Gerrit J. Hemmink

Esophageal pH-Impedance Monitoring in Patients With Therapy-Resistant Reflux Symptoms: 'On' or 'Off' Proton Pump Inhibitor?

BACKGROUND:In patients with proton pump inhibitor (PPI)-resistant symptoms, ambulatory 24-h pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Until now, it is unclear whether combined pH-impedance monitoring in these patients should be performed on or off PPI.METHODS:Thirty patients with symptoms of heartburn, chest pain, and/or regurgitation despite PPI twice daily underwent ambulatory 24-h pH-impedance monitoring twice, once on PPI and once after cessation of the PPI for 7 days. The order of the measurements was randomized. Reflux episodes were identified and classified as acid, weakly acidic, or weakly alkaline reflux. In addition, the symptom association probability (SAP) was calculated for each measurement.RESULTS:The total number of reflux episodes and proximal extent were not affected by PPI therapy. On PPI, there were fewer acid reflux episodes (49 ± 34 off PPI vs 20 ± 25 on PPI) while more weakly acidic reflux episodes were identified (24 ± 17 off PPI vs 48 ± 31 on PPI). Symptom association analysis identified 15 and 11 patients with a positive SAP in the measurement off and on PPI, respectively, the difference in yield of the SAP not being statistically significant. Eight of the 19 patients who had no symptoms or a negative SAP during measurement on PPI had a positive SAP off PPI therapy. In contrast, only 4 patients with a positive SAP on PPI were missed in the measurement off PPI therapy.CONCLUSIONS:In order to demonstrate or exclude GERD in patients with PPI-resistant symptoms, ambulatory 24-h pH-impedance monitoring should preferably be performed after cessation of PPI therapy because this approach seems to offer the best chance to assess a relationship between symptoms and reflux episodes.

Esophageal acid exposure decreases intraluminal baseline impedance levels.

OBJECTIVES:Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in healthy controls.METHODS:Ambulatory 24-h pH–impedance monitoring was performed in (i) 24 GERD patients with and 24 without pathological esophageal acid exposure as well as in 10 healthy controls and in (ii) 20 patients with refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline impedance levels in the most distal and the most proximal impedance channels were assessed.RESULTS:Median (interquartile range) distal baseline impedance in patients with physiological (2,090 (1,537–2,547) Ω) and pathological (781 (612–1,137) Ω) acid exposure was lower than in controls (2,827 (2,127–3,270) Ω, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure time and baseline impedance was observed (r=−0.7, P<0.001). In patients measured off and on PPI, median distal baseline impedance off PPI was significantly lower than on PPI (886 (716–1,354) vs. 1,372 (961–1,955) Ω, P<0.05) and distal baseline impedance in these groups was significantly lower than in healthy controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ significantly between the patients off PPI and on PPI (1,793 (1,384–2,489) vs. 1,893 (1,610–2,561) Ω); however, baseline impedance values in both measurements were significantly lower than in healthy controls (3,648 (2,815–3,932) Ω, both P<0.001).CONCLUSIONS:These findings suggest that baseline impedance is related to esophageal acid exposure and could be a marker of reflux-induced changes to the esophageal mucosa.

Supragastric belching in patients with reflux symptoms.

OBJECTIVES:Supragastric belching is a distinct belch pattern found in patients with excessive belching (aerophagia). Patients with gastroesophageal reflux disease (GERD) may also complain of belching. It has been shown that GERD patients swallow air more frequently and have more air-containing reflux episodes than do healthy controls. It is not known whether supragastric belches occur in patients with reflux symptoms.METHODS:Fifty consecutive patients with typical reflux symptoms and 10 healthy volunteers underwent ambulatory 24-h pH-impedance monitoring off proton pump inhibitor therapy. Patients filled out a questionnaire regarding their symptoms. The number and type of reflux episodes and supragastric belches during the measurement were assessed.RESULTS:In 24 of the 50 patients with reflux symptoms, supragastric belches were identified with a median incidence of 13 per 24 h (interquartile range: 6–52). In 5 of the 10 healthy volunteers 2, (1–6) supragastric belches were identified. In patients with reflux symptoms, 48% of the supragastric belches occurred in close temporal association with reflux episodes. Two different association patterns were observed. In 19 patients supragastric belches occurred immediately prior (<1 s) to the onset of the reflux episode. This pattern was observed in 30% of all supragastric belches. In 15 patients the supragastric belch occurred during the reflux episode, with the onset being 4–10 s after the start of the reflux episode. This pattern was observed in 18% of all identified supragastric belches.CONCLUSIONS:Supragastric belches occur more frequently in patients with typical reflux symptoms than in healthy subjects. These belches often occur in close association with acid and weakly acidic reflux episodes. Our findings suggest that supragastric belching elicits reflux in some cases and is the patients response to an unpleasant esophageal sensation in others.

