Normalization Of Esophageal Acid Exposure Research Articles

The Discrepancy Between Subjective and Objective Clinical Endpoints in Gastroesophageal Reflux Disease.

Therapeutic outcome in gastroesophageal reflux disease (GERD) is commonly determined by both subjective and objective clinical endpoints. Clinicians frequently use symptom improvement as a key benchmark of clinical success, in conjunction with normalization of objective parameters such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have demonstrated that a substantial number of patients rendered asymptomatic, whether through medical, surgical, or endoscopic intervention, continue to have persistent abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been demonstrated in therapeutic trials, where patients remained symptomatic despite normalization of esophageal acid exposure and complete resolution of esophageal inflammation. Moreover, there is no substantive evidence that symptomatic response to antireflux treatment requires complete esophageal mucosal healing or normalization of esophageal acid exposure. Thus, it appears that a certain level of improvement in objective parameters is needed to translate into meaningful changes in symptoms and health-related quality of life of GERD patients. This supports the need to reconsider the commonly used "hard" clinical endpoints to evaluate therapeutic trials in GERD.

The Impact of Magnetic Sphincter Augmentation (MSA) on Esophagogastric Junction (EGJ) and Esophageal Body Physiology and Manometric Characteristics.

To evaluate the impact of MSA on lower esophageal sphincter (LES) and esophageal body using high resolution impedance manometry. MSA is an effective treatment in patients with gastroesophageal reflux disease, but there is limited data on its impact on esophageal functional physiology. Patients who underwent MSA were approached 1-year after surgery for objective foregut testing consists of upper endoscopy, esophagram, high resolution impedance manometry, and esophageal pH-monitoring. Postoperative data were then compared to the preoperative measurements. A total of 100 patients were included in this study. At a mean follow up of 14.9(10.1) months, 72% had normalization of esophageal acid exposure. MSA resulted in an increase in mean LES resting pressure [29.3(12.9) vs 25(12.3), P < 0.001]. This was also true for LES overall length [2.9(0.6) vs 2.6(0.6), P = 0.02] and intra-abdominal length [1.2(0.7) vs 0.8(0.8), P < 0.001]. Outflow resistance at the EGJ increased after MSA as demonstrated by elevation in intrabolus pressure (19.6 vs 13.5 mmHg, P < 0.001) and integrated relaxation pressure (13.5 vs 7.2, P < 0.001). MSA was also associated with an increase in distal esophageal body contraction amplitude [103.8(45.4) vs 94.1(39.1), P = 0.015] and distal contractile integral [2647.1(2064.4) vs 2099.7(1656.1), P < 0.001]. The percent peristalsis and incomplete bolus clearance remained unchanged ( P = 0.47 and 0.08, respectively). MSA results in improvement in the LES manometric characteristics. Although the device results in an increased outflow resistance at the EGJ, the compensatory increase in the force of esophageal contraction will result in unaltered esophageal peristaltic progression and bolus clearance.

Systematic Review of Therapeutic Interventions for PPI Non-responsive Gastroesophageal Reflux Disease

Introduction: While laparoscopic fundoplication (LF) has been the treatment of choice for patients with gastroesophageal reflux disease (GERD) who remain symptomatic despite proton pump inhibitor (PPI) therapy, emerging interventions offer an alternative option. The aim of this study was to perform a systematic literature review to report symptomatic and physiologic impacts of therapeutic interventions to treat PPI nonresponsive GERD. Methods: A review of the PubMed, Cochrane, and EMBASE databases from 2005-2015 for GERD therapeutic interventions identified 2928 unique citations. All full-text, English language studies reporting interventions in adult populations with typical GERD symptoms on at least once daily PPI were included. Fifty-one studies met inclusion criteria and were categorized according therapy type: LF (21), endoscopic fundoplication (EF) (11), radiofrequency delivery (RFD) (10), magnetic sphincter augmentation (MSA) (6) and other (3) [Figure 1].Figure 1Results: As far out as 10 years, LF improves symptoms and physiologic parameters as measured by pH testing according; but PPI use increases (8.8% to 18.2%). EF improves GERD symptoms and eliminates PPI use in 58-93% of cases, but longest follow-up time is 3 years. In the only comparison of EF and LF, an open-label trial found better symptom remission rates (100% vs. 30%) and normalization of esophageal acid exposure (100% vs. 50%) with LF. RFD has mixed results. PPI independence ranges from 6.25-86.3% with RFD and only modest reductions in esophageal acid exposure (11.6% to 8.5%). MSA improves symptoms as far out as 5 years with normalization of acid exposure in 80% of patients and elimination of PPI in 75.3%. In an observational study, MSA, as compared to LF, provides similar improvements in GERD-HQRL scores, greater reduction in PPI use and better preservation of the ability to belch and vomit. Electrical stimulation of the lower esophageal sphincter, submucosal dissection and mucosal resection are emerging techniques that warrant further study. Results summarized in Figure 2.Figure 2Conclusion: LF remains the most proven option for the treatment of PPI nonresponsive GERD. EF and MSA are promising techniques with potentially fewer side effects, while evidence forRFD is mixed. Longer term, randomized trials comparing new techniques with LF are needed.

Issue Highlights

Issue Highlights

Magnets in the GI tract

Magnets in the GI tract

The Dose of Omeprazole Required to Achieve Adequate Intraesophageal Acid Suppression in Patients with Gastroesophageal Junction Specialized Intestinal Metaplasia and Barrett’s Esophagus

The mainstay of medical therapy for Barrett's esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown. The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett's esophagus (LSBE). Patients with GEJSIM and Barrett's esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated. A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526). The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett's mucosa.

Esophageal Sphincter Device for Gastroesophageal Reflux Disease

BackgroundPatients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter.MethodsWe prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported.ResultsThe primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed.ConclusionsIn this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.)

Laparoscopic Sphincter Augmentation Device Eliminates Reflux Symptoms and Normalizes Esophageal Acid Exposure

One- and 2-year evaluation of a feasibility trial (clinicaltrials.gov registration numbers NCT01057992, NCT01058070, and 01058564) to assess the safety and efficacy of a laparoscopically implanted sphincter augmentation device for the treatment of gastroesophageal reflux disease (GERD). A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients. At baseline, all patients had abnormal esophageal acid exposure on 24-hour pH monitoring and improved, but persistent, typical GERD symptoms while on acid suppression therapy with proton pump inhibitors (PPIs). The device comprises a miniature string of interlinked titanium beads, with magnetic cores, placed around the gastroesophageal junction. The magnetic bond between adjacent beads augments sphincter competence. The beads temporarily separate to accommodate a swallowed bolus, allow belching or vomiting, and reapproximate to augment the LES in the closed position. Patients were evaluated after surgery by GERD Health-Related Quality of Life symptom score, PPI usage, endoscopy, esophageal manometry, and 24-hour esophageal pH monitoring. The total mean GERD Health-Related Quality of Life symptom scores improved from a mean baseline value of 25.7 to 3.8 and 2.4 at 1- and 2-year follow-up, representing an 85% and 90% reduction, respectively (P < 0.0001). Complete cessation of PPI use was reported by 90% of patients at 1 year and by 86% of patients at 2 years. Early dysphagia occurred in 43% of the patients and self-resolved by 90 days. One device was laparoscopically explanted for persistent dysphagia without disruption of the anatomy or function of the cardia. There were no device migrations, erosions, or induced mucosal injuries. At 1 and 2 years, 77% and 90% of patients had a normal esophageal acid exposure. The mean percentage time pH was less than 4 decreased from a baseline of 11.9% to 3.1% (P < 0.0001) at 1 year and to 2.4% (P < 0.0001) at 2 years. Patient satisfaction was 87% at 1 year and 86% at 2 years. The new laparoscopically implanted sphincter augmentation device eliminates GERD symptoms without creating undue side effects and is effective at 1 and 2 years of follow-up.

Esophageal Acid Exposure on Proton Pump Inhibitors in Unselected Asymptomatic Gastroesophageal Reflux Disease Patients

Efficacy of proton pump inhibitors (PPIs) on symptoms of gastroesophageal reflux (GER) is supposed to result from normalization of esophageal acid exposure; however, recent data in selected severe patients have challenged this concept. The aim of the study was to investigate 24-hour esophagogastric pH in unselected patients with GER disease in symptomatic remission during PPIs. Thirty of the 31 consecutive patients with heartburn enrolled achieved adequate symptom control (<or=1 heartburn episode/wk) on PPIs o.d. (n=22) or b.d. (n=8); 3 refused pH monitoring, thus 27 tracings were analyzed. Medians (Interquartile Range); Intragastric tracings showed a wide range of inhibition of acid secretion, 61.2% (49.7% to 80.2%) time at pH>4, nocturnal acid breakthrough being shorter (P=0.03) on PPIs b.d. compared with PPIs o.d., 125 minutes (90 to 247) versus 253 minutes (210 to 340). Esophageal acid exposure was 3.3% (1.4% to 7.9%) time at pH<4, 9 patients having increased exposure (ie, >5.5%), 7 of whom on PPIs o.d. Patients with increased acid GER on PPIs had a higher prevalence of esophagitis (67% vs. 22%, P<0.05) and hiatus hernia (78% vs. 39%, P<0.1) at endoscopy off PPIs. One third of unselected patients with GER disease asymptomatic on PPIs have an increased esophageal acid exposure, especially if their PPI is administered o.d.

