記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.

DOI： 10.1111/jgh.16065

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞・消化管運動賦活薬は,読んで字のごとく消化管運動を"賦活"するものと解釈され,低下した消化管運動の状態において,口腔から摂取した内容物をより前方(肛門側)に移送する運動を促進する薬剤である.しかし,単純に内容物の移送を促進するのではなく,生理的状況に近い"適切な速さ"で内容物を移送することを目的としている.・機械的イレウス,消化管出血,消化管穿孔などの疾患が疑われる際には禁忌である.・metoclopramideは褐色細胞腫,domperidoneはプロラクチノーマの病態を悪化させるため,使用禁忌である.・感染を契機とした機能性ディスペプシア(FD)症状が明らかであり,体重減少を伴う症例や早期飽満感を強く訴える症例などは早めに専門施設に紹介する.・消化管運動賦活薬は多岐にわたる作用機序があり,臨床において症状改善に有用であるが,症状の原因は多様であるため,漫然と長期使用をせず,問診と身体診察にて原因疾患を絞ることが重要である.

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00974&link_issn=&doc_id=20230414290050&doc_link_id=10.15106%2Fj_naika131_744&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_naika131_744&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests. METHODS: Serum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS-CoV-2 S-RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851). RESULTS: The NAb (SARS-CoV-2 S-RBD IgG) titer peaked on day 90 after vaccination (30,808.0 μg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 μg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT-sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA). CONCLUSIONS: Neutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT-sVNT is rapid and user-friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.

DOI： 10.1002/jcla.24545

PubMed

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記述言語：日本語   出版者・発行元：(株)先端医学社  

今まで、機能性ディスペプシア(FD)を考えるうえではHelicobacter pylori(H.pylori)感染の存在は曖昧であった。FDにおいてH.pylori陽性とH.pylori陰性に違いがあるのか?という疑問は、ここ数年の議論の結果、H.pylori関連ディスペプシア(HpD)とFDを明確に区別することで決着がついてきた。H.pylori感染は、内視鏡検査で認める萎縮性変化、腸上皮化生などの明らかな器質的変化を引き起こす。そのため、HpDは器質的疾患として考えるようになったわけである。今後はFD診療をおこなう際に、H.pylori未感染または除菌後のH.pylori陰性FD患者を対象とすることになるであろう。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan. METHODS: One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively. RESULTS: There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan. CONCLUSIONS: Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

DOI： 10.1111/jgh.15874

PubMed

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02312&link_issn=&doc_id=20220511060022&doc_link_id=%2Faq9syokd%2F2022%2F003404%2F023%2F0621-0624%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9syokd%2F2022%2F003404%2F023%2F0621-0624%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

DOI： 10.1007/s00535-021-01843-7

PubMed

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

＜Headline＞1 刺激性下剤は浸透圧性下剤の1つである、酸化マグネシウムによる慢性便秘症に対する治療が治療の大部分を占めているとされている。刺激性下剤による治療を適正に行うことが重要である。2 刺激性下剤による強い排便作用は、消化管の大蠕動を誘発する作用によるものであり、排便における爽快感などが生じる。3 「慢性便秘症診療ガイドライン2017」にもあるように、「慢性便秘症に対して刺激性下剤は有効であり、頓用または短期間の投与を提案する」とされている。慢性便秘症患者のQOLを改善することを念頭に、刺激性下剤の使用法を患者背景を参考に改めて見直す時期にきている。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00697&link_issn=&doc_id=20220113090010&doc_link_id=%2Fae4digta%2F2022%2F011001%2F012%2F0065-0068%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4digta%2F2022%2F011001%2F012%2F0065-0068%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：The Society for Free Radical Research Japan  

DOI： 10.3164/jcbn.21-67

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor. METHODS: Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated. RESULTS: There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients. CONCLUSIONS: Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P.

DOI： 10.1371/journal.pone.0275341

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Gastric atrophy is a precancerous lesion. We aimed to clarify whether gastric atrophy determined by artificial intelligence (AI) correlates with the diagnosis made by expert endoscopists using several endoscopic classifications, the Operative Link on Gastritis Assessment (OLGA) classification based on histological findings, and genotypes associated with gastric atrophy and cancer. METHODS: Two hundred seventy Helicobacter pylori-positive outpatients were enrolled. All patients' endoscopy data were retrospectively evaluated based on the Kimura-Takemoto, modified Kyoto, and OLGA classifications. The AI-trained neural network generated a continuous number between 0 and 1 for gastric atrophy. Nucleotide variance of some candidate genes was confirmed or selectively assessed for a variety of genotypes, including the COX-21195, IL-1β 511, and mPGES-1 genotypes. RESULTS: There were significant correlations between determinations of gastric atrophy by AI and by expert endoscopists using not only the Kimura-Takemoto classification (P < 0.001), but also the modified Kyoto classification (P = 0.046 and P < 0.001 for the two criteria). Moreover, there was a significant correlation with the OLGA classification (P = 0.009). Nucleotide variance of the COX-2, IL-1β, and mPGES-1genes was not significantly associated with gastric atrophy determined by AI. The area under the curve values of the combinations of AI and the modified Kyoto classification (0.746) and AI and the OLGA classification (0.675) were higher than in AI alone (0.665). CONCLUSION: Combinations of AI and the modified Kyoto classification or of AI and the OLGA classification could be useful tools for evaluating gastric atrophy in patients with H. pylori infection as the risk of gastric cancer.

DOI： 10.1002/jgh3.12810

PubMed

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

早期慢性膵炎は臨床症状,膵機能検査,超音波内視鏡検査所見を基に総合的に診断する.難治性心窩部痛患者に対し,trypsinを含む複数の膵酵素を測定し膵酵素異常を認めた場合に,積極的に超音波内視鏡検査を施行することが早期慢性膵炎の拾い上げに有効である.難治性心窩部痛患者に対しては,安易にPPIによる治療継続を行わず,非アルコール性早期慢性膵炎に対しては慢性膵炎に準じた治療により超音波内視鏡像の改善が期待できる.アルコール性の早期慢性膵炎患者もしくは非アルコール性早期慢性膵炎患者においても,dilated side branchesなどの超音波内視鏡所見をともなう患者に対しては慎重な経過観察が必要である.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01118&link_issn=&doc_id=20211216460002&doc_link_id=%2Fck8syokb%2F2021%2F011812%2F002%2F1098-1106%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck8syokb%2F2021%2F011812%2F002%2F1098-1106%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

＜文献概要＞機能性ディスペプシア(FD)はさまざまな要因が複合的に関与し症状発現につながるが,近年,十二指腸粘膜の炎症が注目されている.これまでにもFD患者では十二指腸粘膜のバリア機能障害と透過性亢進が報告されてきた.ストレスによる脳腸相関,胃酸や腸内細菌などの影響が十二指腸粘膜の炎症を引き起こし,バリア機能障害へとつながる可能性が指摘されており,今後の十二指腸の位置づけも含めて概説した.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Gastrointestinal endoscopy and biopsy-based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN). METHODS: We compared the accuracy of physician-performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)-based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR-148a, miR-124a-3, NKX6-1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty-two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions. RESULTS: The board-certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588). CONCLUSION: AI with miR148s DNA methylation-based diagnosis is a potential modality for diagnosing GIN.

DOI： 10.1002/jcla.24122

PubMed

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担当区分：筆頭著者  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：The Society for Free Radical Research Japan  

Since there were no available data about colonic diverticular bleeding in extremely elderly patients (>80 years old) treated with direct oral anticoagulants (DOACs), we tried to determine clinical characteristics in those with colonic diverticular bleeding taking DOACs and to compare clinical outcomes of those in DOAC-treated to those in warfarin-treated . We enrolled DOAC-treated (n = 20) and warfarin-treated (n = 23) extremely elderly patients with diverticular bleeding diagnosed by colonoscopy. We performed a retrospective review of patients' medical charts and endoscopic findings. We classified colonic diverticular bleeding based on endoscopic features due to modified previous study following three groups, type A (active bleeding), type B (non-active bleeding) and type C (bleeding suspected). Clinical outcomes such as number of recurrent bleeding, thrombotic events and mortality were estimated. There were no differences in endoscopical features and clinical characteristics between patients treated with DOAC and warfarin therapy. However, the number of recurrent bleeding, frequency of required blood transfusions and units of blood transfusion in warfarin-treated patients were significantly higher (p<0.05) compared to those in DOAC-treated groups. In addition, mortality and thrombotic events did not differ between DOAC- and warfarin-treated patients. Clinical outcomes suggest that DOACs can be recommended for extremely elderly patients with colonic diverticular disease.

DOI： 10.3164/jcbn.20-140

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have reported that refractory functional dyspepsia patients with pancreatic enzyme abnormalities (FD-P). We tried to analyze the prevalence of exocrine pancreatic insufficiency (EPI) in FD-P patients to clarify whether the pathophysiology of FD patients including clinical symptoms and quality of life were associated with EPI. We enrolled forty-nine patients presenting with typical symptoms of FD-P patients (n = 20) and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 29). Five pancreatic enzymes (p-amylase, lipase, elastase-1, trypsin, and PLA2) were measured and STAI-state/-trait and SF-8 were evaluated. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). There were no significant differences in patient background between FD-P and AP-P patients. BT-PABA test scores for FD-P patients (61.67 ± 5.55) were significantly (p = 0.01) lower than in AP-P patients (95.38 ± 2.36). Physical component scale (PCS) in FD-P patients was significantly (p = 0.002) lower than that in AP-P patients. STAI-state was relatively (p = 0.054) associated with BT-PABA test in FD-P and AP-P patients by multiple logistic regression analysis. The prevalence of EPI in FD-P patients was significantly higher than that in AP-P patients and was relatively associated with state of anxiety. Further studies will be needed to clarify how EPI or pancreatic enzyme abnormalities are associated with the pathophysiology of FD-P patients.

DOI： 10.3164/jcbn.21-67

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11405/nisshoshi.118.1098

PubMed

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記述言語：日本語   出版者・発行元：(株)医学出版  

機能性胸やけ(functional heartburn)は、胸骨後方の焼けるような不快感や痛みがあるものの、酸の逆流が症状の原因ではないとされ、機能性消化管障害(Functional gastrointestinal disorders:FGIDs)の1つとして定義されている。診断基準は、(1)胸骨後方の焼けるような不快感や痛みがある、(2)酸の胃食道逆流が症状の原因ではない、(3)病理組織学的に食道運動障害を認めない、(4)PPIで症状が改善しない、などの4項目が少なくとも半年以上前からあり、少なくとも最近3ヵ月間症状が持続するものとされ、最新のRome IV基準でも定義されている。近年、機能性胸やけを含むFGIDsは増加傾向にあるとされ、その病態解明に注目が集まっている。食道粘膜局所の問題だけではなく、ストレスや不安によって生じる中枢神経における感受性の亢進も指摘されていることから考えると、機能性胸やけはGERDの一部として扱うのではなく、機能性ディスペプシアや過敏性腸症候群などの機能性消化管障害の一部としてとらえる方が妥当であると考えられる。機能性胸やけ患者の診断は、PPI抵抗性胸やけ患者の20～50%に及ぶとの報告がなされている。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)医学出版  

機能性ディスペプシア(functional dyspepsia:FD)は、上腹部症状を主体とする機能性消化管障害(functional gastrointestinal functional disorders:FGIDs)に属する疾患である。2014年に、わが国においてもFD診療ガイドラインが作定された。このFD診療ガイドラインを基に、酸分泌抑制剤あるいは消化管運動機能改善薬あるいはその両剤を併用することでFDの診療が行われてきた。最近我々は、超音波内視鏡を用いて、プロトンポンプインヒビターやカリウムイオン競合型アシッドブロッカー(ボノプラザン)の内服によっても心窩部痛が改善しない、いわゆる難治性心窩部痛症候群の中に、早期慢性膵炎などの膵疾患が含まれていることを報告してきた。難治性FDとして長い間外来でフォローされていたFD群に対して、超音波内視鏡を行うことで見出した、早期慢性膵炎の患者に対して、慢性膵炎の治療を行った群と、アコチアミド+PPI製剤を用いたFDの1次治療を行った群を比較検討すると、慢性膵炎治療を行った群のほうが、心窩部痛が有意に改善された。このことは、超音波内視鏡を用い、難治性FDと考えられた患者群の中で、早期慢性膵炎の診断をつけ慢性膵炎に対する治療を行うことで、症状が軽快する患者群が確かに認められるため、超音波内視鏡を用いた診断を行う臨床的意義は大きいと考えられる。膵酵素異常を伴うディスペプシア群のごくわずかな患者は、超音波内視鏡を用いた経過観察において、早期慢性膵炎群へと進行することがわかっている。Masamuneらの多施設共同研究によれば、早期慢性膵炎患者の2年間の経過観察では、進行する患者は少数であり、進行する患者の多くはアルコール性であることがわかってきている。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：The Society for Free Radical Research Japan  

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.

DOI： 10.3164/jcbn.19-130

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Helicobacter pylori (H. pylori) are a primary factor in the pathogenesis of gastric cancer (GC); GC ranks third among cancer-related mortality. A clear understanding of the H. pylori genome factors underlying GC is necessary to develop more effective methods to prevent GC. A single-molecule real-time DNA sequencing-based H. pylori genome-wide association study analysis was performed using the H. pylori genome present in five early-stage GC (EGC) and five non-GC clinical DNA samples recovered from gastric washes. A total of 275 genes with 702 nucleotide variants (NVs) were found to be common to three or more patients with EGC but no non-GC patients (single-NV: 654/702, 93.2%; multi-NV: 40/702, 5.7%; deletion: 3/702, 0.4%; insertion: 3/702, 0.7%). Gene ontology analysis of H. pylori revealed that genes involved in the mitochondrial electron transport system, glycolytic processes and the TCA cycle were highly enriched. Cancer-related NVs were most frequently found in a member of the Helicobacter outer membrane protein family, hopL. In particular, one of the NVs in hopL was a novel six-nucleotide insertion (1159095̂1159096, TACTTC); this mutant was detected more frequently in a validation set of 50 additional EGC samples (22/50, 44.0%) than in 18 non-GC samples (3/18, 16.7%, P = .04). These results suggest that the hopL variant is associated with the development of GC and may serve as a genetic biomarker of H. pylori virulence and GC risk. Our assay can serve as a potent tool to expand our understanding of bacteria-associated tumorigenesis.

DOI： 10.1002/ijc.33257

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

BACKGROUND: To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. METHODS: Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. KEY RESULTS: Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells. CONCLUSIONS AND INFERENCES: Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.

