Persistent Reflux Symptoms Research Articles

Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis

Background and AimsHeartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment. MethodsA decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported. ResultsWithout insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts. DiscussionWe demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

Laparoscopic Gastrogastrostomy – An Alternative Procedure for Stenosis after Sleeve Gastrectomy

Abstract Introduction: Reflux symptoms associated with stenosis after laparoscopic sleeve gastrectomy can occur secondary to anatomical abnormality including mechanical stenosis and axial deviation, commonly occurring mid-sleeve. Treatment options include endoscopic intervention, including dilatation, stenting, myotomy, and surgical revision, with Roux-en-Y gastric bypass (RYGB) being preferred by many. In this case series, we report six patients who have undergone laparoscopic gastrogastrostomy (GG) for gastric stenosis and propose this as a possible surgical alternative for appropriately selected patients with symptomatic angularis stenosis. Patients and Methods: Medical records for six patients who underwent laparoscopic GG for treatment of persistent reflux symptoms due to angularis stenosis were reviewed. All patients were preoperatively investigated with endoscopy and abdominal three-dimensional computed tomography. Hiatal hernia and esophageal dilation were excluded. After further consultation, patients proceeded to laparoscopic GG. Results: Complete resolution of symptoms was reported in three of six patients, with Visick score 1, while the other three reported significantly improved symptoms. Postoperative body mass index remained similar to prerevision baseline. There were no postoperative complications. Conclusion: Revision to RYGB is effective for stenosis and reflux but can be challenging with the potential for long-term nutritional deficiencies and surgical complications. For patients with angularis stenosis, laparoscopic GG is a simpler revisional procedure that has shown adequate initial outcomes with no short or anticipated long-term complications in this case series. Patients with persisting symptoms could undergo subsequent gastric bypass if needed.

412. INTRAOPERATIVE APPLICATION OF ENDOFLIP FOR THE REPAIR OF HIATUS HERNIA AND FUNDOPLICATION

Abstract https://drive.google.com/file/d/1N3wVZ2UvO3eGBScjHMwtcJiCqfU0wUp1/view Background There is no objective measurement during repair of hiatus hernia and fundoplication intraoperatively. Whether the patient needs Nissen, Toupet or other fundoplication requires individual consideration. If the wrap repaired too tight, patient will develop dysphagia after surgery. If the wrap fold too loose, then the patient may experinced persistent reflux symptoms. This video demonstrate the application of EndoFlip intraoperatively to objectively measure the distensibility of the lower esophageal sphincter. Method Patient underwent laparoscopic hiatus hernia and fundoplication after symptoms assessment and confirmation of diagnosis. Intraoperatively, EndFlip probe was inserted and distensibility were measured as pre-dissection, post abdominal resection, post crural repair and after fundoplication. Tightness of fundoplication is adjusted aming at distenisbiliary index ranged 2–4. Results This study demonstrate the intraoperative aspproach for using EndoFlip as the tool to adjust the appropriate tightness on creating the wrap. Fpr this particular patient, before crus dissection, the distensibility index (DI) was 4.5, after crural dissection, DI was 5.5. After crural repair and Toupet fundoplication, the DI was 2.5. Post-operatively, patient had all the proton pump inhibitor stopped and enjoying good quality of life. Conclusion Objective intraoperative measurement during fundoplication is now available. Appropriate tightness of the wrap can be adjusted to avoidf post operative dysphagia or persistent reflus.

