Persistent Reflux Research Articles

Gastro-oesophageal reflux in infancy

Gastro-oesophageal reflux is very common in infancy. It is important to differentiate benign physiological reflux from gastro-oesophageal reflux disease, which is associated with significant morbidity. This review summarises the approach to infants with symptoms and signs of reflux, differential diagnosis, investigations and management including non-pharmacological, pharmacological and surgical treatments. Most infants with physiological gastro-oesophageal reflux do not require any medical management if the infant is thriving. Severe cases require a careful diagnostic work, treatment of associated conditions and aggressive medical management of the reflux. Involvement of the multidisciplinary team is essential and in persistent refractory reflux surgical intervention may need to be considered.

Third-time ("redo-redo") anti-reflux surgery: patient-reported outcomes after a thoracoabdominal approach.

Approximately 3-6% of patients undergoing anti-reflux surgery require "redo" surgery for persistent gastroesophageal reflux disease (GERD). Further surgery for patients with two failed prior anti-reflux operations is controversial due to the morbidity of reoperation and poor outcomes. We examined our experience with surgical revision of patients with at least two failed anti-reflux operations. Adults undergoing at least a second-time revision anti-reflux surgery between 1999 and 2017 were eligible. The primary outcomes were general and disease-specific quality-of-life (QoL) scores determined by Short-Form-36 (SF36) and GERD-Health-Related QoL (GERD-HRQL) instruments, respectively. Secondary outcomes included perioperative morbidity and mortality. Eighteen patients undergoing redo-redo surgery (13 with 2 prior operations, 5 with 3 prior operations) were followed for a median of 6years [IQR 3, 12]. Sixteen patients (89%) underwent open revisions (14 thoracoabdominal, 2 laparotomy) and two patients had laparoscopic revisions. Indications for surgery included reflux (10 patients), regurgitation (5 patients), and dysphagia (3 patients). Intraoperative findings were mediastinal wrap herniation (9 patients), misplaced wrap (2 patients), mesh erosion (1 patient), or scarring/stricture (6 patients). Procedures performed included Collis gastroplasty + fundoplication (6 patients), redo fundoplication (5 patients), esophagogastrectomy (4 patients), and primary hiatal closure (3 patients). There were no deaths and 13/18 patients (72%) had no postoperative complications. Ten patients completed QoL surveys; 8 reported resolution of reflux, 6 reported resolution of regurgitation, while 4 remained on proton-pump inhibitors (PPI). Mean SF36 scores (± standard deviation) in the study cohort in the eight QoL domains were as follows: physical functioning (79.5 [± 19.9]), physical role limitations (52.5 [± 46.3]), emotional role limitations (83.3 [± 36.1]), vitality (60.0 [± 22.7]), emotional well-being (88.4 [± 8.7]), social functioning (75.2 [± 31.0]), pain (66.2 [± 30.9]), and general health (55.0 [± 39.0]). An open thoracoabdominal approach in appropriately selected patients needing third-time anti-reflux surgery carries low morbidity and provides excellent results as reflected in QoL scores.

Vesicoureteral antireflux surgery with Lich–Gregoir technique without vesical drainage: Long-term results

ObjectiveTo describe our long-term experience with patients with vesicoureteral reflux (VUR) who underwent conventional surgery without postoperative bladder drainage. Material and methodsRetrospective review of 45 patients surgically treated by extravesical Lich–Gregoir's ureterovesical reimplantation without postoperative bladder drainage between 2010 and 2013. Results37 women (82.2%) and 8 men (17.8%). 28 patients with unilateral reflux, and 17 patients with bilateral reflux with a total of 62 operated kidneys. The mean age at surgery was 6 years (2–11 years).The main cause of surgical indication was the persistence of reflux in patients older than 6 years (73.3%); with grade III VUR (75.6%) being the most frequent. The mean surgical time was 44min (35–70) for unilateral reimplantation, and 70min (53–98) for bilateral ones.All patients presented spontaneous urination in the immediate postoperative period, without pain, no hematuria, full incontinence, and without a bladder balloon. None required bladder catheter placement, and hospital discharge was indicated between 7 and 36h postoperatively (mean 11h).All continued with spontaneous micturitions, without postvoid residual or voiding dysfunction during the 5-year follow-up. ConclusionThe thorough selection of the patients, the detailed surgical gestures, the bladder emptying without instrumentation of the urethra, together with a correct use of analgesics and early ambulation allowed excellent outcomes obtained in these patients managed with a short hospital stay and without bladder drainage, also demonstrating the safety of the procedure at 5 years of follow-up.

