ACG clinical guidelines: diagnosis and management of achalasia

Achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter. Patients most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. High-resolution manometry has identified 3 subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In this American College of Gastroenterology guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to provide clinical guidance on how best to diagnose and treat patients with achalasia.

Relationship between extralaryngeal endoscopic findings, proton pump inhibitor (PPI) response, and pH measures in suspected laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a clinical entity diagnosed by history laryngoscopic findings that has a variable response to empiric proton-pump inhibitor (PPI) therapy. While the reflux finding score (RFS), an endoscopic scoring scheme, has been advanced as a measure of LPR, it has not been externally validated against symptom severity in practice. Extralaryngeal pharyngeal endoscopic findings may have diagnostic utility but remain underexplored. This study assesses the correlation between extralaryngeal findings and (1) 24-hour oropharyngeal pH & (2) PPI response in patients with suspected LPR. Subjects presented to a tertiary care center with laryngeal symptoms ≥1 month and reflux symptom index (RSI) ≥13. Following baseline questionnaires, laryngoscopy, and a 24-hour oropharyngeal pH probe study, subjects were prescribed 8-12 week omeprazole trials. Baseline endoscopic findings were scored in a blinded fashion using the RFS and extralaryngeal score criteria, summatively the 'ELS.' PPI response was defined as ≥50% improvement in RSI. Thirty-three subjects with flexible endoscopic recordings completed baseline and follow-up questionnaires. The cohort's baseline mean RSI was 23.0 ± 7.2 with a ΔRSI = 9.8 after PPI therapy. The baseline RFS score averaged 5.3 ± 2.7. 45% of our subjects was found to be PPI responsive. The Cohen's kappa for the ELS but not the RFS was significant. There were no significant differences between the RFS (P = 0.10) or ELS (P = 0.07) for PPI responders & nonresponders. Oropharyngeal pH measures did not correlate with the RFS or ELS. In conclusion, endoscopic scores of laryngeal and extralaryngeal findings did not predict PPI response or oropharyngeal acid exposure in suspected LPR.

Trajectory assessment is useful when day-to-day esophageal acid exposure varies in prolonged wireless pH monitoring.

Acid exposure time commonly varies from day-to-day in prolonged wireless pH monitoring. Thus, diagnosis based on the number of days with abnormal acid burden may be misleading or inconclusive. We hypothesize that assessing longitudinal patterns of acid exposure may be diagnostically useful. Therefore, this study aims to describe acid exposure trajectories and evaluate agreement between identified trajectory patterns and conventional grouping. In this retrospective cohort study, we assessed patients with nonresponse to proton pump inhibitor therapy who underwent wireless pH monitoring (≥72 h) off therapy between August 2010 and September 2016. The primary outcome was esophageal acid exposure time. Subjects were grouped as 0, 1, 2, and 3+ days positive based on number of days with an acid exposure time >5.0%. Latent class group-based mixture model identified distinct longitudinal acid exposure trajectory groups. Of 212 subjects included 44%, 18%, 14%, and 24% had 0, 1, 2, 3+ days positive, respectively. Group-based modeling identified three significantly stable acid exposure trajectories: low (64%), middle (28%), and high (8%). Trajectory grouping and days positive grouping agreed substantially (weighted K 0.69; 95% CI: 0.63-0.76). Trajectory grouping identified 62% of subjects with conventionally inconclusive studies (one or two days positive) into the low trajectory. Agreement between trajectory groups when using three versus four days of monitoring was substantial (K 0.70; CI: 0.61-0.78). In summary, we found that patients with nonresponse to proton pump inhibitors follow three acid exposure trajectories over prolonged pH-monitoring periods: low, middle, and high. Compared to conventional day positive grouping, the trajectory modeling identified the majority of inconclusive days positive into the low trajectory group. Analyzing prolonged wireless pH data according to trajectories may be a complimentary method to conventional grouping, and may increase precision and accuracy in identifying acid burden.

Dysplasia severity is associated with poor quality of life in patients with Barrett's esophagus referred for endoscopic eradication therapy.

