High-dose Proton Pump Inhibitor Research Articles

Improving clinical outcomes of Barrett’s esophagus with high dose proton pump inhibitors and cryoablation

Introduction Esophageal adenocarcinoma incidence has increased significantly despite surveillance endoscopy for Barrett’s esophagus (BE) and gastric acid supression medications. This prospective, cohort study’s aims were to determine the long-term efficacy of proton-pump inhibitors twice daily (PPI-BID) with cryotherapy (CRYO) for complete ablation of BE. Materials and Methods Consecutive BE patients were managed with a PPI-BID, CRYO ablation, follow-up protocol. Primary outcomes were to determine complete ablation rate of intestinal metaplasia (IM) or dysplasia/carcinoma, and factors affecting recurrence. Results Sixty-two patients were enrolled: advanced disease (11%), low-grade or indefinite dysplasia (26%), non-dysplastic BE (63%). In 58 completing CRYO, eradication was confirmed in 100% on surveillance endoscopy. Adverse events (5%) were minor (mild pain 4%). IM recurred in 9% after a mean of 52 months, all successfully re-ablated. No second recurrence occurred. The primary predictor of recurrence was noncompliance with PPI-BID. BE or cardia IM recurred in 35% of those taking proton pump inhibitors once daily or less compared with 0% in those on PPI-BID or dexlansoprazole daily (p<.001). Conclusions Minimizing acid reflux with at least PPI-BID combined with CRYO ablation appears to be the optimal cost-effective and safe BE treatment for any stage to minimize progression to adenocarcinoma by addressing both the stimulus that causes BE and the presence of goblet cells.

Laparoscopic Nissen Fundoplication

After medical management with high dose proton pump inhibitors proves to be refractory, a 63-year-old man with gastroesophageal reflux disease (GERD) prese

Urea Breath Testing to Detect Helicobacter pylori in Patients with Peptic Ulcer Bleeding During Proton Pump Inhibitor Treatment.

This was a descriptive study carried out from January to December 2021, at Quanzhou First Hospital, an affiliated hospital of Fujian Medical University, to investigate the efficacy of the urea breath test in detecting Helicobacter pylori infection in patients with peptic ulcer bleeding affected with proton pump inhibitors. A total of 77 patients with peptic ulcer bleeding, who underwent urea breath testing after active bleeding, were divided into two groups. The Helicobacter pylori infection positivity rate in patients with peptic ulcer bleeding was 66.2%. The time from bleeding to detection and from admission to detection was not significantly different between the Helicobacter pylori-positive and -negative groups (p=0.840 and 0.285, respectively). Even with high-dose proton pump inhibitor treatment, a urea breath test can be performed after peptic ulcer bleeding ceases and results in an acceptable positivity rate. There was no significant difference in the accuracy of Helicobacter pylori detection between the time from bleeding to testing and from admission to testing. Key Words: Peptic ulcer, Helicobacter pylori, Upper gastrointestinal bleeding, Urea breath test, Proton pump inhibitor.

Comprehensive Review: Acute Esophageal Necrosis in the Setting of Gastric Volvulus.

Acute esophageal necrosis (AEN) in the setting of gastric volvulus is a rare condition with only a handful of cases reported. Volvulus may contribute to AEN by limiting tissue perfusion and promoting massive reflux of gastric contents on compromised esophageal mucosa. We reviewed 225 original articles, literature reviews, case series, brief reports, case reports, and discuss six total cases of co-occurring esophageal necrosis and gastric volvulus. We present the first comprehensive analysis of all reported cases in the literature to date and formulate management strategies for the co-occurrence of AEN and volvulus. Management of AEN should be directed at correcting underlying medical conditions, providing hemodynamic support, initiating nil-per-os restriction, and administering high-dose proton pump inhibitor therapy. Surgical intervention is typically reserved for cases of esophageal perforation with mediastinitis and abscess formation.

Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review.

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Endoscopic Transoral Outlet Reduction for the Treatment of Biliary Reflux Symptoms in Patients After One-Anastomosis Gastric Bypass-a Case Series.