Ambulatory oesophageal pH monitoring: a comparison between antimony, ISFET, and glass pH electrodes.

Background and aim Ambulatory oesophageal pH-impedance monitoring is a widely used test to evaluate patients with reflux symptoms. Several types of pH electrodes are available: antimony, ion sensitive field effect transistor (ISFET), and glass electrodes. These pH electrodes have not been compared directly, and it is uncertain whether these different types of pH electrodes result in similar outcome. Methods In an in-vitro model the response time, sensitivity, and drift of an antimony, ISFET, and glass pH electrode were assessed simultaneously after calibration at 22 °C and at 37 °C. All measurements were performed at 37 °C and repeated five times with new catheters of each type. Fifteen patients with reflux symptoms underwent 24-h pH monitoring off PPI therapy using antimony, ISFET, and glass pH electrodes simultaneously. Results After calibration at 22 °C, pH electrodes had similar response times, sensitivity and drift. In contrast to glass electrodes, antimony electrodes performed less accurately after calibration at 37 °C than after calibration at 22 °C. Calibration temperature did not affect ISFET electrodes significantly. During in-vivo experiments, significant differences were found in acid exposure times derived from antimony (4.0±0.8%), ISFET (5.7±1.1%), and glass pH electrodes (9.0±1.7%). Conclusion In vitro, antimony and glass pH electrodes are affected by different buffer components and temperature, respectively. In vivo, significant higher acid exposure times are obtained with glass electrodes compared with antimony and ISFET pH electrodes. ISFET electrodes produce stable in-vitro measurements and result in the most accurate in-vivo measurements of acid exposure time.

Computer analysis of 24-h esophageal impedance signals

Abstract Objective. To assess the accuracy of newly developed software for detection of gastro-esophageal reflux episodes in ambulatory 24-h impedance tracings. Material and methods. 24-h esophageal impedance recordings obtained from 60 consecutive patients with reflux symptoms were used in this study. The impedance tracings of the first 10 consecutive patients were analyzed manually by three investigators. Liquid-containing reflux episodes and their proximal extent were scored. A consensus between the three investigators was used as a gold standard. Computer analysis using dedicated software was performed, and the results were compared with the results of the consensus agreement. In addition, in order to assess the accuracy of symptom association analysis 24-h impedance tracings of all 60 patients were analyzed both manually by one investigator and using computer software. The number of reflux episodes and the results of symptom association analysis obtained by the human and computer analysis software were compared. Results. The consensus meeting resulted in a total of 625 reflux episodes. The mean sensitivity and the percentage of true-positives of analysis by individual investigators was 89 ± 1% and 94 ± 1%, respectively. Automated analysis had a sensitivity of 73 ± 4% and a proportion of true-positive reflux episodes of 62 ± 8%. Symptom association analysis performed by the computer and a human observer showed concordant results in 83% of the patients. Conclusions. Although not as good as manual analysis by experts, computer analysis can be a helpful tool to identify reflux episodes and to assess the relationship between reflux episodes and symptoms.