DOI： 10.1111/nmo.13813

PubMed

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/nmo.13813

記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：日本臨床生理学会  

血液検査や上下部内視鏡検査、腹部CT検査などで異常を認めない機能性消化管障害(FGIDs)は、主に非びらん性逆流性食道炎、機能性ディスペプシア(FD)、過敏性腸症候群の3つの疾患からなるとされている。FDでは他疾患とのオーバーラップの存在も知られている。筆者らの施設データを用いて、FDと早期慢性膵炎との関係性、超音波内視鏡を用いた鑑別診断について述べた。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01210&link_issn=&doc_id=20191211380001&doc_link_id=%2Fcc8jjapf%2F2019%2F004905%2F001%2F0151-0154%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcc8jjapf%2F2019%2F004905%2F001%2F0151-0154%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01205&link_issn=&doc_id=20190925180008&doc_link_id=%2Fag6niria%2F2019%2F007710%2F008%2F1625-1631%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2019%2F007710%2F008%2F1625-1631%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：日本臨床生理学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: To determine whether serum acylated ghrelin levels were associated with anxiety, clinical symptoms, depressive status, quality of life, gastric motility and endoscopic findings based on Kyoto classification in functional dyspepsia (FD) patients. METHODS: We enrolled three groups, FD patients (n = 15) with high levels of acylated ghrelin, FD patients (n = 33) with normal levels of acylated ghrelin and FD patients (n = 35) with low levels of acylated ghrelin. There was no significant differences in the positivity of Helicobacter pylori infection among the three groups. Clinical symptoms were evaluated by Gastrointestinal Symptom Rating Scale (GSRS) and FD symptoms based on Rome III classification. Acylated ghrelin levels were measured by ELISA methods. Depressive status, anxiety, sleep disturbance were respectively asscessed by Self-rating questionnaire for depression (SRQ-D) score, STAI-state/-trait, Pittsburgh sleep quality index (PSQI) scores. Endoscopic findings were evaluated based on Kyoto classification. RESULTS: Body Mass Index (BMI) in FD patients with low levels of acylated ghrelin was significantly higher (p<0.001 and p = 0.008, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. SRQ-D scores in FD patients with low levels of acylated ghrelin was significantly lower (p = 0.008 and p<0.001, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. Scoring of gastric atrophy, intestinal metaplasia, xanthoma and mucus based on Kyoto classification in FD patients with low levels of acylated ghrelin were significantly higher (p<0.001, p = 0.0077, p = 0.036 and p = 0.0063, respectively) compared to those in FD patients with more than low levels of acylated ghrelin. CONCLUSION: Acylated ghrelin levels were associated with BMI, depressive status, and endoscopic findings based on Kyoto classification in FD patients.

DOI： 10.3164/jcbn.18-111

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本潰瘍学会  

ラットにLPS 600μgを腹腔内投与し、8日目にUrocortin 2.016μgを脳槽内に投与し、9日目に消化管粘膜を摘出した。LPS単独投与群、LPS+Urocortin投与群の2群に分け、ラットの回腸・空腸粘膜におけるCD68、CCR2の免疫染色を行い、粘膜内・筋層内で比較検討した。LPS+Urocortin II投与群における回腸・空腸粘膜の粘膜内・筋層内のCD68陽性細胞・CCR2陽性細胞数はLPS単独投与群と比べ有意に増加していた。さらにLPS+MCP-1刺激したラット由来マクロファージcell-line(NR8383)の上清中のIL-6、TNF-αレベルはLPS単独刺激群と比較して増加していた。LPS刺激Urocortin脳槽内投与ラットモデルではUrocortin投与により粘膜内・筋層内炎症細胞浸潤を認めたが、その増加にはラット由来マクロファージのIL-6やTNF-αが関与している可能性があることが示唆された。

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記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

日本では急速に超高齢社会を迎え、消化器疾患構造においてもパラダイムシフトが起きている。現代において患者数が増加している疾患群として機能性消化管障害が知られているが、高齢者層においてもこの領域の疾患患者が増加している。胸やけ、呑酸などを訴える、非びらん性胃食道逆流症(Non-erosive gastroesophgeal reflux disease:NERD)や食後膨満感、早期飽満感、心窩部痛、心窩部灼熱感などの症状を訴える機能性ディスペプシア(Functional dyspepsia:FD)、便通異常と連動する腹痛・腹部不快感・腹部膨満感を訴える過敏性腸症候群(Irritable bowel syndrome:IBS)などである。いずれの疾患も内視鏡的に器質的疾患を認めないところが特徴である。高齢者のFD患者には、胃粘膜萎縮が進行したFD患者とH.pylori未感染の胃酸過多によるFD患者が認められる。一方で、高齢者の便秘症患者においては、IBS-C(便秘型IBS)に比較して機能便秘症(Functional constipation:FC)の割合が若年者より多い傾向にある。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04693&link_issn=&doc_id=20191029220010&doc_link_id=10.1007%2Fs00535-019-01602-9&url=https%3A%2F%2Fdoi.org%2F10.1007%2Fs00535-019-01602-9&type=Crossref&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00002_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Aims: Three-dimensional (3D) rigid endoscopy has been clinically introduced in surgical fields to enable safer and more accurate procedures. To explore the feasibility of 3D flexible endoscopy, we conducted a study comparing 2-dimensional (2D) and 3D visions for the performance of esophageal endoscopic submucosal dissection (ESD). Methods: Six endoscopists (3 experts and 3 trainees) performed ESD of target lesions in isolated porcine esophagus using a prototype 3D flexible endoscope under 2D or 3D vision. Study endpoints were procedure time, speed of mucosal incision and submucosal dissection, number of technical adverse events (perforation, muscle layer damage, and sample damage), and degree of sense of security, fatigue, and eye strain. Results: Procedure time and speed of mucosal incision/submucosal dissection were equivalent for 2D and 3D visions in both experts and trainees. The number of technical adverse events using 2D vision (mean [standard deviation], 3.5 [4.09]) tended to be higher than that using 3D vision in trainees (1.33 [2.80]; P = .06). In experts, 2D and 3D visions were equivalent. The degree of sense of security using 3D vision (3.67 [0.82]) was significantly higher than that using 2D vision (2.67 [0.52]) in trainees (P = .04), but was equivalent in experts. The degree of eye strain using 3D vision (3.00 [0.00]) was significantly higher than that using 2D vision (2.17 [0.41]) in trainees, but was equivalent in experts. Conclusions: 3D vision improves the sense of security during ESD and may reduce technical errors, especially in trainees, indicating the feasibility of a clinical trial of ESD under 3D vision.

DOI： 10.1155/2019/4051956

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0200664

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000492813

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0205165

PubMed

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/tgh.2018.09.12

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本臨床生理学会  

近年、機能性消化管障害(Functional gastrointestinal disorders:FGIDs)の患者数は増加の一途を辿っている。機能性ディスペプシア(Functional dyspepsia:FD)はRome分類第IV版に従い、心窩部痛症候群(Epigastric pain syndrome:EPS)と食後愁訴症候群(Postprandial distress syndrome:PDS)の2つのグループに分けられる。Rome分類第IV版の中でも、FDの病因において脳腸相関は重要な役割を果たしていると述べられている。ほとんどのFD患者に非びらん性逆流性食道炎(Non-erosive reflux diseases:NERD)と過敏性腸症候群(Irritable bowel syndrome:IBS)のoverlapを認めており、さらに慢性膵炎とのoverlapも報告されている。我々は超音波内視鏡を用いてEPS患者群に含まれる早期慢性膵炎の有病率を調査した。5つの膵酵素を測定し、EPS患者の約40%に早期慢性膵炎を認めた。私たちは膵酵素の測定と超音波内視鏡による評価が機能性消化管障害の診断に有用であると考えている。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本潰瘍学会  

LPS刺激脳槽内urocortin投与ラットを用いて、ストレス下での感染刺激状態を作り出し、消化管粘膜内・筋層内炎症細胞浸潤に及ぼす影響について検討した。9週齢のSDラットをLPS単独投与群(n=4)、LPS+urocortin投与群(n=2)に分け、全ラットにLPS 600μgを腹腔内投与し1日目とした。2日目に脳室内手術を行った。空腸粘膜内では、LPS+urocortin投与群におけるCD68陽性細胞数、CCR2陽性細胞数は、LPS単独投与群でのCD68陽性細胞数、CCR2陽性細胞数に比較してともにそれぞれ有意に増加していた。また、空腸筋層下層においても同様に、LPS+urocortin投与群におけるCD68陽性細胞数、CCR2陽性細胞数は、LPS単独投与群でのCD68陽性細胞数、CCR2陽性細胞数に比較してともにそれぞれ有意に増加していた。加えて回腸筋層下層においても、LPS+urocortin投与群におけるCD68陽性細胞数、CCR2陽性細胞数は、LPS単独投与群でのCD68陽性細胞数、CCR2陽性細胞数に比較してともにそれぞれ有意に増加していた。

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

十二指腸は、胃内容物をアルカリ分泌によって中和する働きを持っている。加えてI細胞、K細胞、L細胞といったCCK、GIP、GLP-1産生細胞が十二指腸粘膜・小腸粘膜に局在しており、これらの消化管ホルモン産生により、栄養輸送に関わる消化管運動を制御しており、急激な十二指腸内腔への食物の流入を制限しているとされている。現在注目されている機能性消化管障害患者において、特に機能性ディスペプシア(FD)患者や慢性膵炎患者においても、食直後の胃・十二指腸運動の異常が報告されている。FD患者で報告されている十二指腸粘膜炎症および透過性の亢進との関連性については、その詳細な解析が待たれる。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01118&link_issn=&doc_id=20180223480005&doc_link_id=1390282681379822976&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390282681379822976&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications Ltd  

Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain–gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS. A previous study has reported that proton pump inhibitors (PPIs) and H2-blockers were equally effective in functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and cholinesterase inhibitor, has been shown to improve gastric motility in rodents and dogs, and to reduce PDS symptoms in patients in double-blind multicenter studies. The pharmacological mechanisms of acotiamide remain unknown
whether acotiamide alters gastric emptying and gastric accommodation in patients with functional dyspepsia remains an open question. Other emerging treatment options include Rikkunshito, a herbal medicine that improves gastric emptying through 5-hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic antidepressants (TCAs). Different drugs are needed to accommodate the clinical symptoms and etiology in individual patients.

DOI： 10.1177/2040622317725479

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記述言語：日本語   出版者・発行元：一般財団法人 日本消化器病学会  

十二指腸は，胃内容物をアルカリ分泌によって中和する働きを持っている．加えてI細胞，K細胞，L細胞といったCCK，GIP，GLP-1産生細胞が十二指腸粘膜・小腸粘膜に局在しており，これらの消化管ホルモン産生により，栄養輸送に関わる消化管運動を制御しており，急激な十二指腸内腔への食物の流入を制限しているとされている．現在注目されている機能性消化管障害患者において，特に機能性ディスペプシア（FD）患者や慢性膵炎患者においても，食直後の胃・十二指腸運動の異常が報告されている．FD患者で報告されている十二指腸粘膜炎症および透過性の亢進との関連性については，その詳細な解析が待たれる．

DOI： 10.11405/nisshoshi.115.177

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CiNii Research

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.115.177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

There was not available data about the overlap between functional dyspepsia (FD) and pancreatic diseases. We aimed to determine whether epigastric pain syndrome (EPS) accompanying with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by Japan Pancreas Society (JPS) using endosonography. We enrolled 99 consecutive patients presenting with typical symptoms of FD, including patients with postprandial distress syndrome (PDS) (n = 59), EPS with pancreatic enzyme abnormalities (n = 41) and EPS without pancreatic enzyme abnormalities (n = 42) based on Rome Ill criteria. Gastric motility was evaluated using the C-13-acetate breath test. Early chronic pancreatitis was detected by endosonography and graded from 0 to 7. The ratio of female patients among EPS patients (34/41) with pancreatic enzyme abnormalities was significantly (p = 0.0018) higher than the ratio of female EPS patients (20/42) without it. Postprandial abdominal distention and physical component summary (PCS) scores in EPS patients with pancreatic enzyme abnormalities were significantly disturbed compared to those in EPS patients without it. Interestingly, AUC(5) and AUC(15) values (24.85 +/- 1.31 and 56.11 +/- 2.51, respectively) in EPS patients with pancreatic enzyme abnormalities were also significantly (p = 0.002 and p = 0.001, respectively) increased compared to those (19.75 +/- 1.01 and 47.02 +/- 1.99, respectively) in EPS patients without it. Overall, 64% of EPS patients with pancreatic enzyme abnormalities were diagnosed by endosonography as having concomitant early chronic pancreatitis proposed by JPS. Further studies are warranted to clarify how EPS patients with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by JPS.

DOI： 10.3164/jcbn.17-41

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: We aimed to clarify whether cyclooxygenase- 2 (COX-2) and microsomal prostaglandin E synthase- 1 (mPGES-1) genotypes were associated with certain histological findings and endoscopical appearances based on Kyoto classification. Methods: We enrolled 285 Helicobacter pylori -infected gastritis patients. Genotypes of COX-2 1195, COX-2 1290, mPGES-1, interleukin-1 beta (IL-1 beta) 511 and tumour necrosis factor-alpha (TNF-alpha) 308 were analyzed. Genotyping was performed by polymerase chain reaction. Endoscopic appearances and histological assessment were determined by using Kyoto classification, operative link on gastritic intestinal metaplasia assessment and the updated Sydney system. Results: There was a significant (p = 0.027) relationship between the IL-1 beta 511 C-carrier and histological gastric inflammation in H. pylori -infected gastritis patients. There was a significant (p = 0.009) correlation between the COX-2 1195 G-carrier genotype and histological intestinal metaplasia in the gastric antrum of H. pylori -infected gastritis patients and gastric xanthoma (p = 0.027). The COX-2 1195 G-carrier genotype was also significantly (p = 0.038) associated with the score of endoscopic intestinal metaplasia based on Kyoto classification. The mPGES-1 genotype was significantly (p = 0.002) associated with endoscopic swelling of area. Conclusion: Our results suggest that in Japan, there exists a significant correlation between the COX-2 1195 Gcarrier genotype and intestinal metaplasia in histological and endoscopic findings based on Kyoto classification in H. pylori -infected gastric mucosa. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000479864

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk. Methods: Three hundred sixty-four patients with gastric neoplasms were treated with ESD at our hospital between October 2005 and December 2012. Seventy-four patients with interrupted antithrombotic therapy were undertaken with ESD. Early and delayed postoperative bleeding patterns were estimated. Various clinical characteristics such as gender, age, tumor location, tumor size, ESD procedure time, platelet count, and comorbidity were evaluated. Results: There was a significant difference (p = 0.042) in the ESD procedure time between the patients with postoperative bleeding and those without it. There was no significant difference in postoperative bleeding between the patients on anti thrombotic therapy and not on it. Moreover, interrupted anti thrombotic therapy and platelet count were significantly (p = 0.0461 and p = 0.0059, respectively) associated with early postoperative bleeding in multivariate analysis. In addition, in univariate analysis, ESD procedure time was significantly (p = 0.041) associated with delayed postoperative bleeding. Conclusions: Antithrombotic therapy and prolonged ESD procedure time were significantly associated with early and delayed postoperative bleeding, respectively. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000475924

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan An 81-year-old man was admitted with upper abdominal pain and weight loss. Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle to the body. Histological analysis of a biopsy revealed a moderately differentiated adenocarcinoma. Computed tomography revealed metastases in the liver and lung and the patient was subsequently diagnosed with metastatic advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m(2)) and cisplatin (CDDP) (60 mg/m(2)). Twenty-two months after chemotherapy, the gastric tumor, and the nodules in the liver and lung, had disappeared. We subsequently diagnosed a clinical complete response. The patient was treated with further S-1 monotherapy for 7 months after complete response assessment. He has lived for more than 7 years since the initial diagnosis without recurrence. Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival in elderly patients with advanced gastric cancer.