OAGB is the third most common bariatric surgery. Biliary reflux (BR) is an inherent complication of this unique anatomy, although there is still controversy regarding its significance and long-term risks including carcinogenesis. To date, there is no effective treatment for BR with conversion to RYGB reserved for refractory patients. TORe is an effective treatment for weight-regain and dumping syndrome after RYGB. We hypothesized that narrowing the anastomosis would decrease the amount of bile refluxate entering the stomach and esophagus in patients with BR symptoms after OAGB and alleviate symptoms. The purpose of this study is to evaluate the efficacy of TORe for the treatment of BR symptoms after OAGB. BR was diagnosed clinically in patients after OAGB using the gastroesophageal reflux disease health-related quality of life (GERD-HRQL) instrument after treatment with high-dose proton pump inhibitor (PPI) excluded possible acid reflux. TORe was carried out using a suture pattern that narrowed and elongated the anastomosis. All patients were prospectively followed. Twelve patients, post-OAGB, underwent TORe for BR. Symptoms resolved in 9 (75%) patients. GERD-HRQL score at 6months declined from an average of 33.7 (SD 1.9) before the procedure to 16.1 (SD 10, p < 0.001). In one case, a small perforation was identified during the procedure and was immediately sutured with no further sequela. TORe appears a safe and effective treatment for BR symptoms after OAGB, at least in the short term. Accurate tools for BR diagnosis, a larger cohort, and longer follow-up periods are needed to better show the effectiveness and durability of this treatment option.

Rescue therapy for refractory Helicobacter pylori infection: current status and future concepts.

Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.

Prescribing Patterns of Proton Pump Inhibitors in Germany: A Retrospective Study Including 472 146 Patients.

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the "management of gastroesophageal reflux disease and eosinophilic esophagitis," by the DGVS.

Comparative effectiveness of first-line therapies for eradication of antibiotic-resistant Helicobacter pylori strains: A network meta-analysis.

As a first-line treatment regimen for Helicobacter pylori (H. pylori) infection, antibiotic therapy is widely used worldwide. However, the question of increasing antibiotic resistance must be considered. Given this issue, we need to find ways to reduce drug resistance. This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials (RCTs). To compare first-line treatment regimens for eradication of antibiotic-resistant H. pylori strains. To compare the effectiveness of the first-line regimens for treating H. pylori infection, a Bayesian network meta-analysis was applied to process data extracted from RCTs. The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve (SUCRA). In addition, we conducted a relevant search by reference citation analysis. Twenty-five RCTs involving 12029 participants [including 1602 infected with clarithromycin (CAM)-resistant strains and 1716 infected with metronidazole (MNZ)-resistant strains] were included, in which a total of seven regimens were used for H. pylori eradication. The results showed that dual therapy containing a high-dose proton pump inhibitor (HDDT) [odds ratio (OR): 4.20, 95% confidence interval (CI): 2.29-8.13] was superior to other therapies for all patients, including those with CAM/MNZ-resistant H. pylori infection. In the comparative effectiveness ranking, for CAM-resistant H. pylori, HDDT (OR: 96.80, 95%CI: 22.46-521.9) had the best results, whereas standard triple therapy ranked last (SUCRA: 98.7% vs 0.3%). In the subgroup of high cure rates (≥ 90%), HDDT was also generally better than other therapies. For the eradication of CAM- and MNZ-resistant H. pylori strains, HDDT exhibited considerable advantages. The studies of CAM-resistant H. pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs, but the results showed that all patients, including those with CAM-resistant H. pylori infection, had a concordant trend. Overall, HDDT may be a reference for RCTs and other studies of H. pylori eradication.

Key Considerations From a Health Authority Perspective When Proton Pump Inhibitors Are Used to Treat Gastroesophageal Reflux Disease (GERD) and Their Implications.

