Skip to main content
SpringerLink
Log in

New Developments in the Diagnosis and Management of Gastroesophageal Reflux

  • Esophagus (P Iyer, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of review

To examine recent key developments in the pathophysiology, diagnosis, and treatment of gastroesophageal reflux disease (GERD).

Recent findings

Newer research has suggested cytokine-mediated inflammation may play a role in the physiology of GERD, implying that the underlying mechanism may not be entirely related to chemical damage due to acid. Aided by novel technologies, diagnostic testing is also moving toward elucidating individual mechanisms and better defining specific GERD phenotypes with the goal of providing directed therapy. This is especially important in current times given the increase in coverage of adverse events reportedly linked to long-term proton pump inhibitor use.

Summary

As patients are looking for potential alternatives, we highlight the key recent updates in pathophysiology and understanding of GERD and current medical and endoscopic/surgical options and explore the exciting treatments in the pipeline.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871–80. https://doi.org/10.1136/gutjnl-2012-304,269.

    Article  PubMed  Google Scholar 

  2. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308–28; quiz 29. https://doi.org/10.1038/ajg.2012.444.

    Article  PubMed  Google Scholar 

  3. Vela MF. Diagnostic work-up of GERD. Gastrointestinal endoscopy clinics of North America. 2014;24(4):655–66. https://doi.org/10.1016/j.giec.2014.07.002.

    Article  Google Scholar 

  4. Schumock GT, Li EC, Suda KJ, Wiest MD, Stubbings J, Matusiak LM, et al. National trends in prescription drug expenditures and projections for 2016. Am J Health-Syst Pharm: AJHP: official journal of the American Society of Health-System Pharmacists. 2016;73(14):1058–75. https://doi.org/10.2146/ajhp160205.

    Article  Google Scholar 

  5. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017;153(1):35–48. https://doi.org/10.1053/j.gastro.2017.04.047A review of studies examing PPI related adverse effects that concludes there is inadequate evidence to establish causal relationships of many reported effects. Recommends continued use in those with proven indication for PPI but discourages dose escalation and chronic therapy for those unresponsive to initial empiric trial.

    Article  PubMed  CAS  Google Scholar 

  6. Dunbar KB, Agoston AT, Odze RD, Huo X, Pham TH, Cipher DJ, et al. Association of acute gastroesophageal reflux disease with esophageal histologic changes. Jama. 2016;315(19):2104–12. https://doi.org/10.1001/jama.2016.5657A study examining esophageal biopsies of those with reflux esophagitis which showed an increase in T lymphocytes, providing evidence to suggest that cytokine mediated inflammation plays a role in mucosal injury.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Souza RF, Huo X, Mittal V, Schuler CM, Carmack SW, Zhang HY, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137(5):1776–84. https://doi.org/10.1053/j.gastro.2009.07.055.

    Article  PubMed  CAS  Google Scholar 

  8. Huo X, Agoston AT, Dunbar KB, Cipher DJ, Zhang X, Yu C, et al. Hypoxia-inducible factor-2alpha plays a role in mediating oesophagitis in GORD. Gut. 2017;66(9):1542–54. https://doi.org/10.1136/gutjnl-2016-312,595.

    Article  PubMed  CAS  Google Scholar 

  9. Woodland P, Shen Ooi JL, Grassi F, Nikaki K, Lee C, Evans JA, et al. Superficial esophageal mucosal afferent nerves may contribute to reflux hypersensitivity in nonerosive reflux disease. Gastroenterology. 2017;153(5):1230–9. https://doi.org/10.1053/j.gastro.2017.07.017.

    Article  PubMed  Google Scholar 

  10. Corning B, Copland AP, Frye JW. The esophageal microbiome in health and disease. Curr Gastroenterol Rep. 2018;20(8):39. https://doi.org/10.1007/s11894-018-0642-9.

    Article  Google Scholar 

  11. Okereke I, Hamilton C, Wenholz A, Jala V, Giang T, Reynolds S, et al. Associations of the microbiome and esophageal disease. J Thorac Disease. 2019;11(Suppl 12):S1588–s93. https://doi.org/10.21037/jtd.2019.05.82.

    Article  Google Scholar 

  12. Hirano I, Pandolfino JE, Boeckxstaens GE. Functional lumen imaging probe for the management of esophageal disorders: expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association. 2017;15(3):325–34. https://doi.org/10.1016/j.cgh.2016.10.022.

