Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus(1,2). This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ beta 1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 x 10(-19)). In addition, two amino acid substitutions in the. extracellular …

Achalasia with megaesophagus and tracheal compression in a young patient: A case report.

Highlights • This report emphasizes that physicians should be alert and consider airway obstruction and signs of dyspnea as severe and threatening symptoms in extensive cases of achalasia with megaesophagus. • Early surgical treatment provides a therapeutic option to obviate the occurrence of acute respiratory distress and consecutive complications. • In particular, difficulties in intubation prior to surgery must be considered. Due to potential tracheomalacia, the status of “bull frog neck” in achalasia, including severe tracheal compression caused by megaesophagus with concomitant cervical swelling, may also lead to extubation problems and deserves special care in the postoperative period.

Achalasia—an unnecessary long way to diagnosis

Although achalasia presents with typical symptoms such as dysphagia, regurgitation, weight loss, and atypical chest pain, the time until first diagnosis often takes years and is frustrating for patients and nevertheless associated with high costs for the healthcare system. A total of 563 patients were interviewed with confirmed diagnosis of achalasia regarding their symptoms leading to diagnosis along with past clinical examinations and treatments. Included were patients who had undergone their medical investigations in Germany. Overall, 527 study subjects were included (male 46%, female 54%, mean age at time of interview 51 ± 14.8 years). Dysphagia was present in 86.7%, regurgitation in 82…

Prävalenz von Komorbiditäten bei Patienten mit Barrett Ösophagus-Adenokarzinom

Systematic analysis of esophageal pressure topography in high-resolution manometry of 68 normal volunteers

Summary The introduction of high-resolution manometry (HRM) has been a significant advance in esophageal diagnostics. Normative values however are currently based upon a single set of published reference values, and multiple new metrics have been added over the past several years. Our goal was to provide a second set of ‘normal-values’ and to include all current metrics suggested by the 2012 Chicago classification. Sixty-eight subjects without foregut symptoms or previous surgery (median age 25.5 years, ranging from 20–58 years, 53% female) underwent esophageal motility assessment via an established standardized protocol. Normative thresholds were calculated for esophago-gastric junction (E…

Poor Esophageal Motility: A Tailored Approach?

New onset dysphagia following antireflux surgery is among the most undesirable side effects of an otherwise excellent therapy. While its cause is multifactorial, insufficient circular muscle strength of the esophageal body, not powerful enough to force the bolus through the distal neo-high pressure zone, can be a component of the pathophysiology. The relative merits of “tailoring” the degree of fundoplication based upon esophageal body motility and/or other clinical features have been debated for decades. Herein we discuss the rationale for a tailored approach, its pros and cons and review data published to date available to guide the clinician in individual patient decision-making.

Risk and Complication Management in Esophageal Cancer Surgery: A Review of the Literature

Esophagectomy for cancer is a highly complex and demanding two-cavity procedure associated with a considerable morbidity and mortality. There are several controversies with regard to the optimal risk and complication management. Strategies include patient selection, optimization of malnutrition, hospital and surgeon volume, intraoperative anesthesiological and surgical measures, and postoperative management of complications. In this article, we review the literature on these aspects that have an impact on outcomes after esophagectomy.

The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central E…

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic…

Prognostic scoring system predictive of survival after surgical resection of esophageal carcinoma.

BACKGROUND The aim of our study was to develop a prognostic index score for patients undergoing surgical resection for esophageal cancer that accurately determines survival with specific clinicopathological characteristics. METHODS Clinical, histological, and demographical variables of 475 patients were entered in an univariate and multivariate regression model, followed by individual calculation of the Prognostic Indicator Score and model validation via simulation. RESULTS Significant variables included in the scoring system were number of positive lymph nodes, pT, pL, R, obesity, and American Society of Anesthesiologist classification. Survival probability and its associated hazard functi…