The growing prevalence of gastroesophageal reflux disease (GERD) needs to be carefully managed to relieve the symptoms and prevent complications. Complications of GERD can include erosive esophagitis, Barrett's esophagus and gastrointestinal (GI) bleeding. Proton pump inhibitors (PPIs) are typically first-line treatment for GERD alongside lifestyle changes in view of their effectiveness and cost-effectiveness. However, there are concerns with adherence to dosing regimens and recommended lifestyle changes reducing their effectiveness. There are also concerns about potential complications from chronic high-dose PPIs. These include an increased risk of chronic kidney disease, cardiovascular events and infections. Recommendations to physicians include prescribing or dispensing the lowest dose of PPI for the shortest time, with ongoing patient monitoring. Activities among community pharmacists and others have resulted in increased dispensing of PPIs without a prescription, which can be a challenge. PPIs are among the most prescribed and dispensed medicines in view of their effectiveness in managing GERD. However, there are concerns with the doses prescribed and dispensed as well as adherence to lifestyle advice. These issues and challenges need to be addressed by health authorities to maximize the role and value of PPIs.

Management of Helicobacter pylori infection.

Helicobacter pylori infection exhibits a wide disease spectrum ranging from asymptomatic gastritis, peptic ulcer disease, to gastric cancer. H. pylori can induce dysbiosis of gastric microbiota in the pathway of carcinogenesis and successful eradication can restore gastric homeostasis. Diagnostic testing and treatment for H. pylori infection is recommended in patients with active or past history of peptic ulcer, chronic dyspepsia, chronic non-steroidal anti-inflammatory drugs (NSAID) or aspirin use, precancerous gastric lesions, gastric cancer, mucosa-associated lymphoid tissue (MALT) lymphoma, family history of gastric cancer, family history of peptic ulcers, household family member having active H. pylori infection, iron deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency. Recommended first-line regimens for H. pylori eradication are classified according to clarithromycin resistance. In areas of high clarithromycin resistance (≥15%), we recommend 14-day concomitant therapy or 14-day bismuth quadruple therapy (BQT) as first-line regimen. In areas of low clarithromycin resistance (<15%), we recommend 14-day triple therapy or 14-day BQT as first-line treatment. Second-line regimens are 14-day levofloxacin triple therapy or 14-day BQT if BQT is not previously used. For patients with multiple treatment failure, antimicrobial susceptibility testing (AST) should be performed. If AST is not available, we recommend using antibiotics not previously used or for which resistance is unlikely, such as amoxicillin, tetracycline, bismuth, or furazolidone. High-dose potent proton pump inhibitor or vonoprazan is recommended to achieve adequate acid suppression. Probiotics can be used as an adjuvant treatment to reduce the side effects of antibiotics and enhance eradication rate.

Signal and Noise: Proton Pump Inhibitors and the Risk of Dementia?

The association between proton pump inhibitor (PPI) use and dementia remains controversial. This cohort study re-examines this issue, addressing shortcomings identified in previous publications using a population-based and a high-dimension propensity-score matched cohort to follow patients for up to 22 years. Cox regression models using baseline characteristics, a lag period, and time-varying variables were used to examine the risk of dementia by cumulative PPI exposure. High-dose PPI users (> 180 days of use) had significantly higher risk of dementia in crude Cox models. After adjustment for medical diagnoses and prescription drug use, these associations disappeared. Among high-dose users starting PPI therapy between 46 and 55 years old, the unadjusted hazard ratio (HR) was 1.55 (95% confidence interval (CI) 1.14, 2.10); the adjusted hazard ratio (aHR) was 1.10 (95% CI 0.80, 1.51). For high-dose users starting therapy between 56 and 65 years, HR=1.22 (95% CI1.03, 1.44); aHR=0.99 (95% CI 0.83, 1.17). High-dose users between the ages of 66 and 75 years had no association with the risk of dementia. The use of lag models or time-varying parameters similarly found some association with dementia in crude, but not multivariable Cox models. Although high-dose PPI users were more likely to develop dementia, they were more likely to be diagnosed with dementia risk factors, such as diabetes and cardiovascular disease, which are risk factors for dementia. Controlling for these conditions using multivariable models or a propensity-score matched cohort eliminated this association.