Laparoscopic Roux-en-Y Gastric Bypass After Gastroesophageal Reflux Disease Surgical Procedure: Analysis of 85 Consecutive Patients with Pre- and Post-Operative Endoscopy Control.

Background: Most of the obese patients undergoing an anti-reflux operation experience recurrence of gastroesophageal reflux disease (GERD). Laparoscopic Roux-en-Y gastric bypass (LRNYGB) has been accepted as the bariatric surgery of choice for a previous GERD-operated obese patients. Methods: We present 85 consecutive patients from a single institution, previously submitted to antireflux surgery and then to LRNYGB. Preoperative endoscopy was carried out in all patients; 49 (57.64%) patients had findings of fundoplication failure or signs of persistent GERD, of those 20 (40.81%) with esophagitis. Results: From the bypass, per or postoperative minor to moderate complications occurred in 12 patients (14.11%): 2 (2.35%) conversions to laparotomy, 1 (1.17%) melena, 8 (9.41%) stenosis of gastrojejunostomy, treated by a simple endoscopic dilatation with a balloon, and 1 (1.17%) gastrogastric fistula. A follow-up endoscopy of 79 of 85 (92.9%) patients was carried out after 6 months of LRNYGB. Eight of 79 (10.12%) patients had persistent esophagitis that represented 40% (8 of 20 patients) of persistent reflux esophagitis even after LRNYGB. All of them were men. Conclusion: LRNYGB after laparoscopic fundoplication is a feasible procedure with an excepted higher rate of complications because of the complexity of the procedure. Nevertheless esophagitis still persisted in many of those patients.

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.

Resultados a largo plazo de cirugía antirreflujo vesicoureteral con técnica de Lich-Gregoir sin drenaje vesical

ObjectiveTo describe our long-term experience with patients with vesicoureteral reflux (VUR) who underwent conventional surgery without postoperative bladder drainage. Material and methodsRetrospective review of 45 patients surgically treated by extravesical Lich-Gregoir's ureterovesical reimplantation without postoperative bladder drainage between 2010 and 2013. Results37 women (82.2%) and 8 men (17.8%). 28 patients with unilateral reflux, and 17 patients with bilateral reflux with a total of 62 operated kidneys. The mean age at surgery was 6 years (2 to 11 years).The main cause of surgical indication was the persistence of reflux in patients older than 6 years (73.3%); with grade III VUR (75.6%) being the most frequent. The mean surgical time was 44minutes (35-70) for unilateral reimplantation, and 70minutes (53-98) for bilateral ones.All patients presented spontaneous urination in the immediate postoperative period, without pain, no hematuria, full incontinence, and without a bladder balloon. None required bladder catheter placement, and hospital discharge was indicated between 7 and 36hours postoperatively (mean 11h).All continued with spontaneous micturitions, without postvoid residual or voiding dysfunction during the 5-year follow-up. ConclusionThe thorough selection of the patients, the detailed surgical gestures, the bladder emptying without instrumentation of the urethra, together with a correct use of analgesics and early ambulation allowed excellent outcomes obtained in these patients managed with a short hospital stay and without bladder drainage, also demonstrating the safety of the procedure at 5 years of follow-up.

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.

