東北大学研究者紹介

研究者詳細

ホーム

日本語 English

顔写真

イマタニ　アキラ

今谷　晃

Akira Imatani

所属

大学院医学系研究科　保健学専攻　家族支援看護学講座（成人看護学分野）

職名

教授

学位

博士（医学）（東北大学）

researchmap

https://researchmap.jp/m4398h3190y3180

J-GLOBAL ID

202001013106323780

経歴 5

2012年3月～継続中

東北大学病院　消化器内科　（兼務）
2012年3月～継続中

東北大学医学系研究科　保健学専攻　教授
2010年10月～ 2012年2月

東北大学病院　消化器内科　講師
2008年4月～ 2010年8月

東北大学医学系研究科　消化器病態学分野　助教
1994年8月～ 1998年1月

米国国立衛生研究所国立がん研究所（NIH, NCI）

学歴 1

東北大学医学部

～ 1989年3月

所属学協会 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

︎全件表示 ︎最初の5件までを表示

研究キーワード 7

幹細胞
胃癌
食道癌
Helicobacter pylori
発癌
分化制御
老化

研究分野 2

ライフサイエンス / 消化器内科学 /
ライフサイエンス / 腫瘍生物学 /

論文 366

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells. 国際誌査読有り

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年3月10日

DOI： 10.4049/immunohorizons.2000007 　

詳細を見る詳細を閉じる

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.
Sox2 induces tumorigenesis and angiogenesis of early stage esophagealsquamous cell carcinoma through secretion of Suprabasin. 国際誌査読有り

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年2月14日

DOI： 10.1093/carcin/bgaa014 　

詳細を見る詳細を閉じる

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.
Notch1 directly induced CD133 expression in human diffuse type gastric cancers. 国際誌査読有り

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年8月30日

DOI： 10.18632/oncotarget.10967 　

詳細を見る詳細を閉じる

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.
Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses. 国際誌査読有り

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年3月1日

DOI： 10.1158/0008-5472.CAN-15-2272 　

詳細を見る詳細を閉じる

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.
Gender differences in oesophageal mucosal injury in a reflux oesophagitis model of rats. 国際誌査読有り

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年1月

DOI： 10.1136/gutjnl-2011-301389 　

詳細を見る詳細を閉じる

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.
Gene polymorphisms of NOD1 and interleukin-8 influence the susceptibility to erosive esophagitis in Helicobacter pylori infected Japanese population. 国際誌査読有り

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年11月

DOI： 10.1016/j.humimm.2012.08.004 　

詳細を見る詳細を閉じる

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.
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. 国際誌査読有り

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年10月

eISSN：1502-7708

詳細を見る詳細を閉じる

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.
Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression. 国際誌査読有り

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年8月

DOI： 10.1152/ajpgi.00518.2007 　

詳細を見る詳細を閉じる

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.
The polymorphism interleukin-8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population 査読有り

OHYAUCHI M

Gut　54　(3)　330-335　2005年3月1日
出版者・発行元：
DOI： 10.1136/gut.2003.033050 　

ISSN：0017-5749
Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines 査読有り

IMATANI A

Oncogene　19　(2)　223-231　2000年1月
In situ analysis of tissue dynamics and p53 expression in human gastric mucosa. 査読有り

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

J Pathol.　179　(1)　39-42　1996年5月
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年4月3日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s00535-025-02247-7 　

ISSN：0944-1174

eISSN：1435-5922

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： Wiley
DOI： 10.1111/den.15026 　

ISSN：0915-5635

eISSN：1443-1661

詳細を見る詳細を閉じる

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

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年3月25日

DOI： 10.1159/000545253 　

詳細を見る詳細を閉じる

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.
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年1月

DOI： 10.1007/s00535-024-02171-2 　

詳細を見る詳細を閉じる

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.
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年10月
出版者・発行元： (一社)日本消化器がん検診学会
ISSN：1880-7666

eISSN：2185-1190
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年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
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年8月1日

DOI： 10.2169/internalmedicine.3645-24 　

詳細を見る詳細を閉じる

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.
The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers. 国際誌

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年7月18日

DOI： 10.3390/ijms25147854 　

詳細を見る詳細を閉じる

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.
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年7月
出版者・発行元：日本消化器内視鏡学会-東北支部
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年7月
出版者・発行元：日本消化器病学会-東北支部
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年6月
出版者・発行元： (一社)日本ヘリコバクター学会
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年4月1日
出版者・発行元： Japanese Society of Internal Medicine
DOI： 10.2169/internalmedicine.2211-23 　

ISSN：0918-2918

eISSN：1349-7235
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年2月5日

DOI： 10.3390/gastroent15010010 　
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年2月
出版者・発行元：日本消化器内視鏡学会-東北支部
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年2月
出版者・発行元：日本消化器内視鏡学会-東北支部
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年1月17日
出版者・発行元： Georg Thieme Verlag KG
DOI： 10.1055/a-2248-5110 　

ISSN：2364-3722

eISSN：2196-9736

詳細を見る詳細を閉じる

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

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年1月10日

DOI： 10.1159/000536217 　

詳細を見る詳細を閉じる

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.
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年11月9日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1007/s10620-023-08142-6 　

ISSN：0163-2116

eISSN：1573-2568
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年10月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
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年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
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年7月
出版者・発行元：日本消化器病学会-東北支部
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年7月
出版者・発行元：日本消化器病学会-東北支部
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年6月
出版者・発行元： (一社)日本消化器がん検診学会
ISSN：1880-7666

eISSN：2185-1190
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年6月
出版者・発行元： (一社)日本消化器がん検診学会
ISSN：1880-7666

eISSN：2185-1190
Role of T-box transcription factor 3 in gastric cancers. 国際誌

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年3月22日

DOI： 10.4291/wjgp.v14.i2.12 　

詳細を見る詳細を閉じる

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.
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年2月
出版者・発行元：日本消化器内視鏡学会-東北支部
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年2月
出版者・発行元：日本消化器病学会-東北支部
早期胃癌治療後の早期・後期死亡関連因子

尾形洋平, 八田和久, 大原祐樹, 小池智幸, 阿部寛子, 齊藤真弘, 金笑奕, 菅野武, 宇野要, 浅野直喜, 今谷晃, 山村明寛, 田中直樹, 亀井尚, 海野倫明, 中村智洋, 中谷直樹, 正宗淳

日本消化器内視鏡学会雑誌　65　(2)　162-172　2023年
出版者・発行元：一般社団法人日本消化器内視鏡学会
DOI： 10.11280/gee.65.162 　

