No abstract

Barrett’s Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett’s Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett’s Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10−9, OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (Pcombined=2.74×10−10, OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett’s Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett’s Esophagus.

Background & AimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.MethodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.ResultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9).ConclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Transition from open to minimally invasive techniques of esophagogastric resection for cancer is possible without compromising patient safety or incurring excessive financial expenses, and the minimally invasive procedure results in similar or potentially better outcomes.

Background: Laparoscopic cholecystectomy is commonly performed, and several factors increase the

Background: Minimally invasive oesophagectomy (MIO; thoracoscopy, laparoscopy, cervical anastomosis) is a complex procedure and few substantial series have been published. This study documented the morbidity, mortality and challenges of adopting MIO in a specialist unit in the UK. Conclusion: MIO can be performed with acceptable mortality and morbidity rates in an unselected series of patients. There was more morbidity related to gastric tube ischaemia than was expected.

Hypothesis: Obesity impairs the antireflux function of a structurally intact barrier.Design: Retrospective analysis of body mass index in patients with normal esophageal manometric findings but with symptomatic and objectively confirmed gastroesophageal reflux.Setting: Specialist esophageal center.Patients: Patients symptomatic and diagnostic for gastroesophageal reflux, referred between October 1, 1998, and June 30, 2000. Exclusion criteria were a defective barrier, motility disorders, or previous surgery.Main Outcome Measures: Reflux was defined and quantified using the DeMeester score, and body mass index was calculated.Results: There was a strong correlation between body mass index and severity of gastroesophageal reflux. Patients who were overweight had significantly higher distal esophageal acid exposure. No significant difference in manometric findings was demonstrated between patients with normal weight and those who were overweight. Conclusion:The barrier to gastroesophageal reflux is rendered insufficient in patients who are overweight.

HRQL outcomes are relevant to surgical decision making. Methods to communicate HRQL outcomes to patients are required to inform consent and clinical practice.