Gastroenteritis, overseas travel and antibiotic use and irritable bowel syndrome (IBS) and functional dyspepsia (FD) : a population based study

The pathophysiology of IBS and FD remains unclear but a bout of gastroenteritis prior to symptoms which may have occurred during overseas travel has been associated with patients with IBS. Antibiotic use prior to the development of IBS has also been reported in patients, possibly by affecting bowel flora. We aimed to determine whether a previous bout of gastroenteritis, overseas travel and antibiotic use in the year prior to gastrointestinal symptoms is associated with people with IBS and FD from the general population. Participants (n=670) (response rate = 54%) were a random population sample from Sydney, Australia who responded to a valid survey in 1997, 2009 and the current survey in 2011 and agreed to be contacted for future research. IBS and FD were defined using Rome III criteria. Controls did not meet criteria for IBS or FD. We asked about the sudden onset of stomach and bowel problems, a bout of gastroenteritis and travel overseas in the year before stomach and bowel problems first started. Antibiotic use in the three months before stomach and bowel problems first started was also assessed. We found individuals with IBS alone (n=78) and those with IBS and/or FD (n=55), were more likely than controls (n=592) to report a sudden onset of symptoms whereas this was not the case for FD alone (n=35). Similarly, IBS alone and IBS  FD were more likely to report gastroenteritis preceding their onset of symptoms whereas this was not true of FD. Neither overseas travel nor antibiotic use were reported to a statistically significant extent preceding onset of symptoms in either IBS or FD although there was a trend to elevated antibiotic use among those with overlapping IBS and FD. Our population based data are consistent with patient studies that indicate that there is a subgroup of about one fifth of people with IBS who have post infectious IBS with the onset of symptoms associated with a prior bout of acute gastroenteritis, although onset of stomach and bowel disturbance only followed gastroenteritis in 6% of FD patients and 8% of controls.2 page(s

Identification of early environmental risk factors for irritable bowel syndrome and dyspepsia

BACKGROUND: The role of childhood environment including exposure to infection via siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively unknown. We assessed proxy measures of microbial exposure in early childhood to assess if these are associated with IBS and functional dyspepsia in later life. METHODS: Participants (n = 767, response rate = 53%) were a random population sample from Sydney, Australia who previously responded to a validated survey. IBS and functional dyspepsia were defined using Rome III criteria. Early environmental risk factors assessed included type of birth delivery, premature birth, breastfeeding, bedroom sharing, and pet exposure (the latter two then combined as early hygiene factors) up to 5 years of age. Post infectious IBS (PI-IBS) was assessed by development of IBS following gastroenteritis. KEY RESULTS: In this sample, in adult life 17% developed IBS (of which 20% had PI-IBS) and 12% functional dyspepsia. Development of IBS was associated with childhood factors-a shorter duration of breastfeeding (odds ratios [OR] = 0.87, 95% CI: 0.78-0.97, p = 0.01), sharing a bedroom (OR = 1.89, 95% CI: 1.73-3.08, p = 0.01), exposure to a herbivore pet (OR = 1.65 (1.10, 2.48), p = 0.02), and hygiene factors (OR = 4.39; 95% CI: 1.89-10.21, p = 0.001). The sole factor associated with functional dyspepsia was exposure to a herbivore pet (1.79; 95% CI: 1.19-2.87, p = 0.02). CONCLUSIONS & INFERENCES: Childhood environment factors, particularly bedroom sharing and pet exposure, combined with subsequent risk of microbial exposure are a risk factor for IBS in later life. These associations however need confirmation to rule out any risk of a type I error.9 page(s

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma

BACKGROUND: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers. METHODS: Relevant articles were identified via Ovid medline 1946–2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis. RESULTS: A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15–3.79), CD3 (HR=0.51, 95% CI=0.32–0.70), CD8 (HR=0.55, CI=0.31–0.80) and EGFR (HR=1.65, 95% CI=1.14–2.16). DISCUSSION: Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers

Multi-colour FISH in oesophageal adenocarcinoma-predictors of prognosis independent of stage and grade.

BACKGROUND Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is increasing in incidence and stratification of prognosis might improve disease management. Multi-colour fluorescence in situ hybridisation (FISH) investigating ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the diagnosis of dysplasia and cancer using cytological samples. METHODS To identify markers of prognosis we targeted four selected gene loci using multi-colour FISH applied to a tissue microarray containing 130 EAC samples. Prognostic predictors (P1, P2, P3) based on genomic copy numbers of the four loci were statistically assessed to stratify patients according to overall survival in combination with clinical data. RESULTS The best stratification into favourable and unfavourable prognoses was shown by P1, percentage of cells with less than two ZNF217 signals; P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73 months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour grade P2 subdivided patients into distinct prognostic groups independently within each grade, with different median survival times of at least 35 months. CONCLUSIONS Cell signal number of the ERBB2 and ZNF217 loci showed independence from tumour stage and differentiation grade. The prognostic value of multi-colour FISH-assays is applicable to EAC and is superior to single markers