Jan van den Brande

Endoscopic trimodal imaging detects colonic neoplasia as well as standard video endoscopy.

BACKGROUND & AIMS Endoscopic trimodal imaging (ETMI) is a novel endoscopic technique that combines high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) that has only been studied in academic settings. We performed a randomized, controlled trial in a nonacademic setting to compare ETMI with standard video endoscopy (SVE) in the detection and differentiation of colorectal lesions. METHODS The study included 234 patients scheduled to receive colonoscopy who were randomly assigned to undergo a colonoscopy in tandem with either ETMI or SVE. In the ETMI group (n=118), first examination was performed using HRE, followed by AFI. In the other group, both examinations were performed using SVE (n=116). In the ETMI group, detected lesions were differentiated using AFI and NBI. RESULTS In the ETMI group, 87 adenomas were detected in the first examination (with HRE), and then 34 adenomas were detected during second inspection (with AFI). In the SVE group, 79 adenomas were detected during the first inspection, and then 33 adenomas were detected during the second inspection. Adenoma detection rates did not differ significantly between the 2 groups (ETMI: 1.03 vs SVE: 0.97, P=.360). The adenoma miss-rate was 29% for HRE and 28% for SVE. The sensitivity, specificity, and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87%, 63%, and 75%, respectively; corresponding values for AFI were 90%, 37%, and 62%, respectively. CONCLUSIONS In a nonacademic setting, ETMI did not improve the detection rate for adenomas compared with SVE. NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificity.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

Background & Aims Barretts esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barretts and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. Methods We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. Results We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9). Conclusions We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Binding of Somatomedin-A and -C, NSILA-S and Insulin to Human Placental Cell Membranes

Binding of labeled SM-A, SM-C, NSILA-S and insulin to human placental cell membranes was studied in trying to answer the question how many receptor populations were involved using one single organ system. The data suggest that all labeled SM-like substances bind to closely related if not identical receptor populations. The binding is reduced by very low concentrations of SM-like material and only by very high concentrations of insulin. In contrast, as already known from the literature, 125I-insulin binds mostly to a different receptor population, which is sensitive both to insulin and SM-like substances.Furthermore, the data indicate that 125I-SM-A and 125I-SM-C, in addition to binding to similar or identical receptors, also bind to separate receptor populations, suggesting that the labels are composed of more than one component.

Su1313 Epidemiology and Characteristics of Inflammatory Bowel Disease in a Large Population-Based Cohort in the Netherlands

Background and aims: The epidemiology of inflammatory bowel disease (IBD) is changing. In Europe, recent incidence and prevalence rates are lacking. The primary objective of this study is to update incidence and prevalence figures in a large well-phenotyped populationbased IBD cohort.Methods: All IBD patients living in the adherence area of 2 non-academic hospitals between 20042010 were identified. Patients were searched in 3 independent hospital databases case finding sources. 1378 Possible IBD cases were scrutinized, IBD diagnosis was based on established clinical, endoscopic and pathologic criteria. Location and behaviour of IBD was reported according to the Montreal classification. Results: 768 IBD patients were included. 255 (33.2%) patients were diagnosed with Crohns disease (CD), 432 (56.3%) with ulcerative colitis (UC) and 81 (10.5%) with IBD-Unspecified (IBDU). The male-female ratio of IBD was 1:1.3 (P<0.001). The mean incidence for IBD was 28.0 per 100,000 inhabitants per year; 7.4 for CD, 17.4 for UC and 3.3 for IBD-U. The point prevalence on 01-01-2009 was 345.7 per 100,000 inhabitants; 113.3 for CD, 194.8 for UC and 37.6 for IBD-U. A peak in the mean age-specific incidence for CD was found at the age of 2125 years. For UC 3 peaks were found at the age of 2125, 5155, and 6165 years. In CD, 64 patients (25%) had ileitis without colitis, 91 patients (35.7%) had a colitis, 86 patients (33.7%) had an ileocolitis. 14 Patients (5.5%) had upper GI involvement. Nonstricturing, nonpenetrating behaviour of CD was found in 139 patients (54.5%), stricturing, nonpenetrating was found in 59 (23.1%) patients, penetrating was found in 53 (20.8%) patients. 118 UC patients (27.3%) had a proctitis, 189 patients (43.8%) a left-sided colitis and 124 patients (28.7%) a pancolitis. Male patients had a more extensive UC than female patients (P= 0.003). Conclusion: The population based incidence for IBD was: 28.0 per 100,000 inhabitants per year, with a point prevalence of 345.7 per 100,000 inhabitants. In UC, male patients have a more extensive colitis than female patients.

Methotrexate therapy for Crohns disease: long-term efficacy and safety

pide enema therapy (150 nrg rebamipide in 60 ml saline containing 1.5 % carboxymethylcellulose, twice a day) tot 20 days, during which the doses of predrnsolone were kept constant. Resuhs: When cdonic T84 ceils were stimulated with intiammatory cytokines, rebamipide suppressed the production o{ IL-1 [3 at the concemration ranges of 1-100 p.g/ml. In comrast, prednisolone (0.1 to 10 ~g/ml) and 5-ASA (0.1 to 10 lag/ml) did not show a W inhibitory eft~:cts on cytokine production by epithelial cells. In the experiments of wound repair, addition of reba mipide (1-100 tag/mI) recovered the delay o[ epithelial cell restitution induced by hydroxyperoxide. Clinically, at 20 days after rebamipide therapy, thirteen patients (93%/showed an improvement in clinical symptoms and QOL scores, an d 10 (71%) were judged to be colonoscopically responders with decreases in 1L-113 contents in organ cultures of mucosaI tissues and their histological activity of inflammation. No significant side effects were observed after recta} rebamipide administration Conclusions: The effects of rebamipide on cytokme production and restitution by epithelial cells may be related to clinical efficacy of its enema therapy in UC patients..