    Article  Google Scholar 

  13. Scarpulla G, Camilleri S, Galante P, Manganaro M, Fox M. The impact of prolonged pH measurements on the diagnosis of gastroesophageal reflux disease: 4-day wireless pH studies. Am J Gastroenterol. 2007;102(12):2642–7. https://doi.org/10.1111/j.1572-0241.2007.01461.x.

    Article  PubMed  Google Scholar 

  14. Barrett C, Choksi Y, Vaezi MF. Mucosal impedance: a new approach to diagnosing gastroesophageal reflux disease and eosinophilic esophagitis. Curr Gastroenterol Rep. 2018;20(7):33. https://doi.org/10.1007/s11894-018-0639-4.

    Article  PubMed  Google Scholar 

  15. Bakalar N Heartburn drugs can lead to fatal heart or kidney disease. New York Times. 2019 .

  16. Sifrim D, Castell D, Dent J, Kahrilas PJ. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53(7):1024–31. https://doi.org/10.1136/gut.2003.033290.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout A, et al. Modern diagnosis of GERD: the Lyon consensus. Gut. 2018;67(7):1351–62. https://doi.org/10.1136/gutjnl-2017-314,722Consensus statement defining specific GERD populations. Highlights conclusive endoscopic criteria for GERD, pH testing indications on/off PPI, abnormal pH testing parameters and current role of high resolution manometry.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chae S, Richter JE. Wireless 24, 48, and 96 hour or impedance or oropharyngeal prolonged pH monitoring: which test, when, and why for GERD. Curr Gastroenterol Rep. 2018;20(11):52. https://doi.org/10.1007/s11894-018-0659-0.

    Article  PubMed  Google Scholar 

  19. Hirano I, Zhang Q, Pandolfino JE, Kahrilas PJ. Four-day Bravo pH capsule monitoring with and without proton pump inhibitor therapy. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association. 2005;3(11):1083–8.

    Article  Google Scholar 

  20. Garrean CP, Zhang Q, Gonsalves N, Hirano I. Acid reflux detection and symptom-reflux association using 4-day wireless pH recording combining 48-h periods off and on PPI therapy. Am J Gastroenterol. 2008;103(7):1631–7. https://doi.org/10.1111/j.1572-0241.2008.01829.x.

    Article  PubMed  Google Scholar 

  21. Patel RCS, Jacobs J, Kumar A, Richter J. 96-h esophageal pH monitoring: the tiebreaker for abnormal DeMeester score and symptom index. Gastroenterology. 2018;154(6):S-487-7.

    Google Scholar 

  22. Patel DA, Vaezi MF. Utility of esophageal mucosal impedance as a diagnostic test for esophageal disease. Curr Opin Gastroenterol. 2017;33(4):277–84. https://doi.org/10.1097/mog.0000000000000367.

    Article  PubMed  Google Scholar 

  23. Frazzoni M, de Bortoli N, Frazzoni L, Tolone S, Furnari M, Martinucci I et al. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring. Neurogastroenterol Motil: the official journal of the European Gastrointestinal Motility Society. 2017;29(3). doi:https://doi.org/10.1111/nmo.12947.

    Article  Google Scholar 

  24. Patel A, Wang D, Sainani N, Sayuk GS, Gyawali CP. Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2016;44(8):890–8. https://doi.org/10.1111/apt.13777.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Saritas Yuksel E, Higginbotham T, Slaughter JC, Mabary J, Kavitt RT, Garrett CG, et al. Use of direct, endoscopic-guided measurements of mucosal impedance in diagnosis of gastroesophageal reflux disease. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association. 2012;10(10):1110–6. https://doi.org/10.1016/j.cgh.2012.05.018.

    Article  Google Scholar 

  26. Ates F, Yuksel ES, Higginbotham T, Slaughter JC, Mabary J, Kavitt RT, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology. 2015;148(2):334–43. https://doi.org/10.1053/j.gastro.2014.10.010.

    Article  PubMed  Google Scholar 

  27. Patel DA, Higginbotham T, Slaughter JC, Aslam M, Yuksel E, Katzka D, et al. Development and validation of a mucosal impedance contour analysis system to distinguish esophageal disorders. Gastroenterology. 2019;156(6):1617–26.e1. https://doi.org/10.1053/j.gastro.2019.01.253.

    Article  PubMed  Google Scholar 

  28. Tucker E, Sweis R, Anggiansah A, Wong T, Telakis E, Knowles K, et al. Measurement of esophago-gastric junction cross-sectional area and distensibility by an endolumenal functional lumen imaging probe for the diagnosis of gastro-esophageal reflux disease. Neurogastroenterol Motil: the official journal of the European Gastrointestinal Motility Society. 2013;25(11):904–10. https://doi.org/10.1111/nmo.12218.

