Background Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns. Methods We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by 2 expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes. Key Results Manometry studies were categorized as follows: type I (n=20), type II (n=20), type III (n=3), and esophagogastric junction outflow obstruction (EGJOO) (n=3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs. 13/20, p=0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p=0.016). CD3+/CD8+ cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO). Conclusions and Inferences The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings – from complete neuronal loss to lymphocytic inflammation to apparently normal histopathology – emphasizes that ‘achalasia’ represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.

Background Esophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy. Methods 1,638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split-half reliability, ceiling and floor effects, and construct validity. Key Results The BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split-half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter-item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant. Conclusions & Inferences The BEDQ represents a rapid, reliable and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction.

Background-Achalasia has three distinct manometric phenotypes. This study aimed to determine if there were corresponding histopathologic patterns. Methods-We retrospectively examined surgical muscularis propria biopsies obtained from 46 patients during laparoscopic esophagomyotomy. Pre-operative (conventional) manometry tracings were reviewed by 2 expert gastroenterologists who categorized patients into Chicago Classification subtypes. Pathology specimens were graded on degree of neuronal loss, inflammation, fibrosis, and muscle changes. Key Results-Manometry studies were categorized as follows: type I (n=20), type II (n=20), type III (n=3), and esophagogastric junction outflow obstruction (EGJOO) (n=3). On histopathology, complete ganglion cell loss occurred in 74% of specimens, inflammation in 17%, fibrosis in 11%, and muscle atrophy in 2%. Comparing type I and type II specimens, there was a statistically significant greater proportion of type I specimens with aganglionosis (19/20 vs. 13/20, p=0.044) and a statistically significant greater degree of ganglion cell loss in type I specimens (Wilcoxon Rank-Sum, p=0.016). CD3+/CD8+ cytotoxic T cells represented the predominant inflammatory infiltrate on immunohistochemistry. Three patients had completely normal appearing tissue (1 each in type II, type III, EGJOO). Conclusions and Inferences-The greater degree, but similar pattern, of ganglion cell loss observed in type I compared to type II achalasia specimens suggests that type I achalasia represents a progression from type II achalasia. The spectrum of histopathologic findings-from complete neuronal loss to lymphocytic inflammation to apparently normal histopathologyemphasizes that 'achalasia' represents a pathogenically heterogeneous patient group with the commonality being EGJ outflow obstruction.

Disclosure of potential conflict of interest: I. Hirano has consultant arrangements with Receptos, Regeneron, and Meritage; has received research support from the National Institutes of Health and the American Society of Gastrointestinal Endoscopy; and has received royalties from UpToDate. J. Sodikoff declares no relevant conflicts of interest.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease that is increasingly recognized as one of the most common causes of dysphagia and foregut symptoms in adults and children. Topical corticosteroids, elimination diets, and esophageal dilations are effective options for both induction and maintenance therapy in EoE. Current pharmacologic options are being used off-label as no agent has yet been approved by regulatory authorities. Little is known about the natural history of EoE, however, raising controversy regarding the necessity of maintenance and therapy in asymptomatic or treatment-refractory patients. Furthermore, variability in treatment endpoints used in EoE clinical trials makes interpretation and comparability of EoE treatments challenging. Recent validation of a patient-related outcome (PRO) instruments, a histologic scoring tool, and an endoscopic grading system for EoE are significant advances toward establishing consistent treatment endpoints.