S2274 Bravo Capsule Aspiration

Introduction: Bravo wireless capsule is a catheter-free pH monitoring system used to diagnose GERD in patients who fail anti-secretory therapy. Several adverse events have been reported in the literature; these include nose or throat discomfort and dislocation from positioned sites. Case Description/Methods: A 72-year-old man with a history of GERD, prostate cancer, hypothyroidism, obstructive sleep apnea, presented for esophagogastroduodenoscopy (EGD) with Bravo™ placement due to persistent esophageal reflux symptoms despite appropriate therapy. The Bravo™ capsule (Medtronic, Minneapolis, MN) with a delivery system was introduced through the mouth and advanced into the esophagus. The device was placed with visual confirmation; however, the patient had severe a coughing fit. Suction was applied and the delivery system was then withdrawn. Repeat EGD was performed and no Bravo™ was seen in esophagus, stomach, or duodenum. Due to suspicion of dislodgement, a chest x-ray was performed and Bravo™ was seen in the left lung (figure 1, panel A). The patient was admitted to the hospital, and the pulmonology service was consulted for device removal. Bronchoscopy was performed successfully with the extraction of a capsule from the left main bronchus (Figure 1, panel B). After 24 hours observation, the patient did not have any symptoms or signs of aspiration pneumonitis and was discharged home. Discussion: We present a case of an adult patient with aspiration of the capsule into the lungs. This is an unusual complication with pH monitoring techniques(3). Given the limited number of cases of Bravo™ aspiration, there are no definite guidelines or gold-standard treatment up to date. A patent airway and good oxygenation must be maintained. The initial diagnostic evaluation includes chest radiographs, since the Bravo™ capsule is radiopaque(4).Once located, bronchoscopic tools can usually reveal the capsule, as was done with our patient.Figure 1.: Panel A, left: X-ray showing bravo capsule in left lung panel B, right: bronchoscopy showing reveals bravo capsule in left main bronchus.

Effectiveness of esophagogastroduodenoscopy in changing treatment outcome in refractory gastro-esophageal reflux disease

Background/aims The effectiveness of screening esophagogastroduodenoscopy (EGD) for refractory gastroesophageal reflux disease (GERD) symptoms alone has not been validated. Methods We performed an observational study of patients with refractory GERD who underwent EGD from 2013 to 2016 at a tertiary hospital. Among 928 patients with GERD, we excluded patients with other alarm features, other indications for EGD, history of gastroesophageal surgery, or EGD done for other diagnostic procedures, and identified 301 patients who underwent EGD solely for persistent reflux symptoms such as heartburn or regurgitation. Results Among 301 patients with refractory GERD, 81.4% of patients were taking PPIs. 49.8% of patients had completely normal EGD findings and 33.6% of patients had benign or incidental findings. Two patients (0.6%) had LA grade C or D esophagitis, and 16.3% of patients had irregular Z line or salmon-colored mucosa. 91.0% (122/134) who had a biopsy had normal or benign findings. 4.0% (12/301) of patients had biopsy-proven intestinal metaplasia which is similar to the previously known prevalence of intestinal metaplasia in patients without heartburn (5.6%) and none had dysplasia or malignancy. Male sex was associated with endoscopic intestinal metaplasia suspected lesions in multivariate analysis (OR: 1.96, 95% CI: 1.04–3.70, p = .036) but not biopsy-proven intestinal metaplasia. Elderly age, obesity, alcohol or cigarette consumption, PPI use, GERD duration >3–5 years did not predict endoscopically suspected or biopsy-proven intestinal metaplasia. Only 5% of patients had a pH-impedance study for refractory reflux symptoms. Conclusions Most patients who underwent EGD for refractory GERD symptoms alone did not have pathological findings requiring a change in management. Screening EGD for patients only with persistent reflux symptoms should not be routinely recommended.

Endoscopic gastric plication for the treatment of GERD and underlying class I obesity.

Endoscopic gastric plication for the treatment of GERD and underlying class I obesity.

Postreflux swallow-induced peristaltic wave index from pH-impedance monitoring associates with esophageal body motility and esophageal acid burden.

Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study. pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio>1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve. Of 296 patients (52.8±0.8yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P≤.002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P≤.001). PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve.

Prolonged Wireless pH Monitoring in Patients With Persistent Reflux Symptoms Despite Proton Pump Inhibitor Therapy

Wireless pH monitoring measures esophageal acid exposure time (AET) for up to 96 hours. We evaluated competing methods of analysis of wireless pH data. Adult patients with persisting reflux symptoms despite acid suppression (n= 322, 48.5 ± 0.9 years, 61.7% women) from 2 tertiary centers were evaluated using symptom questionnaires and wireless pH monitoring off therapy, from November 2013 through September 2017; 30 healthy adults (control subjects; 26.9 ± 1.5 years; 60.0% women) were similarly evaluated. Concordance of daily AET (physiologic <4%, borderline 4%-6%, pathologic>6%) for 2 or more days constituted the predominant AET pattern. Each predominant pattern (physiologic, borderline, or pathologic) in relation to data from the first day, and total averaged AET, were compared with other interpretation paradigms (first 2 days, best day, or worst day) and with symptoms. At least 2 days of AET data were available from 96.9% of patients, 3 days from 90.7%, and 4 days from 72.7%. A higher proportion of patients had a predominant pathologic pattern (31.4%) than control subjects (11.1%; P = .03). When 3 or more days of data were available, 90.4% of patients had a predominant AET pattern; when 2 days of data were available, 64.1% had a predominant AET pattern (P < .001). Day 1 AET was discordant with the predominant pattern in 22.4% of patients and was less strongly associated with the predominant pattern compared with 48 hour AET (P = .059) or total averaged AET (P = .02). Baseline symptom burden was higher in patients with a predominant pathologic pattern compared with a predominant physiologic pattern (P = .02). The predominant AET pattern on prolonged wireless pH monitoring can identify patients at risk for reflux symptoms and provides gains over 24 hours and 48 hours recording, especially when results from the first 2 days are discordant or borderline.

