Nicolaas Fedde Rinsma

Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease.

Objectives:Transoral incisionless fundoplication (TIF) was developed in an attempt to create a minimally invasive endoscopic procedure that mimics antireflux surgery. The objective of this trial was to evaluate effectiveness of TIF compared with proton pump inhibition in a population consisting of gastroesophageal reflux disease (GERD) patients controlled with proton pump inhibitors (PPIs) who opted for an endoscopic intervention over lifelong drug dependence.Methods:Patients with chronic GERD were randomized (2:1) for TIF or continuation of PPI therapy. American Society of Anesthesiologists >2, body mass index >35 kg/m2, hiatal hernia >2 cm, and esophageal motility disorders were exclusion criteria. Primary outcome measure was GERD-related quality of life. Secondary outcome measures were esophageal acid exposure, number of reflux episodes, PPI usage, appearance of the gastroesophageal valve, and healing of reflux esophagitis. Crossover for the PPI group was allowed after 6 months.Results:A total of 60 patients (TIF n=40, PPI n=20, mean body mass index 26 kg/m2, 37 male) were included. At 6 months, GERD symptoms were more improved in the TIF group compared with the PPI group (P<0.001), with a similar improvement of distal esophageal acid exposure (P=0.228) compared with baseline. The pH normalization for TIF group and PPI group was 50% and 63%, respectively. All patients allocated for PPI treatment opted for crossover. At 12 months, quality of life remained improved after TIF compared with baseline (P<0.05), but no improvement in esophageal acid exposure compared with baseline was found (P=0.171) and normalization of pH was accomplished in only 29% in conjunction with deteriorated valve appearances at endoscopy and resumption of PPIs in 61%.Conclusion:Although TIF resulted in an improved GERD-related quality of life and produced a short-term improvement of the antireflux barrier in a selected group of GERD patients, no long-term objective reflux control was achieved.

The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients.

Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro‐esophageal reflux disease (GERD) patients as reflected by an increase in baseline impedance. The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor (PPI) PPI therapy on baseline impedance and heartburn severity in GERD patients.

Electrical Stimulation Therapy for Gastroesophageal Reflux Disease

Electrical stimulation therapy (EST) of the lower esophageal sphincter is a relatively new technique for the treatment of gastroesophageal reflux disease (GERD) that may address the need of GERD patients, unsatisfied with acid suppressive medication and concerned with the potential risks of surgical fundoplication. In this paper we review available data about EST for GERD, including the development of the technique, implant procedure, safety and results from open-label trials. Two short-term temporary stimulation and long-term open-label human trials each were initiated to investigate the safety and efficacy of EST for the treatment of GERD and currently up to 2 years follow-up results are available. The results of EST are promising as the open-label studies have shown that EST is a safe technique with a significant improvement in both subjective outcomes of symptoms and objective outcomes of esophageal acid exposure in patients with GERD. However, long-term data from larger number of patients and a sham-controlled trial are required before EST can be conclusively advised as a viable treatment option for GERD patients.

Effect of Vagus Nerve Integrity on Short and Long-Term Efficacy of Antireflux Surgery

OBJECTIVES:Vagus nerve injury is a feared complication of antireflux surgery (ARS) that may negatively affect reflux control. The aim of the present prospective study was to evaluate short-term and long-term impact of vagus nerve injury, evaluated by pancreatic polypeptide response to insulin-induced hypoglycemia (PP-IH), on the outcome of ARS.METHODS:In the period from 1990 until 2000, 125 patients with gastroesophageal reflux disease (GERD) underwent ARS at a single center. Before and 6 months after surgery, vagus nerve integrity testing (PP-IH), 24-h pH-monitoring, gastric emptying, and reflux-associated symptoms were evaluated. In 2014, 14–25 years after surgery, 110 patients were contacted again for evaluation of long-term symptomatic outcome using two validated questionnaires (Gastrointestinal Symptom Rating Scale (GSRS) and GERD-Health Related Quality of Life (HRQL)).RESULTS:Short-term follow-up: vagus nerve injury (PP peak ≤47 pmol/l) was observed in 23 patients (18%) 6 months after fundoplication. In both groups, a comparable decrease in reflux parameters and symptoms was observed at 6-month follow-up. Postoperative gastric emptying was significantly delayed in the vagus nerve injury group compared with the vagus nerve intact group. Long-term follow-up: patients with vagus nerve injury showed significantly less effective reflux control and a higher re-operation rate.CONCLUSIONS:Vagus nerve injury occurs in up to 20% of patients after ARS. Reflux control 6 months after surgery was not affected by vagus nerve injury. However, long-term follow-up showed a negative effect on reflux symptom control and re-operation rate in patients with vagus nerve injury.