PMON40 A Rare Etiology of Chronic Diarrhea: Zollinger-Ellison Syndrome

Abstract Introduction Zollinger-Ellison Syndrome (ZES) is a rare etiology of chronic diarrhea caused by a gastrin-secreting neuroendocrine tumor. Early suspicion can prevent multiple readmissions for recurrent diarrhea thus improving clinical outcomes through prompt diagnosis and treatment, as the following case highlights. Case presentation A 74-year-old African-American female with hypertension and chronic atrial fibrillation presented to the ED complaining of watery, non-bloody diarrhea for the past 3 weeks. She reports her symptoms worsened after completing a course of amoxicillin for pharyngitis one week prior. On further questioning, she reported intermittent diarrhea for over 20 years lasting approximately two days per episode. She denied recent travel, sick contacts, pet reptiles, and recent ingestion of undercooked meat. On arrival, she was afebrile and hemodynamically stable. She was admitted for an acute kidney injury with an elevated creatinine of 3.23 mg/dL (N: 0.6-1.1 mg/dL) due to dehydration. Her renal function improved with fluids, but she developed bloody diarrhea for which gastroenterology was consulted. Stool studies were negative for Shiga-toxin, C. difficile, lactoferrin, and parasites. Computed Tomography of the abdomen showed enteritis with fluid noted throughout the colon consistent with colitis. Unprepped colonoscopy revealed blood throughout the length of the colon, suggestive of an upper gastrointestinal bleed. Esophagogastroduodenoscopy (EGD) revealed multiple bleeding duodenal ulcers controlled with hemostasis. Her symptoms improved and she was discharged home on oral pantoprazole, and told to follow up outpatient. Two weeks later, she denied any new episodes of diarrhea, and a random serum gastrin level was elevated at 413 pg/mL (N: &amp;lt;180 pg/mL). Repeat gastrin level off pantoprazole for 7 days was also elevated at 678 pg/mL, and a serum Chromogranin A level was elevated at 629 pg/mL (N: &amp;lt;390 pg/mL). Repeat EGD found her Gastric pH to be 1 with multiple non-bleeding duodenal ulcers. Somatostatin receptor scintigraphy revealed a high intensity signal consistent with a duodenal gastrinoma causing ZES. She elected for surgical resection, and was discharged home on high dose pantoprazole. Three months later, she stated that her diarrhea had completely resolved. Conclusion This case confirms ZES as a rare cause of chronic diarrhea in the setting of multiple duodenal ulcers refractory to proton pump inhibitors. Diagnosis can be made with a fasting serum gastrin level &amp;gt;1000 pg/mL or &amp;gt;400 pg/mL with a gastric pH &amp;lt;1. A Secretin Stimulation Testing can also be used. Treatment starts with high dose proton pump inhibitors, octreotide for hormonal regulation, and surgical resection if necessary. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

284 DO MEDICATIONS GET OPTIMISED DURING AN ACUTE ADMISSION TO HOSPITAL?

Abstract Background Potentially Inappropriate Prescriptions (PIPs) and Potential Prescribing Omissions (PPOs) are common in hospitalised older adults and associated with poor outcomes. The aim of this study was to assess whether PIPs and PPOs are reduced during an acute hospital admission. Methods All inpatients on 5 gerontological wards (1 acute, 1 subacute, 2 rehabilitation, 1 long-stay) on October 31st 2021 were eligible for inclusion. Medical records were retrospectively reviewed. Medication appropriateness was assessed by two assessors at admission and discharge using STOPP/START version 2. Records were consecutively reviewed according to discharge date. Ethical approval was received from the local research and innovation office (ref6275) Results Of 144 eligible patients, 41 were included; mean age 82.1 (SD6.8) years; 48.8% female, 95.1% under the care of geriatricians. The median length of stay was 24 (IQR10-67.5) days. Mean number of conditions was 5.6 (SD2.9) with dementia present in 22.5%. The mean number of medications increased during admission from 7.2 (SD3.2) to 9 (SD3.1); p=0.006 The number of patients prescribed at least 1 STOPP-PIP reduced by 20.6%; 82.9% (admission) vs 65.9% (discharge), p&amp;lt;0.001. The most common PIPs at were (i) drugs without a clear indication, 34.1% (admission) vs 14.6% (discharge), (ii) high dose proton pump inhibitors, 34.1% (admission) vs 34.1% (discharge) and (iii) Z-drugs in fallers; 17.1% (admission) vs 12.2% (discharge). Of 41 patients, 35 could have START criteria applied. START PPOs were reduced by 53%; 47.2% (admission) vs 22.2% (discharge), p=0.001. The largest improvement was seen in bone absorptive therapy (11.4% (admission) vs 2.9% (discharge) and vitamin d in those experiencing falls/osteopenia; 5.57% (admission) vs 2.9% (discharge). Of the 134 STOPP/START criteria listed, 36 (19.4%) were identified in this cohort. Conclusion Although the average number of medications increased, PIPs reduced significantly. Only 19.4% of STOPP/START criteria were identified, suggesting that focusing on a number of key PIPs going forward could improve prescribing practices.

