The aim of this study was to assess expert gastroenterologists’ opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms.


Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy.


Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association.


For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

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  1. Anschutz Medical Campus, University of Colorado, Aurora, CO, USA

    • Rena Yadlapati MD, MSHS
  2. Vanderbilt Medical Center, Nashville, TN, USA

    • Michael F. Vaezi MD, PhD
  3. Mayo Clinic, Scottsdale, AZ, USA

    • Marcelo F. Vela MD
  4. Baylor Health Care System, Dallas, TX, USA

    • Stuart J. Spechler MD
  5. University of North Carolina, Chapel Hill, NC, USA

    • Nicholas J. Shaheen MD, MPH
  6. University of South Florida, Tampa, FL, USA

    • Joel Richter MD
  7. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    • Brian E. Lacy MD, PhD
  8. Mayo Clinic, Rochester, MN, USA

    • David Katzka MD
  9. Weill Cornell Medical Center, New York, NY, USA

    • Philip O. Katz MD
  10. Northwestern University, Chicago, IL, USA

    • Peter J. Kahrilas MD
    • , Jenna Craft MPH
    •  & John E. Pandolfino MD, MS
  11. Washington University, St. Louis, MO, USA

    • C. Prakash Gyawali MD
  12. California Pacific Medical Center, San Francisco, CA, USA

    • Lauren Gerson MD, MSc
  13. Metro Health Medical Center, Cleveland, OH, USA

    • Ronnie Fass MD
  14. Medical University of South Carolina, Charleston, SC, USA

    • Donald O. Castell MD
  15. University of Wisconsin, Madison, WI, USA

    • Luke Hillman MD


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Guarantor of the article

Rena Yadlapati

Specific author contributions

Planning and conducting the study (RY, MFV, JC, JEP); Collecting and interpreting data (RY, MFV, MFV, SJS, NJS, JR, BEL, DK, POK, PJK, CPG, LG, RF, DOC, JC, LH, JEP); Drafting the manuscript (RY, MFV, MFV, SJS, NJS, JR, BEL, DK, POK, PJK, CPG, RF, DOC, JC, LH JEP); and Approving final manuscript draft (RY, MFV, MFV, SJS, NJS, JR, BEL, DK, POK, PJK, CPG, RF, DOC, JC, LH, JEP).

Financial support

RY and JEP supported by NIH R01 DK092217 (JEP).

Potential competing interests

MFV, MFV, SJS, JR, DK, POK, PJK, CPG, LG, RF, DOC, JC, LH: None. RY: Consultant for Ironwood. CPG: Research: Medtronic; Consultant: Ironwood, Torax, Quintiles; and Teaching: Medtronic, Sandhill. NJS: Research funding: Boston Scientific, CSA Medical, C2 Therapeutics, CDx Medical, Interpace Diagnostics, and Medtronic. Consultant for Shire and Cook Medical. BEL: Scientific advisory board member for Ironwood, Salix. JEP: Consultant for Crospon, Ironwood, Torax, Astra Zeneca, Takeda, Impleo, Medtronic, and Sandhill.

Corresponding author

Correspondence to Rena Yadlapati MD, MSHS.

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