D L Morris

Paramyxovirus infections in childhood and subsequent inflammatory bowel disease

BACKGROUND & AIMS Measles virus has been implicated in the etiology of both inflammatory bowel diseases (IBDs), Crohns disease and ulcerative colitis. Subacute sclerosing panencephalitis (SSPE) is caused by atypical measles infection. This study investigated the patterns of infection that are risks for SSPE, early infection and a close temporal relationship between measles and another infection, as potential risks for IBD. METHODS The data are from 7019 members of a nationally representative 1970 British Cohort Study. The ages of five childhood infections were recorded before onset of IBD symptoms. Diagnoses of IBD and insulin-dependent diabetes mellitus (IDDM), as a control disease, were identified by age 26 years. RESULTS Mumps infection before age 2 years was a risk for ulcerative colitis (odds ratio, 25.12; 95% confidence interval, 6. 35-99.36). Measles and mumps infections in the same year of life were significantly associated with ulcerative colitis and Crohns disease, with odds ratios of 7.47 (2.42-23.06) and 4.27 (1.24-14.46), but not with IDDM. These relationships are independent of each other as well as sex, social class at birth, household crowding in childhood, and family history of IBD. CONCLUSIONS Atypical paramyxovirus infections in childhood may be risk factors for later IBD.

Asian ethnic origin and the risk of inflammatory bowel disease.

OBJECTIVE To assess whether inflammatory bowel disease (IBD) is more prevalent in young Asians than Europeans living in Great Britain. DESIGN Longitudinal birth cohort study of all those born 5-11 April 1970 in Great Britain--the 1970 British Cohort Study (BCS70). METHODS The relationship of a diagnosis of ulcerative colitis or Crohns disease by age 26 years with ethnic origin was investigated among 8,432 cohort members with complete data using multiple logistic regression. We adjusted for potential confounding factors, household crowding and sex, as well as for a family history of IBD. RESULTS Young Asians born in Britain were significantly more likely than indigenous Europeans to have a diagnosis of IBD by age 26 years, with relative odds of 6.10 (95% CI 2.14-17.33). This group of cohort members had ethnic origins in India, Pakistan or Bangladesh (although none of those from Bangladesh had IBD). This relationship remained statistically significant after adjustment for the potential confounding factors and family history of IBD. CONCLUSION Young Asians who were born in Britain are at a significantly higher risk of developing IBD than the indigenous European population. This may reflect a greater genetic predisposition to IBD that is uncovered by exposure to environmental factors.

Evaluation of a Minimally Invasive Cell Sampling Device Coupled with Assessment of Trefoil Factor 3 Expression for Diagnosing Barrett's Esophagus: A Multi-Center Case-Control Study

Background Barretts esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE. Methods and Findings A case–control study was performed across 11 UK hospitals between July 2011 and December 2013. In total, 1,110 individuals comprising 463 controls with dyspepsia and reflux symptoms and 647 BE cases swallowed a Cytosponge prior to endoscopy. The primary outcome measures were to evaluate the safety, acceptability, and accuracy of the Cytosponge-TFF3 test compared with endoscopy and biopsy. In all, 1,042 (93.9%) patients successfully swallowed the Cytosponge, and no serious adverse events were attributed to the device. The Cytosponge was rated favorably, using a visual analogue scale, compared with endoscopy (p < 0.001), and patients who were not sedated for endoscopy were more likely to rate the Cytosponge higher than endoscopy (Mann-Whitney test, p < 0.001). The overall sensitivity of the test was 79.9% (95% CI 76.4%–83.0%), increasing to 87.2% (95% CI 83.0%–90.6%) for patients with ≥3 cm of circumferential BE, known to confer a higher cancer risk. The sensitivity increased to 89.7% (95% CI 82.3%–94.8%) in 107 patients who swallowed the device twice during the study course. There was no loss of sensitivity in patients with dysplasia. The specificity for diagnosing BE was 92.4% (95% CI 89.5%–94.7%). The case–control design of the study means that the results are not generalizable to a primary care population. Another limitation is that the acceptability data were limited to a single measure. Conclusions The Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.

Measles vaccination and inflammatory bowel disease: a national British Cohort Study

OBJECTIVE:Measles vaccination has been suggested as a risk for inflammatory bowel disease. Atypical age of measles infection has also been associated with Crohns disease. This study was designed to examine the relationship of measles vaccination and age of measles vaccination with later inflammatory bowel disease.METHODS:A prospective population-based national birth cohort was used, of those born in 1 wk in April 1970 in Great Britain. The data are from 7616 responding members of the 1970 British Cohort Study with complete vaccination data, who were traced at age 26 yr. A diagnosis of Crohns disease, ulcerative colitis, and diabetes mellitus (a control disease) was obtained by survey at age 26 yr, and confirmed by physicians. Vaccination data were from survey at age 5 yr. Measles and mumps infection data were obtained from the survey at age 10 yr. Adjustment was made for sex, household crowding in childhood, and fathers social class at birth.RESULTS:No statistically significant association was found between measles vaccination status at 5 yr and Crohns disease (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.27–1.63), ulcerative colitis (adjusted OR 0.57, 95% CI 0.20–1.61), or diabetes (adjusted OR 0.75, 95% CI 0.33–1.74). There was a statistically significant trend (p= 0.040) with increasing age of measles vaccination for risk of Crohns disease, although this was based on very few cases vaccinated after age 2 yr.CONCLUSIONS:In this cohort, monovalent measles vaccination status is not associated with inflammatory bowel disease by age 26 yr. Older age at measles vaccination needs to be examined in other studies to confirm whether it is a genuine risk for Crohns disease.

Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort.

Inflammatory bowel disease has become more common in developed countries this century. Mayberry et al reported incidences of Crohns disease in Wales of 0.18 cases/105/year in the 1930s and 5.95 cases/105/year in the 1970s.1 We investigated the prevalence of inflammatory bowel disease at age 26 years in a nationally representative birth cohort. Associations of sex and social class with risk of the disease have previously been shown,1-3 and these were also investigated. View this table: Inflammatory bowel disease among 26 year olds in 1970 British cohort study. Values are numbers (%) unless stated otherwise A postal survey of the 1970 British cohort study was conducted in 1995-6 among individuals aged 25 or 26 years, asking if respondents had a diagnosis of Crohns disease or ulcerative colitis. The cohort study is a longitudinal study of those living in England, Scotland, and Wales born 5 to 11 April 1970.4 The target population was estimated as 16 000, and we sent questionnaires to the 13 099 cohort …

The initial care of newborn infants and subsequent hay fever

Background: Patterns of neonatal exposure to microorganisms have changed substantially over the last 100 years, and it has been suggested that this has influenced the risk of immune‐mediated disease. Using a proxy measure, we tested the hypothesis that the initial handling of newborn infants, which is known to affect the pattern of exposure to microorganisms, may alter the risk of developing subsequent atopy, as indicated by hay fever.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study

BACKGROUND Barretts oesophagus predisposes to adenocarcinoma. However, most patients with Barretts oesophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and the subjective assessment of dysplasia. We investigated whether a non-endoscopic device, the Cytosponge, could be coupled with clinical and molecular biomarkers to identify a group of patients with low risk of progression suitable for non-endoscopic follow-up. METHODS In this multicentre cohort study (BEST2), patients with Barretts oesophagus underwent the Cytosponge test before their surveillance endoscopy. We collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia, and TP53 mutation status. We used a multivariable logistic regression model to compute the conditional probability of dysplasia status. We selected a simple model with high classification accuracy and applied it to an independent validation cohort. The BEST2 study is registered with ISRCTN, number 12730505. FINDINGS The discovery cohort consisted of 468 patients with Barretts oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barretts oesophagus segment. 162 (35%) of 468 of patients fell into the low-risk category and the probability of being a true non-dysplastic patient was 100% (99% CI 96-100) and the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 0% (0-4). 238 (51%) of participants were classified as of moderate risk; the probability of having high-grade dysplasia was 14% (9-21). 58 (12%) of participants were classified as high-risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5-27), whereas the probability of having high-grade dysplasia or intramucosal adenocarcinoma was 87% (73-95). In the validation cohort (65 patients), 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being non-dysplastic was 96·0% (99% CI 73·80-99·99). The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group (8% of the cohort) had no non-dysplastic cases and five patients with high-grade dysplasia. INTERPRETATION A combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be avoided. This strategy could help to avoid overdiagnosis and overtreatment in patients with Barretts oesophagus. FUNDING Cancer Research UK.

Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry

BACKGROUND AND STUDY AIM Mucosal neoplasia arising in Barretts esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barretts mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION The Registry reports on endoscopic therapy for Barretts neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

PWE-076 Specialist Centre Patient Volume Does Not Impact on Endoscopic Outcomes for Treatment of Barrett’s Dysplasia. Results from The UK Registry

Introduction Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is first line treatment for mucosal Barrett’s oesophagus (BE) related neoplasia. The UK Registry collects data from patients at 28 sites undergoing RFA/EMR. We examine differences in outcomes between sites by patient volume. Methods All visible lesions were entirely removed by EMR. Patients then underwent RFA every 3 months until all visible BE was ablated. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Centres were grouped by total numbers treated; low <50, medium 50–100 & high >100 patients. Only outcomes of those who had completed treatment were analysed. Results 675 patients completed treatment at 24 centres (median follow up 26 months), 414 at high volume (n = 5), 143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in entry criteria or demographics between groups. CR-D & CR-IM at 12 months are no different between the groups (CR-D 86–90%, CR-IM 74–81%). IM recurrence is significantly lower in high volume centres (16.1% vs 20.3% and 19.2%, Log Rank p < 0.001) but dysplasia recurrence is no different (Log Rank p = 0.12). Rescue EMR was performed less frequently in medium volume centres (0% vs high 5.3% and low volume 10%, p = 001). Conclusion Endotherapy for Barrett’s dysplasia is highly effective whatever the centre volume. The rescue EMR rate in medium volume centres is unexplained. Despite lower IM recurrence in high volume centres, dysplasia recurrence rates are not significantly different. Caseload volume of a centre in the UK Registry does not appear to affect outcome. Disclosure of Interest None Declared

841 Residual Intestinal Metaplasia After Successful Endoscopic Therapy for Barrett's Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of the UK RFA Registry

Introduction Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. Methods Visible lesions were removed by EMR. Patients then underwent RFA 3 monthly. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Dysplasia recurrence was compared in patients who had complete reversal of BE and neoplasia (CR-IM) to those in whom dysplasia alone was eradicated (CR-D only). Residual BE was confirmed with visible columnar epithelium proximal to the OGJ with biopsies showing IM. Results 517 patients achieved CR-IM & 96 patients achieved CR-D only after 12 months treatment . Sex & ER rates were not significantly different between groups. The CR-D only group were older (mean age 70 vs 67, p Conclusion Endotherapy should aim to clear neoplasia and underlying metaplastic BE to improve long term outcome. Patients with CR-D but not CR-IM at the end of treatment have an increased risk of neoplasia recurrence. This may have implications for post treatment surveillance intervals. Disclosure of Interest None Declared