Withdrawal Of Proton Pump Inhibitors Research Articles

Comparative evaluation of endoscopic anti-reflux mucosectomy and stretta radiofrequency ablation in the management of gastroesophageal reflux disease: insights from a retrospective multicenter cohort study.

Treatment options for gastroesophageal reflux disease (GERD) that is unresponsive to proton pump inhibitors (PPIs) remain limited. Therefore, we compared the therapeutic effects of anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for intractable GERD in over 400 individuals who underwent either procedure. We conducted a retrospective study between 2016 and 2023 to evaluate the effectiveness of SRF and ARMS treatments for refractory GERD. The primary measure of success was the change in the GERD questionnaire (GERDQ) score. The secondary outcomes were various GERD-related indicators, including endoscopic Los Angeles (LA) classification, Hill's type-based flap valve grade (FVG), EndoFLIP™ distensibility index (DI), rate of PPI discontinuation, resolution rate of Barrett's esophagus, and incidence of adverse events. The ARMS group included patients with high GERDQ scores, FVG, LA grade, and Barrett's esophagus. Both groups had similar rates of improvements in GERDQ score (P = 0.884) and PPI withdrawal (P = 0.866); however, the ARMS group had significantly more side effects and improvements in the median change in GERDQ score (P = 0.011), FVG (P < 0.001), LA grade (P < 0.001), EndoFLIP™ DI (P < 0.001), and resolution of Barrett's esophagus (P < 0.001). The ARMS group had a greater GERDQ score improvement than the SRF group but had symptom relief and PPI discontinuation rates similar to those of the SRF group. However, objective measures, including EndoFLIP™ DI and endoscopic evaluations, were better in the ARMS group than in the SRF group.

The Impact of Sex on the Response to Proton Pump Inhibitor Treatment.

Proton pump inhibitor (PPI) treatment is responsible for substantial gastrin elevation secondary to reduced intragastric acidity. Due to the increasing global prevalence of PPI users, concerns have been raised about the clinical significance of continuous gastrin elevation and its potential long-term side effects. Hypergastrinemia secondary to PPIs has trophic effects on gastric mucosa, leading to enterochromaffin-like cell hyperplasia and gastric (fundic) polyp formation, and it is believed to provoke acid rebound following PPI withdrawal that induces PPI overutilization. Previous studies have found higher gastrin release following PPI therapy in females compared with males, and sex differences have also been demonstrated in pharmacokinetic parameters and dose requirements for acid reflux. It is conceivable that females might be at increased risk of PPI overuse, because they often receive higher milligram-per-kilogram doses. The prevalence of PPI use is more common among females, and the female sex is a risk factor for adverse drug reactions. This non-systematic review outlines the current knowledge of the impact of biological sex on the response to PPIs. The aim is to highlight the female sex as a potential risk factor that could be a step toward precision medicine and should be considered in future research on the response to PPI treatment.

Proton Pump Inhibitor Use and Complications of Cirrhosis Are Linked With Distinct Gut Microbial Bacteriophage and Eukaryotic Viral-Like Particle Signatures in Cirrhosis.

Proton pump inhibitors (PPIs) modulate the progression of cirrhosis to hepatic encephalopathy (HE) and can affect the bacterial microbiome. However, the impact of PPI on the virome in cirrhosis using viral-like particle (VLP) analysis is unclear. We determined the VLP in the stool microbiome in patients with cirrhosis cross-sectionally (ascites, HE, and PPI use analyzed) who were followed up for 6-month hospitalizations and through 2 clinical trials of PPI withdrawal and initiation. In a cross-sectional study, PPI users had greater ascites prevalence and 6-month hospitalizations, but VLP α diversity was similar. Among phages, PPI users had lower Autographviridae and higher Streptococcus phages and Herelleviridae than nonusers, whereas opposite trends were seen in ascites and HE. Trends of eukaryotic viruses (higher Adenoviridae and lower Virgaviridae/Smacoviridae) were similar for PPI, HE, and ascites. Twenty-one percent were hospitalized, mostly due to HE. α Diversity was similar in the hospitalized/nonhospitalized/not groups. Higher Gokushovirinae and lower crAssphages were related to hospitalizations such as HE-related cross-sectional VLP changes. As part of the clinical trial, PPIs were added and withdrawn in 2 different decompensated groups over 14 days. No changes in α diversity were observed. Withdrawal reduced crAssphages, and initiation reduced Gokushovirinae and Bacteroides phages. In cirrhosis, PPI use has a gut microbial VLP phage signature that is different from that in HE and ascites, and VLP changes are linked with hospitalizations over 6 months, independent of clinical biomarkers. Eukaryotic viral patterns were consistent across PPI use, HE, and ascites, indicating a relationship with the progression of cirrhosis. PPIs alone showed modest VLP changes with withdrawal or initiation. Distinct phage and eukaryotic viral patterns are associated with the use of PPIs in cirrhosis.

