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Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population

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World Journal of Gastroenterology 2006年第39期12卷 6361-6365页

作者： Yasuyuki Goto takafumi ando Mariko Naito Hidemi Goto Nobuyuki Hamajima Depart-ment of Preventive Medicine/Biostatistics and Medical Decision Making Nagoya University Graduate School of Medicine 65 Tsurumai-cho Showa-ku Nagoya 466-8550 Japan Department of Gastroenterology Nagoya University Graduate School of Medicine 65 Tsurumai- cho Showa-ku Nagoya 466-8550 Japan

AIM: To examine the association of inducible nitric oxide synthase (iNOS) C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity. METHODS: A single nucleotide polymorphism of iNOS C150T was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 years without a history of cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma. RESULTS: The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio (OR) of the C/T + T/T for gastric cancer was increased without statistical significance (OR=1.19, 95% confidence interval (CI): 0.68-2.08). In the differentiated subgroup (n = 113), however, the OR of the C/T genotype for gastric cancer was significant (OR = 2.02, 95% CI: 1.04-3.92) relative to the C/C genotype. In addition, considering the location of gastric cancer (n = 105), there were significant differences between the controls and non-cardia group with the OR of 2.13 (95% CI: 1.08-4.18) for C/T and 1.94 (95% CI: 1.00-3.78) for C/T + T/T. CONCLUSION: The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancerin a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

关键词：一氧化氮基因多态性胃癌幽门螺杆菌

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

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World Journal of Gastroenterology 2007年第5期13卷 754-760页

作者： Masaaki Minami Michio Ohta Teruko Ohkura takafumi ando Naoki Ohmiya Yasumasa Niwa Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine 65 Tsurumai-cho Showa-ku Nagoya 466-8550 Japan Department of Bacteriology Nagoya University Graduate School of Medicine 65 Tsurumai-cho Showa-ku Nagoya 466-8550 Japan

AIM: To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC).METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9) enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%). There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION: Our results suggest that active CMVinfection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immuno-suppressive therapy.

关键词：巨细胞病毒感染重症溃疡性大肠炎环孢霉素A 静脉内注射治疗

Causal role of Helicobacter pylori infection in gastric cancer

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World Journal of Gastroenterology 2006年第2期12卷 181-186页

作者： takafumi ando Yasuyuki Goto Osamu Maeda Osamu Watanabe Kazuhiro Ishiguro Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of MedicineJapan

胃的癌症是在世界，为在亚洲的所有癌症盒子的一个大比例的财务，拉丁美洲，和在欧洲的一些国家上的第二很经常的癌症。Helicobacter pylori (H pylori ) 被认为是在萎缩性胃炎的发展起一个特定的作用，它多代表最公认的小径在走肠类型... 详细信息

胃的癌症是在世界，为在亚洲的所有癌症盒子的一个大比例的财务，拉丁美洲，和在欧洲的一些国家上的第二很经常的癌症。Helicobacter pylori (H pylori ) 被认为是在萎缩性胃炎的发展起一个特定的作用，它多代表最公认的小径在走肠类型的胃的致癌作用。最近的研究建议那联合招待基因因素，细菌的毒力因素，并且环境并且生活方式因素决定胃的损坏和 H pylori 感染的最终的临床的结果的严厉。胃的癌症的领先的原因应该导致有效根除策略的 H pylori 的精液的发现。胃的癌症的预防要求更好屏蔽的策略为根除识别候选人。

关键词：胃癌宿主遗传因素细菌毒力因素幽门螺旋杆菌病理

Clinical utility of a new endoscopic scoring system for Crohn's disease

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World Journal of Gastroenterology 2015年第34期21卷 9974-9981页

作者： Kazuhiro Morise takafumi ando Osamu Watanabe Masanao Nakamura Ryoji Miyahara Osamu Maeda Kazuhiro Ishiguro Yoshiki Hirooka Hidemi Goto Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine Department of Endoscopy Nagoya University Hospital

AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group, 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating

关键词： Crohn’s disease Modified Simple Endoscopic Score M

Value of colonoscopy for prediction of prognosis in patients with ulcerative colitis

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World Journal of Gastroenterology 2008年第14期14卷 2133-2138页

作者： takafumi ando Yuji Nishio Osamu Watanabe Hironao Takahashi Osamu Maeda Kazuhiro Ishiguro Daisuke Ishikawa Naoki Ohmiya Yasumasa Niwa Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya 4668550 Japan Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya 4668550 Japan Department of Gastroenterology Meitetsu Hospital Nagoya 4518511 Japan

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. Some UC patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side-effects. Recently, cyclosporine and leukocyte removal therapy have been used for refractory UC patients. To predict the efficacy of these therapies is important for appropriate selection of treatment options and for preparation for colectomy. Endoscopy is the cornerstone for diagnosis and evaluation of UC. Endoscopic parameters in patients with severe or refractory UC may predict a clinical response to therapies, such as cyclosporine or leukocyte removal therapy. As for the patients with quiescent UC, relapse of UC is difficult to predict by routine colonoscopy. Even when routine colonoscopy suggests remission and a normal mucosal appearance, microscopic abnormalities may persist and relapse may occur later. To more accurately identify disease activity and to predict exacerbations in UC patients with clinically inactive disease is important for deciding whether medical treatment should be maintained. Magnifying colonoscopy is useful for the evaluation of disease activity and for predicting relapse in patients with UC.

