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1.
Am. j. gastroenterol ; 115(9): 1393-1411, Sep. 2020.
Article in English | BIGG - GRADE guidelines | ID: biblio-1146637

ABSTRACT

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.


Subject(s)
Humans , Esophageal Achalasia/diagnosis , Esophageal Achalasia/therapy , Esophagogastric Junction/pathology , Endoscopy, Digestive System , Disease Management , Manometry
2.
Dis Esophagus ; 32(3)2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30124795

ABSTRACT

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.


Subject(s)
Esophageal pH Monitoring/statistics & numerical data , Gastroesophageal Reflux/diagnosis , Time Factors , Esophageal pH Monitoring/methods , Esophagus/chemistry , Female , Gastroesophageal Reflux/drug therapy , Humans , Hydrogen-Ion Concentration , Latent Class Analysis , Longitudinal Studies , Male , Proton Pump Inhibitors/therapeutic use , Reproducibility of Results , Retrospective Studies
3.
Dis Esophagus ; 31(9)2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30169645

ABSTRACT

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.


Subject(s)
Esophageal Achalasia/diagnosis , Esophageal Achalasia/therapy , Adult , Botulinum Toxins/therapeutic use , Child , Dilatation/methods , Dilatation/standards , Disease Management , Esophageal Achalasia/physiopathology , Esophagoscopy/methods , Esophagoscopy/standards , Evidence-Based Medicine , Female , Humans , Male , Myotomy/methods , Myotomy/standards , Risk Factors , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/standards
4.
Neurogastroenterol Motil ; 30(9): e13344, 2018 09.
Article in English | MEDLINE | ID: mdl-29644765

ABSTRACT

BACKGROUND AND AIMS: We recently developed 2 novel 3D high-resolution manometry (HRM) metrics of esophagogastric junction (EGJ) contractility to differentiate the lower esophageal sphincter (LES) and crural diaphragm (CD) elements of EGJ pressure. This study aimed to compare these metrics to the EGJ-contractile integral (EGJ-CI) and to analyze their correlation with esophageal acid exposure time (AET) on pH-metry. METHODS: Thirty-one gastro-oesophageal reflux disease (GERD) patients and 20 control subjects underwent 24-hour pH-metry and HRM using a 3D-HRM catheter. EGJ metrics were calculated during 3 consecutive respiratory cycles at rest. The EGJ-CI was calculated using the DCI tool in the ManoView software. 3D LES pressure (3D-LESP) and 3D-DHA, a metric quantifying the CD component of the 3D-HRM pressure topography, were calculated using a MATLAB program. Pearson correlation was used to calculate correlations with AET. KEY RESULTS: 3D-LESP, 3D-DHA, and EGJ-CI were all significantly lower in GERD patients than in control subjects (P < .05) and all were significantly correlated with AET (R = -.48, -.42, -.52, respectively, all P < .01). The 3D-DHA and EGJ-CI also strongly correlated with each other (R = .84, P < .001). CONCLUSIONS & INFERENCES: Both 3D-EGJ metrics were correlated with AET emphasizing the importance of both LES and CD function as a determinant of EGJ competence. 3D-DHA also strongly correlated with the EGJ-CI suggesting that EGJ-CI is strongly driven by the asymmetrical CD pressure component.


Subject(s)
Esophagogastric Junction/diagnostic imaging , Gastroesophageal Reflux/diagnostic imaging , Imaging, Three-Dimensional/methods , Manometry/methods , Adult , Esophageal Sphincter, Lower/diagnostic imaging , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged
5.
Aliment Pharmacol Ther ; 47(9): 1270-1277, 2018 May.
Article in English | MEDLINE | ID: mdl-29528128

