Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett’s esophagus
Francisco Baldaque-Silva, Michael Vieth, Mumen Debel, Bengt Håkanson, Anders Thorell, Nuno Lunet, Huan Song, Miguel Mascarenhas-Saraiva, Gisela Pereira, Lars Lundell, Hanns-Ulrich Marschall
Francisco Baldaque-Silva, Institute of Medicine, Karolinska Institutet, Karolinska University Hospital, 14186 Stockholm, Sweden
Michael Vieth, Mumen Debel, Department of Pathology, Klinikum Bayreuth, 95445 Bayreuth, Germany
Bengt Håkanson, Anders Thorell, Department of Surgery, Ersta Hospital, 11691 Stockholm, Sweden
Bengt Håkanson, Anders Thorell, Department of Clinical Sciences, Danderyd, Karolinska Institutet, 11691 Stockholm, Sweden
Nuno Lunet, Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, 4200-319 Porto, Portugal
Huan Song, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden
Miguel Mascarenhas-Saraiva, Gisela Pereira, Department of Gastroenterology, ManopH and Instituto CUF, 4460-188 Porto, Portugal
Lars Lundell, Clintec, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden
Hanns-Ulrich Marschall, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
Author contributions: Baldaque-Silva F, Lundell L and Marschall HU designed the study; Baldaque-Silva F, Vieth M, Håkanson B, Thorell A and Marschall HU collected the data; Baldaque-Silva F, Lundell L and Marschall HU analyzed the data under supervision of Lunet N and Song H (Biostatisticians); Baldaque-Silva F, Pereira G, Mascarenhas-Saraiva M, Lundell L and Marschall HU interpreted the data and wrote the paper; all authors have read and revised the manuscript; Baldaque-Silva F, Lundell L and Marschall HU bear the primary responsibility for the content.
Institutional review board statement: The study was approved by the Regional Research Ethics Committee of Stockholm (approval No. 04534).
Clinical trial registration statement: The study is registrered in the Regional Research Ethics Committee of Stockholm database http://www.epn.se/stockholm/om-naemnden/.
Informed consent statement: All participants gave oral and written informed consent to participate in study.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: All collected data are presented within the core of the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Francisco Baldaque-Silva, MD, Gastrocentrum, Institute of Medicine, Karolinska Institutet, Karolinska University Hospital, Karolinska vägen, 14186 Stockholm, Sweden. fbaldaquesilva@gmail.com
Telephone: +46-8-58582328 Fax: +46-8-58582335
Received: October 5, 2016
Peer-review started: October 7, 2016
First decision: November 9, 2016
Revised: December 2, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: May 7, 2017
Processing time: 213 Days and 14.9 Hours
AIM
To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication.
METHODS
Two cohorts of long-segment Barrett’s esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2 (n = 30) consisted of patients with a previous fundoplication.
RESULTS
In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores (P = 0.001), which were most pronounced after the starting dose of PPI (P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium.
CONCLUSION
This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.
Core tip: This study evaluated the effects of increasing, acid-reflux-adjusted doses of proton pump inhibitors (PPI) on symptoms and histology in Barrett’s esophagus (BE) patients in comparison to BE patients with a clinically successful fundoplication. All patients went through an extensive prospective protocol with symptom assessment, upper endoscopy with biopsies, 24 h pH-monitoring and manometry. In the non-operated group, 42% of patients needed more than the standard PPI dose to reach acid control which then was associated with improvement of symptom scores up to the same levels as after successful fundoplication. In addition, acid reflux control was associated with changes in the esophageal columnar and squamous epithelium, regardless of medical or surgical treatment.