DOI： 10.1272/jnms.83.199

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan An 81-year-old man was admitted with upper abdominal pain and weight loss. Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle to the body. Histological analysis of a biopsy revealed a moderately differentiated adenocarcinoma. Computed tomography revealed metastases in the liver and lung and the patient was subsequently diagnosed with metastatic advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m(2)) and cisplatin (CDDP) (60 mg/m(2)). Twenty-two months after chemotherapy, the gastric tumor, and the nodules in the liver and lung, had disappeared. We subsequently diagnosed a clinical complete response. The patient was treated with further S-1 monotherapy for 7 months after complete response assessment. He has lived for more than 7 years since the initial diagnosis without recurrence. Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival in elderly patients with advanced gastric cancer.

DOI： 10.1272/jnms.83.199

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01118&link_issn=&doc_id=20161026140006&doc_link_id=1390001206402987008&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206402987008&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background The aim of this study is to clarify whether acotiamide and rabeprazole combination therapy can improve clinical symptoms, gastric emptying, and satisfaction with treatment in functional dyspepsia (FD) patients more effectively than acotiamide or rabeprazole monotherapy alone. We also aimed to determine whether acotiamide affects these changes via its effect on gastric emptying and appetite-related hormones such as ghrelin. Methods We used Rome III criteria to evaluate upper abdominal symptoms and anxiety by the State-Trait Anxiety Inventory (STAI). Gastric motility was evaluated by the 13 C-acetate breath test. Eighty-one FD patients were treated with acotiamide (300 mg/day) (n = 35), acotiamide (300 mg/day) and rabeprazole (10 mg/day) (n = 28), or rabeprazole (10 mg/day) (n = 18) for a period of 4 weeks and followed after 4 weeks of no treatment. Adenocorticotropic hormone (ACTH), cortisol, leptin and ghrelin levels were measured in all FD patients. Key Results Acotiamide and rabeprazole combination therapy significantly improved postprandial distress syndrome (PDS)-like symptoms (p = 0.018, p = 0.04 and p = 0.041, respectively) and epigastric pain (p = 0.024) as wells as STAI-state scores (p = 0.04) compared to rabeprazole monotherapy. Both acotiamide monotherapy, and acotiamide taken in combination with rabeprazole, significantly (p = 0.001 and p = 0.02, respectively) improved satisfaction with treatment, compared to rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy had no significant effect on ACTH and cortisol levels in FD patients. Of interest, acotiamide monotherapy, and acotiamide and rabeprazole combination therapy, significantly (p &lt; 0.0001 and p = 0.018, respectively) increased acylated ghrelin/total ghrelin ratios and significantly (p = 0.04) improved impaired gastric emptying compared to rabeprazole monotherapy. Conclusions & Inferences Further studies are warranted to clarify how acotiamide treatment improves clinical symptoms in FD patients.

DOI： 10.1111/nmo.12805

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本潰瘍学会  

国際的診断基準のRome IIIに従い診断された機能的ディスペプシア患者で、胃痛を主体とするepigastric pain syndrome(EPS)群と、食後の腹部膨満感などを主体とするpostprandial distress syndrome(PDS)群の消化器症状はGSRSを用いてスコア化(7段階)した。胃運動能は13C-acetate呼気試験を用い、Tmax≦65minを胃排出能異常とした。血液検査で血清ACTH、cortisol、膵酵素を測定し、心気症状(不安)はState-Trait Anxiety Inventoryの自己記入式で評価した。心窩部痛症候群のGSRSは平均3.05であり、超音波・ERCP所見で膵機能障害を認めた患者のGSRSは平均1.90と有意に低く、膵機能障害を合併する心窩部痛症候群の平均ACTH値(pg/ml)/Cortisol値(μg/ml)は20.42/11.8、膵機能が正常のEPS群では25.09/12.04と有意差はなかった。超音波内視鏡所見では、膵実質の点状エコーや膵管壁肥厚を認め、早期慢性膵炎の診断基準を満たす症例を認めた。

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本潰瘍学会  

上部消化管症状を訴えた機能性ディスペプシア(FD)患者25名を対象に、acotiamideを4週間投与し、上部消化管症状をVASで、下部消化管症状をGSRSで評価し、空腹時・安静下で採血して血清ACTH、cortisol値を測定した。Acotiamide投与後の食後腹満感、早期満腹感とも有意に改善し、便秘症状、下痢症状は改善傾向となった。STAIを用いた心気症状(不安)では有意な改善は得られなかった。血清ACTH値、cortisolとも投与後に有意な変化は認めなかった。

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.55.6223

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一財)日本消化器病学会  

機能性ディスペプシア(Functional Dyspepsia;FD)患者に対する治療薬acotiamideの登場により、FD診療の環境が整ってきた。H.pylori関連性FDの概念も注目され、心窩部痛症候群患者の病態として、膵機能異常が併存している可能性がある。また、FDの責任臓器として十二指腸粘膜が注目されており、炎症細胞の浸潤と粘膜透過性の亢進などの病態が注目されている。また、胃-十二指腸運動を制御するgut hormone分泌の起点としても重要である。機能性消化管障害において重要な役割を果たしている。脳腸相関についても解明が進んでいる。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2016&ichushi_jid=J01118&link_issn=&doc_id=20160623110002&doc_link_id=1390001206403074944&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390001206403074944&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11405/nisshoshi.113.927

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background: Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship.
Methods: Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography.
Results: 538 patients were enrolled (males, 74.4%; mean age 67.4 +/- 10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88).
Conclusions: In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dld.2015.05.020

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜ポイント＞機能性ディスペプシア(FD)の病態は胃酸分泌や消化管運動機能異常以外に,感染症や心理的因子が関連しているため,消化器症状以外の他症状や患者背景まで考慮する必要がある.FDは食後愁訴症候群と心窩部痛症候群に分類され,消化管運動賦活薬,酸分泌抑制薬を用いることが多い.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J01440&link_issn=&doc_id=20150904040008&doc_link_id=10.11477%2Fmf.1402223695&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1402223695&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world's first country to list "functional dyspepsia" as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor-patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). H. pylori eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.

DOI： 10.1007/s00535-014-1022-3

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記述言語：英語   出版者・発行元：WILEY  

BackgroundThe prevalence of functional dyspepsia (FD) following infectious gastroenteritis has not been systematically reviewed.
AimTo conduct a systematic review and calculate the summary odds ratio (OR) for the development of FD following infectious gastroenteritis, as compared to a control population.
MethodsPublished studies in PubMed, EmBASE, and Cochrane Database and abstracts from standard sources were screened for eligible studies. Data from studies meeting inclusion criteria were pooled for meta-analysis.
ResultsNineteen studies were eligible for inclusion. The mean prevalence of FD following acute gastroenteritis (AGE) was 9.55% (FD, n=909; AGE, n=9517) in adult populations. The summary OR for the development of post-infectious FD was 2.54 (95% CI=1.76-3.65) at more than 6months after AGE, as compared to the prevalence in controls within the same population. This is compared with the summary OR (3.51; 95% CI=2.05-6.00) for the development of post-infectious irritable bowel syndrome (IBS) in the same population at more than 6months after AGE. There was significant statistical heterogeneity with an I-2 of 72.8% for the summary OR of post-infectious FD. Several pathogens, including Salmonella spp., Escherichia coli O157, Campylobacter jejuni, Giardia lamblia and Norovirus have been shown to be associated with post-infectious FD symptoms.
ConclusionsInfectious gastroenteritis is associated with an increased risk for subsequent dyspepsia as well as for irritable bowel syndrome. Post-infectious FD and post-infectious irritable bowel syndrome may represent different aspects of the same pathophysiology. Further studies will be needed to determine this.

DOI： 10.1111/apt.13006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY  

Background/Aims
There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome Ill classification.
Methods
We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the C-13-acetate breath test. We used Rome Ill criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51GIn (346G &gt; A), preproghrelin (3056T&gt;C), Leu72Met (408C&gt;A), GIn90Leu (3412T&gt;A) and G-protein beta 3 (825C&gt;T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction.
Results
There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC(15)) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying.
Conclusions
The Leu72Met (408C&gt;A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

DOI： 10.5056/jnm14086

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY  

Background/Aims
There is no available data on factors associated with healthcare-seeking behavior for functional dyspepsia (FD) symptoms at either tertiary or primary clinics in Japan. Therefore, we aimed to compare clinical symptoms and life styles such as sleep disorders and eating attitude in FD patients visiting general practitioners at primary clinics with those consulting gastroenterologists at tertiary clinics to clarify healthcare-seeking patterns in Japanese patients.
Methods
Fifty-one FD outpatients in a tertiary clinic (college hospital), 50 FD outpatients visiting primary clinics and 50 healthy volunteers were enrolled. Clinical symptoms, quality of life, sleep disorders, eating attitude and anxiety were estimated using the Gastrointestinal Symptom Rating Scale (GSRS), Social Functioning-8 (SF-8) test, Pittsburg Sleep Quality Index (PSQI) test and State-Trait Anxiety Inventory (STAI) for FD outpatients and healthy volunteers.
Results
FD outpatients exhibited higher mean scores of GSRS than healthy volunteers. The SF-8 physical component summary scores in the tertiary clinic group were significantly lower than those in the primary clinic group. GSRS scores were significantly (P &lt; 0.001, P = 0.002) associated with global PSQI scores in FD outpatients as well as with STAI-trait scores (P = 0.006, P = 0.001) compared to healthy volunteers. The frequency of eating between meals in the primary clinic group was significantly (P &lt; 0.05) higher than that in the tertiary clinic group.
Conclusions
It may be important for clarification of healthcare-seeking behavior to determine the difference in both impairment of physical quality of life and eating attitudes between tertiary clinic and primary clinic FD outpatients in Japan.

DOI： 10.5056/jnm14015

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physiological Society  

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship ( P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

DOI： 10.1152/ajpgi.00057.2013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KOREAN SOC NEUROGASTERONTEROL & MOTILITY  

Background/Aims
The association between clinical symptoms, gastric emptying, quality of life and sleep disorders in distinct functional dyspepsia (FD) patients has not been studied yet in detail.
Methods
We enrolled 79 FD patients (postprandial distress syndrome [PDS], n = 65; epigastric pain syndrome [EPS], n = 47; EPS-PDS overlap, n = 33) and 44 healthy volunteers. Gastric motility was evaluated. We used Rome III criteria to evaluate clinical symptoms and State-Trait Anxiety Inventory (STAI) scores to determine anxiety status. Sleep disorder was evaluated using the Pittsburgh Sleep Quality Index scores.
Results
There were no significant differences in age, sex and Helicobacter pylori positivity between FD subtypes and healthy volunteers. The scores of Glasgow dyspepsia severity scores (GDSS), SF-8 and Pittsburgh Sleep Quality Index (PSQI) in distinct subtypes of FD patients were significantly different from those in healthy volunteers. However, there were not significant differences in these scores, Tmax and T-1/2 among 3 subtypes of FD patients. PSQI score was significantly (P = 0.027, P = 0.002 and P = 0.039, respectively) associated with GDSS among EPS, PDS and EPS-PDS overlap patients. In addition, 8-item short form health survey (SF-8; Physical Component Score and Mental Component Score) was significantly associated with global PSQI score in PDS and EPS-PDS overlap patients. In contrast, SF-8 (Mental Component Score) only was significantly linked to global PSQI score in EPS patients.
Conclusions
Prevalences for sleep disorders, gastric motility and quality of life in 3 subtypes of FD patients were similar levels. In PDS and EPS-PDS overlap patients, SF-8 was significantly associated with global PSQI score.

DOI： 10.5056/jnm.2014.20.1.104

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Background and aim : Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT. Methods : Two hundred and thirty-eight outpatients with rheumatoid arthritis under long-term NSAIDs therapies underwent upper endoscopy and were divided into the following four groups according to the pattern (presence : + or absence : -) of AT cotherapy/EPU, respectively : A, -/- (n = 165) : B, -/+ (n = 44) ; C, +/- (n = 25) ; and D, +/+ (n = 4). Results : EPU were found in 48 of the 238 studied patients (20.2%). After significant interactions among four groups hadstatistically been identified, hemoglobin (Hb) and mean corpuscular volume (MCV) as biomarkers for potential bleeding were compared between the groups. Hb and MCV were significantly lower in the D group than in the A, B, or C groups (Hb : P &lt; 0.01, respectively ; P &lt; 0.05, MCV ; P &lt; 0.01 or P &lt; 0.05, respectively). Conclusions : Patients with NSAIDs-associated EPU and AT cotherapy indicated significantly more severe microcytic anemia pattern than those without EPU or AT cotherapy, despite no evidence of overt bleeding. Even uncomplicated-EPU without overt bleeding when ATs were cotherapied may be of potential bleeding sites.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：消化器心身医学研究会  

機能性ディスペプシア(FD)の病態は複雑であり、(1)知覚過敏、(2)消化管運動異常、(3)精神的ファクターなどが原因として挙げられている。最近になり、急性消化管感染症が改善した後にも、FD症状が持続する感染後FDが注目されている。この感染後FDは難治性であり、体重減少、早期飽満感などを伴うことが多いとされている。これら、感染後FDの原因となる病原体は様々であり、機序を含め今後の解明が待たれる。(著者抄録)

DOI： 10.11415/jpdd.21.12

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J02916&link_issn=&doc_id=20150728250003&doc_link_id=%2Fcw8jmpdd%2F2014%2F002101%2F003%2F0012-0015%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw8jmpdd%2F2014%2F002101%2F003%2F0012-0015%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI PUBLISHING CORPORATION  

The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 mu g tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 mu g tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE.

DOI： 10.1155/2014/879595

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

Background: Since the publication of the Rome III criteria for functional dyspepsia (FD), the evidence about the efficacy of half-dose of proton pump inhibitors for dyspepsia symptoms have been limited.
Objective: To examine the efficacy of lansoprazole for functional dyspepsia (FD) diagnosed with the Rome III criteria by the multicentre, double-blind, randomized, placebo-controlled study in Japan.
Methods: A total of 54 FD participants were randomized to lansoprazole 15 mg once daily or placebo for a 4-week double-blind treatment period. The primary efficacy endpoint was an overall dyspeptic symptom relief rate evaluated by 5-point Likert scale scores. The alteration of dyspeptic symptom scores during the study period was also assessed.
Results: At week 4, the overall dyspeptic symptom relief rates were higher in the lansoprazole group (30.4%) than in the placebo group (6.7%) (p = 0.045). The scores for epigastric pain (p = 0.045) and epigastric burning (p = 0.03) were significantly improved in the lansoprazole group compared to the placebo group, whereas the improvement of the scores for postprandial fullness (p = 0.81) and early satiation (p = 0.33) was not different between lansoprazole and placebo groups.
Conclusions: Lansoprazole 15 mg ameliorates dyspeptic symptoms, particularly the epigastric pain syndrome-related symptoms of FD.

