Abstract

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Highlights

  • Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal diseases [1]

  • A clinical trial showed that fermentable oligo, di, mono- saccharides and polyols (FODMAPs), fructans, increased the number of TLESRs in healthy patients [95], and in proven Refractory GERD (rGERD) patients a low- FODMAP diet was shown not to significantly decrease reflux symptoms when compared to usual dietary advice [96]

  • Additional pharmacological therapy should target the potential underlying pathophysiology according to the results of instrumental diagnostic tests (e.g., EGD, High-resolution esophageal manometry (HREM), multichannel intraluminal impedance-pH (MII-pH) monitoring and gastric emptying tests)

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Summary

Frontiers in Medicine

Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient’s compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators.

INTRODUCTION
DIAGNOSTIC WORKUP
Diagnostic test
PPI Compliance
PPI Metabolism
Different PPI Agents
Duodenogastroesophageal or Bile Reflux
Antireflux Barrier
Esophageal Clearance
Delayed Gastric Emptying
Esophageal Hypersensitivity and Hypervigilance
THERAPY OF rGERD
Diet and Lifestyle
PPI Therapy
ENDOSCOPIC AND SURGICAL MANAGEMENT
Laparoscopic Antireflux Surgery
Alternative Invasive Procedures
AND CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS

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