Effect of aspirin, warfarin, and proton-pump inhibitors on performance of fecal immunochemical test in colorectal cancer screening: a systematic review and meta-analysis.

This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science, Cochrane Central, and Google Scholar were searched from inception until September 3, 2023. Studies comparing the diagnostic performance of FIT between medicine users and non-users in average-risk colorectal cancer screening populations were included. Pooled sensitivity, specificity, and positive predictive values (PPVs) for advanced neoplasia (AN) of FIT were compared by reporting pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. Twenty-two studies enrolling 5,572,367 individuals were included. For aspirin, pooled sensitivity and specificity for AN were 57.2% and 88.4% in users versus 60.2% and 93.2% in non-users; while pooled ORs were 1.49 (95% CI 0.89-2.48, P = 0.13) and 0.72 (95% CI 0.62-0.83, P < 0.001), respectively. In subgroup analysis, there was no difference in sensitivity and specificity between the two groups at the cutoff of 20μg Hb/g (P = 0.57 and 0.29, respectively) but a significantly lower specificity in users compared with non-users at lower cutoffs (P < 0.001). Moreover, a significantly lower PPVAN in users compared with non-users was observed after matching age and sex confounders (P = 0.001). Warfarin had no significant influence on PPVAN of FIT (P = 0.43). PPIs were associated with a significantly lower PPVAN in users (P < 0.001). Aspirin use was associated with lower specificity and PPV of FIT. Aspirin discontinuation before FIT to reduce false-positive results should be interpreted with caution given concerns about cardiovascular events. Increasing cutoff values of FIT in aspirin users may be another possible approach. Additionally, warfarin withdrawal before FIT is unnecessary but PPIs withdrawal before FIT is recommended to reduce false-positive results.

Proton-Pump Inhibitor Therapy in Patients with Erosive Esophagitis: A Real-World Scenario

Background: Gastroesophageal reflux disease (GERD) has three classical phenotypes, namely erosive esophagitis (EE), nonerosive reflux disease, and Barrett’s esophagus. Patients with GERD are managed with lifestyle changes, dietary interventions, and proton-pump inhibitors (PPI). Aim: To determine the patterns of PPI use in patients with documented EE. Methods: This prospective study recruited all patients with symptoms of GERD (heartburn and/or regurgitation with or without chest pain) and documented significant reflux esophagitis (Los Angeles grading LA-B or beyond on endoscopy). Lifestyle and dietary changes were initiated and all patients were prescribed twice daily PPI for 8 weeks. PPI was tapered as the requirement beyond 8 weeks. Follow-up was done at weeks 8, 12, and 24. The outcomes analysed included number of patients where complete PPI withdrawal was possible at week 24 and determinants of continued PPI use at 24 weeks of therapy. Statistical analysis was performed using Chi-square test, Mann–Whitney U-test, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. P &lt; 0.05 was considered statistically significant. Results: The study cohort included 53 patients-42 with reflux esophagitis LA-B and 11 with reflux esophagitis LA-C (median age 46 years [22–77 years]; 28 [52.3%] males). There was significant difference in consumption pattern of PPI between week 12 and 24 (P = 0.008). At week 12, 15.1% were off PPI and 67% required intermittent dosing. At week 24, 45.3% of cases were off PPI therapy and 43.4% required intermittent dosing. Only 11.3% patients continued drug use at once a day dosing. Lower body mass index (BMI) (P 0.01) and age (P 0.01) were linked with complete PPI withdrawal at week 24. Conclusion: The present study highlights that PPI withdrawal is possible in 15.1% and 45.3% cases with EE after week 12 and week 24 of therapy, respectively. Lower BMI and age are likely to be associated with PPI withdrawal at week 24.

Randomised clinical trial: the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden

Background/aimsInvestigation of gastro-oesophageal reflux disease is usually performed off proton pump inhibitors (PPIs). This can exacerbate symptoms, potentially impacting investigation accuracy if patients circumvent the preinvestigation instructions. There are no...

Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial

BackgroundNon-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone.MethodThis multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD–HRQL, and TCM syndromes scales.DiscussionPrevious research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients’ physical and psychological burdens, and achieve good social benefits.Trial registrationClinicaltrials.gov NCT04340297. Registered on April 9, 2020

Clinical efficacy of endoscopic antireflux mucosectomy vs. Stretta radiofrequency in the treatment of gastroesophageal reflux disease: a retrospective, single-center cohort study.

BackgroundCurrently, antireflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) are the most commonly used minimally invasive antireflux therapies. To date, there have not been any reports comparing ARMS and SRF. Our aim was to compare the clinical efficacies of these two therapeutic methods.MethodsWe analyzed data from gastroesophageal reflux disease (GERD) patients, including 39 who received ARMS treatment and 30 who received SRF treatment between January 2020 and May 2021. Symptom control, gastroesophageal reflux disease questionnaire (GERDQ) score, gastroesophageal reflux disease health-related quality of life (GERD-HRQL) score, proton pump inhibitor (PPI) withdrawal, and PPI reduction were analyzed and compared.ResultsAfter 6 months of follow-up, the results showed that both therapies were effective in improving symptoms and quality of life. No difference was found between the ARMS group and SRF group in GERDQ score, GERD-HRQL score, PPI withdrawal rate, or PPI reduction rate (P>0.05). There was no significant difference in the PPI withdrawal rate between the two therapies among patients with gastroesophageal flap valve (GEFV) grade II and grade III (P>0.05), but the PPI withdrawal rate in the ARMS group was significantly higher than that in the SRF group among patients with GEFV grade IV (P<0.05).ConclusionsThe clinical efficacies of ARMS and SRF 6 months postoperation were equivalent. The results showed that both ARMS and SRF treatment were acceptable for patients with GEFV grades II and III, while ARMS should be selected for patients with GEFV grade IV.

De-Prescribing Proton Pump Inhibitors in Patients With End Stage Kidney Disease: A Quality Improvement Project.

Background:Proton pump inhibitors (PPIs) are widely prescribed and may be associated with harm; hypomagnesemia and reduced effectiveness of calcium carbonate phosphate binders may be important in end-stage kidney disease (ESKD).Objectives:Our objectives included (1) discontinuing PPIs and H2 blockers and (2) assessing the impact on serum magnesium and markers of mineral metabolism.Design:Prospective cohort.Setting:Satellite hemodialysis unit of a tertiary care hospital.Patients:Incident and prevalent patients with ESKD treated with hemodialysis.Measurements:We assessed the impact of stopping PPI/H2 blockers in patients who did not have an absolute indication as per guidelines in the general population; serum magnesium, calcium, and phosphate were measured before and approximately 8 weeks later. Analysis of variance (ANOVA) test and Kruskal-Wallis was used to describe the population. Wilcoxon signed rank test for the paired change scores (from pre to post)Methods:The electronic medical record (EMR) was extensively searched for absolute indications for a PPI. Results were reviewed with the primary nephrology team before approaching patients about stopping the PPI. Basic demographic information and select medications were also collected.Results:Electronic medical records were reviewed for 179 patients, 74 had a PPI or H2 antagonist or both on their medication list (43%); 23 (31%) were assessed as appropriate. After primary team and patient review, 29 patients agreed to a trial of PPI withdrawal. Fourteen patients restarted their PPI, most for gastroesophageal reflux disease. Three patients had a GI bleed, 1 fatally. Serum calcium (P = .17) and the dose of phosphate binders (P = .075) did not change but serum phosphate increased (1.55 [0.29] to 1.85 [0.34] mmol/L; P = .0005). Serum magnesium also increased (1.01 [0.16] to 1.06 [0.14] mmol/L; P = .01).Limitations:Small patient numbers and observational nature of the study does not establish causation in this population at high risk to experience a gastrointestinal bleed.Conclusions:Our results suggest that PPI deprescribing as recommended in the general population may be associated with harm in patients with ESKD and requires further study.Trial Registration:Not registered.

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia.

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.

Magnetic sphincter augmentation in treating refractory gastroesophageal reflux disease: A systematic review and meta-analysis.