Esophageal motility and impedance characteristics in patients with Barrett's esophagus before and after radiofrequency ablation

Introduction Radiofrequency ablation (RFA) is a valuable treatment option in Barrett’s esophagus resulting in eradication of dysplasia and conversion of all Barrett’s epithelium into normal squamous epithelium. In Barrett’s esophagus, esophageal impedance monitoring is hampered by low baseline impedance values. Whether these low baselines are caused by an intrinsically low impedance of cylindrical epithelium or by the excessive reflux itself is hitherto unknown. Data on esophageal motility after RFA are scarce. Our aim was to examine the effect of RFA on esophageal motility and esophageal baseline impedance in patients with Barrett’s esophagus. Methods In 10 patients, conventional esophageal manometry and 24-h pH-impedance measurements were performed before and after RFA. The number and type of reflux episodes were assessed and baseline impedance values were measured in all recording segments. In another five patients, high-resolution manometry was performed before and after RFA. Results Complete regression of all Barrett’s epithelium was achieved in all 15 patients after 3±1 RFA sessions. Overall, no significant motility changes were found after RFA. Patients had excessive acid exposure times before and after RFA [25 (17–42) and 16 (9–24)%, respectively]. Baseline esophageal impedance values were low, with the lowest values in the distal recording segments. RFA increased baseline impedance in all recording segments in the upright position; in the supine position, the effect just failed to reach statistically significant levels. Conclusion RFA did not alter esophageal motility significantly. Low esophageal baseline impedance levels in patients with Barrett’s esophagus reflect, at least in part, intrinsic impedance properties of cylindrical epithelium, as baselines increased after conversion into neosquamous epithelium.

Esophageal pH-Impedance Monitoring in Patients With Therapy-Resistant Reflux Symptoms

BACKGROUND:In patients with proton pump inhibitor (PPI)-resistant symptoms, ambulatory 24-h pH-impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Until now, it is unclear whether combined pH-impedance monitoring in these patients should be performed on or off PPI.METHODS:Thirty patients with symptoms of heartburn, chest pain, and/or regurgitation despite PPI twice daily underwent ambulatory 24-h pH-impedance monitoring twice, once on PPI and once after cessation of the PPI for 7 days. The order of the measurements was randomized. Reflux episodes were identified and classified as acid, weakly acidic, or weakly alkaline reflux. In addition, the symptom association probability (SAP) was calculated for each measurement.RESULTS:The total number of reflux episodes and proximal extent were not affected by PPI therapy. On PPI, there were fewer acid reflux episodes (49 ± 34 off PPI vs 20 ± 25 on PPI) while more weakly acidic reflux episodes were identified (24 ± 17 off PPI vs 48 ± 31 on PPI). Symptom association analysis identified 15 and 11 patients with a positive SAP in the measurement off and on PPI, respectively, the difference in yield of the SAP not being statistically significant. Eight of the 19 patients who had no symptoms or a negative SAP during measurement on PPI had a positive SAP off PPI therapy. In contrast, only 4 patients with a positive SAP on PPI were missed in the measurement off PPI therapy.CONCLUSIONS:In order to demonstrate or exclude GERD in patients with PPI-resistant symptoms, ambulatory 24-h pH-impedance monitoring should preferably be performed after cessation of PPI therapy because this approach seems to offer the best chance to assess a relationship between symptoms and reflux episodes.

T1100 Computer Analysis of 24-h Esophageal Impedance Signals

G A A b st ra ct s parameter positive in 66.0%. Similar numbers of subjects 50 yrs underwent pH testing (890, 47.8% vs. 970, 52.2%), while females outnumberedmales (F=1244, 66.9%); proportions of subjects with individual symptoms did not differ by age or gender. The likelihood of elevated AET was higher in males compared to females (66.6% vs. 54.0%, p= 0.01), and this difference was maintained for all symptoms except cough. The likelihood of positive SAP, and both AET and SAP positive were similar in both genders. Males were less likely to have a normal pH study compared to females (26.9% vs. 36.5%, p=0.03), which remained true for all symptoms. When segregated by age, younger subjects (<50 yr) were more likely to have a positive SAP compared to older subjects (44.9% vs. 33.0%, p= 0.01), while older subjects were more likely to have elevated AET without a positive SAP (20.6% vs. 32.6%, p=0.01). These differences remained significant when individual symptoms were separately analyzed, except for cough, where the likelihood of a normal study was higher in younger subjects. CONCLUSIONS: Males are less symptomatic despite higher rates of abnormal AET, while younger subjects are more likely to demonstrate refluxsymptom associations with or without abnormal AET. These results support greater esophageal sensation in women and younger subjects that may decay with age. This observation may have important bearing on the interpretation of ambulatory pH results.