Testicular doppler in male infertility

Varicocele is a common cause of infertility in men that affects 15% of the population and 21-40% of men with fertility disorders. It involves the left testicle in 75-90%, the right testicle in 15-20% and bilaterally in up to 10%. In a study of 1372 infertile men, the findings were varicocele in 29.7%, testicular tumor in 0.5%, testicular cyst in 0.7%, testicular microlithiasis in 0.9%, epididymal cyst in 7.6% and hydrocele in 3.2%. 60% of the varicoceles, as well as 67% of the findings detected in the ultrasound were not suspected in the physical examination. Ultrasound with the use of Color Doppler, is the method of choice for the assessment of patients with infertility, since it has a sensitivity of 97% and specificity of 94% compared with phlebography. Sonography allows adequate evaluation of testicular size and volume, characteristics of the parenchyma, as well as detection the presence of dilated veins, their diameter and location. It is precisely with these findings and presence of venous reflux that we can estimate the degree of severity of the varicocele. There are several classifications that take into consideration whether the reflux is with the Valsalva maneuver or is spontaneous (more severe). One of the simplest classifications that are used with Color Doppler is: Grade 0, mild reflux during Valsalva (physiological), Grade 1, reflux that ends before finishing Valsalva, Grade 2, persistent reflux throughout Valsalva and Grade 3, reflux basal, persistent and no change with Valsalva. The diameter of the veins is increased > 2 mm. The classifications relating the diameter and the reflux time with the Valsalva maneuver have also been validated, as well as the location of the dilatations: at the level of the spermatic cord, superior pole of the testicle, middle third or to the lower testicular pole, as per example the Classification of Sarteschi. In many cases of severe varicocele, a decrease in testicular size and volume is associated. The normal volume is 15 +/- 7 cc. The use of linear transducers with frequency >/= 10 MHz is recommended, setting the system for low flow detection by decreasing PRF and increasing gain.

Alginate on demand as add-on for patients with gastro-oesophageal reflux disease and insufficient PPI effect

Chronic reflux patients with long-term PPI therapy frequently have persistent symptoms. A critical source of the persistent acid reflux is the acid pocket, which can be treated effectively by the non-systemic reflux suppressing action of alginates. GERD patients with at least one year of PPI long-term therapy, who were dissatisfied with their therapy, were treated over a period of 14 days with alginate as add-on and when required (up to 4 times daily) in a prospective, multi-centre, non-randomised, non-interventional and uncontrolled study in GP practices. The frequency of symptoms in the week before treatment was recorded, as well as in the second week of the study phase and the consumption of alginate. The validated GERD Q score was also applied. The patients assessed satisfaction with the therapy on a five-point Likert scale (very unhappy - happy) before the beginning and at the end of the study. The primary endpoint of the study was improvement in satisfaction with the therapy by ≥ 1 point. 155 patients (54 % women, median age 57 (18 - 85) years) entered the study. Six patients had to be excluded from the final efficacy analysis (no intake of study drug, lost to follow-up). The median duration of GORD was 8 (1 - 50) years and the median time on PPI therapy was 6 years. On average the patients took 3 sachets of alginate per day. The alginate therapy led to an improvement by at least 1 point on the Likert scale in 72 % of patients (1 step n = 45, 2 steps n = 41, 3steps n = 16, 4 steps n = 5). Patients with a Gerd Q score > 8 showed a higher response rate at 81 %. There was improvement in all typical reflux symptoms and sleep disorders. The treatment was generally well-tolerated. A reflux blocking alginate taken on demand is an effective and safe option for the treatment of breakthrough symptoms in GERD patients on PPI.

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.

A207 - Type 3 Hiatal hernia complicating a mediogastric stenosis after gastric banding: cure of hiatal hernia and revision to Roux en Y Gastric Bypass

Background: We present the case of a 54-year-old woman with a residual BMI of 35.4 kg/m2 after failure of gastric banding. She complained of persistent Gastro-Esophageal Reflux Disease (GERD) and dysphagia despite removal of the gastric band 3 years before.

