Identification of iatrogenic perforation in paediatric gastrointestinal endoscopy

Objectives: Iatrogenic viscus perforation in paediatric gastrointestinal endoscopy (GIE) is a very rare, yet potentially life-threatening event. There are no evidence-based recommendations relating to immediate post-procedure follow-up to identify perforations and allow for timely management. This study aims to characterize the presentation of children with post-GIE perforation to better rationalize post-procedure recommendations. Methods: Retrospective study based on unrestricted pooled data from centers throughout Europe North America and the Middle East affiliated with the Endoscopy Special Interest Groups of European Society for Paediatric Gastroenterology Hepatology and Nutrition and North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Procedural and patient data relating to clinical presentation of the perforation were recorded on standardized REDcap case-report forms. Results: Fifty-nine cases of viscus perforation were recorded (median age 6 years (IQR 3-13)). 29/59 (49%) occurred following esophagogastroduodenoscopy (EGD), 26/59 (44%) following ileocolonoscopy, with 2/59 (3%) cases each following balloon enteroscopy and ERCP.28/59 (48%) of perforations were identified during the procedure (26/28 (93%) endoscopically, 2/28 (7%) by fluoroscopy), a further 5/59 (9%) identified within 4 hours. Overall 80% of perforations were identified within 12 hours.Amongst perforations identified subsequent to the procedure 19/31 (61%) presented with pain, 16/31 (52%) presented with fever and 10/31 (32%) presented with abdominal rigidity or dyspnea.30/59 (51%) were managed surgically, 17/59 (29%) managed conservatively and 9/59 (15%) endoscopically. 4/59 (7%) patients died, all following esophageal perforation. Conclusions: Iatrogenic perforation was identified immediately in over half of cases and in 80% of cases within 12 hours. This novel data can be utilized to generate guiding principles of post-procedural follow-up and monitoring

First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 x 10(-8); odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 x 10(-10); OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 x 10(-16); OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% +/- 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes