Leonardo Rodríguez1, Patricia Rodriguez2, Beatriz Gómez2, Juan C Ayala3, Danny Oxenberg3, Alberto Perez-Castilla3, Manoel G Netto4, Edy Soffer5, W John Boscardin6, Michael D Crowell7. 1. Department of Surgery, CCO Obesidad y Diabetes, Santiago, Chile. Electronic address: doctor@leonardorodriguez.cl. 2. Department of Surgery, CCO Obesidad y Diabetes, Santiago, Chile. 3. Department of Gastroenterology, Clinic Indisa, Santiago, Chile. 4. Department of Surgery, Gastro Obeso Center, Sao Paulo, Brazil. 5. University of Southern California, Los Angeles, CA. 6. University of San Francisco, San Francisco, CA. 7. Mayo Clinic in Arizona, Scottsdale, AZ.
Abstract
BACKGROUND: Lower esophageal sphincter (LES) electrical stimulation therapy (EST) has been shown to improve outcome in gastroesophageal reflux disease (GERD) patients at 1 year. The aim of this open-label extension trial (NCT01578642) was to study the 2-year safety and efficacy of LES-EST in GERD patients. METHODS: GERD patients responsive partially to proton pump inhibitors (PPI) with off-PPI GERD health-related quality of life (HRQL) of ≥20, 24-hour esophageal pH ≤4.0 for >5% of the time, hiatal hernia ≤3 cm, and esophagitis LA grade C or lower participated in this trial. Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, The Netherlands) were implanted laparoscopically. LES-EST at 20 Hz, 215 μs, 3-8 mAmp was delivered over 30-minute sessions, 6-12 sessions per day, starting on day 1 after implantation. Patients were evaluated using GERD-HRQL, symptom diaries, Short Form-12, and esophageal pH testing at regular intervals. Stimulation sessions were optimized based on residual symptoms and esophageal pH at follow-up. RESULTS: Twenty-five patients (mean age [SD] = 52 [12] years; 14 men) were implanted successfully; 23 patients participated in the 2-year extension trial, and 21 completed their 2-year evaluation. At 2 years, there was improvement in their median GERD-HRQL on LES-EST compared with both their on-PPI (9 vs 0; P = .001) and off-PPI (23.5 vs. 0; P < .001) baseline scores. Median 24-hour distal esophageal acid exposure improved from 10% at baseline to 4% (per-protocol analysis; P < .001) at 2 years with 71% demonstrating either normalization or a ≥50% decrease in their distal esophageal acid exposure. All except 5 patients (16/21) reported complete cessation of PPI use; only 2 patients were using a PPI regularly (≥50% of days). There was significant improvement in sleep quality and daily symptoms of heartburn and regurgitation on LES-EST. At baseline, 92% of the subjects (22/24) reported that they were "unsatisfied" with their condition off-PPI and 71% (17/24) on-PPI compared with 0% (0/21) "unsatisfied" at the 24-month visits on LES-EST. There were no device- or therapy-related serious adverse events and no untoward sensation or dysphagia reported with LES-EST. CONCLUSION: LES-EST is safe and effective for treating patients with GERD over a period of 2 years. LES-EST resulted in a significant and sustained improvement in GERD symptoms, and esophageal acid exposure and eliminated PPI use in majority of patients (16 of 21). Further, LES-EST was not associated with any gastrointestinal side effects or adverse events.
BACKGROUND: Lower esophageal sphincter (LES) electrical stimulation therapy (EST) has been shown to improve outcome in gastroesophageal reflux disease (GERD) patients at 1 year. The aim of this open-label extension trial (NCT01578642) was to study the 2-year safety and efficacy of LES-EST in GERDpatients. METHODS:GERDpatients responsive partially to proton pump inhibitors (PPI) with off-PPI GERD health-related quality of life (HRQL) of ≥20, 24-hour esophageal pH ≤4.0 for >5% of the time, hiatal hernia ≤3 cm, and esophagitis LA grade C or lower participated in this trial. Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, The Netherlands) were implanted laparoscopically. LES-EST at 20 Hz, 215 μs, 3-8 mAmp was delivered over 30-minute sessions, 6-12 sessions per day, starting on day 1 after implantation. Patients were evaluated using GERD-HRQL, symptom diaries, Short Form-12, and esophageal pH testing at regular intervals. Stimulation sessions were optimized based on residual symptoms and esophageal pH at follow-up. RESULTS: Twenty-five patients (mean age [SD] = 52 [12] years; 14 men) were implanted successfully; 23 patients participated in the 2-year extension trial, and 21 completed their 2-year evaluation. At 2 years, there was improvement in their median GERD-HRQL on LES-EST compared with both their on-PPI (9 vs 0; P = .001) and off-PPI (23.5 vs. 0; P < .001) baseline scores. Median 24-hour distal esophageal acid exposure improved from 10% at baseline to 4% (per-protocol analysis; P < .001) at 2 years with 71% demonstrating either normalization or a ≥50% decrease in their distal esophageal acid exposure. All except 5 patients (16/21) reported complete cessation of PPI use; only 2 patients were using a PPI regularly (≥50% of days). There was significant improvement in sleep quality and daily symptoms of heartburn and regurgitation on LES-EST. At baseline, 92% of the subjects (22/24) reported that they were "unsatisfied" with their condition off-PPI and 71% (17/24) on-PPI compared with 0% (0/21) "unsatisfied" at the 24-month visits on LES-EST. There were no device- or therapy-related serious adverse events and no untoward sensation or dysphagia reported with LES-EST. CONCLUSION: LES-EST is safe and effective for treating patients with GERD over a period of 2 years. LES-EST resulted in a significant and sustained improvement in GERD symptoms, and esophageal acid exposure and eliminated PPI use in majority of patients (16 of 21). Further, LES-EST was not associated with any gastrointestinal side effects or adverse events.