In this systematic review and meta-analysis we aimed to determine the efficacy and safety of magnetic sphincter augmentation (MSA) in the management of refractory gastroesophageal reflux disease (rGERD). Literature search was conducted in PubMed, the Cochrane Library, EMBASE, Web of Science, OpenGrey and ClincalTrials.gov for single-arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) serving as the control published until April 2020. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GERD-health-related quality of life (GERD-HRQL), normalization of acid exposure time (AET) and incidence of procedure-related adverse events (AE). Ten single-arm studies, one randomized controlled trial and three cohort studies involving 1138 participants were included. Post-MSA PPI withdrawal, significant GERD-HRQL improvement and AET normalization were achieved in 87.0%, 88.0% and 75.0% of the patients, respectively. The incidence of postoperative dysphagia was 29% and endoscopic dilation was required in 7.4% of patients undergoing MSA. MSA showed a better efficacy in symptom control than PPI (PPI cessation: 91% vs 0%; GERD-HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas-bloat syndrome (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.51-0.93, P=0.01) and better reserved ability to belch (RR 1.48, 95% CI 0.76-2.86, P=0.25) compared with LNF. MSA was an effective and safe therapy for rGERD. Well-designed randomized trials that compare the efficacy of MSA with other therapies are needed.

Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma-induced hypergastrinemia causing excessive gastric acid secretion. Secretin stimulation tests (SSTs) are required for diagnosis in the majority of patients. Two case reports suggest that proton pump inhibitors (PPIs) cause false SST results. Consequently, PPIs are discontinued to allow hyperchlorhydria to recur; however, uncontrolled acidity can cause life-threatening complications in those with underlying undiagnosed ZES. The aim of this study was to determine whether PPIs influence the validity of SSTs for the diagnosis of ZES. A retrospective chart review was performed. Charts of patients who underwent SSTs were reviewed to determine whether they were performed on or off PPI and the test's accuracy by comparing the results with gold standard tests (diagnostic laboratory testing performed off PPI or surgical pathology consistent with gastrinoma). Sensitivity, specificity, and positive predictive value (PPV) of SST on PPI were calculated and results compared with SST off PPI using noninferiority analyses. Twenty-eight patients corresponding to 29 SSTs were performed on PPI, and 70 patients corresponding to 107 SSTs were performed off PPI. Most of them were female and white and had multiple endocrine neoplasia type 1. We found no false-positive or false-negative SSTs on PPI. Sensitivity, specificity, and PPV of SSTs on PPI were determined to be noninferior to SSTs off PPI (P ≤ 0.05 for all). In our cohort, SSTs on PPI compared with SSTs off PPI were noninferior for sensitivity, specificity, and PPV. These results suggest that PPI withdrawal before SSTs may not be necessary.

Снижение риска рецидива симптоматики при применении эзофагопротектора у пациентов, которым требуется временная отмена антисекреторной терапии

Objective: to evaluate the effectiveness of an esophagoprotector in reducing the risk of recurrent symptoms of gastroesophageal reflux disease (GERD) in patients who requiring temporary cancellation of therapy with proton pump inhibitors (PPIs). Material and methods. For the prospective comparative study there were selectively chose patients who had been taking PPIs for a long time (at least one month) for the underlying disease and who required temporary discontinuation of antisecretory therapy due to objective medical reasons. The study included patients with endoscopically and/or pH-metrically verified GERD, as well as histologically verified Barrett's esophagus. In the process of randomization of patients, two equal groups were formed, depending on the therapy received at the time of PPI withdrawal: group 1 received antacids on demand, group 2 received antacids on demand, as well as the esophagoprotector Alfasoxx at a dose of 10 ml four times a day (after each meal and at night). The follow-up period was two weeks. The patients recorded episodes of heartburn in their personal diaries. Results. The study included 60 patients (28 men and 32 women). The average age of the examined patients was 43.1 ± 5.3 years. By the end of the two-week follow-up period, the frequency of recurrent symptoms in group 1 was 36.7%, while in group 2 it was 13.3%. The use of the esophagoprotector Alfasoxx contributed to the significant regression of the risk of heartburn recurrence (odds ratio 0.2657; 95% confidence interval (CI) 0.07328-0.9637; p = 0.0438) in comparison with the group of patients who received only antacids in the on-demand mode. When analyzing the population of patients who had relapsed symptoms, it was demonstrated that the average number of heartburn episodes in group 1 was 6.18 (95% CI 4,1930-8,1706), and in group 2 – 4.50 (95% CI 0,7121-8,2879). Conclusion. This prospective comparative study demonstrated that the use of the esophagoprotector Alfasoxx helps to reduce the risk of relapse of GERD symptoms in patients requiring temporary cancellation of PPI therapy.

