Antireflux Therapy Research Articles

Gabapentin versus baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough

Refractory gastroesophageal reflux-induced chronic cough (GERC) is a special type of gastroesophageal reflux disease (GERD) with predominant cough resistant to pragmatic standard anti-reflux therapy including antisecretory agents alone or in combination with promotility agents but with a favorable response to intensified anti-reflux treatment. The condition is not rare and is difficult to treat. Neuromodulators such as baclofen and gabapentin are considered potential therapeutic options for refractory GERC. Limited data indicate that gabapentin and baclofen could attenuate the cough symptom in patients with refractory GERC by blockade of gastroesophageal reflux or by direct antitussive effects. However, no study has compared the efficacy of these two drugs in treatment of refractory GERC. In an open-labeled randomized clinical study, we demonstrated that, as add-on therapy, gabapentin and baclofen had a similar prevalence of therapeutic success for suspected refractory GERC but gabapentin may be more preferable because of its fewer central side effects. The efficacy of baclofen and gabapentin was suboptimal, so further studies are needed to select the patients with refractory GERC suitable for precise treatment using these two neuromodulators.

Extraesophageal syndrome of gastroesophageal reflux: relationships with lung disease and transplantation outcome.

Gastroesophageal reflux disease (GERD) is prevalent and may be associated with both esophageal and extraesophageal syndromes, which include various pulmonary conditions. GERD may lead to pulmonary complications through the "reflux" (aspiration) or "reflex" (refluxate-triggered, vagally mediated airway spasm) mechanisms. While GERD may cause or worsen pulmonary disorders, changes in respiratory mechanics due to lung disease may also increase reflux. Typical esophageal symptoms are frequently absent and objective assessment with reflux monitoring is often needed for diagnosis. Impedance monitoring should be considered in addition to traditional pH study due to the involvement of both acidic and weakly acidic/nonacidic reflux. Antireflux therapy may improve outcomes of some pulmonary complications of GERD, although careful selection of a candidate is paramount to successful outcomes. Further research is needed to identify the optimal testing strategy and patient phenotypes that would benefit from antireflux therapy to improve pulmonary outcomes.

Paroxysmal Laryngospasm: A Rare Condition That Respiratory Physicians Must Distinguish from Other Diseases with a Chief Complaint of Dyspnea.

Background In recent years, we have observed respiratory difficulty manifested as paroxysmal laryngospasm in a few outpatients, most of whom were first encountered in a respiratory clinic. We therefore explored how to identify and address paroxysmal laryngospasm from the perspective of respiratory physicians. Methods The symptoms, characteristics, auxiliary examination results, treatment, and prognosis of 12 patients with paroxysmal laryngospasm treated in our hospital from June 2017 to October 2019 were analyzed. Results Five males (42%) and 7 females (58%) were among the 12 Han patients sampled. The average age of the patients was 49.25 ± 13.02 years. The disease course ranged from 14 days to 8 years and was characterized by sudden dyspnea, an inability to inhale and exhale, a sense of asphyxia, and voice loss during an attack. Eight patients with gastroesophageal reflux were cured after antacid treatment. One case of upper respiratory tract infection (URI) was completely relieved after symptomatic treatment. One patient with left vocal cord paralysis experienced complete relief after specialist treatment by an otorhinolaryngologist. Episodes in 1 patient were significantly reduced after lifestyle improvement. One patient experienced spontaneous relief after rejecting treatment. Conclusions Paroxysmal laryngospasm is a rare laryngeal disease that generally occurs secondary to gastroesophageal reflux disease (GERD), and antireflux therapy is frequently effective for its treatment. A respiratory physician should master and identify the symptoms and differentiate this condition from hysterical stridor, reflux-related laryngospasm, and asthma. Timely referral to otolaryngologists, gastroenterologists, and other specialists for standardized examination and regular treatment should be provided when necessary.

