Research papers relating to acid reflux · Reflux UK
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Scientific papers

In this section we have selected scientific papers which we have found to be of interest or that are acknowledged as important. The selection is intended as a resource for those wishing to read academic evidence supporting the treatment of Gastro Oesophageal Reflux Disease. Where possible, the links are to the full article but for copyright reasons, if this is not possible, they are links to abstracts.

We will be adding more scientific papers with comments from our expert reflux surgeons. The first two papers below are such papers.

We will add more papers as well as recommendations from professional associations and societies. We welcome any further suggestions from interested readers.

Selected papers

The American College of Gastroenterology guidelines on the diagnosis and treatment of SIBO

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Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms.

Patients with acid, high‐fat and low‐protein diet have higher laryngopharyngeal reflux episodes at the impedance‐pH monitoring

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To assess the impact of diet on the occurrence of proximal reflux episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) in patients with laryngopharyngeal reflux (LPR).

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn

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Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).

Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-year Randomized Trial

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Regurgitative gastroesophageal reflux disease (GERD) refractive to medical treatment is common and caused by mechanical failure of the anti-reflux barrier. We performed a trial to compare the effects of magnetic sphincter augmentation (MSA) with those of protonpump inhibitors (PPIs) in patients with regurgitation and GERD.


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Patients with GERD with moderate-to-severe regurgitation, especially despite once-daily PPI treatment, should be considered for minimally invasive treatment with MSA rather than increased PPI therapy. (Clinical trial registration number: NCT02505945.) (Gastrointest Endosc 2018;-:1-9.)

Long LINX results

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Magnetic sphincter augmentation in patients with large hiatal hernias demonstrates improved outcomes with respect to postoperative PPI requirement and mean GERDHRQL scores. The incidence of symptom resolution or improvement and dysphagia requiring intervention are similar to patients with smaller or no hiatal hernia. Shortterm outcomes of MSA are encouraging in patients with gastroesophageal reflux disease and large hiatal hernias.

A Modern Magnetic Implant for Gastroesophageal Reflux Disease

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A magnetic implant for the treatment of gastroesophageal reflux disease (GERD) was Food and Drug Administration– approved in 2012 and has been extensively evaluated. The device is a ring of magnets that are placed around the gastroesophageal junction, augmenting the native lower esophageal sphincter and preventing reflux yet preserving lower esophageal sphincter physiologic function and allowing belching and vomiting. Magnetic force is advantageous, being permanent and precise, and forces between magnets decrease with esophageal displacement. Multiple patient cohorts have been studied using the magnetic device, and trials establish consistent, long-term improvement in pH data, GERD symptom scores, and proton-pump inhibitor use. A 5-year Food and Drug Administration trial demonstrated that most patients achieved normal pH scores, 85% stopped proton-pump inhibitors, and GERD health-related quality of life symptom scores improved from 27 to 4 at 5 years. Seven studies have compared magnetic augmentation with laparoscopic Nissen fundoplication and demonstrated that the magnetic device achieved comparable efficacy with regard to protonpump inhibitor cessation, GERD symptom score improvement, and heartburn and regurgitation scores. However, to date there have been no randomized, controlled trials comparing the 2 techniques, and the study cohorts are not necessarily comparable regarding hiatal hernia size, severity of reflux, body mass index scores, or esophagitis scores. Dysphagia incidence was similar in both groups. Reoperation rates and safety profiles were also comparable, but the magnetic device demonstrated significant beneficial differences in allowing belching and vomiting. The magnetic device is safe, with the main adverse event being dysphagia with an approximate 3%– 5% chronic incidence. Device removals in clinical trials have been between 0% and 7% and were uneventful. There have been no erosions, perforations, or infections in FDA clinical trials; erosions have rarely been noted in practice. Magnetic augmentation of the lower esophageal sphincter is a safe and effective operation for GERD, and should be considered a surgical option for those seeking a fundicsparing operation, particularly those with parameters consistent with study cohorts. Additional randomized, controlled trials are underway

Lower Esophageal Sphincter Augmentation for Gastroesophageal Reflux Disease: The Safety of a Modern Implant

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During a 4-year period in more than 3000 patients, no unanticipated MSAD complications have emerged, and there is no data to suggest a trend of increased events over time. The presentation and management of device-related issues have been less complicated than revisions for laparoscopic fundoplication or other interventions for GERD. MSAD is considered safe for the widespread treatment of GERD.

