Causal role of Helicobacter pylori infection in gastric cancer

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。

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

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

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 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

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

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.

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

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.

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

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).CONCLUSION: Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.

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

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.

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

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,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 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 the risk of surgery-free survival in patients with CD.

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

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.