Refractory Gastroesophageal Reflux Disease Research Articles

Laparoscopic Nissen fundoplication mainly reduces the volume of acid reflux and potentially improves mucosal integrity up to the middle esophagus in neurologically impaired children detected by esophageal combined pH–multichannel intraluminal impedance measurements

BackgroundThe aim of this study was to evaluate detailed changes of gastroesophageal reflux disease (GERD) in children before and after laparoscopic Nissen fundoplication (LNF) utilizing esophageal combined pH–multichannel intraluminal impedance (pH/MII) measurements. Patients and methodsThirteen patients with neurological impairment, who received laparoscopic Nissen fundoplication (LNF) owing to refractory pathological GERD, were enrolled in this study. 24h pH/MII was conducted in all patients before and one year after LNF. Each parameter of the pH/MII was evaluated and compared each other. ResultsBoth the mean pH index and bolus exposure index after LNF were significantly lower than those before LNF. The mean numbers of total and nonacid reflux episodes after LNF were significantly lower than those before LNF. The mean numbers of total, acid and nonacid proximal reflux episodes after LNF were significantly lower than those before LNF. The mean baseline impedance values from Z3 to Z6 after LNF were significantly higher than those before LNF. ConclusionsThe present study provides new insights into the effects of LNF in pediatric patients, which prevents mainly acid reflux episodes from rising to the proximal esophagus, and is expected to improve the mucosal integrity up to the middle esophagus.

Transoral Incisionless Fundoplication for Refractory Gastroesophageal Reflux Disease: Where Do We Stand?

Gastroesophageal reflux disease (GERD) is a chronic, progressive, and costly medical condition affecting a substantial proportion of the world population, predominantly the Western population. The available treatment options for patients with refractory GERD symptoms are limited to either laparoscopic surgery with significant sequelae or potentially lifelong, high-dose proton pump inhibitor therapy. The restoration of the antireflux competence of the gastroesophageal junction at the anatomic and physiologic levels is critical for the effective long-term treatment of GERD. Transoral incisionless fundoplication (TIF) surgery is a safe, well-tolerated, and effective treatment that has yielded significant symptomatic improvement in patients with medically refractory GERD symptoms. In this review article, we have summarized case series and reports describing the role of TIF for patients with gastroesophageal reflux symptoms. The reported indications, techniques, complications, and success rates are also discussed.

Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring.

About 30% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI failure in Asian GERD patients has rarely been studied, and the therapy remained unclear. The aims were to explore the possible reasons for PPI failure and to treat these patients with the guidance of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. Thirty-nine consecutive patients with refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The refractory GERD patients were grouped into acid overexposure, non-acid reflux, and functional heartburn after the MII-pH monitoring. Double dose of either PPI or paroxetine was administered to refractory GERD patients within different groups. The number of patients in groups of acid overexposure, non-acid reflux, and functional heartburn was 6, 12, and 21, respectively. The acid overexposure group had the most acid reflux events. Among the acid overexposure group, five (5/6) patients accomplish symptom relief with double dose of esomeprazole. For the patients in non-acid reflux group, double dose of esomeprazole made half (6/12) of the patients obtain symptom relief. For the patients in functional heartburn group, the paroxetine had relieved the symptoms in 14 patients among all the 21 patients. In total, with the guidance of MII-pH monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom relief. Acid overexposure, non-acid reflux, and functional heartburn were the common reasons for persistent reflux symptoms despite PPI. With the guidance of MII-pH, a tailored therapy could resolve the persistent reflux symptoms among two-third of patients.

Evaluation of conventional laparoscopic versus robot-assisted laparoscopic redo hiatal hernia and antireflux surgery: a cohort study.

