Long-term Use Of Proton Pump Inhibitors Research Articles

Prolonged Use of Proton Pump Inhibitors, but Not Histamine-2 Receptor Antagonists, Is Associated With Lower Bone Mineral Density in Males Aged Over 70.

Aims: The association of acid suppressants use with bone mineral density (BMD) is still unclear, especially in older adult with prolonged use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). In this study, our aim was to investigate the association between PPI or H2RA use and BMD in general US older adults.Methods: We conducted a cross-sectional study on a sample from National Health and Nutrition Examination Survey. Association between long-term use of PPIs or H2RAs and lumber spine BMD in elderly was evaluated using weighted multivariate linear regression models. Sensitive and subgroup analysis were also performed in this study.Results: Long-term PPI use is correlated with lower lumber spine BMD in our multivariable regression model after adjusting for known confounding factors. Further analysis showed PPI use with a duration over 1 year was negatively associated with lumber spine BMD in male, elderly aged over 70 years, and white elderly. There is no significant association between long-term H2RA use and lumber spine BMD.Conclusions: Our results indicated that the association between long-term use of PPI and lumber spine BMD differed by gender. Long term use of PPIs would reduce lumber spine BMD in older men, while H2RA use is not significantly linked with lumber spine BMD. Patients that are at high risk of bone loss should shortened the duration of PPI use (<1 year) or use H2RAs as alternative if possible.

Effect of Long-Term Proton Pump Inhibitor Use on Glycemic Control in Patients with Type Two Diabetes Mellitus.

There have been conflicting results regarding the effect of proton pump inhibitors (PPIs) as an adjunctive therapy to oral antidiabetic medication (OAM) in those with type 2 diabetes (T2DM). PPIs increase gastrin levels, causing a rise in insulin. No studies have evaluated the duration of PPI therapy and its effect on glycemic control. Medical records across 8 hospitals between 2007 and 2016 were reviewed for 14,602 patients with T2DM (not on insulin therapy) taking PPIs. Values of HbA1c (baseline, follow-up, and the difference between the two) in those prescribed with PPIs and years of therapy were compared to HbA1c values of those who had no record of PPI use. Baseline and follow-up HbA1c for patients on PPIs were 6.8 and 7.0, respectively, compared to 7.1 and 7.2 in their untreated counterparts (p < 0.001 in both comparisons). For both groups, an increase in baseline HbA1c was seen with time. Those on PPI had an increase in HbA1c of 0.16 compared to 0.08 in those not prescribed PPI. Our results show no relationship between the length of PPI therapy and HbA1c reduction.

Proton Pump Inhibitors and Gastric Cancer

Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.

Enterochromaffin-like Cell Hyperplasia–Associated Gastric Neuroendocrine Tumors May Arise in the Setting of Proton Pump Inhibitor Use

Hypergastrinemia states such as achlorhydria from gastric mucosal atrophy or a gastrin-producing tumor in humans have been associated with the development of enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumors (GNETs). Whether drugs that can elevate serum gastrin levels, such as proton pump inhibitors (PPIs), can produce the same tissue effect is not known, and there is no concrete evidence linking the use of PPIs to GNETs outside animal models and case reports. To explore the clinicopathologic association for GNETs of presumed ECL cell origin that cannot be reliably placed into any of the 3 established categories currently recognized by the World Health Organization. This is a retrospective clinicopathologic study of GNETs in the body/fundus during a period of 15 years (2005-2019). Of a total of 87 cases, 57 (65.5%) were associated with atrophic gastritis, 2 (2.3%) were associated with Zollinger-Ellison syndrome, and 28 (32.2%) were unclassified. Of the latter, 11 were consistent with true sporadic/type 3 GNETs, while 17 had background mucosal changes of parietal cell and ECL cell hyperplasia but without underlying detectable gastrinoma, and 88.2% (15 of 17) of patients from this group had documented long-term PPI use. This subtype of GNETs was more commonly multifocal and of higher grade (P = .03) than "true" sporadic GNETs. A subset of GNETs arises in the background of gastric mucosal changes suggestive of hypergastrinemia, but without underlying gastrinoma, and could be linked to long-term PPI use.