ISSN：0387-1207

eISSN：1884-5738

詳細を見る詳細を閉じる

【目的】早期胃癌患者の大部分は非胃癌が原因で死亡するが，早期胃癌のリンパ節転移リスクと非胃癌死を含めた全死亡との関連については分かっていない．本研究では，早期死亡と後期死亡の関連因子を明らかにすることを目的とした．【方法】2003年から2017年に早期胃癌に対し内視鏡的切除，外科切除を施行した患者を後ろ向きに解析した．リンパ節転移リスク，治療法，そのほか９つの非胃癌関連の因子について，３年をカットオフとして早期死亡，後期死亡に分けて関連因子を解析した．【結果】経過観察期間中央値79カ月で，1,439例が解析された．５年全生存率は86.8％であった．多変量解析で，早期死亡，後期死亡の最も重要な予測因子は，年齢85歳以上［ハザード比（hazard ratio；HR）2.88（早期死亡）；4.54（後期死亡）］，Eastern Cooperative Oncology Group Performance Status≥２（HR 3.00；4.19）であった．チャールソン併存疾患指数≥２（HR 2.76；1.99），米国麻酔科学会術前身体状態分類≥３（HR 2.35；1.79），CRP/アルブミン比≥0.028（HR 2.30；1.58）も早期死亡，後期死亡の関連因子であった．男性（HR 2.26），eCura systemでみたリンパ節転移中リスク（HR 2.12）と高リスク（HR 1.85），腸腰筋の断面積で評価したサルコペニア（HR 1.70）は早期死亡の関連因子であった．【結語】様々な予後関連因子の総合的評価は，早期胃癌患者の早期死亡，後期死亡を予測するのに有用な可能性がある．eCura systemは早期死亡に関連していた．
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年
出版者・発行元： Japanese Society of Internal Medicine
DOI： 10.2169/internalmedicine.1137-22 　

ISSN：0918-2918

eISSN：1349-7235
The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia. 国際誌

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

International journal of molecular sciences　23　(22)　2022年11月12日

DOI： 10.3390/ijms232213947 　

詳細を見る詳細を閉じる

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.
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年10月13日
出版者・発行元： MDPI AG
DOI： 10.3390/ijms232012210 　

eISSN：1422-0067

詳細を見る詳細を閉じる

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.
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年10月
出版者・発行元： (一社)日本潰瘍学会
ISSN：2189-7956
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年10月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年10月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年10月
出版者・発行元： (一社)日本潰瘍学会
ISSN：2189-7956
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年9月
出版者・発行元： (NPO)日本食道学会
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年7月14日
出版者・発行元： American Association for Cancer Research (AACR)
DOI： 10.1158/2767-9764.crc-22-0084 　

eISSN：2767-9764

詳細を見る詳細を閉じる

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.
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年4月8日
出版者・発行元： Oxford University Press (OUP)
DOI： 10.1093/jcag/gwac012 　

ISSN：2515-2084

eISSN：2515-2092
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年4月
出版者・発行元： Wiley
DOI： 10.1002/deo2.60 　

ISSN：2692-4609

eISSN：2692-4609
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年2月1日

DOI： 10.2169/internalmedicine.8253-21 　

詳細を見る詳細を閉じる

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.
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年
出版者・発行元： Tohoku University Medical Press
DOI： 10.1620/tjem.2022.j077 　

ISSN：0040-8727

eISSN：1349-3329
Is Additional Gastrectomy Required for Elderly Patients after Endoscopic Submucosal Dissection with Endoscopic Curability C-2 for Early Gastric Cancer? 国際誌

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

Digestion　103　(1)　83-91　2022年

DOI： 10.1159/000519514 　

詳細を見る詳細を閉じる

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

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年1月1日

DOI： 10.1152/ajpgi.00124.2021 　

詳細を見る詳細を閉じる

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.
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. 国際誌

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

Diagnostics (Basel, Switzerland)　11　(11)　2021年10月20日

DOI： 10.3390/diagnostics11111941 　

詳細を見る詳細を閉じる

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.
Predictors of early and late mortality after the treatment for early gastric cancers. 国際誌

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年10月18日

DOI： 10.1111/den.14172 　

詳細を見る詳細を閉じる

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.
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年10月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (NPO)日本食道学会
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年9月
出版者・発行元： (NPO)日本食道学会
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年9月
出版者・発行元： (NPO)日本食道学会
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年8月

DOI： 10.1007/s12328-021-01346-1 　

詳細を見る詳細を閉じる

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.
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年7月

DOI： 10.1007/s00535-021-01781-4 　

詳細を見る詳細を閉じる

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.
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年5月15日

DOI： 10.2169/internalmedicine.6321-20 　

詳細を見る詳細を閉じる

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.
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年2月
出版者・発行元：日本消化器病学会-東北支部
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年2月
出版者・発行元：日本消化器病学会-東北支部
【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年2月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
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年

DOI： 10.2169/internalmedicine.6674-20 　

詳細を見る詳細を閉じる

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.
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年1月
出版者・発行元： (一社)日本消化管学会
ISSN：2433-3840
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年1月
出版者・発行元： (一社)日本消化管学会
ISSN：2433-3840
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年1月

DOI： 10.1620/tjem.253.29 　

詳細を見る詳細を閉じる

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.
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年12月
出版者・発行元： (NPO)日本食道学会
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年10月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年10月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Localized Gastric Amyloidosis that Displayed Morphological Changes over 10 Years of Observation. 査読有り

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年9月30日

DOI： 10.2169/internalmedicine.5031-20 　

詳細を見る詳細を閉じる

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.
A Case of the Development of Foveolar-type Gastric Adenocarcinoma during Maintenance Therapy of Vonoprazan for Reflux Esophagitis. 査読有り

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年8月29日

DOI： 10.2169/internalmedicine.5431-20 　

詳細を見る詳細を閉じる

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.
Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease. 国際誌査読有り

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年8月12日

DOI： 10.1159/000508661 　

詳細を見る詳細を閉じる

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.
A rare case of gastric squamous-cell carcinoma metastasized from the cervix. 査読有り

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年7月25日

DOI： 10.1007/s12328-020-01191-8 　

詳細を見る詳細を閉じる

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.
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年7月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Correction: TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells. 国際誌

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年4月23日

DOI： 10.4049/immunohorizons.2000022 　
The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease. 国際誌査読有り

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年2月14日

DOI： 10.1159/000506152 　

詳細を見る詳細を閉じる

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.
Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease. 国際誌査読有り

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年

DOI： 10.1159/000500133 　

詳細を見る詳細を閉じる

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.
Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016. 査読有り

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年12月

DOI： 10.1007/s00535-019-01658-7 　

ISSN：0944-1174

eISSN：1435-5922
Continuous liquid-suction catheter attachment for endoscope reduces volume of liquid reflux to the mouth in esophageal endoscopic submucosal dissection. 国際誌査読有り

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年9月

DOI： 10.1111/den.13392 　

詳細を見る詳細を閉じる

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).
A Primary Barrett's Adenocarcinoma with a Squamous Cell Carcinoma Component. 査読有り

