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World Journal of Gastroenterology 2014年第21期20卷 6400-6411页

作者： mitsushige sugimoto Takahisa Furuta First Department of Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Center for Clinical Research Hamamatsu University School of MedicineHamamatsu 431-3192Japan

The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.

关键词： Helicobacter pylori Tailored eradication therapy Proton pomp inhibitor Cytochrome P450 2C19 Clarithromycin

Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer

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World Journal of Gastroenterology 2010年第10期16卷 1188-1200页

作者： mitsushige sugimoto Yoshio Yamaoka Takahisa Furuta Center for Clinical Research Hamamatsu University School of Medicine Department of Environmental and Preventive Medicine Faculty of MedicineOita University

Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL

关键词： Helicobacter pylori Cytokines Genetic polymorphism Stomach neoplasms Peptic ulcer

Nutrition status and Helicobacter pylori infection in patients receiving hemodialysis

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World Journal of Gastroenterology 2018年第15期24卷 1591-1600页

作者： mitsushige sugimoto Hideo Yasuda Akira Andoh Division of Digestive Endoscopy Shiga University of Medical Science Hospital First Department of Medicine Hamamatsu University School of Medicine Department of Gastroenterology Shiga University of Medical Science Hospital

Chronic kidney disease(CKD) patients receiving hemodialysis(HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting(PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori(H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mildto-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.

关键词： Helicobacter pylori Hemodialysis Ghrelin Gastric mucosa Anti-bacterial agents

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

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World Journal of Gastroenterology 2023年第19期29卷 2916-2931页

作者： mitsushige sugimoto Masaki Murata Takashi Kawai Department of Gastroenterological Endoscopy Tokyo Medical University HospitalTokyo 160-0023Japan Department of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 612-8555Japan

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal *** rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD *** fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving ***,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical *** that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

关键词： Direct oral anticoagulants Gastrointestinal tumors Endoscopic submucosal dissection Delayed bleeding Adverse events Anticoagulants

Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population:Meta-analysis

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World Journal of Gastroenterology 2020年第15期26卷 1820-1840页

作者： mitsushige sugimoto Masaki Murata Yoshio Yamaoka Department of Gastroenterological Endoscopy Tokyo Medical University HospitalSinjukuTokyo 1600023Japan Department of Gastroenterology National Hospital Organization Kyoto Medical CenterKyoto 6128555Japan Department of Gastroenterology Department of Environmental and Preventive MedicineOita University Faculty of MedicineYufuOita 8795593Japan

BACKGROUND Helicobacter pylori(***)infection is a risk factor for gastric cancer(GC),especially in East Asian *** East Asian populations infected with *** are at higher risk for GC than ***-positive European and United States *** eradication therapy reduces gastric cancer risk in patients after endoscopic and operative resection for GC,as well as in non-GC patients with atrophic *** To clarify the chemopreventive effects of *** eradication therapy in an East Asian population with a high incidence of *** PubMed and the Cochrane library were searched for randomized control trials(RCTs)and cohort studies published in English up to March *** analyses were conducted with regard to study designs(i.e.,RCTs or cohort studies),country where the study was conducted(i.e.,Japan,China,and South Korea),and observation periods(i.e.,≤5 years and>5 years).The heterogeneity and publication bias were also *** For non-GC patients with atrophic gastritis and patients after resection for GC,4 and 4 RCTs and 12 and 18 cohort studies were included,*** RCTs,the median incidence of GC for the untreated control groups and the treatment groups was 272.7(180.4–322.4)and 162.3(72.5–588.2)per 100000 person-years in non-GC cases with atrophic gastritis and 1790.7(406.5–2941.2)and 1126.2(678.7–1223.1)per 100000 person-years in cases of after resection for *** with non-treated ***-positive controls,the eradication groups had a significantly reduced risk of GC,with a relative risk of 0.67[95%confidence interval(CI):0.47–0.96]for non-GC patients with atrophic gastritis and 0.51(0.36–0.73)for patients after resection for GC in the RCTs,and 0.39(0.30–0.51)for patients with gastritis and 0.54(0.44–0.67)for patients after resection in cohort *** In the East Asian population with a high risk of GC,*** eradication effectively reduced the risk of GC,irrespective of past histo

关键词： Helicobacter pylori Eradication therapy Gastric cancer Metachronous cancer East Asia Prevention

Lymphomatoidgastropathy mimicking extranodal NK/T cell lymphoma,nasal type:A case report

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World Journal of Gastroenterology 2012年第17期18卷 2140-2144页