关键词：结肠镜检查疾病预防溃疡性结肠炎临床表现治疗方法

Magnifying chromoscopy, a novel and useful technique for colonoscopy in ulcerative colitis

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World Journal of Gastroenterology 2007年第18期13卷 2523-2528页

作者： takafumi ando Hironao Takahashi Osamu Watanabe Osamu Maeda Kazuhiro Ishiguro Daisuke Ishikawa Motofusa Hasegawa Naoki Ohmiya Yasumasa Niwa Hidemi Goto Naoki Ohmiya Yasumasa Niwa Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya Japan

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. The degree of inflammation as assessed by conventional colonoscopy is a reliable parameter of disease activity. However, even when conventional colonoscopy suggests remission and normal mucosal findings, microscopic abnormalities may persist, and relapse may occur later. Patients with long-standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. Ulcerative colitis-associated colorectal cancer is characterized by an early age at onset, poorly differentiated tumor cells, mucinous carcinoma, and multiple lesions. Early detection of dysplasia and colitic cancer is thus a prerequisite for survival. A relatively new method, magnifying chromoscopy, is thought to be useful for the early detection and diagnosis of dysplasia and colitic cancer, as well as the prediction of relapse.

关键词：溃疡性结肠炎放大彩色显象管结肠镜检查应用

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization

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World Journal of Gastroenterology 2005年第40期11卷 6305-6311页

作者： Tomokazu Mizuno takafumi ando Kazuo Nobata Tomoyuki Tsuzuki Osamu Maeda Osamu Watanabe Masaaki Minami Kenji Ina Kazuo Kusugami Richard M. Peek Hidemi Goto Department of Gastroenterology Division of Gastroenterology

AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 μg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori(H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26 695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P<0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1356 pg/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P<0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r= 0.62, P<0.0001; antrum: r = 0.61, P<0.0001) in GU patients. RhIL-17 and H pylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17

关键词：白细胞介素-17 胃黏膜幽门螺杆菌消化疾病

Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis

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World Journal of Gastroenterology 2015年第1期21卷 254-261页

作者： Nobuyuki Miyake takafumi ando Kazuhiro Ishiguro Osamu Maeda Osamu Watanabe Yutaka Hirayama Keiko Maeda Kazuhiro Morise Masanobu Matsushita Kazuhiro Furukawa Kohei Funasaka Masanao Nakamura Ryoji Miyahara Naoki Ohmiya Hidemi Goto Department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineNagoya CityAichi 466-8550Japan Department of Gastroenterology Fujita Health University School of MedicineToyoakeAichi 470-1192Japan

AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion.All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy.Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL.Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score,with a reduction of ≥ 5 considered to indicate a response.Among responders,we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine.Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex,age,disease duration,clinical activity index score,C-reactive protein level,hemoglobin level,disease extent,endoscopic findings,and clinical course.RESULTS: Cyclosporine was not discontinued due to side effects in any patient.Nineteen(65.5%) of 29 patients were considered responders.A statistically significant(P = 0.004) inverseas sociation wa s observed between an endoscopic finding of "mucosal bleeding" and responsive cases.Fifteen(9 males,6 females) of these 19 patients were followed for 5 years or more,of whom 9(60%) exhibited long-termefficacy of cyclosporine.Of the 10 non-responders,9(90%) underwent surgery within 6 mo of cyclosporine therapy.None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex,age,duration of disease,clinical activity index score,C-reactive protein level,hemoglobin level,extent of disease,endoscopic findings,or clinical course.In contrast,a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy(P = 0.0014).

关键词： Ulcerative colitis Cyclosporine Maintenance therap

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

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World Journal of Gastrointestinal Endoscopy 2016年第6期8卷 301-309页

作者： Yutaka Hirayama takafumi ando Yoshiki Hirooka Osamu Watanabe Ryoji Miyahara Masanao Nakamura Takeshi Yamamura Hidemi Goto Department of Gastroenterology and Hepatolgy Nagoya University Graduate School of Medicine Department of Endoscopy Nagoya University Hospital

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.

关键词： Colonoscopy Risk factor Ulcerative colitis Antigenemia Cytomegalovirus