuki Kawa, Kazuichi Okazaki, Tooru Shimosegawa

    Gut 66 (3) 487-494 2017/03/01

    DOI: 10.1136/gutjnl-2016-312049  

    ISSN: 0017-5749

    eISSN: 1468-3288

  121. 早期胃癌ESD後除菌患者における異時性胃癌発生 喫煙を中心とした生活因子との関連性

    八田 和久, 阿見 麗子, 飯島 克則, 小池 智幸, 菅野 武, 荒 誠之, 淺沼 清孝, 浅野 直喜, 今谷 晃, 下瀬川 徹

    胃病態機能研究会誌 49 18-18 2017/02

    Publisher: (株)勁草書房コミュニケーション事業部

    ISSN: 1880-3652

  122. 胃酸分泌能の内視鏡診断

    八田 和久, 飯島 克則, 小池 智幸, 近藤 穣, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 58 (10) 2222-2231 2016/10

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  123. Usefulness of Endoscopic Imaging to Visualize Regional Alterations in Acid Secretion of Noncancerous Gastric Mucosa after Helicobacter pylori Eradication. Peer-reviewed

    Uno K, Iijima K, Abe Y, Koike T, Takahashi Y, Ara N, Shimosegawa T

    Journal of gastric cancer 16 (3) 152-160 2016/09

    DOI: 10.5230/jgc.2016.16.3.152  

    ISSN: 2093-582X

  124. 日本における抗血栓薬継続下での内視鏡生検後出血リスクに関する前向き検討

    荒 誠之, 飯島 克則, 前嶋 隆平, 近藤 穣, 日下 玄, 八田 和久, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 58 (8) 1367-1374 2016/08

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  125. Preferential location of idiopathic peptic ulcers. Peer-reviewed

    Iijima K, Kanno T, Abe Y, Yagi M, Asonuma S, Ohyauchi M, Ito H, Koike T, Shimosegawa T

    Scandinavian journal of gastroenterology 51 (7) 782-787 2016/07

    DOI: 10.3109/00365521.2016.1141316  

    ISSN: 0036-5521

  126. Helicobacter pylori-negative and non-steroidal anti-inflammatory drugs-negative idiopathic peptic ulcers show refractoriness and high recurrence incidence: Multicenter follow-up study of peptic ulcers in Japan. Peer-reviewed

    Kanno T, Iijima K, Abe Y, Yagi M, Asonuma S, Ohyauchi M, Ito H, Koike T, Shimosegawa T

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 28 (5) 556-563 2016/07

    DOI: 10.1111/den.12635  

    ISSN: 0915-5635

  127. A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old. Peer-reviewed

    Iijima K, Koike T, Abe Y, Ohara S, Shimosegawa T

    The Tohoku journal of experimental medicine 239 (3) 237-241 2016/07

    DOI: 10.1620/tjem.239.237  

    ISSN: 0040-8727

  128. GERDへの新たな取組み PPI抵抗性NERD患者における24hr MII-pHによる診断と、Vonoprazanの有用性の検討

    齊藤 真弘, 小池 智幸, 菊池 弘樹, 乗田 一明, 八田 和久, 荒 誠之, 淺沼 清孝, 浅野 直喜, 今谷 晃, 下瀬川 徹

    日本食道学会学術集会プログラム・抄録集 70回 35-35 2016/07

    Publisher: (NPO)日本食道学会

  129. Feasibility of optical coherence tomography for the evaluation of Barrett's mucosa buried underneath esophageal squamous epithelium. International-journal Peer-reviewed

    Waku Hatta, Kaname Uno, Tomoyuki Koike, Nobuyuki Ara, Naoki Asano, Katsunori Iijima, Akira Imatani, Fumiyoshi Fujishima, Tooru Shimosegawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 28 (4) 427-433 2016/05

    DOI: 10.1111/den.12576  

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    OBJECTIVES: The evaluation of Barrett's glands buried underneath esophageal squamous epithelium becomes increasingly important to achieve curative treatments. However, clinically available endoscopies have critical limitations in depicting the subsurface structure, resulting in non-curative treatments. Optical coherence tomography (OCT) can acquire a high-resolution cross-sectional image, equivalent to an 'optical biopsy'. We aimed to assess the feasibility of the in vivo use of probe-type OCT imaging to evaluate Barrett's mucosa buried underneath esophageal squamous epithelium METHODS: We conducted a single-center prospective study with 14 consecutive patients with Barrett's adenocarcinoma from 2008 to 2014. The enrolled patients were examined by a probe-type OCT in vivo, followed by en bloc endoscopic submucosal dissection (ESD) with electric marking. Then, the one-to-one correlations between the OCT images of the buried mucosa and their histological assessment were examined. RESULTS: The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the buried mucosa in the OCT imaging were 85.7% (12/14), 77.8% (7/9), 100% (5/5), 100% (7/7) and 71.4% (5/7), respectively. However, OCT could not easily distinguish non-dysplastic glands from dysplastic glands. Additionally, the linear distance from the histological squamo-columnar junction in correct cases tended to be longer than that in incorrect cases (mm, median [range]: 2.0 [0.7-7.5] vs. 0.5 [0.5-0.5]). CONCLUSIONS: We demonstrated, for the first time, that pre-operative OCT imaging might be feasible for detecting the oral side extension of buried Barrett's mucosa to remove the entire area with malignant potential by ESD. This article is protected by copyright. All rights reserved.

  130. A Japanese case of lymphocytic esophagitis. International-journal Peer-reviewed

    Ryuhei Maejima, Kaname Uno, Katsunori Iijima, Fumiyoshi Fujishima, Tetsuya Noguchi, Nobuyuki Ara, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 28 (4) 476-480 2016/05

    DOI: 10.1111/den.12578  

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    We report the case of a 68-year-old Japanese man diagnosed with lymphocytic esophagitis (LE), a rare disease associated with refractory dysphagia. He has had severe dysphagia and heartburn since 2007. Findings of esophagogastroduodenoscopy (EGD) carried out by a local physician in 2010 showed pale mucosa with white exudate and lateral furrows in the esophagus. He was referred to Tohoku University Hospital in 2012, because the symptoms did not improve, despite regular use of a proton pump inhibitor (PPI). At that time, EGD revealed the coexistence of a slight stricture in the upper esophagus, the histopathological findings of which included a predominantly peri-papillary distribution of abundant, infiltrating CD3+ /CD4+ /CD8+ /CD20- lymphocytes without any granulocytes (CD4+  : CD8+  = 3.3:1). These were consistent with a diagnostic criteria of LE. Thereafter, severe dysphagia with food impaction occurred twice a month, despite the long-term use of a PPI, and EGD showed worsened strictures, where endoscopic ultrasonography findings showed marked circumferential thickness of the mucosal and submucosal layers. Then, one session of endoscopic balloon dilatation dramatically improved the dysphagia. Accordingly, LE should be considered an important differential diagnosis of refractory dysphagia based on the characteristic features of endoscopic and pathological findings.

  131. 難治性嚥下障害を呈したリンパ球性食道炎の一例

    前嶋 隆平, 宇野 要, 飯島 克則, 藤島 史喜, 野口 哲也, 本田 純也, 菅野 武, 日下 玄, 近藤 穣, 八田 和久, 荒 誠之, 淺沼 清孝, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 58 (Suppl.1) 785-785 2016/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  132. Gastric cancer development after the successful eradication of Helicobacter pylori. Peer-reviewed

    Uno K, Iijima K, Shimosegawa T

    World journal of gastrointestinal oncology 8 (3) 271-281 2016/03

    DOI: 10.4251/wjgo.v8.i3.271  

  133. PPI抵抗性NERD患者における24hr MLL-pHモニタリングの基線値の検討

    菊池 弘樹, 小池 智幸, 乗田 一明, 齊藤 真弘, 菅野 武, 近藤 穣, 日下 玄, 八田 和久, 荒 誠之, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 113 (臨増総会) A229-A229 2016/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  134. 早期胃癌ESD後異時性多発胃癌発生に対する関連因子の検討

    阿見 麗子, 八田 和久, 飯島 克則, 小池 智幸, 荒 誠之, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 113 (臨増総会) A230-A230 2016/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  135. Gender difference in gastro-esophageal reflux diseases. Peer-reviewed

    Asanuma K, Iijima K, Shimosegawa T

    World journal of gastroenterology 22 (5) 1800-1810 2016/02

    DOI: 10.3748/wjg.v22.i5.1800  

    ISSN: 1007-9327

  136. Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis. Peer-reviewed

    Kusaka G, Uno K, Iijima K, Shimosegawa T

    World journal of gastrointestinal pathophysiology 7 (1) 131-137 2016/02

    DOI: 10.4291/wjgp.v7.i1.131  

  137. Endoscopic findings for predicting gastric acid secretion status

    Waku Hatta, Katsunori Iijima, Tomoyuki Koike, Yutaka Kondo, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Gastroenterological Endoscopy 58 (10) 2222-2231 2016

    Publisher: Japan Gastroenterological Endoscopy Society

    ISSN: 0387-1207

  138. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan

    Nobuyuki Ara, Katsunori Iijima, Ryuhei Maejima, Yutaka Kondo, Gen Kusaka, Waku Hatta, Kaname Uno, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    Gastroenterological Endoscopy 58 (8) 1367-1374 2016

    Publisher: Japan Gastroenterological Endoscopy Society

    ISSN: 0387-1207

  139. DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma. Peer-reviewed

    Thanan R, Ma N, Hiraku Y, Iijima K, Koike T, Shimosegawa T, Murata M, Kawanishi S

    Mediators of inflammation 2016 7937814 2016

    DOI: 10.1155/2016/7937814  

    ISSN: 0962-9351

  140. Usefulness of Optical Coherence Tomography Diagnosis for Superficial Esophageal Cancer

    Uno K., Koike T., Shimosegawa T.

    Nihon Kikan Shokudoka Gakkai Kaiho 67 (2) 65-65 2016

    Publisher: The Japan Broncho-esophagological Society

    DOI: 10.2468/jbes.67.65  

    ISSN: 0029-0645

  141. Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients. Peer-reviewed

    Nakagawa K, Koike T, Iijima K, Saito M, Kikuchi H, Hatta W, Ara N, Uno K, Asano N, Shimosegawa T

    World journal of gastroenterology 21 (47) 13352-13359 2015/12

    DOI: 10.3748/wjg.v21.i47.13352  

    ISSN: 1007-9327

  142. 早期胃癌ESD後の二次胃癌、食道癌発生に対する関連因子の検討

    阿見 麗子, 八田 和久, 飯島 克則, 大方 英樹, 榛澤 崇, 荒 誠之, 淺沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 57 (Suppl.2) 2080-2080 2015/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  143. 食道ESDにおける内視鏡外付け持続吸引カテーテルの開発

    八田 和久, 飯島 克則, 榛澤 崇, 荒 誠之, 淺沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 57 (Suppl.2) 2119-2119 2015/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  144. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review. International-journal Peer-reviewed

    Naoki Asano, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    World journal of gastroenterology 21 (26) 8014-20 2015/07/14

    DOI: 10.3748/wjg.v21.i26.8014  

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    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-κB) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-κB activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status.

  145. [New trends of acid-related diseases treatment]. Peer-reviewed

    Koike T, Nakagawa K, Kanno T, Iijima K, Shimosegawa T

    Nihon rinsho. Japanese journal of clinical medicine 73 (7) 1136-1146 2015/07

    ISSN: 0047-1852

  146. Endoscopic findings for predicting gastric acid secretion status. International-journal Peer-reviewed

    Waku Hatta, Katsunori Iijima, Tomoyuki Koike, Yutaka Kondo, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 27 (5) 582-9 2015/07

    DOI: 10.1111/den.12427  

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    BACKGROUND AND AIM: Gastric acidic abnormalities are related to various types of diseases in Helicobacter pylori (H. pylori) infection status. However, no studies have shown correlations between many tiny endoscopic findings and the acid secretion level simultaneously. In the present study, we investigated predictive tiny endoscopic findings of hyperchlorhydria and hypochlorhydria. METHODS: A total of 223 subjects without organic diseases who underwent esophagogastroduodenoscopy and endoscopic gastrin test (EGT) for estimating gastrin-stimulated gastric acid secretory response between 1999 and 2012 at our institution were retrospectively analyzed. Two blinded expert endoscopists reviewed the images independently and recorded the endoscopic findings. RESULTS: According to the EGT values, the enrolled subjects were categorized into hyperchlorhydria, normal acid secretion, and hypochlorhydria groups. In all subjects, hematin (odds ratio [95% confidence interval] = 3.32 [1.40-7.84]) and antral erosion(2.88 [1.24-6.70]) were the predictive endoscopic findings for hyperchlorhydria, and swelling of areae gastricae (14.4 [5.74-36.1]) and open-type atrophy (15.1 [7.35-31.1]) were those for hypochlorhydria. In addition, the predictive endoscopic findings for hyperchlorhydria differed according to the H. pylori infection status, hematin in H. pylori-positive subjects and antral erosion in H. pylori-negative subjects, in contrast to those for hypochlorhydria, which were the same irrespective of the H. pylori infection status. CONCLUSIONS: We could predict the acid secretion status based on the endoscopic findings regardless of H. pylori infection status, which would be of some help for evaluating the risk for acid-related diseases.

  147. A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan. Peer-reviewed

    Kanno T, Iijima K, Abe Y, Yagi M, Asonuma S, Ohyauchi M, Ito H, Koike T, Shimosegawa T

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 30 (5) 842-848 2015/05

    DOI: 10.1111/jgh.12876  

    ISSN: 0815-9319

    eISSN: 1440-1746

  148. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan. International-journal Peer-reviewed

    Nobuyuki Ara, Katsunori Iijima, Ryuhei Maejima, Yutaka Kondo, Gen Kusaka, Waku Hatta, Kaname Uno, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 27 (4) 458-464 2015/05

    DOI: 10.1111/den.12407  

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    BACKGROUND AND AIM: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. Antithrombotic medication and its cessation status was checked at enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or direct confirmation by telephone was done within 1 month after the biopsy. RESULTS: Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in six cases (0.15%, 95% CI; 0.09%∼0.22%), but there was only one case that had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics compared with the others (0.35% vs 0.14%, P = 0.38). CONCLUSION: This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy.

  149. Esomeprazole inhibits the pentagastrin-stimulated secretion of gastric acid in healthy Japanese volunteers. Peer-reviewed

    Maejima R, Koike T, Nakagawa K, Iijima K, Shimosegawa T

    The Tohoku journal of experimental medicine 235 (3) 249-253 2015/03

    DOI: 10.1620/tjem.235.249  

    ISSN: 0040-8727

  150. Endoscopic balloon dilatation for pharyngo-upper esophageal stricture after treatment of head and neck cancer. Peer-reviewed

    Maejima R, Iijima K, Koike T, Ara N, Uno K, Hatta W, Ogawa T, Watanabe K, Katori Y, Shimosegawa T

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 27 (3) 310-316 2015/03

    DOI: 10.1111/den.12345  

    ISSN: 0915-5635

  151. エストロゲンによる食道組織傷害抑制作用の機序に関する研究

    本田 純也, 飯島 克則, 日下 玄, 近藤 穣, 八田 和久, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 112 (臨増総会) A389-A389 2015/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  152. 早期胃癌ESD後の二次癌発生関連因子の検討

    八田 和久, 飯島 克則, 阿見 麗子, 日下 玄, 近藤 穣, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 112 (臨増総会) A427-A427 2015/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  153. Accommodation in a refugee shelter as a risk factor for peptic ulcer bleeding after the Great East Japan Earthquake: a case-control study of 329 patients. Peer-reviewed

    Kanno T, Iijima K, Koike T, Abe Y, Shimada N, Hoshi T, Sano N, Ohyauchi M, Ito H, Atsumi T, Konishi H, Asonuma S, Shimosegawa T

    J Gastroenterol. 2015 Jan;50(1):31-40 2015/01

    DOI: 10.1007/s00535-014-0940-4  

    ISSN: 0944-1174

  154. Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration. International-journal Peer-reviewed

    Ryuhei Maejima, Katsunori Iijima, Pertti Kaihovaara, Waku Hatta, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa, Mikko Salaspuro

    PloS one 10 (4) e0120397 2015

    DOI: 10.1371/journal.pone.0120397  

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    Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.

  155. Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men. Peer-reviewed

    Iijima K, Koike T, Abe Y, Ohara S, Nakaya N, Shimosegawa T

    Journal of gastroenterology 50 (8) 853-861 2014/12

    DOI: 10.1007/s00535-014-1031-2  

    ISSN: 0944-1174

  156. 当科における放射線性胃炎に対する内視鏡治療の検討

    遠藤 博之, 村田 次啓, 近藤 穣, 八田 和久, 荒 誠之, 宇野 要, 浅野 直喜, 飯島 克則, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 56 (Suppl.2) 3103-3103 2014/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  157. 上部消化管内視鏡検査における生検後出血の危険因子に関する前向き検討

    荒 誠之, 飯島 克則, 前嶋 隆平, 日下 玄, 近藤 穣, 八田 和久, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 56 (Suppl.2) 3127-3127 2014/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  158. エストロゲンによる食道組織傷害抑制作用の機序に関する研究

    本田 純也, 飯島 克則, 近藤 穣, 八田 和久, 遠藤 博之, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 111 (臨増大会) A832-A832 2014/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  159. ヒトALDH2遺伝子多型、胃酸分泌能と胃液中アセトアルデヒド濃度の関連とL-システインによるアセトアルデヒド除去効果の検討

    前嶋 隆平, 飯島 克則, 近藤 穣, 八田 和久, 遠藤 博之, 荒 誠之, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 111 (臨増大会) A843-A843 2014/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  160. 当院における頭頸部癌治療後消化管狭窄への内視鏡的バルーン拡張術の検討

    前嶋 隆平, 飯島 克則, 本田 純也, 白木 健悠, 中川 健一郎, 金 笑奕, 菅野 武, 新海 洋彦, 伏谷 淳, 近藤 穣, 八田 和久, 遠藤 博之, 荒 誠之, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 56 (Suppl.1) 1070-1070 2014/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  161. 胃酸分泌状態と内視鏡所見の関連性の検討

    八田 和久, 飯島 克則, 小池 智幸, 近藤 穣, 遠藤 博之, 荒 誠之, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 56 (Suppl.1) 1293-1293 2014/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  162. Calcium carbonate breath test for non-invasive estimation of gastric acid secretion. Peer-reviewed

    Hirohiko Shinkai, Katsunori Iijima, Tomoyuki Koike, Kenichiro Nakagawa, Ryuhei Maejima, Hiroyuki Endo, Nobuyuki Ara, Naoki Asano, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 232 (4) 255-61 2014/04

    eISSN: 1349-3329

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    Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO₃) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO₂), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO₃ breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO₃ breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO₂ concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO₃ breath test values well reflected the fasting intragastric acidity. The ¹³CO₂ concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO₃ breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO₃ breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO₃ breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

  163. Comparison of the long-term outcomes of endoscopic resection for superficial squamous cell carcinoma and adenocarcinoma of the esophagus in Japan. International-journal Peer-reviewed

    Kenichiro Nakagawa, Tomoyuki Koike, Katsunori Iijima, Hirohiko Shinkai, Waku Hatta, Hiroyuki Endo, Nobuyuki Ara, Kaname Uno, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    The American journal of gastroenterology 109 (3) 348-56 2014/03

    DOI: 10.1038/ajg.2013.450  

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    OBJECTIVES: Few studies have simultaneously evaluated the long-term outcomes of endoscopic resection (ER) for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus in Japan. The objective of this study was to evaluate the long-term outcomes of ER for superficial esophageal cancer in consecutive patients. METHODS: This was a retrospective study from a single institution. From April 2001 to June 2012, 204 patients with SCC and 26 patients with AC were included from a total of 355 consecutive patients who were treated by esophageal ER at the Tohoku University Hospital. Patients with submucosal invasion deeper than 200 μm and lymphovascular involvement were excluded. The intervention followed was endoscopic therapy. RESULTS: Overall survival, disease-free survival, and recurrence rates were evaluated as long-term outcomes. In the SCC group, during the median observation time of 36.5 months (range, 6-120 months), 22 (10.8%) patients experienced metachronous recurrence, 4 (2.0%) patients experienced local recurrence, and 27 (13.2%) patients died from causes unrelated to SCC. In the AC group, during the median observation time of 45.5 months (range, 6-131 months), one patient (3.8%) experienced metachronous recurrence and two (7.7%) died from causes unrelated to AC. The cumulative 5-year overall survival rates were not significantly different between SCC (75.9%) and AC (88.9%) (P=0.120). The cumulative 5-year disease-free survival rates of SCC (57.1%) were significantly lower than those of AC (85.2%; P=0.017). The cumulative 5-year recurrence rates of SCC (32.0%) were significantly higher than those of AC (4.2%; P=0.023). CONCLUSIONS: The rate of recurrence after ER was higher in patients with SCC than that in patients with AC. These findings suggest that, by detecting AC of the esophagus earlier, a satisfactory prognosis without recurrence can be expected after ER in Japan, and more rigorous endoscopic follow-up is necessary after ER in patients with SCC than in those with AC.

  164. PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan. Peer-reviewed

    Masamune A, Nakano E, Kume K, Takikawa T, Kakuta Y, Shimosegawa T

    GUT 63 (2) 366-366 2014/02

    DOI: 10.1136/gutjnl-2013-304925  

    ISSN: 0017-5749

    eISSN: 1468-3288

  165. NOD2 down-regulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6 Peer-reviewed

    Chiba T, Shimosegawa T, Strober W, Watanabe T, Meng G, Asano N, Arai Y, Yamashita K, Kudo M, Sakurai T, Kitani A, Fuss I.J

    Mucosal Immunol 7 (6) 1312-1325 2014

    DOI: 10.1038/mi.2014.19  

    ISSN: 1933-0219 1935-3456

  166. 東北大学病院における経皮的内視鏡的胃瘻造設術(PEG)の動向と合併症の検討

    前嶋 隆平, 荒 誠之, 小池 智幸, 遠藤 博之, 宇野 要, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹

    在宅医療と内視鏡治療 17 (1) 3-7 2013/09

    Publisher: PEG・在宅医療学会

    ISSN: 1343-1544

  167. 上部消化管内視鏡生検時の抗血栓薬の休薬状況および生検後出血に関する検討

    荒 誠之, 飯島 克則, 前嶋 隆平, 遠藤 博之, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 55 (Suppl.2) 2800-2800 2013/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  168. Collagenous gastritis. International-journal Peer-reviewed

    Xiaoyi Jin, Tomoyuki Koike, Takashi Chiba, Yutaka Kondo, Nobuyuki Ara, Kaname Uno, Naoki Asano, Katsunori Iijima, Akira Imatani, Mika Watanabe, Akio Shirane, Tooru Shimosegawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 25 (5) 547-9 2013/09

    DOI: 10.1111/j.1443-1661.2012.01391.x  

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    In the present paper, we report a case of rare collagenous gastritis. The patient was a 25-year-old man who had experienced nausea, abdominal distention and epigastralgia since 2005. Esophagogastroduodenoscopy (EGD) carried out at initial examination by the patient's local doctor revealed an extensively discolored depression from the upper gastric body to the lower gastric body, mainly including the greater curvature, accompanied by residual mucosa with multiple islands and nodularity with a cobblestone appearance. Initial biopsies sampled from the nodules and accompanying atrophic mucosa were diagnosed as chronic gastritis. In August, 2011, the patient was referred to Tohoku University Hospital for observation and treatment. EGD at our hospital showed the same findings as those by the patient's local doctor. Pathological findings included a membranous collagen band in the superficial layer area of the gastric mucosa, which led to a diagnosis of collagenous gastritis. Collagenous gastritis is an extremely rare disease, but it is important to recognize its characteristic endoscopic findings to make a diagnosis.