作者： Tomohiro Terai mitsushige sugimoto Hiroki Uozaki Tetsushi Kitagawa Mana Kinoshita Satoshi Baba Takanori Yamada Satoshi Osawa Ken sugimoto First Department of Medicine Hamamatsu University School of MedicineHamamatsu 431-3192Japan Seirei Health Care Division Seirei Preventive Health Care CenterHamamatsu 431-3192Japan Department of Diagnostic Pathology Hamamatsu University School of MedicineHamamatsu 431-3192Japan

Extranodal natural killer(NK)/T-cell lymphoma,nasal type,exhibits aggressive tumor behavior and carries a poor ***,lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without *** the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type,it is difficult to distinguish between the two conditions by histopathological evaluation ***,we report a rare case of lymphomatoid gastropathy in a 57-year-old *** on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and *** repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments,at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and *** examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3+,CD4-,CD5-,CD7+,CD8-,CD20-,CD30-,CD56+,CD79a-and T-cell-restricted intracellular antigen-1+ into gastric *** treatment for Helicobacter pylori(***) eradication,the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 ***,we report a case of ***-positive lymphomatoid gastropathy with massive NK-cell proliferation,and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal *** any case,these lesions are evaluated with biopsy specimens,the possibility of this benign entity should be considered,and excessive treatment should be carefully *** follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.

关键词： Gastric lymphomatoid gastropathy Gastric natural killer/T-cell lymphoma nasal type Helicobacter pylori Eradication

Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

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World Journal of Gastroenterology 2011年第14期17卷 1858-1865页

作者： mitsushige sugimoto Masafumi Nishino Chise Kodaira Mihoko Yamade Takahiro Uotani Mutsuhiro Ikuma Kazuo Umemura Takahisa Furuta Center for Clinical Research Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan First Department of Medicine Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan Department of Pharmacology Hamamatsu University School of MedicineShizuoka Hamamatsu 431-3192Japan

AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

关键词： Non-erosive reflux disease Rabeprazole CYP2C19

Relationship between ghrelin, Helicobacter pylori and gastric mucosal atrophy in hemodialysis patients

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World Journal of Gastroenterology 2016年第47期22卷 10440-10449页

作者： Hitomi Ichikawa mitsushige sugimoto Yukitoshi Sakao Shu Sahara Naro Ohashi Akihiko Kato Ken sugimoto Takahisa Furuta Akira Andoh Tadashi Sakao Hideo Yasuda First Department of Medicine Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Division of Digestive Endoscopy Shiga University of Medical Science Hospital Otsu Shiga 520-2192 Japan Hamana Clinic Hamana Clinic Hamamatsu Shizuoka 434-0037 Japan Blood Purification Unit Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Center for Clinical Research Hamamatsu University School of Medicine Hamamastsu Shizuoka 431-3192 Japan Department of Gastroenterology Shiga University of Medical Science HospitalOtsu Shiga 520-2192 Japan

AIM To investigate the relationship between plasma ghrelin level, Helicobacter pylori(H. pylori) infection status and the severity of atrophy in hemodialysis *** One hundred eights patients who received hemodialysis and 13 non-hemodialysis H. pylori-negative controlsunderwent gastroduodenoscopy to evaluate the severity of gastric atrophy. Serum levels of pepsinogen(PG) were measured as serum markers of gastric atrophy. H. pylori infection was evaluated by anti-H. pylori IgG antibody, rapid urease test and culture test. We classified H. pylori infection status as non-infection, present infection and past infection. In addition, plasma acyl-ghrelin and desacyl-ghrelin levels were measured by enzyme-linked immunosorbent assay. RESULTS Infection rate of H. pylori was 45.4%(49/108). Acylghrelin level in the non-infection group(39.4 ± 23.0 fmol/ml) was significantly higher than in the past(23.4 ± 19.9 fmol/ml, P = 0.005) and present infection groups(19.5 ± 14.0 fmol/ml, P < 0.001). Furthermore, desacyl-ghrelin level in the non-infection group(353.2 ± 190.2 fmol/ml) was significantly higher than those in the past(234.9 ± 137.5 fmol/ml, P = 0.008) and present infection groups(211.8 ± 124.2 fmol/ml, P < 0.001). Acyl-ghrelin was positively correlated with the PG Ⅰ level and PG Ⅰ/Ⅱ ratio(|R| = 0.484, P < 0.001 and |R| = 0.403, P < 0.001, respectively). Both ghrelins were significantly decreased in accordance with the progress of endoscopic atrophy(both P < 0.001) and acyl-ghrelin was significantly lower in patients with mild, moderate and severe atrophy(24.5 ± 23.1 fmol/ml, 20.2 ± 14.9 fmol/ml and 18.3 ± 11.8 fmol/ml) than in those with non-atrophy(39.4 ± 22.2 fmol/ml, P = 0.039, P = 0.002 and P < 0.001, respectively).CONCLUSION In hemodialysis patients, plasma ghrelin level was associated with the endoscopic and serological severity of atrophy related to H. pylori infection.