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5years of PPIs use, ruling out confounding by indication. In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

The inappropriate use of proton pump inhibitors and its associated factors among community-dwelling older adults

ObjectivesLittle is known about the inappropriate use of proton pump inhibitors (PPIs) and how mild cognitive impairment (MCI) and high comorbid burden relate to the inappropriate prescribing of PPIs. Therefore, the current study aimed to examine these associations among community-dwelling older adults in Jordan. MethodThis cross-sectional study was conducted on 215 community-dwelling older adults from three local healthcare centers located in Irbid, Jordan. Data about PPI use, including the name of medication, dose, frequency, duration, and indication, were collected retrospectively from a review of the participating older adults’ medication cards for November and December 2019. The collected data were evaluated based on the Food and Drug Administration (FDA) guidelines. MCI was measured using the Arabic version of the Montreal Cognitive Assessment, and comorbid burden was measured using the Cumulative Illness Rating Scale for Geriatrics. ResultsForty-seven percent of the participants were found to have taken a PPI, with 68 % having taken one for a longer period than recommended by the FDA. Older adults with MCI or high comorbid burden were found to be more susceptible than other older adults to the long-term use of PPIs. The logistic regression revealed that MCI is a statistically significant predictor of inappropriate PPI use (p < 0.001). ConclusionInappropriate PPI use is common among community-dwelling older adults in Jordan, with a significantly higher prevalence of inappropriate PPI use in people with MCI than in people with normal cognitive abilities. Future intervention studies are highly recommended to encourage optimal prescribing of PPIs for community-dwelling older adults.

Gastric Hyperplastic Polyps Can Shrink After Discontinuation of Proton Pump Inhibitors: A Case Series Compared With Continuation of Proton Pump Inhibitors.

This study investigated whether gastric hyperplastic polyps (GHPs) shrink after discontinuation of proton pump inhibitor (PPI) alone. Long-term use of PPIs has been reported to increase the incidence of GHPs, which sometimes bleed and cause anemia. We experienced a patient whose recurrent hemorrhagic GHPs associated with long-term use of PPIs had disappeared after discontinuation of PPIs. This study was conducted retrospectively at Kyoto University Hospital. Patients with histologically confirmed GHPs who had been taking PPIs for >6 months and who had undergone a repeat endoscopy within 2 years were included. Polyp shrinkage was defined as the disappearance of polyps or a reduction of >50% in the long diameter of the largest polyp. Six patients who discontinued PPIs were compared with 17 patients who continued PPIs. Polyp shrinkage was significantly more frequent in the PPI-discontinuation group (5/6, 83%) than in the PPI continuation group (0/17, 0%) (P<0.001). In 2 patients in the PPI-discontinuation group, the polyps completely disappeared finally. These findings suggest that discontinuation of PPIs can shrink GHPs in patients using PPIs.

Side effects of long-term use of proton pump inhibitors: practical considerations.

Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs due to the increasing incidence of acid‑related disorders, but a large number of prescriptions are issued with inappropriate indications. Despite PPIs being effective and well tolerated, there have been growing concerns about potential adverse effects associated with long‑term use of these drugs. Indeed, pharmacovigilance agencies have issued broad-based product warnings on the association between treatment with PPIs and long‑term complications, including increased risk of fractures and impaired magnesium absorption. On the contrary, despite plausible underlying biological mechanisms, the available clinical evidence for most side effects is weak or contradictory, and the benefits of PPI treatment seem to outweigh the potential adverse effects. This review aims to discuss the most important and established side effects of long-term use of PPIs and provide practical considerations for their clinical management.

Survey-Based Analysis of Current Trends for Prescribing Gastrointestinal Protectants among Small-Animal General Practitioners in Portugal.