Surgery for refractory gastroesophageal reflux disease (GERD) and hiatal hernia leads to recurrence or persisting dysphagia in a minority of patients. Redo antireflux surgery in GERD and hiatal hernia is known for higher morbidity and mortality. This study aims to evaluate conventional versus robot-assisted laparoscopic redo antireflux surgery, with the objective to detect possible advantages for the robot-assisted approach. A single institute cohort of 75 patients who underwent either conventional laparoscopic or robot-assisted laparoscopic redo surgery for recurrent GERD or severe dysphagia between 2008 and 2013 were included in the study. Baseline characteristics, symptoms, medical history, procedural data, hospital stay, complications and outcome were prospectively gathered. The main indications for redo surgery were dysphagia, pyrosis or a combination of both in combination with a proven anatomic abnormality. The mean time to redo surgery was 1.9 and 2.0 years after primary surgery for the conventional and robot-assisted groups, respectively. The number of conversions was lower in the robot-assisted group compared to conventional laparoscopy (1/45 vs. 5/30, p = 0.035) despite a higher proportion of patients with previous surgery by laparotomy (9/45 vs. 1/30, p = 0.038). Median hospital stay was reduced by 1 day (3 vs. 4, p = 0.042). There were no differences in mortality, complications or outcome. Robotic support, when available, can be regarded beneficial in redo surgery for GERD and hiatal hernia. Results of this observational study suggest technical feasibility for minimal-invasive robot-assisted redo surgery after open primary antireflux surgery, a reduced number of conversions and shorter hospital stay.

Effects of Transcutaneous Electrical Acustimulation on Refractory Gastroesophageal Reflux Disease.

Objective. To investigate effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) performed by a wearable watch-size stimulator for refractory gastroesophageal reflux disease (RGERD). Methods. Twenty patients diagnosed as RGERD were enrolled in the study and randomly divided into four groups: esomeprazole group (Group A), esomeprazole combined with TEA group (Group B), esomeprazole combined with sham-TEA group (Group C), and esomeprazole combined with domperidone group (Group D). HRM and 24 h pH-impedance monitoring and GerdQ score were used to measure related indexes before and after treatment. Results. (1) TEA significantly increased LESP, compared with PPI treatment only or PPI plus sham-TEA. After pairwise comparison, LESP of Group B was increased more than Group A (P = 0.008) or Group C (P = 0.021). (2) PPI plus TEA decreased not only the number of acid reflux episodes but also the number of weak acid reflux episodes (P = 0.005). (3) Heartburn and reflux symptoms were improved more with PPI + TEA than with PPI treatment only or PPI plus sham-TEA (GerdQ scores, P = 0.001). Conclusion. TEA can improve symptoms in RGERD patients by increasing LESP and decreasing events of weak acid reflux and acid reflux; addition of TEA to esomeprazole significantly enhances the effect of TEA.

A Multicenter, Randomized, Open-Label Trial: Efficacy of Once-Daily Versus Twice-Daily Double-Dose Rabeprazole on Refractory Gastroesophageal Reflux Disease-Related Symptoms and Quality of Life

BackgroundApproximately 20% to 40% of patients with gastroesophageal reflux disease (GERD) are refractory to standard-dose proton-pump inhibitor (PPI) treatment. ObjectiveWe compared the efficacy and quality-of-life effects of 20 mg once daily (QD) versus 10 mg twice daily (BID) rabeprazole (RPZ) in patients with refractory GERD-related symptoms and sleep disturbances. MethodsThis multicenter, prospective, randomized, open-label study included patients in whom PPI treatment >4 weeks was ineffective. According to the Global Overall Symptom (GOS) scale, PPI-refractory GERD was defined as ≥1 category with >3 points among 10 specific upper gastrointestinal symptoms. Seventy-eight patients were randomly assigned to 20 mg QD and 10 mg BID RPZ groups for 8 weeks. Efficacy was evaluated using self-reported questionnaires, including the GOS scale and Pittsburg Sleep Quality Index (PSQI), whereas quality of life was assessed using the Short-Form 8 Health Survey (SF-8), at 4 and 8 weeks. Patients showing improvement at 8 weeks received follow-up every 4 to 8 weeks. ResultsGOS scale scores were significantly improved at 8 weeks in both groups, with no significant intergroup differences. Although SF-8 scores showed an increasing trend over 8 weeks in both groups, the physical component summaries in the 10 mg BID group significantly improved. The mental component summaries clearly improved in the 10 mg BID group. Of the 74 cases (4 missing), 51 (68.9%) had PSQI scores ≥5.5. PSQI scores remained unchanged during follow-up in both groups. The recurrence rate was not significantly different (46.1% vs 47.1% in the 20 mg QD and 10 mg BID groups, respectively) during the follow-up period at median (interquartile range) 24.0 (30.5) months. ConclusionsIn patients with refractory GERD, there was no significant difference in GOS scale score, PSQI, or recurrence rate between the groups. With regard to subscores of the SF-8, the 10 mg BID group might be potentially effective.

