Refractory Gastroesophageal Reﬂux
Disease: A Management Update
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.
Gastroesophageal reﬂux disease (GERD) is one of the most frequent gastrointestinal diseases (1). It is deﬁned on the basis of both esophageal and extra-esophageal symptoms, and/or lesions resulting from the reﬂux of gastric contents into the esophagus. GERD symptoms can be typical, such as heartburn and regurgitation, and atypical, such as chest pain, chronic cough, laryngeal burn, globus, and hoarseness. Therapy is commonly based on proton pump inhibitors (PPIs) and alginates as an add- on therapy. PPIs are eﬀective in healing lesions and improving symptoms in most cases (2). However, there is a signiﬁcant proportion of patients, ranging from 10 to 40%, whose symptoms do not adequately respond to PPI therapy (3–6). This condition, commonly known as “refractory GERD” (rGERD), represents a major health problem, given its impact on quality of life and consumption of health care resources (7). The deﬁnition of rGERD is controversial as it has never been clearly established (8). The most commonly used deﬁnition is: symptoms (retrosternal heartburn and/or regurgitation) present at least 3 times per week not responding to a double dose of PPIs for 8–12 weeks (4, 7–10). It must be emphasized that this deﬁnition is only clinical, and it does not take into account the need to have objective evidence of GERD based on endoscopic ﬁndings and pH-impedance monitoring. Indeed, many patients who experience symptoms potentially related to GERD and not responding to PPI are not really aﬀected by GERD (7, 9). In this case the deﬁnition could be changed to “reﬂux-like PPI-refractory symptoms.” The latest ESNM/ANMS consensus paper (11), in accordance with recent recommendations (12–14), deﬁned “refractory GERD symptoms” as the persistence of symptoms on therapy, in patients with prior objective evidence of GERD (erosive esophagitis, peptic stricture, long segment Barrett’s esophagus, or abnormal esophageal acid exposure on reﬂux monitoring performed oﬀ therapy) and rGERD as “persistence of GERD symptoms with objective evidence of GERD (through endoscopic and pH- impedance ﬁndings) despite optimized PPI therapy over at least 8 weeks.” The complex pathogenetic mechanisms underlying rGERD represent a major challenge in gastroenterological clinical practice and need to be further investigated in order to guide eﬀective therapeutic interventions (15). The present paper was aimed at reviewing the treatment of rGERD in light of the most recent research.
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