878 CLINICAL OUTCOMES OF ENDOSCOPIC ANTI-REFLUX TREATMENT METHODS; ANTI-REFLUX MUCOSECTOMY (ARMS) AND ANTI-REFLUX MUCOSAL ABLATION (ARMA)

Gastroesophageal reflux disease (GERD) is a common disorder with an increasing prevalence worldwide. Proton pump inhibitors (PPIs) are effective in achieving symptom control, however, approximately 30-40% of patients are reported to have persistent symptoms despite PPI therapy. While the surgical intervention such as Laparoscopic Nissen Fundoplication remains the gold standard treatment for refractory GERD, minimally invasive anti-reflux therapies are gaining its popularity to fill in the “gap” of conventional medical therapy and surgery. In 2014, we reported Anti-reflux mucosectomy (ARMS) which utilizes ESD or EMR-C to rebuild the flap valve at the gastric cardia by scarring of the artificial ulcer. In 2018, we developed Anti-reflux mucosal ablation (ARMA) where we apply ablation instead of mucosectomy as an alternative therapy for PPI-refractory GERD. The aim of this study is to evaluate the clinical outcomes of ARMS and ARMA. This is a retrospective, single center study from a prospectively collected database performed between April 2012 and November 2019. The indication of ARMS/ARMA is PPI refractory GERD patients without prominent sliding hernia. In ARMS, ESD or EMR-C at the gastric cardia mucosa was performed in order to create artificial ulcer. In ARMA, mucosal ablation using Triangle Tip Knife with spray coagulation mode (50W-120W, effect 2) was utilized to create the ulcer. The efficacy was evaluated by the patient’s symptom score (Frequent Scale for the Symptoms of GERD: FSSG) and the objective findings; Acid Exposure Time (AET) and DeMeester composite score by 24h multi-channel intraluminal impedance-pH monitoring, before and 2-3 months after procedure. A total of 109 patients (Age 54.0±15.7, M:F 63:46) underwent ARMS, and 24 patients (57.6±15.9, M:F 16:8) underwent ARMA. Mean procedure time (minutes) were 54.7 vs. 35.6, respectively. FSSG score improved from 25.1 to 11.6 (p<0.01) by ARMS and from 25 to 10.5 (p<0.01) by ARMA. By ARMS, AET and DeMeester composite score improved from 20.8 to 6.9 (p < 0.01, n=27) and 64.4 to 24.9 (p < 0.01, n=27), respectively. By ARMA, median AET showed a decreasing trend from 9 to 0.5 (p=0.068, n=8), and the DeMeester composite score significantly improved from 33.5 to 2.8 (p<0.05, n=8). Both ARMS and ARMA were effective anti-reflux therapy methods for PPI-refractory GERD which improved GERD related symptoms and objective acid reflux parameters. ARMA may be advantageous on its easiness and simplicity regarding operative time. A larger study with long-term follow-up is required to confirm these results.

981 RESECTION AND PLICATION (RAP): AN ENDOSCOPIC ANTI-REFLUX SOLUTION IN ALTERED ANATOMY

In recent years, significant advances have been made in the treatment of gastroesophageal reflux disease (GERD). Options for therapy have expanded in the surgical field, and new endoscopic options have emerged as alternative means of treating GERD in select populations. However, GERD remains a common problem in many polulations that do not quality for these new therapies, either due to severe co-morbidities or altered anatomy. The Resection and Plication (RAP) procedure is a novel endoscopic option for the treatment of medication refractory GERD. The RAP procedure can uniquely be empolyed in patietns unable to undergo surgical or alternate endoscopic anti-reflux therapies due to gastroesophageal junction (GEJ) anatomy that has been altered, for example in patients with prior nissen fundoplication, roux-en-Y gastric bypass, sleeve gastrectomy, or esophagectomy. The RAP procedure involves band endoscopic mucosal resection (EMR) semi-circumferential mucosectomy at the GEJ followed by full-thickness plication (RAP). Endoscopic suturing creats a gastro-gastric plication which serves to tighten the GEJ and decrease the rate of reflux into the esophagus. The following video demonstrates the RAP procedure in 2 patients with altered anatomy. Case 1, 66-year-old female with GERD previously treated with Nissen Fundoplication 10 years ago presents with refractory GERD symptoms. Case 2, 44-year-old female with history of morbid obesity treated with roux-en-Y gastric bypass with initial weight loss, now with significant weight gain and morbid obesity who is presenting with persistent GERD symptoms. 26 patients have undergone the RAP procedure at our institution. The average procedure time is 31 minutes. Ninety percent of were discharged the same day without major complications. Eighteen patients had altered anatomy (5 Fundoplication, 4 Gastric Bypass, 4 Esophagectomy, 2 failed TIF, 2 Endoscopic Sleeve Gastroplasty, 1 Sleeve Gastrectomy). We observed dramatic improvements in Reflux Disease Questionnaire (RDQ) and GERD Health Related Quality of Life (HRQL) questionnaires (RDQ Frequency 80%, RDQ Severity 76%, GERD-HRQL 85%). Sixty percent of patients were able to stop or decrease PPI use at follow-up. The average follow-up period was 6 months. The Resection and Plication (RAP) procedure is a novel endoscopic endoscopic anti-reflux procedure which results in gastro-gastric plications just below the level of the GEJ, thereby reducing the rate of reflux of gastric contents into the esophagus. This provides an effective endoscopic option in patients who otherwise cannot get other surgical or endoscopic therapies, specifically due to prior surgeries. This is a same day procedure and is overall safe, well tolerated and patients report a high degree of satisfaction following therapy.