DOI： 10.1177/2050640613510904

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CENTER ACADEMIC PUBL JAPAN  

We investigated over time whether contemporary Japanese patients with complicated peptic ulcers have any water-soluble vitamin deficiencies soon after the onset of the complicated peptic ulcers. In this prospective cohort study, fasting serum levels of water-soluble vitamins (vitamins B-1, B-2, B-6, B-12, C, and folic acid) and homocysteine were measured at 3 time points (at admission, hospital discharge, and 3 mo after hospital discharge). Among the 20 patients who were enrolled in the study, 10 consecutive patients who completed measurements at all 3 time points were analyzed. The proportion of patients in whom any of the serum water-soluble vitamins that we examined were deficient was as high as 80% at admission, and remained at 70% at discharge. The proportion of patients with vitamin B-6 deficiency was significantly higher at admission and discharge (50% and 60%, respectively, p&lt;0.05) than at 3 mo after discharge (10%). In conclusion, most patients with complicated peptic ulcers may have a deficiency of one or more water-soluble vitamins in the early phase of the disease after the onset of ulcer complications, even in a contemporary Japanese population.

DOI： 10.3177/jnsv.59.503

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background/Aims: The association between clinical symptoms and sleep disorders in functional dyspepsia (FD)-overlap syndrome has not been studied in detail.
Methods: The subjects were 139 patients with FD, 14 with irritable bowel syndrome (IBS), 12 with nonerosive reflux disease (NERD), and 41 healthy volunteers. Gastric motility was evaluated with the C-13-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and Self-Rating Questionnaire for Depression (SRQ-D) scores to determine depression status. Sleep disorders were evaluated with Pittsburgh Sleep Quality Index (PSQI) scores.
Results: There were no significant differences in age, body-mass index, alcohol intake, and smoking rate between patients with FD alone and those with FD-overlap syndrome. The postprandial abdominal fullness score in patients with FD-NERD-IBS was significantly greater than that in patients with FD-NERD overlap syndrome (p&lt;0.001) or FD alone (p&lt;0.001). The score for the feeling of hunger in patients with FD-NERD-IBS was significantly greater than that in patients with FD alone (p=0.0025), FD-NERD overlap syndrome (p=0.0088), or FD-IBS overlap syndrome (p=0.0057). The heartburn score in subjects with FD-NERD-IBS overlap syndrome was significantly greater than that in subjects with FD alone (p=0.0035) or FD-IBS overlap syndrome (p=0.0026). The Tmax in patients with FD-overlap syndrome or FD alone was significantly higher than that in healthy volunteers. The Pittsburgh Sleep Quality Index score in subjects with FD-NERD-IBS overlap syndrome was significantly greater than that in subjects with FD alone.
Conclusion: Symptom scores, such as those for postprandial abdominal fullness, heartburn, and the feeling of hunger, in patients with FD-overlap syndromes are significantly greater than those in patients with FD alone. Further studies are necessary to clarify whether various symptoms are related to sleep disorders in patients with FD-NERD-IBS overlap syndrome.

DOI： 10.1272/jnms.80.362

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and Aims: The association between functional dyspepsia (FD) and sleep disorders has yet to be studied in detail. The aim of this study is to evaluate the risk factors associated with sleep disorders and the clinical response to nizatidine therapy for sleep disorders in Rome III-based FD patients.
Methods: We enrolled 94 FD patients and 52 healthy volunteers. We used Rome III criteria to evaluate upper abdominal symptoms, and the Self-Rating Questionnaire for Depression scores to determine depression status. Sleep disorder was evaluated using Pittsburgh Sleep Quality Index (PSQI) scores, and degree of anxiety by the State-Trait Anxiety Inventory. Gastric motility was evaluated. Thirty-four FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. The primary end point of this study was to determine whether nizatidine could improve clinical symptoms and sleep disorders in FD patients.
Results: The global PSQI score for FD patients was significantly (P &lt; 0.001) higher compared with healthy volunteers. There were significant correlations between global PSQI scores and total Gastrointestinal Symptom Rating Scale and Self-Rating Questionnaire for Depression scores (P &lt; 0.001, P &lt; 0.0001, respectively) in FD patients than in healthy volunteers. We found significant relationships between subjective sleep quality and both Tmax and T1/2 values in FD patients. Nizatidine significantly improved certain clinical symptoms, gastric emptying, and global PSQI score compared with placebo treatment.
Conclusion: Sleep disorders in FD patients correlated significantly with both clinical symptoms of dyspepsia and depression compared with healthy volunteers. Nizatidine significantly improved gastroesophageal reflux symptoms, gastric emptying, and sleep disorders in FD patients.

DOI： 10.1111/jgh.12236

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BackgroundIn Japanese routine clinical practice, endoscopy is generally carried out without sedation. The present study aimed to identify the factors essential for appropriate selection of transnasal esophagogastroduodenoscopy (TN-EGD) as an alternative to unsedated transoral esophagogastroduodenoscopy (TO-EGD).
Patients and methodsSubjects in this prospective cohort study comprised consecutive outpatients who underwent EGD at a single center. Factors predicting TO-EGD-induced distress were evaluated on a visual analog scale (VAS) and analyzed. Patients were classified into a two-layered system on the basis of these predictive factors, and the severity of distress between the TN-EGD and TO-EGD groups was compared using VAS and the change in the rate-pressure product as subjective and objective indices, respectively.
ResultsIn total, 728 outpatients (390 male, 338 female; mean age, 63.10.5 years; TO-EGD group, 630; TN-EGD group, 98)met the inclusion criteria. Multivariate logistic regression analysis confirmed that age&lt;65 years (P&lt;0.01; odds ratio [OR], 1.69; 95% confidence interval [CI], 1.14-2.52), gender (female; P&lt;0.01; OR,1.97; 95% CI, 1.34-2.91), marital status (single; P&lt;0.01; OR, 1.96; 95% CI, 1.18-3.27), and anxiety towards TO-EGD (P&lt;0.001; OR, 3.62; 95% CI, 2.44-5.37) were independently associated with intolerance. Both indices were significantly higher in the TO-EGD subgroup than in the TN-EGD subgroup in the high predictive class, but not in the low predictive class.
ConclusionPredictive factors for detecting intolerance to unsedated TO-EGD may be useful to appropriately select patients who transpose unsedated TO-EGD to TN-EGD.

DOI： 10.1111/den.12006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3164/jcbn.12-95

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and aim Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT. Methods Two hundred and thirty-eight outpatients with rheumatoid arthritis under long-term NSAIDs therapies underwent upper endoscopy and were divided into the following four groups according to the pattern (presence: + or absence: ) of AT cotherapy/EPU, respectively: A, / (n?=?165); B, /+ (n?=?44); C, +/ (n?=?25); and D, +/+ (n?=?4). Results EPU were found in 48 of the 238 studied patients (20.2%). After significant interactions among four groups hadstatistically been identified, hemoglobin (Hb) and mean corpuscular volume (MCV) as biomarkers for potential bleeding were compared between the groups.Hb and MCV were significantly lower in the D group than in the A,B, or C groups (Hb: P?&lt;?0.01, respectively; P?&lt;?0.05, MCV; P?&lt;?0.01 or P?&lt;?0.05, respectively). Conclusions Patients with NSAIDs-associated EPU and AT cotherapy indicated significantly more severe microcytic anemia pattern than those without EPU or AT cotherapy, despite no evidence of overt bleeding. Even uncomplicated-EPU without overt bleeding when ATs were cotherapied may be of potential bleeding sites.

DOI： 10.1111/j.1443-1661.2012.01334.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective An impairment of gastric motility is strongly associated with the pathophysiology of functional dyspepsia (FD). Plasma ghrelin is one of the key molecules linked to gastric motility. Therefore, this study aimed to evaluate whether ghrelin (GHRL) gene polymorphisms are associated with clinical symptoms, the plasma ghrelin levels and gastric emptying in patients with FD as defined by the Rome III classification.
Methods We enrolled 74 Helicobacter pylori-negative patients presenting with typical symptoms of FD (epigastric pain syndrome (EPS), n=23; postprandial distress syndrome (PDS), n=51) and 102 healthy volunteers. Gastric motility was evaluated according to the Tmax value and T-1/2 using the C-13-acetate breath test. We used the Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine the depression status. The Arg51Gln(346G-&gt;A), preproghrelin3056T-&gt;C, Leu72Met(408C-&gt;A) and Gln90Leu (3412T-&gt;A) polymorphisms were analyzed in DNA in blood samples obtained from the enrolled subjects. Genotyping was performed using polymerase chain reaction.
Results There was a significant relationship (p=0.048) between the preproghrelin 3056TT genotype and the serum levels of acylated ghrelin in the H. pylori-negative FD patients. The preproghrelin 3056TT genotype was significantly (p=0.047) associated with the feeling of hunger in the H. pylori-negative FD patients.
Conclusion The preproghrelin 3056TT genotype is significantly associated with the acylated ghrelin levels and the feeling of hunger in H. pylori-negative FD patients. Further studies are needed to clarify the association between the preproghrelin 3056TT genotype and lower plasma acylated ghrelin levels and the impact of this relationship on the feeling of hunger in H. pylori-negative FD patients.

DOI： 10.2169/internalmedicine.52.8662

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sleep disorder is a common medical problem. Sleep disorder has been associated with several diseases, including pulmonary disease, gastroesophageal reflux disease (GERD) and fibromyalgia. Interest in sleep phenomenology and gastrointestinal functioning has recently increased, because sleep disorder causes significant morbidity, as evidenced by the increased need for general medical and mental health treatment for emotional problems. A number of studies have found an association between sleep disorders and functional gastrointestinal (GI) disorders. Although arousal from sleep serves several protective roles, such as increase in the speed of esophageal clearance and in airway refluxes to prevent aspiration, awakening from sleep unfortunately induces impairment of sleep quality. Some investigations about the relationship between psychogenic factors and gut motility are controversial. In addition, reports of alterations in gut motility during sleep have also been contradictory. We have evaluated sleep disorder in functional dyspepsia (FD) patients using Pittsburgh Sleep Quality Index (PSQI) score. In our recent data, PSQI score of FD patients was significantly higher compared to that in healthy volunteers. Another study has reported that the distribution of subjects who thought that they got enough sleep was significantly lower for the FD/iirritable bowel syndrome (IBS) subjects than for control subjects. Several studies have reported that anti-acid therapy and prokinetic agents are effective for certain FD patients. In addition, previous study has reported tricyclic antidepressants (TCA) drugs are effective for some FD patients. Finally, new drug, actiamide, a muscarinic antagonist and cholinesterase inhibitor, significantly improves Postprandial Distress Syndrome (PDS) symptoms. It might be critical issues for determination of precise mechanism for functional gastrointestinal disorders to clarify the relationship between gut motility and sleep disorders.

DOI： 10.1272/jnms.80.104

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: A study in Japan has found that nizatidine (NIZ) is more effective than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis (RE), although the NIZ group included a greater number of patients with severe RE. As there was no difference in the level of acid suppression among H2RAs, it is possible that NIZ has other effects on esophageal acid exposure (EAE) besides acid suppression. In this study, the effect of NIZ on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects. Methods: In 10 healthy subjects, while in a sitting position, esophageal motility and a pH study were measured for 3 hours after a meal on 2 separate days at least 2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before the meal on one day and a placebo on the other. Both studies were preceded by a week of treatment with either NIZ (150 mg, bid) or a placebo and the order of treatment was randomized. Results: Basal LES pressure in the NIZ group (14.1 mmHg, median) was significantly greater than that of the placebo group (8.5 mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour period was significantly less than that of the placebo group (16.5/3 h) and the rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for the postprandial 3-hour period was also significantly less than that of the placebo group (74.4% and 2.8%, respectively). Conclusion: NIZ significantly reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during TLESRs.

DOI： 10.1540/jsmr.47.157

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)東京内科医会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本臨床生理学会  

器質的には何も問題が認められないにもかかわらず、上腹部の不快感や痛みなどの腹部症状が存在する機能性ディスペプシア(Functional dyspepsia:FD)は、近年発症する患者が増加しており注目されている。今回我々がFD患者の睡眠障害と胃排出能の関連を検討したところ、Control群においては胃排出時間(Tmax)と主観的睡眠・入眠時間とに有意な相関関係があるが、FD群においては相関は見られないという結果が得られた。また、睡眠と酸逆流症状との相関をみると、FD患者では、酸逆流症状と主観的睡眠・睡眠困難との間に有意な相関がみとめられた。このことからGERDだけでなくFDにおいても酸逆流症状と睡眠障害との相関関係が認められる可能性があることが示唆された。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: In this crossover study, we investigated whether nizatidine, a H-2-receptor antagonist, can alleviate clinical symptoms and gastric emptying in patients with Rome III-based functional dyspepsia (FD) with or without impaired gastric emptying. Methods: We enrolled 30 patients presenting with FD symptoms (epigastric pain syndrome, n = 6; postprandial distress syndrome, n = 24). Rome III-based FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. Gastric motility was mainly evaluated with the Tmax value using the 13 C-acetate breath test. Meal-related symptoms were defined as postprandial fullness and early satiation. Gastroesophageal symptom was defined as a burning feeling rising from the stomach or lower chest up toward the neck. Acylated- and desacylated ghrelin levels were evaluated by the ELISA method. Clinical symptoms, gastric emptying and ghrelin levels were evaluated at three different points during the study (pretreatment, after 4 weeks former treatment and after 4 weeks later treatment). The primary end point of this study was to determine whether nizatidine would improve clinical symptoms and gastric emptying in FD patients with or without impaired gastric emptying via affecting ghrelin levels. Results: Meal-related symptoms of the patients treated with nizatidine improved significantly (21/30; 70%) compared to those treated with placebo (3/30; 10%). In addition, nizatidine treatment also significantly improved gastro-esophageal symptoms (16/30; 53%) compared to those treated with placebo (0/30; 0%). Nizatidine treatment in patients with FD accompanied by impaired gastric emptying significantly improved clinical symptoms and T-max value as a marker of gastric emptying (10/11, 91%; 9/11, 82%) compared to placebo therapy, respectively. There were no significant differences in ghrelin levels between nizatidine treatment and placebo therapy. Conclusion: Nizatidine administration significantly improved both gastric emptying and clinical symptoms in FD patients with impaired gastric emptying. Copyright (c) 2012 S. Karger AG, Basel