Effect of laparoscopic novel W-H fundoplication in patients with proton pump inhibitor dependent gastroesophageal reflux disease

Objective: To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). Methods: The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire. Results: A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P<0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation. Conclusions: The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

Эффективность эзофагопротекции при коротких периодах отмены поддерживающей терапии ингибиторами протонной помпы у пациентов с пищеводом Баррета

Aim. Evaluation of the effectiveness of esophagoprotection in covering up short periods of withdrawal of maintenance therapy with proton pump inhibitors (PPIs) in patients with Barrett's esophagus (BE). Materials and methods. A retrospective analysis of the data of patients with histologically verified BE who received outpatient PPI therapy for at least 12 months was carried out. This cohort was divided into two groups to compare depending on the treatment regimen received. The first group included only patients who take PPIs constantly, while the second group included patients who had periodic interruptions in taking PPIs. In the second group, we analyzed only cases where to cover up the periods of PPI withdrawal the patients used the esophagoprotector Alfasoxx (10 ml 4 times a day, after each meal and at night). In the cohort, demographic data (age, gender), risk factors, length of the BE segment, degree of dysplasia, number of relapses of erosive esophagitis, and the data of high-resolution manometry on movement disorders of the thoracic esophagus (ineffective motility and lack of contractility) were analyzed. Results. The study included 39 patients (28 men and 11 women) with histologically verified BE. The average age was 57,1538 years (95% confidence interval 53.4269–60.8808). The gender structure was dominated by men (n=28). The duration of BE history in the analyzed cohort was 5.6769 years (95% confidence interval, 4.6161–6.7378). The first group consisted of 23 patients who take PPIs constantly. The second group consisted of 16 patients who had periodic interruptions in taking PPIs, which were covered by the esophagoprotector Alfasoxx. In the analyzed cohort, there were no significant differences between the groups in the average length of the BE segment, the number of patients with a long BE segment, the degree of dysplasia, the number of relapses of erosive esophagitis, and the rate of movement disorders of the thoracic esophagus. Conclusion. In routine practice, there are reasons for the temporary withdrawal of PPIs in patients with BE, which requires the administration of course esophagoprotection to cover up the risks. The results of this retrospective comparative study demonstrate the effectiveness of this strategy.

Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia

Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs). We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models. The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P= .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts. We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243.

Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.

SAT-121 Secretin Stimulation Test in a Patient Receiving Proton PUMP Inhibitor Therapy- to Do or Not to Do?

Introduction:Complications of gastrinoma cause increase in mortality in patients with MEN syndrome. There are concerns that secretin stimulation test (SST) can produce false positive results in the setting of proton pump inhibitor (PPI) use. However, withholding the PPI treatment in a patient with severe peptic ulcer disease can be potentially unsafe. There is also a theoretical concern that abrupt withdrawal of PPI will cause a surge in gastrin. Here we discuss a case where SST yielded impressive results despite the use of PPI.Case report:78 y.o. Caucasian male presented in December 2018 with chronic nausea, vomiting, diarrhea of 5-year duration. Further evaluation showed severe esophagitis with strictures, multiple gastric and duodenal ulcers and he was initiated on PPI. He also had h/o hyperparathyroidism diagnosed 2 years ago s/p parathyroidectomy (2 of 4 parathyroid glands removed) and one kidney stone in his late 20s and early 70s. He had no family history of any endocrine issues. Physical examination was unremarkable. Labs were significant for gastrin levels (nl <100 pg/mL) of 375 pg/mL in 6/2016 and 219 pg/mL in 11/2018. SST was performed on 12/22/2018 which showed gastrin levels as follows: -10 min=405 pg/mL, - 5 min=404 pg/mL, + 2 min=3201 pg/mL, + 5 min=3439 pg/m, +10 min=2445 pg/mL, +20 min=1218 pg/mL, +30 min=578 pg/mL. He was diagnosed with gastrinoma based on the SST results. Genetic testing did not show any pathogenic sequence variants or deletions/duplications identified in MEN-1; CASR; CDC73; CDKN1B or RET. Given history of hyperparathyroidism and gastrinoma, he was clinically diagnosed with MEN1 syndrome. Ga-68 DOTATATE scan in May 2019 revealed focal radiotracer avidity in the tail the pancreas suspicious for neuroendocrine tumor and multiple radiotracer avid retroperitoneal and abdominal lymph nodes. Focal radiotracer avid lesion was also noted in the sacrum suspicious for osseous metastatic disease. He was started on lantreotide monthly injections in July 2019. Gastrin level decreased to 94 pg/mL 1 week after first injection, however later increased to 304 pg/ml 1 week after third dose of lantreotide. Surgical options are also being explored.Conclusion:An increase in more than 120pg/mL over basal gastrin level within 10 min in SST is consistent with a diagnosis of gastrinoma. Our patient demonstrated an impressive increase in gastrin level with SST while on PPI therapy. Pertinent diagnostic information was successfully obtained without increasing the risk of complications that can occur by withdrawal of PPI therapy.