Fragmented and failed swallows on esophageal high-resolution manometry associate with abnormal reflux burden better than weak swallows.

Association between proportions of hypomotile swallows on esophageal high-resolution manometry (HRM) and esophageal reflux burden remains incompletely understood. We investigated relationships between hypomotility, acid exposure time (AET), and mean nocturnal baseline impedance (MNBI) on ambulatory reflux monitoring. Clinical data, HRM, and ambulatory pH-impedance studies (performed off acid suppression) from patients with persisting reflux symptoms were reviewed from five international centers. AET (abnormal>6%) and MNBI (abnormal<2292ohms) were extracted from pH-impedance studies. Distal contractile integral (DCI) designated esophageal peristalsis into normal (DCI>450mmHg.cm.s), fragmented (DCI>450mmHg.cm.s with breaks>5cm), weak (DCI 100-450mmHg.cm.s), and failed (DCI<100mmmmHg.cm.s) sequences. Univariate and multivariate analyses were performed to identify motor associations of abnormal reflux burden. Of 351 patients (52.1±0.8years, 67%F), 29.3% had AET>6% and 61.8% had MNBI<2292ohms. On univariate analysis, both fragmented peristalsis and IEM associated with abnormal AET (P≤.01) and MNBI (P≤.03); reflux burden was more profound with >70% fragmented as well as ineffective sequences compared to ≤70% for each (P<.05 for each comparison). When weak and failed sequences within IEM were separately analyzed, ≥50% failed sequences predicted abnormal AET (P≤.009), and ≥50% weak sequences did not (P=.14). On multivariate regression, ≥50% failed sequences predicted abnormal AET (P=.02), and >70% ineffective sequences trended strongly (P=.069); >70% ineffective sequences predicted abnormal MNBI (P=.046), and >70% fragmented sequences trended strongly (P=.076). Breaks in esophageal peristaltic integrity seen with fragmented and failed sequences are more relevant to abnormal esophageal acid burden than weak sequences.

373 Routine EGD Has Minimal Impact on Refractory GERD Management

INTRODUCTION: Routine diagnostic esophagogastroduodenoscopy (EGD) is recommended for refractory gastro-esophageal reflux disease (GERD) symptoms despite lack of evidence that it impacts management or outcomes. This study aims to determine if diagnostic EGD impacts management in patients with refractory GERD compared to esophageal manometry, pH testing and intra-luminal impedance. METHODS: We performed an observational study of patients with refractory GERD who underwent EGD from 2013 to 2018 at a tertiary hospital. Among 1,213 patients with GERD, we strictly excluded patients with alarm features such as dysphagia, dyspepsia; history of gastroesophageal surgery, or EGD done for other diagnostic procedures, and identified 339 patients who underwent EGD solely for persistent reflux symptoms. We then identified those who had esophageal manometry or pH-impedance studies for further evaluation of GERD, as well as if the findings of these tests resulted in a change in management (medication change or de-escalation, referral for Nissen fundoplication, etc). RESULTS: Among 339 patients with refractory GERD, 80.5% of patients were taking PPIs prior to and/or at the time of EGD. The majority of patients had completely normal (163/339, 48.1%) or solely benign or incidental findings (106/339, 31.3%) on EGD. Only 10.6% of patients had esophageal manometry or pH-impedance studies for refractory reflux symptoms, of those, 6.2% followed EGD and only 7 patients had these studies after a completely normal EGD. The majority of patients undergoing manometry had normal studies or minor abnormalities (23/32, 71.8%). All patients who had been ordered for intraluminal impedance or 24 hr pH testing alone could not tolerate the procedure. Six of 15 patients (40%) undergoing 24 hr pH-impedance testing had findings leading to a change in management. Undergoing pH-impedance testing after EGD was associated with a change in management (OR 7.33, P = 0.018). PPI use was not associated DeMeester score or with results of manometry, impedance, or pH testing. CONCLUSION: Most patients who underwent EGD for refractory GERD symptoms alone did not have pathological findings prompting a change in management. There were no demographic variables that predicted pathologic findings on EGD. Very few patients underwent subsequent or concomitant esophageal manometry, impedance or pH testing. pH-impedance after EGD was associated with a change in management, and may be a better first step in evaluating patients with refractory GERD symptoms, than EGD.