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients.

Impact of laparoscopic antireflux surgery on belching in pediatric GERD patients

Laparoscopic antireflux surgery (LARS) is a well‐established treatment option for children with proton pomp inhibitor (PPI)‐resistant gastroesophageal reflux disease (GERD). Besides preventing reflux of gastric fluid and solid content, LARS may also impair the ability of the stomach to vent intragastric air (i.e. gastric belching) and induce gas‐related complications, such as bloating and/or hyperflatulence. Furthermore, it was previously hypothesized that LARS induces a behavioral type of belching, not originating from the stomach, called supragastric belching. The aim of this study was to objectively evaluate the impact of LARS on gastric (GB) and supragastric belching (SGB) in children with GERD.

Tu1873 Esophageal Epithelial Barrier Function in GERD Patients and Healthy Controls: An Ex-Vivo Study in the Basal State and in Response to Acid Exposure

Background: Esophageal epithelial integrity is considered an important factor in the prevention of tissue damage by gastric refluxate.We hypothesized that in patients with gastroesophageal reflux disease (GERD) the esophageal epithelial barrier function is impaired and less resistant in response to acid exposure. We therefore investigated esophageal epithelial integrity in GERD patients and in healthy controls both in the basal state and in response to acid exposure Methods: 14 patients with chronic GERD (8 with erosive esophagitis, 6 with non-erosive reflux disease) and 10 healthy controls (HC) were enrolled. Before endoscopy, GERD patients discontinued PPI therapy for 7 days. Six esophageal biopsies frommacroscopically normal mucosa were obtained approximately 5 cm above the gastroesophageal junction and directly transferred to a mini-Ussing chamber system. After an equilibration period, baseline TEER was assessed. Half of the biopsies were then exposed at their luminal side to an acidic solution (pH1) for 30 minutes. During exposure and after removal of the acidic solution, changes in TEER were analyzed relative to baseline TEER. Permeation to the paracellular permeation marker fluorescein (375 DA 1 mg/ml) was assessed in all biopsies (previous acid-exposed and non-exposed) for 120 minutes. Only subjects with at least two adequate biopsies (one for acid exposure, one as a control) were included. Results: Esophageal epithelium of GERD patients showed lower baseline TEER (127.7±13.3 Ω vs. 174.3±17.6 Ω, p=0.04) and a trend toward higher transmucosal permeation of fluorescein in the nonexposed biopsies when compared to healthy controls (serosal concentration (pmol/ml) after 120 min: 48.2 (7.6-66.7) vs. 6.8 (3.6-20.2), p=0.09 and AUC: 79.8 (12.9-135.6) vs. 9.0 (5.5-31.3), p=0.07). Acid exposure provoked a fall in TEER that was equal for the biopsies of GERD patients and healthy controls (-52.1±2.5% vs. -50.0±4.4% of baseline TEER). After removal of the acidic solution, TEER recovered also to a similar extent in GERD patients and healthy controls (89.6±3.8% vs. 93.8±3.0% of baseline TEER). However, maximum TEER was reached earlier in biopsies of GERD patients (54±9 min vs. 83±6 min (HC), p= 0.02) and at the end of the experiment, TEER relative to baseline was lower in biopsies of GERD patients (73.7±5.8% vs. 89.7±3.3% (HC) of baseline TEER, p<0.05). Conclusion: The esophageal epithelial barrier function of GERD patients is impaired, reflected by lower baseline transepithelial electrical resistance and a trend toward higher fluorescein permeation, and seems to be less resistant in response to acid exposure ex-vivo.

