- Email: [email protected]
Caution About Overinterpretation of Number of Reflux Episodes in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease
Accepted Manuscript Caution about Overinterpretation of Number of Reflux in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease Manuele Furnari, MD, Salvatore Tolone, MD, Edoardo Savarino, MD, PhD
PII: DOI: Reference:
S1542-3565(15)00771-5 10.1016/j.cgh.2015.05.036 YJCGH 54320
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 29 May 2015 Please cite this article as: Furnari M, Tolone S, Savarino E, Caution about Overinterpretation of Number of Reflux in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/j.cgh.2015.05.036. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT
Caution about Overinterpretation of Number of Reflux in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease
Manuele Furnari MD1, Salvatore Tolone MD2, Edoardo Savarino MD, PhD4 Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
RI PT
1
2
Division of Surgery, Department of Surgery, Second University of Naples, Naples, Italy 3
Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of
SC
Padua, Padua, Italy
M AN U
Key Words: Weakly Acidic Reflux; NERD; impedance-pH; functional heartburn; reflux events
Authors contribution:
TE D
Running Title: Number of reflux episodes in refractory GERD
- Manuele Furnari, MD, PhD: writing of the manuscript, approving final version - Salvatore Tolone, MD, PhD: writing of the manuscript, approving final version
AC C
EP
- Edoardo Savarino, MD, PhD: writing of the manuscript, approving final version
Financial support: none
Potential competing interests: none
Corresponding author: Manuele Furnari, MD
ACCEPTED MANUSCRIPT
Gastroenterology Unit, Department of Internal Medicine University of Genoa Viale BenedettoXV, 6, Genoa, Italy
AC C
EP
TE D
M AN U
SC
Word count paper (excluding title page, references): 494
RI PT
Email : [email protected]
ACCEPTED MANUSCRIPT To The Editors: We read with great interest the study by Cheng et al (1), who investigated patients with gastroesophageal reflux disease (GERD) refractory to anti-secretory therapy by means of endoscopy and impedance-pH monitoring (Imp-pH) off-therapy and concluded that roughly half of
RI PT
these patients referred for testing, actually underwent investigations and received medications with no evidence of GERD, being affected by functional heartburn, functional disorders other than heartburn or by undetermined disorders. These data confirm previous studies (2,3) on the
SC
importance of investigating refractory patients and, also, emphasized the need of stopping antisecretory therapy in order to reduce proton pump inhibitors overuse (4). However, we believe that
M AN U
the decision taken by the authors of using the impedance-pH parameters (i.e. number of reflux episodes) rather than the symptom association analysis for the categorization of NERD patients requires further comments.
Although the number of reflux episodes has been shown as a reproducible parameter in
TE D
patients investigating twice with impedance-pH testing, its role for the diagnosis and management of patients with GERD is still unknown. To the best of our knowledge, to date, only one retrospective study focused its attention on this issue. Frazzoni and colleague reported as one third
EP
of their refractory patients with persistent symptoms remission at 3-year follow-up after surgical fundoplication had an abnormal distal number of total refluxes as the only preoperative impedance-
AC C
pH finding (5). This suggests that this parameter is promising for GERD management, but further outcome studies are mandatory. On the other hand, a recent study by Patel et al. emphasized the importance of the impedance-detected reflux-symptom association in order to predict a positive outcome after medical or surgical therapy (6). Thus, unless further data will be available on the importance of reflux numbers and given the emerging advantages provided by impedance to symptoms analysis, we believe such approach should be preferred when investigating patients with suspected refractory GERD (). Particularly when the pre-test probability of GERD diagnosis is low. Moreover, we think that the 95th percentile value of 73, set as the upper limit of normality in
ACCEPTED MANUSCRIPT
a previous paper on healthy volunteers, should be regarded with caution. Recently, the French Group of Neuro-Gastroenterology modified their originary cut-off from 75 to 53 (7). The explanation provided by these authors was that after a decade of impedance-pH experience, a more careful manual evaluation of impedance-pH tracings permitted to reduce significantly the number of
RI PT
false positive episodes detected by current available software. Interestingly, in 2006 we published our set of normal values and we found a 95th percentile value of 54, which is in line to that observed by the French Group of Neuro-Gastroenterology (8). As a consequence, a considerable proportion
SC
of patients classified by the authors as “hypersensitive” or “functional”, could be instead subjects with a non-acid reflux disease, which may benefit from different therapeutic approaches (i.e surgery
M AN U
instead of visceral pain modulator). Therefore, further studies on normal impedance values are desirable in order to confirm or not previous data.
AC C
EP
TE D
The authors declared no conflict of interest
ACCEPTED MANUSCRIPT
REFERENCES.
1. Cheng FKF, et al. Clin Gastroenterol Hepatol. 2015;13(5):867-73. 2. Savarino E, et al. J Gastroenterol. 2013;48(4):473-82.
RI PT
3. De Bortoli N, et al. Neurogastroenterol Motil. 2014;26(1):28-35. 4. Saavrino E, et al. Nat Rev Gastroenterol Hepatol. 2013;10(6):371-80 5. Frazzoni M, et al. Surg Endosc. 2013;27(8):2940-6.