T1221 Speech Therapy in Patients with Excessive Supragastric Belching

The circular muscle fibers at the end of the esophagus are traditionally considered the lower esophageal sphincter. However, the first barrier to gastric reflux is actually the clasp/sling fiber complex of the stomach. Relaxation mediates transient lower esophageal sphincter relaxation underlying the pathophysiology of gastroesophageal reflux disease (GERD). This study determined the pharmacologic specificity of the nicotinic receptor mediated relaxation of pre-contracted strips of human and porcine clasp muscle fibers. Human specimens were obtained from organ transplant donors. Clasp fiber muscle strips were exposed to increasing carbachol concentrations (human) or acetylcholine with physostigmine to block cholinesterase (pig). At concentrations higher than 30 uM, abrupt relaxations were produced. After 60 minutes of repeated washing, strips were exposed to various ganglionic and neuromuscular nicotinic receptor antagonists for 30 minutes then rechallenged with cholinergic agonists. Results, as a percentage of relaxation in time control strips are shown in the figure below. The neuromuscular blockers d-tubocurarine, decamethonium (human) and pancuronium (pig) inhibited relaxation whereas the ganglionic blocker hexamethonium (human) and the alpha7 selective antagonist methyllycaconitine did not. Other ganglionic blockers such as MG624, NDNI and TMPH blocked these relaxations whereas mecamylamine was only partially effective in human tissue. These results indicate that the pharmacology of the nicotinic receptor mediating relaxation of the gastric clasp fibers may be unique and a potential target for development of selective agents for treatment of GERD.

S1938 Ambulatory Esophageal pH-Impedance Reflux Monitoring: A Comparison Between Antimony, ISFET and Glass pH Electrodes

Background and Aims: Studies describe adverse pulmonary effects in those who responded to the World Trade Center (WTC) disaster in New York City,with mention of aerodigestive symptoms (sx) described as GERD. Little is known about the mechanism of gastrointestinal sx in the WTC-exposed populations. The WTC Environmental Health Center (WTCEHC) was established to respond to health issues related to the attack on 9/11/01 and serves those exposed to WTC dust or fumes, including local residents, workers, and clean-up workers. We now report biopsy findings of post 9/11 refractory GERD-like sx. Methods: Participants were self-referred for medical sx and WTC exposure within the year after 9/11/2001. A standardized questionnaire was administered, including questions assessing the presence of heartburn and/or “acid indigestion.” Patients with sx were treated with proton pump inhibitors (PPIs); those with refractory sx were referred to a single gastroenterologist. Endoscopic results from patients evaluated between 1/11/07 and 10/23/08 are analyzed. Results: 160 patients were referred for endoscopy for refractory GERD-like symptoms. 33 patients whose sx resolved before their appointment were not endoscoped. 18 patients did not attend their appointment. 109 patients underwent endoscopy (mean age of 49.8, 48.6% male). 41.3% were white, 11.0% black, 8.3% Asian, 0.9% Native American, and 40% were undeclared. 64.2% of patients were Hispanic. Many patients (58.7%) had an income <15K. Visible abnormalities were seen on endoscopic evaluation in most patients (94.5%). On biopsy, 49.5% had reflux esophagitis, 44% had chronic inactive gastritis (CIG) and 43.1% had chronic active gastritis (CAG). 40% had evidence of infection with Helicobacter pylori (HP). CIG and CAG were associated with HP (P<0.0001) and Asian race (p=0.02). In patients who were HP negative, many had CIG (63.5%), CAG (19.1%), and reflux esophagitis (21.7%). Conclusions: GERD-like sx in a WTC exposed population were associated with gastritis as well as reflux esophagitis. Although we identified a high frequency of HP in our population, in patients without HP, gastritis remained common. The high frequency of HP in our population is most likely due to the country of origin of our patients. Further studies are ongoing to characterize the esophageal disease through pH testing and manometry. Biopsy and EGD results