Esophageal mucosal integrity improves after laparoscopic antireflux surgery in children with gastroesophageal reflux disease.

BACKGROUND: Esophageal intraluminal baseline impedance reflects the conductivity of the esophageal mucosa and may be an instrument for in vivo evaluation of mucosal integrity in children with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pump inhibitory (PPI) therapy resistant GERD. The effect of LARS in children on baseline impedance has not been studied in detail. The aim of this study was to evaluate the effect of LARS on baseline impedance in children with GERD. METHODS: This is a prospective, multicenter, nationwide cohort study (Dutch national trial registry: NTR2934) including 25 patients [12 males, median age 6 (range 2-18) years] with PPI-resistant GERD scheduled to undergo LARS. Twenty-four hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after LARS. Baseline impedance was evaluated during consecutive 2-h intervals in the 24-h tracings. RESULTS: LARS reduced acid exposure time from 8.5 % (6.0-16.2 %) to 0.8 % (0.2-2.8 %), p < 0.001. Distal baseline impedance increased after LARS from 2445 Ω (1147-3277 Ω) to 3792 Ω (3087-4700 Ω), p < 0.001. Preoperative baseline impedance strongly correlated with acid exposure time (r -0.76, p < 0.001); however, no association between symptomatic outcome and baseline impedance was identified. CONCLUSIONS: LARS significantly increased baseline impedance likely reflecting recovery of mucosal integrity. As the change in baseline impedance was not associated with the clinical outcome of LARS, other factors besides mucosal integrity may contribute to symptom perception in children with GERD.

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.

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/m(2), 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/m(2), 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.

Effect of transoral incisionless fundoplication on reflux mechanisms.

OBJECTIVES: Transoral incisionless fundoplication (TIF) is a new endoscopic treatment option for gastroesophageal reflux disease (GERD). The mechanisms underlying the anti-reflux effect of this new procedure have not been studied. We therefore conducted this explorative study to evaluate the effect of TIF on reflux mechanisms, focusing on transient lower esophageal sphincter relaxations (TLESRs) and esophagogastric junction (EGJ) distensibility. METHODS: GERD patients (N = 15; 11 males, mean age 41 years, range 23-66), dissatisfied with medical treatment were studied before and 6 months after TIF. We performed 90-min postprandial combined high-resolution manometry and impedance-pH monitoring and an ambulatory 24-h pH-impedance monitoring. EGJ distensibility was evaluated using an endoscopic functional luminal imaging probe before and directly after the procedure. RESULTS: TIF reduced the number of postprandial TLESRs (16.8 ± 1.5 vs. 9.2 ± 1.3; p < 0.01) and the number of postprandial TLESRs associated with reflux (11.1 ± 1.6 vs. 5.6 ± 0.6; p < 0.01), but the proportion of TLESRs associated with reflux was unaltered (67.6 ± 6.9 vs. 69.9 ± 6.3 %). TIF also led to a decrease in the number and proximal extent of reflux episodes and an improvement of acid exposure in the upright position; conversely, TIF had no effect on the number of gas reflux episodes. EGJ distensibility was reduced after the procedure (2.4 ± 0.3 vs. 1.6 ± 0.2 mm(2)/mmHg; p < 0.05). CONCLUSIONS: TIF reduced the number of postprandial TLESRs, the number of TLESRs associated with reflux and EGJ distensibility. This resulted in a reduction of the number and proximal extent of reflux episodes and improvement of acid exposure in the upright position. The anti-reflux effect of TIF showed to be selective for liquid-containing reflux only, thereby preserving the ability of venting gastric air.

The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study.

INTRODUCTION: Esophageal pain is mediated by sensory nerves, most importantly by the activation of the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor. TRPV1 is activated and sensitized by a broad range of pungent compounds, as well as inflammatory mediators and tissue irritants. Luminal stressors are suggested to impair the barrier function, which results in consequent activation of these sensory nerve terminals and pain. In this study, we investigated the effect of the perfusion of capsaicin, a TRPV1 agonist, on mucosal impedance and pain in asymptomatic volunteers. METHODS: Thirteen asymptomatic volunteers completed a single-blind, saline-controlled, randomized crossover study. Capsaicin or saline was perfused for 30 minutes in the distal esophagus. Visual analog scale pain intensity scores and intraluminal impedance indicating mucosal integrity were determined. Distal and proximal biopsies were obtained 10 minutes later to measure TRPV1 messenger RNA and TRPV1 immunopositivity, as well as the intercellular space area. RESULTS: Capsaicin perfusion resulted in significantly greater pain intensity (P = 0.047) and impaired recovery of the mucosal impedance compared with saline-treated controls (P = 0.027). Pain response was significantly associated with decreased mucosal impedance. Similar dynamics were seen in the proximal esophagus, but mucosal impedance recovered entirely to the preinfusion values there. There was a significant association between mucosal impedance and intercellular space width in the distal esophagus. TRPV1 transcription and expression were not significantly altered within this observation period. DISCUSSION: Esophageal capsaicin perfusion results in pain, which is likely to be explained by impaired mucosal impedance and defective restoration capacity in the distal esophagus.

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.