Diagnosis of gastroesophageal reflux: an update on current and emerging modalities.

Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment.

Idiopathic Ulcerative Laryngitis: A National Survey of Academic Laryngologists

Idiopathic ulcerative laryngitis (IUL) is a rare disorder characterized by ulceration in the mid-membranous portions of the vocal folds. The etiology and optimal management of this condition are poorly understood. We aimed to survey laryngologists on their experiences with managing IUL in order to better understand the diagnosis and treatment of this unusual condition. An online survey was sent to 149 laryngologists practicing at academic institutions in the United States. Survey questions assessed respondents' professional backgrounds and clinical experiences with IUL. Individual responses were tallied and calculated as percentages of total responses. A total of 96 out of 149 academic laryngologists completed the survey, leading to an overall response rate of 64.4%. All respondents reported that they had encountered IUL in practice, including 56.3% who reported having seen 1-10 cases, 22.9% reporting 11-20 cases, and 20.8% reporting greater than 20 cases over their careers. Dysphonia (99.0%) and cough (84.4%) were the two co-occurring primary presenting symptoms reported. Most base diagnosis on laryngeal videostroboscopy (93.8%). Fungal/bacterial cultures and operative biopsy had been performed by approximately 30% of respondents with occasional candidiasis reported but otherwise negative or nonspecific results. Common therapies used were empiric: antireflux therapy (91.7%), modified voice rest (91.7%), and oral steroids (80.2%). Among survey respondents with experience managing more than 10 cases of IUL, many found complete voice rest (60.0%), oral steroids (55.9%), behavioral cough suppression (46.7%), and modified voice rest (46.3%) to be at least moderately effective treatment options. Resolution of symptoms was most commonly reported to occur over the course of 1-3 months (59.4%) and recurrences were seen not very often or never (85.4%). However, permanent sequelae were common, including vocal fold stiffness (89.6%) and dysphonia (81.3%). IUL is a rare disorder of unknown etiology. Diagnosis is typically made with laryngeal videostroboscopy and spontaneous resolution occurs over 1-3 months. Laryngologists commonly treat empirically with antireflux therapy, voice rest, antimicrobials, and oral steroids. While no empiric treatment appears to be highly effective for the management of IUL, complete or modified voice rest, oral steroids, and behavioral cough suppression may be the most effective of the currently available options. Further research is necessary to improve the understanding and optimal management of IUL.

Combined pharmacologic antireflux therapy after esophagectomy: effect on symptoms and endoscopic findings at 1-year follow-up