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年9月1日

DOI： 10.2169/internalmedicine.2722-19 　

詳細を見る詳細を閉じる

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.
Strong Intra-Esophageal Reflux May Contribute to the Development of Barrett's Adenocarcinoma and Affect the Localization. 国際誌査読有り

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年8月14日

DOI： 10.1159/000502377 　

詳細を見る詳細を閉じる

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.
Difficult Preoperative Diagnosis of Lymphoepithelioma-Like Carcinoma of the Esophagus. 国際誌査読有り

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年8月

DOI： 10.14309/crj.0000000000000163 　

詳細を見る詳細を閉じる

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.
Is Additional Surgery Always Sufficient for Preventing Recurrence After Endoscopic Submucosal Dissection with Curability C-2 for Early Gastric Cancer? 国際誌査読有り

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年7月

DOI： 10.1245/s10434-019-07579-2 　

ISSN：1068-9265
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. 国際誌査読有り

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年4月

DOI： 10.1111/hepr.13346 　

ISSN：1386-6346
Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan. 国際誌査読有り

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年1月

DOI： 10.3748/wjg.v25.i1.107 　

ISSN：1007-9327
Age Affects Clinical Management after Noncurative Endoscopic Submucosal Dissection for Early Gastric Cancer. 国際誌査読有り

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年

DOI： 10.1159/000499538 　
Long-term prognosis of Japanese patients with biologic-naïve Crohn's disease treated with anti-tumor necrosis factor-α antibodies. 国際誌査読有り

Moroi R, Endo K, Yamamoto K, Naito T, Onodera M, Kuroha M, Kanazawa Y, Kimura T, Kakuta Y, Masamune A, Kinouchi Y, Shimosegawa T

Intestinal research　17　(1)　94-106　2019年1月

DOI： 10.5217/ir.2018.00048 　

ISSN：1598-9100
Prospective study of early chronic pancreatitis diagnosed based on the Japanese diagnostic criteria. 査読有り

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年1月
出版者・発行元：
ISSN：0944-1174

eISSN：1435-5922
Endoscopic Findings of Esophageal Adenosquamous Carcinoma Diagnosed by Endoscopic Mucosal Resection. 査読有り

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年1月

DOI： 10.1159/000499182 　
Recurrence Patterns and Outcomes of Salvage Surgery in Cases of Non-Curative Endoscopic Submucosal Dissection without Additional Radical Surgery for Early Gastric Cancer. 国際誌査読有り

Takizawa K, Hatta W, Gotoda T, Kawata N, Nakagawa M, Takahashi A, Esaki M, Mitoro A, Yamada S, Tanaka K, Matsuda M, Takada J, Oka S, Ito H, Ohnita K, Shimoda R, Hoteya S, Oyama T, Shimosegawa T

Digestion　99　(1)　52-58　2018年12月1日

DOI： 10.1159/000494413 　

ISSN：0012-2823

eISSN：1421-9867
Different risk factors between early and late cancer recurrences in patients without additional surgery after noncurative endoscopic submucosal dissection for early gastric cancer. 国際誌査読有り

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年11月

DOI： 10.1016/j.gie.2018.11.015 　

ISSN：0016-5107
The Use of Higher Dose Steroids Increases the Risk of Rebleeding After Endoscopic Hemostasis for Peptic Ulcer Bleeding. 国際誌査読有り

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年11月

DOI： 10.1007/s10620-018-5209-y 　

詳細を見る詳細を閉じる

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.
Pancreatic Acinar Cell Carcinoma with Multiple Liver Metastases Effectively Treated by S-1 Chemotherapy. 査読有り

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年8月

DOI： 10.2169/internalmedicine.0294-17 　

ISSN：0918-2918
A new manometry device for evaluating the sphincter of Oddi using a fiber-optic pressure sensor. 査読有り

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年8月

DOI： 10.1080/13645706.2017.1412701 　

ISSN：1364-5706
Leptin Aggravates Reflux Esophagitis by Increasing Tissue Levels of Macrophage Migration Inhibitory Factor in Rats. 査読有り

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年5月

DOI： 10.1620/tjem.245.45 　

詳細を見る詳細を閉じる

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.
Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake. 査読有り

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年4月

DOI： 10.1620/tjem.244.317 　

ISSN：0040-8727
Effective and less invasive diagnostic strategy for gastrointestinal GVHD. 国際誌査読有り

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年3月

DOI： 10.1055/s-0043-122226 　

ISSN：2364-3722
Estrogen-Dependent Nrf2 Expression Protects Against Reflux-Induced Esophagitis. 国際誌査読有り

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年2月

DOI： 10.1007/s10620-017-4885-3 　

詳細を見る詳細を閉じる

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.
The Role of an Undifferentiated Component in Submucosal Invasion and Submucosal Invasion Depth After Endoscopic Submucosal Dissection for Early Gastric Cancer. 国際誌査読有り

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年

DOI： 10.1159/000488529 　

ISSN：0012-2823
The slow progressive nature of duodenal neuroendocrine tumor: a case report of long-term observation over 14 years. 査読有り

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年10月

DOI： 10.1007/s12328-017-0758-8 　

詳細を見る詳細を閉じる

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.
Factors Associated With Metachronous Gastric Cancer Development After Endoscopic Submucosal Dissection for Early Gastric Cancer. 国際誌

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年7月

DOI： 10.1097/MCG.0000000000000620 　

詳細を見る詳細を閉じる

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.
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年5月
出版者・発行元： (一社)日本ヘリコバクター学会
ISSN：2187-8005
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Plasma Kallikrein-Dependent Transforming Growth Factor-β Activation in Patients With Chronic Pancreatitis and Pancreatic Cancer. 査読有り

Teraoka R, Hara M, Kikuta K, Hirooka Y, Furutani Y, Shimosegawa T, Masamune A, Kojima S

Pancreas　46　(3)　E20-E22　2017年3月

DOI： 10.1097/MPA.0000000000000736 　

ISSN：0885-3177

eISSN：1536-4828
The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter. 査読有り

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年3月

DOI： 10.1159/000459619 　

ISSN：0012-2823
Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis. 国際誌査読有り

Masamune A, Nishimori I, Kikuta K, Tsuji I, Mizuno N, Iiyama T, Kanno A, Tachibana Y, Ito T, Kamisawa T, Uchida K, Hamano H, Yasuda H, Sakagami J, Mitoro A, Taguchi M, Kihara Y, Sugimoto H, Hirooka Y, Yamamoto S, Inui K, Inatomi O, Andoh A, Nakahara K, Miyakawa H, Hamada S, Kawa S, Okazaki K, Shimosegawa T, Research Committee of, Intractable Pancreas, Diseases in Japan