Current Status of Translational Research on Gastroesophageal Reflux Disease

The prevalence of gastroesophageal reflux disease (GERD) and the incidence of some of its complications have risen strikingly over the last few decades. With the increase in our understanding of the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extra-esophageal manifestations. The aim of this article is to provide a review of available current translational research on GERD. This review includes acid pocket, ambulatory pH monitoring, impedance pH monitoring, mucosa impedance, and high resolution manometry. This article discusses current translational research on GERD.

Evaluation of Gastroesophageal Reflux Disease Using the Bravo Capsule pH System.

Gastroesophageal reflux disease (GERD) is a disease predominantly seen in the West but there is a rising trend in Asia. Ambulatory 24-hour catheter-based pH monitoring has been the de facto gold standard test for GERD that correlates symptoms with acid reflux episodes. However, drawbacks such as patients’ discomfort, and catheter displacement render the test as cumbersome and error-prone. The Bravo pH wireless system is designed to be user-friendly and has an added advantage of prolonged pH monitoring. The system is comparable to the catheter-based pH monitoring system in terms of diagnostic yield and symptom-reflux association. Indications include evaluation of patients with refractory GERD symptoms and prior to anti-reflux surgery. Bravo utilizes a wireless pH-sensing capsule with a complete prepackaged system, and a data processing software. The capsule may be positioned indirectly using endoscopic or manometric landmarks or under direct endoscopic guidance. Optimal threshold cut-off values are yet to be standardized but based on available studies, for the Asian population, it may be recommended for total % time pH < 4 of 5.8 over 48 hours. Cost is a limitation but capsule placement is relatively safe although technical failures may be seen in small percentage of cases.

Food allergy in children with refractory gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) and food allergy are frequent disorders of childhood. The purpose of this study was to determine the frequency of food allergy in children with refractory GERD. A total of 151 children resistant to pharmacologic GERD treatment underwent skin prick test, specific immunoglobulin E, eosinophil count, atopy patch test (APT), and oral food challenge, and were then divided into three groups according to the results of oral milk challenge and allergy work-up: group A1, positive oral milk challenge and positive IgE-mediated allergy test; group A2, positive milk challenge and negative IgE-mediated allergy test; and group B, negative oral milk challenge and negative allergy tests. There were 35, 30 and 86 patients in group A1, group A2 and group B, respectively. A total of 28 of 35 patients in group A1 had cow's milk allergy and the other seven patients had egg allergy. APT positivity was more common in group A2. Endoscopic esophagitis was observed in six group A1 patients and in four group A2 patients. Bloody stools, atopic dermatitis and recurrent wheezing episodes were significantly more common in group A1 than in group A2 and group B (P < 0.001, for both). Cow's milk allergy was observed frequently in children resistant to pharmacologic GERD treatment. Combined skin prick and specific IgE tests, APT and oral food challenge is essential for avoidance of unnecessary elimination diet.