Heartburn, regurgitation, pulmonary aspiration, and remnant esophagitis represent common sequelae of esophagectomy and gastric conduit reconstruction. Proton pump inhibitors are the mainstay of treatment. The aim of the study was to focus on the efficacy of combination therapy with mucosal surface protection. Patients undergoing esophagectomy were followed up to 1 year. Patients in group A received 60 mg/day lansoprazole and those in group B received combination therapy. During follow-up, the dosage of lansoprazole was reduced to 30 mg/day in asymptomatic patients with or without grade A–B esophagitis. The Gastro-Esophageal Reflux Disease – Health-Related Quality of Life (GERD-HRQL) and the Short-Form 36 (SF-36) were used to assess postoperative quality of life, and the foregut symptom questionnaire to assess the prevalence of regurgitation, respiratory symptoms, and sleep disorders. Between August 2017 and August 2018, 56 patients were enrolled in the study. Over follow-up, the incidence of refractory symptoms and/or esophagitis grade C–D was 35.7% in group A and 21.4% in group B (p = 0.024). At 1 year, 18 (64.2%) patients in group A and 22 (78.5%) in group B remained symptom free and without severe esophagitis under treatment with 30 mg of lansoprazole (p = 0.076). The GERD-HRQL score was similar at 3 and 6 months (p = 0.790 and p = 0.812, respectively); at 12 months, patients in group B had a lower score although the difference was not significant (p = 0.216). There were no statistically significant differences in terms of SF-36 scores at 1‑year follow-up. Concerning the foregut symptom questionnaire, group B experienced less respiratory symptoms (p = 0.045) and sleep disorders (p = 0.039). At 1‑year after esophagectomy, combination therapy with 30 mg lansoprazole and Esoxx® appears to be an effective antireflux strategy.

Eosinophilic Esophagitis in Esophageal Atresia.

Recent studies have reported a higher prevalence of eosinophilic esophagitis in children with esophageal atresia. Under recognition of eosinophilic esophagitis in these patients may lead to excessive use of antireflux therapy and an escalation of interventions, including fundoplication, as symptoms may be attributed to gastroesophageal reflux disease. In addition, long-term untreated eosinophilic esophagitis may lead to recurrent strictures due to transmural esophageal inflammation, necessitating repeated dilatations. Eosinophilic esophagitis should be considered when children with esophageal atresia show persistent symptoms on standard antireflux treatment, increasing dysphagia, and recurrent strictures. Treatment has been found to not only significantly reduce intraepithelial eosinophil count, but also to improve symptoms, and to lower the occurrence of strictures and the need for dilatations. Future prospective studies are warranted in this area.

Treatment of Laryngeal Contact Granuloma: Surgical Therapy or Conservative Treatment

Objective: Despite the fact that there are many treatment alternatives, laryngeal contact granuloma has a high tendency of persistence, spontaneous disappearance without treatment, and recurrence. A comparison of the effects of conservative treatment and surgical therapy on laryngeal contact granuloma was made in a retrospective review. Methods: A total of 124 patients with laryngeal contact granuloma were divided into 2 groups according to treatment: simple surgical excision (n = 36) and conservative treatment (n = 84). Additionally, the reflux finding score (RFS) and the reflux symptom index (RSI) were utilized to assess the disease. Results: A total of 124 patients, with a median age of 48.5 years, ranging from 9 to 74 years, were recruited (107 male, 17 female). According to the diagnostic criteria for laryngeal reflux (RSI >13 or RFS >7), there were 67 cases, accounting for 54.03% of the total. Surgery was effective in 15 patients (15/36, 41.67%), and conservative treatment was effective in 62 patients (62/84, 73.81%). The 2 groups had statistically significant differences. Conclusions: Conservative treatment, which is a comprehensive anti-reflux therapy, is better than surgical therapy and plays an important role in the treatment of laryngeal contact granuloma.

The Utility of Esophageal Motility Testing in Gastroesophageal Reflux Disease (GERD).

Here, we discuss how esophageal motor testing plays important roles in patients with suspected gastroesophageal reflux disease (GERD). In addition to guiding appropriate placement of catheters for ambulatory reflux monitoring, esophageal high-resolution manometry (HRM) rules out confounding diagnoses, such as achalasia spectrum disorders, that can present with symptoms similar to that of GERD, but are managed very differently. HRM performed with impedance in the post-prandial setting (PP-HRIM) can assess for rumination syndrome or supragastric belching, which should be directed towards behavioral interventions. The recent GERD Classification of Motor Function recommends a hierarchical approach, focusing on (1) the esophagogastric junction (EGJ), (2) the esophageal body, and (3) esophageal contraction reserve, which can be assessed with provocative maneuvers at HRM, such as multiple rapid swallows (MRS). This approach can inform the appropriate tailoring of antireflux surgery. Novel esophageal motility metrics, such as the EGJ-contractile integral from HRM, or post-reflux swallow-induced peristaltic wave indices from 24-h pH-impedance monitoring, may also assist with GERD diagnosis. Assessment of esophageal motor function can contribute in a significant manner to the care of patients with suspected GERD, particularly when esophageal symptoms do not improve with antisecretory therapy, and/or when surgical or endoscopic antireflux therapies are under consideration.

