Pinjin Hu

Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies.

Background: Fecal calprotectin (FC) is a relatively new marker of intestinal inflammation. Recently, many studies have extended its role in predicting relapse of quiescent inflammatory bowel disease (IBD), but the reported results have been inconsistent. We aimed to perform a meta‐analysis of the predictive capacity of FC in IBD relapse. Methods: We systematically searched the Medline, Web of Science, Cochrane Library, and EMBASE databases for prospective studies that used FC concentrations at remission in predicting relapse of Crohns disease (CD) and ulcerative colitis (UC). Pooled sensitivity, specificity, and other diagnostic indices were evaluated. Results: A total of 672 IBD patients (318 UC and 354 CD) from six different studies were analyzed. The pooled sensitivity and specificity of FC to predict relapse of quiescent IBD was 78% (95% confidence interval [CI]: 72–83) and 73% (95% CI: 68–77), respectively. The area under the summary receiver‐operating characteristic (sROC) curve was 0.83 and the diagnostic odds ratio was 10.31 (95% CI: 5.05–21.06). The capacity of FC to predict relapse was comparable between UC and CD. In CD patients the predictive value of FC in isolated small bowel CD was not assessed due to insufficiency of available data. Compared with all enrolled CD patients, FC appeared to be more accurate in ileocolonic and colonic CD. Conclusions: As a simple and noninvasive marker, FC is useful to predict relapse in quiescent IBD patients. (Inflamm Bowel Dis 2012)

Chemoprevention of gastric cancer by celecoxib in rats

Background: Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis. Aim: We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis. Methods: Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG 100 μg/ml) (n = 16); group C, indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17); group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day) (n = 16). Group B–F animals were treated with 10% sodium chloride (in the initial six weeks) and MNNG in drinking water to induce adenocarinoma in the stomach. All animals received treatment for 40 weeks, and were sacrificed after death or at 48 weeks. Gastric neoplasm was evaluated by histology. Results: The incidences of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume (2.4 v 2805 mm3; p = 0.02). Although tumours had significantly higher COX-2 expression than their adjacent normal tissues (p<0.02), there was no significant difference in COX-2 levels among tumours in the different treatment groups. The lowest tumour prostaglandin E2 level was found in the indomethacin treated group, suggesting that the chemopreventive effect of celecoxib may be mediated by a COX independent pathway. Conclusion: While treatment with indomethacin had no significant effect on tumour development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

Objective The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. Design 442 incident cases (186 Crohns disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. Results In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. Conclusions This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

A Low Rate of Reinfection Following Effective Therapy Against Helicobacter pylori in a Developing Nation (China)

BACKGROUND & AIMS In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. The aim of this study was to determine the rate of reinfection and ulcer recurrence in Chinese patients cured of H. pylori and duodenal ulcer disease. METHODS One hundred eighty-four patients with duodenal ulcer disease shown by endoscopic examination (1 month) and 14C-urea breath test (3 months) after termination of treatment to have cleared their H. pylori were investigated. Patients were followed up by endoscopy (12 and 24 months) and breath test (6, 9, 12, 18, and 24 months). H. pylori status at endoscopic examination was determined by rapid urease, histology, and culture. In reinfected patients, random amplification of polymorphic DNA fingerprinting was used to compare isolates before and after therapy. RESULTS Four patients were reinfected with H. pylori over 24 months (3 within 6 months and 1 at 24 months; average annual recurrence rate, 1.08%). Fingerprinting of isolates from 3 patients showed 1 patient (6 months) to have identical strains and the remainder to have nonidentical strains before and after treatment. Ulcer relapse occurred in 6 patients (4 H. pylori positive). CONCLUSIONS Reinfection with H. pylori is rare in developing countries where treatment is effective.

Association between polymorphisms in interleukin‐17A and interleukin‐17F genes and risks of gastric cancer

Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori‐induced gastric cancer. Interleukin (IL)‐17A and IL‐17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case–control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL‐17A G197A and IL‐17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and DNA sequencing. Logistic regression and Cox‐proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL‐17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22–1.87 for GA; OR 1.61, 95% CI: 1.03–2.51 for GG]. Further stratification analyses indicated that the effect of IL‐17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL‐17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40–65‐year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL‐17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL‐17A 197 may be less relevant.

Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study.

The incidence of inflammatory bowel disease (IBD) is increasing in China with urbanization and socioeconomic development. There is however a lack of prospective, population‐based epidemiology study on IBD in China. The aim of the study is to define the incidence and clinical characteristics of IBD in a developed region of Guangdong Province in China.