Diagnostic yield of ambulatory oesophageal studies on versus off proton pump inhibitors: a systematic review and meta-analysis.

Patients with persistent gastroesophageal reflux disease symptoms despite proton pump inhibitors are increasingly encountered. It remains controversial if proton pump inhibitors should be stopped before functional oesophageal tests. This meta-analysis compares the positive yield of oesophageal studies performed off versus on proton pump inhibitors. Pubmed, Embase and the Cochrane Library were searched for eligible studies. Outcomes assessed were the number of subjects with: elevated oesophageal acid exposure time when studied off versus on proton pump inhibitors; positive symptom index (≥50%) and/or positive symptom association probability (≥95%) for acid reflux; and/or non-acid reflux events off versus on proton pump inhibitors. The random effects model was applied. Fifteen studies (n = 5033 individuals; 33% on proton pump inhibitors; 32% men; mean age 52.1 years) were analysed. Pooled risk ratio for the comparison of high oesophageal acid exposure time off versus on proton pump inhibitors was 2.16 (95% confidence interval (CI) 1.42-3.28). The risk ratio of a positive symptom index (acid reflux) was 2.64 (95% CI 1.52-4.57) and the risk ratio of a positive symptom association probability (acid reflux) was 2.94 (95% CI 2.31-3.74). Conversely, the risk ratio of a positive symptom index (non-acid reflux) was 0.96 (95% CI 0.49-1.88) and risk ratio of a positive symptom association probability (non-acid reflux) was 0.54 (95% CI 0.30-0.99). Oesophageal studies after proton pump inhibitor cessation improve the positive yield for acid reflux-related events but reduce the detection of symptomatic non-acid reflux events.

Clinical Response Is Associated with Improvement in Health-Related Quality of Life in Patients with Persistent GERD Symptoms

Introduction: Responder endpoints are often used in clinical trial design to evaluate treatment efficacy, but positive responder-endpoint results are not necessarily associated with quality-of-life improvements. We evaluate the relationship between clinical responder endpoints and health-related quality of life (HRQOL) measures in patients with persistent gastroesophageal reflux disease (pGERD). Methods: Patients with pGERD - characterized by continued heartburn and regurgitation symptoms despite ongoing proton pump inhibitor (PPI) treatment—were enrolled in an 8-week, randomized, double-blinded, placebo-controlled phase 2b trial of IW-3718, an investigational gastric-retentive formulation of a bile acid sequestrant. Each patient completed a symptom assessment e-dairy (mRESQ-eD) daily, degree of relief assessments weekly, and the EQ-5D HRQOL at week 0 (baseline), 4, & 8. Heartburn and regurgitation responders were defined as having a ≥45% reduction in the mean daily heartburn severity or mean daily regurgitation frequency score, respectively, for ≥4 of 8 weeks, including ≥1 of the last 2 weeks. Degree of relief responders (heartburn, regurgitation, and overall GERD symptoms) were patients who reported significant or moderate relief for ≥4 of 8 weeks. Least-square mean changes from baseline to week 8 in EQ-5D were obtained for responders vs. non-responders using a mixed model for repeated measures (MMRM) with week (categorical), responder status, and week-by-responder status as fixed-effect terms and baseline EQ-5D as a covariate. Results: Patient demographics are shown in the Table. Responders showed better improvement in EQ-5D at week 8 compared with non-responders across all responder endpoints (p<0.05 for heartburn, regurgitation, and degree of GERD relief responder endpoints, Figure). Conclusion: Patients with persistent GERD symptoms who achieved clinical response also showed improvement in health-related quality of life as measured by the EQ-5D utility index; the heartburn, regurgitation, and GERD relief responders show significant improvement in EQ-5D results compared to non-responders. The clinical responder endpoints used in the IW-3718 phase 2b trial may yield results useful to payers as well as clinicians.386_A Figure 1 No Caption available.386_B Figure 2 No Caption available.

