Authors’ reply

Nicola de Bortolia, Teresa Di Chiob, Lucia Mariania, Edoardo V. Savarinoc

University of Pisa; University of Padua, Italy

aGastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa (Nicola de Bortoli, Lucia Mariani), Italy, bPediatrics Unit, Department of Experimental and Clinical Medicine, University of Pisa (Teresa Di Chio), Italy, cGastroenterology Unit, Department Surgery, Oncology and Gastroenterology, University of Padua (Edoardo V. Savarino), Italy

Correspondence to: Nicola de Bortoli, MD, Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 54124 Pisa, Italy, e-mail: nicola.debortoli@unipi.it
Received 28 January 2019; accepted 30 January 2019; published online 12 March 2019
DOI: https://doi.org/10.20524/aog.2019.0369
© 2019 Hellenic Society of Gastroenterology

Annals of Gastroenterology (2019) 32, 318-319

We would like to thank Kountouras et al for their comment on our review recently published in Annals of Gastroenterology [1]. Kountouras et al emphasized the potential effect of trimebutine in modulating symptoms related to both irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD), especially when these symptoms overlap in the same patient.

As reported in the scientific literature, trimebutine seems to have a role in modulating hypermotility and hypomotility disorders, hastening gastric emptying, shortening the lag period, modulating visceral sensitivity and ameliorating gastrointestinal symptoms [2]. However, the use of trimebutine in clinical practice is not strongly supported by current evidence. In fact, some criticisms should be taken into account: a) only one study evaluated the potential effect of trimebutine in controlling gastrointestinal symptoms in patients with GERD-IBS overlap [2]; there are no data supporting the effects of trimebutine in hyper- or hypocontractile motility esophageal disorders; c) there are no data supporting the effects of trimebutine in GERD; and d) the effectiveness of trimebutine in treating IBS and overlapping functional dyspepsia (FD) is barely supported by literature.

Having said that, it is essential to underline the limited overlap between “true” GERD and IBS, as well as between GERD and FD [1,3]. A large number of studies aimed to detect these groups of patients; however, only few of those were performed according to pathophysiologic criteria [4,5]. As previously reported in pathophysiological studies [4-6], IBS appears to overlap more frequently with esophageal functional disorders rather than with GERD. Therefore, we can support the hypothesis that the effects of trimebutine in patients who complain of heartburn and have negative upper endoscopy (who may be hurriedly defined as GERD) are most likely due to its role in treating functional esophageal disorders, rather than controlling the GERD-related presentation. Indeed, recent functional investigations performed with the impedance-pH technique have provided significant evidence that endoscopy-negative patients with typical reflux symptoms are remarkably heterogeneous from a pathophysiological and histological standpoint and can be subdivided into true GERD and functional esophageal disorders [7-9].

Recently, pathophysiological studies have shown that functional esophageal disorders overlap more frequently with IBS or FD than with GERD [1,3,10]. In support of this contention, some studies have suggested that FD and IBS may share common pathophysiological mechanisms, such as visceral hypersensitivity; thus, drugs acting as visceral pain modulators (such as antidepressants) may exert beneficial effects on both disorders when tested in separate trials [3]. The recent Rome IV criteria will probably reduce this previously reported and expected overlap between GERD and IBS or FD. A deeper understanding of the pathophysiology of such disorders might lead towards new therapeutic options in functional gastrointestinal disorders.

References

1. de Bortoli N, Tolone S, Frazzoni M, et al. Gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome:common overlapping gastrointestinal disorders. Ann Gastroenterol 2018;31:639-648.

2. Kountouras J, Chatzopoulos D, Zavos C, Boura P, Venizelos J, Kalis A. Efficacy of trimebutine therapy in patients with gastroesophageal reflux disease and irritable bowel syndrome. Hepatogastroenterology 2002;49:193-197.

3. de Bortoli N, Martinucci I, Bellini M, et al. Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome. World J Gastroenterol 2013;19:5787-5797.

4. de Bortoli N, Frazzoni L, Savarino EV, et al. Functional heartburn overlaps with irritable bowel syndrome more often than GERD. Am J Gastroenterol 2016;111:1711-1717.

5. Savarino E, Pohl D, Zentilin P, et al. Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut 2009;58:1185-1191.

6. Savarino E, Zentilin P, Dulbecco P, Malesci A, Savarino V. The role of acid in functional dyspepsia. Am J Gastroenterol 2011;106:1168.

7. Savarino E, Marabotto E, Zentilin P, et al. The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis 2011;43:542-547.

8. Savarino E, Tutuian R, Zentilin P, et al. Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease:study using combined impedance-pH off therapy. Am J Gastroenterol 2010;105:1053 1061.

9. Savarino E, Zentilin P, Tutuian R, et al. Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients. J Gastroenterol 2012;47:159-168.

10. Savarino V, Savarino E. Is acid relevant in the genesis of dyspeptic symptoms associated with nonerosive reflux disease?Eur J Gastroenterol Hepatol 2008;20:252-254.

Notes

Conflict of Interest: None