Tina Higginbotham

Mucosal Impedance Discriminates GERD From Non-GERD Conditions

BACKGROUND & AIMS Current diagnostic tests for gastroesophageal reflux disease (GERD) are suboptimal and do not accurately and reliably measure chronicity of reflux. A minimally invasive device has been developed to assess esophageal mucosal impedance (MI) as a marker of chronic reflux. We performed a prospective longitudinal study to investigate MI patterns in patients with GERD and common nonreflux conditions, to assess MI patterns before and after treatment with proton pump inhibitors and to compare the performance of MI and wireless pH tests. METHODS We evaluated MI in 61 patients with erosive esophagitis, 81 with nonerosive but pH-abnormal GERD, 93 without GERD, 18 with achalasia, and 15 with eosinophilic esophagitis. MI was measured at the site of esophagitis and at 2, 5, and 10 cm above the squamocolumnar junction in all participants. MI was measured before and after acid suppressive therapy, and findings were compared with those from wireless pH monitoring. RESULTS MI values were significantly lower in patients with GERD (erosive esophagitis or nonerosive but pH-abnormal GERD) or eosinophilic esophagitis than in patients without GERD or patients with achalasia (P < .001). The pattern of MI in patients with GERD differed from that in patients without GERD or patients with eosinophilic esophagitis; patients with GERD had low MI closer to the squamocolumnar junction, and values increased axially along the esophagus. These patterns normalized with acid suppressive therapy. MI patterns identified patients with esophagitis with higher levels of specificity (95%) and positive predictive values (96%) than wireless pH monitoring (64% and 40%, respectively). CONCLUSIONS Based on a prospective study using a prototype device, measurements of MI detect GERD with higher levels of specificity and positive predictive values than wireless pH monitoring. Clinical Trials.gov, Number: NCT01556919.

Symptom reports are not reliable during ambulatory reflux monitoring.

OBJECTIVES:Patient reporting of symptom events during ambulatory reflux monitoring is commonly performed with little data regarding its accuracy. We employed a novel time-synchronized ambulatory audio recording of symptom events simultaneously with prolonged pH/impedance monitoring to assess temporal accuracy of patient-reported symptoms.METHODS:An acoustic monitoring system was employed to detect cough events via tracheal and chest wall sounds and it was temporally synchronized with an ambulatory impedance/pH monitoring system. Patients were instructed to record their symptoms in the usual manner. Six separate observers independently listened to the 24-h audio recordings and logged the exact timing of each cough event. Patients were blinded to study design and the audio reviewers were blinded to their own reports and those of patients and other reviewers. Concurrence of audio recordings and patient-reported symptoms were tested for three separate time thresholds: 1, 2, and 5 min.RESULTS:The median (interquartile range (IQR)) number of cough events by audio detection was significantly (P<0.001) higher than those reported by patients: 216 (90–275) and 34 (22–60), respectively. There was significantly (P<0.001) higher agreement among the audio recording listeners (substantial to almost perfect agreement; kappa=0.77–0.82) than between the audio recording and patient-reported symptoms (slight to fair agreement; kappa=0.13–0.27). Patients did not report 91, 82, and 71% of audible cough events based on 1-, 2-, and 5-min concordance time windows, respectively.CONCLUSIONS:We found that patients do not report the majority of their symptoms during ambulatory reflux monitoring even within a 5-min time window of the true event and advise caution in clinical decision-making based solely on symptom indices.