Gut　66　(3)　487-494　2017年3月1日

DOI： 10.1136/gutjnl-2016-312049 　

ISSN：0017-5749

eISSN：1468-3288
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年2月
出版者・発行元： (株)勁草書房コミュニケーション事業部
ISSN：1880-3652
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年10月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Usefulness of Endoscopic Imaging to Visualize Regional Alterations in Acid Secretion of Noncancerous Gastric Mucosa after Helicobacter pylori Eradication. 査読有り

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

Journal of gastric cancer　16　(3)　152-160　2016年9月

DOI： 10.5230/jgc.2016.16.3.152 　

ISSN：2093-582X
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年8月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Preferential location of idiopathic peptic ulcers. 査読有り

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年7月

DOI： 10.3109/00365521.2016.1141316 　

ISSN：0036-5521
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. 査読有り

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年7月

DOI： 10.1111/den.12635 　

ISSN：0915-5635
A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old. 査読有り

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

The Tohoku journal of experimental medicine　239　(3)　237-241　2016年7月

DOI： 10.1620/tjem.239.237 　

ISSN：0040-8727
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年7月
出版者・発行元： (NPO)日本食道学会
Feasibility of optical coherence tomography for the evaluation of Barrett's mucosa buried underneath esophageal squamous epithelium. 国際誌査読有り

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年5月

DOI： 10.1111/den.12576 　

詳細を見る詳細を閉じる

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.
A Japanese case of lymphocytic esophagitis. 国際誌査読有り

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年5月

DOI： 10.1111/den.12578 　

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Gastric cancer development after the successful eradication of Helicobacter pylori. 査読有り

Uno K, Iijima K, Shimosegawa T

World journal of gastrointestinal oncology　8　(3)　271-281　2016年3月

DOI： 10.4251/wjgo.v8.i3.271 　
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Gender difference in gastro-esophageal reflux diseases. 査読有り

Asanuma K, Iijima K, Shimosegawa T

World journal of gastroenterology　22　(5)　1800-1810　2016年2月

DOI： 10.3748/wjg.v22.i5.1800 　

ISSN：1007-9327
Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis. 査読有り

Kusaka G, Uno K, Iijima K, Shimosegawa T

World journal of gastrointestinal pathophysiology　7　(1)　131-137　2016年2月

DOI： 10.4291/wjgp.v7.i1.131 　
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年
出版者・発行元： Japan Gastroenterological Endoscopy Society
ISSN：0387-1207
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年
出版者・発行元： Japan Gastroenterological Endoscopy Society
ISSN：0387-1207
DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma. 査読有り

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

Mediators of inflammation　2016　7937814　2016年

DOI： 10.1155/2016/7937814 　

ISSN：0962-9351
表在型食道癌に対するOptical Coherence Tomography診断の有用性

宇野要, 小池智幸, 下瀬川徹

日本気管食道科学会会報　67　(2)　65-65　2016年
出版者・発行元：特定非営利活動法人日本気管食道科学会
DOI： 10.2468/jbes.67.65 　

ISSN：0029-0645
Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients. 査読有り

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年12月

DOI： 10.3748/wjg.v21.i47.13352 　

ISSN：1007-9327
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review. 国際誌査読有り

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

World journal of gastroenterology　21　(26)　8014-20　2015年7月14日

DOI： 10.3748/wjg.v21.i26.8014 　

詳細を見る詳細を閉じる

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.
[New trends of acid-related diseases treatment]. 査読有り

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

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

ISSN：0047-1852
Endoscopic findings for predicting gastric acid secretion status. 国際誌査読有り

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年7月

DOI： 10.1111/den.12427 　

詳細を見る詳細を閉じる

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.
A multicenter prospective study on the prevalence of Helicobacter pylori-negative and nonsteroidal anti-inflammatory drugs-negative idiopathic peptic ulcers in Japan. 査読有り

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

J Gastroenterol Hepatol. 2015 May;30(5):842-8.　30　(5)　842-848　2015年5月

DOI： 10.1111/jgh.12876 　

ISSN：0815-9319

eISSN：1440-1746
Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan. 国際誌査読有り

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年5月

DOI： 10.1111/den.12407 　

詳細を見る詳細を閉じる

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.
Esomeprazole inhibits the pentagastrin-stimulated secretion of gastric acid in healthy Japanese volunteers. 査読有り

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

The Tohoku journal of experimental medicine　235　(3)　249-253　2015年3月

DOI： 10.1620/tjem.235.249 　

ISSN：0040-8727
Endoscopic balloon dilatation for pharyngo-upper esophageal stricture after treatment of head and neck cancer. 査読有り

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年3月

DOI： 10.1111/den.12345 　

ISSN：0915-5635
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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. 査読有り

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年1月

DOI： 10.1007/s00535-014-0940-4 　

ISSN：0944-1174
Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration. 国際誌査読有り

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

PloS one　10　(4)　e0120397　2015年

DOI： 10.1371/journal.pone.0120397 　

詳細を見る詳細を閉じる

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.
Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men. 査読有り

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

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

DOI： 10.1007/s00535-014-1031-2 　

ISSN：0944-1174
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Calcium carbonate breath test for non-invasive estimation of gastric acid secretion. 査読有り

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年4月

eISSN：1349-3329

詳細を見る詳細を閉じる

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.
Comparison of the long-term outcomes of endoscopic resection for superficial squamous cell carcinoma and adenocarcinoma of the esophagus in Japan. 国際誌査読有り

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年3月

DOI： 10.1038/ajg.2013.450 　

詳細を見る詳細を閉じる

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.
PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan. 査読有り

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

GUT　63　(2)　366-366　2014年2月

DOI： 10.1136/gutjnl-2013-304925 　

ISSN：0017-5749

eISSN：1468-3288
NOD2 down-regulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6 査読有り

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

Mucosal Immunol　7　(6)　1312-1325　2014年

DOI： 10.1038/mi.2014.19 　

ISSN：1933-0219 1935-3456
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年9月
出版者・発行元： PEG・在宅医療学会
ISSN：1343-1544
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Collagenous gastritis. 国際誌査読有り

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年9月

DOI： 10.1111/j.1443-1661.2012.01391.x 　

詳細を見る詳細を閉じる

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.
Barrett's esophageal cancer in which magnifying narrow-band imaging was useful for diagnosing extension under the squamous epithelium. 査読有り

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年5月

DOI： 10.1111/den.12111 　

ISSN：0915-5635
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年5月
出版者・発行元： (一社)日本消化器がん検診学会
ISSN：1880-7666

eISSN：2185-1190
Peptic ulcers after the Great East Japan earthquake and tsunami: possible existence of psychosocial stress ulcers in humans. 査読有り

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

J Gastroenterol. 2013 Apr;48(4):483-90.　2013年4月

DOI： 10.1007/s00535-012-0681-1 　

ISSN：0944-1174
Pancreatic intraepithelial neoplasia-3 with localized acute pancreatitis in the main pancreatic duct. 査読有り