Endoscopic therapy for GERD: Does it have a future?

Approximately 20% of patients with gastroesophageal reflux disease (GERD) have symptoms refractory to long-term proton pump inhibitor (PPI) therapy. Furthermore, PPI therapy is expensive. Fundoplication is considered the gold standard of GERD therapy in terms of normalization of esophageal acid exposure and symptom control; however, this exposes the patient to the risks of surgery and anesthesia. Therefore, an endoscopic approach to treating GERD that obviates the need for PPIs and avoids surgical morbidity is desirable. Several endoscopic methods have been used, including radiofrequency ablation, implantation of foreign substances as bulking agents, and various tissue apposition strategies. The emerging field of GERD endotherapy is promising, but more rigorous, sham-controlled, long-term studies are required to elucidate its exact role in clinical practice. This review discusses the evolution of these concepts, describes specific endoscopic devices that have been developed, and explores the future of endotherapies as viable treatment alternatives for GERD.

Antireflux Transoral Incisionless Fundoplication Using EsophyX: 12‐Month Results of a Prospective Multicenter Study

BackgroundA novel transoral incisionless fundoplication (TIF) procedure using the EsophyX system with SerosaFuse fasteners was designed to reconstruct a full-thickness valve at the gastroesophageal junction through tailored delivery of multiple fasteners during a single-device insertion. The safety and efficacy of TIF for treating gastroesophageal reflux disease (GERD) were evaluated in a prospective multicenter trial.MethodsPatients (n = 86) with chronic GERD treated with proton pump inhibitors (PPIs) were enrolled. Exclusion criteria included an irreducible hiatal hernia > 2 cm.ResultsThe TIF procedure (n = 84) reduced all hiatal hernias (n = 49) and constructed valves measuring 4 cm (2–6 cm) and 230° (160°–300°). Serious adverse events consisted of two esophageal perforations upon device insertion and one case of postoperative intraluminal bleeding. Other adverse events were mild and transient. At 12 months, aggregate (n = 79) and stratified Hill grade I tight (n = 21) results showed 73% and 86% of patients with ≥50% improvement in GERD health-related quality of life (HRQL) scores, 85% discontinuation of daily PPI use, and 81% complete cessation of PPIs; 37% and 48% normalization of esophageal acid exposure; 60% and 89% hiatal hernia reduction; and 62% and 80% esophagitis reduction, respectively. More than 50% of patients with Hill grade I tight valves had a normalized cardia circumference. Resting pressure of the lower esophageal sphincter (LES) was improved significantly (p < 0.001), by 53%. EsophyX-TIF cured GERD in 56% of patients based on their symptom reduction and PPI discontinuation.ConclusionThe 12-month results showed that EsophyX-TIF was safe and effective in improving quality of life and for reducing symptoms, PPI use, hiatal hernia, and esophagitis, as well as increasing the LES resting pressure and normalizing esophageal pH and cardia circumference in chronic GERD patients.

WIRELESS PH-METRY COMBINED WITH SURVEILLANCE ENDOSCOPY IN BARRETTʼS ESOPHAGUS

Purpose: Recent evidence indicates that normalization of esophageal acid exposure in Barrett's esophagus (BE) may reduce the risk of neoplasia. The aims of this study were (1) assess the adequacy of PPI therapy on esophageal acid exposure in patients with BE, and (2) evaluate the safety and patient tolerance of wireless pH-metry performed in conjunction with surveillance endoscopy and biopsy. Methods: We enrolled 30 patients with BE presenting for surveillance endoscopy. Subjects maintained their usual dose of PPI. The EGD and biopsies were completed according to protocol. A wireless pH capsule (Bravo pH System) was placed immediately following EGD. All pts completed an 8-question satisfaction survey using a 6-point scale for each response (6 = best). Results: The combined procedures were successful in all 30 cases. Sixteen patients (53%) were on once daily (QD) PPI and 14 (47%) were on twice daily (BID) PPI. Fourteen patients had reflux symptoms on therapy. The mean length for BE was 3.3 cm and the mean disease duration 4.8 yrs. An average of 6.4 biopsies was performed per EGD. The % time pH <4 [median (interquartile range)] was 8.4% (11.5), 6.9% (9.4), and 13.2% (18.5) for total, upright and supine time. Esophageal acid exposure was similar in patients with and without GERD symptoms. Normalization of esophageal acid exposure is reported in Table. Ratings from the post-procedural survey demonstrated: satisfaction with the procedure (5.8), ability to carry on usual activities during pH-metry (5.6), and overall assessment of the experience (4.9).TableConclusions: In pts with BE (1) PPI therapy fails to control esophageal acid exposure in 44–57% of patients, (2) the absence of GERD symptoms during PPI therapy does not predict normalization of esophageal acid exposure, and (3) wireless pH-metry is safe and well-tolerated when performed in conjunction with surveillance EGD.