关键词： Acyl-ghrelin Desacyl-ghrelin Helicobacter pylori Hemodialysis Pepsinogen

Efficacy of additional treatment with azathioprine in a patient with prednisolone-dependent gastric sarcoidosis

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World Journal of Gastroenterology 2016年第47期22卷 10471-10476页

作者： Masaki Murata mitsushige sugimoto Yoshihiro Yokota Hiromitsu Ban Osamu Inatomi Shigeki Bamba Ryoji Kushima Akira Andoh Department of Gastroenterology Shiga University of Medical Science Hospital Division of Digestive Endoscopy Shiga University of Medical Science Hospital Department of Clinical Laboratory Medicine Shiga University of Medical Science Hospital

Gastric sarcoidosis with noncaseating granuloma is rare. Although corticosteroid produces a dramatic clinical response, it is unknown whether azathioprine show efficacy in prednisolone-dependent cases. Here, we report a case of gastric sarcoidosis in a 25-year-old man with severe epigastlargia. Gastroendoscopy revealed multiple map-like ulcerations. Histological examination showed multiple noncaseating granulomatous lesions in gastric mucosa, which were incompatible with diagnoses of Crohn's disease or tuberculosis. He was started on prednisolone at 30 mg/d, and his symptoms improved within 7-d. The prednisolone was gradually tapered by 5 mg every 2-wk, but oral azathioprine at 50 mg was added after symptoms recurred at tapered dose of 10 mg. Endoscopy 4-wk later showed healing ulcers, and, lymphocytic infiltration was absent. The efficacy of additional azathioprine in gastric sarcoidosis is not well defined. Here, we report a case of prednisolone-dependent gastric sarcoidosis that improved after additional azathioprine, and also review the literature concerning the treatment, especially for prednisolone-dependent cases.

关键词： Azathioprine Granulomatous inflammation Prednisolone Gastric sarcoidosis Helicobacter pylori

Usefulness of the clip-flap method of endoscopic submucosal dissection: A randomized controlled trial

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World Journal of Gastroenterology 2018年第35期24卷 4077-4085页

作者： Hiromitsu Ban mitsushige sugimoto Taketo Otsuka Masaki Murata Toshiro Nakata Hiroshi Hasegawa Osamu Inatomi Shigeki Bamba Akira Andoh Division of Digestive Endoscopy Shiga University of Medical Science Hospital Department of Gastroenterology Shiga University of Medical Science Hospital Division of Clinical Nutrition Shiga University of Medical Science Hospital

AIM To prospectively investigate the efficacy and safety of clipflap assisted endoscopic submucosal dissection(ESD) for gastric *** From May 2015 to October 2016, we enrolled 104 patients with gastric cancer or adenoma scheduled for ESD at Shiga University of Medical Science Hospital. We randomized patients into two subgroups using the minimization method based on location of the tumor(upper, middle or lower third of the stomach), tumor size( 20 mm) and ulcer status: ESD using an endoclip(the clip-flap group) and ESD without an endoclip(the conventional group). Therapeutic efficacy(procedure time) and safety(complication: Gastrointestinal bleeding and perforation) were assessed. RESULTS En bloc resection was performed in all patients. Four patients had delayed bleeding(3.8%) and two had perforation(1.9%). No significant differences in en bloc resection rate(conventional group: 100%, clip flap group: 100%), curative endoscopic resection rate(conventional group: 90.9%, clip flap group: 89.8%, P = 0.85), procedure time(conventional group: 70.8 ± 46.2 min, clip flap group: 74.7 ± 53.3 min, P = 0.69), area of resected specimen(conventional group: 884.6 ± 792.1 mm^2, clip flap group: 1006.4 ± 1004.8 mm^2, P = 0.49), delayed bleeding rate(conventional group: 5.5%, clip flap group: 2.0%, P = 0.49), or perforation rate(conventional group: 1.8%, clip flap group: 2.0%, P = 0.93) were found between the two groups. Lessexperienced endoscopists did not show any differences in procedure time between the two *** For patients with early-stage gastric tumors, the clipflap method has no advantage in efficacy or safety compared with the conventional method.

关键词： Gastric cancer Clip flap method Endoscopic submucosal dissection Procedure time Complication Randomized clinical trial