  169. Barrett's esophageal cancer in which magnifying narrow-band imaging was useful for diagnosing extension under the squamous epithelium. Peer-reviewed

    Koike T, Endo H, Nakagawa K, Iijima K, Shimosegawa T

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 25 Suppl 2 181-183 2013/05

    DOI: 10.1111/den.12111  

    ISSN: 0915-5635

  170. 検診上部消化管内視鏡検査を契機に診断された膵尾部癌胃直接浸潤の1例

    荒 誠之, 小池 智幸, 遠藤 博之, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹, 藤島 史喜, 菊地 亮介, 加藤 勝章, 渋谷 大助

    日本消化器がん検診学会雑誌 51 (3) 77-77 2013/05

    Publisher: (一社)日本消化器がん検診学会

    ISSN: 1880-7666

    eISSN: 2185-1190

  171. Peptic ulcers after the Great East Japan earthquake and tsunami: possible existence of psychosocial stress ulcers in humans. Peer-reviewed

    Kanno T, Iijima K, Abe Y, Koike T, Shimada N, Hoshi T, Sano N, Ohyauchi M, Ito H, Atsumi T, Konishi H, Asonuma S, Shimosegawa T

    2013/04

    DOI: 10.1007/s00535-012-0681-1  

    ISSN: 0944-1174

  172. Pancreatic intraepithelial neoplasia-3 with localized acute pancreatitis in the main pancreatic duct. Peer-reviewed

    Okada T, Motoi F, Kanno A, Masamune A, Ishida K, Fujishima F, Rikiyama T, Katayose Y, Egawa S, Shimosegawa T, Unno M

    Clinical journal of gastroenterology 6 (2) 164-168 2013/04

    DOI: 10.1007/s12328-013-0368-z  

    ISSN: 1865-7257

  173. Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic β-cells International-journal Peer-reviewed

    Kazuhiro Kikuta, Atsushi Masamune, Shin Hamada, Tetsuya Takikawa, Eriko Nakano, Tooru Shimosegawa

    Biochemical and Biophysical Research Communications 433 (3) 292-297 2013/04

    DOI: 10.1016/j.bbrc.2013.02.095  

    ISSN: 0006-291X

    eISSN: 1090-2104

  174. Identification of novel missense CTRC variants in Japanese patients with chronic pancreatitis. Peer-reviewed

    Masamune A, Nakano E, Kume K, Kakuta Y, Ariga H, Shimosegawa T

    GUT 62 (4) 653-654 2013/04

    DOI: 10.1136/gutjnl-2012-303860  

    ISSN: 0017-5749

    eISSN: 1468-3288

  175. ESDを施行した胃型胃癌4例におけるホメオボックス遺伝子Sox2とCdx2発現の検討

    千葉 隆士, 今谷 晃, 浅野 直喜, 阿部 靖彦, 近藤 穣, 伏谷 淳, 金 笑奕, 荒 誠之, 飯島 克則, 小池 智幸, 下瀬川 徹

    Gastroenterological Endoscopy 55 (Suppl.1) 1144-1144 2013/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  176. Endoscopic resection (endoscopic submucosal dissection/endoscopic mucosal resection) for superficial Barrett's esophageal cancer. Peer-reviewed

    Koike T, Nakagawa K, Iijima K, Shimosegawa T

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 25 Suppl 1 20-28 2013/03

    DOI: 10.1111/den.12047  

    ISSN: 0915-5635

  177. 【PPIをめぐる新たな展開】プロトンポンプ阻害薬の薬物動態に及ぼす食事の影響の検討

    新海 洋彦, 小池 智幸, 島田 美樹, 中川 健一郎, 飯島 克則, 今谷 晃, 松本 洋太郎, 前川 正充, 眞野 成康, 下瀬川 徹

    消化器内科 56 (2) 167-171 2013/02

    Publisher: (有)科学評論社

    ISSN: 1884-2895

  178. 幹細胞マーカーを用いた分化型早期胃癌の腫瘍増殖進展に関する免疫組織化学的検討

    千葉 隆士, 今谷 晃, 浅野 直喜, 金 笑奕, 伏谷 淳, 遠藤 博之, 荒 誠之, 飯島 克則, 小池 智幸, 下瀬川 徹

    日本消化器病学会雑誌 110 (臨増総会) A408-A408 2013/02

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  179. Gastric hypochlorhydria is associated with an exacerbation of dyspeptic symptoms in female patients. Peer-reviewed

    Wataru Iwai, Yasuhiko Abe, Katsunori Iijima, Tomoyuki Koike, Kaname Uno, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Journal of gastroenterology 48 (2) 214-21 2013/02

    DOI: 10.1007/s00535-012-0634-8  

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    BACKGROUND: Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients. METHODS: A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test. RESULTS: The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females. CONCLUSIONS: Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms.

  180. Hemorrhagic ulcers after Great East Japan Earthquake and Tsunami: features of post-disaster hemorrhagic ulcers. Peer-reviewed

    Kanno T, Iijima K, Abe Y, Koike T, Shimada N, Hoshi T, Sano N, Ohyauchi M, Ito H, Atsumi T, Konishi H, Asonuma S, Shimosegawa T

    Digestion 87 (1) 40-46 2013/01

    DOI: 10.1159/000343937  

    ISSN: 0012-2823

  181. 胃集団検診にて発見された胃腺腫様病変のサーベイランス中にリンパ節転移も伴う粘膜下層浸潤胃型腺癌を認めた一例

    荒 誠之, 宇野 要, 小池 智幸, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹, 菊地 亮介, 加藤 勝章, 渋谷 大助

    日本消化器がん検診学会雑誌 51 (1) 131-132 2013/01

    Publisher: (一社)日本消化器がん検診学会

    ISSN: 1880-7666

    eISSN: 2185-1190

  182. Eradication therapy is effective for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma. Peer-reviewed

    Naoki Asano, Katsunori Iijima, Shiho Terai, Xiaoyi Jin, Nobuyuki Ara, Takashi Chiba, Jun Fushiya, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 228 (3) 223-7 2012/11

    eISSN: 1349-3329

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    Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal B-cell lymphomas arising from MALT, and the most commonly affected organ is the stomach. Helicobacter pylori (H. pylori) eradication therapy with proton-pump inhibitors and antibiotics is the first-line therapy for H. pylori-positive gastric MALT lymphomas, but the effectiveness of the therapy for H. pylori-negative gastric MALT lymphomas remains controversial. Hence, we aimed to evaluate the effectiveness of this eradication therapy for H. pylori-negative MALT lymphomas. The H. pylori infection status of 158 gastric MALT lymphoma patients followed in our unit was judged by urea breath test, rapid urease test, histology of the biopsy specimen taken from the stomach during endoscopy, and serum antibody against H. pylori. Seventeen patients that were negative for all four tests and did not have gastric mucosal atrophy were treated with antibiotic eradication therapy. The average age at diagnosis was 56.8 years old (range: 36-73 years), and the median follow-up period after H. pylori eradication in all 17 patients was 5.3 years (range: 0.3-12.7 years). Five patients (29.4%) achieved complete remission (CR) by eradication therapy alone. Comparison between the responding and non-responding patients revealed that the patients endoscopically diagnosed to have a single lesion of gastric MALT lymphoma were seen only in the responding group, whereas all non-responding patients had multiple lesions (P < 0.05). In conclusion, H. pylori eradication therapy achieved a favorable CR rate in H. pylori-negative gastric MALT lymphoma patients and could be considered as a first-line therapy, especially for patients with a single lesion.

  183. 【食道・中下咽頭表在癌の診断と治療】食道表在癌深達度診断におけるOCT(optical coherence tomography)の有効性

    宇野 要, 八田 和久, 横沢 聡, 小池 智幸, 荒 誠之, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹

    消化器内科 55 (4) 424-430 2012/10

    Publisher: (有)科学評論社

    ISSN: 1884-2895

  184. バイアスピリンによる胃酸分泌、胃粘液分泌に及ぼす影響と胃粘膜障害 健常ボランティアにおける服薬前後の変化

    岩渕 利光, 飯島 克則, 荒 誠之, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 109 (臨増大会) A780-A780 2012/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  185. 分化型胃癌における胃関連分化制御遺伝子Sox2および腸関連分化制御遺伝子Cdx2発現の免疫組織学的検討

    千葉 隆士, 今谷 晃, 浅野 直喜, 近藤 穣, 伏谷 淳, 荒 誠之, 宇野 要, 飯島 克則, 小池 智幸, 下瀬川 徹

    日本消化器病学会雑誌 109 (臨増大会) A790-A790 2012/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  186. 13C-炭酸カルシウムを用いた呼気試験による胃酸分泌能の評価についての検討

    新海 洋彦, 飯島 克則, 伏谷 淳, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 109 (臨増大会) A797-A797 2012/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  187. 食道表在癌(扁平上皮癌・腺癌)に対する内視鏡治療後の予後に関する検討

    中川 健一郎, 小池 智幸, 宇野 要, 白木 健悠, 金 笑奕, 菅野 武, 荒 誠之, 浅野 直喜, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 54 (Suppl.2) 2840-2840 2012/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  188. 食道胃接合部腺癌・噴門部癌に対する内視鏡治療後の予後に関する検討

    中川 健一郎, 小池 智幸, 宇野 要, 白木 健悠, 金 笑奕, 菅野 武, 荒 誠之, 浅野 直喜, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 54 (Suppl.2) 2882-2882 2012/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  189. A prospective comparative study of optical coherence tomography and EUS for tumor staging of superficial esophageal squamous cell carcinoma. International-journal Peer-reviewed

    Waku Hatta, Kaname Uno, Tomoyuki Koike, Katsunori Iijima, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Gastrointestinal endoscopy 76 (3) 548-55 2012/09

    DOI: 10.1016/j.gie.2012.05.012  

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    BACKGROUND: The precise assessment of superficial esophageal squamous cell carcinomas (SESCCs) limited to the epithelium (EP) or lamina propria mucosa (LPM), the standard indication for endoscopic resection, is important to ensure good outcomes of endoscopic resection. With regard to tomographic imaging techniques, although the accuracy of EUS is practically insufficient, we previously demonstrated that high-resolution optical coherence tomography (OCT) might enable precise assessment for staging in a noninvasive and real-time manner. OBJECTIVE: To clarify the accuracy of the preoperative staging of SESCCs by using OCT compared with that by using 20-MHz probe-type EUS. DESIGN: A prospective study. SETTING: An academic medical center. PATIENTS: A total of 123 consecutive patients with 131 SESCCs were enrolled from May 2007 to September 2011. INTERVENTIONS: A specialist examined the patients, by using both OCT and EUS, recorded a representative still image for each lesion, and reported the staging immediately after each examination. Another blinded investigator reviewed the recorded images and reported the staging independently. The histological staging was confirmed by the resected specimens. Finally, we calculated the accuracy of staging by using OCT and EUS. MAIN OUTCOME MEASUREMENTS: The accuracy of OCT or EUS for EP/LPM. RESULT: The accuracy for EP/LPM by using OCT was significantly higher than that by using EUS (OCT, 94.6%; HF-EUS, 80.6%; P < .05). Interobserver agreement of OCT and EUS was good and moderate, respectively. LIMITATIONS: The small number of patients; a single-center, single-operator, nonrandomized, crossover study. CONCLUSIONS: We prospectively demonstrated that the preoperative staging of SESCC by using OCT was more useful than that by using EUS.

  190. Endoscopic submucosal dissection combined with endoscopic injection sclerotherapy for early gastric cancer on gastric fundal varices. International-journal Peer-reviewed

    Kaname Uno, Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Naoki Asano, Satoshi Yokosawa, Akira Imatani, Tooru Shimosegawa

    Surgical laparoscopy, endoscopy & percutaneous techniques 22 (4) e226-9 2012/08

    DOI: 10.1097/SLE.0b013e318254d630  

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    Currently, there is little report of treatment strategy for early gastric cancer (EGC) on gastric fundal varices (GFVs), because controlling GFVs was more challenging than controlling gastric cardiac varices associated with esophageal varices. We first report effective endoscopic treatment of EGC on GFVs of a 77-year-old man with Child-B cirrhosis. Endoscopic ultrasound and multidetector-row computed tomography studies revealed intramucosal EGC on variceal components, supplied from posterior gastric vein and drained to subphrenic vein without gastrorenal shunt. With informed consent, we performed endoscopic submucosal dissection (ESD) after eradication of GFVs by endoscopic injection sclerotherapy (EIS). Histologic assessment revealed curability of ESD and inflammation and fibrosis around EIS site. Thereafter, no recurrence and complication had occurred. To avoid life-threatening bleeding from GFVs, we achieved complete resection by ESD under direct visualization of submucosa after eradication of GFVs by EIS based on the examination of hemodynamics and local relationship between EGC and GFVs.

  191. 食道表在癌(扁平上皮癌・腺癌)に対する内視鏡治療後の長期経過に関する検討

    中川 健一郎, 小池 智幸, 宇野 要, 白木 健悠, 金 笑奕, 管野 武, 荒 誠之, 浅野 直善, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 54 (Suppl.1) 1063-1063 2012/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  192. 好酸球性食道炎の症状と内視鏡所見・病理組織所見との関連

    阿部 靖彦, 飯島 克則, 小池 智幸, 荒 誠之, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 54 (Suppl.1) 1241-1241 2012/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  193. 初発Crohn病における胃十二指腸病変の頻度について

    松下 勝則, 遠藤 克哉, 下平 陽介, 奈良 志博, 宮澤 輝子, 平本 圭一郎, 諸井 林太郎, 長澤 仁嗣, 黒羽 正剛, 志賀 永嗣, 飯島 克則, 小池 智幸, 今谷 晃, 高橋 成一, 木内 喜孝, 下瀬川 徹

    Gastroenterological Endoscopy 54 (Suppl.1) 1080-1080 2012/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  194. etodolacとnaproxenの胃酸および胃粘液分泌に及ぼす影響

    岩渕 利光, 飯島 克則, 荒 誠之, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 109 (臨増総会) A252-A252 2012/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  195. Gastric cancers emerging after H. pylori eradication arise exclusively from non-acid-secreting areas. Peer-reviewed

    Katsunori Iijima, Yasuhiko Abe, Tomoyuki Koike, Kaname Uno, Hiroyuki Endo, Waku Hatta, Naoki Asano, Kiyotaka Asanuma, Akira Imatani, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 226 (1) 45-53 2012/01

    eISSN: 1349-3329

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    Although Helicobacter pylori (H. pylori) eradication has some inhibitory effects on the subsequent development of gastric cancer, there are sporadic cases of gastric cancer even after successful eradication. The pathogenesis of gastric cancer emerging after H. pylori eradication remains to be clarified. In this study, employing Congo-red chromoendoscopy, which is capable of visualizing the acid-secreting fundic mucosa, we investigated the topographic relationship of the acid secretion pattern to the occurrence site of gastric cancers emerging after eradication. Fourteen consecutive patients who suffered from new gastric cancer after eradication, defined as lesions that were discovered at least 2 years after the eradication, were prospectively enrolled. Whether the neoplasias arose from acid-secreting or non-acid-secreting areas was evaluated with Congo-red chromoendoscopy. Biopsy specimens taken from the two areas were subjected to histologic evaluation and immunohistochemistry for Ki-67 and p53. The mean period from the eradication to the subsequent occurrence of gastric cancer was 74 (44) months. There were two cancer lesions in 5 cases, and thus there was a total 19 lesions from 14 cases. Congo-red chromoendoscopy revealed that all 19 lesions arose exclusively from non-acid-secreting areas. Histological examination revealed sustained hyperproliferation and accumulation of p53 protein was frequently detectable in non-acid-secreting areas. Genetic alteration such as p53 mutation seems to be already present in the residual non-acid-secreting areas after eradication, areas that could be the origin of gastric carcinogenesis after eradication. Identification of such high-risk areas should be a promising approach for estimating the individual cancer risk after eradication.

  196. 【Barrett食道癌の診断】主題 Barrett食道癌の内視鏡診断 通常観察での拾い上げ診断のポイント

    小池 智幸, 阿部 靖彦, 飯島 克則, 中川 健一郎, 新海 洋彦, 遠藤 博之, 荒 誠之, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹, 大原 秀一

    胃と腸 46 (12) 1800-1814 2011/11

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  197. 【変わったぞ「消化管出血のマネジメント」】上部消化管 出血性消化性潰瘍に対する止血法 純エタノール局注法を中心に

    小池 智幸, 阿部 靖彦, 宇野 要, 中川 健一郎, 新海 洋彦, 千葉 隆士, 岩渕 利光, 岩井 渉, 荒 誠之, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹

    消化器内視鏡 23 (11) 1857-1864 2011/11

    Publisher: (株)東京医学社

    ISSN: 0915-3217

  198. 【Barrett食道腺癌の診断と治療-その問題点と対策-】Barrett食道腺癌のサーベイランスをどう行うか 問題点と対策

    小池 智幸, 阿部 靖彦, 飯島 克則, 中川 健一郎, 新海 洋彦, 荒 誠之, 宇野 要, 今谷 晃, 下瀬川 徹

    消化器の臨床 14 (5) 505-509 2011/10

    Publisher: (株)ヴァンメディカル

    ISSN: 1344-3070

  199. H2O-PETで測定した健常者における食道酸注入刺激による局所脳活動変化

    田代 学, 小林 茂之, 阿部 靖彦, 小池 智幸, 飯島 克則, 今谷 晃, 大原 秀一, 渡辺 諭史, 四月朔日 聖一, 福土 審, 下瀬川 徹

    核医学 48 (3) S289-S289 2011/09

    Publisher: (一社)日本核医学会

    ISSN: 0022-7854

    eISSN: 2189-9932

  200. 内視鏡的切除により診断しえた食道腺扁平上皮癌の一例

    遠藤 博之, 小池 智幸, 新海 洋彦, 浅沼 清孝, 宇野 要, 浅野 直喜, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 53 (Suppl.2) 2605-2605 2011/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  201. ラット逆流性食道炎モデルを用いた食道粘膜傷害に対するエストロゲンの影響

    眞坂 智寛, 飯島 克則, 遠藤 博之, 浅沼 清孝, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 108 (臨増大会) A774-A774 2011/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  202. 胃における腸上皮化生進展時に誘導される新規遺伝子Trib3による発癌・増殖機序の解析

    近藤 穣, 今谷 晃, 浅野 直喜, 伏谷 淳, 千葉 隆士, 小池 智幸, 飯島 克則, 下瀬川 徹

    日本消化器病学会雑誌 108 (臨増大会) A787-A787 2011/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  203. 食道胃接合部癌の治療方針 食道胃接合部腺癌の病態および臨床病理学的特徴と内視鏡治療後の長期予後に関する検討

    小池 智幸, 阿部 靖彦, 飯島 克則, 宇野 要, 今谷 晃, 下瀬川 徹

    日本食道学会学術集会プログラム・抄録集 65回 109-109 2011/09

    Publisher: (NPO)日本食道学会

  204. A case of benign natural killer cell proliferative disorder of the stomach (gastric manifestation of natural killer cell lymphomatoid gastroenteropathy) mimicking extranodal natural killer/T-cell lymphoma. International-journal Peer-reviewed

    Joji Yamamoto, Fumiyoshi Fujishima, Ryo Ichinohasama, Akira Imatani, Naoki Asano, Hideo Harigae

    Leukemia & lymphoma 52 (9) 1803-5 2011/09

    DOI: 10.3109/10428194.2011.573030  

  205. Helicobacter pylori感染症時代の除菌診療 その課題とは何か(第6回) 宮城県におけるHelicobacter pylori除菌診療の現況 東北大学病院消化器内科より

    阿部 靖彦, 小池 智幸, 飯島 克則, 今谷 晃, 下瀬川 徹, 関根 仁

    Helicobacter Research 15 (4) 365-369 2011/08

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  206. Two distinct types of cancer of different origin may be mixed in gastroesophageal junction adenocarcinomas in Japan: evidence from direct evaluation of gastric acid secretion. International-journal Peer-reviewed

    Toru Horii, Tomoyuki Koike, Yasuhiko Abe, Ryosuke Kikuchi, Hiroyuki Unakami, Katsunori Iijima, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Scandinavian journal of gastroenterology 46 (6) 710-9 2011/06

    DOI: 10.3109/00365521.2011.565069  

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    BACKGROUND AND AIMS: Barrett's esophageal cancer is usually included in gastroesophageal (GE) junction adenocarcinoma in Japanese people. No study on the pathogenesis of Barrett's esophageal cancer in comparison with GE junction adenocarcinoma other than Barrett's esophageal cancer has been reported in Japan. The aim of this study was to evaluate the clinical and pathological characteristics and gastric acid secretion of Barrett's esophageal cancer and GE junction adenocarcinoma other than Barrett's esophageal cancer in Japanese subjects. MATERIAL AND METHODS: Twenty-three patients with Barrett's esophageal cancer and 23 patients with GE junction adenocarcinoma other than Barrett's esophageal cancer were enrolled in this study. We evaluated and compared them by assessing the Helicobactor pylori (HP) infection status and gastric acid secretion using the endoscopic gastrin test (EGT). RESULTS: In the patients with Barrett's esophageal cancer, no significant difference was found in the mean EGT value between HP-positive and -negative patients, but in the patients with GE junction adenocarcinoma other than Barrett's esophageal cancer, the mean EGT value in HP-positive patients was significantly lower than that in HP-negative patients. CONCLUSION: Two distinct types of cancer of different origin may be mixed in GE junction adenocarcinomas. One is Barrett's esophageal cancer associated with high gastric acid secretion and reflux of gastric acid into the esophagus, the other is cancer resembling distal gastric cancer associated with gastric atrophy and low gastric acid secretion.