Immunisation against gastric infection with Helicobacter species: First step in the prophylaxis of gastric cancer?

The discovery of the gastric bacterium, Helicobacter pylori and the demonstration of its role in the pathogenesis of gastroduodenal disease, has been one of the major microbiological advances in the last decade. Recent demonstration of long term infection with this bacterium as a risk factor in gastric carcinoma suggests that intervention in a disease of major morbidity and mortality is possible. Using a model of Helicobacter infection in mice it has been shown that oral immunisation with a sonicate of Helicobacter felis plus the adjuvant cholera toxin results in protection against an oral challenge with large numbers of viable bacteria. The success of the immunising regimen has been shown to correlate with the development of local immunity. Formulation of equivalent safe vaccines of H. pylori will make possible the immunisation of children in countries such as China, Japan and Columbia and so prevent the establishment of long term inflammation and thus significantly reduce the incidence of gastric cancer in those societies. This animal model is proposed as a major tool in the development of effective oral immunisation.

Association of interleukin-17F 7488 single nucleotide polymorphism and inflammatory bowel disease in the Chinese population.

Objective. The functional polymorphism of interleukin (IL)-17F 7488 A > G was found to be associated with autoimmune inflammatory diseases and also high IL-17F intestinal expression in inflammatory bowel disease (IBD) was detected. The purpose of this study was to investigate the association between the polymorphism and IBD in the Chinese population and to elucidate potential interactions between IL-17F genotypes and clinical phenotypes. Material and methods. DNA was extracted from peripheral blood cells of 148 ulcerative colitis (UC), 134 Crohns disease (CD) patients and 373 age- and gender-matched healthy controls. The IL-17F 7488 A > G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Results. In UC patients, the homozygous GG genotype frequency was significantly lower than that in the controls (0.0% versus 3.8%, p=0.014); Compared to that of wild-type AA patients, the AG heterozygous carriers have a later onset (43.3±11.1 years versus 34.6±14.8 years, p = 0.012) and a significantly higher incidence of mild severity (94.1% versus 61.0%, p = 0.009, OR = 0.96, 95% CI = 0.94–0.96), respectively, indicating that subjects with the GG genotype have a slightly decreased risk of 0.96 times for UC compared with that of other genotypes. Further analysis also revealed that G carrier subjects were more likely to present mild severity and had 10.2 times higher incidence of getting mild severity than those with AA genotype (OR = 10.2, 95% CI = 1.3–81.0). Conclusions. This study shows that IL-17F 7488 A > G polymorphism is associated with weak UC protection in the Chinese population. The clinical phenotypes of UC are also affected by this polymorphism.

The prevalence of antibody to CagA in children is not a marker for specific disease

BACKGROUND In adults, a high prevalence of antibody to the cytotoxin-associated antigen (CagA) of Helicobacter pylori has been linked to the development of more serious gastroduodenal disease. Few investigators have examined this association in children. The purpose of this study was to investigate the seroprevalence of antibody to the CagA antigen as well as other specific H. pylori antigens in children. METHODS By use of an immunoblot analysis kit, the immune response to specific H. pylori antigens in serum collected from 21 H. pylori-positive symptomatic Australian children, 5 with peptic ulcer disease and 16 with nonulcer dyspepsia, and 33 H. pylori-positive asymptomatic Chinese children. Sera from 20 H. pylori-negative symptomatic Australian children were used as control subjects. RESULTS Antibody responses to the 26.5-kDa, 30-kDa, and 116-kDa (CagA) antigens were found to be the most prevalent, with 81.5%, 79.6%, and 76% of children, respectively, mounting a response. In contrast, antibody responses to the 19.5-kDa, 35-kDa, 45-kDa, 60-kDa, 89 kDa (VacA), and 180-kDa antigens occurred in 55.5%, 24%, 16.7%, 63%, 37%, and 7.4% of children, respectively. A higher prevalence of antibody response to CagA was found in the symptomatic Australian children with peptic ulcer disease (100%) compared with prevalence in those with nonulcer dyspepsia (56.3%), but the difference did not reach statistical significance. No significant difference was found between the prevalence of antibody to CagA in the Australian peptic ulcer disease group (100%) and that in the asymptomatic Chinese children (81.8%). CONCLUSION These results suggest that in children CagA is not a marker of specific disease development.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia

BACKGROUND & AIMS The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohns and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohns disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.