ABSTRACT

BACKGROUND: Oesophageal hypervigilance and anxiety can drive symptom experience in chronic oesophageal conditions, including gastro-oesophageal reflux disease, achalasia and functional oesophageal disorders. To date, no validated self-report measure exists to evaluate oesophageal hypervigilance and anxiety. AIMS: This study aims to develop a brief and reliable questionnaire assessing these constructs, the oesophageal hypervigilance and anxiety scale (EHAS). METHODS: Questions for the EHAS were drawn from 4 existing validated measures that assessed hypervigilance and anxiety adapted for the oesophagus. Patients who previously underwent high-resolution manometry testing at a university-based oesophageal motility clinic were retrospectively identified. Patients were included in the analysis if they completed the EHAS as well as questionnaires assessing symptom severity and health-related quality of life at the time of the high-resolution manometry. RESULTS: Nine hundred and eighty-two patients aged 18-85 completed the study. The EHAS demonstrates excellent internal consistency (α = 0.93) and split-half reliability (Guttman = 0.87). Inter-item correlations indicated multicollinearity was not achieved; thus, no items were removed from the original 15-item scale. Principal components factor analysis revealed two subscales measuring symptom-specific anxiety and symptom-specific hypervigilance. Construct validity for total and subscale scores was supported by positive correlations with symptom severity and negative correlations with health-related quality of life. CONCLUSIONS: The EHAS is a 15-item scale assessing oesophageal hypervigilance and symptom-specfic anxiety. The EHAS could be useful in evaluating the role of these constructs in several oesophageal conditions in which hypersensitivity, hypervigilance and anxiety may contribute to symptoms and impact treatment outcomes.


Subject(s)
Anxiety/diagnosis , Esophageal Diseases/diagnosis , Gastroesophageal Reflux/diagnosis , Adult , Aged , Anxiety/complications , Anxiety/pathology , Chronic Disease , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/pathology , Esophageal Diseases/etiology , Esophageal Diseases/pathology , Female , Gastroesophageal Reflux/pathology , Humans , Male , Middle Aged , Quality of Life , Reproducibility of Results , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome
6.
Neurogastroenterol Motil ; 30(6): e13287, 2018 06.
Article in English | MEDLINE | ID: mdl-29315993

ABSTRACT

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.


Subject(s)
Esophageal Achalasia/diagnosis , Esophageal Achalasia/physiopathology , Health Surveys/standards , Manometry/standards , Severity of Illness Index , Adult , Aged , Cross-Sectional Studies , Female , Health Surveys/methods , Humans , Male , Manometry/methods , Middle Aged , Registries/standards , Reproducibility of Results , Retrospective Studies , Weight Loss/physiology
7.
Neurogastroenterol Motil ; 30(6): e13289, 2018 06.
Article in English | MEDLINE | ID: mdl-29322591

ABSTRACT

BACKGROUND: Novel high-resolution impedance manometry (HRIM) metrics of bolus flow time (BFT) and esophageal impedance integral (EII) ratio have demonstrated clinical utility, though the reliability of their analysis has not been assessed. We aimed to evaluate the inter-rater agreement of the BFT and EII ratio. METHODS: HRIM studies including five upright, liquid swallows from 40 adult patients were analyzed by two raters using a customized MATLAB program to generate the BFT and EII ratio. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC) for median values generated per patient and also for all 200 swallows. KEY RESULTS: The ICC (95% confidence interval, CI) for BFT was 0.873 (0.759-0.933) for median values and 0.838 (0.778-0.881) for all swallows. The ICC (95% CI) for EII ratio was 0.983 (0.968-0.991) for median values and 0.905 (0.875-0.928) for all swallows. Median values for both BFT and EII ratio were similar between the two raters (P-values .05). CONCLUSIONS AND INFERENCES: The BFT and EII ratio can be reliably calculated as supported by generally excellent inter-rater agreement. Thus, broader utilization of these measures appears feasible and would facilitate further evaluation of their clinical utility.


Subject(s)
Deglutition/physiology , Electric Impedance , Esophagus/physiology , Manometry/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Manometry/standards , Middle Aged , Observer Variation , Time Factors , Young Adult
8.
Neurogastroenterol Motil ; 30(5): e13262, 2018 05.
Article in English | MEDLINE | ID: mdl-29193439

ABSTRACT

BACKGROUND: We hypothesized that symptoms in Jackhammer esophagus (JH) are associated with an imbalance between the prepeak and postpeak phases of contraction. Thus, we developed a method to distinguish the contractile integral components of prepeak and postpeak phase contractile activity to determine the contribution of each phase and their association with dysphagia. METHODS: Patients diagnosed with JH were enrolled and compared to controls. The first five intact swallows during manometry were analyzed. A single swallow was divided into a prepeak and postpeak phase. The contractile integral of each phase and its corresponding time-controlled integral were computed. All metrics were compared between controls and JH patients subcategorized by the impaction dysphagia question (IDQ) score with cut-off of 6. KEY RESULTS: Thirty eight JH patients and 71 controls were included. Twelve JH patients had IDQ ≤ 6 and 26 with IDQ > 6. JH patients had higher contractile integral in both phases, and a higher ratio between postpeak to prepeak contractile integral independent of duration. Similarly, JH patients with an IDQ > 6 had higher contractile metrics than those with IDQ ≤ 6. There was a correlation between the IDQ score and the ratio within the postpeak to prepeak contractile integral (r = .375). CONCLUSIONS: Abnormalities in contractile integral of the postpeak phase are more significant in JH with higher dysphagia scores Although the total postpeak contractile integral was higher in symptomatic patients, this was associated with longer duration of postpeak activity suggesting that dysphagia patients with JH have a defect in the postpeak phase of peristalsis.