In both human and veterinary healthcare, gastrointestinal protectants (GIPs) are considered a staple of clinical practice in that they are prescribed by general practitioners (GPs) and specialists alike. Concerning GIP use, overprescription of proton pump inhibitors (PPIs) has become a growing concern among human healthcare providers. This trend has also been documented within veterinary practice, prompting the American College of Veterinary Internal Medicine (ACVIM) to publish a consensus statement in 2018 concerning evidence-based indications for GIP use. This observational cross-sectional study evaluated self-reported prescribing protocols among Portuguese GPs to determine whether there is adherence to the consensus guidelines. Respondents were Portuguese GPs recruited by social media posts in veterinarian online forums. Data were collected from 124 respondents concerning their GIPs of choice and their rationales for prescribing them. Data were mined for prescription patterns and protocols. Among GIPs, PPIs were prescribed more often. Rationales for use included gastrointestinal ulceration and erosion (GUE), prophylactic management of nonerosive gastritis, pancreatitis, reflux esophagitis, and steroid-induced ulceration. Once-daily administration of PPIs was the most frequent dosing regime among respondents. Ninety-six percent of PPI prescribers advocated that the drug be administered either shortly before or at mealtime. Forty-nine percent of respondents supported long-term use of PPIs. Fifty-nine percent of respondents acknowledged discontinuing PPIs abruptly. This study supports that Portuguese GPs commonly prescribe GIPs in accordance with ACVIM recommendations to medically manage GUE. However, misuse of GIPs does occur, and they have been prescribed where their therapeutic value is debatable. Educational strategies should target GPs in an effort to reduce GIP misuse.

Is there acorrelation between hypomagnesemia linked to long-term proton pump inhibitor use and the active agent?

One of the electrolyte disorders considered to be linked to proton pump inhibitors (PPI) use is hypomagnesemia. The aim of this study was to assess the incidence of hypomagnesemia linked to long-term PPI use and the correlation with active agents. The study included 305patients aged over 18years with PPI use of 1 year or longer and attending the internal diseases clinic for any reason from April 2019 to December 2019. A survey study was performed about the demographic characteristics and PPI use of patients. Laboratory parameters, such as the hemogram, magnesium, phosphorus, calcium and vitamin B12 concentrations were recorded. Magnesium concentrations were measured by a colorimetric method. Of the patients 140 (45.9%) were female and 165 (54.1%) were male. The most commonly used PPI active agent was pantoprazole. The duration of PPI use varied from 1-25 years with a mean of 4.31 ± 4.52 years. Of the patients 51.5% reported no medication side effects. The most commonly observed side effect was constipation (n = 98, 32.1%). The mean magnesium concentration was 1.95 ± 0.02 mg/dL. Hypomagnesemia was identified in 65 (21.3%) patients and the incidence increased as age and duration of use increased. Patients using omeprazole had significantly lower magnesium levels compared to patients using pantoprazole, rabeprazole, esomeprazole and lansoprazole. In light of the data obtained it was concluded that hypomagnesemia linked to PPI use is associated with the type of PPI. While patients using rabeprazole had the lowest rates, those using omeprazole had significantly higher rates of hypomagnesemia. Additionally, there was a proportional correlation between age and duration of use with the risk of development of hypomagnesemia.

The risk of community-acquired pneumonia in children using gastric acid suppressants.

With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.

Use of Proton Pump Inhibitors vs Histamine 2 Receptor Antagonists for the Risk of Gastric Cancer: Population-Based Cohort Study.