SC
6. Patel A, et al. Clin Gastroenterol Hepatol. 2015;13(5):884-91.
M AN U
7. Zerbib F, et al. Clin Gastroenterol Hepatol. 2013;11(4):366-72.
AC C
EP
TE D
8. Zentilin P, et al. Dig Liver Dis. 2006;38(4):226-32.
PII: DOI: Reference:
S1542-3565(15)00771-5 10.1016/j.cgh.2015.05.036 YJCGH 54320
To appear in: Clinical Gastroenterology and Hepatology Accepted Date: 29 May 2015 Please cite this article as: Furnari M, Tolone S, Savarino E, Caution about Overinterpretation of Number of Reflux in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease, Clinical Gastroenterology and Hepatology (2015), doi: 10.1016/j.cgh.2015.05.036. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Clinical Gastroenterology and Hepatology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
ACCEPTED MANUSCRIPT
Caution about Overinterpretation of Number of Reflux in Reflux Monitoring for Refractory Gastroesophageal Reflux Disease
Manuele Furnari MD1, Salvatore Tolone MD2, Edoardo Savarino MD, PhD4 Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
RI PT
1
2
Division of Surgery, Department of Surgery, Second University of Naples, Naples, Italy 3
Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of
SC
Padua, Padua, Italy
M AN U
Key Words: Weakly Acidic Reflux; NERD; impedance-pH; functional heartburn; reflux events
Authors contribution:
TE D
Running Title: Number of reflux episodes in refractory GERD
- Manuele Furnari, MD, PhD: writing of the manuscript, approving final version - Salvatore Tolone, MD, PhD: writing of the manuscript, approving final version
AC C
EP
- Edoardo Savarino, MD, PhD: writing of the manuscript, approving final version
Financial support: none
Potential competing interests: none
Corresponding author: Manuele Furnari, MD
ACCEPTED MANUSCRIPT
Gastroenterology Unit, Department of Internal Medicine University of Genoa Viale BenedettoXV, 6, Genoa, Italy
AC C
EP
TE D
M AN U
SC
Word count paper (excluding title page, references): 494
RI PT
Email : [email protected]
ACCEPTED MANUSCRIPT To The Editors: We read with great interest the study by Cheng et al (1), who investigated patients with gastroesophageal reflux disease (GERD) refractory to anti-secretory therapy by means of endoscopy and impedance-pH monitoring (Imp-pH) off-therapy and concluded that roughly half of
RI PT
these patients referred for testing, actually underwent investigations and received medications with no evidence of GERD, being affected by functional heartburn, functional disorders other than heartburn or by undetermined disorders. These data confirm previous studies (2,3) on the
SC
importance of investigating refractory patients and, also, emphasized the need of stopping antisecretory therapy in order to reduce proton pump inhibitors overuse (4). However, we believe that
M AN U
the decision taken by the authors of using the impedance-pH parameters (i.e. number of reflux episodes) rather than the symptom association analysis for the categorization of NERD patients requires further comments.
Although the number of reflux episodes has been shown as a reproducible parameter in
TE D
patients investigating twice with impedance-pH testing, its role for the diagnosis and management of patients with GERD is still unknown. To the best of our knowledge, to date, only one retrospective study focused its attention on this issue. Frazzoni and colleague reported as one third
EP
of their refractory patients with persistent symptoms remission at 3-year follow-up after surgical fundoplication had an abnormal distal number of total refluxes as the only preoperative impedance-
AC C
pH finding (5). This suggests that this parameter is promising for GERD management, but further outcome studies are mandatory. On the other hand, a recent study by Patel et al. emphasized the importance of the impedance-detected reflux-symptom association in order to predict a positive outcome after medical or surgical therapy (6). Thus, unless further data will be available on the importance of reflux numbers and given the emerging advantages provided by impedance to symptoms analysis, we believe such approach should be preferred when investigating patients with suspected refractory GERD (). Particularly when the pre-test probability of GERD diagnosis is low. Moreover, we think that the 95th percentile value of 73, set as the upper limit of normality in
ACCEPTED MANUSCRIPT
a previous paper on healthy volunteers, should be regarded with caution. Recently, the French Group of Neuro-Gastroenterology modified their originary cut-off from 75 to 53 (7). The explanation provided by these authors was that after a decade of impedance-pH experience, a more careful manual evaluation of impedance-pH tracings permitted to reduce significantly the number of
RI PT
false positive episodes detected by current available software. Interestingly, in 2006 we published our set of normal values and we found a 95th percentile value of 54, which is in line to that observed by the French Group of Neuro-Gastroenterology (8). As a consequence, a considerable proportion
SC
of patients classified by the authors as “hypersensitive” or “functional”, could be instead subjects with a non-acid reflux disease, which may benefit from different therapeutic approaches (i.e surgery
M AN U
instead of visceral pain modulator). Therefore, further studies on normal impedance values are desirable in order to confirm or not previous data.
AC C
EP
TE D
The authors declared no conflict of interest
ACCEPTED MANUSCRIPT
REFERENCES.
1. Cheng FKF, et al. Clin Gastroenterol Hepatol. 2015;13(5):867-73. 2. Savarino E, et al. J Gastroenterol. 2013;48(4):473-82.
RI PT
3. De Bortoli N, et al. Neurogastroenterol Motil. 2014;26(1):28-35. 4. Saavrino E, et al. Nat Rev Gastroenterol Hepatol. 2013;10(6):371-80 5. Frazzoni M, et al. Surg Endosc. 2013;27(8):2940-6.
SC
6. Patel A, et al. Clin Gastroenterol Hepatol. 2015;13(5):884-91.
M AN U
7. Zerbib F, et al. Clin Gastroenterol Hepatol. 2013;11(4):366-72.
AC C
EP
TE D
8. Zentilin P, et al. Dig Liver Dis. 2006;38(4):226-32.