Mean Nocturnal Baseline Impedance Correlates With Symptom Outcome When Acid Exposure Time Is Inconclusive on Esophageal Reflux Monitoring

Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results. We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic, >6%; physiologic, <4%; borderline or inconclusive, 4%-6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal, <2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients' answers on standardized visual analog scales. Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P < .0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P= .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P < .0001 for each comparison). When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy.

DOZ047.63: Closing the gap: transitioning adolescents with esophageal atresia to adult care

Abstract Introduction Evidence supports engaging adolescents and carers in an individualized transition process to improve health outcomes through increased patient knowledge, skills, adherence, quality of life and ultimately, engagement with adult services. Further, a comprehensive transition process promotes confidence in navigating adult health services. While transition for chronic medical cohorts has received considerable attention over decades, there is increasing recognition of the importance of transition for adolescents with surgical conditions. Background It is widely held that the transition of adolescents born with esophageal atresia (OA) from pediatric to adult services is important, and if not managed well, may compromise outcomes. We designed and implemented a transition process for adolescent OA patients at our hospital (with establishment of a transfer pathway in partnership with adult health services) in 2017. Methods Following implementation of a transition process a retrospective review was undertaken in 2019 to identify themes from the dedicated Transition Support Service (TSS) Clinics (October, 2017–December, 2018) for OA patients aged 15–19 years. Patients were identified from an institutional database (Nate Myers Oesophageal Atresia Database, Royal Children's Hospital, Melbourne). These patients had previously been invited to: Attend TSS Clinics as part of routine clinical care.Re-engage in multidisciplinary follow-up (if necessary) including with a consultant surgeon, OA nurse and respiratory physician. Institutional ethics approval was obtained prior to commencement of the study (HREC #QA/51265/RCHM-2019). Results A total of 18 adolescent OA patients and their parents attended RCH TSS and associated follow-up clinics. We observed three key themes in attendees reports and experiences: Poor health knowledge: 56% of adolescents had poor knowledge about their OA, including previous surgery, possible complications and their symptoms;Poor compliance: 54% of adolescents reported poor compliance with prescribed regular medications (e.g. anti-reflux therapy);Mental health issues: 39% of adolescents identified as having mental health concerns, e.g. low mood or clinical depression, anxiety, anger or had engaged in self-harm. Anxiety about transfer to adult services was moderate to high in the majority (61%) of adolescents and their parents. Conclusions The themes identified in this study support the need for, and importance of, a structured process to transition adolescents born with OA to adult services.

Oesophageal Adenocarcinoma after Surgery and Medication Against Gastro-Oesophageal Reflux Disease in a Nordic Cohort Study

Background: Gastro-oesophageal reflux disease (GORD) increases risk of oesophageal adenocarcinoma (OAC), but whether antireflux therapy prevents OAC is uncertain. We aimed to clarify this issue and assess potential differences after surgical and medical treatment. Methods: Multinational, population-based cohort study including individuals with GORD from the five Nordic countries in 1964-2014. The exposure was antireflux surgery or medication and the outcome was OAC. First, OAC risk after antireflux surgery and medication in the cohort was compared with the respective corresponding background population by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (95%CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95%CIs, was used to compare antireflux surgery with medication in relation to OAC risk. Findings: Among 942,071 GORD patients, 48,863 underwent surgery and 893,208 received medication. Compared to the background population, OAC risk did not decrease following surgery (SIR=4.90 [95%CI 3.62-6.47] 1-<5 years and SIR=4.57 [95%CI 3.44-5.95] ≥15 years after surgery) or medication (SIR=2.37 [95%CI 2.17-2.59] 1-<5 years and SIR=3.07 [95%CI 2.65-3.54] ≥15 years after medication). Similarly, no decrease was found for patients with severe GORD over time after surgical (SIR=6.09 [95%CI 4.39-8.23] 1-<5 years and SIR=5.27 [95%CI 3.73-7.23] ≥15 years) or medical (SIR=3.61 [95%CI 3.19-4.07] 1-<5 years and SIR=3.82 [95%CI (3.19-4.55] ≥15 years) antireflux therapy. The HRs of OAC were stable over time over time after surgery compared with medication (HR=1.71 [95%CI 1.26-2.33] 1-<5 years and HR=1.69 [95%CI 1.24-2.30] ≥15 years after treatment), and remained stable over time after treatment in participants with severe GORD (HR=1.56 [95%CI 1.11-2.20] 1-<5 years and HR=1.57 [95%CI 1.08-2.26] ≥15 years after treatment). Interpretation: Medical and surgical treatment of GORD does not seem to reduce OAC risk. Funding: Nordic Cancer Union, Swedish Cancer Society and Swedish Research Council. Declaration of Interest: None. Ethical Approval: All required ethical and data permissions were retrieved from the relevant authorities within each country (The Danish Data Protection Agency; Population Register Centre, National Institute for Health and Welfare, Statistics Finland; The Icelandic Data Protection Authority, The National Bioethics Committee; Regional Ethics Committee, Norway; and Regional Ethics Committee, Sweden).