  207. Gastric acid secretion level modulates the association between Helicobacter pylori infection and low-dose aspirin-induced gastropathy. Peer-reviewed

    Katsunori Iijima, Nobuyuki Ara, Yasuhiko Abe, Tomoyuki Koike, Wataru Iwai, Kaname Uno, Naoki Asano, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology 46 (5) 612-9 2011/05

    DOI: 10.1007/s00535-011-0385-y  

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    BACKGROUND: The relative contribution of gastric acid secretion and Helicobacter pylori infection to low-dose aspirin-induced gastropathy remains to be clarified. This is partly because the capability of the infection to modify gastric acid secretion complicates the interaction. The aim of this study was to estimate the association of aspirin-induced mucosal injury, as well as H. pylori infection, with gastric acid output. METHODS: A total of 186 male outpatients, comprising 60 aspirin takers, on 100 mg of enteric-coated aspirin daily and 126 non-aspirin takers were prospectively enrolled in this study. Gastrin-stimulated acid output was estimated by the endoscopic gastrin test. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score. Multiple logistic regression analyses were used to adjust for potential confounders. RESULTS: The gastric acid secretion level, with an odds ratio (OR) (95% confidence interval [CI]) of 10.5 (3.0-36.9) and aspirin administration, with an OR (95% CI) of 7.4 (3.0-18.3) were independently associated with gastric mucosal injury, and the co-existence of both factors greatly elevated the risk of mucosal injury, with an OR (95% CI) of 77.0 (13.5-440.0). H. pylori infection, itself, did not show any significant effect on the aspirin-induced mucosal injury after adjusting for gastric acid secretion. CONCLUSIONS: This study has demonstrated that aspirin-induced gastropathy is directly associated with gastric acid secretion. In addition, it also suggested that the gastric acid secretion level modulates the association between H. pylori infection and aspirin-induced gastropathy.

  208. Signet Ring Cell Gastric Cancer Occurring after Radiation Therapy for Helicobacter pylori-Uninfected Mucosa-Associated Lymphoid Tissue Lymphoma. International-journal Peer-reviewed

    Naoki Asano, Katsunori Iijima, Shiho Terai, Kaname Uno, Hiroyuki Endo, Tomoyuki Koike, Wataru Iwai, Toshimitsu Iwabuchi, Waku Hatta, Yasuhiko Abe, Akira Imatani, Tooru Shimosegawa

    Case reports in gastroenterology 5 (2) 325-9 2011/05

    DOI: 10.1159/000329559  

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    Helicobacter pylori infection is the major cause for mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancers. On the other hand, gastric cancers are known to arise from gastric mucosal atrophy. We here report a case of signet ring cell gastric cancer that developed after radiation therapy for MALT lymphoma in H. pylori-uninfected patient whose stomach did not show gastric mucosal atrophy. A 58-year-old female was referred to our hospital for treatment of gastric MALT lymphoma. This patient was not infected with H. pylori, and upper gastrointestinal endoscopy revealed that she did not have gastric mucosal atrophy but had submucosal tumor-like MALT lymphoma lesion in the anterior wall of the upper gastric body. Since conventional eradication therapy was ineffective, her whole stomach was irradiated as a second-line therapy. The MALT lymphoma lesion turned into complete remission state after the therapy. The patient was followed every 6 months by upper gastrointestinal endoscopy for 4 years as complete remission until a newly developed decolorized depressed lesion was detected in the greater curvature of the proximal antrum, a completely different location from the MALT lymphoma lesion. A biopsy specimen from the lesion contained signet ring cell carcinoma, and she was successfully treated by endoscopic submucosal dissection. No signs of recurrence have been detected so far. The radiation therapy for MALT lymphoma might be associated with the occurrence of this signet ring cell gastric cancer, and since MALT lymphoma is indolent in nature, this case suggests that careful consideration is required when choosing the second-line therapy for MALT lymphoma patients.

  209. 【難治性GERDの治療戦略】好酸球性食道炎の臨床像 内視鏡像・病理組織像を中心に

    阿部 靖彦, 飯島 克則, 小池 智幸, 今谷 晃, 下瀬川 徹

    消化器内科 52 (4) 349-354 2011/04

    Publisher: (有)科学評論社

    ISSN: 1884-2895

  210. バレット食道・食道腺癌病態形成におけるNOの役割

    日下 玄, 宇野 要, 飯島 克則, 遠藤 博之, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 108 (臨増総会) A220-A220 2011/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  211. 好酸球性食道炎の内視鏡像に関する検討

    阿部 靖彦, 飯島 克則, 小池 智幸, 遠藤 博之, 浅沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 108 (臨増総会) A283-A283 2011/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  212. 【Helicobacter pylori除菌後GERDの実態】Helicobacter pylori除菌後のGERD 発生メカニズムは?

    小池 智幸, 飯島 克則, 阿部 靖彦, 遠藤 博之, 浅沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 下瀬川 徹, 大原 秀一

    Helicobacter Research 15 (1) 32-41 2011/02

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  213. A Japanese case series of 12 patients with esophageal eosinophilia. Peer-reviewed

    Yasuhiko Abe, Katsunori Iijima, Shuichi Ohara, Tomoyuki Koike, Nobuyuki Ara, Kaname Uno, Naoki Asano, Akira Imatani, Katsuaki Kato, Daisuke Shibuya, Tooru Shimosegawa

    Journal of gastroenterology 46 (1) 25-30 2011/01

    DOI: 10.1007/s00535-010-0295-4  

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    BACKGROUND: Eosinophilic esophagitis (EoE) has been a rarely recognized condition in Asian populations, and its clinical manifestation is rarely documented. Our aim was to describe clinically, endoscopically, and pathologically the features of patients with esophageal eosinophilia, including EoE. METHODS: Twelve patients histologically proven to have esophageal eosinophilia were investigated. The histological diagnostic cutoff value was defined as a peak of ≥15 eosinophils/high-power field (HPF) in esophageal biopsies. Symptoms, endoscopic and pathological findings, and treatment outcome were evaluated. RESULTS: Nine of the 12 patients were male and the 12 patients had a mean age of 47.7 years. Allergic conditions were concurrent in a total of 3 patients. Mild peripheral eosinophilia was observed in only 2 patients. The predominant symptom was solid-food dysphagia, but some patients complained of heartburn, or chest, epigastric, or back pain. Three asymptomatic subjects were also incidentally diagnosed during endoscopic screening. Linear furrows, concentric rings, and white exudates in the esophagus were frequently observed. In 4 of 5 patients who were administered a proton pump inhibitor (PPI), esophageal eosinophilia was histologically decreased or disappeared with symptom relief and endoscopic improvement. In 2 patients unresponsive to PPI, topical steroid therapy, administered by the swallowing of fluticasone propionate, led to symptomatic and histological remission. CONCLUSIONS: The endoscopic recognition of linear furrows, concentric rings, and white exudates is important in the diagnosis of eosinophilic esophageal inflammation. In a subset of patients this condition improves clinicopathologically with PPI treatment, and typical EoE, as strictly defined by unresponsiveness to PPI, appears to be a rather rare condition.

  214. Low serum levels of pepsinogen and gastrin 17 are predictive of extensive gastric atrophy with high-risk of early gastric cancer. Peer-reviewed

    Ryousuke Kikuchi, Yasuhiko Abe, Katsunori Iijima, Tomoyuki Koike, Nobuyuki Ara, Kaname Uno, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 223 (1) 35-44 2011/01

    eISSN: 1349-3329

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    Atrophic gastritis (AG) is a well-recognized high-risk condition for developing gastric cancer (GC). Gastrin 17 (G17), a hormone secreted from antral G cells, regulates gastric acid secretion, and its serum level is a possible indicator of antral atrophy. Serum pepsinogen is well established as the indicator of AG involving the corpus. Here we investigated whether serum PG and G17 levels would be useful for determining the topographic pattern of AG and estimating the risk of GC. Enrolled were 122 Japanese patients with early GC (114 well- to moderate-differentiated cancers and 8 poorly-differentiated cancers). In addition, 178 subjects without GC were recruited as control from those undergoing endoscopic examination (non-GC group). All subjects were histologically assigned to the following four groups: non-AG, antrum-predominant AG, corpus-predominant AG, and multifocal AG, affecting the antrum and corpus. Serum concentrations of pepsinogen and G17 were determined using ELISA. Multifocal AG was more frequent in the GC group than in the adjusted non-GC group, and had the highest risk of GC (OR 25.1). Serum G17 was significantly decreased with the exacerbation of antral atrophy in the coexistence of corpus atrophy. Serum biomarker profiles showed that the low levels of pepsinogen and G17 could discriminate between multifocal AG and other types of AG, but not with pepsinogen level alone. Serologically defined multifocal AG had the highest cancer risk among other serologically defined AG groups (OR 26.9). In conclusion, the low serum levels of pepsinogen and G17 are predictive of extensive gastric atrophy with high-risk of early GC.

  215. Esophageal Adenocarcinoma Developing after Eradication of Helicobacter pylori. International-journal Peer-reviewed

    Yasuhiko Abe, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Kazuhiko Ishida, Toyohiko Yuki, Go Miyata, Tooru Shimosegawa

    Case reports in gastroenterology 5 (2) 355-60 2011

    DOI: 10.1159/000329878  

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    A 75-year-old man underwent endoscopic hemostatic therapy for hemorrhagic gastric ulcer in September 2002. After healing of the gastric ulcer, he underwent Helicobacter pylori eradication therapy in February 2003. In August 2007, an irregular tumor was detected in the lower esophagus at annual checkup for gastric cancer screening using X-ray. Endoscopic examination showed that the lower margin of the tumor almost coincided with the esophagogastric junction and that a short segment of Barrett's epithelium existed near the tumor. Biopsies of the tumor showed moderately to poorly differentiated adenocarcinoma. Mild reflux esophagitis and minor hiatal hernia was also observed, and the previously treated gastric ulcer was not recurrent. Absence of H. pylori was confirmed by serum antibody and urea breath test. Surgical resection of the lower esophagus and proximal stomach was performed. The tumor invaded into the muscularis propria of the esophageal wall but had no evidence of lymph node metastasis. Based on macroscopic and pathological findings, the tumor was recognized as esophageal adenocarcinoma. Previous endoscopic examination did not detect any apparent signs of tumor in the esophagogastric junction. As far as we know, this is the first report documenting a newly developed esophageal adenocarcinoma after the successful eradication of H. pylori.

  216. Brain activity following esophageal acid infusion using positron emission tomography. International-journal Peer-reviewed

    Shigeyuki Kobayashi, Yasuhiko Abe, Manabu Tashiro, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Shuichi Ohara, Satoshi Watanabe, Shin Fukudo, Tooru Shimosegawa

    World journal of gastroenterology 16 (43) 5481-9 2010/11/21

    eISSN: 2219-2840

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    AIM: To investigate symptoms and brain activity following esophageal acid infusion. METHODS: Fifteen healthy volunteers were recruited for the study. Hydrochloric acid (pH 1 and 2) and distilled water (pH 7) were randomly and repeatedly infused into the esophagus. The brain activity was evaluated by positron emission tomography. The severity of heartburn elicited by the infusion was rated on an auditory analog scale of 0-10. RESULTS: The severity of heartburn following each infusion showed a step-wise increase with increasing acidity of the perfusate. The heartburn scores were significantly higher in the second pH 1 infusion compared with the first infusion. Acid and distilled water infusion induced activation of various brain areas such as the anterior insula, temporal gyrus, and anterior/posterior cingulate cortex. At pH 1 or 2, in particular, activation was observed in some emotion-related brain areas such as the more anterior part of the anterior cingulate cortex, parahippocampal gyrus, or the temporal pole. Strong activation of the orbitofrontal cortex was found by subtraction analysis of the two second pH 1 infusions, with a significant increase of heartburn symptoms. CONCLUSION: Emotion-related brain areas were activated by esophageal acid stimulation. The orbitofrontal area might be involved in symptom processing, with esophageal sensitization induced by repeated acid stimulation.

  217. 【日常診療で診る感染症 この疾患を見落とすな】よく見かける感染症 診断・治療の最新事情 Helicobacter pylori感染症

    今谷 晃, 浅野 直喜, 阿部 靖彦, 小池 智幸, 飯島 克則, 下瀬川 徹

    内科 106 (5) 830-834 2010/11

    Publisher: (株)南江堂

    ISSN: 0022-1961

    eISSN: 2432-9452

  218. Exogenous luminal nitric oxide exposure accelerates columnar transformation of rat esophagus. International-journal Peer-reviewed

    Hiroyuki Endo, Katsunori Iijima, Kiyotaka Asanuma, Nobuyuki Ara, Hirotaka Ito, Naoki Asano, Kaname Uno, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    International journal of cancer 127 (9) 2009-19 2010/11/01

    DOI: 10.1002/ijc.25227  

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    Exposure of the esophageal mucosa to refluxed gastroduodenal contents is recognized to be an important risk factor for Barrett's esophagus (BE). At the human gastroesophageal junction, nitric oxide is generated luminally through the enterosalivary recirculation of dietary nitrate, and in cases with gastroesophageal reflux, the site of luminal nitric oxide generation could shift to the distal esophagus. The aim of this study is to investigate whether exogenous luminal nitric oxide could promote the development of BE in rats. Sodium nitrite plus ascorbic acid were administered to a rat surgical model of BE, in which the gastroduodenal contents were refluxed into the esophagus to generate exogenous luminal nitric oxide in the esophagus by the acid-catalyzed chemical reaction between the 2 reagents. The emergence of BE was evaluated histologically in the early phase (several weeks) after the surgery with or without exogenous nitric oxide administration. To elucidate the histogenesis of BE, CDX2, MUC2 and MUC6 expressions were investigated immunohistochemically. Coadministration of sodium nitrite plus ascorbic acid significantly accelerated the timing of emergence and increased the area of BE compared with controls. Administration of either reagent alone did not show any promotive effects on BE formation. Immunohistochemically, the columnar epithelium thus induced was similar to the specialized intestinal metaplasia in human BE. The results of this animal model study suggest that exogenous luminal nitric oxide could be involved in the pathogenesis of the columnar transformation of the esophagus. Further studies in human are warranted.

  219. Deficient aldehyde dehydrogenase 2 is associated with increased risk for esophageal squamous cell carcinoma in the presence of gastric hypochlorhydria. International-journal Peer-reviewed

    Tomoyuki Oikawa, Katsunori Iijima, Tomoyuki Koike, Kaname Uno, Toru Horii, Wataru Iwai, Yasuhiko Abe, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    Scandinavian journal of gastroenterology 45 (11) 1338-44 2010/11

    DOI: 10.3109/00365521.2010.495419  

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    OBJECTIVE: In Orientals, deficient aldehyde dehydrogenase 2 (ALDH2) is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). The local metabolism of carcinogenic acetaldehyde in the upper gastrointestinal tract could be involved in the association, but the underlying mechanism has not been fully elucidated. Since an anacidic stomach can promote bacteria-catalyzed local acetaldehyde production, the gastric acid level could also affect acetaldehyde metabolism. This study investigated whether ALDH2-related susceptibility to ESCC differs depending on the gastric secretion level. MATERIAL AND METHODS: Sixty-two patients with ESCC and sex- and age-matched normal controls were enrolled in this study. ALDH2 polymorphism was analyzed by polymerase chain-restriction fragment length polymorphism, and those with an inactive allele (ALDH2-1/2-2 or ALDH2-2/2-2) were defined as ALDH2 deficient. Gastrin-stimulated acid output was assessed by endoscopic gastrin test and hypochlorhydria was defined as 0.6 mEq/10 min or lower. Multiple logistic regression analyses were used to adjust for other potential confounders. RESULTS: ALDH2 deficiency or hypochlorhydria was more prevalent in ESCC compared with controls and both showed increased independent associations with ESCC in multivariate analysis. Stratified analysis by the gastric acid secretion level revealed that the associations between the ALDH2 genotype and ESCC differed according to the individual gastric acid secretion levels and that ALDH2 deficiency was a significant risk factor for ESCC exclusively in individuals with hypochlorhydria with an odds ratio (95% confidence interval): 5.0 (1.2-21.2). CONCLUSION: Microbial production of carcinogen acetaldehyde in the presence of gastric hypochlorhydria is most probably involved in the mechanism of ALDH2-related susceptibility to ESCC.

  220. 表在型食道扁平上皮癌深達度診断におけるOCT(optical coherence tomography)の有用性

    八田 和久, 宇野 要, 小池 智幸, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 52 (Suppl.2) 2405-2405 2010/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  221. ラット逆流性食道炎における雌雄間での食道粘膜傷害の違いについて

    眞坂 智寛, 飯島 克則, 荒 誠之, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 107 (臨増大会) A775-A775 2010/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  222. 上腹部症状と胃酸分泌能に関する検討

    岩井 渉, 阿部 靖彦, 小池 智幸, 飯島 克則, 浅野 直喜, 宇野 要, 荒 誠之, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 107 (臨増大会) A776-A776 2010/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  223. Gastric Hyposecretion in Esophageal Squamous-Cell Carcinomas Peer-reviewed

    K. Iijima, T. Koike, Y. Abe, H. Yamagishi, N. Ara, K. Asanuma, K. Uno, A. Imatani, N. Nakaya, S. Ohara, T. Shimosegawa

    DIGESTIVE DISEASES AND SCIENCES 55 (5) 1349-1355 2010/05

    DOI: 10.1007/s10620-009-0853-x  

    ISSN: 0163-2116

  224. Optical coherence tomography for the staging of tumor infiltration in superficial esophageal squamous cell carcinoma. International-journal Peer-reviewed

    Waku Hatta, Kaname Uno, Tomoyuki Koike, Satoshi Yokosawa, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    Gastrointestinal endoscopy 71 (6) 899-906 2010/05

    DOI: 10.1016/j.gie.2009.11.052  

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    BACKGROUND: Optical coherence tomography (OCT) is a noninvasive technology that can produce high-resolution cross-sectional images in real-time without acoustic coupling, enabling precise assessment of tumor invasion in superficial esophageal squamous cell carcinomas (SESCCs). OBJECTIVE: To elucidate the usefulness of in vivo OCT for the staging of SESCCs. DESIGN: A single-center, prospective study in 2 phases: phase I to establish the OCT criteria classified into 3 categories (epithelium or lamina propria mucosa [EP/LPM], muscularis mucosa [MM], submucosa [SM]) and phase II to evaluate these criteria. SETTING: An academic medical center. PATIENTS: Sixty-two patients with a histological diagnosis of SESCC by routine endoscopy. In the phase I study, 35 images from 16 patients were used. In the phase II study, 109 images from 46 subsequent consecutive patients enrolled from January 2007 to May 2009 were used. INTERVENTIONS: We performed OCT for preoperative staging followed by endoscopic submucosal dissection or a surgical procedure and compared precisely the visualized OCT sites with the corresponding tissue sections. MAIN OUTCOME MEASUREMENTS: The accuracy of OCT for the staging. RESULTS: The overall accuracy rate was 92.7% (EP/LPM, 94.9%; MM, 85.0%; SM, 90.9%). The OCT signal penetration depth was sufficient to depict the boundary of the deepest region of cancer, the thickness of which was less than 1.5 mm. LIMITATIONS: The small number of patients. CONCLUSIONS: To our knowledge, this is the first study demonstrating that OCT might be useful for the preoperative staging of SESCCs with a high degree of accuracy.

  225. 外因性一酸化窒素(NO)によるバレット食道発生に対する影響について

    遠藤 博之, 浅沼 清孝, 飯島 克則, 荒 誠之, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    Therapeutic Research 31 (4) 491-496 2010/04

    Publisher: ライフサイエンス出版(株)

    ISSN: 0289-8020

  226. Reactive nitrogen oxide species induce dilatation of the intercellular space of rat esophagus Peer-reviewed

    H. Ito, K. Iijima, N. Ara, K. Asanuma, H. Endo, N. Asano, T. Koike, Y. Abe, A. Imatani, T. Shimosegawa

    SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 45 (3) 282-291 2010/03

    DOI: 10.3109/00365520903469956  

    ISSN: 0036-5521

  227. 当科に於けるPEGの現状

    岩井 渉, 荒 誠之, 小池 智幸, 日下 玄, 近藤 穣, 真坂 智寛, 海上 寛之, 八田 和久, 伊藤 博敬, 遠藤 博之, 菊地 亮介, 小西 秀知, 堀井 享, 石山 文威, 及川 智之, 小林 茂之, 寺井 志保, 浅沼 清孝, 宇野 要, 阿部 靖彦, 飯島 克則, 今谷 晃, 朝倉 徹, 大原 秀一, 下瀬川 徹

    静脈経腸栄養 25 (2) 627-627 2010/03

    Publisher: (株)ジェフコーポレーション

    ISSN: 1344-4980

    eISSN: 1881-3623

  228. 大学病院に於けるPEG造設の現状

    荒 誠之, 小池 智幸, 岩渕 利光, 千葉 隆士, 日下 玄, 近藤 穣, 真坂 智寛, 海上 寛之, 八田 和久, 伊藤 博敬, 遠藤 博之, 菊地 亮介, 小西 秀知, 堀井 享, 宇野 要, 浅野 直喜, 阿部 靖彦, 飯島 克則, 今谷 晃, 朝倉 徹, 下瀬川 徹

    静脈経腸栄養 25 (2) 631-631 2010/03

    Publisher: (株)ジェフコーポレーション

    ISSN: 1344-4980

    eISSN: 1881-3623

  229. 加齢に伴う胃酸分泌能の経時的変化に関する検討

    堀井 享, 飯島 克則, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 107 (臨増総会) A301-A301 2010/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  230. 胃酸分泌低下、ALDH2遺伝子多型と食道扁平上皮癌の関連

    飯島 克則, 小池 智幸, 阿部 靖彦, 宇野 要, 今谷 晃, 及川 智之, 下瀬川 徹

    日本消化器病学会雑誌 107 (臨増総会) A314-A314 2010/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  231. 低用量アスピリン内服者における胃粘膜傷害の検討

    荒 誠之, 飯島 克則, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 107 (臨増総会) A335-A335 2010/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  232. 【Barrett食道の最前線 腺癌発生のメカニズム】食道胃接合部癌の臨床病理学的特徴と病態 とくにHelicobacter pylori感染と胃酸分泌の面からみた病態について

    阿部 靖彦, 大原 秀一, 小池 智幸, 堀井 享, 飯島 克則, 浅野 直喜, 宇野 要, 荒 誠之, 今谷 晃, 下瀬川 徹

    G.I.Research 18 (1) 24-30 2010/02

    Publisher: (株)先端医学社

    ISSN: 0918-9408

  233. 【H.pylori除菌後に発見された胃癌】H.pylori除菌後に発見された胃癌症例の検討

    菊地 亮介, 阿部 靖彦, 飯島 克則, 小池 智幸, 今谷 晃, 下瀬川 徹

    消化器内科 50 (1) 19-23 2010/01

    Publisher: (有)科学評論社

    ISSN: 1884-2895

  234. Identification of the layered morphology of the esophageal wall by optical coherence tomography. International-journal Peer-reviewed

    Satoshi Yokosawa, Tomoyuki Koike, Yasushi Kitagawa, Waku Hatta, Kaname Uno, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    World journal of gastroenterology 15 (35) 4402-9 2009/09/21

    eISSN: 2219-2840

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    AIM: To assess each layer of the optical coherence tomography (OCT) image of the esophageal wall with reference to the histological structure. METHODS: Resected specimens of fresh pig esophagus was used as a model for the esophageal wall. We injected cyanoacrylate adhesive into the specimens to create a marker, and scanned them using a miniature OCT probe. The localization of these markers was assessed in the OCT images. Then we compared the OCT-imaged morphology with the corresponding histological section, guided by the cyanoacrylate adhesive markers. We prepared a second set of experiments using nylon sutures as markers. RESULTS: The OCT image of the esophageal specimen has a clear five-layered morphology. First, it consisted of a relatively less reflective layer; second, a more reflective layer; third, a less reflective layer; fourth, a more reflective layer; and fifth, a less reflective layer. Comparing the OCT images with marked histological sections showed that the first layer corresponded to stratified squamous epithelium; the second to lamina propria; the third to muscularis mucosa; fourth, submucosa; and fifth, muscularis propria with deeper structures of the esophageal wall. CONCLUSION: We demonstrated that the OCT image of the normal esophageal wall showed a five-layered morphology, which corresponds to histological esophageal wall components.