Entire list of papers


Esophageal Sphincter Device for Gastroesophageal Reflux Disease New England Journal of Medicine. Ganz et al. 2013

Laparoscopic Magnetic Sphincter Augmentation vs Laparoscopic Nissen Fundoplication: A Matched-Pair Analysis of 100 Patients. J Am Coll Surg. Reynolds et al. 2015

Long-Term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux. Clin Gastroenterol Hepatol. Ganz et al. 2015

One Hundred Consecutive Patients Treated with Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease: 6 Years of Clinical Experience from a Single Center. Journal American College of Surgeons. Bonavina et al. 2013

Fundoplication papers

Laparoscopic Antireflux Surgery vs Esomeprazole Treatment for Chronic GERD The LOTUS Randomized Clinical Trial. Journal American Medical Association. Galmiche et al. 2011

Seven-year follow-up of a randomized clinical trial comparing proton-pump inhibition with surgical therapy for reflux oesophagitis. British Journal of Surgery. Lundell et al. 2007

Prospective trial of laparoscopic Nissen fundoplication versus proton pump inhibitor therapy for gastroesophageal reflux disease: Seven-year follow-up. J Gastrointest Surg. Mehta et al. 2006

Long-Term Results of a Randomized Prospective Study Comparing Medical and Surgical Treatment of Barrett’s Esophagus. Annals of Surgery. Parrilla et al. 2003

A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up. Surgical Innovations. Anvari et al. 2006

Long-term Outcome of Medical and Surgical Therapies for Gastroesophageal Reflux Disease Follow-up of a Randomized Controlled Trial. Journal of American Medical Association. Spechler et al. 2001

Long-Term Results of a Randomized Prospective Study Comparing Medical and Surgical Treatment of Barrett’s Esophagus. Annals of Surgery. Parilla et al. 2003

EndoStim papers

Su1131 Preliminary Results of a Prospective Multi-Center Observational Registry of Lower Esophageal Sphincter Stimulation for GERD: The Less-GERD Registry

Su1123 Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (LES) is Successful in Treating GERD - Long-term 4 Year Results

Long-term results of electrical stimulation of the lower esophageal sphincter for treatment of proximal GERD

Stretta papers

Clinical data

PPI use after fundoplication

Lodrup 2013 Retrospec

PPI related complications

Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study | The BMJ

Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. Journal American Medical Association. Lazarus et al. 2016

FDA Safety Announcement 2012 PPIs & C Diff

Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. British Medical Journal. Khalili et al. 2012

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS One. Shah et al. 2015

Proton Pump Inhibitors: The Culprit for Barrett’s Esophagus? Frontiers in Oncology. Alsalah et al. 2014

Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden

Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans

Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

Oesophageal cancer and anti-reflux surgery

Antireflux Surgery and Risk of Esophageal Adenocarcinoma: A Systematic Review and Meta-analysis. Annals of surgery. Maret-Ouda et al. 2015

Risk factors for esophageal adenocarcinoma after antireflux surgery. Löfdahl et al. Annals of Surgery. 2013

Antireflux Surgery and the Risk of Esophageal Adenocarcinoma. An Antithetical View of the Data From Sweden. Annals of Surgery. DeMeester. 2013

Oesophageal cancer

Symptomatic Gastroesophageal Reflux as a Risk Factor for Esophageal Adenocarcinoma. New England Journal of Medicine. Lagergren et al. 1999

Systematic review: the epidemiology of gastro-oesophageal reflux disease in primary care, using the UK General Practice Research Database Alimentary Pharmacology & Therapeutics. El-Seragi et al. 2008

Risk factors affecting the Barrett's metaplasia-dysplasia-neoplasia sequence. World J Gastrointest Endosc. Craig S Brown and Michael B Ujiki. 2015

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