Diagnosis and Treatment of Refractory Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD) was a damage in mucosal layer caused by gastric acid reflux. GERD was found about 10-20% in Western Countries and less in Asia, about 2,6-6,7%. Among different type of GERD, refractory GERD was a problem found in daily clinical practice. This terminology was used in patients with regurgitation and heartburn symptoms which is not responsive to 8 weeks proton pump inhibitor (PPI) therapy. There were several mechanisms underlying the etiology and pathophysiology of refractory GERD. In general, refractory GERD diagnosis was based on clinical findings, objective endoscopic examination, ambulatory reflux monitoring, and response to antiacid-secretion therapy. Reevaluation of patients compliance should be the first step in refractory GERD management. A further treatment strategies could be started, consist of medical and surgical therapies. A basic clinical knowledge of refractory GERD would help clinician in deciding the best approach for diagnosis and therapy.

Acupuncture and Integrative Medicine for Pediatric Gastroesophageal Reflux and Functional Dyspepsia

Abstract Background: Acupuncture for gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), while not previously described in a pediatric cohort, may be a safe and effective alternative to pharmacologic treatment. This article provides a description of the authors' experience in treating children with refractory GERD or FD wherein acupuncture was used as a part of an integrative medicine treatment approach. Materials and Methods: A retrospective chart review was performed from 2013 to 2014. Results: Seven patients were treated: 5 of 6 reported reduction of nausea and 3 of 4 reported reductions in pain. Four of 4 patients were successfully weaned off proton pump inhibitors. The patients in this cohort tolerated acupuncture very well. Conclusions: Acupuncture in children is well-tolerated and safe, and has minimal adverse effects. It may be an effective adjunct to standard care for treating children with GERD or FD.

Issue Highlights

Issue Highlights

Interference With Daily Activities and Major Adverse Events During Esophageal pH Monitoring With Bravo® Wireless Capsule Versus Conventional Intranasal Catheter: A Systematic Review of Randomized Controlled Trials

Introduction: For three decades, ambulatory 24-hour intranasal pH monitoring has been the established gold standard for detecting acid reflux in patients with refractory gastroesophageal reflux disease. However, device-associated adverse events and unpleasant experiences, reported by patients during pH monitoring have led to the invention of more convenient pH monitors such as Bravo wireless capsule.Table 1: Device Interference with Daily ActivitiesMethods: PubMed, Cochrane Library, Clinical Trials.gov and Google Scholar were searched up to March 20, 2015. Only randomized controlled trials (RCTs) in adult patients that compared the interference with routine daily activities and adverse events between Bravo and catheter pH monitors were included. Results: After screening a total of 574 articles( figure 1), three unique RCTs with 167 patients met our inclusion criteria. The average age of patients enrolled in these RCT's was 51 years. Interference with normal daily activities (table 1) was more in the catheter group than Bravo: 75+/-5 versus 92+/-2, P < 0.001 (Andrews et al, findings were reported as100mm, mean Visual analogue scale (VAS) +/-standard error of the mean (SEM),100 = completely normal); Wong et al (mean+/-SEM):1.3+/-0.2 versus 0.32+/-0.1, P 0.001 and Wenner et al using 10cm median VAS, Interquartile range (IQR), 10 been the worst is 5.7(2.3-8.0) compared to 0.7(0.2-3.4), P < 0.0001 respectively. As elucidated in table 2, Overall adverse events were more in the catheter group than Bravo (39+/-4 versus 26+/-4, P 0.012 for Andrews et al (100 been the worst) and 5.1 (2.0-6.6) versus 2.1 (0.5-4.6), P < 0.001 (for Wenner et al). No overall adverse events recorded for Wong et al. However, Most patients in catheter group complained of nasal and or throat symptoms while Majority of the patients randomized to Bravo group reportedly perceived chest pain higher than those in catheter group.Figure 1Conclusion: The result of our study revealed that Bravo wireless capsule with or without sedation and regardless of the route of insertion (transnasal or per-oral placement) is better tolerated; had lesser adverse events and provided overall patient's satisfaction than conventional intranasal catheter. A significant number of patients in the Bravo when compared to catheter group were able to continue their routine daily activities including returning to work during pH testing period with overall less discomfort score in their normal daily life. In addition, Bravo group patients were better able to tolerate food than the catheter- based group.Table 2: Device Associated Adverse Events