  235. 好酸球性食道炎10例の内視鏡像・病理組織像

    阿部 靖彦, 大原 秀一, 飯島 克則, 荒 誠之, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 51 (Suppl.2) 2213-2213 2009/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  236. 食道内腔で発生する一酸化窒素の粘膜上皮防御機構と細胞間隙拡大に及ぼす影響

    伊藤 博敬, 飯島 克則, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増大会) A750-A750 2009/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  237. H.pylori感染における自然免疫応答タンパクNOD1の+32656位遺伝子多型の機能解析

    及川 智之, 今谷 晃, 浅野 直喜, 阿部 靖彦, 飯島 克則, 小池 智幸, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増大会) A767-A767 2009/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  238. 噴門部小彎からの出血を繰り返し治療に難渋した胃食道静脈瘤の1例

    荒 誠之, 小池 智幸, 宇野 要, 浅野 直喜, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹, 及川 圭介, 杉山 幸一

    日本門脈圧亢進症学会雑誌 15 (1) 95-95 2009/08

    Publisher: (一社)日本門脈圧亢進症学会

    ISSN: 1344-8447

    eISSN: 2186-6376

  239. 食道静脈瘤を伴う食道表在癌に対する内視鏡治療

    宇野 要, 小池 智幸, 飯島 克則, 阿部 靖彦, 浅野 直喜, 荒 誠之, 今谷 晃, 下瀬川 徹, 萱場 尚一

    日本門脈圧亢進症学会雑誌 15 (1) 108-108 2009/08

    Publisher: (一社)日本門脈圧亢進症学会

    ISSN: 1344-8447

    eISSN: 2186-6376

  240. Clinical Characteristics of Gastroesophageal Reflux Disease in Japan Peer-reviewed

    Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Katsuaki Kato, Daisuke Shibuya, Shigemitsu Aida, Tooru Shimosegawa

    HEPATO-GASTROENTEROLOGY 56 (93) 1032-1034 2009/07

    ISSN: 0172-6390

  241. 【バレット食道の取扱い】Barrett食道癌を含む食道胃接合部癌の病態

    小池 智幸, 堀井 享, 阿部 靖彦, 荒 誠之, 宇野 要, 浅野 直喜, 飯島 克則, 今谷 晃, 下瀬川 徹

    消化器科 49 (1) 62-68 2009/07

    Publisher: (有)科学評論社

    ISSN: 0289-8756

  242. Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers. Peer-reviewed

    Shiho Terai, Katsunori Iijima, Kiyotaka Asanuma, Nobuyuki Ara, Kaname Uno, Yasuhiko Abe, Tomoyuki Koike, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 218 (1) 73-9 2009/05

    eISSN: 1349-3329

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    Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers.

  243. 食道粘膜上皮の防御機構に対する一酸化窒素の影響

    伊藤 博敬, 飯島 克則, 荒 誠之, 浅沼 清孝, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増総会) A250-A250 2009/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  244. 外因性NOによるバレット食道発生に対する影響

    遠藤 博之, 浅沼 清孝, 飯島 克則, 荒 誠之, 宇野 要, 浅野 直喜, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増総会) A250-A250 2009/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  245. 血清pepsinogen値、gastrin17値を用いた胃粘膜萎縮の評価に関する検討

    菊地 亮介, 大原 秀一, 阿部 靖彦, 飯島 克則, 荒 誠之, 宇野 要, 浅沼 清孝, 浅野 直喜, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増総会) A313-A313 2009/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  246. 逆流性食道炎に対するon-demand療法の有用性の検討

    海上 寛之, 小池 智幸, 大原 秀一, 堀井 亨, 菊地 亮介, 小林 茂之, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 106 (臨増総会) A322-A322 2009/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  247. Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. Peer-reviewed

    Katsunori Iijima, Tomoyuki Koike, Hitoshi Sekine, Yasuhiko Abe, Kiyotaka Asanuma, Nobuyuki Ara, Kaname Uno, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology 44 (1) 47-55 2009

    DOI: 10.1007/s00535-008-2270-x  

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    BACKGROUND: We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa. METHODS: In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acid-secreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index. RESULTS: After a gradual increase in acid-secreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well. CONCLUSIONS: Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.

  248. Exogenous luminal nitric oxide exacerbates esophagus tissue damage in a reflux esophagitis model of rats. International-journal Peer-reviewed

    Fumitake Ishiyama, Katsunori Iijima, Kiyotaka Asanuma, Nobuyuki Ara, Jun Yoshitake, Yasuhiko Abe, Tomoyuki Koike, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Scandinavian journal of gastroenterology 44 (5) 527-37 2009

    DOI: 10.1080/00365520802699260  

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    OBJECTIVE: Cytotoxic concentrations of nitric oxide are generated luminally at the gastroesophageal junction through the entero-salivary recirculation of dietary nitrate in humans. The site of luminal nitric oxide generation shifts to the lower esophagus when gastric acid is refluxed into the esophagus. The aim of this study was to investigate the influence of persistent administration of exogenous nitric oxide on esophageal damage. MATERIAL AND METHODS: 0.1% sodium nitrite and/or 1% ascorbic acid was administered in an established rat acid-refluxed esophagitis model. Co-administration of both reactants in this model is thought to induce high concentrations of nitric oxide luminally in the esophagus by an acid-catalyzed chemical reaction when refluxed gastric acid is present. The tissue damage was evaluated by a macroscopic lesion index and myeloperoxidase activity. Nitrotyrosin was assessed immunohistochemically as a footprint of peroxynitrite formation. RESULTS: Co-administration of sodium nitrite and ascorbic acid induced a 4- to 5-fold increase in the esophageal damage compared with baseline reflux esophagitis, while the damage was unchanged when either of the reagents alone was given. Nitrotyrosine was strongly stained in the tissue from the co-administration. Treatment of superoxide scavengers efficiently prevented the exacerbation of esophageal damage by exogenous nitric oxide exposure, suggesting an essential role of superoxide in esophageal damage. CONCLUSIONS: Exogenous luminal nitric oxide greatly exacerbated the tissue damage of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent superoxide-enriched inflamed tissue of the esophagus could lead to the production of the highly toxic agent peroxynitrite, thus causing exacerbation of the esophageal damage.

  249. Barrett's esophagus is characterized by the absence of Helicobacter pylori infection and high levels of serum pepsinogen I concentration in Japan. International-journal Peer-reviewed

    Yasuhiko Abe, Katsunori Iijima, Tomoyuki Koike, Kiyotaka Asanuma, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology and hepatology 24 (1) 129-34 2009/01

    DOI: 10.1111/j.1440-1746.2008.05691.x  

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    BACKGROUND AND AIM: It has been reported that patients with Barrett's esophagus (BE) may have gastric acid hypersecretion. Serological markers such as serum pepsinogen or gastrin have been used to estimate the gastric secretory function. The aim of this study was to compare the serum pepsinogen and gastrin concentrations in view of Helicobacter pylori infection status between BE patients and the controls. METHODS: Thirty-six patients with long-segment BE were enrolled in this study. Three age- and sex-matched controls were assigned to each patient. Serum pepsinogen and gastrin concentrations were measured by radioimmunoassay and H. pylori infection was determined by histology and serum IgG antibodies. RESULTS: Helicobacter pylori infection was present in 4 of 36 patients (11%) with BE and in 80 of 108 controls (74%), being less prevalent in BE patients than in the controls (P < 0.0001). When examined in the H. pylori-negative subjects, both the serum pepsinogen I and pepsinogen II concentrations in BE patients were significantly higher than those in the controls (mean pepsinogen I:BE 51.0 +/- 14.0 ng/mL vs control 38.9 +/- 13.5 ng/mL, P = 0.0012; mean pepsinogen II:BE 10.8 +/- 4.0 ng/mL vs control 7.9 +/- 2.0 ng/mL, P = 0.0097). There was no significant difference in the serum gastrin levels between BE patients and the controls irrespective of the H. pylori infection status. CONCLUSIONS: Most of the Japanese BE patients are characterized by the absence of H. pylori infection and high levels of serum pepsinogen. Determination of the serum pepsinogen level in combination with the H. pylori infection status could be a useful serological marker for BE screening.

  250. Alteration of correlation between serum pepsinogen concentrations and gastric acid secretion after H. pylori eradication. Peer-reviewed

    Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Nobuyuki Ara, Kaname Uno, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology 44 (8) 819-25 2009

    DOI: 10.1007/s00535-009-0066-2  

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    PURPOSE: The measurement of serum pepsinogens is clinically useful to represent gastric acid secretion. Since both serum pepsinogens and gastric acid secretion are considerably altered by H. pylori eradication, the correlation between these two parameters could be different prior to and after eradication. In this study, we investigated the correlation between the two parameters prior to and after eradication. METHODS: One hundred eighteen H. pylori-positive patients with peptic ulcers or chronic gastritis were enrolled in this retrospective analysis. In all participants both the measurement of serum pepsinogens and the determination of gastric acid secretion were performed prior to and at 1 month after successful eradication. In 85 subjects, the same assessments were repeated at 7 months. Correlations between serum pepsinogens and gastric acid secretion were assessed using linear regression analysis. RESULTS: The pepsinogen I/II ratio (r = 0.56) was a better indicator of gastric acid secretion in H. pylori-infected subjects than pepsinogen I itself (r = 0.31). Eradication of H. pylori altered the association, causing pepsinogen I (r = 0.55) to become a better indicator of gastric acid secretion compared with the pepsinogen I/II ratio (r = 0.40) at 1 month after eradication, followed by similar tendencies at 7 months. CONCLUSION: Using different serum biomarkers (pepsinogen I/II ratio prior to eradication or pepsinogen I after eradication), the measurement of serum pepsinogens is useful for predicting the individual gastric acid secretion level not only in H. pylori-infected subjects, but also in subjects with histories of eradication of the infection.

  251. 健常者における食道内酸還流時の食道知覚に関する検討 PETを用いた脳内反応の解析

    小林 茂之, 阿部 靖彦, 小池 智幸, 淺沼 清孝, 飯島 克則, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A738-A738 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  252. 食道内腔で発生する一酸化窒素の食道粘膜上皮細胞間隙に対する影響

    伊藤 博敬, 飯島 克則, 荒 誠之, 浅沼 清孝, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A738-A738 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  253. NOD1+32656およびIL-8-251遺伝子多型のH.pylori陽性胃食道逆流症発症に与える影響

    及川 智之, 今谷 晃, 浅野 直喜, 阿部 靖彦, 小池 智幸, 飯島 克則, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A740-A740 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  254. 食道扁平上皮癌症例における胃酸分泌能の検討

    飯島 克則, 小池 智幸, 阿部 靖彦, 堀井 亨, 山岸 初志, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A741-A741 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  255. 外因性NO曝露によるバレット食道への影響

    遠藤 博之, 飯島 克則, 荒 誠之, 浅沼 清孝, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A745-A745 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  256. H.pylori除菌後に発生したBarrett腺癌の一例

    阿部 靖彦, 大原 秀一, 小池 智幸, 飯島 克則, 今谷 晃, 下瀬川 徹, 猪股 芳文, 結城 豊彦, 石田 一彦

    日本消化器病学会雑誌 105 (臨増大会) A750-A750 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  257. 13C-オクタン酸呼気試験を用いた硝酸塩摂取による胃排出能に及ぼす影響

    寺井 志保, 飯島 克則, 浅沼 清孝, 阿部 靖彦, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A755-A755 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  258. 血清pepsinogen、gastrin17値を用いた胃粘膜萎縮の診断に関する検討

    菊地 亮介, 阿部 靖彦, 飯島 克則, 浅沼 清隆, 今谷 晃, 小池 智幸, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増大会) A770-A770 2008/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  259. Tongue-like Barrett's esophagus is associated with gastroesophageal reflux disease. International-journal Peer-reviewed

    Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Shigeyuki Kobayashi, Ken Ariizumi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Yoshifumi Inomata, Katsuaki Kato, Daisuke Shibuya, Shigemitsu Aida, Tooru Shimosegawa

    World journal of gastroenterology 14 (26) 4196-203 2008/07/14

    ISSN: 1007-9327

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    AIM: To test this hypothesis of barrett esophagus (BE) classified into two types and to further determine if there was any correlation between the shape of endoscopically suspected esophageal metaplasia (ESEM), prevalence of reflux esophagitis (RE) and heartburn. METHODS: A total of 6504 Japanese who underwent endoscopy for their annual stomach check-up were enrolled in this study. BE was detected without histological confirmation that is ESEM. We originally classified cases of ESEM into 3 types based on its shape: Tongue-like (T type), Dome-like (D type) and Wave-like (W type) ESEM. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a one-month period. RESULTS: ESEM was observed in 10.3% of 6504 subjects (ESEM < 1 cm, 9.4%; 1 cm < or = ESEM < 3 cm, 1.7%; ESEM > or = 3 cm, 0.5%). The frequency of ESEM was significantly higher in males compared with female subjects. Statistical analysis showed that the prevalence of heartburn and RE were significantly higher in the T type ESEM than in the W type ESEM (P < 0.05). CONCLUSION: The T type ESEM was strongly asso-ciated with reflux symptoms and RE whereas the W type ESEM was not associated with GERD.

  260. Incidence of reflux esophagitis and H pylori infection in diabetic patients. International-journal Peer-reviewed

    Ken Ariizumi, Tomoyuki Koike, Shuichi Ohara, Yoshifumi Inomata, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Tomoyoshi Oka, Tooru Shimosegawa

    World journal of gastroenterology 14 (20) 3212-7 2008/05/28

    ISSN: 1007-9327

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    AIM: To investigate the incidence of reflux esophagitis (RE) and H pylori infection in the diabetic patient. METHODS: The incidence of RE and H pylori infection were investigated in 85 patients with diabetes mellitus and the results were compared with controls. RESULTS: The incidence of RE in diabetic patients was 17.6%. Although this tended to be higher in diabetic patients, there were no statistically significant differences between diabetic patients and controls. The incidence of H pylori infection in diabetic patients was 53.7% but no statistically significant difference was seen between diabetic patients and controls in the incidence of H pylori infection. CONCLUSION: No significant differences could be seen between diabetic patients and controls in the incidence of RE and H pylori infection.

  261. Stronger inhibition of gastric acid secretion by lafutidine, a novel H2 receptor antagonist, than by the proton pump inhibitor lansoprazole. International-journal Peer-reviewed

    Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Toru Horii, Ryousuke Kikuchi, Shigeyuki Kobayashi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Kaori Suzuki, Takanori Hishinuma, Junichi Goto, Tooru Shimosegawa

    World journal of gastroenterology 14 (15) 2406-10 2008/04/21

    ISSN: 1007-9327

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    AIM: To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg. METHODS: Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug. RESULTS: The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg. CONCLUSION: In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidine than by LPZ.

  262. Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers. International-journal Peer-reviewed

    Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Toru Horii, Ryousuke Kikuchi, Shigeyuki Kobayashi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Kaori Suzuki, Takanori Hishinuma, Junichi Goto, Tooru Shimosegawa

    World journal of gastroenterology 14 (13) 2049-54 2008/04/07

    ISSN: 1007-9327

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    AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori -negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.

  263. 成人好酸球性食道炎の5例

    荒 誠之, 阿部 靖彦, 飯島 克則, 浅沼 清孝, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹, 白根 昭男

    Gastroenterological Endoscopy 50 (Suppl.1) 922-922 2008/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  264. Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan. International-journal Peer-reviewed

    Hatsushi Yamagishi, Tomoyuki Koike, Shuichi Ohara, Shigeyuki Kobayashi, Ken Ariizumi, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Yoshifumi Inomata, Katsuaki Kato, Daisuke Shibuya, Shigemitsu Aida, Tooru Shimosegawa

    World journal of gastroenterology 14 (9) 1358-64 2008/03/07

    ISSN: 1007-9327

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    AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan. METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged>40 years. A total of 160983 Japanese (60774 male, 100209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160983 subjects, we randomly selected a total of 82894 (34275 male, 48619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year age group. Dysphagia was also significantly more frequent in female patients. CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group.

  265. 食道内酸還流時の食道知覚と脳内反応に関する検討

    小林 茂之, 阿部 靖彦, 大原 秀一, 小池 智幸, 浅沼 清孝, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増総会) A167-A167 2008/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  266. ホメオボックス遺伝子Sox2によるBarrett食道発生機序の解析

    阿曽沼 祥, 今谷 晃, 阿部 靖彦, 小池 智幸, 浅野 直喜, 小西 秀知, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増総会) A170-A170 2008/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  267. 日本の一般住民における上腹部症状のオーバーラップの検討

    山岸 初志, 小池 智幸, 大原 秀一, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増総会) A319-A319 2008/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  268. 前庭部萎縮性胃炎の診断における血清ガストリン値の有用性に関する検討

    菊地 亮介, 阿部 靖彦, 飯島 克則, 浅沼 清隆, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 105 (臨増総会) A346-A346 2008/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  269. 【H.pylori除菌療法の現状と問題点】消化性潰瘍に対するH.pylori除菌療法の効率的な判定時期および適切な治療法

    小池 智幸, 関根 仁, 大原 秀一, 阿部 靖彦, 浅沼 清孝, 飯島 克則, 今谷 晃, 下瀬川 徹

    消化器科 46 (1) 42-46 2008/01

    Publisher: (有)科学評論社

    ISSN: 0289-8756

  270. Long-term outcomes of gastric mucosa-associated lymphoid tissue lymphomas after Helicobacter pylori eradication therapy. Peer-reviewed

    Shiho Terai, Katsunori Iijima, Katsuaki Kato, Naohiro Dairaku, Tatsuhiko Suzuki, Masayoshi Yoshida, Tomoyuki Koike, Yasushi Kitagawa, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Tooru Shimosegawa

    The Tohoku journal of experimental medicine 214 (1) 79-87 2008/01

    ISSN: 0040-8727

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    Mucosa-associated lymphoid tissue (MALT) lymphomas are localized primarily in the gastrointestinal tract and are characterized by an indolent nature and favorable outcome with specific therapy. Gastric MALT lymphomas are closely linked to Helicobacter pylori (H. pylori) infection, for which eradication therapy is recognized as an effective primary treatment for the disease. However, there is little information about long-term outcomes after the therapy. In the present study, we elucidated the long-term outcomes of 74 patients (70 H. pylori-positive and 4 negative cases) followed up by endoscopy at least 12 months after exclusive eradication therapy alone. The median follow-up period was 46 months. When the remission status was estimated at the time point of 12 months post-eradication, the numbers of patients with complete remission (CR), histologically residual disease with macroscopic normalization (hRD), partial remission with more than 50% tumor reduction (PR) or no response (NR) were 56, 12, 2 and 4, respectively. During follow-ups of over 12 months post-eradication, 11 of the 12 hRD cases were belatedly induced to CR but one CR case histologically relapsed into hRD. One of the 2 PR cases eventually turned into hRD 20 months later. Therefore, 66 CR, 3 hRD, 1 PR, and 4 NR cases (including 3 H. pylori-negative) were identified at the last follow-up of the present study. All 74 patients were followed up without any second-line therapies, but none exhibited disease progression. Thus, the long-term outcome of localized gastric MALT lymphoma after H. pylori eradication therapy was favorable. A watch and wait strategy may be a reasonable approach for hRD since the majority might be in the process of turning into delayed CR.

  271. Pathophysiological role of the activation of p38 mitogen-activated protein kinases in poorly differentiated gastric cancer. International-journal Peer-reviewed

    Tomoaki Atsumi, Katsuaki Kato, Kaname Uno, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Syuichi Ohara, Tooru Shimosegawa

    Pathology international 57 (10) 635-44 2007/10

    ISSN: 1320-5463

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    p38 mitogen-activated protein kinases (MAPK) contribute to the loss of cell-cell contact and the round cell shape characteristic of poorly differentiated gastric cancer. In the present study it is demonstrated that phospho-p38 MAPK level significantly increased in poorly differentiated gastric cancers in comparison to differentiated cancers and normal gastric mucosa by immunohistochemistry. Next, the pathophysiological roles of p38 MAPK activation were investigated in differentiated gastric cancer cell lines MKN7 and MKN28 and poorly differentiated gastric cancer cell lines KATO-III and MKN45 cells by incubating with specific p38 inhibitor SB203580 or inactivating analog SB202474. The distribution of F-actin on phalloidin staining was identified as fine cytoskeletal filaments in MKN7 and MKN28, but as dense membranous accumulation in KATO-III and MKN45 cells. The treatment with SB203580 but not SB202474 reduced irregular accumulation of F-actin in KATO-III and MKN45 cells. The expression of E-cadherin, ZO-1, occludin and claudin 4 was higher in MKN7 and MKN28 than KATO-III and MKN45 cells. The expression of E-cadherin in KATO-III cells was increased following treatment with SB203580, suggesting the suppression of E-cadherin at the transcriptional level independent of its genetic alterations. Thus, p38 MAPK signaling might contribute to the acquisition of malignant properties in poorly differentiated phenotypes.

