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 × 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 × 10-10; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 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.
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- časopisecké články MeSH
1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence.
- MeSH
- gastrointestinální endoskopie * MeSH
- kolon diagnostické zobrazování MeSH
- lidé MeSH
- prekancerózy * MeSH
- rektum diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence.
Background and study aims Oral sulphate solution (OSS) is a sulphate-based, low-volume bowel cleansing preparation taken in two doses of 500 mL, each followed by 1000mL of water or clear liquid. The primary objective of this observational study was to document compliance with the recommended hydration guidelines in a representative sample of the European population. Patients and methods Prospective, non-interventional, multicentre study (NCT02630680, EUPAS9361) in patients prescribed OSS for colonoscopy preparation in routine clinical practice in Europe. Patients were included according to pre-agreed consecutive enrolment rules. Patients recorded the volume of OSS and water or clear liquid intake, and occurrence of adverse events (AEs). Compliance with hydration was calculated as a ratio of actual volume of water/clear liquid taken versus prescribed 2,000 mL, and non-compliance defined as < 75 % intake. Colon cleansing level was assessed on a 4-point scale. Results Between October 2015 and January 2017, 1,281 patients were recruited in 16 centres in four European countries (safety population n = 1,206; registry population n = 1,177). Of patients, 94.5 % were ≥ 75 % and 86.8 % 100 % compliant with hydration guidelines. Patients took an average of 96.8 % of the recommended OSS volume; 46 patients (3.9 %) were non-compliant. Colon cleansing levels were good-to-excellent in 87.6 % of patients. Three hundred and twenty-nine patients (27.3 %) experienced 758 treatment-related AEs, mostly gastrointestinal (82.9 %), all were mild-to-moderate. Non-compliant patients had no AEs suggestive of dehydration. Conclusion In this non-interventional study in a real-life setting, treatment compliance with hydration guidelines was good-to-excellent in 94.5 % of patients receiving OSS. The safety profile of OSS was similar to the prescribing information.
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