Genomic profiling of intestinal T-cell receptor repertoires in inflammatory bowel disease.

Growing evidence shows that inflammatory bowel disease (IBD) results from dysregulation of immune responses to gut microbes. T-cell receptors (TCRs) expressed on the T-cell surface play critical roles in discriminating pathogens from commensal intestinal microorganisms at the front line of the adaptive immune system. The breakdown of this interaction may trigger persistent inflammatory responses to gut bacteria, resulting in IBD. Taking advantage of high-throughput sequencing, we developed an integrated approach to dissect the intestinal TCR repertoires underlying IBD by collecting peripheral blood and inflamed intestine from the same set of 11 IBD cases. The intestinal TCR repertoires show lower clonotype diversity (p < 0.05) and stronger clonal expansion (p < 0.02) than those in the blood. This pattern becomes more profound in TCRs unique to the inflamed tissue compared with shared TCRs. Our approach further identified the increased usage of TRAV12-3 (false discovery rate, FDR < 5%), which biases its choices of J genes towards the reduction of TRAJ37 and TRAJ43 usage (FDR < 20%) in the inflamed intestine. Our genomic profiling suggests that this selective bias of V and J gene usage may lead to a loss of diversity in the intestinal TCR repertoires and result in mucosal inflammation in IBD.

Strictureplasty versus bowel resection for the surgical management of fibrostenotic Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Strictureplasty (SPX) conserves bowel length and minimizes the risk of developing short bowel syndrome in patients undergoing surgery for Crohn's disease (CD). However, SPX may be associated with a higher risk of recurrence compared with bowel resection (BR). AIM: We sought to compare morbidity and recurrence following SPX and BR in patients with fibrostenotic CD. METHODS: A systematic review was performed according to PRISMA and MOOSE guidelines. Observational studies that compared outcomes of CD patients undergoing either SPX or BR were identified. Log hazard ratios (InHR) for recurrence-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots or Cox regression models and pooled using the inverse variance method. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Continuous variables were pooled as weighted mean differences. RESULTS: Twelve studies of 1026 CD patients (SPX n = 444, 43.27%; BR with or without SPX n = 582, 56.72%) were eligible for inclusion. There was an increased likelihood of disease recurrence with SPX than with BR (OR 1.61; 95% CI, 1.03, 2.52; p = 0.04; I2 = 0%). Patients who had a SPX alone had a significantly reduced RFS than those who underwent BR (HR 1.47; 95% CI, 1.08, 2.01; p = 0.02; I2 = 0%). There was no difference in morbidity between the groups (OR 0.58; 95% CI, 0.26, 1.28; p = 0.18; I2 = 0%). CONCLUSION: SPX should only be performed in those patients with Crohn's strictures that are at high risk for short bowel syndrome and intestinal failure; otherwise, BR is the favored surgical technique for the management of fibrostenotic CD.

Lower gastrointestinal symptoms and symptoms-based triaging systems are poor predictors of clinical significant disease on colonoscopy.

Introduction: Lower gastrointestinal symptoms (LGS) are a common cause of referral to the gastroenterology service. International guidelines are available to prioritise referrals. Some studies have reported that symptoms alone are a poor marker of clinically significant disease (CSD) but symptoms remain the main way to prioritise referrals in routine clinical practice. Aims/background: To correlate LGS with colonoscopy findings in an unselected patient cohort and to investigate whether using National Institute for Health and Care Excellence (NICE) guidelines improve risk stratification. Method: Colonoscopy data over a 2-year period were obtained from our endoscopy database. Only patients with assessment of symptoms as their primary indication for colonoscopy were included. Patient records were retrospectively reviewed. Exclusion criteria: known inflammatory bowel disease (IBD), familial cancer syndromes, polyp and colorectal cancer (CRC) surveillance, and prior colonoscopy within 5 years. Demographics, symptoms and colonoscopy findings were recorded and analysed. Results: 1116 cases were reviewed; 493 (44%) males, age 54.3 years (16-91). CSD occurred in only 162 (14.5%); CRC 19 (1.7%), high-risk adenoma 40 (3.6%), inflammation 97 (8.7%) (IBD 65 (5.8%), microscopic colitis 9 (0.8%) and indeterminate-inflammation 23 (2%)), angiodysplasia 6 (0.5%). Diarrhoea gave the highest diagnostic yield for CSD of 5.3% (OR 3.15, 95% CI 2.2 to 4.7, p<0.001), followed by PR bleeding, 2.9% (OR 1.9, 95% CI 1.24 to 2.9, p=0.003). Weight loss gave the lowest diagnostic yield of 0.4%; (OR 0.79, 95% CI 0.28 to 2.24, p=0.65). 592 (53%) and 517 (46%) fitted the NICE guidelines for CRC and IBD, respectively. Using NICE positivity improved detection but overall yield remained low 3% vs 0.4% (OR 7.71, 95% CI 1.77 to 33.56, p=0.0064) for CRC, and 9% vs 2.8% (OR 3.5, 95% CI 1.99 to 6.17, p<0.0001) for IBD. Conclusions: The overall prevalence of CSD in our unselected symptomatic patients is low (14.5%). A holistic approach including combining symptoms and demographics with novel tools including stool biomarkers and minimally invasive colonoscopy alternatives should be applied to avoid unnecessary colonoscopy.

Molecular detection of Helicobacter pylori antibiotic resistance in stool vs biopsy samples.

AIM: To compare (1) demographics in urea breath test (UBT) vs endoscopy patients; and (2) the molecular detection of antibiotic resistance in stool vs biopsy samples. METHODS: Six hundred and sixteen adult patients undergoing endoscopy or a UBT were prospectively recruited to the study. The GenoType HelicoDR assay was used to detect Helicobacter pylori (H. pylori) and antibiotic resistance using biopsy and/or stool samples from CLO-positive endoscopy patients and stool samples from UBT-positive patients. RESULTS: Infection rates were significantly higher in patients referred for a UBT than endoscopy (overall rates: 33% vs 19%; treatment-naïve patients: 33% vs 14.7%, respectively). H. pylori-infected UBT patients were younger than H. pylori-infected endoscopy patients (41.4 vs 48.4 years, respectively, P < 0.005), with a higher percentage of H. pylori-infected males in the endoscopy-compared to the UBT-cohort (52.6% vs 33.3%, P = 0.03). The GenoType HelicoDR assay was more accurate at detecting H. pylori infection using biopsy samples than stool samples [98.2% (n = 54/55) vs 80.3% (n =53/66), P < 0.005]. Subset analysis using stool and biopsy samples from CLO-positive endoscopy patients revealed a higher detection rate of resistance-associated mutations using stool samples compared to biopsies. The concordance rates between stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION: Differences between endoscopy and UBT patients provide a rationale for non-invasive detection of H. pylori antibiotic resistance. However, the GenoType HelicoDR assay is an unsuitable approach.

A randomized-controlled study to compare the efficacy of sequential therapy with standard triple therapy for Helicobacter pylori eradication in an Irish population.

INTRODUCTION: Eradication rates for the standard first-line triple therapy for Helicobacter pylori infection have decreased in recent years. Sequential therapy has been suggested as an alternative. The efficacy of sequential therapy has not been assessed to date in an Irish population. OBJECTIVE: The aim of this study was to compare the efficacy of standard triple therapy with sequential therapy for H. pylori eradication. PATIENTS AND METHODS: A prospective randomized-controlled study was carried out. Treatment-naive H. pylori-infected patients were randomized to receive either standard triple therapy or sequential therapy. RESULTS: In all, 87 eligible patients were recruited into the study, one of whom dropped out. Fifty-one per cent (N=44) patients received standard triple therapy and 49% (N=42) patients received sequential therapy. The eradication efficacy by intention-to-treat analysis was 56.8% [N=25/44; 95% confidence interval (CI) 42.2-71.4%] for standard triple therapy and 69% (N=29/42; 95% CI 55.0-83.0%) for sequential therapy. The eradication rates by per-protocol analysis for standard triple therapy and sequential therapy were 61% (N=25/41; 95% CI 46.1-76.0%) and 69% (N=29/42; 95% CI 55.0-83.0%), respectively. The differences in eradication rates for each treatment by either intention-to-treat or per-protocol analysis were not statistically significant (P=0.24 and 0.44, respectively). In addition, incidence in adverse events was not significantly different between the study groups. The most common adverse event reported was mild nausea at 15% (95% CI 7.5-22.6%). CONCLUSION: Sequential therapy had a nonstatistically significant advantage over standard triple therapy in our patient cohort. However, eradication rates for both standard triple therapy and sequential therapy were suboptimal. Further studies are required to identify potential alternatives to standard first-line triple therapy.