  272. H.pylori感染におけるNOD1遺伝子多型の胃食道逆流症および胃粘膜萎縮に与える影響

    及川 智之, 今谷 晃, 阿曽沼 祥, 小西 秀和, 阿部 靖彦, 小池 智幸, 飯島 克則, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 104 (臨増大会) A574-A574 2007/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  273. 尿素呼気試験によるH.pylori感染診断能に対する食事摂取の影響の検討

    寺井 志保, 大原 秀一, 飯島 克則, 浅沼 清孝, 阿部 靖彦, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 104 (臨増大会) A587-A587 2007/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  274. 【Helicobacter pylori感染と生活習慣のかかわり】H.pylori胃癌と食事の相互作用 硝酸塩と酸分泌 噴門部癌、非噴門部胃癌との関連

    飯島 克則, 浅沼 清孝, 小池 智幸, 阿部 靖彦, 荒 誠之, 今谷 晃, 大原 秀一, 下瀬川 徹

    Helicobacter Research 11 (4) 335-339 2007/08

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  275. Extensive gastric atrophy: an increased risk factor for superficial esophageal squamous cell carcinoma in Japan. International-journal Peer-reviewed

    Katsunori Iijima, Tomoyuk Koike, Yasuhiko Abe, Yoshifumi Inomata, Hitoshi Sekine, Akira Imatani, Naoki Nakaya, Shuichi Ohara, Tooru Shimosegawa

    The American journal of gastroenterology 102 (8) 1603-9 2007/08

    ISSN: 0002-9270

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    OBJECTIVES: A recent study in Sweden has reported that gastric atrophy is associated with an increased risk for esophageal squamous cell carcinoma. However, this finding needs to be confirmed in other ethnic groups due to the wide geographic variation of this cancer. OBJECTIVES: To investigate whether gastric atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of H. pylori infection and accompanying gastric atrophy. METHODS: Seventy-three patients who had undergone endoscopic mucosal resection for superficial esophageal squamous cell carcinoma, and 73 sex- and age-matched controls, were enrolled prospectively. Gastric fundic atrophy was evaluated by histology of biopsy specimens and serum pepsinogen I level (cutoff level 25 ng/mL). Conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. RESULTS: Gastric atrophy, defined histologically or serologically, was independently associated with an increased risk for esophageal squamous cell carcinoma and the risk seemed to increase with the progression of the atrophy. Multivariate odds ratio (95% confidence interval) for histological fundic atropy, fundic intestinal metaplasia, and serological atrophy are 4.2 (1.5-11.7), 10.7 (2.3-50.4), and 8.2 (2.2-30.4), respectively. CONCLUSIONS: Gastric atrophy, a newly recognized risk factor for esophageal squamous cell carcinoma in Sweden, is likely to be a risk factor in other areas. Further studies are warranted to explore the causal relationship.

  276. Effect of Helicobacter pylori status on intragastric pH during administration of lafutidine or famotidine. International-journal Peer-reviewed

    Tomoyuki Koike, Shuichi Ohara, Hitoshi Sehine, Masashi Kawamura, Yasuhiko Abe, Yoshifumi Inomata, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    Hepato-gastroenterology 54 (76) 1280-4 2007/06

    ISSN: 0172-6390

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    BACKGROUND/AIMS: There has been no study attempting to compare the effects of lafutidine, a novel H2-receptor antagonist and other H2-receptor antagonists in the same subjects and relating them to H. pylori status. The first aim of this study was to investigate the effect of H. pylori status on intragastric pH in healthy volunteers receiving lafutidine or famotidine. The second aim was to compare the effects of the two antisecretory drugs. METHODOLOGY: The study was carried out in 11 healthy asymptomatic male volunteers. H. pylori infection was present in 5 subjects. Subjects were first examined by an ambulatory pH monitoring for 24 hours without medication. The second and third 24-hour pH monitoring study was performed on all subjects. Subjects took 10 mg lafutidine or 20mg famotidine at 9:00 and 21:00. RESULTS: During administration of lafutidine or famotidine, the percentage of period holding intragastric pH >4 was not significantly different between the H. pylori-negative and -positive subjects. Among the H. pylori negative subjects, the percentage of daytime period holding intragastric pH >4 was significantly greater with lafutidine than with famotidine (p < 0.05). CONCLUSIONS: The effect of lafutidine to increase intragastric pH was not affected by the H. pylori status. Among H. pylori-negative subjects, lafutidine was proven to be more effective than famotidine for acid control during the daytime in Japanese healthy volunteers.

  277. 【消化器の炎症からの腫瘍】GERDからのBarrett食道の発生

    小池 智幸, 大原 秀一, 阿部 靖彦, 飯島 克則, 今谷 晃, 下瀬川 徹

    臨床消化器内科 22 (7) 777-784 2007/05

    Publisher: (株)日本メディカルセンター

    ISSN: 0911-601X

    eISSN: 2433-2488

  278. 【Helicobacter pyloriと胃癌】Helicobacter pyloriと噴門部癌

    阿部 靖彦, 大原 秀一, 小池 智幸, 猪股 芳文, 浅沼 清孝, 堀井 享, 飯島 克則, 今谷 晃, 下瀬川 徹

    胃と腸 42 (6) 1011-1024 2007/05

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  279. The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with gastroesophageal junction adenocarcinoma in Japan. (Inflammopharmacology)

    Koike T, Ohara S, Inomata Y, Abe Y, Iijima K, Shimosegawa T

    Inflammopharmacology 15 (2) 61-64 2007/04

    DOI: 10.1007/s10787-006-1549-x  

  280. H.pylori除菌後に発見された胃癌症例の検討

    菊地 亮介, 大原 秀一, 阿部 靖彦, 堀井 亨, 浅沼 清孝, 北川 靖, 小池 智幸, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 49 (Suppl.1) 837-837 2007/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  281. Optical Coherence Tomography(OCT)を用いた、ヒト生体内食道壁断層画像の基礎的検討

    横沢 聡, 大原 秀一, 北川 靖, 浅沼 清孝, 阿部 靖彦, 飯島 克則, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 49 (Suppl.1) 857-857 2007/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  282. 食道内酸還流時の症状と脳内反応に関する検討

    小林 茂之, 阿部 靖彦, 大原 秀一, 小池 智幸, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 104 (臨増総会) A123-A123 2007/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  283. 胃癌検診受診者における逆流性食道炎、Barrett粘膜、食道裂孔ヘルニアと胃食道逆流症状との関連の検討

    山岸 初志, 小池 智幸, 大原 秀一, 阿部 靖彦, 菊地 亮介, 小林 茂之, 有泉 健, 浅沼 清孝, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹, 猪股 芳文, 加藤 勝章, 渋谷 大助

    日本消化器病学会雑誌 104 (臨増総会) A126-A126 2007/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  284. 症候性胃食道逆流症患者のQOL及びラフチジンの効果の検討

    堀井 享, 小池 智幸, 大原 秀一, 菊地 亮介, 小林 茂之, 山岸 初志, 有泉 健, 浅沼 清孝, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 104 (臨増総会) A127-A127 2007/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  285. H.pylori陰性胃MALTリンパ腫についての臨床経過についての検討

    寺井 志保, 飯島 克則, 加藤 勝章, 鈴木 達彦, 吉田 雅義, 大楽 尚弘, 浅沼 清孝, 阿部 靖彦, 北川 靖, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 104 (臨増総会) A184-A184 2007/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  286. [Nitric oxide generated at gastro-oesophageal junction]. Peer-reviewed

    Iijima K, Asanuma K, Ohara S, Shimosegawa T

    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 104 (1) 17-22 2007/01

    Publisher: The Japanese Society of Gastroenterology

    DOI: 10.11405/nisshoshi.104.17  

    ISSN: 0446-6586

  287. Regional differences in the recovery of gastric acid secretion after Helicobacter pylori eradication: evaluations with Congo red chromoendoscopy. International-journal Peer-reviewed

    Hitoshi Sekine, Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Akira Imatani, Katsuaki Kato, Suichi Ohara, Tooru Shimosegawa

    Gastrointestinal endoscopy 64 (5) 678-85 2006/11

    ISSN: 0016-5107

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    BACKGROUND: Gastric-acid secretion is reduced in Helicobacter pylori-positive fundic atrophic gastritis, but it is restored by the eradication. However, changes in the distribution of acid-secreting mucosa after the eradication remain unknown. Congo red chromoendoscopy is capable of visualizing the acid-secreting fundic mucosa. OBJECTIVE: To evaluate the effect of H pylori eradication on the distribution of acid-secreting mucosa in the fundus by using Congo red chromoendoscopy. DESIGN: An assessment of the distribution of acid-secreting mucosa by the visualized images of Congo red chromoendoscopy and a histologic evaluation of biopsy specimens were performed before and 1 and 7 months after the eradication. The areas of the acid-secreting mucosa in the lesser and greater curvatures of the fundus were evaluated semiquantitatively. PATIENTS: Thirty-seven patients positive for H pylori and with fundic atrophic gastritis. RESULTS: The area of the acid-secreting mucosa increased in 27 cases (73%) by 1 month after eradication, and in 32 cases (86%) by 7 months. This expansion of the acid-secreting mucosa coincided with the improvement of inflammatory changes rather than with that of the mucosal atrophy and was more prominent on the greater curvature than on the lesser curvature. CONCLUSIONS: The acid-secreting mucosa in the fundus expanded in most cases with fundic atrophic gastritis after H pylori eradication, which could be responsible for the increase in acid secretion after the treatment. Regional differences in the recovery of local acid secretion may be associated with site-specific susceptibility to the development of gastric cancer after successful eradication.

  288. 逆流性食道炎の長期経過に関する検討

    有泉 健, 小池 智幸, 大原 秀一, 小林 茂之, 猪股 芳文, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増大会) A760-A760 2006/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  289. 食道扁平上皮癌における胃酸分泌能の検討

    飯島 克則, 大原 秀一, 小池 智幸, 阿部 靖彦, 猪股 芳文, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増大会) A773-A773 2006/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  290. Lafutidine錠の酸分泌抑制効果発現時期の検討

    山岸 初志, 大原 秀一, 小池 智幸, 小林 茂之, 有泉 健, 猪股 芳文, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増大会) A788-A788 2006/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  291. 13C-Bicarbonate呼気テストによる胃内酸度測定の可能性についての検討

    寺井 志保, 大原 秀一, 飯島 克則, 阿部 靖彦, 北川 靖, 小池 智幸, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増大会) A788-A788 2006/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  292. PPIによる逆流性食道炎の治癒率に及ぼす背景因子の検討

    小池 智幸, 大原 秀一, 有泉 健, 菊地 亮介, 堀井 享, 小林 茂之, 山岸 初志, 浅沼 清孝, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    胃病態機能研究会誌 38 13-13 2006/07

    Publisher: (株)勁草書房コミュニケーション事業部

    ISSN: 1880-3652

  293. 糖尿病患者における逆流性食道炎罹患率、H.pylori感染率の検討

    有泉 健, 大原 秀一, 小池 智幸, 菊地 亮介, 堀井 享, 小林 茂之, 山岸 初志, 浅沼 清孝, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    胃病態機能研究会誌 38 17-17 2006/07

    Publisher: (株)勁草書房コミュニケーション事業部

    ISSN: 1880-3652

  294. Preservation of gastric acid secretion may be important for the development of gastroesophageal junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status. International-journal Peer-reviewed

    Yoshifumi Inomata, Tomoyuki Koike, Shuichi Ohara, Yasuhiko Abe, Hitoshi Sekine, Katsunori Iijima, Ken Ariizumi, Hatsushi Yamagishi, Yasushi Kitagawa, Akira Imatani, Tooru Shimosegawa

    The American journal of gastroenterology 101 (5) 926-33 2006/05

    ISSN: 0002-9270

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    BACKGROUND: We have previously reported that Helicobacter pylori infection prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including Barrett's adenocarcinoma, has been thought to be a complication of gastroesophageal reflux disease (GERD). However, the relationship between H. pylori infection, gastric acid secretion, and GE junction adenocarcinoma has not yet been investigated in Japan. The aim of this study was to evaluate this relationship in the Japanese population. METHODS: A total of 168 Japanese patients (RE alone: 80, short-segment BE (SSBE): 16, long-segment BE (LSBE): 20, GE junction adenocarcinoma: 12, distal early gastric cancer (EGC): 40; male/female = 106/62; mean age 61.5 yr) and 80 Japanese control subjects who had no localized lesions in the upper gastrointestinal tract (male/female = 43/37, mean age 58.1 yr) were enrolled for this study. The prevalence of H. pylori infection was determined by biopsy, the rapid urease test, and measurement of the serum H. pylori IgG antibody. Gastric acid secretion was assessed by the endoscopic gastrin test (EGT). RE was diagnosed according to the Los Angeles classification. RESULTS: The prevalence of H. pylori infection in the patients with RE alone (30%) was significantly lower than that in control subjects (71.2%). There was also a tendency for the prevalence of H. pylori infection to be lower in patients with BE (SSBE, 18.7%; LSBE, 0%) when compared to that in patients with RE alone. On the other hand, while the prevalence of H. pylori infection in patients with GE junction adenocarcinoma (58.3%) was significantly lower than that in patients with EGC (87.5%), it tended to be higher than that in patients with RE alone or BE. The mean EGT value in patients with RE alone (3.74 mEq/10 min) was significantly higher than that in control subjects (1.83). The mean EGT value in patients with BE (SSBE, 4.74; LSBE, 4.76) tended to be even higher than that in patients with RE alone. The mean EGT value in patients with GE junction adenocarcinoma (3.94) was significantly higher than that in control subjects and patients with EGC (0.67), but it was comparable to that independent of the H. pylori infection status in patients with RE alone or BE. CONCLUSION: Preservation of gastric acid secretion may be important for the development of GE junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status.

  295. 当科におけるBarrett食道の臨床的特徴と経過

    阿部 靖彦, 大原 秀一, 小池 智幸, 猪股 芳文, 飯島 克則, 有泉 健, 山岸 初志, 小林 茂之, 北川 靖, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 48 (Suppl.1) 710-710 2006/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  296. PPIによる逆流性食道炎の治癒率に及ぼす背景因子の検討

    有泉 健, 大原 秀一, 小池 智幸, 小林 茂之, 山岸 初志, 猪股 芳文, 三浦 敦司, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹, 川村 昌司

    Gastroenterological Endoscopy 48 (Suppl.1) 714-714 2006/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  297. 胃体部潰瘍に対するファモチジンとオメプラゾールの治癒効果の比較

    小林 茂之, 大原 秀一, 小池 智幸, 及川 智之, 寺井 志保, 石山 史威, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 48 (Suppl.1) 763-763 2006/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  298. 当科におけるEMRで診断された胃SM1癌の検討

    北川 靖, 大原 秀一, 阿部 靖彦, 飯島 克則, 小池 智幸, 今谷 晃, 下瀬川 徹

    Gastroenterological Endoscopy 48 (Suppl.1) 768-768 2006/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  299. Lansoprazole OD錠の酸分泌抑制効果発現時期の検討

    山岸 初志, 大原 秀一, 小池 智幸, 小林 茂之, 有泉 健, 猪股 芳文, 阿部 靖彦, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増総会) A191-A191 2006/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  300. H.pylori除菌後,酸分泌非回復胃粘膜の組織学的特徴(コンゴレッド色素内視鏡を用いた検討)

    飯島 克則, 関根 仁, 小池 智幸, 阿部 靖彦, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増総会) A251-A251 2006/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  301. 当院における特発性血小板減少性紫斑病に対するH.pylori除菌療法の治療成績

    阿部 靖彦, 大原 秀一, 小池 智幸, 山岸 初志, 熱海 智章, 有泉 健, 飯島 克則, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増総会) A252-A252 2006/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  302. 胃MALTリンパ腫に対するH.pylori除菌療法後の長期経過

    寺井 志保, 飯島 克則, 加藤 勝章, 鈴木 達彦, 吉田 雅義, 大楽 尚弘, 阿部 靖彦, 北川 靖, 小池 智幸, 今谷 晃, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 103 (臨増総会) A253-A253 2006/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  303. 【Helicobacter胃炎の諸像 Helicobacter胃炎はどのような姿を呈するのか】Helicobacter pylori除菌による萎縮性胃炎の回復 コンゴーレッド色素内視鏡検査および組織学的検討

    小池 智幸, 大原 秀一, 関根 仁, 飯島 克則, 阿部 靖彦, 今谷 晃, 下瀬川 徹

    Helicobacter Research 10 (1) 39,5-6 2006/02

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  304. Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects. Peer-reviewed

    Katsunori Iijima, Hitoshi Sekine, Tomoyuki Koike, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology 40 (10) 938-44 2005/10

    ISSN: 0944-1174

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    BACKGROUND: Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. METHODS: The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. RESULTS: In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. CONCLUSIONS: The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

  305. PPIによる逆流性食道炎の治癒率に及ぼす背景因子の検討

    有泉 健, 大原 秀一, 小池 智幸, 山岸 初志, 猪股 芳文, 阿部 靖彦, 川村 昌司, 北川 靖, 飯島 克則, 今谷 晃, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 102 (臨増大会) A695-A695 2005/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  306. 胃癌検診者におけるGERDの頻度・程度

    山岸 初志, 大原 秀一, 小池 智幸, 有泉 健, 猪股 芳文, 飯島 克則, 今谷 晃, 関根 仁, 下瀬川 徹, 相田 重光, 加藤 勝章, 渋谷 大助

    日本消化器病学会雑誌 102 (臨増大会) A698-A698 2005/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  307. 食道扁平上皮癌症例におけるH.pylori感染率,胃粘膜萎縮の検討

    飯島 克則, 大原 秀一, 小池 智幸, 関根 仁, 猪股 芳文, 今谷 晃, 下瀬川 徹

    日本消化器病学会雑誌 102 (臨増大会) A704-A704 2005/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  308. Interleukin4受容体+3044A/G遺伝子多型と組織学的胃炎との関連性について

    三浦 敦司, 今谷 晃, 大矢内 幹, 飯島 克則, 小池 智幸, 関根 仁, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 102 (臨増大会) A721-A721 2005/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  309. 【Barrett食道の病態,診断,治療】Barrett食道/癌の病態および内視鏡的特徴と治療

    小池 智幸, 大原 秀一, 猪股 芳文, 阿部 靖彦, 山岸 初志, 有泉 健, 北川 靖, 飯島 克則, 今谷 晃, 下瀬川 徹

    消化器科 41 (1) 29-34 2005/07

    Publisher: (有)科学評論社

    ISSN: 0289-8756

  310. 【今,改めて胃酸関連疾患を見直す】H.pylori除菌治療後の食道と胃の機能と形態

    小池 智幸, 大原 秀一, 関根 仁, 飯島 克則, 大矢内 幹, 山岸 初志, 有泉 健, 猪股 芳文, 阿部 靖彦, 北川 靖, 今谷 晃, 下瀬川 徹

    消化器内視鏡 17 (3) 308-316 2005/03

    Publisher: (株)東京医学社

    ISSN: 0915-3217

  311. Rabeprazoleによる逆流性食道炎治療における薬物代謝酵素(CYP2C19)の遺伝子多型の影響の検討 維持療法の成績を含めて

    有泉 健, 大原 秀一, 小池 智幸, 山岸 初志, 猪股 芳文, 川村 昌司, 北川 靖, 飯島 克則, 今谷 晃, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 102 (臨増総会) A219-A219 2005/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  312. 【Helicobacter pylori非侵襲的診断法の実際 診療現場の最前線より】Helicobacter pylori尿素呼気試験の進歩とその問題点

    大原 秀一, 佐野 望, 小池 智幸, 関根 仁, 飯島 克則, 今谷 晃, 下瀬川 徹

    Helicobacter Research 9 (1) 30-37 2005/02

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  313. 13C-尿素呼気試験における口腔内・咽頭内ウレアーゼ活性の影響の検討

    佐野 望, 大原 秀一, 小池 智幸, 関根 仁, 今谷 晃, 北川 靖, 大楽 尚弘, 飯島 克則, 加藤 勝章, 下瀬川 徹

    日本消化器病学会雑誌 101 (12) 1302-1308 2004/12

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  314. 【逆流性食道炎をめぐる新しい流れ】逆流性食道炎の治療 薬物治療 酸分泌抑制薬による治療戦略

    大原 秀一, 川村 昌司, 有泉 健, 小池 智幸, 今谷 晃, 関根 仁, 飯島 克則, 下瀬川 徹

    臨床消化器内科 19 (12) 1627-1633 2004/10

    Publisher: (株)日本メディカルセンター

    ISSN: 0911-601X

    eISSN: 2433-2488

  315. 表在性Barrett腺癌の臨床・病理学的検討

    猪股 芳文, 大原 秀一, 小池 智幸, 浅沼 清孝, 三浦 敦司, 北川 靖, 飯島 克則, 今谷 晃, 関根 仁, 下瀬川 徹

    Gastroenterological Endoscopy 46 (Suppl.2) 1944-1944 2004/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  316. The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett's esophagus in Japan. International-journal Peer-reviewed

    Yasuhiko Abe, Shuichi Ohara, Tomoyuki Koike, Hitoshi Sekine, Katsunori Iijima, Masashi Kawamura, Akira Imatani, Katsuaki Kato, Tooru Shimosegawa

    The American journal of gastroenterology 99 (7) 1213-21 2004/07

    ISSN: 0002-9270

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    OBJECTIVES: The acidity of the refluxate into the esophagus is a key factor for the pathogenesis of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) infection can influence gastric acid secretion. We have reported that H. pylori infection prevents reflux esophagitis by decreasing gastric acid secretion in Japanese patients, but the role of this organism in Barrett's esophagus is unclear. The aim of this study was to investigate the prevalence of H. pylori infection and gastric acid secretion in Japanese patients with reflux esophagitis with or without Barrett's esophagus. METHODS: We enrolled 112 reflux esophagitis patients who were examined for the status of H. pylori and acid secretion in this study. They were divided into three groups, according to the presence or absence of Barrett's esophagus as follows: reflux esophagitis group without Barrett's esophagus (reflux esophagitis alone) (80 patients); short-segment Barrett's esophagus group (16 patients); and long-segment Barrett's esophagus group (LSBE) (16 patients). Age- and sex-matched control subjects were also assigned to the 80 patients with reflux esophagitis alone. The prevalence of H. pylori infection was determined by histology, rapid urease tests, and serum IgG antibodies. Gastric acid secretion was evaluated by the endoscopic gastrin test (EGT). RESULTS: The overall prevalence of H. pylori infection in the reflux esophagitis patient group (24.1%) was significantly lower than the control group (71.2%) (odds ratio 0.13, 95% confidence interval 0.07-0.24; p < 0.0001). The prevalence of H. pylori infection in the patients with Barrett's esophagus tended to be lower than that in the patients with reflux esophagitis alone (reflux esophagitis alone; 30.0%, SSBE; 18.7%, LSBE; 0%), especially in the patients with LSBE compared with the reflux esophagitis alone group (p < 0.01). The EGT value of the respective reflux esophagitis patient group was significantly higher than the control group. The EGT value in the patients with Barrett's esophagus tended to be higher than that in the patients with reflux esophagitis alone, but the difference was not statistically significant. When examined in H. pylori-negative subjects, no difference was found in the EGT value between the control subjects and the patients with reflux esophagitis alone, but it was significantly higher in patients with Barrett's esophagus than the control subjects (p < 0.05). On the other hand, when examined in the H. pylori-positive subjects, the EGT value was significantly higher in the patients with reflux esophagitis alone than in the control subjects (p < 0.01). CONCLUSIONS: H. pylori infection may play a protective role in the development of Barrett's esophagus, especially in the development of LSBE in Japan. Gastric acid hypersecretion may be concerned with the development of Barrett's esophagus in addition to the absence of H. pylori infection.