DOI： 10.1159/000339111

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background G-protein dysfunction related alteration of intracellular signal transduction might be linked to various abnormalities of functional gastrointestinal (GI) disorders. Serotonin (5-hydroxytryptamine; 5-HT) as well as G-protein is also key signaling molecule sensorimotor functions in the GI tract. Thus, this study aims to evaluate the correlation between gastric emptying and GNβ3 and 5-HTs polymorphisms in functional dyspepsia (FD) as defined by Rome III classification. Methods Seventy-four patients presenting with typical symptoms of FD (epigastric pain syndrome: EPS, n=24; postprandial distress syndrome: PDS, n=51) and sixty-four healthy volunteers were enrolled. Gastric motility was evaluated with the Tmaxvalue using the13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine depression status. GNβ3-C825T, 5-HT1A-C1019G, 5-HT2A-G1438A, 5-HT3A-C42T, and 5-HT4A-G353+6A polymorphisms were analyzed in DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Key Results There was a significant relationship (P=0.045) between GNβ3 825CC genotype and PDS patients without gastro-esophageal reflux symptoms with impaired gastric emptying. In Japanese, GNβ3 825CC genotype in FD patients was significantly associated (P=0.0485) with the feeling of hunger compared with GNβ3 825CT and TT genotypes. Conclusions &amp; Inferences Our results suggest that the GNβ3 825CC genotype is significantly associated with PDS patients without gastro-esophageal reflux with impairments of gastric emptying and also with the feeling of hunger in patients with FD. Further studies are needed to clarify whether the GNβ3 825CC genotype is linked to disturbances of gastric emptying via altered signal transduction responses. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2982.2011.01781.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

Functional dyspepsia is a highly prevalent and heterogeneous disorder. Functional dyspepsia involves many pathogenic factors, such as gastric motility disorders, visceral hypersensitivity, psychological factors, Helicobacter pylori infection, and excessive gastric acid secretion. The present article provides pathophysiologic mechanisms. (J Nippon Med Sch 2011; 78: 280-285)

DOI： 10.1272/jnms.78.280

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: Endoscopic submucosal dissection (ESD) is more invasive than other common endoscopic procedures and may increase the risk for deep vein thrombosis (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has not been adequately studied.
Objective: To evaluate DVT incidence and disease-specific features of D-dimer levels in ESD patients.
Design: Prospective cohort study.
Setting: Single academic center.
Patients: This study involved 60 patients with superficial gastric neoplasms indicated for ESD.
Intervention: For all patients who underwent ESD, ultrasonography of the lower limbs was performed to detect DVT the day after ESD. D-dimer levels were measured 3 times: before ESD, immediately after ESD, and the day after ESD.
Main Outcome Measurements: DVT incidence after ESD.
Results: The DVT incidence was 10.0% (6/60). At all 3 time points, D-dimer measurements were higher in patients with DVT than in patients without DVT. According to receiver operating characteristic curve analysis, the resulting cut-off value of the D-dimer level the day after ESD was 1.9 mu g/mL (sensitivity 83.3%; specificity 79.6%) for ESD patients, with superior association to pre-ESD or immediately after ESD. In univariate analyses, high D-dimer levels the day after ESD and the presence of comorbidities were significantly associated with DVT development.
Limitations: Single center and small number of patients.
Conclusion: ESD procedures have a moderate risk for venous thromboembolism. In patients undergoing ESD, D-dimer levels, especially on the day after ESD, may have specific features associated with DVT development. (Gastrointest Endosc 2011;74:798-804.)

DOI： 10.1016/j.gie.2011.06.015

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記述言語：日本語   出版者・発行元：日本臨床生理学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

著者らは75歳以上の切除不能胃癌20例(高齢者群)を対象にS-1ベース化学療法を施行し、治療成績を75歳未満の非高齢者群20例と比較検討した。化学療法のレジメンはS-1単独療法、S-1+低用量CDDP療法、S-1+CDDP療法のいずれが施行された。その結果、BSCとなった症例は高齢者群で7例(35%)、非高齢者群で2例(10%)であった。推定50%生存期間中央値は非高齢者群18例で11.3ヵ月、高齢者群13例で14.5ヵ月と有意差はなかった。grade 3/4の有害事象は非高齢者群では白血球減少、貧血が3例(16.5%)、好中球減少が2例(11%)、食欲不振、吐気、口内炎、疲労、皮疹がそれぞれ1例(5.5%)で、高齢者群では好中球減少と血小板減少が2例(15%)、白血球減少、貧血、Cre上昇、食欲不振、下痢がそれぞれ1例(7.5%)と、両群間で有意差はなく、いずれの群も治療関連死はなかった。尚、在宅期間率は、非高齢者群で60.4%、高齢者群で78.8%と有意差はみられなかった。

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

OBJECTIVES: Recent studies have shown that postinfectious functional dyspepsia (FD) symptoms may persist after elimination of gastrointestinal (GI) infection as well as postinfectious irritable bowel syndrome accompanying colonic inflammation. However, it is unclear whether intestinal chronic inflammation can contribute to clinical symptoms of certain FD patients such as postinfectious FD. To determine the relationship between local inflammation of the duodenum and clinical symptoms, we evaluated the infiltration of several phenotypes of duodenal inflammatory cells as well as gastric motility using (13)C urea breath test in postinfectious FD patients.
METHODS: We enrolled 136 consecutive patients diagnosed with FD according to Rome III criteria, and 20 healthy controls, after upper GI endoscopy. Gastric motility was evaluated by gastric emptying time (T-max) using the (13)C-acetate breath test. Upper abdominal symptoms including epigastric pain, epigastric burning, postprandial fullness, abdominal distension, and early satiety were assessed by questionnaire scores. We obtained biopsy specimens from the stomach and duodenum during upper GI endoscopy. Histological gastritis and duodenitis were assessed as mild, moderate, or severe according to previously described criteria. Characteristics of inflammatory cells and neuroendocrine cells were determined immunohistochemically with antibodies to CD3, CD68, CCR2, Vdelta1 TCR, and serotonin.
RESULTS: Endoscopic duodenitis was observed in only 5.7% of postinfectious FD patients. However, the rates of histological duodenitis in duodenal biopsies of postinfectious FD patients were 17% for mild, 26% for moderate, and 57% for severe grades of duodenitis. The degree of histological duodenitis of postinfectious FD patients was significantly greater than that of healthy volunteers. There was a significant correlation between epigastric burning and the degree of duodenitis in postinfectious FD patients. There was no significant difference in histological duodenitis and T-max value in the postinfectious FD patients with or without Helicobacter pylori infection. In addition, CD68-positive cell number in postinfectious FD patients was significantly increased compared with the numbers in subjects with epigastric pain syndrome or postprandial distress syndrome and in healthy volunteers. CCR2-/CD68-double positive cell number in postinfectious FD patients was significantly (P = 0.009) increased compared with those in healthy volunteers.
CONCLUSIONS: Migration of inflammatory cells, in particular, duodenal CCR2-positive macrophages, may have an important function in the pathophysiology of postinfectious FD patients.

DOI： 10.1038/ajg.2010.151

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記述言語：日本語   出版者・発行元：(株)勁草書房コミュニケーション事業部  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Previous studies have shown that non-erosive reflux disease (NERD) patients are less sensitive to proton pump inhibitor (PPI) treatment than patients with erosive reflux disease. The aim of this study was to investigate whether treatment with prokinetics in addition to omeprazole therapy would improve clinical symptoms, gastric emptying and esophageal peristalsis in PPI-resistant NERD patients with or without delayed gastric emptying.
Subjects were 64 consecutive patients presenting with typical symptoms of PPl-resistant NERD (n = 44) and 20 healthy volunteers. PPI-resistant NERD patients underwent mosapride citrate (15 mg/day) and omeprazole (20 mg/day) co-therapy for 12 weeks. We evaluated the clinical symptoms as well as gastric emptying and esophageal manometry before and after combined therapy. We measured both acylated- and des-acylated plasma ghrelin levels by the ELISA method. The primary endopoint was to investigate whether co-administration of mosapride citrate and omeprazole would improve clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.
T (max) value in PPI-resistant NERD patients was significantly higher than in healthy volunteers. Combination therapy with the prokinetic agent mosapride citrate and omeprazole significantly improved reflux symptoms and T (max) value in T (max) &gt; 65 min NERD patients. Co-therapy also significantly reduced des-acylated-ghrelin levels in NERD patients with delayed gastric emptying.
Administration of mosapride citrate in addition to omeprazole improved gastro-esophageal reflux and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying.

DOI： 10.1007/s00535-009-0173-0

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

切除不能胃癌症例において、75歳以下のPS良好例に対してはS-1ベース化学療法が生存期間延長に有効であると報告されている。今回、我々は75歳以上の切除不能胃がん症例を対象にS-1ベース化学療法の有効性を検討した。75歳以上の患者12例と75歳未満の患者12例を対象としレトロスペクティブに解析した。S-1ベース化学療法の生存期間中央値は非高齢者(75歳未満)群で9.7ヵ月、高齢者(75歳以上)群で9.5ヵ月であった。各群の有害事象は容認できる範囲であった。75歳以上の切除不能胃癌症例であってもPS良好例ではS-1ベース化学療法は生存期間延長に有用である可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

75歳以上の切除不能胃癌症例を対象に、S-1ベース化学療法が有効か検討した。切除不能胃癌と診断した75歳以上の患者(高齢者群)8例と、75歳未満の患者(非高齢者群)10例を対象とした。S-1単独療法かS-1+低用量CDDP療法のいずれかを施行した。S-1ベース化学療法全体の生存期間中央値(MST)は、非高齢者群9.7ヵ月、高齢者群9.5ヵ月で有意差はなかった。非高齢者群でのS-1単独療法と、S-1+低用量CDDP療法のMSTはそれぞれ、15ヵ月、8.65ヵ月、高齢者群でそれぞれ10.5ヵ月、7.75ヵ月であった。grade3/4の有害事象は、非高齢者群では10例中、白血球減少、貧血、疲労、皮疹が各1例で、高齢者群では8例中、白血球減少が2例、貧血、クレアチニン上昇、食欲不振、下痢が各1例であった。いずれも治療関連死はなく、容認可能な範囲であった。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: To see whether celecoxib prevents gastric cancer occurrence by disrupting the progression of chronic gastritis into gastric carcinoma through its inhibition of the migration of CD133-positive cells, one of the surface markers of bone marrow-derived cells, in Helicobacter pylori infected gerbils. Methods: 70 gerbils were divided into six groups. Group 1 gerbils served as control (n = 6). 10 gerbils were given N-methyl-N-nitrosourea (MNU), 30 ppm (group 2). 6 short-term Helicobacter pylori-infected gerbils (group 3) were sacrificed after 8 weeks of H. pylori infection and 6 long-term H. pylori-infected gerbils were sacrificed after 42 weeks of H. pylori infection (group 4). 20 gerbils were given MNU pretreatment and long-term H. pylori infection (group 5). In addition, after H. pylori inoculation, 22 gerbils also received a celecoxib in their diet (group 6). CD133 and CCR2 expression in gastric tissues was evaluated by Western blot analysis and immunostaining. Results: CD133-positive cells were mainly localized in the bottom of the gastric epithelial cells. CD133-positive cells also migrated into gastric cancer tissues in this model. CD133-positive cells in MNU-pretreated H. pylori-infected gerbils were significantly increased compared to those in H. pylori short-term infected gerbils. Celecoxib treatment significantly reduced CD133-positive cell migration and CCR2 expression levels. CD133- and CCR2-positive cells were colocalized in H. pylori-infected gastritis and gastric cancer tissues. Celecoxib treatment significantly reduced the number of CD133- and CCR2-positive cells. Conclusions: Celecoxib inhibits CD133-positive cell migration via the reduction of CCR2 in this model. Further studies are needed to clarify the precise mechanisms driving H. pylori infection-induced CD133-positive cell migration and its link to the progression of chronic gastritis into gastric cancer. Copyright (C) 2010 S. Karger AG, Basel

DOI： 10.1159/000252790

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Aim: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. Methods: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. Results: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. Conclusions: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception. Copyright (C) 2010 S. Karger AG, Basel

DOI： 10.1159/000309483

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：GEORG THIEME VERLAG KG  

Background and study aims: Endoscopic submucosal dissection (ESD) may cause excessive duodenogastric reflux (DGR) in a similar manner to distal gastrectomy, particularly after antral resections. We aimed to examine the occurrence of DGR after ESD.
Patients and methods: Patients with gastric neoplasm for whom ESD was indicated were categorized according to lesion site: the antral group (lower [L] stomach, n=46) and the nonantral group (upper or middle [U or M] stomach, n=49). Endoscopy was performed before ESD, the day after ESD, and 3 months after ESI), and the fasting bile acid concentration (BAC) in the gastric juice was analyzed.
Results: BAC values showed significant interaction between time point and group, although this association differed in the antral and nonantral groups. BACs on the day after ESD were higher in the antral group than in the nonantral group, but not the pre-ESD and 3 months post-ESD levels. In the antral group only, fasting BACs increased significantly the day after ESD and decreased to baseline levels 3 months post-ESD. There was also a correlation between BAC and lesion location in the antral subgroups, with significantly higher BACs found the day after ESD in patients with lesser curvature lesions.
Conclusions: ESD of lesions in the antral lesser curvature may lead to a transient early increase in DGR. However, ESD does not result in long-term DGR, a factor that is known to increase the risk of carcinogenesis following gastrectomy.

DOI： 10.1055/s-0029-1215221

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection.
Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by (13)C-urea breath tests performed 2 to 3 months post-therapy.
As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group.
In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.

DOI： 10.1111/j.1523-5378.2009.00664.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment.
This retrospective cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least 3 months. Potential risk factors for endoscopic PU were analyzed in RA outpatients on longterm NSAID treatment.
PU incidence was 31% with bisphosphonate co-therapy and 17% without the co-therapy. PU incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogues (PG) co-therapy, 14% with histamine-H(2) receptor antagonists(H2RA) co-therapy, and 27% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for PU (OR, 2.29; 95% CI, 1.09-4.81). Other risk factors for ulcer development were advanced age (greater than 60 years) and smoking (OR, 2.58; 95% CI, 1.03-6.49 and OR, 2.71; 95% CI, 1.13-5.53, respectively.) Factors that significantly reduced the incidence of PU were H2RA or PPI/PG cotherapies (OR, 0.29; 95% CI, 0.12-0.68.).
Bisphosphonate co-therapy as well as advanced age and smoking was found to be a significant risk factor in PU, while co-therapies of standard-dose H2RA or PPI/PG proved effective in preventing PU in Japanese RA patients on long-term NSAID treatment.

DOI： 10.1007/s00535-008-2278-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. Methods: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the T(max) value as a marker of gastric emptying using the (13)C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. Results: The T(max) value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and T(max) value in PDS patients but not in EPS or NERD patients. Conclusion: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000205740

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

Recent studies have shown that CD40, a key player in angiogenesis and tubular formation, is an extracellular receptor of the heat shock protein 70 (HSP70)-peptide complex in endothelial cells. The aim of the present study was to determine the effect of extracellular HSP70 treatment on CD40L-suppressed apoptosis and CD40L-induced tubular formation in human umbilical vein endothelial cells (HUVEC).
The apoptotic index of CD40L-stimulated HUVEC with or without recombinant human HSP70 was evaluated using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay analysis. Binding of HSP70-peptide complex to CD40 on HUVEC was determined by double-labeling immunofluorescence methods. To evaluate the biological activity of CD40 engagement pretreated with rhHSP70 (0.5, 1 and 3 ng/mL), the extent of new capillary-like networking structure (tubular formation) formation in HUVEC was counted using an Olympus digital camera. Vascular invasion into MNK-28 cell clusters was assessed by counting the number of tubular structures extending from the HUVEC into growth factor-depleted Matrigel. Scores for CD34, HSP70 and CD40L expression levels in gastric cancer tissues were determined by immunostaining.
CD40L stimulation inhibited vincristine-induced apoptosis of HUVEC in a dose-dependent manner. Extracellular HSP70 treatment significantly blocked the inhibition of apoptosis by CD40L in HUVEC exposed to vincristine. HSP70-peptide complex bound to CD40 on HUVEC. Extracellular HSP70 treatment also significantly reduced CD40L-induced tubular formation in a dose-dependent manner. HSP70 treatment also suppressed invasive tubular formation into MKN-28 cells clusters by CD40L-activated HUVEC. There was a significant relationship between CD40L expression levels and microvessel density; however, the relationship between HSP70 expression level and microvessel density in gastric cancer tissues was not significant.
Extracellular HSP70 treatment blocks CD40L inhibition of apoptosis and CD40L induction of tubular formation in HUVEC.