Proton pump inhibitors (PPIs) are commonly prescribed medications. Long-term use of PPIs has been suspected to have a provocative effect on gastric cancer. This study was to determine the association between PPI vs histamine 2 receptor antagonist (H2RA) use and the risk of gastric cancer in a region where the risk of this malignancy is high. A population-based cohort study using the Korean National Health Insurance Services Database. The participants with first prescription of PPIs and H2RA with normal esophagogastroduodenoscopy finding from 2004 through 2015 were collected. Among them, 50% of participants were systematic stratified randomly sampled. There were 122,118 users of PPIs or H2RAs who use medication more than cumulative defined daily dose of 180 days. The users were followed up from long-term use threshold until gastric cancer, death from non-gastric cancer cause, gastric surgery, or study end (December 2017). After calculating propensity score weights, we included 39,799 PPI and 38,967 H2RA users. Among the new PPI and H2RA users, we identified 411 cases of incident gastric cancer from 182,643 person-years of follow-up observation and 397 cases from 178,846 person-years of follow-up observation, respectively. Compared with H2RA users, PPI users did not experience significantly different gastric cancer incidence (adjusted hazard ratio, 1.01; 95% confidence interval, 0.88-1.16; P = 0.89). Sensitivity analyses confirmed that gastric cancer incidence did not differ between PPI and H2RA users. In this large study, long-term treatment with PPIs vs H2RAs did not show higher risk of gastric cancer even in a high-risk region.

Association of proton pump inhibitor use with endothelial function and metabolites of the nitric oxide pathway: A cross-sectional study.

Long-term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition. We analyzed the association between regular daily PPI intake and flow-mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring. Data of 1298 participants from two independent cohorts of the population-based Study of Health in Pomerania were used. Participants of the population-based Study of Health in Pomerania are a stratified random sample of the study region. Regular daily intake of PPIs. FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine. Eighty-seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: -1.96 to -0.02) lower FMD and 3.03µmol/L (95% CI: -4.96 to -1.10) lower plasma citrulline levels as compared to non-users. Our data provide evidence that long-term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long-term PPI use.

Correlation of Long Term Proton Pump Inhibitors (PPI) Use with Iron and Vitamin B12 Deficiency Anaemia

The Suppression of gastric acid by long term use of PPI may decrease iron and vitamin B12 absorption and might be causing iron and vitamin B12 deficiency anaemia. This comparative cross-sectional study was conducted among patients with peptic ulcer disease from November 2017 to March 2020; attending in the Internal Medicine department of Bangabandhu Sheikh Mujib Medical University (BSMMU). A total of 80 patients were included and divided into group-A (PPIs user) and group-B (non-PPI user), each group containing 40 patients each. The group-A included patients who were taking PPIs for more than one year and aged from 18 to 70 years and group-B the control group who were not taking PPIs for atleast 1(one) year. The data were analysed by Statistical Package for the Social Sciences (SPSS) version 20.0 (SPSS Inc., Chicago, IL, USA).The study shown that male were 18(45%) and 19(47.5%) in group A and B respectively and female were 22(55%) and 21(52.5%) in group A and B respectively. The mean age of male and female was (year) 45.35 ± 12.46, 44.85 ± 15.24, respectively. Most of the patient took omeprazole 62.5% follwed by, esomeprazole 20%, pantoprazole 12.5%, rabeprazole 5%. About 47.5% of the patient took PPI for more than 2 years, and 52.5% took between 1-2 years. The mean (±SD) haemoglobin (Hb) level was 10.93±2.00 g/dl amongst group-A and 13.16±1.68g/dl in group-B, the difference is statistically significant (P&lt;0.001). The mean serum iron of the PPI users (group-A) was 46.43±22.79, and of non-PPI users (group-B) was 84.95±33.18, the difference between iron level between two group was statistically significant (odds ratio -6.38 ; CI-2.28-17.84 and P-value &lt;0.001). The PPI user group, mean vitamin B12 was 449±166.99 and in non-PPI group it was 432.85±175.93, which was statistically nonsignificant (P-value -1.00). Amongst all the participant low serum concentrations of iron, ferritin and transferrin were found 23(57.5%), 18(45%) and 27(67.5%), respectively in Group-A (PPI user group) and 7(17.5%), 7(17.5%) and 8(20%) respectively in Group-B (PPI-non user).The difference was statistically significant (p&lt;0.05) between the two groups. But the value of TIBC was found to be high in 36 (90.0%) participants in both groups, which was statistically non-significant(p=0.33). Hematocrit (HCT) were low in 35 (87.5%) participants in Group-A and 25(62.5%) in Group-B. The difference was statistically significant (p&lt;0.05). Low MCV was found in 10(25%) in the PPI user group and 4(10%) in the non-user group, whish was statistically non-significant. No significant differences in vitamin B12 concentrations (pg/ml) 449±166.99 vs 432.85±175.93 were found between groups A and group B, respectively. There was a weak negative Pearson’s correlation shown in ascatter diagram between duration of PPI use, and the iron level of group A (n=40) (r=-.311, p=.051). A negligible Pearson’s correlation was seen in the scatter diagram between the duration of PPI use, and vitamin B12 level of group A (r=+.05 p=.977). This study showed a significant decrease in haemoglobin, haematocrit, iron, ferritin, transferrin saturation in participants taking PPIs for more than one year, compared with age and gender-matched controls. No significant change of MCV, TIBC (Total Iron Binding Capacity) and vitamin B12 were noticed between groups. In conclusion, the study found a significant decrease in hematologic indices and iron profile among patients receiving PPIs for longer than one year. There was no substantial change of Vitamin B12 levels was detected between long-term PPIs users and non PPIs user groups. So, from the study it is suggested that judicial prescription of long-term PPIs must be practiced. However, the small sample size and short study duration were the limitation of the study.&#x0D; Bangladesh Med J. 2021 January; 50(1) : 27-32