Control of esophageal acid exposure in Barrett’s — many ways to skin a cat!

Purpose: Current opinion suggests that continued abnormal esophageal acid exposure in Barrett's may play a role in progression to dysplasia and cancer. Normalization of esophageal acid has been shown to reduce the expression of proliferating cell nuclear antigen, suggesting that normalization of esophageal acid exposure may be a desirable goal in Barrett's patients. Our goal was to investigate which antisecretory therapy achieves optimal esophageal acid suppression in Barrett's esophagus patients.

Impact of esophageal acid exposure on the endoscopic reversal of Barrett’s esophagus

OBJECTIVE: Normalization of esophageal acid exposure had been assumed to be necessary for the reversal of Barrett’s esophagus with endoscopic therapy. This assumption is examined by evaluating the esophageal pH in a group of patients undergoing reversal therapy with fixed high-dose proton pump inhibitor therapy and endoscopic multipolar electrocoagulation (MPEC). METHODS: Patients with Barrett’s esophagus of 2–6 cm in length were treated with omeprazole (40 mg b.i.d.). They underwent 24-h esophageal pH monitoring 5 cm above the upper margin of the lower esophageal sphincter determined by a water-perfused catheter. They then underwent MPEC therapy to an endpoint of elimination of Barrett’s (reversal) by both endoscopy and biopsy 6 months after the last MPEC session or failure to achieve visual (endoscopic) reversal after six treatment sessions. RESULTS: Twenty patients had 24-h pH testing and reached a reversal endpoint. Three patients had abnormal pH tests, two total and supine and one supine only. These patients had documented reversal. The remaining 17 patients had normal pH testing but five failed reversal therapy. CONCLUSION: Barrett’s esophagus can be completely reversed with endoscopic therapy despite abnormal esophageal acid exposure. Also, patients can fail reversal even with normal esophageal acid exposure. The necessary reduction of esophageal acid exposure for reversal therapy has yet to be defined.

Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole

Background: Barrett's esophagus is mainly regarded as an acquired condition related to increased gastroesophageal reflux. Thus it is conceivable that abolition of acid reflux would lead to its regression. The aim of this study was to assess whether long-term treatment with high-dose omeprazole (60 mg/day) produces a consistent control of gastric acid production and normalizes the esophageal acid exposure, thus reducing the length of Barrett's epithelium. Methods: Fourteen patients (8 men and 6 women, mean age 52 years) with histologic diagnosis of columnar epithelium longer than 3 cm in the distal part of the esophagus were enrolled and began receiving 60 mg of omeprazole in a single daily morning dose. Before therapy and after 6 and 12 months of therapy, all patients had endoscopy with four-quadrant biopsies at 2 cm intervals. A 24-hour esophagogastric pH recording was performed at entry and after 10 days, 6 months, and 12 months of treatment in all patients. Results: The initial length of Barrett's epithelium (4.5 ± 1.9 cm) was significantly reduced after 6 months (3.1 ± 1.1; p < 0.01) and 12 months (2.1 ± 1.6; p < 0.005) of treatment. Values were significantly lower at 12 than at 6 months ( p < 0.03). The 24-hour mean gastric pH after 10 days (5.89 ± 0.58), 6 months (5.71 ± 0.55), and 12 months (5.54 ± 0.76) of therapy was always higher ( p < 0.001) than the basal level (1.9 ± 0.49). No significant difference in gastric pH was seen over the treatment period. The 24-hour mean percent of time in which pH in the esophagus was below 4.0 decreased significantly ( p < 0.001) from a basal rate of 29.4% to 3.5%, 3.0%, and 4.9% in the various time intervals of therapy. There was a normalization of esophageal acid exposure in all patients but two. Conclusions: It can be concluded that the antisecretory effect of 60 mg/day of omeprazole is consistent and is kept constant throughout the entire 1-year treatment period. The consequent normalization of esophageal acid exposure in almost all patients in our series led to a partial, but significant, regression in the length of Barrett's epithelium. (Gastrointest Endosc 1996;44:700-5)