    Article  CAS  Google Scholar 

  29. Rinsma NF, Smeets FG, Bruls DW, Kessing BF, Bouvy ND, Masclee AA, et al. Effect of transoral incisionless fundoplication on reflux mechanisms. Surg Endosc. 2014;28(3):941–9. https://doi.org/10.1007/s00464-013-3250-7.

    Article  PubMed  Google Scholar 

  30. Ilczyszyn A, Botha AJ. Feasibility of esophagogastric junction distensibility measurement during Nissen fundoplication. Diseases Esophagus: official journal of the International Society for Diseases of the Esophagus. 2014;27(7):637–44. https://doi.org/10.1111/dote.12130.

    Article  CAS  Google Scholar 

  31. Oshima T, Miwa H. Potent potassium-competitive acid blockers: a neweEra for the treatment of acid-related diseases. J Neurogastroenterol Motil. 2018;24(3):334–44. https://doi.org/10.5056/jnm18029.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ashida K, Sakurai Y, Hori T, Kudou K, Nishimura A, Hiramatsu N, et al. Randomized clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016;43(2):240–51. https://doi.org/10.1111/apt.13461.

    Article  PubMed  CAS  Google Scholar 

  33. Di Stefano M, Papathanasopoulos A, Blondeau K, Vos R, Boecxstaens V, Farre R, et al. Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Diseases Esophagus: official journal of the International Society for Diseases of the Esophagus. 2012;25(5):470–6. https://doi.org/10.1111/j.1442-2050.2011.01275.x.

    Article  Google Scholar 

  34. Karamanolis GP, Panopoulos S, Denaxas K, Karlaftis A, Zorbala A, Kamberoglou D, et al. The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial. Arthritis Res Ther. 2016;18:195. https://doi.org/10.1186/s13075-016-1094-y.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Aggarwal N, Thota PN, Lopez R, Gabbard S. A randomized double-blind placebo-controlled crossover-style trial of buspirone in functional dysphagia and ineffective esophageal motility. Neurogastroenterol Motil: the official journal of the European Gastrointestinal Motility Society. 2018;30(2). doi:https://doi.org/10.1111/nmo.13213.

    Article  CAS  Google Scholar 

  36. Thomas E, Wade A, Crawford G, Jenner B, Levinson N, Wilkinson J. Randomized clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2014;39(6):595–602. https://doi.org/10.1111/apt.12640.

    Article  PubMed  CAS  Google Scholar 

  37. Wilkinson JWA, Thomas SJ, Jenner B, Hodgkinson V, Coyle C. Randomized clinical trial: a double-blind, placebo-controlled study to assess the clinical efficacy and safety of alginate-antacid (Gaviscon Double Action) chewable tablets in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2019;31(1):86–93.

    Article  CAS  Google Scholar 

  38. Clarke JO, Fernandez-Becker NQ, Regalia KA, Triadafilopoulos G. Baclofen and gastroesophageal reflux disease: seeing the forest through the trees. Clin Transl Gastroenterol. 2018;9(3):137. https://doi.org/10.1038/s41424-018-0010-y.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Lei WY, Hung JS, Liu TT, Yi CH, Chen CL. Influence of GABA-B agonist baclofen on capsaicin-induced excitation of secondary peristalsis in humans. Clin Transl Gastroenterol. 2017;8(10):e120. https://doi.org/10.1038/ctg.2017.46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Vaezi MF, Fass R, Vakil N, Mittleman R, Hall M, Reasner DS, et al. 875 - Iw-3718, a novel gastric-retentive bile acid sequestrant, improved heartburn and regurgitation symptoms in patients with persistent gerd despite PPI treatment: a double-blind, placebo-controlled study. Gastroenterology. 2018;154(6):S-174. https://doi.org/10.1016/S0016-5085(18)30995-8.

    Article  Google Scholar 

  41. Lipka S, Kumar A, Richter JE. No evidence for efficacy of radiofrequency ablation for treatment of gastroesophageal reflux disease: a systematic review and meta-analysis. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association. 2015;13(6):1058–67.e1. https://doi.org/10.1016/j.cgh.2014.10.013.

    Article  Google Scholar 

  42. Fass R, Cahn F, Scotti DJ, Gregory DA. Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease. Surg Endosc. 2017;31(12):4865–82. https://doi.org/10.1007/s00464-017-5431-2.