Detection of pepsin and IL-8 in saliva of adult asthmatic patients.

Objective: Asthma and gastric reflux disease are widespread and often coexisting diseases with complex interactions, leading some to suspect that asthma symptoms of patients with reflux may improve with anti-reflux therapy. The objective of this study was to determine whether pepsin in saliva, indicative of airway reflux, could be detected in patients with asthma of varying severity and test the requirement of citric acid as a pepsin preservative.Methods: Saliva samples were collected in the clinic (with/without citric acid) and upon waking the following morning from 25 asthmatic patients. Enzyme-linked immunosorbent assay was performed for pepsin and interleukin-8 (IL-8), an inflammatory cytokine induced by pepsin in other airway epithelia. Pepsin induction of IL-8 was tested in a lung epithelial cell culture model.Results: Pepsin was detected in saliva from 14/25 patients (56%; mean concentration of pepsin in specimens where observed ±SD =80.3±87.5 ng/mL); significant agreement was found between samples collected in the presence/absence of citric acid. No significant associations were found with pepsin and clinical measures of asthma severity. IL-8 was detected in saliva from 22/25 patients (88%; mean IL-8 in all specimens where observed =3.27±3.91 ng/mL). IL-8 was significantly upregulated in human lung epithelial cells exposed to pepsin at pH7 in vitro (P=0.041).Conclusion: In summary, more than half of the asthma patients in this study were found to have pepsin in their saliva, indicative of airway reflux. These data support the use of salivary pepsin as a noninvasive tool for future investigation of airway reflux in a larger cohort. The data further suggest that collection in citric acid as a sample preservative is not warranted and that pooling of multiple saliva samples collected at various timepoints may improve sensitivity of pepsin detection and reduce costs incurred by multiple sample analysis in future studies.

Proximal Gastric Resection with Posterior Esophago-Gastrostomy and Partial Neo-Fundoplication in the Treatment of Advanced Upper Gastric Carcinoma

Background: Proximal gastric resection (PGR) is rarely used in western countries because of frequent postoperative reflux and uncommon diagnosis of early gastric cancer (GC). Objectives: We hypothesized that the PGR with an anti-reflux procedure may be an attractive option even in advanced proximal GC after downstaging with the neo-adjuvant chemotherapy. Method: A novel technique of end-to-side esophago-gastrostomy with the posterior wall of the gastric stump and partial neo-fundoplication to prevent reflux symptoms has been introduced. An observational retrospective study was undertaken to evaluate early and late outcomes of the innovative technique in patients with advanced proximal GC after neoadjuvant chemotherapy. Results: Twenty consecutive patients with the diagnosis of loco-regionally advanced GC, localized in the subcardiac region or proximal upper third of the stomach, were selected for the study. Eleven (55%) patients completed preoperative neo-adjuvant chemotherapy. The mean postoperative hospitalization time was 13.3 (± 8.3) days. There was one postoperative in-hospital death due to acute circulatory insufficiency. The mean comprehensive complication index was 11.94 (±24.82). Two patients were diagnosed with a complete pathological response (ypT0N0). Median survival was 41.8 (95% CI 27.9–41.8) months. The 5-year survival rate was 42%. At a median follow-up of 26 months, reflux symptoms were present in 7 (35%) patients who had to use antireflux medication. Anastomotic stenosis was observed in 1 patient during the follow-up. Mean scores of reflux symptoms on medication were not significantly different to those in patients without medication. The Overall Satisfaction Score for patients on medication was 7.57 ± 1.92, whereas it was 8.83 ± 1.34 (p = 0.2; Student t test) for those with no medication. Conclusions: Proximal gastrectomy is feasible and may be safely used in patients with advanced GC after neo-adjuvant chemotherapy with acceptable survival. Posterior esophago-gastrostomy with partial neo-fundoplication reduces the postoperative reflux, while patients with persistent reflux symptoms can be effectively treated with an antireflux therapy.