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年4月

DOI： 10.1007/s12328-013-0368-z 　

ISSN：1865-7257
Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic β-cells. 国際誌査読有り

Kikuta K, Masamune A, Hamada S, Takikawa T, Nakano E, Shimosegawa T

Biochemical and biophysical research communications　433　(3)　292-297　2013年4月

DOI： 10.1016/j.bbrc.2013.02.095 　

ISSN：0006-291X

eISSN：1090-2104
Identification of novel missense CTRC variants in Japanese patients with chronic pancreatitis. 査読有り

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

GUT　62　(4)　653-654　2013年4月

DOI： 10.1136/gutjnl-2012-303860 　

ISSN：0017-5749

eISSN：1468-3288
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Endoscopic resection (endoscopic submucosal dissection/endoscopic mucosal resection) for superficial Barrett's esophageal cancer. 査読有り

Koike T, Nakagawa K, Iijima K, Shimosegawa T

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society　25 Suppl 1　20-28　2013年3月

DOI： 10.1111/den.12047 　

ISSN：0915-5635
【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年2月
出版者・発行元： (有)科学評論社
ISSN：1884-2895
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年2月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Gastric hypochlorhydria is associated with an exacerbation of dyspeptic symptoms in female patients. 査読有り

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

Journal of gastroenterology　48　(2)　214-21　2013年2月

DOI： 10.1007/s00535-012-0634-8 　

詳細を見る詳細を閉じる

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.
Hemorrhagic ulcers after Great East Japan Earthquake and Tsunami: features of post-disaster hemorrhagic ulcers. 査読有り

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. 2013;87(1):40-6.　87　(1)　40-46　2013年1月

DOI： 10.1159/000343937 　

ISSN：0012-2823
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年1月
出版者・発行元： (一社)日本消化器がん検診学会
ISSN：1880-7666

eISSN：2185-1190
Eradication therapy is effective for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma. 査読有り

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年11月

eISSN：1349-3329

詳細を見る詳細を閉じる

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.
【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年10月
出版者・発行元： (有)科学評論社
ISSN：1884-2895
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
A prospective comparative study of optical coherence tomography and EUS for tumor staging of superficial esophageal squamous cell carcinoma. 国際誌査読有り

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

Gastrointestinal endoscopy　76　(3)　548-55　2012年9月

DOI： 10.1016/j.gie.2012.05.012 　

詳細を見る詳細を閉じる

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.
Endoscopic submucosal dissection combined with endoscopic injection sclerotherapy for early gastric cancer on gastric fundal varices. 国際誌査読有り

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年8月

DOI： 10.1097/SLE.0b013e318254d630 　

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Gastric cancers emerging after H. pylori eradication arise exclusively from non-acid-secreting areas. 査読有り

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年1月

eISSN：1349-3329

詳細を見る詳細を閉じる

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.
【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年11月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
【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年11月
出版者・発行元： (株)東京医学社
ISSN：0915-3217
【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年10月
出版者・発行元： (株)ヴァンメディカル
ISSN：1344-3070
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年9月
出版者・発行元： (一社)日本核医学会
ISSN：0022-7854

eISSN：2189-9932
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (NPO)日本食道学会
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. 国際誌査読有り

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

Leukemia & lymphoma　52　(9)　1803-5　2011年9月

DOI： 10.3109/10428194.2011.573030 　
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年8月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
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. 国際誌査読有り

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年6月

DOI： 10.3109/00365521.2011.565069 　

詳細を見る詳細を閉じる

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.
Gastric acid secretion level modulates the association between Helicobacter pylori infection and low-dose aspirin-induced gastropathy. 査読有り

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年5月

DOI： 10.1007/s00535-011-0385-y 　

詳細を見る詳細を閉じる

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.
Signet Ring Cell Gastric Cancer Occurring after Radiation Therapy for Helicobacter pylori-Uninfected Mucosa-Associated Lymphoid Tissue Lymphoma. 国際誌査読有り

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年5月

DOI： 10.1159/000329559 　

詳細を見る詳細を閉じる

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.
【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年4月
出版者・発行元： (有)科学評論社
ISSN：1884-2895
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年2月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
A Japanese case series of 12 patients with esophageal eosinophilia. 査読有り

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年1月

DOI： 10.1007/s00535-010-0295-4 　

詳細を見る詳細を閉じる

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.
Low serum levels of pepsinogen and gastrin 17 are predictive of extensive gastric atrophy with high-risk of early gastric cancer. 査読有り

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年1月

eISSN：1349-3329

詳細を見る詳細を閉じる

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.
Esophageal Adenocarcinoma Developing after Eradication of Helicobacter pylori. 国際誌査読有り

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年

DOI： 10.1159/000329878 　

詳細を見る詳細を閉じる

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.
Brain activity following esophageal acid infusion using positron emission tomography. 国際誌査読有り

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年11月21日

eISSN：2219-2840

詳細を見る詳細を閉じる

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.
【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年11月
出版者・発行元： (株)南江堂
ISSN：0022-1961

eISSN：2432-9452
Exogenous luminal nitric oxide exposure accelerates columnar transformation of rat esophagus. 国際誌査読有り

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年11月1日

DOI： 10.1002/ijc.25227 　

詳細を見る詳細を閉じる

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.
Deficient aldehyde dehydrogenase 2 is associated with increased risk for esophageal squamous cell carcinoma in the presence of gastric hypochlorhydria. 国際誌査読有り

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年11月

DOI： 10.3109/00365521.2010.495419 　

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Gastric Hyposecretion in Esophageal Squamous-Cell Carcinomas 査読有り

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年5月

DOI： 10.1007/s10620-009-0853-x 　

ISSN：0163-2116
Optical coherence tomography for the staging of tumor infiltration in superficial esophageal squamous cell carcinoma. 国際誌査読有り

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

Gastrointestinal endoscopy　71　(6)　899-906　2010年5月

DOI： 10.1016/j.gie.2009.11.052 　

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元：ライフサイエンス出版(株)
ISSN：0289-8020
Reactive nitrogen oxide species induce dilatation of the intercellular space of rat esophagus 査読有り

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年3月

DOI： 10.3109/00365520903469956 　

ISSN：0036-5521
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年3月
出版者・発行元： (株)ジェフコーポレーション
ISSN：1344-4980

eISSN：1881-3623
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年3月
出版者・発行元： (株)ジェフコーポレーション
ISSN：1344-4980

eISSN：1881-3623
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年2月
出版者・発行元： (株)先端医学社
ISSN：0918-9408
【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年1月
出版者・発行元： (有)科学評論社
ISSN：1884-2895
Identification of the layered morphology of the esophageal wall by optical coherence tomography. 国際誌査読有り

