Electrical stimulation of the lower esophageal sphincter to address gastroesophageal reflux disease after sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) can result in de novo and worsen preexisting gastroesophageal reflux disease (GERD). Post-LSG patients with GERD refractory to proton pump inhibitors (PPI) usually undergo more invasive, anatomy-altering Roux-en-Y gastric bypass surgery. Lower esophageal sphincter (LES) electrical stimulation (ES) preserves the anatomy and has been shown to improve outcomes in GERD patients. OBJECTIVE: To evaluate the safety and efficacy of LES-ES in post-LSG patients with GERD not controlled with maximal PPI therapy. SETTING: Prospective, international, multicenter registry. METHODS: Patients with LSG-associated GERD partially responsive to PPI underwent LES-ES. GERD outcomes pre- and poststimulation were evaluated based on quality of life, esophageal acid exposure (after 6-12 mo), and PPI use. RESULTS: Seventeen patients (11 female, 65%), treated at 6 centers between May 2014 and October, 2016 with a median follow-up of 12 months (range 6-24), received LES-ES. Median age was 48.6 years (interquartile range, 40.5-56), median body mass index 31.7 kg/m2 (27.9-39.3). All patients were on at least daily PPI preoperatively; at last follow-up, 7 (41%) were completely off PPI, 5 (29%) took PPI on an intermittent basis, and 5 (29%) were on single-dose PPI. Median GERD-health-related quality of life scores improved from 34 (on-PPI, 25-41) at baseline to 9 (6-13) at last follow-up (off-PPI, P<.001). Percentage of time with esophageal pH<4 improved from 13.2% (3.7-30.7) to 5.8% (1.1-54.4), P = .01. CONCLUSION: LES-ES in post-LSG patients suffering from symptomatic, PPI-refractory GERD resulted in significant improvement of GERD-symptoms, esophageal acid exposure, and need for PPI. Preserving the post-LSG anatomy, it offers a valid option for patients unable or unwilling to undergo Roux-en-Y gastric bypass surgery.

Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia.

BACKGROUND AND AIM: Although an eight-residue insertion in HLA-DQß1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype-phenotype (G×P) analysis to gain further insights into the etiology of achalasia. METHODS: We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls). For the G×P analysis, we stratified the patients into HLA-DQß1 insertion carriers and noncarriers. RESULTS: Our data show that patients are more often affected by viral infections before achalasia onset (P<0.0001, most significantly for varicella zoster virus infections). In addition, allergic (P=0.0005) and autoimmune disorders (P=0.0007, most significantly for psoriasis and Sjögren's syndrome) represent comorbid disease conditions. First-degree relatives of patients also show higher prevalence rates of allergic disorders (P=0.0007) and psoriasis (P=0.016) compared with control relatives. Moreover, the G×P analysis reveals that achalasia is triggered by pregnancies in female HLA-DQß1 insertion carriers (P=0.031). CONCLUSION: Our data point to a role of viral infections in the development of achalasia. In addition, they provide evidence for a relationship between achalasia and allergic, as well as autoimmune, disorders. Furthermore, pregnancy seems to be a disease-triggering factor in female HLA-DQß1 insertion carriers, which points to hormonal and/or immunosuppressive factors influencing disease development.

The HLA-DQß1 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-DQß1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQß1 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 Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

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. 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-DQß1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P=1.73×10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.60×10(-10)) and of HLA-DQß1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P=1.20×10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.