DOI： 10.1111/j.1440-1746.2008.05442.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background andAim: Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme in DNA base excision repair (BER), linked to cancer chemosensitivity. However, little is known about the localization of APE-1 in Helicobacter pylori-infected gastric mucosa or its role in the development of gastric cancer. To investigate the role of APE-1 in the development of gastric cancer, we examined APE-1 expression and localization in cultured cells and gastric biopsies from patients with H. pylori-infected gastritis or gastric adenoma, and from surgically resected gastric cancer.
Methods: APE-1 mRNA and protein expression were determined in H. pylori (CagA+) water-extract protein (HPWEP)-stimulated MKN-28 cells, gastric adenocarcinoma cell-line (AGS) cells, and human peripheral macrophages by real-time polymerase chain reaction and Western blot analysis. APE-1 expression and 8-OHdG as a measure of oxidative DNA damage were evaluated by immunostaining. Localization of APE-1 and I kappa B alpha phosphorylation in gastric adenoma and gastric cancer tissues were evaluated by single- and double-label immunohistochemistry.
Results: In studies in vitro, HPWEP-stimulation significantly increased APE-1 mRNA expression levels in both MKN-28 cells and human peripheral macrophages. Hypo/reoxygenation treatment significantly increased APE-1 protein expression in HPWEP-stimulated MKN-28 cells. HPWEP stimulation significantly increased both APE-1 expression and I kappa B alpha phosphorylation levels in MKN-28 and AGS cells. In human tissues, APE-1 expression in H. pylori-infected gastritis without goblet cell metaplasia was significantly increased as compared to that in tissues from uninfected subjects. Eradication therapy significantly reduced both APE-1 and 8-OHdG expression levels in the gastric mucosa. APE-1 expression was mainly localized in epithelial cells within gastric adenoma and in mesenchymal cells of gastric cancer tissues. APE-1 expression in gastric cancer tissues was significantly reduced compared to that in H. pylori-infected gastric adenoma, while 8-OHdG index and I kappa B alpha phosphorylation levels did not differ between these two neoplastic tissue types. Co-localization of APE-1 and I kappa B alpha phosphorylation was observed not in gastric cancer cells but in gastric adenoma cells.
Conclusion: H. pylori infection is associated with increased APE-1 expression in human cell lines and in gastric tissues from subjects with gastritis and gastric adenomas. The observed distinct expression patterns of APE-1 and 8-OHdG in gastric adenoma and gastric cancer tissues may provide insight into the progression of these conditions and warrants further investigation.

DOI： 10.1111/j.1523-5378.2008.00605.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Background. Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2 expression. Methods. COX-2, prostaglandin E(2) (PGE(2)), and VEGF production were evaluated in CD40 ligand (CD40L)-stimulated macrophages. CD40L and MCP-1 mRNA levels in gastric cancer tissues were evaluated by real-time polymerase chain reaction (PCR). Localizations of MCP-1, CD40L, CD34, CD40, and CCR2 in 34 gastric cancer tissue specimens were evaluated by single-or double-label immunohistochemistry. Results. COX-2 expression levels were significantly higher in CD40L-stimulated macrophages and correlated with increased PGE(2) and VEGF production. Addition of MCP-1 to CD40L-stimulated macrophages had a synergistic effect on COX-2 expression and subsequent PGE(2) and VEGF production. CD40L and MCP-1 mRNA levels were significantly higher in poorly differentiated gastric cancers than in H. pylori-infected gastritis patients. High microvessel density was significantly associated with MCP-1 and CCR2 scores and lymph node metastasis. Conclusions. MCP-1 and CD40L had a synergistic effect on COX-2 expression and subsequent VEGF production in gastric cancer.

DOI： 10.1007/s00535-007-2151-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2 expression. The aim of this study was to examine the effect of MCP-1/CCR2 and CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells. We also investigated the localization of these proteins in gastric cancer tissue. COX-2 and CCR2 levels were evaluated in CD40L-stimulated HUVECs by Western blot and real-time PCR. VEGF secreted in the culture media was quantified by EliSA. Localizations of MCP-1, CD40L, CD34, CD40 and CCR2 in 34 gastric cancer tissue specimens were evaluated by immunohistochemistry. CD40-CD40L interaction-induced COX-2 production and subsequently, upregulated COX-2 production contributed to elevated VEGF and CCR2 levels in CD40L-stimulated HUVECs. CD40L-stimulated VEGF production was COX-2 but not COX-1 dependent. RS-102895, a CCR2-specific antagonist, significantly reduced VEGF production in CD40L- and MCP-1-stimulated HUVECs. MCP-1 had a synergistic effect on COX-2, CCR2 and VEGF levels in Cd40L-stimulated HUVECs. In gastric cancer tissue, there was significant correlation between microvessel density and scores for CD40L, MCP-1 and CCR2 protein expression. Thus, MCP-1 had a synergistic effect on COX-2 and CCR2 protein expression in CD40L-stimulated HUVECs and thereby stimulated VEGF production in these cells. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.plefa.2007.10.030

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Aims: The aim of this study was to see whether administration of celecoxib, a selective cyclooxy-genase-2 (COX-2) inhibitor, could prevent the development of gastric cancer via inhibition of apurinic/apyrimidinic endonuclease-1 (APE-1) expression induced by Helicobacter pylori infection. Methods: 70 Mongolian gerbils were divided into 6 groups. Group 1 gerbils served as controls (n=6). Ten gerbils were given N-methyl-N-nitrosourea (MNU), 30 ppm, 5 times biweekly (group 2). Short-term H. pylori infection was induced in 6 gerbils which were sacrificed 8 weeks after H. pylori infection (group 3). Long-term H. pylori infection was induced in 6 other gerbils which were sacrificed 44 weeks after H. pylori infection (group 4). Twenty gerbils were given MNU pretreatment 5 times biweekly and long-term H. pylori infection (group 5). In addition, after H. pylori inoculation, group 6 gerbils also received celecoxib with their diet for 26 weeks. APE-1 expression alone or with COX-2 in gastric tissues was evaluated by Western blot and immunohistological analysis. Myeloperoxidase (MPO) activity and thiobarbituricacid-reactive substance (TBARS) levels were also evaluated. Results: APE-1 was localized in gastric epithelial cells and mesenchymal cells including macrophages in H. pylori-infected gerbils. The numbers of APE-1-positive cells in group 4 and 5 were significantly increased compared to those of group 3. Celecoxib treatment significantly reduced MPO activity, TBARS levels and the incidence of gastric cancer. APE-1 and I kappa B alpha phosphorylation levels were significantly increased in MNU-pretreated H. pylori-infected gerbils compared to those in MNU-only gerbils. Celecoxib significantly reduced APE-1 and I kappa B alpha phosphorylation levels in MNU-pretreated H. pylori-infected gerbils. COX-2 and APE-1 were coexpressed in the macrophages of H. pylori-infected gerbils. Conclusion: Celecoxib prevented gastric cancer in MNU-pretreated H. pylori-infected gerbils with a reduction in APE-1 expression thereby suggesting the implication of APE-1 in gastric carcinogenesis in this model. Copyright (c) 2008 S. Karger AG, Basel

DOI： 10.1159/000167978

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Studies have linked microsomal prostaglandin E synthase (mPGES)-1 with gastric cancer. The purpose of this study was to determine mPGES-1, mPGES-2, and cytosolic PGES (cPGES) expression in gastric cancer and to evaluate the correlation between mPGES-1 and mPGES-2 expression and clinicopathological factors and cyclooxygenase-2 expression. PGES protein expression was examined by Western blot in gastric cancer cell lines and in biopsy samples from patients with gastric cancer. mPGES-1, mPGES-2, and cPGES protein localizations were examined immunohistochemically in 129 archival gastric cancer surgical resections. mPGES-1 protein expression was found in gastric cancer biopsies and cancer cell lines with differentiated or undifferentiated adenocarcinoma. There was no mPGES-1 expression in nonneoplastic biopsies. All cell lines and tissue samples expressed mPGES-2 and cPGES. Immunohistochemical analysis showed cancer cells expressed mPGES-1 in 47% of cases. mPGES-2 immunoreactivity was seen both in nonneoplastic glandular epithelium and cancer cells; however, cancer cell immunoreactivity was significantly more pronounced in 29% of cases. cPGES expression was constitutive both in nonneoplastic and neoplastic tissues, with no significant variation among cases. mPGES-1 and mPGES-2 expression correlated with cyclooxygenase-2 expression. mPGES-1 and mPGES-2 expression, and tumor-node-metastasis stage had independent prognostic significance under multivariate analysis in patients with gastric cancer overall and in patients with differentiated cancers. However, only tumor-node-metastasis stage and mPGES-2 expression retained independent prognostic significance in patients with poorly differentiated cancers. mPGES-1 and mPGES-2 correlate with clinicopathological factors and may be valuable prognostic factors in gastric cancer. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2007.04.020

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記述言語：日本語   出版者・発行元：(株)先端医学社  

non-erosive reflux disease(NERD)患者の食道運動機能を評価すると、LES圧、一次蠕動波(波高、出現率)は、健常者と同様であったが、二次蠕動波の出現率は、健常者にくらべ有意な低下がみられた。二次蠕動波は食道内の空気、液体などの伸展刺激により出現し、食道内に逆流した内容の排出に重要である。逆流発生時の逆流症状は、多因子の関与により出現していると考えられているが、その因子の一つとして、食道口側へ達する逆流、食道内の胃酸曝露時間の延長が考えられている。逆流後に二次蠕動波が出現しない場合には、逆流液のより食道口側への上昇、また逆流液の排出遅延の原因となり、二次蠕動波の出現率低下がNERD患者の症状出現に関連する可能性も考えられる。(著者抄録)

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記述言語：英語  

COX (cyclooxygenase) is one of the key enzymes involved in the synthesis of a variety of prostaglandins (PGs), some of which have been strongly linked to inflammation. One of its two well-known isoforms, COX-2, is an inducible enzyme whose induction and expression is dynamically regulated by growth factors, mitogens, and tumor promoters. Several animal and clinical studies have reported the chemopreventive effect of celecoxib, a selective COX-2 inhibitor
and in particular, a few studies have shown that celecoxib prevents the development of gastric cancer. Administration of celecoxib also showed increases in cardiovascular risk and disruption of renal physiology. Therefore, studies hoping to clarify how selective COX-2 inhibitors modulate gastric cancer must keep in mind that coxibs have also been linked to serious cardiovascular events and disruption of renal physiology. © 2007 Birkhäuser Verlag.

DOI： 10.1007/s10787-006-1541-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

We have previously shown heregulin (HRG)-alpha expression in human gastric fibroblasts and its stimulation of gastric epithelial cell growth. Although cyclooxygenase (COX)-2 has also been shown to stimulate growth factor production in these cells, the interaction between COX-2 and HRG remains unknown. Conditioned media (CM) from gastric fibroblasts incubated with PGE(2) or interleukin (IL)-1 beta, a well known COX-2 inducer, were analyzed for their effect on erbB3 tyrosine phosphorylation in MKN28 gastric epithelial cells. HRG protein expression in fibroblast lysates and CM was also examined by western blot. HRG-alpha and HRG-beta mRNA expression in gastric fibroblasts and human gastric tissue was examined by real-time quantitative PCR. HRG and COX-2 expressions in surgical resections of human gastric ulcer tissue were examined immunohistochemically. CM from fibroblasts incubated with PGE(2), or IL-1 beta, stimulated erbB3 phosphorylation in MKN28 cells. Preincubation of the fibroblasts with celecoxib, a selective COX-2 inhibitor, suppressed CM-induced erbB3 phosphorylation. This inhibition was reversed by exogenous PGE(2). As with erbB3 phophorylation, IL-1 beta stimulated both HRG-alpha and HRG-alpha mRNA expression, as well as HRG release into gastric fibroblast CM. IL-1 beta-stimulated HRG expression and release were also inhibited by celecoxib, and exogenous PGE(2) restored this inhibitory effect, suggesting the activation of an IL-1 beta-COX-2-PGE(2) pathway that culminates in the release of HRG from fibroblasts. HRG-alpha and HRG-beta mRNA levels were significantly higher in gastric ulcer tissue than in normal gastric mucosa. HRG immunoreactivity was found in interstitial cells of the gastric ulcer bed and coexpressed with COX-2. These results suggest that HRG might be a new member of the growth factor family involved in the COX-2-dependent ulcer repair process.

DOI： 10.1152/ajpgi.00253.2005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：B M J PUBLISHING GROUP  

Background and aims: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria.
Methods: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E-2 and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood.
Results: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 ( 19.9) pg/ mg protein) and severe dysplasia (227.9 (35.4) pg/ mg protein) than in normal colonic mucosa (55.8 (4.2)pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1 alpha and MIP-1 beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP- 1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP- 1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-(2) inhibitor, inhibited MCP-1- induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP- 1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation.
Conclusions: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

DOI： 10.1136/gut.2004.059824

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Background and Aims: The purpose of this study was to investigate possible factors that could impact on gamma delta T cell accumulation in the gastric mucosa.
Method: Subjects were 22 Helicobacter pylori (H. pylori)-free and 75 H. pylori-infected mucosa biopsies classified into grades I similar to III gastritis as per our previous study. The number of gamma delta- and 45 RO-positive T cells were determined by immunostaining. Gastric mucosal anti-H. pylori urease specific antibodies and interleukin (IL)-1 beta, IL-2, 4, 7, 10 and IL-12 levels were assayed by enzyme-linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in gamma delta T cells stimulated by H. pylori urease were also evaluated.
Results: The gamma delta T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. gamma delta T cell count was significantly correlated with IL-1 beta and interleukin-7 (IL-7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many gamma delta T cells. After H. pylori eradication therapy, the gamma delta T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL-7 stimulation in both peripheral and mucosal gamma delta T cells. Interferon (IFN)-gamma and IL-10 production was also stimulated by H. pylori urease in peripheral gamma delta T cells.
Conclusions: Gastric mucosal increases in IL-7 and IL-1 beta closely corresponded to the accumulation of gamma delta T cells in gastric mucosa. An association was also seen between gamma delta T cell accumulation and H. pylori urease-specific Ig levels.