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年9月21日

eISSN：2219-2840

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年8月
出版者・発行元： (一社)日本門脈圧亢進症学会
ISSN：1344-8447

eISSN：2186-6376
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年8月
出版者・発行元： (一社)日本門脈圧亢進症学会
ISSN：1344-8447

eISSN：2186-6376
Clinical Characteristics of Gastroesophageal Reflux Disease in Japan 査読有り

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年7月

ISSN：0172-6390
【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年7月
出版者・発行元： (有)科学評論社
ISSN：0289-8756
Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers. 査読有り

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年5月

eISSN：1349-3329

詳細を見る詳細を閉じる

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.
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. 査読有り

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年

DOI： 10.1007/s00535-008-2270-x 　

詳細を見る詳細を閉じる

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.
Exogenous luminal nitric oxide exacerbates esophagus tissue damage in a reflux esophagitis model of rats. 国際誌査読有り

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年

DOI： 10.1080/00365520802699260 　

詳細を見る詳細を閉じる

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.
Barrett's esophagus is characterized by the absence of Helicobacter pylori infection and high levels of serum pepsinogen I concentration in Japan. 国際誌査読有り

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

Journal of gastroenterology and hepatology　24　(1)　129-34　2009年1月

DOI： 10.1111/j.1440-1746.2008.05691.x 　

詳細を見る詳細を閉じる

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.
Alteration of correlation between serum pepsinogen concentrations and gastric acid secretion after H. pylori eradication. 査読有り

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

Journal of gastroenterology　44　(8)　819-25　2009年

DOI： 10.1007/s00535-009-0066-2 　

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Tongue-like Barrett's esophagus is associated with gastroesophageal reflux disease. 国際誌査読有り

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年7月14日

ISSN：1007-9327

詳細を見る詳細を閉じる

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.
Incidence of reflux esophagitis and H pylori infection in diabetic patients. 国際誌査読有り

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年5月28日

ISSN：1007-9327

詳細を見る詳細を閉じる

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.
Stronger inhibition of gastric acid secretion by lafutidine, a novel H2 receptor antagonist, than by the proton pump inhibitor lansoprazole. 国際誌査読有り

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年4月21日

ISSN：1007-9327

詳細を見る詳細を閉じる

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.
Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers. 国際誌査読有り

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年4月7日

ISSN：1007-9327

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan. 国際誌査読有り

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年3月7日

ISSN：1007-9327

詳細を見る詳細を閉じる

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.
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年1月
出版者・発行元： (有)科学評論社
ISSN：0289-8756
Long-term outcomes of gastric mucosa-associated lymphoid tissue lymphomas after Helicobacter pylori eradication therapy. 査読有り

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年1月

ISSN：0040-8727

詳細を見る詳細を閉じる

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.
Pathophysiological role of the activation of p38 mitogen-activated protein kinases in poorly differentiated gastric cancer. 国際誌査読有り

Tomoaki Atsumi, Katsuaki Kato, Kaname Uno, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Syuichi Ohara, Tooru Shimosegawa

Pathology international　57　(10)　635-44　2007年10月

ISSN：1320-5463

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年8月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
Extensive gastric atrophy: an increased risk factor for superficial esophageal squamous cell carcinoma in Japan. 国際誌査読有り

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年8月

ISSN：0002-9270

詳細を見る詳細を閉じる

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.
Effect of Helicobacter pylori status on intragastric pH during administration of lafutidine or famotidine. 国際誌査読有り

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年6月

ISSN：0172-6390

詳細を見る詳細を閉じる

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.
【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年5月
出版者・発行元： (株)日本メディカルセンター
ISSN：0911-601X

eISSN：2433-2488
【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年5月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
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年4月

DOI： 10.1007/s10787-006-1549-x 　
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
[Nitric oxide generated at gastro-oesophageal junction]. 査読有り

Iijima K, Asanuma K, Ohara S, Shimosegawa T

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology　104　(1)　17-22　2007年1月
出版者・発行元： The Japanese Society of Gastroenterology
DOI： 10.11405/nisshoshi.104.17 　

ISSN：0446-6586

詳細を見る詳細を閉じる

近年，食道・胃接合部領域に発生する癌が欧米を中心に増加しており，本邦においても将来的にその増加が危惧されている．この部位の癌の発癌因子に関して，これまで胃酸，ペプシン，胆汁酸を中心に検討がなされているが，いまだその原因は不明である．最近の研究でヒトの食道・胃接合部において限局して高濃度の一酸化窒素は発生していることが明らかにされた．一酸化窒素は生体機能の維持・調節に深く関わっており，発癌を含め，同部における種々の病態と関連している可能性が指摘されている．今後は食道・胃接合部の発癌因子に関して，一酸化窒素，および，それにともなうニトロソ化ストレスとの関連との検討も必要と考えられる．<br>
Regional differences in the recovery of gastric acid secretion after Helicobacter pylori eradication: evaluations with Congo red chromoendoscopy. 国際誌査読有り

Hitoshi Sekine, Katsunori Iijima, Tomoyuki Koike, Yasuhiko Abe, Akira Imatani, Katsuaki Kato, Suichi Ohara, Tooru Shimosegawa

Gastrointestinal endoscopy　64　(5)　678-85　2006年11月

ISSN：0016-5107

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年7月
出版者・発行元： (株)勁草書房コミュニケーション事業部
ISSN：1880-3652
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年7月
出版者・発行元： (株)勁草書房コミュニケーション事業部
ISSN：1880-3652
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. 国際誌査読有り

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年5月

ISSN：0002-9270

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年2月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects. 査読有り

Katsunori Iijima, Hitoshi Sekine, Tomoyuki Koike, Akira Imatani, Shuichi Ohara, Tooru Shimosegawa

Journal of gastroenterology　40　(10)　938-44　2005年10月

ISSN：0944-1174

詳細を見る詳細を閉じる

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.
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年7月
出版者・発行元： (有)科学評論社
ISSN：0289-8756
【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年3月
出版者・発行元： (株)東京医学社
ISSN：0915-3217
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年2月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
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年12月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年10月
出版者・発行元： (株)日本メディカルセンター
ISSN：0911-601X

eISSN：2433-2488
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett's esophagus in Japan. 国際誌査読有り

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年7月

ISSN：0002-9270

詳細を見る詳細を閉じる

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.
Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues. 国際誌

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年4月15日

ISSN：0303-7207

詳細を見る詳細を閉じる

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.
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
【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年3月
出版者・発行元： (株)日本臨床社
ISSN：0047-1852
【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年3月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Oligomycin and antimycin A prevent nitric oxide-induced apoptosis by blocking cytochrome C leakage. 国際誌査読有り

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年3月

ISSN：0022-2143

詳細を見る詳細を閉じる

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.
【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年2月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
Expression of Mg2+-dependent, HCO3- -stimulated adenine triphosphatase in the human duodenum. 国際誌査読有り