  317. Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues. International-journal

    Norihiro Shimada, Takashi Suzuki, Satoshi Inoue, Katsuaki Kato, Akira Imatani, Hitoshi Sekine, Syuichi Ohara, Tooru Shimosegawa, Hironobu Sasano

    Molecular and cellular endocrinology 218 (1-2) 147-53 2004/04/15

    ISSN: 0303-7207

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    Estrogen-responsive finger protein (Efp), a target gene product of estrogen receptor (ER), is considered essential for estrogen-dependent cell proliferation. The biological significance of Efp remains unclear in human tissues, and therefore, we examined systemic distribution of Efp in human adult and fetal tissues using RT-PCR and immunohistochemistry. Efp mRNA expression was marked in the placenta and uterus, high in the thyroid gland, aorta, and spleen in adult, and relatively low in other human adult and fetal tissues examined in this study. Efp immunoreactivity was detected in epithelium of various adult tissues, and was also detected in cytotrophoblasts of the placenta and splenic macrophages. Efp immunolocalization in human fetus was generally similar as that in adult. These Efp-positive cells were previously reported to be associated with ERalpha and/or ERbeta expression. Therefore, these results indicate that Efp is widely expressed and may play important roles in various human tissues possibly through ERs.

  318. H.pylori除菌が逆流性食道炎に及ぼす長期的影響

    猪股 芳文, 大原 秀一, 関根 仁, 小池 智幸, 有泉 健, 三浦 淳司, 浅沼 清孝, 北川 靖, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 下瀬川 徹

    Gastroenterological Endoscopy 46 (Suppl.1) 648-648 2004/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  319. 【胃・十二指腸潰瘍 基礎・臨床の最新動向】治療学の進歩 現状・評価と課題 H.pylori感染潰瘍(除菌療法) 逆流性食道炎

    小池 智幸, 大原 秀一, 関根 仁, 飯島 克則, 有泉 健, 猪股 芳文, 北川 靖, 大楽 尚弘, 今谷 晃, 加藤 勝章, 下瀬川 徹

    日本臨床 62 (3) 499-504 2004/03

    Publisher: (株)日本臨床社

    ISSN: 0047-1852

  320. 【胃MALTリンパ腫 除菌治療後の経過と予後】胃MALTリンパ腫除菌後の長期経過と予後 内視鏡像を中心に

    大楽 尚弘, 加藤 勝章, 大原 秀一, 北川 靖, 飯島 克則, 小池 智幸, 今谷 晃, 関根 仁, 下瀬川 徹

    胃と腸 39 (3) 277-283 2004/03

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  321. Rabeprazoleによる逆流性食道炎の治癒に及ぼす薬物代謝酵素CYP2C19遺伝子多型の影響

    有泉 健, 大原 秀一, 小池 智幸, 猪股 芳文, 北川 靖, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹, 川村 昌司

    日本消化器病学会雑誌 101 (臨増総会) A193-A193 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  322. Interleukin4受容体+3044A/GSNPの胃粘膜萎縮への影響についての検討

    三浦 敦司, 今谷 晃, 大原 秀一, 米地 真, 浅野 直喜, 大矢内 幹, 小池 智幸, 飯島 克則, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A233-A233 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  323. 日本人におけるInterleukin-1β,Tumor necrosis factorα,Interleukin-10遺伝子多型とH.pylori感染,および上部消化管疾患との関連ついての検討

    米地 真, 今谷 晃, 大原 秀一, 三浦 敦司, 大矢内 幹, 浅野 直喜, 小池 智幸, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A234-A234 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  324. 糖尿病患者における逆流性食道炎罹患率,H.pylori感染率の検討

    有泉 健, 大原 秀一, 小池 智幸, 猪股 芳文, 北川 靖, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A275-A275 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  325. H.pylori感染胃粘膜におけるNotchレセプターならびにId-1の発現

    熱海 智章, 加藤 勝章, 大楽 尚弘, 浅沼 清孝, 宇野 要, 飯島 克則, 小池 智幸, 今谷 晃, 関根 仁, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A311-A311 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  326. Oligomycin and antimycin A prevent nitric oxide-induced apoptosis by blocking cytochrome C leakage. International-journal Peer-reviewed

    Naohiro Dairaku, Katsuaki Kato, Kennichi Honda, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hiroshi Matsui, Tooru Shimosegawa

    The Journal of laboratory and clinical medicine 143 (3) 143-51 2004/03

    ISSN: 0022-2143

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    Nitric oxide (NO) is a potent inducer of apoptosis, and its cytotoxicity is closely related to mitochondrial dysfunction. In this study we investigated the effects of a F0F1-ATPase inhibitor, oligomycin, and a mitochondrial respiratory chain complex III inhibitor, antimycin A, on NO-induced apoptosis. We used a normal rat gastric-epithelium cell line, RGM-1, treated with a pure NO donor, NOC-1 -1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene - in the presence or absence of oligomycin or antimycin A. Changes in the expressions of Bax or Bcl-2 proteins, release of cytochrome C from mitochondria into the cytosol, activation of caspase-3, and changes in the mitochondrial membrane potential (DeltaPsi) were measured with the use of Western blotting, c43 lorimetric assays, and a mitochondrial potential sensor, JC-1 dye. Treatment with NOC-18 induced dose-dependent apoptotic cell death in RGM-1 cells. Cell death was accompanied by mitochondrial depolarization, increases in Bax protein expression and cytochrome C leakage, and, subsequently, caspase-3 activation. Oligomycin and antimycin A prevented NO-induced apoptosis in a dose-dependent fashion by preventing cytochrome C release independent of Bcl-2 expression. However, neither compound affected the up-regulation of Bax protein. On the one hand, oligomycin treatment was not accompanied by a decline in DeltaPsi. On the other hand, antimycin A treatment decreased DeltaPsi regardless of NOC-18 treatment. The findings of this study suggest that various functional molecules that constitute the mitochondrial respiratory chain may contribute to cytochrome C release that occurs during NO-induced apoptosis.

  327. 【尿素呼気試験をめぐる諸問題】酸分泌抑制薬による尿素呼気試験の偽陰性化

    小池 智幸, 大原 秀一, 関根 仁, 佐野 望, 飯島 克則, 北川 靖, 大楽 尚弘, 今谷 晃, 加藤 勝章, 下瀬川 徹

    Helicobacter Research 8 (1) 31-36 2004/02

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  328. Expression of Mg2+-dependent, HCO3- -stimulated adenine triphosphatase in the human duodenum. International-journal Peer-reviewed

    Yutaka Konno, Katsuaki Kato, Naohiro Dairaku, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Tooru Shimosegawa

    Journal of gastroenterology and hepatology 19 (1) 18-23 2004/01

    ISSN: 0815-9319

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    BACKGROUND AND AIM: Mg2+-dependent, HCO3- -stimulated adenine triphosphatase (Mg2+-HCO3- -ATPase) is an enzyme that catabolizes ATP in the presence of HCO3- and Mg2+. The activity of this ATPase is known to be present in the duodenum, but its physiological role remains unclear. In the present study, the aim was to study the distribution and biochemical profiles of Mg2+-HCO3- -ATPase in the human duodenum. METHODS: The histochemistry of Mg2+-HCO3- -ATPase, its localization using electron microscopy (EMS), and the measurement of enzyme activity were carried out by using mucosal samples of the bulb, and the second and third portions of the duodenum, obtained from six volunteers by endoscopic biopsy. RESULTS: The Mg2+-HCO3- -ATPase was detected in the brush border along the luminal surface of human duodenal epithelial cells. The EMS confirmed its localization to the surface of microvilli. The activity of Mg2+-HCO3- -ATPase was higher in the distal portions of the human duodenum than in the bulb. Its maximal activity was obtained under a pH of 8.5, and in the presence of 1.0 mmol/L MgCl2 and 50 mmol/L NaHCO3, but the activity was undetectable in pH <7.4 or >9.5. CONCLUSION: The results of the present study suggested that Mg2+-HCO3- -ATPase may work for luminal alkalization in the distal portions of the human duodenum and may contribute to maintaining the activity of pancreatic digestive enzymes.

  329. Contribution of glutamine synthetase to ammonia-induced apoptosis in gastric mucosal cells. International-journal Peer-reviewed

    Yuuji Kubota, Katsuaki Kato, Naohiro Dairaku, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hiroshi Matsui, Tooru Shimosegawa

    Digestion 69 (3) 140-8 2004

    ISSN: 0012-2823

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    BACKGROUND/AIMS: Glutamine synthetase is a key enzyme necessary for ammonia detoxification in the brain, but excessive activation of this enzyme can be cytotoxic to neural cells as a consequence of excessive consumption of ATP and glutamate. The stomach also expresses high levels of glutamine synthetase and this study aimed to investigate a possible pathophysiological role of glutamine synthetase in ammonia-induced gastric mucosal injury. METHODS: Normal rat gastric mucosal epithelial (RGM-1) cells were treated with ammonia, and a specific glutamine synthetase inhibitor (methionine sulfoximine) was used to assess the action of glutamine synthetase. RESULTS: Treatment with ammonia induced apoptotic cell death. Increased expression of p21 and Bax, decreased expression of Bcl-2, cytochrome C release from the mitochondria into the cytosol and subsequent activation of caspase-9 and -3 were identified in the cells treated with ammonia, although there was no apparent change in p53 expression. On the other hand, pretreatment with various concentrations of methionine sulfoximine reduced the glutamine synthetase activity in ammonia-treated RGM-1 cells, and prevented the induction of apoptosis and the reduction in intracellular ATP levels in a dose-dependent manner. CONCLUSIONS: Our results suggested that the energy exhaustion which resulted from an overload of ammonia to glutamine synthetase may have initiated the apoptotic signaling in gastric mucosal cells.

  330. High levels of intracellular ATP prevent nitric oxide-induced apoptosis in rat gastric mucosal cells. International-journal Peer-reviewed

    Kenichi Honda, Katsuaki Kato, Naohiro Dairaku, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hiroshi Matsui, Tooru Shimosegawa

    International journal of experimental pathology 84 (6) 281-8 2003/12

    ISSN: 0959-9673

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    Nitric oxide (NO) plays an important role in gastric mucosal injury in the human stomach. Exposure to excessive NO leads to apoptosis; however, the mechanism remains largely unknown in gastric epithelial cells. The apoptotic process is modulated by energy states in cells. This study investigated molecular mechanisms of NO-induced apoptosis in gastric epithelial cells and influence of high glucose on those mechanisms. Normal rat gastric mucosal epithelial (RGM-1) cells were cultured in media containing either 1000 (low) or 4500 mg/l (high) of D-glucose. When the cells were incubated with a chemical NO donor NOC18, apoptosis was induced in a dose-dependent manner. Intracellular adenosine triphosphate (ATP) levels significantly increased in the cells cultured with high glucose in comparison with the low-glucose condition. The cells with high ATP levels were more resistant to NO-induced apoptosis than the cells with low ATP levels. NO-induced apoptosis was followed by mitochondrial depolarization, upregulation of Bax protein, cytochrome C release from mitochondria to the cytosol and subsequent caspases activation. These results suggest that NO inhibition of mitochondrial respiratory system and acute ATP depletion initiate apoptotic signalling in gastric epithelial cells. High glucose may prevent NO-induced apoptosis by leading to high levels of intracellular ATP or other metabolic changes in this cell line.

  331. Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury. International-journal Peer-reviewed

    Jing Yang, Katsuaki Kato, Kenji Noguchi, Naohiro Dairaku, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hironobu Sasano, Tooru Shimosegawa

    Life sciences 73 (25) 3245-56 2003/11/07

    ISSN: 0024-3205

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    The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.

  332. 13C-尿素呼気試験における口腔内・咽頭内ウレアーゼ活性の影響の検討 Peer-reviewed

    佐野望, 大原秀一, 小池智幸, 関根仁, 今谷晃, 北川靖, 大楽尚弘, 飯島克則, 加藤勝章, 下瀬川徹

    日本消化器病学会雑誌 100 (臨増大会) A612-A612 2003/09

    Publisher:

    DOI: 10.11405/nisshoshi.101.1302  

    ISSN: 0446-6586

    eISSN: 1349-7693

  333. 自動ブラッシング機構内蔵内視鏡洗浄装置を用いた内視鏡洗浄消毒効果の検討

    有泉 健, 大原 秀一, 関根 仁, 小池 智幸, 今谷 晃, 大楽 尚弘, 飯島 克則, 下瀬川 徹

    Gastroenterological Endoscopy 45 (Suppl.2) 1719-1719 2003/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  334. Barrett腺癌を含む食道胃接合部癌の臨床・病理学的検討

    猪股 芳文, 大原 秀一, 小池 智幸, 阿部 靖彦, 浅沼 清孝, 三浦 敦司, 北川 靖, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹

    Gastroenterological Endoscopy 45 (Suppl.2) 1733-1733 2003/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  335. 日本人におけるInterleukin-4受容体遺伝子多型と上部消化管疾患との関連性について

    三浦 敦司, 今谷 晃, 大原 秀一, 米地 真, 浅野 直喜, 大矢内 幹, 小池 智幸, 飯島 克則, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 100 (臨増大会) A658-A658 2003/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  336. H.pylori感染におけるinterleukin-1β及びinterleukin-8遺伝子多型の胃酸分泌に与える影響について

    今谷 晃, 大原 秀一, 米地 真, 大矢内 幹, 浅野 直喜, 三浦 敦司, 小池 智幸, 飯島 克則, 関根 仁, 下瀬川 徹

    胃分泌研究会誌 35 31-33 2003/05

    Publisher: 胃病態機能研究会

    ISSN: 0289-2057

  337. 図解 Helicobacter pylori 技術講座 インターロイキン1β遺伝子群の分析

    今谷 晃, 大原 秀一, 米地 真, 大矢内 幹, 浅野 直喜, 三浦 敦司, 小池 智幸, 飯島 克則, 関根 仁, 下瀬川 徹

    Helicobacter Research 7 (2) 109-114 2003/04

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  338. 胃噴門部及びBarrett粘膜の組織学的炎症に及ぼすH.pylori感染,逆流性食道炎の影響に関する検討

    猪股 芳文, 大原 秀一, 小池 智幸, 阿部 靖彦, 関根 仁, 浅沼 清孝, 川村 昌司, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 下瀬川 徹

    Gastroenterological Endoscopy 45 (Suppl.1) 549-549 2003/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  339. Barrett腺癌,噴門部胃癌におけるH.pylori感染,胃酸分泌能に関する検討 非噴門部胃癌と比較して

    阿部 靖彦, 大原 秀一, 関根 仁, 小池 智幸, 猪股 芳文, 浅沼 清孝, 飯島 克則, 今谷 晃, 加藤 勝章, 下瀬川 徹

    Gastroenterological Endoscopy 45 (Suppl.1) 549-549 2003/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  340. ラフチジンの13C-尿素呼気試験に与える影響およびクエン酸内服併用の有用性

    小池 智幸, 大原 秀一, 佐野 望, 猪股 芳文, 三浦 敦司, 浅野 直善, 米地 真, 川村 昌司, 阿部 靖彦, 北川 靖, 吉田 雅義, 高野 信夫, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 100 (臨増総会) A168-A168 2003/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  341. Interleukin-8遺伝子多型の胃粘膜萎縮に与える影響についての臨床的検討

    大矢内 幹, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 飯島 克則, 阿部 靖彦, 川村 昌司, 吉田 雅義, 米地 真, 浅野 直喜, 三浦 敦司, 下瀬川 徹

    日本消化器病学会雑誌 100 (臨増総会) A169-A169 2003/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  342. IL-1β遺伝子多型と上部消化管疾患との関連 多型がH.pylori感染へ及ぼす影響を踏まえて

    米地 真, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 飯島 克則, 浅野 直喜, 大矢内 幹, 三浦 敦司, 下瀬川 徹

    日本消化器病学会雑誌 100 (臨増総会) A247-A247 2003/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  343. ラフチジンとファモチジンの酸分泌抑制効果に対するHP感染の影響

    小池 智幸, 大原 秀一, 猪股 芳文, 川村 昌司, 阿部 靖彦, 浅沼 清孝, 大谷内 幹, 大楽 尚弘, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹

    日本消化器病学会雑誌 100 (臨増総会) A306-A306 2003/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  344. 【実地診療とバレット食道】Barrett食道におけるHelicobacter pylori感染の役割

    阿部 靖彦, 大原 秀一, 小池 智幸, 川村 昌司, 猪股 芳文, 飯島 克則, 今谷 晃, 加藤 勝章, 関根 仁, 下瀬川 徹

    消化器の臨床 5 (6) 641-646 2002/12

    Publisher: (株)ヴァンメディカル

    ISSN: 1344-3070

  345. 【Helicobacter pylori感染と宿主反応】IL-1β polymorphismと酸分泌

    今谷 晃, 大原 秀一, 米地 真, 大矢内 幹, 浅野 直喜, 小池 智幸, 飯島 克則, 関根 仁, 下瀬川 徹

    Helicobacter Research 6 (5) 335-340 2002/10

    Publisher: (株)先端医学社

    ISSN: 1342-4319

  346. 【H.pylori除菌と食道・胃の腺癌】Helicobacter pylori感染と胃食道逆流症 Barrett食道,食道腺癌を含めて

    阿部 靖彦, 大原 秀一, 小池 智幸, 川村 昌司, 北川 靖, 吉田 雅義, 米地 真, 相田 重光, 飯島 克則, 今谷 晃, 関根 仁, 下瀬川 徹

    消化器内視鏡 14 (6) 891-901 2002/06

    Publisher: (株)東京医学社

    ISSN: 0915-3217

  347. 【Helicobacter pylori除菌に伴う問題点】Helicobacter pylori除菌非奏効病変の特徴 胃十二指腸潰瘍 難治例

    関根 仁, 大原 秀一, 杉山 幸一, 今谷 晃, 小池 智幸, 野口 謙治, 相田 重光, 佐野 俊和, 下瀬川 徹

    胃と腸 37 (4) 505-510 2002/03

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  348. Interleukin-8(IL-8)遺伝子多型と上部消化管疾患・組織学的胃炎との関連性について

    大矢内 幹, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 阿部 靖彦, 川村 昌司, 米地 真, 下瀬川 徹

    日本消化器病学会雑誌 99 (臨増総会) A163-A163 2002/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  349. IL-1β遺伝子多型と上部消化管疾患との関係 酸分泌能の検討を踏まえて

    米地 真, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 阿部 靖彦, 川村 昌司, 大矢内 幹, 下瀬川 徹

    日本消化器病学会雑誌 99 (臨増総会) A163-A163 2002/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  350. H.pylori感染における上部消化管疾患とIL-1βおよびTNFα遺伝子多型との関連

    米地 真, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 阿部 靖彦, 川村 昌司, 大矢内 幹, 下瀬川 徹

    日本消化器病学会雑誌 99 (臨増総会) A369-A369 2002/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  351. Analysis of cell damage in Helicobacter pylori-associated gastritis. International-journal Peer-reviewed

    Kenji Noguchi, Katsuaki Kato, Takuya Moriya, Takashi Suzuki, Michiya Saito, Tohru Kikuchi, Jing Yang, Akira Imatani, Hitoshi Sekine, Syuichi Ohara, Takayoshi Toyota, Tooru Shimosegawa, Hironobu Sasano

    Pathology international 52 (2) 110-8 2002/02

    ISSN: 1320-5463

    More details Close

    Helicobacter pylori infection is currently considered to be a major cause of acute and chronic gastritis, and of gastric and duodenal ulcers. Superoxide dismutase (SOD) is well known for scavenging superoxide radicals such as reactive oxygen species (ROS), subsequently protecting cells from oxidative injury, and for maintaining tissue homeostasis. In this study, we therefore evaluated the level of SOD activity and protein expression, as well as various factors associated with oxidative injury, in H. pylori-positive (n = 46) and -negative (n = 28) gastric mucosa obtained from endoscopy, in order to elucidate the possible biological significance of SOD in these mucosa. Overall SOD activity was significantly higher in H. pylori-positive mucosa (15.5 +/- 7.0 U/mg protein) than in negative mucosa (9.2 +/- 10.6 U/mg protein), and decreased markedly following H. pylori eradication (8.2 +/- 4.2 U/mg protein). Enzyme-linked immunosorbent assay (ELISA) analysis of SOD revealed that the manganese SOD (Mn-SOD) level in H. pylori-positive mucosa (1166.7 +/- 435.2 ng/mg protein) was significantly higher than in control tissues (446.3 +/- 435.3 ng/mg protein) and in mucosa obtained following eradication therapy (431.9 +/- 189.9 ng/mg protein). The level of Mn-SOD protein showed a significant correlation with degree of inflammation in the gastric mucosa. Moreover, Mn-SOD immunolocalization patterns were well correlated with the activity and protein levels evaluated by ELISA. Factors presumably associated with oxidative injury in human gastric mucosa, including terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, Ki-67, 8-hydroxydeoxyguanosine and single-stranded DNA, were all significantly higher in H. pylori-positive gastric mucosa than in control tissue and in tissue following eradication. These results all suggest that Mn-SOD, but not cytoplasmic copper-zinc SOD, plays an important role as an anti-oxidant against ROS generated in H. pylori-infected gastric mucosa and, subsequently, in the maintenance of cell turnover in gastric mucosa.