Robotic-assisted conversion of Nissen fundoplication to Roux-en-Y gastric bypass (avoiding pitfalls)

Abstract Laparoscopic anti-reflux surgery (LARS) utilizing fundoplication plays a major role in the treatment of gastroesophageal reflux disease (GERD). It is important to consider that long term control of reflux in the patient with obesity has been shown to be worse (failure up to four times more likely) than in normal weight patients following Nissen fundoplication. Recurrence of symptoms after LARS may benefit from medical management in some cases, while in others revisional surgery should be considered. Concomitantly, Roux-en-Y gastric bypass has an excellent track record of alleviating GERD in de novo obese patients. For individuals with obesity with recurrent or persistent reflux symptoms despite previous LARS, conversion to a gastric bypass versus redo LARS should be considered. Conversion of Nissen fundoplication to Roux-en-Y gastric bypass can be technically challenging due to factors present for any re-operation - presence of scar tissue, altered tissue planes, and often times unclear anatomy. Meticulous hiatus and wrap dissection, repair of hiatal hernia if present, complete unwrapping of the fundoplication and clarification of gastric redundancy prior to pouch creation, and preservation of the left gastric artery are keys to improving outcomes and reducing morbidity. Particularly, takedown of the fundoplication can be aided with landmark identification such as prior sutures. Ensuring full mobilization of the wrap from the lower esophagus, stomach, and hiatus prior to gastric pouch creation is paramount. The posterior fundic wrap can often unknowingly be left in situ, leading to thicker tissue to staple across and a larger than intended gastric pouch. This area in particular is where most leaks and stapling misadventures occur. Robotic assistance in this operation provides excellent visualization and surgical dexterity in a re-operative setting. We present a video demonstrating robotic assisted conversion of Nissen fundoplication to Roux-en-Y-gastric bypass, and specifically emphasize technical features of this operation to avoid peri-operative complications.

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.

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.

Can Impedance-pH Testing on Medications Reliably Identify Patients with GERD as Defined by Pathologic Esophageal Acid Exposure off Medications?

IntroductionImpedance-pH testing (MII-pH) while patients are on acid suppression medications is frequently used to evaluate persistent reflux symptoms. The aim of this study was to determine whether MII-pH on medications can reliably identify patients with gastroesophageal reflux disease (GERD) as defined by pathologic esophageal acid exposure off medications, and to determine if there is a threshold of total reflux episodes on medications where pH testing off medications may be unnecessary. MethodsA retrospective review identified all patients between 1/2010 and 4/2017 who underwent MII-pH testing on PPI medications and subsequently had pH testing off medications. GERD was defined on pH testing off medications by an abnormal DeMeester Score (DMS) and on MII-pH on medications by ≥ 48 total reflux episodes. Patients with an abnormal DMS by MII-pH on medications were excluded. ResultsThere were 71 patients, (22 males; 49 females), with a median age of 52 years. Based on ≥ 48 total reflux episodes by MII-pH testing on medications, 42 patients (59%) had GERD. When tested off medications, an abnormal DMS was present in 44 patients (62%). Among those with GERD based on impedance testing on medications, 31% did not have GERD based on pH testing off medications. Further, in the 29 patients with ≤ 48 total reflux episodes on MII-pH (normal test), 15 patients (52%) had pathologic acid exposure off medications. When there were > 73 reflux events with MII-pH on medications, all 15 patients in our series had pathologic acid exposure on pH testing off medications. ConclusionMII-pH testing on medications in patients with refractory GERD symptoms does not reliably correlate with a diagnosis of GERD as defined by pathologic esophageal acid exposure off medications. The commonly used abnormal MII-pH test value of ≥ 48 total reflux episodes is not validated and should not be used. However, in our series, patients with > 73 total reflux episodes had a high likelihood of having pathologic acid exposure off medications. Overall, the preferred strategy to evaluate patients with persistent GERD symptoms on acid suppression therapy should be pH testing off medications.