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年1月

ISSN：0815-9319

詳細を見る詳細を閉じる

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.
Contribution of glutamine synthetase to ammonia-induced apoptosis in gastric mucosal cells. 国際誌査読有り

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年

ISSN：0012-2823

詳細を見る詳細を閉じる

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.
High levels of intracellular ATP prevent nitric oxide-induced apoptosis in rat gastric mucosal cells. 国際誌査読有り

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年12月

ISSN：0959-9673

詳細を見る詳細を閉じる

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.
Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury. 国際誌査読有り

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年11月7日

ISSN：0024-3205

詳細を見る詳細を閉じる

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.
13C-尿素呼気試験における口腔・咽頭内ウレアーゼ活性の影響の検討査読有り

佐野望, 大原秀一, 小池智幸, 関根仁, 大矢内幹, 米地真, 北川靖, 大楽尚弘, 下瀬川徹

日本消化器病学会雑誌　100　(臨増大会)　A612-A612　2003年9月
出版者・発行元： (一財)日本消化器病学会
DOI： 10.11405/nisshoshi.101.1302 　

ISSN：0446-6586

eISSN：1349-7693
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年5月
出版者・発行元：胃病態機能研究会
ISSN：0289-2057
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年4月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年12月
出版者・発行元： (株)ヴァンメディカル
ISSN：1344-3070
【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年10月
出版者・発行元： (株)先端医学社
ISSN：1342-4319
【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年6月
出版者・発行元： (株)東京医学社
ISSN：0915-3217
【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年3月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
Analysis of cell damage in Helicobacter pylori-associated gastritis. 国際誌査読有り

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年2月

ISSN：1320-5463

詳細を見る詳細を閉じる

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.
【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年9月
出版者・発行元： (株)東京医学社
ISSN：0915-3217
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年9月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年9月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年3月
出版者・発行元： (有)科学評論社
ISSN：0289-8756
【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年2月
出版者・発行元： (株)医薬ジャーナル社
ISSN：0913-2384
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN：0446-6586

eISSN：1349-7693
【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年10月
出版者・発行元： (株)医学書院
ISSN：0536-2180

eISSN：1882-1219
Characterization of the Drosophila ortholog of mouse eIF-3p48/INT-6. 査読有り

Miyazaki S, Rasmussen S, Imatani A, Diella F, Sullivan DT, Callahan R

Gene　233　(1-2)　241-247　1999年6月
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年4月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN：0387-1207

eISSN：1884-5738
The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas. 査読有り

Miyazaki S, Imatani A, Ballard L, Marchetti A, Buttitta F, Albertsen H, Nevanlinna HA, Gallahan D, Callahan R

Genomics.　46　(1)　155-158　1997年11月
Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma. 査読有り

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年9月
Analysis of p53 abnormalities in endoscopic gastric biopsies. 査読有り

Imatani A, Sasano H, Asaki S, Toyota T, Saito M, Masuda T, Nagura H

Anticancer Res　16　(4A)　2049-2056　1996年7月
Cell proliferation and apoptosis in normal and pathologic human adrenal. 査読有り

Sasano H, Imatani A, Shizawa S, Suzuki T, Nagura H

Mod Pathol.　8　(1)　11-17　1995年8月
Double immunostaining for c-erbB-2 and p53 in human stomach cancer cells. 査読有り

Sasano H, Date F, Imatani A, Asaki S, Nagura H

Hum Pathol　24　(6)　584-589　1993年6月

︎全件表示 ︎最初の5件までを表示

MISC 86

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, 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(Web)　121　2024年

ISSN： 1349-7693
食道扁平上皮癌患者の背景食道非腫瘍粘膜におけるアルコール曝露後のNRF2標的遺伝子発現低下

外田修裕, 八田和久, 正宗淳, 淺沼清孝, 浅野直喜, 齊藤真弘, 金笑奕, 菅野武, 小池智幸, 今谷晃

日本消化器病学会雑誌(Web)　119　2022年

ISSN： 1349-7693
難治性食道狭窄を呈した微小ガストリノーマの1例

草野啓介, 宇野要, 小池智幸, 三浦晋, 齊藤真弘, 金笑奕, 菅野武, 八田和久, 浅野直喜, 今谷晃, 正宗淳, 益田邦洋, 大塚英郎, 海野倫明, 藤島史喜, 中堀昌人

日本消化器病学会東北支部例会誌　212th　2022年
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

日本消化管学会雑誌(CD-ROM)　6　(Supplement)　2022年

ISSN： 2433-3840
内視鏡的に完全切除した胃平滑筋肉腫の一例

谷地一真, 八田和久, 小池智幸, 齊藤真弘, 菅野武, 金笑奕, 宇野要, 浅野直喜, 今谷晃, 渡邊裕文, 藤島史喜, 正宗淳

日本消化器病学会東北支部例会誌　212th　2022年
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(Web)　118　2021年

ISSN： 1349-7693
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(Web)　118　2021年

ISSN： 1349-7693
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年

ISSN： 1349-7693
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年

ISSN： 1349-7693
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年
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年
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年
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年

ISSN： 1349-7693
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年7月
出版者・発行元：日本消化器病学会-東北支部
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年5月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN： 0387-1207
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年5月
出版者・発行元： (一社)日本消化器内視鏡学会
ISSN： 0387-1207
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年2月
出版者・発行元： (一社)日本消化管学会
ISSN： 2433-3840
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年2月
出版者・発行元： (一社)日本消化管学会
ISSN： 2433-3840
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年2月
出版者・発行元：日本消化器病学会-東北支部
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年

ISSN： 2435-8967
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年9月
出版者・発行元：日本癌学会
ISSN： 0546-0476
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年9月
出版者・発行元：日本癌学会
ISSN： 0546-0476
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年4月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
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年4月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
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年11月

ISSN： 0815-9319

eISSN： 1440-1746
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年11月

ISSN： 0815-9319

eISSN： 1440-1746
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年4月

ISSN： 0016-5085

eISSN： 1528-0012
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年4月

ISSN： 0016-5085

eISSN： 1528-0012
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年
酸関連疾患 IV.特論災害ストレスと消化性潰瘍の関連性:東日本大震災後の新しい知見を中心に

Kanno T, Iijima K, Koike T, Shimosegawa T

Nihon rinsho. Japanese journal of clinical medicine　73　(7)　1209-1214　2015年7月
出版者・発行元：日本臨床社
ISSN： 0047-1852
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年5月

ISSN： 0016-5107

eISSN： 1097-6779
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年5月

ISSN： 0016-5107

eISSN： 1097-6779
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年4月

ISSN： 0016-5085

eISSN： 1528-0012
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年4月

ISSN： 0016-5085

eISSN： 1528-0012
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年4月

ISSN： 0016-5085

eISSN： 1528-0012
Bismuth classification is associated with the requirement for multiple biliary drainage in preoperative patients with malignant perihilar biliary stricture 国際誌