  352. 【EVLはこれでいいのか】超音波内視鏡所見からみたEVLの適応

    杉山 幸一, 大原 秀一, 関根 仁, 今谷 晃, 小池 智幸, 野口 謙治, 及川 圭介, 相田 重光, 浅木 茂, 下瀬川 徹

    消化器内視鏡 13 (9) 1273-1278 2001/09

    Publisher: (株)東京医学社

    ISSN: 0915-3217

  353. H.pylori除菌前後におけるHbindex(IHb)の検討

    相田 重光, 浅木 茂, 小池 智幸, 川村 昌司, 阿部 靖彦, 北川 靖, 今谷 晃, 関根 仁, 大原 秀一, 下瀬川 徹

    Gastroenterological Endoscopy 43 (Suppl.2) 1734-1734 2001/09

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  354. Interleukin-1(IL-1)β遺伝子多型と上部消化管疾患との関連性について

    米地 真, 今谷 晃, 大原 秀一, 関根 仁, 小池 智幸, 阿部 靖彦, 川村 昌司, 下瀬川 徹

    日本消化器病学会雑誌 98 (臨増大会) A463-A463 2001/09

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  355. 【H.pylori感染症の診断と治療】H.pylori除菌後の再陽性化

    関根 仁, 大原 秀一, 今谷 晃, 小池 智幸, 下瀬川 徹

    消化器科 32 (3) 261-265 2001/03

    Publisher: (有)科学評論社

    ISSN: 0289-8756

  356. 【ヘリコバクター・ピロリの基礎から臨床まで】除菌治療のメリットとデメリット

    大原 秀一, 関根 仁, 小池 智幸, 杉山 幸一, 今谷 晃, 下瀬川 徹

    化学療法の領域 17 (3) 509-515 2001/02

    Publisher: (株)医薬ジャーナル社

    ISSN: 0913-2384

  357. OLYMPUS社製新写真撮影システムの使用経験

    鈴木 達彦, 浅木 茂, 相田 重光, 野口 謙治, 小池 智幸, 今野 豊, 及川 圭介, 今谷 晃, 杉山 幸一, 加藤 勝章

    Gastroenterological Endoscopy 42 (Suppl.1) 622-622 2000/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  358. 逆流性食道炎,Barrett上皮・食道におけるHPの影響

    阿部 靖彦, 大原 秀一, 関根 仁, 小池 智幸, 吉田 雅義, 相田 重光, 今谷 晃, 杉山 幸一, 下瀬川 徹, 豊田 隆謙

    日本消化器病学会雑誌 97 (臨増総会) A185-A185 2000/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  359. 【胃MALTリンパ腫 Helicobacter pylori除菌後の経過】胃MALTリンパ腫のHelicobacter pylori除菌後の経過 内視鏡像・病理組織像と治療後の変化

    鈴木 達彦, 加藤 勝章, 一迫 玲, 大楽 尚弘, 久保田 祐司, 相田 重光, 今野 豊, 及川 圭介, 野口 謙治, 小池 智幸, 今谷 晃, 杉山 幸一, 関根 仁, 大原 秀一, 下瀬川 徹, 豊田 隆謙

    胃と腸 34 (11) 1367-1379 1999/10

    Publisher: (株)医学書院

    ISSN: 0536-2180

    eISSN: 1882-1219

  360. Characterization of the Drosophila ortholog of mouse eIF-3p48/INT-6. Peer-reviewed

    Miyazaki S, Rasmussen S, Imatani A, Diella F, Sullivan DT, Callahan R

    Gene 233 (1-2) 241-247 1999/06

  361. H.pylori除菌後の発見胃癌例の検討

    関根 仁, 大原 秀一, 加藤 勝章, 飯島 克則, 小池 智幸, 杉山 幸一, 有川 正志, 今谷 晃, 菅田 英明, 浅木 茂

    Gastroenterological Endoscopy 41 (Suppl.1) 787-787 1999/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

    eISSN: 1884-5738

  362. The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas. Peer-reviewed

    Miyazaki S, Imatani A, Ballard L, Marchetti A, Buttitta F, Albertsen H, Nevanlinna HA, Gallahan D, Callahan R

    Genomics. 46 (1) 155-158 1997/11

  363. Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma. Peer-reviewed

    Yabuki N, Sasano H, Tobita M, Imatani A, Hoshi T, Kato K, Ohara S, Asaki S, Toyota T, Nagura H

    Am J Pathol. 151 (3) 821-829 1997/09

  364. Analysis of p53 abnormalities in endoscopic gastric biopsies. Peer-reviewed

    Imatani A, Sasano H, Asaki S, Toyota T, Saito M, Masuda T, Nagura H

    Anticancer Res 16 (4A) 2049-2056 1996/07

  365. Cell proliferation and apoptosis in normal and pathologic human adrenal. Peer-reviewed

    Sasano H, Imatani A, Shizawa S, Suzuki T, Nagura H

    Mod Pathol. 8 (1) 11-17 1995/08

  366. Double immunostaining for c-erbB-2 and p53 in human stomach cancer cells. Peer-reviewed

    Sasano H, Date F, Imatani A, Asaki S, Nagura H

    Hum Pathol 24 (6) 584-589 1993/06

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    日本消化器病学会雑誌(Web) 118 2021

    ISSN: 1349-7693

  8. 40年に及ぶ疫学的評価による本邦における食道胃接合部腺癌,食道腺癌の増加

    畑山裕, 菅野武, 菅野武, 金笑奕, 八田和久, 宇野要, 浅野直喜, 今谷晃, 小池智幸, 金村政輝, 正宗淳

    日本消化器病学会雑誌(Web) 118 2021

    ISSN: 1349-7693

  9. Helicobacter pylori感染による分化制御遺伝子Notch1の発現抑制を介した胃粘膜萎縮機序の解明

    金笑奕, 浅野直喜, 今谷晃, 齋藤方志, 竹内章夫, 斉藤真弘, 中川健一郎, 菅野武, 八田和久, 宇野要, 小池智幸, 正宗淳

    日本消化器病学会雑誌(Web) 118 2021

    ISSN: 1349-7693

  10. 壁細胞機能不全に伴う胃の多発NETの1例

    阿部泰明, 八田和久, 小池智幸, 齊藤真弘, 金笑奕, 中川健一郎, 菅野武, 淺沼清孝, 宇野要, 浅野直喜, 今谷晃, 阿曽沼祥, 正宗淳

    日本消化器病学会東北支部例会誌 208th 2020

  11. 内視鏡下生検施行後に発症した巨大食道粘膜下血腫の一例

    伊丹英昭, 淺沼清孝, 金笑奕, 齊藤真弘, 八田和久, 宇野要, 浅野直喜, 今谷晃, 小池智幸, 正宗淳

    日本消化器病学会東北支部例会誌 208th 2020

  12. 食道限局性アミロイドーシスの一例

    藤谷拓, 八田和久, 小池智幸, 齊藤真弘, 中川健一郎, 菅野武, 金笑奕, 淺沼清孝, 宇野要, 浅野直喜, 今谷晃, 正宗淳

    日本消化器病学会東北支部例会誌 208th 2020

  13. 食道扁平上皮癌における分化制御遺伝子Sox2の発現増強による発癌・血管新生機序の解明

    高橋貴一, 浅野直喜, 今谷晃, 金笑奕, 竹内章夫, 齋藤方志, 齊藤真弘, 中川健一郎, 菅野武, 八田和久, 宇野要, 小池智幸, 正宗淳

    日本消化器病学会雑誌(Web) 117 2020

    ISSN: 1349-7693

  14. 難治性胃潰瘍を呈した好酸球性胃腸炎の一例

    大原 祐樹, 斉藤 真弘, 中川 健一郎, 金 笑奕, 八田 和久, 淺沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 207回 47-47 2019/07

    Publisher: 日本消化器病学会-東北支部

  15. LCIは表在型Barrett食道腺癌の視認性向上に有用である

    齊藤 真弘, 小池 智幸, 八田 和久, 阿部 泰明, 大方 智樹, 金 笑奕, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    Gastroenterological Endoscopy 61 (Suppl.1) 892-892 2019/05

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

  16. BLI・NBI拡大内視鏡による表在型食道扁平上皮癌深達度診断の比較検討

    八田 和久, 小池 智幸, 荒 誠之, 近藤 穣, 齊藤 真弘, 金 笑奕, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    Gastroenterological Endoscopy 61 (Suppl.1) 893-893 2019/05

    Publisher: (一社)日本消化器内視鏡学会

    ISSN: 0387-1207

  17. 消化管出血(静脈瘤破裂を除く)の予後不良症例の検討 高用量ステロイド投与は出血性胃十二指腸潰瘍内視鏡治療後再出血の危険因子である

    八田 和久, 小池 智幸, 齊藤 真弘, 金 笑奕, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化管学会雑誌 3 (Suppl.) 157-157 2019/02

    Publisher: (一社)日本消化管学会

    ISSN: 2433-3840

  18. 消化管出血(静脈瘤破裂を除く)の予後不良症例の検討 高用量ステロイド投与は出血性胃十二指腸潰瘍内視鏡治療後再出血の危険因子である

    八田 和久, 小池 智幸, 齊藤 真弘, 金 笑奕, 淺沼 清孝, 宇野 要, 浅野 直喜, 今谷 晃, 正宗 淳

    日本消化管学会雑誌 3 (Suppl.) 157-157 2019/02

    Publisher: (一社)日本消化管学会

    ISSN: 2433-3840

  19. 症状の季節変動を繰り返す好酸球性食道筋炎の1例

    外田 修裕, 宇野 要, 齊藤 真弘, 金 笑奕, 八田 和久, 淺沼 清孝, 浅野 直喜, 小池 智幸, 今谷 晃, 庄司 知隆, 佐藤 千晃, 亀井 尚, 正宗 淳

    日本消化器病学会東北支部例会プログラム・抄録集 206回 85-85 2019/02

    Publisher: 日本消化器病学会-東北支部

  20. 高用量ステロイド投与は出血性胃十二指腸潰瘍内視鏡治療後再出血の危険因子である

    八田和久, 小池智幸, 齊藤真弘, 金笑奕, 淺沼清孝, 宇野要, 浅野直喜, 今谷晃, 正宗淳

    日本消化管学会雑誌 3 (Supplement) 2019

    ISSN: 2435-8967

  21. ヘリコバクター・ピロリ感染は転写因子Sox2の発現をプロモーター上のKLF4結合部位のDNAメチル化を介して抑制する(Helicobacter pylori infection down-regulates Sox2 expression through the methylation of its KLF4 binding site)

    越後 紘治, 浅野 直喜, 今谷 晃, 金 笑奕, 正宗 淳

    日本癌学会総会記事 77回 2275-2275 2018/09

    Publisher: 日本癌学会

    ISSN: 0546-0476

  22. ヘリコバクター・ピロリ感染は転写因子Sox2の発現をプロモーター上のKLF4結合部位のDNAメチル化を介して抑制する(Helicobacter pylori infection down-regulates Sox2 expression through the methylation of its KLF4 binding site)

    越後 紘治, 浅野 直喜, 今谷 晃, 金 笑奕, 正宗 淳

    日本癌学会総会記事 77回 2275-2275 2018/09

    Publisher: 日本癌学会

    ISSN: 0546-0476

  23. 飲酒後の食道組織中アセトアルデヒドに関する検討

    大方 英樹, 八田 和久, 飯島 克則, 淺沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 濱田 晋, 正宗 淳, 下瀬川 徹

    日本消化器病学会雑誌 115 (臨増総会) A266-A266 2018/04

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

  24. 飲酒後の食道組織中アセトアルデヒドに関する検討

    大方 英樹, 八田 和久, 飯島 克則, 淺沼 清孝, 宇野 要, 浅野 直喜, 小池 智幸, 今谷 晃, 濱田 晋, 正宗 淳, 下瀬川 徹

    日本消化器病学会雑誌 115 (臨増総会) A266-A266 2018/04

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

  25. The analysis for use of percutaneous endoscopic gastrostomy placed prophylactically for head and neck cancer treated with chemoradiotherapy

    Nobuyuki Ara, Takeshi Kanno, Waku Hatta, Kiyotaka Asanuma, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 351-352 2016/11

    ISSN: 0815-9319

    eISSN: 1440-1746

  26. Factors associated with the development of secondary esophageal squamous cell carcinomas after endoscopic resection for superficial esophageal squamous cell carcinomas

    Waku Hatta, Kazuaki Norita, Tomoyuki Koike, Takeshi Kanno, Nobuyuki Ara, Kiyotaka Asanuma, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 12-12 2016/11

    ISSN: 0815-9319

    eISSN: 1440-1746

  27. Intense Gastro-Esophageal Reflux May Influence the Localization of Barrett's Adenocarcinoma: Measured by 24-h pH-Impedance Monitoring

    Masahiro Saito, Tomoyuki Koike, Hiroki Kikuchi, Kazuaki Norita, Kenichirou Nakagawa, Takeshi Kanno, Gen Kusaka, Yutaka Kondo, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Katsunori Iijima, Tooru Shimosegawa

    GASTROENTEROLOGY 150 (4) S483-S483 2016/04

    ISSN: 0016-5085

    eISSN: 1528-0012

  28. NOD1 Expression in Gastric Epithelial Cells Is Down-Regulated by Helicobacter pylori Infection Through the Methylation of Its CpG Island by DNA Methyltransferases

    Tetsuhiko Mikami, Naoki Asano, Akira Imatani, Xiaoyi Jin, Yutaka Kondo, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 150 (4) S299-S299 2016/04

    ISSN: 0016-5085

    eISSN: 1528-0012

  29. エストロゲンはNrf2を介して逆流性食道炎を抑制する

    鳥畑勇大, 淺沼清孝, 田口恵子, 浅野直喜, 今谷晃, 山本雅之, 下瀬川徹

    日本消化器病学会大会(Web) 58th 2016

  30. [Relationship between disaster stress and peptic ulcers].

    Kanno T, Iijima K, Koike T, Shimosegawa T

    Nihon rinsho. Japanese journal of clinical medicine 73 (7) 1209-1214 2015/07

    Publisher: 日本臨床社

    ISSN: 0047-1852

  31. The Usefulness of Optical Coherence Tomography in Evaluating the Extension of Barrett's Mucosa Underneath the Squamous Epithelium

    Waku Hatta, Kaname Uno, Tomoyuki Koike, Nobuyuki Ara, Naoki Asano, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROINTESTINAL ENDOSCOPY 81 (5) AB392-AB392 2015/05

    ISSN: 0016-5107

    eISSN: 1097-6779

  32. The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter: a Multicenter Retrospective Trial in Japan

    Waku Hatta, Tomoyuki Koike, Katsunori Iijima, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Akira Imatani, Atsuko Kasajima, Fumiyoshi Fujishima, Hironobu Sasano, Tooru Shimosegawa

    GASTROINTESTINAL ENDOSCOPY 81 (5) AB126-AB126 2015/05

    ISSN: 0016-5107

    eISSN: 1097-6779

  33. Pseudokinase Tribbles 3 Enhances SHP2-Dependent ERK Signaling in Helicobacter pylori-Induced Gastric Carcinogenesis

    Yutaka Kondo, Naoki Asano, Akira Imatani, Xiaoyi Jin, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 148 (4) S528-S528 2015/04

    ISSN: 0016-5085

    eISSN: 1528-0012

  34. Restoration of Notch1 Receptor Expression Contributes to Tumor Suppressive Roles in Gastric Cancer Cells Through the Regulation of p53

    Xiaoyi Jin, Naoki Asano, Akira Imatani, Yutaka Kondo, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 148 (4) S6-S6 2015/04

    ISSN: 0016-5085

    eISSN: 1528-0012

  35. Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression

    Junya Honda, Katsunori Iijima, Gen Kusaka, Yutaka Kondo, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Kaname Uno, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 148 (4) S740-S741 2015/04

    ISSN: 0016-5085

    eISSN: 1528-0012

  36. Bismuth classification is associated with the requirement for multiple biliary drainage in preoperative patients with malignant perihilar biliary stricture International-journal

    Miura S, Kanno A, Masamune A, Hamada S, Takikawa T, Nakano E, Yoshida N, Hongo S, Kikuta K, Kume K, Hirota M, Yoshida H, Katayose Y, Unno M, Shimosegawa T

    Surg Endosc 29 (7) 1862-70 2015

    DOI: 10.1007/s00464-014-3878-y  

    More details Close

    BACKGROUND: Single preoperative biliary drainage for malignant perihilar biliary stricture occasionally fails to control jaundice and cholangitis. Multiple biliary drainage is required in such cases, but their clinical background is unclear. We determined the clinical characteristics associated with the requirement for multiple biliary drainage. METHODS: The consecutive 122 patients with malignant perihilar biliary stricture were enrolled in a single-center retrospective study. Preoperative biliary drainage was initially performed on the future remnant hepatic lobe. Additional drainage was performed if jaundice failed to improve or cholangitis developed in undrained hepatic lobes. Detailed clinical characteristics and the number of preoperative biliary drainage procedures required before operation were analyzed. RESULTS: Thirty-one patients (25.4%) initially underwent multiple biliary drainage. However, 69 (56.7%) required multiple biliary drainage by the time of the operation. In the univariate analysis, the initial serum bilirubin level, cholangitis, percutaneous portal vein embolization, history of inserted endoscopic biliary stenting, length of preoperative period, operative procedure, and Bismuth classification were significant factors. In the multivariate analysis using these factors, Bismuth classification was independently associated with the requirement for multiple biliary drainage. The number of patients who required multiple biliary drainage was higher in those with Bismuth-II (91.9%), Bismuth-IIIa (65.7%), and Bismuth-IV (92.9%) than in those with Bismuth-I (22.2%) and Bismuth-IIIb (18.2%). CONCLUSIONS: Patients with Bismuth-II, Bismuth-IIIa, and Bismuth-IV are at higher risk for multiple biliary drainage. A strategy based on the Bismuth classification for performing preoperative biliary drainage is important for patients with malignant perihilar biliary stricture.

  37. Loss of Notch1 Function in Helicobacter pylori Contributes to Gastric Mucosal Atrophy and Carcinogenesis

    Xiaoyi Jin, Naoki Asano, Akira Imatani, Jun Fushiya, Yutaka Kondo, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 146 (5) S502-S502 2014/05

    ISSN: 0016-5085

    eISSN: 1528-0012

  38. Impaired NOD1 Function Induce Dysplasia in Helicobacter pylori Infected Stomach Through Wnt/beta-Catenin Signaling

    Jun Fushiya, Naoki Asano, Akira Imatani, Yutaka Kondo, Xiaoyi Jin, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 146 (5) S47-S48 2014/05

    ISSN: 0016-5085

    eISSN: 1528-0012

  39. Identification of a high-risk group for low-dose aspirin-induced gastropathy by measuring serum pepsinogen in H. pylori-infected subjects.

    Iijima, K, Koike, T, Ara, N, Nakagawa, K, Kondo, Y, Uno, K, Hatta, W, Asano, N, Imatani, A, Shimosegawa, T

    J Gastroenterol 2014

    DOI: 10.1007/s00535-014-0976-5  

  40. The Clonal Expansion of CD24 and SOX2 Positive Cancer Cells Occur in the Initiation of Gastric Cancer Through the Nuclear beta-Catenin Accumulation

    Takashi Chiba, Akira Imatani, Naoki Asano, Jun Fushiya, Xiaoyi Jin, Yutaka Kondo, Hiroyuki Endo, Nobuyuki Ara, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 144 (5) S286-S286 2013/05

    ISSN: 0016-5085

    eISSN: 1528-0012

  41. Calcium Carbonate Breath Test for Non-Invasive Measurement of Gastric Acid Secretion

    Hirohiko Shinkai, Katsunori Iijima, Hiroyuki Endo, Nobuyuki Ara, Naoki Asano, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 144 (5) S478-S478 2013/05

    ISSN: 0016-5085

    eISSN: 1528-0012

  42. Deficiency of NOD1, Innate Immunity Related Molecule, Leads to Formation of Helicobacter pylori Induced Gastric Intestinal Metaplasia Not Only by Inducing CDx2 but Also by Suppressing SOX2 Expression

    Naoki Asano, Akira Imatani, Jun Fushiya, Takashi Chiba, Xiaoyi Jin, Yutaka Kondo, Hiroyuki Endo, Nobuyuki Ara, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 144 (5) S325-S325 2013/05

    ISSN: 0016-5085

    eISSN: 1528-0012

  43. Does the Japanese GERD Management Guideline Adapt to GERD Treatment of Gastroenterology Physicians ?

    Tomoyuki Koike, Kenichiro Nakagawa, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 142 (5) S593-S594 2012/05

    ISSN: 0016-5085

  44. Pseudokinase Tribbles Homolog 3 is Induced in Helicobacter pylori Infected Gastric Mucosa and Contributes to Gastric Carcinogenesis Through Phosphorylation of Oncogenic Protein SHP-2

    Yutaka Kondo, Akira Imatani, Naoki Asano, Jun Fushiya, Takashi Chiba, Yasuhiko Abe, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    GASTROENTEROLOGY 142 (5) S57-S58 2012/05

    ISSN: 0016-5085

  45. Paradoxical Effects of H-pylori Infection on Low-Dose Aspirin Induced Gastropathy Depending on the Gastric Acid Secretion Level

    Katsunori Iijima, Nobuyuki Ara, Yasuhiko Abe, Tomoyuki Koike, Toshimitsu Iwabuchi, Kaname Uno, Hiroyuki Endo, Naoki Asano, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 142 (5) S103-S103 2012/05

    ISSN: 0016-5085

  46. Influence of Meals on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

    Hirohiko Shinkai, Tomoyuki Koike, Nobuyuki Ara, Kaname Uno, Naoki Asano, Yasuhiko Abe, Katsunori Iijima, Akira Imatani, Masamitsu Maekawa, Yotaro Matsumoto, Miki Shimada, Nariyasu Mano, Tooru Shimosegawa

    GASTROENTEROLOGY 142 (5) S215-S215 2012/05

    ISSN: 0016-5085

  47. Gastric Cancers Emerging After H. pylori Eradication Arise Exclusively From Functionally Irreversible Non-Acid Secreting Areas

    Katsunori Iijima, Yasuhiko Abe, Tomoyuki Koike, Hiroyuki Endo, Naoki Asano, Kiyotaka Asanuma, Kaname Uno, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 140 (5) S186-S186 2011/05

    ISSN: 0016-5085

  48. NOD1,the Innate Immunity Related Molecule, Suppresses the Formation of Helicobacter pylori Induced Gastric Intestinal Metaplasia Through Regulation of Homeobox Gene CDx2

    Naoki Asano, Akira Imatani, Yutaka Kondo, Takashi Chiba, Jun Fushiya, Yasuhiko Abe, Katsunori Iijima, Tomoyuki Koike, Toom Shimosegawa

    GASTROENTEROLOGY 140 (5) S125-S126 2011/05

    ISSN: 0016-5085

  49. Gender Differences in Esophageal Mucosal Injury in a Reflux Esophagitis Model of Rats

    Tomohiro Masaka, Katsunori Iijima, Tooru Shimosegawa, Akira Imatani, Tomoyuki Koike, Yasuhiko Abe, Naoki Asano, Kiyotaka Asanuma, Kaname Uno

    GASTROENTEROLOGY 140 (5) S627-S627 2011/05

    ISSN: 0016-5085

  50. Direct Measurement of Gastroesophageal Reflux Episodes in Patients With Squamous Cell Carcinoma by 24-h pH-Impedance Monitoring.