Differentiation of esophageal pH-impedance characteristics classified by the mucosal integrity marker in human neonates

BACKGROUND:In adults, distal baseline impedance (BI) is a determinant of esophageal mucosal integrity with values <900Ω indicating inflammation. Relationships between acid gastroesophageal reflux (GER) and BI in neonates are unclear.METHODS:NICU infants (N=198, 30.4±0.3 weeks gestation) were evaluated at 43±0.4 weeks postmenstrual age using 24-hour pH-impedance. Ten randomly selected one-minute windows during rest from the distal impedance channel (Z6) were averaged. Chi-square, t-tests, and ANOVA were used to compare pH-impedance and symptom characteristics by BI severity (BI<900Ω, BI 900-2000Ω, BI>2000Ω). Regression analysis was used to identify potential contributing factors of BI.RESULTS:In BI<900Ω: 1) pH-impedance characteristics were increased (acid reflux event frequency, duration, and severity, all P<0.05 vs. BI>2000Ω), and 2) positive symptom correlations were noted with bolus (73%) and acid events (55%). Significant predictors of BI included chronological age, acid reflux index, and BPD diagnosis (all P<0.05).CONCLUSIONS:Low BI is associated with prolonged acid exposure, delayed clearance, and greater aerodigestive symptom prevalence, likely associated with inflammation and or increased mucosal permeability. BI>2000Ω likely involves little or no inflammation because acid exposure is minimal. Combination of SAP, pH-impedance metrics and BI along with clarification of dysmotility mechanisms provides the rationale for personalized anti-reflux therapies as needed.

Voice therapy associated with a decrease in the reflux symptoms index in patients with voice complaints.

Patients with muscle tension dysphonia often demonstrate an elevation in Reflux Symptom Index (RSI) and 10-item Voice Handicap Index (VHI-10) scores, and may be erroneously diagnosed with laryngopharyngeal reflux disease. In this study we assessed the effects of voice therapy on RSI and VHI-10 scores in patients with voice complaints not responsive to antireflux medications. Retrospective cohort study. A study of patients was conducted at a single tertiary-care center over 1 year (January 2012-January 2013). Patients were included if they had dysphonia not responsive to proton pump inhibition, did not have neurologic or neoplastic disease, and participated in at least three voice-therapy sessions in the absence of antireflux therapy. Primary analysis assessed change in RSI scores between the initial and follow-up visits with a laryngologist. A total of 18 patients were included (mean age = 49.9 ± 14.5 years, 89% female, 83% with a primary complaint of dysphonia). From initial to follow-up visit, the median RSI score (18.5 [interquartile range {IQR}, 9.5-22.8] vs. 10.5 [IQR, 4.5-14]; P = .02) and median VHI-10 score (25.5 [IQR, 11.3-30.0] vs. 13.5 [IQR, 9.5-20.8]; P = .03) significantly decreased. A significant inverse correlation was found between the number of voice therapy sessions/month and change in RSI score (r = -0.4; P = .05). In this study of patients with muscle tension dysphonia or vocal hyperfunction not responsive to antireflux therapy, RSI and VHI-10 scores improved following voice therapy. Results suggest that self-reported symptoms typically attributed to laryngopharyngeal reflux disease may actually be secondary to inefficient voice use patterns or anxiety about dysphonia that are responsive to voice therapy. 4 Laryngoscope, 129:1169-1173, 2019.