S3666 Severe Hemorrhagic Gastritis in a Patient Receiving PD-1 Inhibitor Treated With High Dose Proton Pump Inhibitor

Introduction: The programmed death 1 (PD-1) immune checkpoint is a negative regulator of T-cell function. Pembrolizumab is a monoclonal antibody which inhibits PD-1 receptor and is commonly used to treat many types of malignancies. While this therapy allows for an enhanced immune response against tumor cells, it can also cause immune-mediated adverse events with the gastrointestinal (GI) tract being the most commonly affected. Systemic corticosteroids are frequently used in patients who develop these side effects. We present a rare case of a patient with clear cell renal cell carcinoma (ccRCC) presenting with hemorrhagic gastritis while on Pembrolizumab, successfully treated with high dose proton pump inhibitor (PPI). Case Description/Methods: A 61-year-old man with metastatic ccRCC treated with Pembrolizumab, presented to the hospital with intractable vomiting and significant weight loss secondary to poor oral intake. Upper endoscopy showed diffusely friable gastric mucosa with oozing of blood (Image 1a). Biopsy revealed mucosa with regenerative changes and active non-specific inflammation with ulcerated granular tissue, negative for CMV, H. pylori, atypical infiltrating cells, or malignancy (Image 1b). These findings were compatible with Pembrolizumab induced autoimmune gastritis. He was started on pantoprazole 40 mg BID with significant clinical improvement; thus, steroid therapy was not initiated. Repeat endoscopy a month later showed resolution of prior endoscopic findings (Image 1c). Pembrolizumab was restarted two months later while on PPI therapy without recurrence of symptoms. Discussion: Gastrointestinal side effects from immunotherapy are common. However, isolated PD-1 blockage-associated gastritis is rare and hemorrhagic gastritis is even more with only a few cases reported in literature. The management of this condition is not well established although systemic steroids are usually used to suppress the immune response. In our case, high dose PPI therapy alone led to resolution of symptoms and mucosal healing. No clinical or histological signs of hemorrhagic gastritis were noted after resuming Pembrolizumab. Whether PPI therapy has a role in preventing or minimizing this immune-induced gastritis is still unknown and more studies are needed to establish this therapy as standard.Figure 1.: (a) Initial endoscopy showing hemorrhagic gastritis. (b) H&E stain at 20× showing inflammatory infiltrate. (c) Repeat endoscopy showing healing mucosa.