Microscopic colitis: a guide for general practice.

Irritable bowel syndrome (IBS) affects 10%–20% of the population1 but other conditions have similar symptoms. Microscopic colitis is a cause of chronic, non-bloody, watery diarrhoea, particularly in older patients in whom the impact on quality of life can be significant. Microscopic colitis affects 0.12% of the population but 12.80% of those with unexplained chronic, watery diarrhoea. The median age at diagnosis is 60,2 reflecting an older population than those typically diagnosed with other types of inflammatory bowel disease. Risk factors include smoking and long-term use of proton-pump inhibitors, non-steroidal anti-inflammatory drugs, and selective serotonin reuptake inhibitors, although a causal relationship has not been established.2 The most common symptom in microscopic colitis is chronic, non-bloody, watery, diarrhoea, frequently associated with faecal urgency, the passage of stools at night, and faecal incontinence. Cramping abdominal pain may be present. These symptoms can be severe enough to make patients effectively housebound. Patients may …

Magnetic sphincter augmentation device placement for treatment of gastroesophageal reflux.

Gastroesophageal reflux disease typically is treated with lifestyle modifications and proton pump inhibitors (PPIs). Surgery is effective in treating the symptoms associated with gastroesophageal reflux, but common procedures involve invasive techniques that can leave the patient unable to belch or vomit. Research has raised concerns regarding the long-term use of PPIs, leaving few treatment options for patients with refractory reflux symptoms. The magnetic sphincter augmentation device demonstrates similar efficacy to existing antireflux procedures, avoids complex surgery techniques, and preserves normal physiologic functions at the lower esophageal sphincter. This device is a safe and effective alternative to more invasive procedures for patients whose GERD does not respond to medical management.

Patient Awareness of Reported Adverse Effects Associated with Proton Pump Inhibitors in a Medically Underserved Community.

