Achalasia is a major esophageal motor disorder featured by the altered relaxation of the esophagogastric junction in the absence of effective peristaltic activity. As a consequence of the esophageal outflow obstruction, achalasia patients present with clinical symptoms of dysphagia, chest pain, weight loss, and regurgitation of indigested food. Other less specific symptoms can also present including heartburn, chronic cough, and aspiration pneumonia. The delay in diagnosis, particularly when the presenting symptoms mimic those of gastroesophageal reflux disease, may be as long as several years. The widespread use of high-resolution manometry has permitted earlier detection and uncovered achalasia phenotypes which can have prognostic and therapeutic implications. Other tools have also emerged to help define achalasia severity and which can be used as objective measures of response to therapy including the timed barium esophagogram and the functional lumen imaging probe. Such diagnostic innovations, along with the increased awareness by clinicians and patients due to the availability of alternative therapeutic approaches (laparoscopic and robotic Heller myotomy, and peroral endoscopic myotomy) have radically changed the natural history of the disorder. Herein, we report the most recent advances in the diagnosis, classification, and management of esophageal achalasia and underline the still-grey areas that needs to be addressed by future research to reach the goal of personalizing treatment.

BACKGROUND/AIMS: Bitter taste receptors are expressed throughout the digestive tract. Data on animals have suggested these receptors are involved in the gut hormone release, but no data are available in humans. Our aim is to assess whether bitter agonists influence food intake and gut hormone release in healthy subjects. METHODS: Twenty healthy volunteers were enrolled in a double-blind cross-over study. On 2 different days, each subject randomly received an acid-resistant capsule containing either placebo or 18 mg of hydrochloride (HCl) quinine. After 60 minutes, all subjects were allowed to eat an ad libitum meal until satiated. Plasma samples were obtained during the experiment in order to evaluate cholecystokinin (CCK) and ghrelin levels. Each subject was screened to determine phenylthiocarbamide (PTC) tasting status. RESULTS: Calorie intake was significantly lower when subjects received HCl quinine than placebo (514 +/- 248 vs 596 +/- 286 kcal; P = 0.007). Significantly higher CCK DeltaT90 vs T0 and DeltaT90 vs T60 were found when subjects received HCl quinine than placebo (0.70 +/- 0.69 vs 0.10 +/- 0.86 ng/mL, P = 0.026; 0.92 +/- 0.75 vs 0.50 +/- 0.55 ng/mL, P = 0.033, respectively). PTC tasters ingested a significantly lower amount of calories when they received HCl quinine compared to placebo (526 +/- 275 vs 659 +/- 320 kcal; P = 0.005), whereas no significant differences were found for PTC non-tasters (499 +/- 227 vs 519 +/- 231 kcal; P = 0.525). CONCLUSIONS: This study showed that intra-duodenal release of a bitter compound is able to significantly affect calorie intake and CCK release after a standardized meal. Our results suggest that bitter taste receptor signaling may have a crucial role in the control of food intake.
Animals ; Cholecystokinin* ; Cross-Over Studies ; Eating ; Gastrointestinal Tract ; Ghrelin ; Healthy Volunteers ; Humans ; Meals ; Phenylthiourea ; Plasma ; Quinine*