Does Voiding Cystourethrogram Exclude Posterior Urethral Valves in Late Presenting Cases?

Delayed presentation of posterior urethral valves (PUVs) is a rare condition. Presentation and diagnosis of the patients with late PUVs are challenging. Voiding cystourethrogram (VCUG) is mainly practiced. In this study, we aimed to evaluate the children with late-presented PUVs, and the reliability of VCUG in this group. Between January 2003 and December 2017 records of patients who were diagnosed with late-presented PUVs were analyzed. Delayed presentation of PUV was defined as patients who were diagnosed and treated after infancy. Cases were examined in terms of age at diagnosis, presenting symptoms, urinalysis, urinary ultrasound, urodynamic studies, VCUG, and dimercaptosuccinic acid scintigraphy findings. Postoperative follow-up conditions were also assessed. Seventeen boys were diagnosed with late-presented PUVs (mean age was 7.35 years). The most common symptoms at presentation were frequency (58.8%), day and nighttime incontinence (47%), and febrile urinary infection (41%). PUV was noted by VCUG in 10 patients alone. The classical sign of dilated posterior urethra was detected in 9 patients. The 10th patient had posterior urethral irregularity. Urethra could not be evaluated due to unsuccessful voiding in one patient. Six patients had normally appearing urethra on VCUG. Reflux was detected in nine (52.9%) patients. Late-presented PUVs may be missed on VCUG. Whether a PUV might be present is crucial in boys with a history of recurrent urinary infection, persistent reflux, and repetitive daytime incontinence. Based on our results, we conclude that cystoscopic examination should be preferred for those cases to diagnose PUVs regardless of VCUG results.

Predictors of becoming overweight among pediatric patients at risk for urinary tract infections

The association between obesity and urinary dysfunction in childhood has been described, albeit through retrospective analysis, making temporal relationships difficult to establish. The objective of this study was to determine risk factors for significant weight gain in children at risk for recurrent urinary tract infections. A secondary analysis of the Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation trials was conducted. The outcome of interest in these children was significant increase in body mass index (BMI) percentile (>85th BMI percentile for sex and age) in previously normal-weight children. Multivariable logistic regression was used to determine the independent effects of predetermined risk factors. In total, 446 patients were included in the study. Most patients aged less than 1 year at study entry (229, 51%), and 399 (89%) of patients were female. Eighty-four patients (17%) became clinically overweight. Patients assigned to prophylactic antibiotics were not more likely to gain significant BMI percentiles (adjusted odds ratio [aOR]=1.1, 95% confidence interval [CI]=0.6-1.8). Significant BMI percentiles were gained in Hispanic/Latino patients compared with whites (aOR=3.3, 95% CI=1.7-6.4), in children who were infants at study enrollment compared with non-infants (aOR=2.1, 95% CI=1.2-3.8), and in those with persistent reflux during the study period (aOR=2.1, 95% CI=1.0-4.3). Neither patients assigned to prophylactic antibiotics (aOR=1.1, 95% CI=0.6-1.8) nor patients with bladder and bowel dysfunction (BBD) (aOR=1.2, 95% CI=0.6-2.3) were more likely to gain significant BMI percentiles. Significant BMI percentile gain is common in patients at risk for UTIs. Hispanic/Latino ethnicity, persistent reflux, and younger age, specifically infants than non-infants, were identified as independent risk factors for becoming overweight in this population. Exposure to prophylactic antibiotics and BBD were not associated with becoming overweight. Risk for becoming overweight should be discussed when managing patients at risk for UTIs, especially in the subpopulations identified.

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.

440 - The Utility of Pharmacogenetic Testing in Managing Children with Persistent Gastroesophageal Reflux Disease Despite Therapy

440 - The Utility of Pharmacogenetic Testing in Managing Children with Persistent Gastroesophageal Reflux Disease Despite Therapy