Reports of adverse effects associated with proton pump inhibitors (PPIs) are concerning because of high usage and over-the-counter availability. We sought to determine the awareness of PPI adverse effects among our patient population, which is medically underserved, low-income, and racially diverse. A 21-item survey was administered to gastroenterology-clinic outpatients. It collected information about age, gender, education, race, specialty of the prescriber, specific PPI, indication, knowledge of dose, adherence, duration of use and awareness of any risks. Medical records were reviewed to verify survey responses pertaining to indication, dosing, and adherence. A vast majority (96%) of 101 participants were not aware of PPI adverse effects. In total, 63% of the patients completed a high school education or less, which was associated with a higher risk of long-term PPI use than completion of at least an undergraduate degree (p = 0.05). In contrast to other studies, the shockingly low patient awareness about PPI adverse effects in our patient population is particularly concerning, especially as it is tied to their demographic attributes. This may lead to long-term and high-dose PPI use. Our study highlights the need for effective provider-driven education regarding medication risks, especially in the communities with significant health disparities.

Long-term Continued Proton Pump Inhibitor Use is Common in Patients Diagnosed with Eosinophilic Esophagitis Despite Failure of Histologic Response: Data from a two-centre study: Long-term PPI Use in Patients with EoE.

Treatment paradigms for proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE) are evolving. We aimed to determine patterns of long-term PPI use after EoE diagnosis in PPI histologic non-responders. We conducted a retrospective review at University of Colorado (UCH) and University of North Carolina (UNC) of EoE patients who were histologic non-responders to PPIs. Data were extracted from electronic medical records related to demographics, PPI use, and reasons for continuing or stopping PPI. Of 67 patients in the UCH cohort, PPIs were initially discontinued in 9 (13%). Of 58 remaining on PPI, 48% were not instructed to discontinue therapy and 26% continued for symptom improvement. Of 675 patients at UNC, PPI was stopped in 185 (27%). Of patients remaining on PPI, 15% were not told to discontinue therapy and 62% were continued for symptom improvement. At last contact, >50% of patients remained on PPI at both centres with most common reasons for continuation being symptom improvement and not telling patients to discontinue. In the UNC cohort, clinical features associated with remaining on PPI included children younger than 18 years (p=0.01), males (p<0.001), heartburn symptoms (p<0.001) and hiatal hernia (p=0.004). Patients with dysphagia were less likely to remain on PPIs (p<0.001). Long-term PPI use is common in EoE patients even without histologic response. Failure to instruct patients to discontinue therapy was a common reason for long-term use, thus PPI use should be revisited in all EoE patients to confirm clinical benefit.

S2948 Long-Term Proton Pump Inhibitor-Induced Gastric Microcystic Glandular Changes Leading to Gastric Wall Thickening

INTRODUCTION: Long term (LT) proton pump inhibitor (PPI) induced gastric microcystic glandular mucosal changes could lead to significant gastric wall thickening which must be further evaluated to exclude underlying neoplastic process. CASE DESCRIPTION/METHODS: An 81-year-old male with GERD and Barrett’s esophagus (BE) on chronic omeprazole 40mg BID was evaluated by endoscopic ultrasound (EUS) for 1cm gastroesophageal junction (GEJ) sub epithelial lesion (SEL) seen on EGD and thickened gastric mucosa (2.6 cm) normalizing just proximal to GEJ identified on an otherwise negative CT abdomen done to evaluate for epigastric pain. EGD showed irregular carpet-like thickened gastric folds with cobble stoning sparing the gastric antrum. EUS showed a small cystic SEL at GEJ and marked diffuse thickening of gastric body mucosa (16 mm) with intact muscularis propria and absence of regional lymphadenopathy. Endoscopic biopsies revealed no H. pylori but gastric mucosa with microcystic glandular changes consistent with gastric mucosal trophic changes secondary to chronic PPI use. Due to BE however, patient was continued on PPI. DISCUSSION: PPIs remain the cornerstone for GERD treatment. Adverse effects from inappropriate PPI use are more clinically manifested in the elderly population. These include drug-drug interactions and increased risk of LT PPI adverse effects on digestive and extra-digestive organs (such as dementia, decreased bone density, and community acquired pneumonia). LT PPI use can lead to fundic gland polyp formation, small intestinal bacterial overgrowth, and collagenous colitis. Gastric trophic changes were found to occur secondary to LT PPI use in the form of parietal cell protrusion into the gastric lumen and fundic gland polyp formation resulting from increased serum gastrin level. Hypertrophic changes due to LT PPI induce gastric mucosal changes that can be appreciated endoscopically as gastric cobblestone-like lesions (GCLL). Sparing of the antrum in our patient of such changes can be explained by parietal cells being anatomically present in gastric fundic glands located primarily in the gastric fundus and body. Histopathology of gastric biopsies in these cases show fundic microcystic glandular change, parietal cell hyperplasia, and cytoplasmic vacuolation. A gastroenterologist should be familiar with such changes due to LT PPI use and, yet, must biopsy the gastric mucosa to exclude any underlying gastric infiltrative and neoplastic process.Figure 1.: Endoscopic view of gastric corpus showing thickened folds, carpet like polypoid lesions.Figure 2.: Radial EUS showing markedly thickened gastric mucosa and intact muscularis propria.Figure 3.: Histopathology of gastric corpus biopsies showing microcystic glandular conformation.