DOI： 10.1111/j.1440-1746.2005.04148.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aim: The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori-infected Mongolian gerbils. Methods: Fifty-two Mongolian gerbils were divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (MNU; 30 ppm). At week 12, group 2 (n = 20) and group 3 ( n = 22) gerbils were then given an injection of H. pylori, while group 1 controls ( n = 10) received Brucella broth alone. In addition, 7 weeks after H. pylori inoculation, at week 19, group 3 gerbils also received a 36-week administration course of celecoxib ( 1,500 ppm) in their diet. The incidence of gastric adenocarcinoma was determined at week 54 by histological analysis. COX-2 and Cdx2 protein expression and COX activity were evaluated for each group. The extent of intestinal metaplasia, Cdx2 and MUC2 expression, and the apoptotic index were evaluated semi-quantitatively by immunohistochemistry. Results: The incidence of gastric adenocarcinoma was: group 1, 0% (0/10); group 2, 65% (13/20), and group 3, 23% (5/22; p &lt; 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in group 3 gerbils was also shown by Western blot analysis. Conclusions: Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in MNU-pretreated H. pylori-infected Mongolian gerbils. Copyright (c) 2006 S. Karger AG, Basel.

DOI： 10.1159/000100503

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pretreatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM- 1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.

DOI： 10.1007/s10620-005-2811-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS AS  

Objective. Neutrophil activation followed by free radical production is a feature that is common to the various forms of gastric injury. However, the roles of cyclooxygenase (COX)-1 and -2 in neutrophil activation have yet to be clarified in the gastric mucosa. We examined the roles of both COX-1 and COX-2 in neutrophil activation and free radical production in ischemia-reperfusion (IR) injury in the gastric mucosa of mice. Material and methods. Ischemia was induced by clamping the celiac artery for 30 min, then removing the clamp for 90 min. SC-560, a selective COX-1 inhibitor; NS-398, a selective COX-2 inhibitor, or rebamipide, a mucoprotective agent, was administered to mice 60 min before ischemia. Gastric damage was evaluated histologically and by measuring myeloperoxidase (MPO) activity. Expressions of COX protein and intercellular adhesion molecule (ICAM)-1 were evaluated by Western blot analysis and ELISA, respectively. Effects of these drugs on thiobarbituric acid reactive substances (TBARS) and gastric blood flow were also evaluated. Results. COX-2 expression was induced in gastric mucosa 60 min after reperfusion, whereas COX-1 expression remained unaltered. Localization of COX-1 and ICAM-1 in IR-injured mucosa was observed mainly in endothelial cells, while COX-2 expression was detected in mesenchymal cells such as mononuclear cells, spindle-like cells and endothelial cells. SC-560 significantly decreased gastric blood flow at the reperfusion point and reduced gastric mucosal injury in IR mice. Furthermore, SC-560 pretreatment significantly reduced MPO activity, TBARS levels and ICAM-1 expression. In contrast, NS-398 significantly increased ICAM-1 expression, MPO activity and TBARS levels, and aggravated gastric damage in IR mice. Rebamipide pretreatment reduced both COX-2 expression and IR injury. Conclusions. In IR mice, COX-2 protects the gastric mucosa by down-regulating ICAM-1 expression, whereas COX-1 is involved in up-regulating reperfusion flow, thereby aggravating the mucosa.

DOI： 10.1080/00365520510015827

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. Aim: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. Methods: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group)
those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. Results: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P &lt
0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. Conclusions: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSADD therapy. © 2005 Blackwell Publishing Ltd.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PACINI EDITORE  

Background. Helicobacter pylori eradication decreases recurrence of peptic ulcers with marked improvement in histological inflammation, but gastric mucosal injuries may be developed even after eradication.
Purpose. To investigate the mechanisms responsible for the development of gastric erosions after eradication, we analysed the relationship between clinicopathological risk factors and the occurrence of gastric erosion after curing H. pylori infection.
Patients. Sixty patients underwent endoscopy before, and 3, 6 and 12 months after the completion of H. pylori eradication.
Methods. Risk factors associated with the development of gastric erosions after eradication were assessed by multivariate analysis, and cyclooxygenase- I and -2 immunoreactivity was histologically examined in the gastric mucosa before and after eradication.
Results. The cumulative prevalence of gastric erosions after H. pylori eradication was 38.3% within I year. Using multivariate analysis, corpus gastritis scores (inflammation score+ activity score), corpus atrophy scores and an age of more than 50 years were found to be independent factors associated with the development of gastric erosion after eradication with odds ratios of 7.39, 0.13 and 5.00, respectively. Cyclooxygenase-2 immunoreactivity of the corpus was decreased for the non-erosion group after eradication, but not for the erosion group.
Conclusions. Severe gastritis or less severe atrophy in oxyntic glands but not in pyloric glands before eradication may be involved in the development of gastric erosions after curing H. pylori infection. (c) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dld.2004.12.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Background: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan.
Aim: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. Methods: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin El analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. Results: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P &lt; 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two.
Conclusions: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.

DOI： 10.1111/j.1365-2036.2005.02477.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Recently, three different prostaglandin E-2 synthases have been identified: microsomal prostaglandin E synthase (mPGES)-1, cytosolic PGES (cPGES), and mPGES-2; however, their role and connection to cyclooxygenase (COX)-2 in the gastric ulcer repair process remain unknown. Therefore, we examined mPGES-1, cPGES, and mPGES-2 expression and localization in the stomach in vitro and in vivo. Tissues were obtained from Helicobacter pylori ( H. pylori)-infected patients and consisted of surgical resections of gastric ulcers, or biopsies of gastric ulcers or gastritis. mPGES-1 mRNA and protein expression levels were examined by real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. mPGES-1, cPGES, and mPGES-2 localization were analyzed immunohistochemically. Induction of PGES expression in response to interleukin ( IL)-1beta was examined in vitro in the cultured human gastric fibroblast line Hs262. St. Real-time PCR analysis of mPGES-1 mRNA expression in biopsy samples showed significantly higher expression levels in open than in closed gastric ulcer tissue. Western blot analysis showed mPGES-1 protein expression limited to open ulcer tissue, while mPGES-2 and cPGES immunoreactivities were seen in both open and closed ulcer tissue. Immunohistochemical analysis showed strong mPGES-1 expression in fibroblasts and macrophages of the ulcer bed, paralleling COX-2 expression. cPGES and mPGES-2 expression levels were seen in both fibroblasts of the ulcer bed and in epithelial cells. Furthermore, stronger cPGES and mPGES-2 immunoreactivities were seen in scattered mast cell-like cells and neuroendocrine-like cells, respectively. Induction of mPGES-1 expression in response to IL-1beta was seen in cultured gastric fibroblasts in vitro, and double immunostaining showed mPGES-1 coexpression with COX-2 in fibroblasts of the ulcer bed in vivo. In conclusion, mPGES-1, cPGES, and mPGES-2 are all expressed in gastric ulcer tissue, but only mPGES-1 parallels COX-2 expression in mesenchymal and inflammatory cells of the ulcer bed, suggesting a key role for this enzyme in the ulcer repair process.

DOI： 10.1038/labinvest.3700200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

We have previously shown that the cyclooxygenase (COX)2/PGE2 pathway plays a key role in VEGF production in gastric fibroblasts. Recent studies have identified three PGE synthase (PGES) isozymes: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1 and -2, but little is known regarding the expression and roles of these enzymes in gastric fibroblasts. Thus we examined IL-1beta-stimulated mPGES-1 and cPGES mRNA and protein expression in gastric fibroblasts by quantitative PCR and Western blot analysis, respectively, and studied both their relationship to COX-1 and -2 and their roles in PGE2 and VEGF production in vitro. IL-1beta stimulated increases in both COX-2 and mPGES-1 mRNA and protein expression levels. However, COX-2 mRNA and protein expression were more rapidly induced than mPGES-1 mRNA and protein expression. Furthermore, MK-886, a nonselective mPGES-1 inhibitor, failed to inhibit IL-1beta-induced PGE2 release at the 8-h time point, while totally inhibiting PGE2 at the later stage. However, MK-886 did inhibit IL-1beta-stimulated PGES activity in vitro by 86.8%. N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS-398), a selective COX-2 inhibitor, totally inhibited PGE2 production at both the 8-h and 24-h time points, suggesting that COX-2-dependent PGE2 generation does not depend on mPGES-1 activity at the early stage. In contrast, NS-398 did not inhibit VEGF production at 8 h, and only partially at 24 h, whereas MK-886 totally inhibited VEGF production at each time point. These results suggest that IL-1beta-induced mPGES-1 protein expression preferentially coupled with COX-2 protein at late stages of PGE2 production and that IL-1beta-stimulated VEGF production was totally dependent on membrane-associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily proteins, which includes mPGES-1, but was partially dependent on the COX-2/PGE2 pathway.

DOI： 10.1152/ajpgi.00313.2004

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

OBJECTIVES: One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori.
METHODS: Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and C-13-urea breath test to confirm H. pylori eradication. H. Pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm 2 of the lamina propria mucosa.
RESULTS: There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy.
CONCLUSIONS: These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.

DOI： 10.1111/j.1572-0241-2004.30291.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PHYSIOLOGICAL SOC  

VEGF is a highly specific stimulator of endothelial cells and may play an important role in angiogenesis in the process of tissue regeneration. We previously showed that cyclooxygenase-2 (COX-2) expressed in mesenchymal cells of the ulcer bed is involved in the ulcer repair process. To clarify the role of COX-2 in angiogenesis during gastric ulcer healing, we investigated the relation between COX-2 expression and VEGF production in human gastric fibroblasts in vivo and in vitro. Gastric fibroblasts were cultured in RPMI 1640 with and without IL-1alpha or IL-1beta in the presence or absence of NS-398, a selective COX-2 inhibitor. Supernatant VEGF and PGE(2) concentrations were measured by enzyme-linked immunosorbent assay. COX-2 expression in fibroblasts was determined by Western blot analysis. VEGF and COX-2 expression in surgical resections of human gastric ulcer tissue was examined immunohistochemically. IL-1 dose dependently enhanced VEGF release in cultured gastric fibroblasts after a 24-h stimulation. IL-1 also stimulated PGE(2) production in gastric fibroblasts via COX-2 induction. NS-398 significantly suppressed VEGF and PGE(2) release from IL-1-stimulated gastric fibroblasts; concurrent addition of PGE(2) restored NS-398-inhibited VEGF release. COX-2 and VEGF immunoreactivity were colocalized in fibroblast-like cells in the ulcer bed of gastric tissues. These results suggest that COX-2 plays a key role in VEGF production in gastric fibroblasts stimulated by IL-1 in vitro and that angiogenesis induced by the COX-2-VEGF pathway might be involved in gastric ulcer healing.

DOI： 10.1152/ajpgi.00537.2003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 52-year-old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.

DOI： 10.1111/j.1443-1661.2003.00335.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING INC  

Background. The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined.
To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylon colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells.
Materials and Methods. A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA).
Results. Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylon density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23,p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24,p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylon-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner.
Conclusions. Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.

DOI： 10.1111/j.1083-4389.2004.00209.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: ErbB2 expression in esophageal adenocarcinoma has been shown to correlate with its clinicopathological features. However, expression levels for EGF receptor, erbB2 and erbB3 in specialized columnar epithelium ( SCE) of Barrett's esophagus have yet to be determined. To investigate the relationship between EGF family receptors and Barrett's esophagus, we examined expression levels for EGF receptor, erbB2 and erbB3 in SCE of Barrett's esophagus. Methods: 10 consecutive patients with short- and long-segment Barrett's esophagus, and 10 control subjects without organic esophago-gastric diseases were enrolled. Biopsy samples of Barrett's mucosa stained or not stained with methylene blue applied endoscopically were used for histological evaluation and Western blot analysis of EGF receptor, erbB2 and erbB3 proteins. Results: Mean length of Barrett's esophagus was 2.6 cm ( range 1-8 cm) and all tissue samples from methylene blue stained Barrett's mucosa consisted of non-dysplastic SCE. In the Barrett's group, Western blot analysis showed that EGF receptor and erbB2 were equally and strongly expressed in SCE and squamous epithelium; in contrast, erbB3 expression in SCE was considerably weaker. In control subjects, all proteins showed strong expression for all samples. Immunohistochemical analysis of SCE in Barrett's esophagus showed positive EGF receptor and erbB2 expression, and no erbB3 expression. Conclusions: ErbB2 is strongly expressed in both non-dysplastic SCE and squamous epithelium, whereas erbB3 expression is essentially limited to the squamous epithelium.

DOI： 10.1159/000080928

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記述言語：日本語   出版者・発行元：(一社)東京内科医会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BRITISH MED JOURNAL PUBL GROUP  

Background and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation.
Methods: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry.
Results: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related.
Conclusions: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.

DOI： 10.1136/gut.52.9.1257

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal injury by upregulating ICAM-1 expression, and thus activating neutrophils in the gastric mucosa in vivo. However, studies differ on just how NSAIDs affect ICAM-1 expression in vitro. We therefore examined the effects of the NSAIDs indomethacin and NS-398, a non-selective and a selective cycloxygenase-2 (COX-2) inhibitor, respectively, on ICAM-1 expression in human umbilical vein endothelial cells (HUVEC) and gastric fibroblasts in vitro. IL-1β at 10 ng/ml strongly stimulated increases in ICAM-1 expression in HUVEC and gastric fibroblasts. Indomethacin and NS-398 did not affect ICAM-1 expression in endothelial cells, while both indomethacin and NS-398 significantly inhibited IL-1β-stimulated ICAM-1 expression in gastric fibroblasts without any influence on COX-2 expression. To our interest, the addition of prostaglandin E2 not only reversed the suppression, but synergistically down-regulated ICAM-1 expression with indomethacin in gastric fibroblasts. MG-132 pretreatment strongly suppressed IL-β-stimulated ICAM-1 expression in both cell types. The results suggest that NSAIDs-stimulated ICAM-1 expression is not likely to directly affect the endothelial cells in the gastric mucosa, and that COX-2 plays no role in NSAID-stimulated increases in ICAM-1 expression in endothelial cells and gastric fibroblasts.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. Aim: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. Methods: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-bIocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. Results: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. Conclusions: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication. © 2002 Blackwell Science Ltd.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING LTD  

Background The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial.
Aim: To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury.
Methods: Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity.
Results: A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days.
Conclusions: Our results suggest that cyclo-oxygenase-2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non-steroidal anti-inflammatory drugs. Therefore, inhibition of cyclo-oxygenase-2 activity may enhance non-steroidal anti-inflammatory drug-caused gastric damage in H. pylori-infected animals.

DOI： 10.1046/j.1365-2036.2002.01211.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING LTD  

Background: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury.
Aim: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions.
Methods: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication.
Results: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis.
Conclusions: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG TOKYO  

Background. Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice. Methods. Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined. Results. Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment. Conclusions. Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant.

DOI： 10.1007/s005350200016

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to gain insight into how this antibody affects urease activity, the epitope that was recognized by the antibody was determined. By screening a panel of overlapping synthetic peptides covering the entire sequence of the two subunits (UreA and UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB-33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from either end allowed us to determine the minimal epitope as 8 amino acid residues (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short sequence which formed a flap over the active site of urease, suggesting that binding of the L2 antibody sterically inhibits access of urea, the substrate of urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8-mer minimal epitope resulted in generation of antiurease antibodies that were capable of inhibiting the enzymatic activity. Since urease is critical for virulence of H. pylori, antigenic peptides that induce production of antibodies to inhibit its enzymatic activity may potentially be a useful tool as a vaccine for prevention and treatment of H. pylori infection.