Tu1110 Lower Esophageal Sphincter (LES) Electrical Stimulation Improves Sleep Quality and Work Productivity in Patients With Refractory GERD

Background Gastroesophageal reflux disease (GERD) has been identified as a possible contributor of aspiration after lung transplantation that leads to graft failure and increased mortality. This study was designed to investigate whether the usage of proton pump inhibitor (PPI) pre-transplant is associated with decreased posttransplant mortality and/or retransplant. Methods A total of 324 consecutive patients who underwent lung transplant from January 2009 to June 2012 were retrospectively reviewed. Demographic information and baseline clinical characteristics of lung transplant recipients were collected. Clinical variables were compared between patients with and without clinical events determined as all-cause mortality and/or re-transplant. Usage of PPI were analyzed between recipients with clinical events (n= 78) and those without events (n= 246). Perioperative events were defined as events that occurred within 30 days after transplant. Results The cohort comprised of 58.3% male (189 of 324) with mean age (SD) of 58(13). Majority of patients had double lung transplant (62.8%; 203 of 324). Mean (SD) follow up interval was 2.0 (1.2) year. Idiopathic pulmonary fibrosis was the leading primary lung pathology (46.9%), followed by COPD (23.1%) and cystic fibrosis (6.5%). Prevalence of GERD prior to transplant was 42% (137 of 324). Clinical events occurred in 25% (78 of 324) of the cohort (66 death and 12 retransplants). Of those, 29.5% (23 of 78) were perioperative. There was no statistically significant difference in percentage use of PPI between patients with and without events (54.7% VS 53.0% respectively; p 0.927). Subgroup analysis in patients with diagnosis of GERD pre-transplant also demonstrated no significant difference in PPI use in the two groups (78.8% VS 83.7%; p 0.522). Kaplan Meier survival analysis revealed no significant difference in both mortality (p 0.874) and overall graft survival (p 0.806) as shown in Figure 1. Conclusion Use of proton pump inhibitors prior to transplantation is not associated with increased allografts survival in lung transplant recipients. Baseline characteristics and study variables categorized by clinical events.

658 Surgical and Medical Treatment of GERD Lead to a Comparable Increase in Baseline Impedance Levels

BACKGROUND: Presence of pepsin in bronchoalveolar lavage fluid, laryngeal biopsy and sputum may be a consequence of gastroesophageal reflux disease (GERD). A novel noninvasive test to detect it in saliva/sputum (PEP-Test) has been proposed to diagnose GERD. A correlation between PEP-Test and multichannel impedance pH monitoring (MII-pH) has never been performed. AIM: The aim was to evaluate the PEP-Test accuracy for the diagnosis of GERD in patients with reflux symptoms by means of MII-pH. PATIENTS ANDMETHODS: 35 patients with GER symptoms were studied. All patients with negative endoscopy underwent pathophysiological examinations, after wash-out from proton pump inhibitors. Samples of saliva/sputum were obtained by requesting the patient to cough up and spit into a tube containing 0.01 M citric acid within 15 minutes from experiencing reflux symptoms. Patients were grouped on the basis of MII-pH results as follows: True-NERD (increased acid exposure time, AET/reflux number); Hypersensitive Esophagus, HE (normal AET/reflux number, positive symptom association probability index, SAP); no-GERD patients (normal AET/reflux number, negative SAP). Roc curve was performed to obtain diagnostic accuracy of test. RESULTS: Male/Female was 18/17, mean age was 49.8 yrs, mean BMI was 24.9. The mean BMI was similar in three sub-groups. Nine patients were abitudinary smokers and five had a regular alimentary alcohol use. Eleven out of thirty-five patients presented hiatal hernia. No patients showed abnormal esophageal motility. MII-pH results showed: 16 True-NERD patients (median AET 9.5); 12 HE (median AET 3); 7 no-GERD (median AET 1.1). PEPTest was positive in 93.7% of True-NERD, in 58.3% of HE, and negative in 100% of noGERD patients. Accuracy of PEP-Test is reported in Table 1. CONCLUSIONS: PEP-Test is a simple, economic, reproducible, highly specific test to detect the presence of GERD. Accuracy PEP-Test

Mo1062 Effect of Transoral Incisionless Fundoplication on the Occurrence of Transient Lower Esophageal Sphincter Relaxations (TLESRs) in GERD Patients

unanticipated adverse events, or untoward sensation due to LES-EST. There were no reports of treatment related dysphagia and the manometric evaluation of swallow was also normal. Conclusion: Long-term follow-up of 6 months showed LES-EST to be safe and effective for treating GERD patients with incomplete response to PPI therapy. Importantly, LES-EST can be optimized to individual patient needs to further improve patient outcomes. All patients had received significant clinical benefit from LES-EST and the trial has been extended with one-year follow-up results available after March 2012.