Limited data exist regarding patient-reported outcomes and quality of life (QOL) experienced by patients with Barrett's esophagus (BE) referred for endoscopic eradication therapy (EET). Specifically, the impact of grade of dysplasia has not been explored. The purpose of this study is to measure patient-reported symptoms and QOL and identify factors associated with poor QOL in BE patients referred for EET. This was a prospective multicenter study conducted from January 2015 to October 2017, which included patients with BE referred for EET. Participants completed a set of validated questionnaires to measure QOL, symptom severity, and psychosocial factors. The primary outcome was poor QOL defined by a PROMIS score >12. Multivariable logistic regression analysis was performed to identify factors associated with poor QOL. In total, 193 patients participated (mean age 64.6 years, BE length 5.5 cm, 82% males, 92% Caucasians) with poor QOL reported in 104 (53.9%) participants. On univariate analysis, patients with poor QOL had lower use of twice daily proton pump inhibitor use (61.5% vs. 86.5%, P = 0.03), shorter disease duration (4.9 vs. 5.9 years, P = 0.04) and progressive increase in grade of dysplasia (high-grade dysplasia: 68.8% vs. 31.3%, esophageal adenocarcinoma: 75.5% vs. 24.5%, P < 0.001). Multivariate analysis demonstrated that high-grade dysplasia was independently associated with poor QOL (OR: 5.57, 95% CI: 1.05, 29.5, P = 0.04). In summary, poor QOL is experienced by the majority of patients with BE referred for EET and the degree of dysplasia was independently associated with poor QOL, which emphasizes the need to incorporate patient-centered outcomes when studying treatment of BE-related dysplasia.

Evaluating the reliability and construct validity of the Eckardt symptom score as a measure of achalasia severity.

BACKGROUND: Achalasia is a disease of mechanical esophageal dysfunction characterized by dysphagia, chest pain, regurgitation, and malnutrition. The Eckardt symptom score (ESS) is the gold standard self-report assessment tool. Current guidelines outline a three-step approach to patient reported outcomes measure design. Developed prior to these policies, the ESS has not undergone rigorous testing of its reliability and validity. METHODS: Adult achalasia patients retrospectively identified via a patient registry were grouped based on treatment history. Patients were grouped PREPOST (completed ESS, GERDQ, brief esophageal dysphagia questionnaire, NIH PROMIS Global Health, high resolution manometry, timed barium esophagram prior to treatment and after) and POST (completed measures only after treatment). Clinical characteristics, treatment type and date were obtained via medical record. Standardized psychometric analyses for reliability and construct validity were performed. KEY RESULTS: 107 patients identified; 83 POST and 24 PREPOST. The ESS has fair internal consistency and split-half reliability with a single factor structure. Dysphagia accounts for half the variance in ESS, while chest pain and weight loss account for 10% each. Pre-post-surgical assessment demonstrates improvements in ESS, except for weight loss. Effect sizes range from 0.24 to 2.53, with greatest change in regurgitation. Validity of the ESS is supported by modest correlations with GERDQ, HRQOL, and physiological data. CONCLUSIONS & INFERENCES: The ESS demonstrates fair reliability and validity, with a single factor structure mostly explained by dysphagia. Based on psychometric findings, weight loss and chest pain items may be decreasing ESS reliability and validity. Further assessment of the ESS under FDA guidelines is warranted.

Review of antireflux procedures for proton pump inhibitor nonresponsive gastroesophageal reflux disease.

Up to 40% of patients with gastroesophageal reflux disease (GERD) report persistent symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for surgical and endoscopic therapies for the treatment of PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 45 unique articles specific to surgical and endoscopic therapies for PPI nonresponsive GERD were reviewed. Laparoscopic fundoplication (n = 19) provides symptomatic and physiologic relief out to 10 years, though efficacy wanes with time. Magnetic sphincter augmentation (n = 6) and transoral incisionless fundoplication (n = 9) improve symptoms in PPI nonresponders and may offer fewer side effects than fundoplication, though long-term follow-up is lacking. Radiofrequency energy delivery (n = 8) has insufficient evidence for routine use in treating PPI nonresponsive GERD. Electrical stimulator implantation (n = 1) and endoscopic mucosal surgery (n = 2) are newer therapies under evaluation for the treatment of GERD. Laparoscopic fundoplication remains the most proven therapeutic approach. Newer antireflux procedures such as magnetic sphincter augmentation and transoral incisionless fundoplication offer alternatives with varying degrees of success, durability, and side effect profiles that may better suit individual patients. Larger head-to-head comparison trials are needed to better characterize the difference in symptom response and side effect profiles.