    Article  PubMed  Google Scholar 

  43. Ganz RA, Edmundowicz SA, Taiganides PA, Lipham JC, Smith CD, De Vault KR, et al. Long-term outcomes of patients receiving a magnetic sphincter augmentation device for gastroesophageal reflux. Clin Gastroenterol Hepatol: the official clinical practice journal of the American Gastroenterological Association. 2016;14(5):671–7. https://doi.org/10.1016/j.cgh.2015.05.028Five year follow up of an initial multicenter trial of patients receiving MSA which showed a significant decrease in GERD-HRQL scores, moderate to severe regurgitation symptoms and PPI use (100% of patients initially to 15.3% of patients at follow up).

    Article  Google Scholar 

  44. Skubleny D, Switzer NJ, Dang J, Gill RS, Shi X, de Gara C, et al. LINX((R)) magnetic esophageal sphincter augmentation versus Nissen fundoplication for gastroesophageal reflux disease: a systematic review and meta-analysis. Surg Endosc. 2017;31(8):3078–84. https://doi.org/10.1007/s00464-016-5370-3.

    Article  PubMed  Google Scholar 

  45. Tatum JM, Lipham JC. Extraluminal approaches to gastroesophageal reflux disease. Thorac Surg Clin. 2018;28(4):521–6. https://doi.org/10.1016/j.thorsurg.2018.07.003.

    Article  PubMed  Google Scholar 

  46. Hunter JG, Kahrilas PJ, Bell RC, Wilson EB, Trad KS, Dolan JP, et al. Efficacy of transoral fundoplication vs omeprazole for treatment of regurgitation in a randomized controlled trial. Gastroenterology. 2015;148(2):324–33.e5. https://doi.org/10.1053/j.gastro.2014.10.009.

    Article  PubMed  CAS  Google Scholar 

  47. Testoni PA, Testoni S, Mazzoleni G, Vailati C, Passaretti S. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc. 2015;29(9):2770–80. https://doi.org/10.1007/s00464-014-4008-6.

    Article  PubMed  Google Scholar 

  48. Trad KS, Barnes WE, Prevou ER, Simoni G, Steffen JA, Shughoury AB, et al. The TEMPO Trial at 5 years: transoral fundoplication (TIF 2.0) is safe, durable, and cost-effective. Surg Innov. 2018;25(2):149–57. https://doi.org/10.1177/1553350618755214.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Satodate H, Inoue H, Yoshida T, Usui S, Iwashita M, Fukami N, et al. Circumferential EMR of carcinoma arising in Barrett’s esophagus: case report. Gastrointest Endosc. 2003;58(2):288–92. https://doi.org/10.1067/mge.2003.361.

    Article  PubMed  Google Scholar 

  50. Inoue H, Ito H, Ikeda H, Sato C, Sato H, Phalanusitthepha C, et al. Anti-reflux mucosectomy for gastroesophageal reflux disease in the absence of hiatus hernia: a pilot study. Ann Gastroenterol. 2014;27(4):346–51.

    PubMed  PubMed Central  Google Scholar 

  51. Inoue H, Sumi K, Tatsuta T, Ikebuchi Y, Tuason J. 998 clinical results of antireflux mucosectomy (ARMS) for refractory Gerd. Gastrointest Endosc. 2017;85(5):AB120. https://doi.org/10.1016/j.gie.2017.03.196Research describing experience and results of a novel technique currently used in Japan for refractory GERD. This 67 patient cohort study, expanding on an initial pilot study, shows significant decrease in reflux symptoms, endoscopic flap valve grade, percent time clearance pH, and PPI use 1 year post procedure.

    Article  Google Scholar 

  52. Kappelle WF, Bredenoord AJ, Conchillo JM, Ruurda JP, Bouvy ND, van Berge Henegouwen MI, et al. Electrical stimulation therapy of the lower oesophageal sphincter for refractory gastro-oesophageal reflux disease - interim results of an international multicentre trial. Aliment Pharmacol Ther. 2015;42(5):614–25. https://doi.org/10.1111/apt.13306.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Yan Jiang MD & John O. Clarke MD

  2. Redwood City, USA

    John O. Clarke MD

Authors
  1. Yan Jiang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John O. Clarke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Conflict of interest

JC is a consultant for Sanofi, Medtronic, and Isothrive; YJ has no conflicts to report.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Esophagus

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Y., Clarke, J.O. New Developments in the Diagnosis and Management of Gastroesophageal Reflux. Curr Treat Options Gastro 18, 69–81 (2020). https://doi.org/10.1007/s11938-020-00275-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-020-00275-1

Keywords

Search

Navigation