Use of Direct, Endoscopic-Guided Measurements of Mucosal Impedance in Diagnosis of Gastroesophageal Reflux Disease

BACKGROUND & AIMS Diagnostic tests for gastroesophageal reflux disease (GERD) are constrained because measurements are made at a single time point, so the long-term effects on the mucosa cannot be determined. We developed a minimally invasive system to assess changes in esophageal mucosal impedance (MI), a marker of reflux. We measured the extent of changes in MI along the esophagus and show that the device to assess MI can be used to diagnose patients with GERD. METHODS A single-channel MI catheter composed of a unique sensor array was designed to easily traverse the working channel of an upper endoscope. We performed a prospective longitudinal study of patients with erosive esophagitis (n = 19), nonerosive but pH-positive GERD (n = 23), and those without GERD (n = 27). MI was measured at the site of esophagitis as well as 2, 5, and 10 cm above the squamocolumnar junction. The MI values were compared among groups, at different levels along the esophageal axis. RESULTS Median MI values were significantly lower at the site of erosive mucosa (811 Ω; range, 621-1272 Ω) than other nonerosive regions (3723 Ω; range, 2421-4671 Ω; P = .001), and were significantly lower at 2 cm above the squamocolumnar junction in patients with GERD (2096 Ω; range, 1415-2808 Ω), compared with those without GERD (3607 Ω; range, 1973-4238 Ω; P = .008). There was a significant and graded increase in MI along the axis of the distal to proximal esophagus in patients with GERD that was not observed in individuals without reflux (P = .004). CONCLUSIONS Measurements of MI along the esophagus can be used to identify patients with GERD. ClinicalTrials.gov, number NCT01194323.

The role of impedance monitoring in patients with extraesophageal symptoms

Ambulatory esophageal impedance monitoring is commonly employed to assess for nonacid reflux in patients with extraesophageal reflux. We aimed to determine if on therapy impedance data can be predicted from off therapy upper endoscopy, manometry, or pH parameters.

Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux

Background & Aims The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. Methods We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow‐up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52–77 mo). Results The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31–4.17) and poor preoperative symptom response to acid‐suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05–7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P < .01). The rate of symptom recurrence was lowest among patients with primary typical reflux symptoms who had a partial or full symptom response to AST (P < .01). The severity of acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. Conclusions In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with extraesophageal symptoms of GERD than in patients with typical GERD. Response to AST before surgery was associated with ARS effectiveness in patients with extraesophageal reflux symptoms. Caution should be exercised when advocating ARS for patients with extraesophageal symptoms that do not respond to AST.

Symptom association probability does not reliably distinguish functional heartburn from reflux hypersensitivity

Symptom association probability (SAP) is thought to distinguish reflux hypersensitivity from functional disorders. A diagnosis of hypersensitive oesophagus (SAP‐positive) indicates that gastro‐oesophageal reflux disease (GERD) is the cause of continued symptoms.

Video on Diet Before Outpatient Colonoscopy Does Not Improve Quality of Bowel Preparation: A Prospective, Randomized, Controlled Trial

Objectives:Successful outpatient colonoscopy (CLS) depends on many factors including the quality of a patient’s bowel preparation. Although education on consumption of the pre-CLS purgative can improve bowel preparation quality, no study has evaluated dietary education alone. We have created an educational video on pre-CLS dietary instructions to determine whether dietary education would improve outpatient bowel preparation quality.Methods:A prospective randomized, blinded, controlled study of patients undergoing outpatient CLS was performed. All patients received a 4 l polyethylene glycol-based split-dose bowel preparation and standard institutional pre-procedure instructions. Patients were then randomly assigned to an intervention arm or to a no intervention arm. A 4-min educational video detailing clear liquid diet restriction was made available to patients in the intervention arm, whereas those randomized to no intervention did not have access to the video. Patients randomized to the video were provided with the YouTube video link 48–72 h before CLS. An attending endoscopist blinded to randomization performed the CLS. Bowel preparation quality was scored using the Boston Bowel Preparation Scale (BBPS). Adequate preparation was defined as a BBPS total score of ≥6 with all segment scores ≥2. Wilcoxon rank-sum and Pearson’s χ2-tests were performed to assess differences between groups.Results:Ninety-two patients were randomized (video: n=42; control: n=50) with 47 total video views being tallied. There were no demographic differences between groups. There was no statistically significant difference in adequate preparation between groups (video=74%; control=68%; P=0.54).Conclusions:The availability of a supplementary patient educational video on clear liquid diet alone was insufficient to improve bowel preparation quality when compared with standard pre-procedure instruction at our institution.