    Uno K, Iijima K, Hatta W, Koike T, Abe Y, Asano N, Kusaka G, Shimosegawa T

    Am J Gastroenterol - 2011

    DOI: 10.1038/ajg.2011.282  

  51. 【難治性GERDの治療戦略】 好酸球性食道炎の臨床像 内視鏡像・病理組織像を中心に (消化器内科)

    阿部靖彦, 飯島克則, 小池智幸, 今谷晃, 下瀬川徹

    消化器内科 107 (臨増総会) A136-A136 2010/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

    eISSN: 1349-7693

  52. Clinicopathological Characteristics of Barrett&apos;s Esophageal Cancer in Japanese Patients and Long-Term Results of Therapy

    Tomoyuki Koike, Toru Horii, Shuichi Ohara, Yasuhike Abe, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 136 (5) A459-A459 2009/05

    ISSN: 0016-5085

  53. On-Demand Proton Pump Inhibitor Therapy for Erosive Gastroesophageal Reflex Disease in Japanese Patients

    Hiroyuki Unakami, Tomoyuki Koike, Shuichi Chara, Wataru Iwai, Toru Horii, Ryosuke Kikuchi, Shigeyuki Kobayashi, Yasuhiko Abe, Katsumori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 136 (5) A445-A446 2009/05

    ISSN: 0016-5085

  54. CD133 Positive Cancer Stem-Like Cells Are Induced Through Notch Signaling Pathway in Poorly Differentiated Human Gastric Cancer

    Hidetomo Konishi, Naoki Asano, Akira Imatani, Yutaka Kondo, Tomoyuki Koike, Katsunori Iijima, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 136 (5) A460-A460 2009/05

    ISSN: 0016-5085

  55. The Aggravative Effect of Gastric Acid On Low Dose Aspirin Induced Gastric Mucosal Injury: Examination By Endoscopic Gastrin Test

    Nobuyuki Ara, Katsunori Iijima, Akira Imatani, Tomoyuki Koike, Yasuhiko Abe, Naoki Asano, Kaname Uno, Kiyotaka Asanuma, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 136 (5) A185-A185 2009/05

    ISSN: 0016-5085

  56. NOD1 Gene Polymorphism Affects NOD1 Protein Expression, Leading to Higher Susceptibility to GERD

    Tomoyuki Oikawa, Akira Imatani, Naoki Asano, Hidetomo Konishi, Yutaka Kondo, Tomoyuki Koike, Katsunori Iijima, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 136 (5) A547-A547 2009/05

    ISSN: 0016-5085

  57. Brain Activity Following Esophageal Acid Infusion Using Positron Emission Tomography

    Kobayashi S., Abe Y., Tashiro M., Koike T., Iijima K., Imatani A., Ohara S., Watanabe S., Fukudo S., Shimosegawa T.

    CYRIC annual report 2009 200-207 2009

    Publisher: Cyclotron and Radioisotope Center, Tohoku University

  58. Preservation of gastric acid secretion is important for the development of Barrett&apos;s esophageal cancer in Japanese people, irrespective of the H. pylori infection status

    Tom Horii, Tomoyuki Koike, Shuichi Ohara, Yasuhiko Abe, Ryosuke Kikuchi, Hatsushi Yamagishi, Viyotaka Asanuma, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 134 (4) A450-A450 2008/04

    ISSN: 0016-5085

  59. Increased risk of gastroesophageal reflux disease associated with gene polymorphisms in NOD1 signaling pathway in Helicobacter pylori infected patients

    Tomoyuki Oikawa, Akira Imatani, Sho Asonuma, Naoki Asano, Yasuhiko Abe, Tomoyuki Koike, Katsunori Iijima, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 134 (4) A592-A592 2008/04

    ISSN: 0016-5085

  60. Not only reflux esophagitis but H-pylori infection may be a causal factor for the gastroesophageal junction cancer in Japanese people

    Tomoyuki Koike, Shuichi Ohara, Yasuhiko Abe, Toru Horii, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 134 (4) A294-A295 2008/04

    ISSN: 0016-5085

  61. The down-regulation of a HMG box gene Sox2 by exposure to acid and bile induces the progression of Barrett's esophagus

    Sho Asonuma, Akira Imatani, Yasuhiko Abe, Tomoyuki Koike, Naoki Asano, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 134 (4) A437-A437 2008/04

    ISSN: 0016-5085

  62. Periostin, secreted from stromal cells, has biphagic effect on cell migration and correlates with the epithelial mesenchymal transition of human pancreatic cancer cells. International-journal

    Kanno A. Satoh, K. Masamune, A. Hirota, M. Kimura, K. Umino, J, Hamada, S. Satoh, A. Egawa, S. Motoi, F, Unno M, Shimosegawa T

    Int J Cancer. 122 (12) 2707-2712 2008

    DOI: 10.1002/ijc.23332  

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    Periostin is a secretory protein that has been suggested to function as a cell adhesion molecule and promote the invasiveness or growth rate of tumors. However, little is known about the association of its expression and epithelial to mesenchymal transition (EMT), which is considered to play a crucial role in cancer cell metastasis. Thus, the authors investigated whether periostin could be involved in the process of EMT and the role of this gene in pancreatic cancer development. The expression of periostin was observed mainly in stromal cells but very little in cancer cells by immunohistochemistry and real-time RT-PCR. In vitro, pancreatic stellate cells (PSCs) exhibited a much higher basal expression of periostin compared with cancer cells. Periostin secreted in the supernatant from 293T cells that expressed periostin (approximately 150 ng/ml) inhibited the migration of pancreatic cancer cells. Coculture assay revealed that periostin expression in PSC was induced by pancreatic cancer cells. To assess the direct role of periostin in pancreatic cancer cells, the authors generated pancreatic cancer cell lines that stably express periostin. The induced expression of periostin (to 150 ng/ml) altered the morphology of cancer cells, changing them from mesenchymal to epithelial phenotypes with the induction of epithelial markers and a reduction of mesenchymal markers, and showed reduced cell migration in vitro and formed smaller tumors as well as suppressed metastasis in vivo. On the other hand, high concentration of recombinant periostin (1 microg/ml) promoted cell migration with AKT activation. The findings suggest that periostin has biphasic effect on the development of pancreatic cancer.

  63. NOD1 gene polymorphism influences the susceptibility to gastroesophageal reflux disease and progression of gastric atrophy in Helicobacter pylori infection

    Tomoyuki Oikawa, Akira Imatani, Sho Asonuma, Naoki Asano, Tomoyuki Koike, Katsunori Iijima, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 132 (4) A275-A275 2007/04

    ISSN: 0016-5085

  64. Hypochlorhydria in esophageal squamous-cell carcinoma

    Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Hatsushi Yamagishi, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 132 (4) A418-A418 2007/04

    ISSN: 0016-5085

  65. Long-term clinical outcome of patients with gastric low-grade mucosa associated lymphoid tissue lymphoma after H-pylori eradication therapy

    Shiho Terai, Katsunori Iijima, Katsuaki Kato, Naohiro Dairaku, Tatsuhiko Suzuki, Masayoshi Yoshida, Tomoyuki Koike, Yasushi Kitagawa, Akira Imatani, Hiroshi Sekine, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 132 (4) A311-A311 2007/04

    ISSN: 0016-5085

  66. Fe-S cluster proteins are intracellular targets for nitric oxide generated luminally at the gastro-oesophageal junction.

    Asanuma K, Iijima K, Ara N, Koike T, Yoshitake J, Ohara S, Shimosegawa T, Yoshimura T

    Nitric Oxide 16 (4) 395-402 2007

    DOI: 10.1016/j.niox.2007.02.002  

  67. Helicobacter pylori itself and interferon-gamma suppresses the expression of a HMG box protein Sox2 through stat6-mediated interleukin-4 signaling in gastric epithelial cells

    Sho Asonuma, Akira Imatani, Naoki Asano, Tomoyuki Oikawa, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 130 (4) A526-A526 2006/04

    ISSN: 0016-5085

  68. Gastric atrophy may be associated with the development of squamous cell carcinoma of the esophagus in Japan

    KaLsunori Iijima, Tomoyuki Koike, Hitoshi Sekine, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

    GASTROENTEROLOGY 130 (4) A411-A411 2006/04

    ISSN: 0016-5085

  69. Prevalence and the degree of GERD symptoms in Japanese general population

    Hatsushi Yamagishi, Shuichi Ohara, Tomoyuki Koike, Ken Anizumi, Yoshifumi Inomata, Katsumori Iijima, Akira Imatani, Tooru Shimosegawa, Shigemitsu Aida, Ktsuaki Kato, Daisuke Shibuya

    GASTROENTEROLOGY 130 (4) A632-A632 2006/04

    ISSN: 0016-5085

  70. Multivariate analysis of factors affecting the healing of reflux esophagitis in Japan

    Ken Ariizumi, Shuichi Ohara, Tomoyuki Koike, Shigeyuki Kobayashi, Hatushi Yamagishi, Atushi Miura, Yoshifumi Inomata, Yasuhiko Abe, Masashi Kawamura, Yasushi Kitagawa, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa

    GASTROENTEROLOGY 130 (4) A178-A179 2006/04

    ISSN: 0016-5085

  71. Intestinal metaplasia related gene Cdx2 is regulated by not only h pylori itself but also interferon-?? and tumor necrosis factor-?? in gastric epithelial cells through Nf-?? b signaling.

    N Asano, A Imatani, M Ohyauchi, A Miura, S Asonuma, S Ohara, T Shimosegawa

    GASTROENTEROLOGY 128 (4) A593-A593 2005/04

    ISSN: 0016-5085

  72. Helicobacter pylori infection stimulates interleukin-8 transcriptional activity through a novel transcriptional site of IL-8-251.

    M Ohyauchi, A Imatani, N Asano, A Miura, S Asonuma, A Masamune, S Ohara, T Shimosegawa

    GASTROENTEROLOGY 128 (4) A596-A596 2005/04

    ISSN: 0016-5085

  73. IL-4 receptor plus 3044g/a polymorphism is associated with antral gastritis and an increased the risk of duodenal ulcers in the H pylori-infected Japanese population

    A Miura, A Imatani, M Ohyauchi, N Asano, M Yonechi, T Koike, K Iijima, K Takahashi, S Ohara, T Shimosegawa

    GASTROENTEROLOGY 128 (4) A475-A476 2005/04

    ISSN: 0016-5085

  74. H.pylori刺激によるin vitroでの腸上皮化生関連遺伝子Cdx2の誘導とそのシグナル伝達機構の解析

    浅野 直喜, 今谷 晃, 大矢内 幹, 正宗 淳, 大原 秀一, 下瀬川 徹

    胃分泌研究会誌 36 33-35 2004/07

    Publisher: 胃病態機能研究会

    ISSN: 0289-2057

  75. Helicobacter pylori infection induces intestinal metaplasia related gene Cdx2 in gastric epithelial cells via PTEN-PI3K/Akt-NF kappa B pathway

    N Asano, A Imatani, A Masamune, M Ohyauchi, M Yonechi, S Ohara, T Shimosegawa

    GASTROENTEROLOGY 126 (4) A530-A531 2004/04

    ISSN: 0016-5085

  76. The polymorphism interleukin-8-251A is associated with enhanced transcriptional activity and a progression of gastric atrophy in Helicobacter pylori infection

    M Ohyauchi, A Imatani, M Yonechi, S Ohara, A Masamune, T Koike, K Iijima, N Asano, A Miura, T Shimosegawa

    GASTROENTEROLOGY 126 (4) A259-A259 2004/04

    ISSN: 0016-5085

  77. The therapeutic effects of rabeprazole at a dose of 10mg on reflux esophagitis may not be influenced by CYP2C19 polymorphism

    K Ariizumi, S Ohara, T Koike, M Kawamura, Y Inomata, Y Kitagawa, N Dairaku, K Iijima, A Imatani, K Kato, H Sekine, T Shimosegawa

    GASTROENTEROLOGY 126 (4) A340-A340 2004/04

    ISSN: 0016-5085

  78. H.pylori刺激によるin vitroでのホメオボックス遺伝子Cdx2の発現・制御についての検討

    浅野 直喜, 今谷 晃, 米地 真, 大矢内 幹, 三浦 敦司, 正宗 淳, 関根 仁, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A191-A191 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

  79. H.pylori感染におけるInterleukin-8-251A/T遺伝子多型別転写活性の検討

    大矢内 幹, 今谷 晃, 浅野 直喜, 三浦 敦司, 米地 真, 正宗 淳, 関根 仁, 大原 秀一, 下瀬川 徹

    日本消化器病学会雑誌 101 (臨増総会) A192-A192 2004/03

    Publisher: (一財)日本消化器病学会

    ISSN: 0446-6586

  80. Not only reflux esophagitis but H-pylori infection may be a causal factor for the inflammation of columnar-lined esophagus

    Y Inomata, S Ohara, Y Abe, T Koike, H Sekine, K Iijima, M Kawamura, N Dairaku, A Imatani, K Kato, T Shimosegawa

    GASTROENTEROLOGY 124 (4) A642-A642 2003/04

    ISSN: 0016-5085

  81. IL-8 polymorphism increases the risk of gastric cancer gastric ulcer, and atrophic gastritis in Japanese population

    M Ohyauchi, A Imatani, S Ohara, H Sekine, T Koike, K Iijima, Y Abe, M Kawamura, M Yoshida, N Asano, M Yonechi, T Shimosegawa

    GASTROENTEROLOGY 124 (4) A402-A402 2003/04

    ISSN: 0016-5085

  82. Effect of lafutidine on C-13-urea breath test (UBT): intragastric acidification reduces the frequency of false negative UBT results

    T Koike, S Ohara, N Sano, N Dairaku, K Iijima, Y Abe, Y Inomata, A Imatani, K Kato, H Sekine, T Shimosegawa

    GASTROENTEROLOGY 124 (4) A177-A178 2003/04

    ISSN: 0016-5085

  83. Acid secretion of reflux esophagitis and other upper gastrointestinal diseases in Japanese

    T Koike, S Ohara, K Iijima, H Sekine, Y Abe, Y Inomata, M Kawamura, N Dairaku, A Imatani, K Kato, T Shimosegawa

    GASTROENTEROLOGY 124 (4) A54-A54 2003/04

    ISSN: 0016-5085

  84. Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines

    KANEKO K, SATOH K, MASAMUNE A, SATOH A, SHIMOSEGAWA T

    17 (3) 254-255 2002/06/25

    ISSN: 0913-0071

  85. Interleukin-1B polymorphisms are associated with the risk of not only gastric carcinoma but also gastric ulcer in the Japanese population

    M Yonechi, A Imatani, S Ohara, H Sekine, T Koike, M Kawamura, Y Abe, M Ooyauchi, T Shimosegawa

    GASTROENTEROLOGY 122 (4) A425-A425 2002/04

    ISSN: 0016-5085

  86. Lysophosphatidylcholine induces apoptosis in AR42J cells

    MASAMUNE A, SAKAI Y, SATOH A, FUJITA M, YOSHIDA M, SHIMOSEGAWA T

    17 (1) 85-86 2002/02/25

    ISSN: 0913-0071

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Presentations 12

  1. Aberrant Sox2 expression directly up-regulated the expression of Suprabasin leading to angiogenesis and cell proliferation in esophageal squamous cell carcinogenesis

    Kiichi Takahashi, Naoki Asano, Akira Imatani, Yutaka Kondo, Masashi Saito, Akio Takeuchi, Xiaoyi Jin, Masahiro Saito, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    DDW2020 2020/05/04

  2. Suprabasin expression induced by Sox2 overexpression promoted cell proliferation and angiogenesis contributing to esophageal squamous cell carcinogenesis

    Kiichi Takahashi, Naoki Asano, Akira Imatani, Xiaoyi Jin, Akio Takeuchi, Masashi Saito, Tomoyuki Koike, Atsushi Masamune

    THE 2019 NIH-Japan-JSPS Symposium 2019/10/28

  3. NOD1 deficient gastric stem cells fail to differentiate to parietal cells and cause gastric mucosal atrophy

    Naoki Asano, Akira Imatani, Akio Takeuchi, Kiichi Takahashi, Hiroharu Echigo, Xiaoyi Jin, Masahiro Saito, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    DDW2019 2019/05/19

  4. Increased Sox2 expression in the early stage of esophageal squamous cell carcinogenesis induce cell proliferation and tumor angiogenesis

    Kiichi Takahashi, Naoki Asano, Akira Imatani, Xiaoyi Jin, Masahiro Saito, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Tomoyuki Koike, Atsushi Masamune

    DDW2019 2019/05/19

  5. Sox2 expression is down-regulated through the methylation of its KLF4 binding site in human gastric cancer cells

    Hiroharu Echigo, Naoki Asano, Akira Imatani, Xiaoyi Jin, Waku Hatta, Kiyotaka Asanuma, Kaname Uno, Tomoyuki Koike, Atsushi Masamune, Tooru Shimosegawa

    DDW2018 2018/06/02

  6. Insufficiency of NOD1 leads to Helicobacter pylori-induced gastric intestinal metaplasia through induction of Cdx2

    Naoki Asano, Akira Imatani, Tomohiro Watanabe, Jun Fushiya, Yutaka Kondo, Xiaoyi Jin, Tetsuhiko Mikami, Takeshi Kanno, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Tomoyuki Koike, Warren Strober, Tooru Shimosegawa

    The 2017 Japan-NIH Joint Symposium 2017/02/15

  7. NOD1 expression in gastric epithelial cells is down-regulated by Helicobacter pylori infection through the methylation of its CpG Island by DNA methyltransferases

    Tetsuhiko Mikami, Akira Imatani, Naoki Asano, Xiaoyi Jin, Yutaka Kondo, Waku Hatta, Nobuyuki Ara, Kiyotaka Asanuma, Tomoyuki Koike, Tooru Shimosegawa

    DDW2016 2016/05/22

  8. Pseudokinase Tribbles 3 enhances SHP2-mediated ERK signaling in H.pylori-induced gastric carcinogenesis

    Yutaka Kondo, Akira Imatani, Naoki Asano, XiaoYi Jin, Jun Fushiya, Tomoyuki Koike, Katsunori Iijima, Tooru Shimosegawa

    DDW2015 2015/05/16

  9. Restoration of Notch1 receptor expression contributes to tumor suppressive roles in gastric cancer cells through the regulation of p53

    Xiaoyi Jin, Naoki Asano, Akira Imatani, Yutaka Kondo, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    DDW2015 2015/05/16

  10. NOD1 insufficiency induces dysplasia in Helicobacter pylori infected stomach via Akt/GSK3β/β-catenin signaling

    Jun Fushiya, Naoki Asano, Akira Imatani, Yutaka Kondo, Warren Strober, Tooru Shimosegawa

    NIH-Japan-JSPS Symposium 2014 2014/10/23

  11. Impaired NOD1 Function Induce Dysplasia in Helicobacter pylori Infected Stomach Through Wnt/beta-catenin Signaling

    Jun Fushiya, Naoki Asano, Akira Imatani, Yutaka Kondo, Xiaoyi Jin, Katsunori Iijima, Tomoyuki Koike, Warren Strober, Tooru Shimosegawa

    DDW2014 2014/05/03

  12. Loss of Notch1 function in Helicobacter pylori contributes to gastric mucosal atrophy and carcinogenesis

    Xiaoyi Jin, Naoki Asano, Akira Imatani, Jun Fushiya, Yutaka Kondo, Katsunori Iijima, Tomoyuki Koike, Tooru Shimosegawa

    DDW2014 2014/05/03

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Research Projects 3

  1. ヒト胃オルガノイド培養に基づく幹細胞老化に伴う発癌ポテンシャル獲得機序の解明

    今谷 晃

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  2. Elucidation of regeneration-mechanisms through notch signaling and establishment of novel stem cell transplantation in pancreas

    SHIMOSEGAWA Tooru, IMATANI Akira, KIMURA Kenji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2002 - 2004

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    [Background] Notch signaling is known to have a crucial role on organogenesis in various organs. Recentry it is reported that Notch signaling is activated in cancer in various organs. But the precise role of Notch signaling on regeneration of pancreatic ductal cells and oncogenesis are still largely unknown. [Aim] To elucidate the role of Notch signaling on regeneration and oncogenesis. [Results] 1)Notch1 expression was observed not only in invasive carcinoma but also in PanIn-1Alesion. Very faint expression of Notch1 was observed in normal pancreatic ducts. Notch1 was expressed intensely in tubular complex in tumor flee area. 2)Nestin, a marker of progenitor cells was expressed in pancreatic cancer cells. 3)Cell growth and Notch1 expression in cancer cells were inhibited by retinoic acid. Nestin expression was also reduced by retinoic acid. In contrast, carbonic anhydrase II and cytokeratin 19 were upregulated. 4)Nestin expression was downregulated by Notch inhibitor. In contrast, carbonic anhydrase II and cytokeratin 19 were upregulated by Notch inhibitor. 5)MSX was downregulated by Notch signaling inhibition. 6)MSX2 promoted cell growth and induced epithelial mesenchymal transition. [Conclusion] It is suggested that Notch regulates malignant potential in pancreatic cancer cells. It is also suggested that Notch could regulate malignant potential through MSX2.

  3. Fiber-optic approaches for diagnosis of gastrointestinal disease

    SHIMOSEGAWA Tooru, ASAKURA Tohru, TASHIRO Hideo, SATO Hidetoshi, IMATANI Akira, AIZAWA Katuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2000 - 2003

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    To clarify the usefulness of the second-generation photosensitizer, mono-L-aspartyl chlorin e6(NPe6), we examined the possibility of photodynamic diagnosis and photodynamic therapy for intestinal tumors in a mouse model. (1) The intestinal tumor sites were irradiated with a 664-nm diode laser constant intervals after the administration of photosensitizers, respectively. (2) The tumors were excised and processed for the frozen section to observe the fluorescence by a microscope. We observed the fluorescent image and calculated that the mean fluorescence intensity was significantly higher in the tumors than the normal mucosa during 6 hours (P<0.001). The fluorescence of NPe6 was chiefly accumulated in the intestinal tumors as red fluorescence on the fluorescent microphotographic image. We conclude that NPe6 may be a valuable photosensitizer for the photodynamic diagnosis and photodynamic therapy of intestinal tumors. Our major goal is to develop advanced analytical techniques for biomedical researches based on the Raman spectroscopic applications of an electronically tuned Ti:sapphire laser and the developments of advanced spectroscopic tools.