S2933 Vanishing Polyps: Can Switching From a PPI to an H2 Blocker Cause Regression of Fundic Gland Polyps?

INTRODUCTION: Fundic gland polyps (FGPs) are identified as a sequalae of prolonged acid suppression. Though some studies show that acid suppression with a proton pump inhibitor (PPI) or Histamine 2 receptor blockers (H2RB) may cause FGPs, stronger evidence supports PPIs as a culprit. Studies have shown improvement of FGPs with cessation of acid suppression, but few studies investigated the effect of changing therapy to an H2RB. This case demonstrates a reduction of polyp size and number upon transition to an H2RB in a patient who developed FGPs as a result of long-term PPI use. CASE DESCRIPTION/METHODS: An 85-year-old female with rheumatoid arthritis on methotrexate and prednisone and on chronic PPI for 15 years for acid reflux presented to the gastroenterology clinic for possible gastritis. Upper endoscopy was performed and showed multiple 5–50 mm pedunculated and sessile polyps throughout the entire stomach. A majority of the polyps were about 3–5 cm. A hot snare and a Roth net were used to remove polyps to confirm histopathology (Figure 1). Gastric biopsies revealed FGPs without evidence of H. pylori, intestinal metaplasia, dysplasia or malignancy. Despite concern for FAP, malignancy, or high-grade dysplasia, the patient elected for continued endoscopic surveillance. She transitioned from a PPI to an H2RB. Serial endoscopies showed marked improvement in the size and number of gastric polyps at 6-months (Figure 2) and at 1-year (Figure 3). DISCUSSION: Some studies have shown a 4 fold increased risk of FGP formation in patients on chronic PPI. These polyps likely form as a response to low acid production causing increased parietal cell growth due to increased gastrin and chromogranin-A circulation causing gland proliferation. Few case reports demonstrate improvement of polyp size and number with transitioning therapy from PPI to H2RB and no large trials support changing therapy to H2RB. Still, H2RBs may be an ideal alternative since studies have shown an improvement in polyp size with cessation of PPI. Though FGPs are benign, PPI may increase the risk of adenomatous polyps and biopsy is necessary to differentiate these, particularly in patients with FAP. Our case demonstrates that discontinuing PPI for H2RB may lead to a sheer reduction in both number of polyps and polyp size, making lesions more amenable to continued resection and sampling and, therefore decreasing and minimizing risk of malignancy.Figure 1.: Initial endoscopy showing multiple large Fundic Gland Polyps in patient on chronic PPI for 15 years.Figure 2.: Repeat Endoscopy 6 months after transitioning from PPI to H2RB and showing smaller and fewer number of Fundic Gland Polyps.Figure 3.: Repeat Endoscopy 1 year after transitioning to H2RB and demonstrating continued, marked improvement in the size and number of Fundic Gland Polyps.