IW-3718, a Novel Gastric-Retentive Bile Acid Sequestrant, Improved Symptoms of Refractory GERD in a Double-Blind, Placebo-Controlled Phase 2a Study

Introduction: Refractory GERD (rGERD) is characterized by continued heartburn (HB) and/or regurgitation (RG) despite PPI treatment. Bile acid reflux appears to be an important contributing factor in rGERD. IW-3718 is a novel, investigational, gastric-retentive formulation of a bile acid sequestrant designed to bind to bile acids in the refluxate. Our aim was to determine if IW-3718 improves HB and/or RG in patients with continued symptoms despite receiving standard dose PPI therapy (SD PPIs). Methods: We conducted a phase 2a, double-blind, placebo-controlled study with a 2-week baseline and a 4-week treatment period. Eligible patients were taking SD PPIs, had HB or RG ≥2 days/week for 8 weeks before the study, and reported HB ≥4 of the last 7 days of baseline. Patients underwent optional 24h ambulatory Bilitec monitoring on SD PPI therapy and were stratified: pathological bile reflux (PBR=esophageal bilirubin absorbance >0.14 for >6% of time), normal bile reflux (NBR), and unknown bile reflux (UBR) if Bilitec was declined. Patients continued their SD PPIs and were randomly assigned 1:1 to IW-3718 1000 mg BID or placebo within each stratum. GERD symptoms were assessed twice daily via e-diary. Treatment satisfaction and degree of relief were measured weekly. This exploratory study included no predefined primary or secondary endpoints. AEs were recorded. Results: ITT Population included 93 patients (33 PBR, 19 NBR, 41 UBR). Demographics were generally similar between the IW-3718 and placebo groups within each stratum. Overall, the percent of patients free of RG at Week 4 was significantly higher among patients on IW-3718 compared with placebo (p=0.03), with greater improvement seen in PBR patients (p=0.01) (Figure). Degree of relief for overall GERD symptoms (p=0.07) and % of patients free of HB (p=0.25) were numerically greater for IW-3718 vs placebo (Figure). Change from baseline in severity of daytime HB, severity of daytime RG, and percent of days free of HB and RG were also improved at Week 4 for IW-3718 patients (vs placebo) in the overall population and in the PBR subgroup (Table). AEs were reported by 48% and 32% of IW-3718 and placebo patients, respectively; the most common AE was constipation (13% vs 0%, respectively). Conclusion: IW-3718 was well tolerated and improved RG and HB in GERD patients with continued symptoms while taking SD PPIs. The results of this study support the hypothesis that bile acid sequestration can reduce rGERD symptoms.Figure 1Table 1: Improvement in Heartburn and Regurgitation from Baseline to Week 4 (ITT Population)

Symptomatic Outcomes and Safety of Combined Transoral Incisionless Fundoplication and Laparoscopic Hiatal Hernia Repair