Adding Acotiamide to Gastric Acid Inhibitors Is Effective for Treating Refractory Symptoms in Patients with Non-erosive Reflux Disease

BackgroundApproximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief.AimsThis study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD.MethodsThis was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible.ResultsSeventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes.ConclusionAdding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.

RA06.06: PATHOGENESIS OF POTASSIUM-COMPETITIVE ACID BLOCKER (P-CAB)-RESISTANT NON-EROSIVE REFLUX DISEASE, AND GASTRIC ACID SECRETION-INHIBITORY EFFECTS OF P-CAB

Abstract Background In PPI-resistant NERD patients with symptoms related to acid reflux due to insufficient acid suppression, the symptoms may be improved by the administration of potassium-competitive acid blocker (P-CAB), which is a potent acid inhibitor. However, there are patients with P-CAB-resistant NERD, in whom symptoms persist despite the administration of P-CAB. The objective of this study was to clarify the pathogenesis of P-CAB-resistant NERD. Methods Forty-three patients with NERD (20 males, mean age 57.7 ± 2.5 years old), who had persistent reflux symptoms despite the administration of P-CAB (vonoprazan, 20 mg/day for 2 to 4 weeks), were included in this study. After excluding eosinophilic esophagitis (EoE) and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed on P-CAB therapy. The relationship between reflux and symptoms was evaluated according to the symptoms index (SI). Reflux episodes were characterized by pH measurement as acid, weakly acidic or weakly alkaline according to a published consensus report. In symptom index (SI)-positive patients, the mechanism of SI positivity and percent time with intragastric pH &gt; 4 and with esophageal pH &lt; 4 were investigated according to the presence or absence of Helicobacter pylori infection. Results One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid- and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. The percent time with intragastric pH &gt; 4 and esophageal pH &lt; 4 were 98.1 ± 0.8% and 0.18 ± 0.1% (mean ± SE), respectively, in H. pylori-positive patients and 79.9 ± 4.3% and 0.28 ± 0.1%, respectively, in H. pylori-negative patients, demonstrating that gastric acid was sufficiently suppressed by P-CAB regardless of the presence or absence of H. pylori infection. Conclusion The pathogenesis of P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB. Disclosure All authors have declared no conflicts of interest.

Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease

Background: The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). Methods: Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. Results: One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. Conclusions: The pathogenesis of ­P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB.

Hiatal hernia recurrence following magnetic sphincter augmentation and posterior cruroplasty: intermediate-term outcomes.

We have previously reported short-term outcomes after hiatal hernia repair (HHR) at the time of magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease (GERD). Here we report intermediate-term outcomes and hernia recurrence rate after concomitant MSA and HHR. This is a retrospective cohort study of patients who underwent repair of a hiatal hernia 3cm or larger at the time of MSA implantation between May 2009 and December 2015. The primary endpoint was hiatal hernia recurrence identified by routine postoperative videoesophagography or endoscopy. Recurrence was defined by a 2cm or greater upward displacement of the stomach through the diaphragmatic esophageal hiatus. Secondary endpoints included cessation of proton-pump inhibitor (PPI), persistent dysphagia requiring intervention, and GERD health-related quality-of-life (HRQL) scores 1year from surgery. During the study period, 47 of 53 (89%) patients underwent concomitant MSA with HHR and complied with surveillance. Hiatal hernias ranged from 3 to 7cm (mean 4 ± 1). Mean clinical follow-up time was 19months (range 1-39). GERD-HRQL score decreased from 20.3 to 3.1 (p < .001), 89% of patients remained off PPIs, and 97% of patients reported improvement or resolution of symptoms. Two recurrent hiatal hernias were identified on surveillance imaging for a recurrence rate of 4.3% at a mean 18 (± 10) months after initial operation. Persistent dysphagia occurred in 13% (6/47) over the first year, which resolved after a single balloon dilation in 67% (4/6). Two patients elected for device removal due to dilation-refractory dysphagia and persistent reflux symptoms. Concomitant magnetic sphincter augmentation and hiatal hernia repair in patients with gastroesophageal reflux disease and a moderate-sized hiatal hernia demonstrates durable subjective reflux control and an acceptable hiatal hernia recurrence rate at 1- to 2-year follow-up.