Subject(s)
Deglutition Disorders/diagnosis , Deglutition/physiology , Esophageal Motility Disorders/diagnosis , Esophagus/physiopathology , Adult , Aged , Deglutition Disorders/physiopathology , Esophageal Motility Disorders/physiopathology , Female , Humans , Male , Manometry , Middle Aged , Muscle Contraction , Peristalsis/physiology , Retrospective Studies , Symptom Assessment
9.
Article in English | MEDLINE | ID: mdl-29110377

ABSTRACT

BACKGROUND: Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. METHODS: In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. KEY RESULTS: On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P < .001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. CONCLUSIONS & INFERENCES: Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.


Subject(s)
Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use , Scleroderma, Systemic/drug therapy , Case-Control Studies , Endoscopy, Gastrointestinal , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/etiology , Humans , Male , Manometry , Middle Aged , Retrospective Studies , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnosis , Treatment Outcome
10.
Article in English | MEDLINE | ID: mdl-29098750

ABSTRACT

BACKGROUND: Increased esophagogastric junction (EGJ) distensibility is thought to contribute to gastroesophageal reflux disease (GERD). Using the functional lumen imaging probe (FLIP), we aimed to assess the esophageal response to distension among patients undergoing esophageal pH monitoring. METHODS: 25 patients (ages 22-73; 13 females) who underwent ambulatory wireless esophageal pH testing while off proton-pump inhibitors were evaluated with FLIP during sedated upper endoscopy. Esophageal reflux was quantified by total percent acid exposure time (AET; <6% was considered normal). FLIP studies were analyzed using a customized program generate FLIP topography plots to identify esophageal contractility patterns and to calculate the EGJ-distensibility index (DI). Reflux symptoms were assessed with the GERDQ. Values reflect median (interquartile range). RESULTS: Among all patients, the AET was 7.2% (3.7-11.1) and EGJ-DI was 4.2 (2.5-7.6) mm2 /mm Hg. Repetitive antegrade contractions (RACs) were induced in 19/25 (76%) of patients; AET was lower among patients with (6.1%, 3-7.8) than without (14.9, 8.5-22.3) RACs (P = .009). Correlation was weak and insignificant between AET and EGJ-DI, GERDQ and AET, and GERDQ and EGJ-DI. Patients with abnormal AET (n = 16) and normal AET (n = 9) had similar EGJ-DI, 4.6 mm2 /mm Hg (2.9-9.2) vs 3.2 (2.2-5.1), P = .207 and GERDQ, P = .138. CONCLUSIONS: Abnormal esophageal acid exposure was associated with an impaired contractile response to volume distention of the esophagus. This supports that acid exposure is dependent on acid clearance mechanisms.


Subject(s)
Esophageal Motility Disorders/physiopathology , Esophagogastric Junction/physiopathology , Gastroesophageal Reflux/physiopathology , Adult , Aged , Esophageal Motility Disorders/complications , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/complications , Humans , Male , Middle Aged , Muscle Contraction , Young Adult
11.
Article in English | MEDLINE | ID: mdl-28730686

