Davor Radić

NOD2/CARD15 mutations in Croatian patients with Crohn's disease : prevalence and genotype-phenotype relationship

Background Crohns disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohns patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohns disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P=0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P=0.041, P=0.162, P=0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.

A pilot study of transrectal endoscopic ultrasound elastography in inflammatory bowel disease

BackgroundUsing standard diagnostic algorithms it is not always possible to establish the correct phenotype of inflammatory bowel disease which is essential for therapeutical decisions. Endoscopic ultrasound elastography is a new endoscopic procedure which can differentiate the stiffness of normal and pathological tissue by ultrasound. Therefore, we aimed to investigate the role of transrectal ultrasound elastography in distiction between Crohns disease and ulcerative colitis.MethodsA total 30 Crohns disease, 25 ulcerative colitis, and 28 non-inflammatory bowel disease controls were included. Transrectal ultrasound elastography was performed in all patients and controls. In all ulcerative coltis patients and 80% of Crohns disease patients endoscopy was performed to assess disease activity in the rectum.ResultsSignificant difference in rectal wall thickness and strain ratio was detected between patients with Crohns disease and controls (p = 0.0001). CD patients with active disease had higher strain ratio than patients in remission (p = 0.02). In ulcerative colitis group a significant difference in rectal wall thickness was found between controls and patients with active disease (p = 0.03). A significant difference in rectal wall thickness (p = 0.02) and strain ratio (p = 0.0001) was detected between Crohns disease and ulcerative colitis patient group. Crohns disease patients with active disease had a significantly higher strain ratio compared to ulcerative colitis patients with active disease (p = 0.0001).ConclusionTransrectal ultrasound elastography seems to be a promising new diagnostic tool in the field of inflammatory bowel disease. Further study on a larger cohort of patients is needed to definitely assess the role of transrectal ultrasound elastography in inflammatory bowel disease.

Endoscopic ultrasound elastography as a method for screening the patients with suspected primary sclerosing cholangitis.

Objectives Currently, magnetic resonance cholangiography is being used for establishing the diagnosis of primary sclerosing cholangitis, whereas endoscopic retrograde cholangiography is reserved for therapeutic interventions. The aim of this study was to determine the role of endoscopic ultrasound elastography in the detection of inflammatory and fibrotic lesions of the common bile duct. Methods Linear endoscopic ultrasound elastography of the common bile duct was performed in 41 patients. The patients were divided into two groups: disease group (20 patients with both, primary sclerosing cholangitis and inflammatory bowel disease) and control group (21 patients). Main outcome measurements were diameter, wall thickness and wall qualitative Elasto Score of the common bile duct. Results The disease group consisted of nine females and 11 males, whereas the control group consisted of 13 females and eight males, with no sex differences observed (χ2 = 0.6, d.f. = 1, P = 0.443). There was no significant difference in the diameter of common bile duct between the studied groups: 4.67±1.83 mm in the disease group and 5.88±2.47 mm in controls (t = −1.77, d.f.  = 39, P = 0.085). Hard or mixed Elasto Score was found in 16 patients and four controls, being significantly different compared with the soft Elasto Score found in four patients and 17 controls (χ2 = 1.8, d.f.  = 1, P<0.001). A significant difference was observed in the common bile duct wall thickness: 0.89±0.59 mm in the disease group and 0.39±0.14 mm in controls (t = 3.75, d.f.  = 39, P<0.001). Conclusion Endoscopic ultrasound elastography might be a useful noninvasive method in diagnosing primary sclerosing cholangitis.