Long-term results of electrical stimulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease

Background and study aims: In patients with gastroesophageal reflux disease (GERD), temporary electrical stimulation of the lower esophageal sphincter (LES) increases LES pressure without interference with LES relaxation. The aim of the current study was to investigate the safety and efficacy of long term LES electrical stimulation therapy (LES–EST), using a permanently implanted stimulator for the treatment of GERD.

Patients and methods: Patients with GERD who were at least partially responsive to proton pump inhibitors (PPIs) and who had hiatal hernia of ≤ 3 cm and esophagitis of Los Angeles Grade A, B, or C were included in the study. Stimulation electrodes were placed in the LES and a pulse generator (EndoStim LES Stimulation System; EndoStim BV, The Hague, The Netherlands) was implanted laparoscopically. LES stimulation was delivered at 20 Hz, 215 μs, 3 – 8 mA in multiple 30-minute sessions. Patients were evaluated at follow-up using the GERD Health-Related Quality of Life (HRQL) questionnaire, daily symptom and medication diaries, the SF-12 Health Survey, esophageal pH testing, and high resolution manometry.

Results: A total of 24 patients (mean age 53 ± 12 years; 14 men) were implanted and 23 completed the 12-month evaluation. No serious implantation or stimulation-related adverse affects or sensations were reported. Median composite GERD–HRQL score at 12 months was 2.0 (interquartile range [IQR] 0 – 3.0), which was significantly better than baseline scores both on PPI therapy (median 9.0, IQR 6.0 – 10.0; P = 0.002) and off PPIs (median 23.5, IQR 21 – 25.75; P < 0.001). The median percentage of the 24-hour period with esophageal pH < 4.0 at baseline was 10.1 % (IQR 7.7 – 15.5), which was reduced to 3.3 % (1.8 – 6.9) at 12 months (P < 0.001), with 69 % of patients showing either normalization or > 50 % improvement in their distal esophageal pH. At 12 months, 96 % of patients (22/23) were completely off PPI medication.

Conclusion: During the long term follow-up of 12 months, LES – EST was safe and effective for the treatment of GERD. There was a significant and sustained improvement in GERD symptoms, reduction in esophageal acid exposure with elimination of daily PPI usage, and no stimulation-related adverse effects.

• References

• 1 Sandler RS, Everhart JE, Donowitz M et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002; 122: 1500-1511
• 2 Everhart JE ed. Digestive diseases in the United States: epidemiology and impact. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Everhart JE. Washington, DC: US Government Printing Office; 1994. NIH publication no. 94-1447
• 3 El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol 2007; 5: 17-26
• 4 Wahlqvist P, Reilly M, Barkun A. Systematic review: the impact of gastro-oesophageal reflux disease on health-related productivity. Aliment Pharmacol Ther 2006; 24: 259-272
• 5 McQuaid KR, Laine L. Early heartburn relief with proton pump inhibitors: a systematic review and metaanalysis of clinical trials. Clin Gastroenterol Hepatol 2005; 3: 553-563
• 6 Sifrim D, Mittal R, Fass R et al. Review article: acidity and volume of the refluxate in the genesis of gastro-oesophageal reflux disease symptoms. Aliment Pharmacol Ther 2007; 25: 1003-1017
• 7 Vakil N, Shaw M, Kirby R. Clinical effectiveness of laparoscopic fundoplication in a US community. Am J Med 2003; 114: 1-5
• 8 Lodato F, Azzaroli F, Turco L et al. Adverse effects of proton pump inhibitors. Best Pract Res Clin Gastroenterol 2010; 24: 193-201
• 9 Rothstein RI. Endoscopic therapy of gastroesophageal reflux disease outcomes of the randomized-controlled trials done to date. J Clin Gastroenterol 2008; 42: 594-602
• 10 Ellis F, Berne TV, Settevig K. The prevention of experimentally induced reflux by electrical stimulation of the distal esophagus. Am J Surg 1968; 115: 482-487
• 11 Clarke JO, Jagannath SB, Kalloo AN et al. An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model. Endoscopy 2007; 39: 72-76
• 12 Sanmiguel CP, Hagiike M, Mintchev MP et al. Effect of electrical stimulation of the LES on LES pressure in a canine model. Am J Physiol Gastrointest Liver Physiol 2008; 295: 389-394
• 13 Banerjee R, Pratap N, Kalapala R et al. In patients with GERD electrical stimulation therapy (EST) significantly and consistently increases lower esophageal sphincter (LES) pressure. J Gastroenterol Hepatol 2010; 25: A16
• 14 Rodríguez L, Rodríguez P, Neto MG et al. Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease. Neurogastroenterol Motil 2012; 24: 446-450
• 15 Rodríguez L, Rodriguez P, Gómez B et al. Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial. Surg Endosc 2013; 27: 1083-1092
• 16 Velanovich V. Comparison of generic (SF-36) vs. disease specific quality-of-life (GERD-HRQL) scales for gastroesophageal reflux disease. J Gastrointestinal Surg 1998; 2: 141-145
• 17 Vakil N, van Zanten SV, Kahrilas P et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101: 1900-1920
• 18 American Gastroenterological Association. GERD patient study: patients and their medications. Rochester, NY: Harris Interactive Inc; 2008
• 19 Kahrilas PJ, Shaheen NJ, Vaezi MF et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135: 1383-1391 , e1-5
• 20 Stefanidis D, Hope WW, Kohn GP et al. Guidelines for surgical treatment of gastroesophageal reflux disease. Surg Endosc 2010; 24: 2647-2669
• 21 Galmiche JP, Hatlebakk J, Attwood S et al. Laparoscopic antireflux surgery vs. esomeprazole treatment for chronic GERD. The LOTUS randomized clinical trial. JAMA 2011; 305: 1969-1977
• 22 Spechler SJ, Lee E, Ahnen D et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease. Follow-up of a randomized controlled trial. JAMA 2001; 285: 2331-2338
• 23 Kahrilas PJ. Magnetic enhancement of the lower esophageal sphincter. Gastrointest Endosc 2008; 67: 295-296
• 24 Kahrilas PJ, Boeckxstaens G. Failure of reflux inhibitors in clinical trials: bad drugs or wrong patients?. Postgrad Med J 2013; 89: 111-119
• 25 Cadière GB, Van Sante N, Graves JE et al. Two-year results of a feasibility study on antireflux transoral incisionless fundoplication using EsophyX. Surg Endosc 2009; 23: 957-964
• 26 Bonavina L, DeMeester T, Fockens P et al. Laparoscopic sphincter augmentation device eliminates reflux symptoms and normalizes esophageal acid exposure: one- and 2-year results of a feasibility trial. Ann Surg 2010; 252: 857-862
• 27 LINX® Reflux Management System. Gastroenterology and Urology Medical Devices Panel Meeting. 11 January 2012; Gaithersburg, Maryland, USA. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/Gastroenterology-UrologyDevicesPanel/UCM287512.pdf Last accessed: April 2013
• 28 McCallum RW, Zhiyue L, Forester J et al. Gastric electrical stimulation improves outcomes of patients with gastroparesis for up to 10 years. Clin Gastroenterol Hepatol 2011; 9: 314-319
• 29 Kahrilas PJ, Howden CW, Hughes N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011; 106: 1419-1425
• 30 Das A, Rodriguez R, Siersema PD et al. A cost-effectiveness analysis of lower esophageal sphincter – electrical stimulation therapy for management of refractory GERD. J Gastroenterol Hepatol 2012; 27: 324