ABSTRACT

BACKGROUND: The Chicago Classification v3.0 proposed extending the distal contractile integral (DCI) measurement domain to include the lower esophageal sphincter (LES) to enhance the detection of esophageal hypercontractility. However, normative and clinical data for this approach are unreported. We aimed to describe the application of an extended DCI measurement in asymptomatic controls and patients. METHODS: High-resolution manometry (HRM) of 65 asymptomatic controls and 72 patients with normal motility were evaluated retrospectively. Dysphagia and chest pain symptoms were assessed using the brief esophageal dysphagia questionnaire (BEDQ); ≥10 was considered abnormal. HRM studies of 10 supine swallows were evaluated via the standard DCI and an extended DCI measurement domain (DCI+) to include the lower esophageal sphincter (LES) during and after the peristaltic wave. The DCI-increment was calculated as the DCI+ minus DCI. KEY RESULTS: Among controls, the median (5-95th percentile) DCI+ was 1915 (1359-6921) mm Hg/cm/s and DCI-increment was 534 (126-1488) mm Hg/cm/s. Two patients (3%) had ≥2 swallows with DCI+ >8000 mm Hg/cm/s and seven (10%) patients had at least one swallow with DCI+ >8000 mm Hg/cm/s, ie, had potential motility reclassification by application of DCI+. Seven of these nine patients (78%) were evaluated for dysphagia or chest pain, but only 3/9 (33%) had an abnormal BEDQ. CONCLUSIONS AND INFERENCES: Extension of the DCI measurement domain may aid quantifying hypercontractility that involves the LES. However, adjusting management strategies based on reclassification of patients with otherwise normal motility should be cautiously considered.


Subject(s)
Esophageal Sphincter, Lower/diagnostic imaging , Esophageal Sphincter, Lower/physiopathology , Manometry/methods , Muscle Contraction , Adult , Deglutition Disorders/diagnostic imaging , Female , Humans , Male , Retrospective Studies , Young Adult
12.
Dis Esophagus ; 30(9): 1-14, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28859357

ABSTRACT

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.


Subject(s)
Fundoplication/methods , Gastroesophageal Reflux/therapy , Gastroesophageal Reflux/drug therapy , Humans , Laparoscopy , Magnets , Proton Pump Inhibitors/therapeutic use , Radiofrequency Therapy , Retreatment , Treatment Failure
13.
Dis Esophagus ; 30(9): 1-15, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28859358

ABSTRACT

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.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/genetics , Proton Pump Inhibitors/therapeutic use , Baclofen/therapeutic use , Benzamides/therapeutic use , Esophageal Sphincter, Lower/drug effects , Gastrointestinal Agents/therapeutic use , Genotype , Histamine H2 Antagonists/therapeutic use , Humans , Morpholines/therapeutic use , Muscle Relaxants, Central/therapeutic use , Muscle Relaxation/drug effects , Treatment Failure
14.
Neurogastroenterol Motil ; 29(12)2017 Dec.
Article in English | MEDLINE | ID: mdl-28544357

ABSTRACT

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.


Subject(s)
Gastroesophageal Reflux/physiopathology , Esophagogastric Junction/physiopathology , Esophagus , Humans , Manometry/methods
15.
Article in English | MEDLINE | ID: mdl-28544141

ABSTRACT

BACKGROUND: The current paradigm of measuring esophageal contractile vigor assesses the entirety of a pressure wave using a single measurement, the distal contractile integral (DCI). We hypothesize that an assessment identifying separate phases of the contractile pressure wave before and after the pressure peak may help distinguish abnormalities in patients presenting with chest pain and dysphagia. The aim of the present study was to develop a technique to assess the individual phases and report on the values in healthy controls. METHODS: Seventy-one healthy controls were enrolled. High-resolution manometry studies of five intact liquid swallows in both supine and upright positions were analyzed using a customized MATLAB program to divide swallows into a prepeak phase and postpeak phase, and compute the contractile integral of both phases. The contractile integrals were also controlled by duration over each phase. KEY RESULTS: The composite DCI measurement in healthy controls appears to be weighted toward slightly higher contractile activity during postpeak phase based on postpeak to prepeak ratios in both the supine and upright position (1.50 and 1.49, respectively). The contribution of postpeak phase on the composite DCI was weakened when controlled by time (0.92 and 0.96 in both supine and upright position, respectively). CONCLUSIONS AND INFERENCES: We developed a novel measurement focused on separating the prepeak and postpeak components of the peristaltic contractile activity during swallowing. Using this technique, it appears that overall contractile activity is higher during postpeak phase and this is related to the longer time component during this phase.


Subject(s)
Deglutition/physiology , Esophagus/physiology , Manometry/methods , Peristalsis/physiology , Adult , Female , Humans , Male , Middle Aged , Muscle Contraction/physiology , Muscle, Smooth/physiology , Pressure , Young Adult
16.
Neurogastroenterol Motil ; 29(10): 1-15, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28370768

ABSTRACT

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.