The Effect of Proton Pump Inhibitor Withdrawal on Dabigatran Etexilate Plasma Levels in Patients With Atrial Fibrillation: A Washout Study.

Several studies demonstrated that proton pump inhibitors (PPIs) co-administrated with dabigatran in patients with atrial fibrillation (AF) decreased dabigatran trough and peak plasma levels. However, it is still unknown whether this interaction is reversible or not, and whether the withdrawal of PPI would lead to normalization of dabigatran plasma levels. The aim of this study was to determine the effect of PPI withdrawal on dabigatran plasma levels in patients with AF. This pilot prospective study enrolled 23 AF patients on long-term dabigatran and PPI therapy (omeprazole 20 mg twice daily or pantoprazole 40 mg once daily). Dabigatran trough and peak levels (ng/mL) were tested on PPI and after a 2-week period of PPI withdrawal with Hemoclot Thrombin Inhibitor Assay. The analysis of dabigatran plasma levels demonstrated significant elevation in trough dabigatran levels after 2 weeks of PPI withdrawal (97.2 ± 79.7 vs. 163.8 ± 105.5 ng/mL; P < 0.05). Moreover, significantly higher peak dabigatran levels were observed after 2 weeks of PPI withdrawal (142.4 ± 102.8 vs. 255 ± 129.5 ng/mL; P ≤ 0.001). This study showed that a 2-week period of PPI withdrawal lead to a significant increase in dabigatran trough and peak plasma levels in patients with AF.

2008 Fundic Gland Polyps: Not Always an Innocent Bystander

INTRODUCTION: Fundic gland polyps (FGP) are often found incidentally on endoscopy in 1.9% of patients, with most being asymptomatic. However, as in this case, FGP have been a source of upper gastrointestinal bleeding (UGB) leading to hospitalization. CASE DESCRIPTION/METHODS: An 81-year-old male with GERD and non-dysplastic Barrett’s Esophagus, presented to the emergency department with coffee ground emesis for 2 weeks. He denied NSAID, steroid, or alcohol use. GERD is well controlled on Omeprazole 40 mg daily which he has taken for the past 10 years. He denies dysphagia, abdominal pain or weight loss. No family history of gastric or colon cancer or familial polyposis syndromes. Patient with normal heart rate and blood pressure however with orthostatic hypotension. Physical exam without abdominal tenderness and rectal vault without stool on exam. Hemoglobin 11.1 on presentation with last hemoglobin 13.3 four months ago. Last EGD 2 years ago revealed non-dysplastic Barrett’s Esophagus, along with a few sub centimeter non-bleeding FGP, confirmed with biopsy. A colonoscopy 4 years prior had one tubular adenoma. Patient underwent EGD and was found to have multiple gastric body polyps; several of the largest polyps had active oozing blood. The bleeding polyps measured 12 mm in size and were removed via hot snare polypectomy. Normal remainder of exam. Afterward he remained clinically stable with no further bleeding and was discharged with Omeprazole daily. Histology revealed FGP with low grade dysplasia. H.pylori was negative on biopsies. Repeat EGD 8 weeks later removed the remaining polyps and gastric mapping was performed. Histology revealed FGP without dysplasia and no gastric intestinal metaplasia was noted. Patient has done well since with no further bleeding. DISCUSSION: Bleeding gastric FGP are rarely considered in the differential of UGB, however in this case, led to the patient’s hospitalization. Long-term (&gt;5 years) proton-pump inhibitors (PPI) have been associated with fourfold increased risk of FGP, with regression often seen upon withdrawal of PPI. This patient brings a unique case in which guidelines recommend long-term daily PPI for his Barrett’s Esophagus, however has already had complications from his growing FGP on Omeprazole. FGP can also be associated with polyposis syndromes. Malignancy is rare in sporadic and PPI induced FDG but can be seen in up to 4.2% of patients with familial adenomatous polyposis. The removal of FGP can potentially limit the risk of future bleeding as seen in this case.