A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease.

Up to 40% of patients report persistent gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for medical therapy for PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 40 unique articles specific to the impact of PPI metabolizer genotype on PPI response and the use adjunctive medical therapies were identified. Thirteen articles reported impacts on CYP genotypes on PPI metabolism demonstrating lower endoscopic healing rates in extensive metabolizers; however, outcomes across genotypes were more uniform with more CYP independent PPIs rabeprazole and esomeprazole. Twenty-seven publications on 11 adjunctive medications showed mixed results for adjunctive therapies including nocturnal histamine-2 receptor antagonists, promotility agents, transient lower esophageal sphincter relaxation inhibitors, and mucosal protective agents. Utilizing PPI metabolizer genotype or switching to a CYP2C19 independent PPI is a simple and conservative measure that may be useful in the setting of incomplete acid suppression. The use of adjunctive medications can be considered particularly when the physiologic mechanism for PPI nonresponse is suspected. Future studies using adjunctive medications with improved study design and patient enrollment are needed to better delineate medical management options before proceeding to antireflux interventions.

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

BACKGROUND: High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. METHODS: Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. KEY RESULTS: Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. CONCLUSIONS & INFERENCES: Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

BACKGROUND: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). METHODS: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. KEY RESULTS: Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. CONCLUSIONS AND INFERENCES: The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

Benchmarks for the interpretation of esophageal high-resolution manometry.

BACKGROUND: Competent interpretation of esophageal high-resolution manometry (HRM) is integral to a quality study. Currently, methods to assess physician competency for the interpretation of esophageal HRM do not exist. The aim of this study was to use formal techniques to (i) develop an HRM interpretation exam, and (ii) establish minimum competence benchmarks for HRM interpretation skills at the trainee, physician interpreter, and master level. METHODS: A total of 29 physicians from 8 academic centers participated in the study: 9 content experts separated into 2 study groups-expert test-takers (n=7) and judges (n=2), and 20 HRM inexperienced trainees ("trainee test-taker"; n=20). We designed the HRM interpretation exam based on expert consensus. Expert and trainee test-takers (n=27) completed the exam. According to the modified Angoff method, the judges reviewed the test-taker performance and established minimum competency cut scores for HRM interpretation skills. KEY RESULTS: The HRM interpretation exam consists of 22 HRM cases with 8 HRM interpretation skills per case: identification of pressure inversion point, hiatal hernia >3 cm, integrated relaxation pressure, distal contractile integral, distal latency, peristaltic integrity, pressurization pattern, and diagnosis. Based on the modified Angoff method, minimum cut scores for HRM interpretation skills at the trainee, physician interpreter, and master level ranged from 65-80%, 85-90% (with the exception of peristaltic integrity), and 90-95%, respectively. CONCLUSIONS & INFERENCES: Using a formal standard setting technique, we established minimum cut scores for eight HRM interpretation skills across interpreter levels. This examination and associated cut scores can be applied in clinical practice to judge competency.

Competency based medical education in gastrointestinal motility.

Traditional apprenticeship-based medical education methods focusing on subjective evaluations and case-volume requirements do not reliably produce clinicians that provide high-quality care in unsupervised practice. Consequently, training approaches are shifting towards competency based medical education, which incorporates robust assessment methods and credible standards of physician proficiency. However, current gastroenterology and hepatology training in the US continues to utilize procedural volume and global impressions without standardized criteria as markers of competence. In particular, efforts to optimize competency based training in gastrointestinal (GI) motility are not underway, even though GI motility disorders account for nearly half of outpatient gastroenterology visits. These deficiencies compromise the quality of patient care. Thus, there is a great need and opportunity to shift our focus in GI motility training towards a competency based approach. First, we need to clarify the variable rates of learning for individual diagnostic tests. We must develop integrated systems that standardize training and monitor physician competency for GI motility diagnostics. Finally, as a profession and society, we must create certification processes to credential competent physicians. These advances are critical to optimizing the quality of GI motility diagnostics in practice.