Introduction: Transoral incisionless fundoplication (TIF) has been shown to improve symptomatic outcomes in chronic refractory GERD. However, patients with large hiatal hernias have typically been excluded due to difficulty in endoscopic reduction. Data is limited on the use of combined TIF with laparoscopic hiatal hernia repair. We aimed to evaluate the symptomatic outcomes and safety of hybrid TIF. Methods: TIFs performed using EsophyX device from February 1, 2011 to December 31, 2014 were evaluated for patient demographics, prior studies (EGD, pH study, and manometry), size of hiatal hernia, and post-procedure complications. Typical and atypical reflux symptoms before and after TIF were retrospectively assessed using 3 validated questionnaires: Gastroesophageal Reflux Disease-Health related Quality of Life (GERD-HQRL), Reflux Symptom Index (RSI), and Gastroesophageal Reflux Symptom Score (GERSS). Results: 19 TIF procedures were reviewed, with 10 standard and 9 hybrid procedures performed. The average age was 49 years with 58% males. The average body mass index was 28. The average size of the hiatal hernia longitudinally in the standard and hybrid groups was 0.5 cm and 3.2 cm, respectively (p < 0.01). The mean GERD-HQRL score improved significantly in both the standard (27.4 to 10.9, p < 0.01) and hybrid group (22.4 to 5.2, p < 0.01). The mean RSI score improved significantly in both the standard (15.3 to 7.2, p < 0.02) and hybrid group (12.1 to 3.4, p < 0.04). The mean GERSS score improved significantly in both the standard (32.4 to 6.7, p < 0.01) and hybrid group (24.7 to 4.9, p < 0.01). There were no major complications in either group. Conclusion: Transoral incisionless fundoplication with concurrent laparoscopic hiatal hernia repair is safe and effective in improving symptoms of refractory GERD. Hybrid TIF may be a less invasive option compared to Nissen fundoplication for patients with large hiatal hernias.

Endoscopic Removal of Bravo® pH Probe: Report of Two Cases

Introduction: The Bravo pH monitoring system is widely used to further investigate the patients with refractory or atypical GERD. The pH probe is attached by deploying a locking pin that is passed through the esophageal mucosa and pulled by appropriate suction into a small cup in the side of the probe. Subsequently, the probe sloughs spontaneously from the mucosa within 1-2 weeks and passes uneventfully through the GI tract. Most patients have no or mild symptoms while the probe is attached, but more severe chest pain, odynophagia, or dysphagia occurs in about 10% of patients. We report two rare cases of patients requiring endoscopic removal of Bravo pH probe. Case 1: 34 year-old female who presented with persistent heartburn despite maximal acid-suppressive therapy underwent endoscopic placement of Bravo pH probe at 6 cm proximal to GEJ. One hour after the procedure, the patient complained of significant chest pain at the site of Bravo pH monitoring probe and after 3 hours, the pain was persistent with no change in severity. Repeat endoscopy was performed. The Bravo pH probe was identified. A cold snare was placed around Bravo pH probe but was unsuccessful at removal. A hot snare was used and Bravo capsule probe was dislodged and advanced to stomach. Probe was snared and removed with endoscope via mouth. Patient's pain resolved immediately. Case 2: 37 year-old male who had persistent chronic mild-to-moderate heartburn even after treatment with maximal proton-pump inhibitor for appropriate duration underwent endoscopic placement of Bravo pH probe at 6 cm proximal to GEJ. However, due to technical difficulties, the probe did not register with the monitor. Subsequently, another EGD was performed and the Bravo pH probe was removed via hot snare, after cold snare was again unsuccessful, and removed via mouth. A second Bravo pH probe was placed successfully and was working properly. Discussion: Bravo pH probes may require removal in certain situations. These cases show that both cold and hot snare techniques are safe and simple endoscopic procedures for the removal of the Bravo pH probe. We recommend the cold snare method as a first option with the hot snare method in cases the former fails.

