Robert T. Kavitt

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.

Importance of Esophageal Manometry and pH Monitoring in the Evaluation of Patients with Refractory Gastroesophageal Reflux Disease: A Multicenter Study.

BACKGROUND Patients who have heartburn are treated with acid-reducing medications on the assumption that gastroesophageal reflux disease (GERD) is causing the symptom. In the absence of a response to therapy, patients are often assumed to have refractory GERD, and they are referred for laparoscopic antireflux surgery (LARS), often without further diagnostic evaluation. HYPOTHESIS We hypothesized that (1) in some patients with refractory GERD, the heartburn is not secondary to reflux, but rather to stasis and fermentation of food in the presence of achalasia and (2) esophageal manometry and pH monitoring are essential to establish proper diagnosis. PATIENTS AND METHODS Five hundred twenty-four patients, whose final diagnosis was achalasia, were referred to two quaternary care centers. Symptomatic evaluation, barium swallow, endoscopy, manometry, and pH monitoring were performed in all patients. RESULTS One hundred fifty-two patients (29%) had been treated with acid-reducing medications for an average of 29.3 months, and were referred for LARS because of lack of response to medical therapy. One patient had already been treated with a Nissen fundoplication. All patients were diagnosed with achalasia and underwent Heller myotomy and partial fundoplication. CONCLUSIONS The results of this study showed that (1) one-third of achalasia patients complained of heartburn and (2) patients with heartburn not responding to medical treatment must be carefully evaluated before referral to surgery. These data confirm the importance of esophageal manometry and pH monitoring in any patient considered for LARS.

Eosinophilic esophagitis: dilate or medicate? a cost analysis model of the choice of initial therapy

Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of

The role of impedance monitoring in patients with extraesophageal symptoms

1078. Similarly, it cost an average of

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

1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first.

Cerebral Edema and Hyperammonemia After Transjugular Intrahepatic Portosystemic Shunt Placement in a Cirrhotic Patient

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.

Diagnosis and Treatment of Eosinophilic Esophagitis in Adults

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.

Management of Helicobacter pylori Infection

Transjugular intrahepatic portosystemic shunt (TIPS) placement has been widely performed for nearly two decades and has been shown to alleviate refractory ascites in patients with cirrhosis. Hepatic encephalopathy after TIPS is rarely severe; however, a risk of cerebral edema resulting from hyperammonemia after TIPS does exist. Here we describe a case demonstrating the development of severe hepatic encephalopathy with cerebral edema caused by hyperammonemia as a complication of TIPS in a patient with chronic liver disease with relatively preserved liver function.