Subject(s)
Esophageal pH Monitoring/methods , Gastroesophageal Reflux/diagnosis , Monitoring, Ambulatory/methods , Humans
17.
Article in English | MEDLINE | ID: mdl-28054418

ABSTRACT

BACKGROUND: Based on a fully coupled computational model of esophageal transport, we analyzed how varied esophageal muscle fiber architecture and/or dual contraction waves (CWs) affect bolus transport. Specifically, we studied the luminal pressure profile in those cases to better understand possible origins of the peristaltic transition zone. METHODS: Two groups of studies were conducted using a computational model. The first studied esophageal transport with circumferential-longitudinal fiber architecture, helical fiber architecture and various combinations of the two. In the second group, cases with dual CWs and varied muscle fiber architecture were simulated. Overall transport characteristics were examined and the space-time profiles of luminal pressure were plotted and compared. KEY RESULTS: Helical muscle fiber architecture featured reduced circumferential wall stress, greater esophageal distensibility, and greater axial shortening. Non-uniform fiber architecture featured a peristaltic pressure trough between two high-pressure segments. The distal pressure segment showed greater amplitude than the proximal segment, consistent with experimental data. Dual CWs also featured a pressure trough between two high-pressure segments. However, the minimum pressure in the region of overlap was much lower, and the amplitudes of the two high-pressure segments were similar. CONCLUSIONS & INFERENCES: The efficacy of esophageal transport is greatly affected by muscle fiber architecture. The peristaltic transition zone may be attributable to non-uniform architecture of muscle fibers along the length of the esophagus and/or dual CWs. The difference in amplitude between the proximal and distal pressure segments may be attributable to non-uniform muscle fiber architecture.


Subject(s)
Esophagus/physiology , Models, Biological , Muscle, Smooth/physiology , Peristalsis , Animals , Computer Simulation , Humans , Muscle Contraction , Muscle, Smooth/anatomy & histology
18.
Article in English | MEDLINE | ID: mdl-27647522

ABSTRACT

BACKGROUND: High-resolution impedance manometry (HRIM) allows evaluation of esophageal bolus retention, flow, and pressurization. We aimed to perform a collaborative analysis of HRIM metrics to evaluate patients with non-obstructive dysphagia. METHODS: Fourteen asymptomatic controls (58% female; ages 20-50) and 41 patients (63% female; ages 24-82), 18 evaluated for dysphagia and 23 for reflux (non-dysphagia patients), with esophageal motility diagnoses of normal motility or ineffective esophageal motility, were evaluated with HRIM and a global dysphagia symptom score (Brief Esophageal Dysphagia Questionnaire). HRIM was analyzed to assess Chicago Classification metrics, automated pressure-flow metrics, the esophageal impedance integral (EII) ratio, and the bolus flow time (BFT). KEY RESULTS: Significant symptom-metric correlations were detected only with basal EGJ pressure, EII ratio, and BFT. The EII ratio, BFT, and impedance ratio differed between controls and dysphagia patients, while the EII ratio in the upright position was the only measure that differentiated dysphagia from non-dysphagia patients. CONCLUSIONS & INFERENCES: The EII ratio and BFT appear to offer an improved diagnostic evaluation in patients with non-obstructive dysphagia without a major esophageal motility disorder. Bolus retention as measured with the EII ratio appears to carry the strongest association with dysphagia, and thus may aid in the characterization of symptomatic patients with otherwise normal manometry.


Subject(s)
Deglutition Disorders/diagnosis , Deglutition Disorders/physiopathology , Electric Impedance , Manometry/methods , Adult , Aged , Aged, 80 and over , Deglutition Disorders/classification , Esophageal Motility Disorders/classification , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/physiopathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
19.
Article in English | MEDLINE | ID: mdl-27739183

ABSTRACT

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.


Subject(s)
Benchmarking/standards , Clinical Competence/standards , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/physiopathology , Manometry/standards , Physician's Role , Benchmarking/methods , Esophagus/physiopathology , Humans , Manometry/methods , Surveys and Questionnaires
20.
Article in English | MEDLINE | ID: mdl-27477826

ABSTRACT

BACKGROUND: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.


Subject(s)
Deglutition/physiology , Esophageal Sphincter, Lower/physiology , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/physiopathology , Manometry/standards , Muscle Relaxation/physiology , Adult , Aged , Female , Humans , Male , Manometry/methods , Middle Aged , Reproducibility of Results
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