A prospective analysis of GERD after POEM on anterior myotomy

BackgroundPeroral endoscopic myotomy (POEM) is an emerging, minimally invasive procedure capable of overcoming limitations of achalasia treatments, but gastroesophageal reflux disease (GERD) after POEM is of concern and its risk factors have not been evaluated. This prospective study examined GERD and the association of POEM with reflux esophagitis.MethodsAchalasia patients were recruited from a single center. The pre- and postoperative assessments included Eckardt scores, manometry, endoscopy, and pH monitoring.ResultsBetween September 2011 and November 2014, 105 patients underwent POEM; 70 patients were followed up 3 months after POEM. Postoperatively, significant reductions were observed in lower esophageal sphincter (LES) pressure [from 40.0 ± 22.8 to 20.7 ± 14.0 mmHg (P < 0.05)], LES residual pressure [from 22.1 ± 13.3 to 11.4 ± 6.6 mmHg (P < 0.05)], and Eckardt scores [from 5.7 ± 2.5 to 0.7 ± 0.8 (P < 0.05)]. Symptomatic GERD and moderate reflux esophagitis developed in 5 and 11 patients (grade B, n = 8; grade C, n = 3), respectively, and were well controlled with proton pump inhibitors. Univariate logistic regression analysis revealed integrated relaxation pressure was a predictor of ≥grade B reflux esophagitis. No POEM factors were found to be associated with reflux esophagitis.ConclusionPOEM is effective and safe in treating achalasia, with no occurrence of clinically significant refractory GERD. Myotomy during POEM, especially of the gastric side, was not associated with ≥grade B (requiring medical intervention) reflux esophagitis. Extended gastric myotomy (2–3 cm) during POEM is recommended to improve outcomes.

Hill procedure for recurrent GERD post-Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is considered to be an optimal surgical treatment option for GERD in the morbidly obese patient. Nevertheless, a subgroup of patients suffer from recurrent or persistent GERD after their gastric bypass. Unfortunately, limited treatment options are available in these patients. Fundoplication via mobilization of the remnant stomach and radiofrequency treatment of the lower esophageal sphincter have been described with some success. Our objective is to illustrate a safe and durable surgical option in the treatment of patients with medically refractory GERD post-RYGB. After placing five trocars in the usual position for a foregut laparoscopic surgery, a lysis of adhesions and standard dissection of the hiatus is performed. The anterior and posterior vagal nerves associated phrenoesophageal tissue bundles are identified. A primary crural repair with interrupted nonabsorbable sutures is performed. Four full-length nonabsorbable sutures are placed sequentially through the anterior and posterior phrenoesophageal bundle, posterior fundus and finally through the pre-aortic fascia. The repair is calibrated on a 44 French bougie. The sutures are tied from medial to lateral in the order of their placement under endoscopic guidance. No peri-procedural complications were encountered. Standard post-antireflux surgery clinical follow-up with the patient completing a validated GERD clinical questionnaire at 1 and 6months after the surgery demonstrated excellent GERD symptom control without any dysphagia. A pH study and EGD performed at 6months post-Hill procedure show the absence of pathological reflux with an intact Hill mechanism. The Hill procedure is a valid treatment for the post-bariatric surgical patient with GERD in which the gastric fundus is absent or inaccessible thus eliminating standard fundoplication as a reasonable option. This also represents a safe and durable treatment of GERD in this uniquely challenging patient population.

Patients with refractory reflux symptoms: What do they have and how should they be managed?

With the widespread use of proton pump inhibitors (PPIs), the frontier of treating reflux disease has shifted from refractory esophagitis to PPI-refractory symptoms. However, symptoms are inherently less specific than mucosal disease and, as noted by Herregods etal. in their contribution appearing in this issue of Neurogastroenterology and Motility, patients with refractory gastroesophageal reflux disease (GERD) symptoms often do not have GERD. This review discusses potential etiologies for PPI-refractory symptoms. Three major concepts are explored: subendoscopic esophagitis, weakly acidic reflux events, and alternative explanations for persistent symptoms. With respect to subendoscopic esophagitis and unsuppressed reflux, ample evidence exists that these are present in PPI-refractory patients. The problem is that these findings are also often present in substantial numbers of individuals with a satisfactory response to PPI therapy. Hence, the emphasis shifts to determinants of symptom perception. The major conclusion of the review is that psychogenic factors such as hyperalgesia, allodynia, hypervigilance, and heightened anxiety are the most plausible explanations as the dominant determinants of PPI-refractory symptoms.

Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca2+ Influx.

Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca2+-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca2+ entry into primary LES cells in addition to intracellular Ca2+ release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca2+influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca2+ influx pathway.