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年

DOI： 10.1007/s00464-014-3878-y 　

詳細を見る詳細を閉じる

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.
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年5月

ISSN： 0016-5085

eISSN： 1528-0012
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年5月

ISSN： 0016-5085

eISSN： 1528-0012
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年

DOI： 10.1007/s00535-014-0976-5 　
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年5月

ISSN： 0016-5085

eISSN： 1528-0012
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年5月

ISSN： 0016-5085

eISSN： 1528-0012
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年5月

ISSN： 0016-5085

eISSN： 1528-0012
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年

DOI： 10.1038/ajg.2011.282 　
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

日本消化器病学会雑誌　107　(臨増総会)　A136-A136　2010年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Clinicopathological Characteristics of Barrett'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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年5月

ISSN： 0016-5085
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年
出版者・発行元： Cyclotron and Radioisotope Center, Tohoku University
Preservation of gastric acid secretion is important for the development of Barrett'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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
Periostin, secreted from stromal cells, has biphagic effect on cell migration and correlates with the epithelial mesenchymal transition of human pancreatic cancer cells. 国際誌

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年

DOI： 10.1002/ijc.23332 　

詳細を見る詳細を閉じる

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.
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年

DOI： 10.1016/j.niox.2007.02.002 　
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年7月
出版者・発行元：胃病態機能研究会
ISSN： 0289-2057
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
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年3月
出版者・発行元： (一財)日本消化器病学会
ISSN： 0446-6586
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
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年4月

ISSN： 0016-5085
ミオシン軽鎖キナーゼ特異的阻害薬は, ヒト膵癌細胞株の運動と接着を阻害する

金子健蔵, 佐藤賢一, 正宗淳, 佐藤晃彦, 下瀬川徹

膵臓 = The Journal of Japan Pancreas Society　17　(3)　254-255　2002年6月25日

ISSN： 0913-0071
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年4月

ISSN： 0016-5085
リゾフォスファチジルコリンはAR42J細胞にアポトーシスを誘導する

正宗淳, 境吉孝, 佐藤晃彦, 藤田基和, 吉田雅義, 下瀬川徹

膵臓 = The Journal of Japan Pancreas Society　17　(1)　85-86　2002年2月25日

ISSN： 0913-0071

︎全件表示 ︎最初の5件までを表示

講演・口頭発表等 12

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年5月4日
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年10月28日
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年5月19日
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年5月19日
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年6月2日
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年2月15日
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年5月22日
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年5月16日
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年5月16日
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年10月23日
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年5月3日
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年5月3日

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 3

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

2022年4月1日～ 2025年3月31日
Notch Systemによる膵再生機構の解明と新しい膵移植法の開発

下瀬川徹, 今谷晃, 木村憲治

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2002年～ 2004年

詳細を見る詳細を閉じる

【背景】 Notch signalingは種々の臓器の発生過程において重要な役割を果たしていることが知られているが、最近種々の癌においてもNotch signalingの活性化が報告されている。しかし、成体膵における膵管上皮の再生機構や癌化における役割についてはいまだ大部分が不明のままである。【目的】 Notch signalingの成体膵の再生機構および膵発癌における役割を明らかにすること。【結果】 1)ヒト膵癌組織において、Notch1はPanIN-1Aの異型度の弱い膵管上皮から浸潤癌に至るまで高発現していた。正常膵管上皮においてはごく一部の上皮細胞に弱い発現を認めるのみだった。また、非腫瘍部において、tubular complexに発現の亢進を認めた。 2)膵癌細胞には、膵前駆細胞のマーカーであるNestinの発現が認められた。 3)膵癌細胞をretinoic acidの存在下で培養すると、増殖が抑制され、Notch1の発現が低下した。また、Nestinの発現も同様に低下し、逆に分化した膵管上皮細胞のマーカーである、carbonic anhydrase IIおよびcytokeratin 19の発現が誘導された。 4)Notch signalingの抑制によっても同様の結果が得られた。 5)Notch signalingの抑制により、MSX2の発現が抑制された。 6)膵癌細胞にMSX2を高発現させると、増殖が促進され、EMTが誘導された。【考察】 Notch signalingが膵発癌過程において、細胞の分化度を調節していることが示された。膵癌の悪性度の規定には一部MSX2 signalingとのクロストークが存在する可能性が示唆された。
光ファイバープローブによる消化器腫瘍の診断

下瀬川徹, 朝倉徹, 田代英夫, 佐藤英俊, 今谷晃, 會沢勝夫, 佐藤賢一, 池田照樹

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (A)

研究機関：Tohoku University

2000年～ 2003年

詳細を見る詳細を閉じる

光線力学的診断並びに治療の基礎検討 Mono-L-aspartyl-chlorine 6(Npe6)の腫瘍親和性を検討し臨床応用の実現性を推測した。自然発症腸腫瘍マウスであるAPC遺伝子ノックアウトマウスにNpe6 3,5,10mg/kgを尾静脈より静注し1,2,4,6,12,24時間後に開腹し各腫瘍への取込みを蛍光画像観測装置により記録、腫瘍の蛍光を画像解析した。2〜6時間後正常粘膜部より有意に取込みが亢進していた。またNpe6,10mg/kg静注2時間後、凍結切片を作成し蛍光顕微鏡写真を撮影した。正常腸管に比べ腫瘍部には明らかなNpe6の橙色蛍光が観察された。特に腫瘍表面に多い傾向が観察された。次に治療への応用について検討した。Npe6,5mg/kgを尾静脈より静注した後、6時間後マウスを開腹し回腸末端部を露出、漿膜側から664nmのダイオードレーザーを50J照射した。照射後1〜7日後照射部を取り出し固定標本を作成したところ、腫瘍部に壊死効果を認めた。腸管腫瘍組織のラマン分析脂質とヘモグロビン分析用に試作した720nm励起専用マイクロラマンプローブと、通常のマクロ試料室を用いた800nm励起での測定を行った。マイクロラマンプローブでの測定では、試料の蛍光が強く、ガンと正常組織でのスペクトル変化は見られなかった。720nmの励起光は脂肪以外の組織観察には適さず、800nm励起での測定ではガン組織に非常に特殊な蛍光バンドが観測されることが示唆された。蛍光バンドを発している生体分子は腫瘍中で径10μm程度の微小領域に局在しており、分子種は特定されていない。800nm近傍数10ナノメートルの励起光だけで蛍光を発し、ラマンバンドの数倍程度の、通常の蛍光バンドに比較して非常に狭いバンド幅を持つ。蛍光強度は正常組織のラマン光強度の100倍程度である。このバンドが腫瘍特異的なものかどうかを今後明らかにする必要がある。