DOI： 10.1128/IAI.69.11.6597-6603.2001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE ASIA  

Background and Aims: The classification of gastritis by using the revised Sydney system suggests that there are two types of Helicobacter pylori-related gastritis. The aim of the present study was to examine the risk factors that might be involved in the presence of either atrophic gastritis or intestinal metaplasia of the gastric corpus of Japanese patients.
Methods: Biopsy samples were obtained from the gastric corpus in 154 patients with dyspepsia, and the degree of atrophy or intestinal metaplasia was determined histologically. The correlation between several variables and presence of atrophy or intestinal metaplasia was evaluated by using multivariate analysis.
Results: Among the 11 variables, which included age, peptic ulcer diseases and H. pylori infection, H. pylori infection was the major risk factor associated with the presence of atrophic gastritis or intestinal metaplasia of the gastric corpus. In contrast, duodenal ulcer (DU) disease reduced the risk of contracting both conditions. Age was an independent risk factor only for intestinal metaplasia of the gastric corpus. When 128 H. pylori-positive subjects were analyzed, DU and age were similarly associated with the presence of both conditions.
Conclusions: These results suggest that DU reduces the risk for contracting atrophic gastritis and intestinal metaplasia, and age is an independent risk factor for intestinal metaplasia of the gastric corpus in dyspeptic Japanese patients. (C) 2000 Blackwell Science Asia Pry Ltd.

DOI： 10.1046/j.1440-1746.2001.02380.x

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：SPRINGER-VERLAG TOKYO  

Because 50% of elderly patients in Japan have Helicobacter pylori infection, many NSAID-induced peptic ulcers, by chance, occur in patients who happen to be H. pylori-positive. Many previous studies have reported the relation between H. pylori and NSAIDs. Chan et al. and Bianchi et al. described increased risk for ulcers in H. pylori-positive NSAID users. In contrast, recent prospective studies show that the presence of H. pylori does not increase the risk of gastric or duodenal ulcers in arthritis patients or healthy subjects taking NSAIDs. Because many H. pylori-positive patients are administered NSAIDs in Japan, it is important to determine whether these offensive factors affected the gastric mucosa additively or independently. Regarding cyclooxygenase-2 (COX-2) protein, which is the target enzyme against NSAIDs, COX-2 expressed at inflammatory sites in the gastrointestinal tract presumably plays a role in the repair process of gastric damage. H. pylori infection elevated COX-2 protein in gastric epithelium and decreased the levels of COX mRNA in the stomachs of mice with experimentally induced gastric erosions or ulcers, although COX-2 mRNA levels were undetectable in controls. Therefore, it seems to be important to determine the role of COX-2 protein in the gastric tissues to clarify the relation between H. pylori infection and NSAIDs.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BRITISH MED JOURNAL PUBL GROUP  

Background-Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear.
Aims-To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration.
Patients and Methods-Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n=9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n=45) and H pylori negative healthy subjects (n=15). COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry.
Results-COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-I immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts.
Conclusions-Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process.

DOI： 10.1136/gut.46.6.782

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL SCIENCE LTD  

Background: Increasing evidence mesothelial cells contribute to the control of inflammation in the peritoneal cavity by secreting prostaglandins. A study has shown that cyclooxygenase (COX)-2 knockout mice die partly as a result of peritonitis.
Aim: To investigate the expression and location of COX in peritonitis associated with peptic ulcer perforation.
Methods: Gastric and duodenal tissues were collected intraoperatively from nine and four patients, respectively, and immunohistochemical staining for COX-1 and COX-2 was performed.
Results: Histologically, all patients had severe peritonitis around the perforation sites, into which many inflammatory cells and fibroblasts had infiltrated, and reactive mesothelial cells exhibited hyperplastic change. The COX-1 protein was not detected, whereas COX-2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site. Macrophages and fibroblasts around the perforation site also revealed immunostaining for COX-2.
Conclusions: Our results showed that COX-2 protein is induced in mesothelial cells, as well as in macrophages and fibroblasts, in inflamed peritoneal tissues associated with peptic ulcer perforation suggesting involvement of COX-2 in tissue repair.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

Background: Increasing evidence suggests that mesothelial cells contribute to the control of inflammation in the peritoneal cavity by secreting prostaglandins. A study has shown that cyclooxygenase (COX)-2 knockout mice die partly as a result of peritonitis. Aim: To investigate the expression and location of COX in peritonitis associated with peptic ulcer perforation. Methods: Gastric and duodenal tissues were collected intraoperatively from nine and four patients, respectively, and immunohistochemical staining for COX-1 and COX-2 was performed. Results: Histologically, all patients had severe peritonitis around the perforation sites, into which many inflammatory cells and fibroblasts had infiltrated, and reactive mesothelial cells exhibited hyperplastic change. The COX-1 protein was not detected, whereas COX-2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site. Macrophages and fibroblasts around the perforation site also revealed immunostaining for COX-2. Conclusions: Our results showed that COX-2 protein is induced in mesothelial cells, as well as in macrophages and fibroblasts, in inflamed peritoneal tissues associated with peptic ulcer perforation, suggesting involvement of COX-2 in tissue repair.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ Publishing Group  

Background - Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pylori infected patients. Aims - To analyse the relation between systemic and local humoral immune responses to H pylori urease and grades of chronic gastritis. Patients - Seventy five patients with chronic gastritis associated with H pylori infection were classified into three groups (grade I, superficial gastritis
II, atrophic gastritis, quiescent
or III, atrophic gastritis, active). Methods - Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis. Results - In the sera of patients with grade I gastritis, weak IgG but relatively strong IgA responses to H pylori urease were observed
dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy. Conclusions - Purified H pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis of H pylori infection.

DOI： 10.1136/gut.43.2.168

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器内視鏡学会 関東支部  

症例は72歳，男性。20歳頃より時折，嚥下困難を認めていた。近医にてびまん性食道痙攣（DES）と診断され経過観察していたが，2ヵ月前より症状が増悪し，6kgの体重減少を認め，精査のため入院。上部消化管内視鏡検査では特記所見なし。食道造影検査では分節状収縮と粘液の貯留を認めた。食道内圧検査ではLES静止圧28mmHg，LES弛緩不完全，静止食道内圧陽圧であり，achalasiaの所見であった。嚥下により蠕動波は出現せず，すべて多峰性同時性収縮であった。波高は40-60mmHg，durationは6秒以上であった。以上より，本症例をDESとachalasiaがオーバーラップした病態のvigorous achalasiaと診断した。nifedipine 10mg内服投与では効果がなく，内視鏡的強制噴門拡張術を施行したところ，症状は完全に消失した。本邦において5例目と極めてまれなDESからの移行が考えられたvigorous achalasiaの1例を報告する。

DOI： 10.11641/pdensks.48.0_89

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記述言語：日本語   出版者・発行元：一般社団法人 日本消化器内視鏡学会 関東支部  

We investigated whether pH and total bile acids concentration in refluxed esophageal fluid reflect those in gastric juice in patients with reflux esophagitis.<br> Thirteen patients with reflux esophagitis (8 men and 5 women ; average age : 71.3 years) were examined. Reflux esophagitis was classified according to the Savary-Miller classification. Refluxed esophageal fluid and gastric juice were collected using a novel device. The total bile acids concentration and pH in the collected samples were measured using the enzymic method and a pH meter.<br> Refluxed esophageal fluid could be collected in 1 of 4 patients with stage I reflux esophagitis and all patients with stage II and IV reflux esophagitis. More than 200µM of bile acids, which may be sufficient cause esophageal injury in acidic conditions could be obtained in the refluxed esophageal fluid. The relationship between total bile acids concentration and pH in refluxed esophageal fluid and gastric juice showed a positive correlation.<br> We concluded that bile acids are one of the major factors in the onset of reflux esophagitis. For evaluation of aggressive factors in reflux esophagitis, gastric juice can be substituted for refluxed esophageal fluid.

DOI： 10.11641/pdensks.48.0_136

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11405/nisshoshi1964.91.2202

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PubMed

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担当ページ：79-85   記述言語：日本語  

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担当ページ：25-32   記述言語：日本語  

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担当ページ：136-138  

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記述言語：英語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞はじめに-なぜ今,便秘症が注目されるのか 便秘症は日常臨床で最も多く遭遇する疾患の一つであるが,その疾患概念についてわが国では定義が定まっていなかった.2017年に日本消化器病学会関連研究会より「慢性便秘症診療ガイドライン」が発刊され,便秘の定義と分類,治療に関するエビデンスが収集され,消化器専門以外の医療従事者でも標準的な診断から治療までの見通しが可能となった.ガイドラインでは,便秘は「排出すべき糞便を十分量かつ快適に排出できない状態」と定義されている.これは疾患概念であり,問診時には次の4項目,(1)便の性状,(2)排便後の気分(残便感など),(3)排便時の気分(排便困難感など),(4)排便の頻度,を参考にするとよい(図1).患者の便秘に対する訴えは複雑であり,また複合的である.したがって臨床医は,排便回数や便の硬さなどの定型的なclosed questionにとどまらず,目の前にいる患者が,どの症状のために"便秘"であると訴えているのかを十分に聴取する必要がある.便秘治療の大きな変化として,新規治療薬の開発が挙げられる.便秘は以前より重要なcommon diseaseの一つであったが,最近まで使用できる薬剤が限られていたため,注目される疾患ではなかった.特に外科医にとっては加療の対象でなかったかもしれない.これまで治療薬としてはおもに,効果発現が早い大腸刺激性下剤であるアントラキノン系のセンノシド(プルゼニド),センナやジフェニール系のピコスルファート(ラキソベロン)などが頻用されてきたが,長期投与による効果減弱が指摘されており,患者の満足度も高くはなかった.しかし,2012年以降,新たな便秘症治療薬として,ルビプロストン(アミティーザ)が承認され,2017年にはリナクロチド(リンゼス),ナルデメジントシル酸塩(スインプロイク),2018年にエロビキシバット(グーフィス),ポリエチレングリコール(モビコール)と,新規治療薬が続々と上市されるに至った.近年登場した新薬は作用機序がそれぞれ異なり,これは,高齢者など多くの合併症をもった患者に対する薬剤処方の選択肢が大きく広がり,便秘治療にinnovationを引き起こすことを期待させる.ガイドラインが策定され,使える薬剤が増えたことで,便秘はもはや"漫然と"薬剤を使用し続ける疾患ではなくなっている.本稿では,特に新薬に着目しながら,慢性便秘症における最近の治療について述べたい.

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01539&link_issn=&doc_id=20210108600021&doc_link_id=10.11477%2Fmf.1407213249&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1407213249&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：日本語   出版者・発行元：(公社)川崎市医師会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01118&link_issn=&doc_id=20201020400006&doc_link_id=%2Fck8syokb%2F2020%2F011710%2F006%2F0876-0887%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck8syokb%2F2020%2F011710%2F006%2F0876-0887%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本潰瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語  

CiNii Books

CiNii Research

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その他リンク： https://search.jamas.or.jp/link/ui/2019369534

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2019.03.1085

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語  

CiNii Research

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その他リンク： https://search.jamas.or.jp/link/ui/2019050165

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本潰瘍学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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J-GLOBAL

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担当区分：責任著者  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：日本語   出版者・発行元：日本臨床生理学会  

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記述言語：日本語   出版者・発行元：(株)東京医学社  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

H.pylori感染率の低下、生活レベルの向上とQOL向上により、機能性消化管疾患への関心が高まっている。機能性ディスペプシア(Functional Dyspepsia:FD)は慢性的に心窩部痛、心窩部灼熱感や食後の腹部膨、早期飽満感を認め、心窩部痛症候群と食後愁訴症候群の2つのsubgroupに分類される。原因は多岐にわたり、胃適応弛緩障害や内臓知覚過敏、H.pylori感染などが考えられている。病態として十二指腸の炎症が考えられており解明が望まれている。本稿ではFDの病態や十二指腸の炎症との関連を踏まえて概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：じほう  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2017338966

記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本ヘリコバクター学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：メディカルレビュー社  

CiNii Research

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会-関東支部  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：日本語   出版者・発行元：診断と治療社  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2015340782

記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

背景および目的:内視鏡的消化性潰瘍は、非ステロイド性抗炎症薬(NSAID)に関連する消化性潰瘍合併症(顕在性の出血および穿孔)の代用マーカーとして偶発的に発見され、潰瘍合併症の疫学的調査に使用されてきた。たとえ偶発的に発見される無症候性の内視鏡的消化性潰瘍でさえ、抗血栓薬の併用が潜在性出血の原因となっているかもしれない。そこで、今回われわれは、潜在性出血を示唆する小球性貧血が、NSAIDに関連する内視鏡的消化性潰瘍または抗血栓薬の併用とどのような関連があるか検討した。方法:238人の長期NSAIDを服用する関節リウマチ患者が上部内視鏡検査を行い、その結果から抗血栓薬の併用および内視鏡的消化性潰瘍の有無のパターンの組み合わせから4つのグループに分類(抗血栓薬の併用/内視鏡的消化性潰瘍があり:+またはなし:-)した:それぞれ:A、-/-(n=165);B、-/+(n=44);C、+/-(n=25);and D、+/+(n=4)。結果:内視鏡的消化性潰瘍は、48人(20.2%)に認められた。4群間に統計学的な有意な相互作用が見られることを同定した上で、ヘモグロビン(Hb)とmean corpuscular volume(MCV)を潜在性出血の指標として、各グループ間において比較した。HbとMCVはいずれも、A、BおよびC群よりD群において有意に低値であった(Hb:それぞれP&lt;0.01;P&lt;0.05、MCV;それぞれP&lt;0.01またはP&lt;0.05)。結論:抗血栓薬を併用しかつ内視鏡的消化性潰瘍を有する長期NSAID服用者は、顕性出血のエビデンスがなくても、他の長期NSAID服用者と比べ、有意に高度な小球性貧血が認められた。たとえ無症候性の内視鏡的消化性潰瘍であったとしても、抗血栓薬併用時には、潜在性に出血すると考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高齢消化器病学会  

低用量アスピリンによる消化管出血のリスクは、非ステロイド性抗炎症薬(NSAIDs)と同等またはそれ以上と考えられ、低用量アスピリン潰瘍の予防として酸分泌抑制薬を併用する機会が増えている。筆者らの検討では、プロトンポンプ阻害薬(PPI)の併用は、従来型のNSAIDsと同様、アスピリンに関連する下部消化管出血のリスクを高める。このPPIの影響は高齢者ではなく、非高齢者において顕著であった。したがって、PPIによる消化性潰瘍予防が一般化すればするほど、低用量アスピリンによる下部消化管傷害や出血が増加する可能性がある。今後、酸分泌抑制薬の併用が、どのようにアスピリン消化管傷害および出血に影響するか、さらなる検討が必要と思われた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：科学評論社