S3677 Tissue Is the Issue: A Rare Case of Collagenous Gastritis

Introduction: Collagenous gastritis (CG), collagenous sprue, and collagenous colitis are rare forms of collagenous gastroenteritides marked by subepithelial collagen deposition of more than 10 mm and inflammatory infiltrate in the lamina propria. CG was first identified in 1989. It's a rare disease, with just 100 cases reported so far. Here, we present a distinct case of collagenous gastritis. Case Description/Methods: 52-year-old female with no chronic medical conditions presented with symptoms of mild reflux, epigastric pain, and intermittent diarrhea up to 5 times per day. She had sporadic Ibuprofen use for headaches. Her mother was diagnosed with lupus and a half-sister with a history of mixed connective tissue disorder. Initial upper endoscopy revealed grade B esophagitis and gastritis, biopsies showed CG. Colonoscopy with random biopsies showed no evidence of collagenous colitis. She was treated with high dose proton pump inhibitor (PPI) and repeat endoscopy in 4 weeks with biopsies via Sydney protocol was performed. Additional blood work was normal including normal thyroid panel, celiac screen (anti-transglutaminase IgA: < 1.0 U/ml, IgA: 2.34 g/L) and IgG4 titer (0.27 g/L.) Repeat EGD with biopsies per Sydney protocol confirmed CG in all gastric quadrants, except fundus. After stopping NSAIDs and continuing on PPI, her symptoms resolved with a plan for surveillance endoscopy in 6 months (Figure 1). Discussion: In our patient, the diagnosis of CG led to further investigations to rule out possible associated autoimmune diseases. The occasional ibuprofen may have been contributory, but the repeat biopsies on the second endoscopy confirmed the presence of CG despite cessation. The only contributing factor in her case is positive family history. There are very few cases reported in the literature with the possible association of lupus with CG. This distinctive case of CG is an important contribution to the limited pool of existing cases as the patient herself did not have any preexisting allergic or autoimmune conditions and it appears that this process occurred idiopathically. Given the rarity of the condition and limited literature available, we emphasize the importance of delineated medical guidelines for appropriate screening and surveillance.Figure 1.: Endoscopic appearance of collagenous gastritis. A, B. body, C. Antrum D. fundus ; E, F: Histology of collagenous gastritis characterized by thickening of sub epithelial basement membrane accompanied by diffuse superficial lymphoplasmacytic infiltrates and surface epithelial degeneration. Table 1. - Summary of Collagenous gastritis (CG) COLLAGENOUS GASTRITIS (CG) - Characterized by marked sub epithelial collagen deposition with associated inflammatory infiltrate. EPIDEMIOLOGY - Female Preponderance - All age groups but primarily affects adults. ETIOLOGY - The etiology is unknown - Stancu et al. outlined three pathogenic mechanisms that may lead to collagen deposition in cases of CG: (1) Chronic inflammation (2) Fibroblast sheath abnormality (3) Leakage of plasma proteins and fibrinogen ASSOCIATIONS - Intestinal and autoimmune disorders, including celiac disease. collagenous enteritis, collagenous colitis, sjogren syndrome, SLE, juvenile arthritis, RA, Hashimoto's thyroiditis, Grave's disease, Diabetes mellitus type 1, and CVID. - Medications such as Olmesartan, Venlafaxine SYMPTOMS AND SIGNS - Epigastric and or abdominal pain, anemia , gastrointestinal bleeding, diarrhea, nausea and vomiting, perforated ulcer, weight loss, abdominal distension, fatigue, dyspepsia, retrosternal pain, constipation and dysphagia. DIAGNOSIS - EGD with biopsy TREATMENT - Anti-secretory agents including PPIs, and H2 receptor antagonists, steroids, iron supplementation and hypoallergenic diets have been tried with limited success. - Other treatment modalities , such as sucralfate, mesalazine, bismuth subsalicylate, furazolidone, sulfasalazine, azathioprine, and parenteral nutrition have also been tested.

Does Chronic Use of High Dose Proton Pump Inhibitors Increase Risk for Pancreatic Cancer?

To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts. p48-Cre/LSL-KrasG12D mice that develop precancerous pancreatic intraepithelial neoplasia (PanINs) were treated with low- or high-dose proton pump inhibitors (PPIs) orally for 1 and 4 months. The mechanism for the cholecystokinin receptor 2 (CCK-2R) activation was investigated in vitro. Two resources were employed to analyze the risk of pancreatic cancer in human subjects with PPI use. Serum gastrin levels were increased 8-fold (P < 0.0001) in mice treated with chronic high-dose PPIs, and this change correlated with an increase (P = 0.02) in PanIN grade and the development of microinvasive cancer. The CCK-2R expression was regulated by microRNA-148a in the p48-Cre/LSL-KrasG12D mice pancreas and in human pancreatic cancer cells in vitro. Proton pump inhibitor consumption in human subjects was correlated with pancreatic cancer risk (odds ratio, 1.54). A validation analysis conducted using the large-scale United Kingdom Biobank database confirmed the correlation (odds ratio, 1.9; P = 0.00761) of pancreatic cancer risk with PPI exposure. This investigation revealed in both murine models and human subjects, PPI use is correlated with a risk for development of pancreatic cancer.