PS01.056: ELECTRICAL STIMULATION OF THE LOWER ESOPHAGEAL SPHINCTER IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE AND IMPAIRED ESOPHAGEAL MOTILITY

Abstract Background Laparoscopic fundoplication (LF) is considered as standard surgical antireflux therapy. However, even if performed in specialized centers, the procedure can be followed by long-term side effects dysphagia, gas bloating or inability to belch. Especially patients with motility disorders (IEM) and concurrent GERD are prone to postoperative dysphagia after LF. The aim of this study is the evaluation of electrical stimulation (EST) of the lower esophageal sphincter (LES) in patients with IEM and GERD and its impact on procedure-related gastrointestinal side effects such as dysphagia. Methods This is a prospective, open-label, non-randomized single-center study. All variables are depicted as median and interquartile range (IQR) or 95% confidence intervals (CIs) or mean with standard deviation (SD). Ineffective esophageal motility (IEM) was defined as a Distal Contractile Integral (DCI) below 450 mmHg-s-cm in ≥ 5 of out 10 swallows. Differences in GERD health-related quality of life (HRQL) scores before and after treatment were compared with paired t-test due to a normal distribution. P-values &lt; 0.05 were considered significant. Results Between 05/2015 and 10/2017 twenty patients were treated with LES-stimulation for GERD. Thirteen patients (61.9%) presented with IEM in esophageal manometry before surgery and were included in this analysis. DCI was 91 (IQR 30.5–331.5) mmHg-s-cm. Median 24-hours esophageal pH at baseline was 10.2% (IQR 4.4–21.5). Fifty-seven percent of patients were treated with PPI at time of surgery. Nine patients (69.2%) presented with typical GERD symptoms whereas 6 patients (46.2%) also presented with atypical GERD symptoms. BMI was 26.1 (SD 4.9). Eight patients (61.5%) showed a hiatal hernia at the time of surgery and underwent also hiatal repair. Operating time was 59 minutes (IQR 34.5–70.25). HRQL for heartburn at baseline was 21.1 (SD 5.4) and improved to 7.3 after surgery (SD 6.7) at follow up of one month (mean difference 13.8 (CI 12.5–15.1) P &lt; 0.001). HRQL for regurgitation at baseline was 18.69 (SD 6.9) and improved to 3.84 (SD 2.4) (mean difference 14.9 (CI 13.95–15.76) P &lt; 0.001). No patients showed any clinical signs of dysphagia nor impaired findings in postoperative contrast swallow. Gastrointestinal side effects such as the inability to belch or bloating were not seen in any patients. There were no severe adverse events related to the procedure, but one patient need re-do surgery and re-implantation of the LES-stimulation due to a breaking of the lead close to the implanted pulse generator after one year. Conclusion LES-EST was introduced as a potential alternative technique to avoid side effects of LF. It was demonstrated that LES-EST significantly raises the LES pressure and improved GERD symptoms such as heartburn and regurgitation. The advantage of this procedure is that the anatomy of the esophageal-gastric junction is not altered dramatically. Disclosure All authors have declared no conflicts of interest.

Endoscopic techniques for treating gastroesophageal reflux

Nearly, a third of patients with medically refractory gastroesophageal reflux disease (GERD) will desire an additional nonsurgical treatment option. Recently, endoscopic therapy has been reintroduced as a minimally invasive antireflux barrier treatment, after addressing prior efficacy and safety concerns. Over the last two decades, additional experience and new technologies have resulted in devices and protocols with favorable short-term outcomes and safety profiles. The current literature in endoscopic antireflux therapies covers new devices, long-term follow-up data and further safety experience. This review discusses the endoscopic antireflux devices on the market and most recent studies in this area. Quality of life and reflux symptom score improvement is observed in 73-90% of patients through a 36-48 month follow-up period, with 41-77% remaining off all reflux medicines. Composite data from several thousand cases indicate a low rate (0.93-2.4%) of serious complications and no late adverse effects, including gas-bloat syndrome. In this review, we describe the four endoscopic antireflux devices on market and summarize the current data in the literature. The short and long-term data demonstrate durable symptom improvement and favorable safety profile. Endoscopic antireflux treatment should be considered in the management of GERD.