Esophageal Mucosal Impedance Patterns Discriminate Patients With Eosinophilic Esophagitis From Patients With GERD

Background & Aims: It is a challenge to make a diagnosis of eosinophilic esophagitis (EoE) because its symptoms and histologic features overlap with those of gastroesophageal reflux disease (GERD). A minimally invasive device was recently developed to detect mucosal impedance (MI) that measures epithelial integrity during upper endoscopy. We aimed to quantify MI along the esophagus and identify patterns that differentiated patients with and without GERD from those with EoE, and determine whether MI values and patterns are sufficient to identify patients with EoE using histologic findings as a reference. Methods: We performed a retrospective analysis of 91 patients with upper gastrointestinal symptoms referred for diagnostic testing for GERD and EoE from 2012 through 2014 (discovery set). During the first endoscopy, MI measurements were obtained at 2, 5, and 10 cm from the squamocolumnar junction. GERD was confirmed by ambulatory pH tests, and histologic analyses of biopsies were used to confirm EoE. We then used statistical modeling to identify MI patterns along the esophagus (at 10 cm, 5 cm, and 2 cm) that associated with GERD vs EoE. We validated our findings in a prospective cohort of 49 patients undergoing elective upper endoscopy for dysphagia, from 2015 through 2016, testing the ability of MI patterns to identify patients with vs. without EoE. Results: We found patients with EoE to have a unique MI pattern, with low values along the esophageal axis. MI measurements at 5 cm could discern patients with normal vs abnormal mucosa with 83% sensitivity and 79% specificity, and patients with EoE vs GERD with 84% sensitivity and 70% specificity; these measurements differentiated the patient populations with the highest level of accuracy of any of the 6 measurements tested. In the validation study, a rater using the esophageal MI pattern identified patients with EoE with 100% sensitivity and 96% specificity. Conclusion: We identified and validated a pattern of MI along the esophagus that can identify patients with EoE vs normal mucosa or GERD with high levels of sensitivity.

Prospective Study of Upper Esophageal Sphincter Assist Device for Treating Extraesophageal Reflux

Background: Extraesophageal reflux (EER) is a heterogeneous disease, caused by the regurgitation of gastroduodenal contents into the larynx. The Upper Esophageal Sphincter (UES) Assist Device is a novel medical device designed to prevent gastroduodenal reflux into the laryngopharynx. Objective: A multicenter prospective study assessing safety and effectiveness of the UES Assist Device in patients with EER. Methods: Patients with Reflux Symptom Index (RSI) >13 were enrolled. The device was fit and adjusted to at least 20 mmHg applied external cricoid pressure. The primary effectiveness end-point was reduction in RSI at 4-weeks compared to baseline. 36-Item Short Form Health Survey or SF-36® Health Survey (SF-36), patient and physician satisfaction, and Functional Outcomes of Sleep Questionnaire (FOSQ) were secondary end-points. Safety was based on reported adverse reactions. Results: Eighty-nine of 95 patients completed the study [mean(Standard Deviation (SD)) age=48.8(+/-13.7); mean(SD) Body Mass Index (BMI)=25.5(+/-4.2); 69.5% female, 81.1% Caucasian]. Most common troublesome symptoms included chronic cough (21.3%) and excess mucus/post nasal drip (20.2%). There was a significant (p<0.0001) reduction in median (Intelligence Quotient (IQ)) RSI at 2and 4-weeks [12.5(8.0-20.0) and 10.0(5.8-16.5), respectively] compared to baseline [25.6(21.0-30.0)]. Eighty-two percent (82%) reported improvement greater than 25% with 30.1% having an improvement of 75% or more. 84.7% of patients and 95.2% of providers reported satisfaction. Adverse events were generally mild and transient with no withdrawals due to adverse events. Conclusion: The UES Assist Device is a safe and effective for the treatment of extraesophageal symptoms and may be an alternative for the many patients that do not respond to Proton Pump Inhibitors (PPI) therapy.