S3741 An Interesting Case of a Double Pylorus

Introduction: Double pylorus also termed double-channel pylorus is an endoscopic finding that refers to the presence of a double connection between the gastric antrum and the duodenal bulb. This connection is typically established through the presence of a gastroduodenal fistula. Despite that double pylorus is reported in the literature, its incidence is extremely low and accounts for less than 0.4% of upper endoscopic findings. Herein we report the case of 74 year-old Albanian man who was found to have a double pylorus in the setting of peptic ulcer disease. Case Description/Methods: A 74 year-old man with history of hypertension presented to the emergency room with a few week history of epigastric pain, nausea and vomiting. He denied NSAIDs intake. Vital signs were within normal range. Physical examination revealed epigastric tenderness. Laboratory tests were unremarkable. Abdominal CT scan showed inflammatory changes of the gastric antrum and proximal duodenum (panel A). Findings on upper endoscopy included erythema and edema of the gastric wall, a 7 mm cratered duodenal bulb ulcer in addition to a gastroduodenal fistula that connected the gastric antrum to the proximal duodenum consistent with a double pylorus (panel B). Routine staining of gastric biopsies identified Helicobacter Pylori (HP) organisms. The patient received high dose proton pump inhibitors and Helicobacter Pylori eradication regimen. His symptoms significantly improved and was successfully discharged home after few days of treatment initiation. He was advised to avoid Non-steroidal anti-inflammatory drugs and was scheduled for an outpatient follow-up to document eradication of HP. Discussion: Double pylorus was first described in 1969. It is twice as common in men compared to women. It can be congenital or acquired. Congenital cases are associated with gastric duplication, heterotrophic pancreatic tissue and pancreas divisum. Acquired double pylorus is usually secondary to systemic diseases, gastric malignancy, drugs or Helicobacter Pylori infection that lead to the formation of a fistulous tract between the gastric antrum and the proximal duodenum. Double pylorus can be asymptomatic or manifest as gastrointestinal bleeding or abdominal pain. Treatment includes acid suppression via proton pump inhibitors or H2-Receptor antagonists. Refractory and complicated cases require advanced endoscopic or surgical interventions.Figure 1.: Panel A: CT scan of the abdomen showing inflammatory changes of the gastric antrum and proximal duodenum; Panel B: Upper endoscopy showing a gastroduodenal fistula connecting the gastric antrum to the proximal duodenum consistent with a double pylorus.

High-dose proton pump inhibitors are associated with hospitalisation in bronchiectasis exacerbation.

BACKGROUND Bronchiectasis is a common respiratory disease complicated by periodic exacerbations. The association with different degrees of gastric acid suppression has not been well studied.METHODS A retrospective cohort study of 350 patients was conducted to investigate the association of different gastric acid suppressants with bronchiectasis exacerbation that required hospitalisation. Components of FACED (FEV1% predicted, age, chronic colonisation by Pseudomonas aeruginosa, radiological extent of the disease, and dyspnoea) were adjusted in multivariate analysis.RESULTS Among patients with exacerbation of bronchiectasis, 52 (14.9%) required hospitalisation. Prescription of a high-dose of proton pump inhibitors (PPI) was associated with increased risk of bronchiectasis exacerbation requiring hospitalisation (adjusted OR 2.77, 95% CI 1.01-7.59; P = 0.05). There was no significant association with use of a histamine-2 receptor antagonist (H2RA) (OR 1.28, 95% CI 0.32-5.06) or low-dose PPI (OR 1.47, 95% CI 0.42-5.13). Nonetheless, patients prescribed a high dose of PPI required a significantly longer hospital stay for exacerbation (13.1 ± 1.4 days) than patients not prescribed a gastric acid suppressant (8.2 ± 2.6 days) or those on a low dose PPI (8.3 ± 1.3 days) and H2RA (6.50 ± 1.50 days).CONCLUSIONS Risk of bronchiectasis exacerbation requiring hospitalisation was increased among high-dose PPI users, but not those prescribed an H2RA or low-dose PPI.