Chronic Proton Pump Inhibitor Therapy Research Articles

Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease.

The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs). To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function. This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means. Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study. CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.

An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care.

Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH<inf>4</inf>) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients. One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH<inf>4</inf> producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH<inf>4</inf> producers. In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH<inf>4</inf> producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH<inf>4</inf> producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH<inf>4</inf> producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H<inf>2</inf> in SIBO patients and of 47.7% for CH<inf>4</inf> was assessed after rifaximin treatment (P<0.05). Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

S2343 Long-Term Omeprazole Use Causing Critical Electrolyte Derangements

Introduction: Proton-pump inhibitors (PPI) are the mainstay therapy for acid-related gastrointestinal entities. Longstanding PPI use is associated with an increased risk of adverse effects; however, clinically significant side effects, such as metabolic derangements, are rare. Here we highlight a case of critical electrolyte derangements secondary to prolonged omeprazole use. Case Description/Methods: A 61-year-old female with a history of hypertension and GERD presented with intermittent numbness for several months involving bilateral upper extremities. Exam showed no focal neurologic deficits with intact sensation and appropriate motor strength. CT head and cervical spine were unremarkable. Initial labs showed significant electrolyte derangements, including hypokalemia 3.3 mmol/L, hypocalcemia 5.7 mg/dL (0.64 mmol/L ionized), and hypomagnesemia 0.5 mg/dL. TSH, PTH, and 25-hydroxyvitamin D levels were intact (Table). EKG showed normal sinus rhythm with QTc prolongation at 542 ms. Despite aggressive intravenous repletion, her electrolytes remained suboptimal. After evaluation by endocrinology, her symptoms were thought to be secondary to PPI-induced hypomagnesemia. The patient had been taking omeprazole for nearly 20 years after evaluation by ENT for vocal cord hoarseness thought to be secondary to GERD. Patient was transitioned from PPI to an H2 blocker. She underwent EGD which showed mild gastritis with biopsies negative for Helicobacter pylori. Fortunately, her symptoms resolved after electrolyte stabilization with potassium 3.9 mmol/L, calcium 8.8 mg/dL, and magnesium 1.8 mg/dL. She was discharged on famotidine with instructions to follow up with gastroenterology. Discussion: Hypomagnesemia has become an increasingly well-recognized, albeit rare side effect of PPI use. The mechanism is thought to involve interference of TRPM6 and TRPM7 located on apical membranes of enterocytes leading to intestinal malabsorption with resulting hypomagnesemia as well as hypocalcemia and hypokalemia. Interestingly, manifestations of hypocalcemia and hypokalemia can be concealed by calcium and potassium-sparing agents, which was likely the case in our patient who was taking candesartan-hydrochlorothiazide combination therapy for hypertension. Our case demonstrates the importance of limiting chronic PPI therapy given the potential for serious consequences. Increased efforts should be aimed at deprescribing PPI therapy. Table 1. - Electrolyte derangements including hypokalemia, hypocalcemia, and hypomagnesemia, which remained suboptimal despite aggressive repletion. Electrolytes finally stabilized after switching from PPI to H2 blocker Day 0 Day 3 Day 5 Day 6 K+ (mmol/L) 3.3 3.2 3.8 3.9 Ca+2 (mg/dL) 5.7 6.6 7.8 9.5 Mg+2 (mg/dL) 0.5 1.6 1.7 1.6

Chronic Proton-Pump Inhibitor Therapy and Fracture Risk in Women Aged Between 50 and 65 years: A Retrospective Case-Control Study.

IntroductionChronic proton-pump inhibitor (PPI) prescription is on the rise in the last decade with an increased prevalence in the elderly population. For most patients, this class of drugs is the primary treatment for various diseases. Even though PPIs are generally safe, long-term use has been associated with multiple adverse effects like bone fractures. The extent of the association between PPI and fracture is still unclear in women aged between 50 and 65 years. Besides, many other variables and risk factors must be accounted for in the analysis of this relation.MethodsThis is a retrospective case-control study looking at women 50-65 years of age who presented to Genesys Health for a low-impact fall. Data were extracted from electronic medical records and fracture outcomes; PPI therapy exposure and duration were determined. Chi-square analysis was performed to determine the association between chronic PPI therapy and fracture outcome and independently analyzed for major risk factors of osteoporosis, including smoking, low body mass index, and cancer.ResultsPatients in the chronic PPI therapy group were found to have a decreased fracture outcome overall in each subcategory of risk factors. When adjusting for all risk factors, there was a significant but weak association between chronic PPI therapy and increased fracture outcome.ConclusionWith different results from previous studies, this study sheds new light on this debate. More studies need to be carried out to determine the association between chronic PPI therapy and fracture outcomes in postmenopausal women.

Factors associated with gastro-duodenal ulcer in compensated type 2 diabetic patients: a Romanian single-center study.

IntroductionHelicobacter pylori infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in countries with a high prevalence of infection. The aim of the study was to investigate the influence of H. pylori infection, medication, associated medical conditions or social habits on endoscopic ulcer occurrence in the compensated type 2 diabetic population.Material and methodsTwo hundred and sixty type 2 diabetic patients investigated on endoscopy (57 patients with peptic ulcer and 203 controls) with a complete set of biopsies, demographic and medical data were enrolled.ResultsOn univariate regression analysis, H. pylori infection (42.1% vs. 35.5%, p = 0.359) or a history of peptic ulcer (61.4% vs. 61.6%, p = 0.981) was not a predictor for ulcer on endoscopy in the diabetic population, and heartburn was more frequent in diabetics without ulcer (21.2% vs. 8.8%, p = 0.033). Anemia was the best predictor for ulcer on endoscopy in both diabetics with (p < 0.001, OR = 4.77, 95% CI: 2.02–11.28) and without (p = 0.027, OR = 2.76, 95% CI: 1.10–6.91) chronic proton pump inhibitor (PPI) therapy. In diabetic patients on PPI more than 1 month anticoagulants – acenocoumarol or low-weight molecular heparin (p = 0.038, OR = 2.37, 95% CI: 1.04–5.40), low-dose aspirin 75–125 mg/day (p = 0.029, OR = 2.61, 95% CI: 1.08–6.28) and alcohol consumption (p = 0.015, OR = 2.70, 95% CI: 1.19–6.13) were predictors for ulcer on endoscopy.ConclusionsIn diabetic patients, anemia is the most important predictor for ulcer on endoscopy, but not H. pylori or digestive symptoms, while low-dose aspirin or anticoagulant therapy and alcohol consumption are the most important predictors for ulcer in diabetics on chronic proton pump inhibitor therapy.

S1340 Risk of Acute Interstitial Nephritis in Patients on Chronic Proton Pump Inhibitor Therapy

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly prescribed medications. Studies suggest a link between PPI use and acute interstitial nephritis (AIN), however data is limited. Our primary aim was to evaluate the prevalence of AIN in patients on chronic PPI therapy. Our secondary aim was to compare the risk of AIN in patients on PPI compared to H2 blockers and compare adverse events (AE). METHODS: We performed a retrospective analysis in the IBM Explorys database 5 (1999-2020), a pooled, national, de-identified clinical database of over 72 million patients from 26 health care networks and 300 hospitals across the United States. Patient populations were identified using SNOMED and ICD codes. PPI included were esomeprazole, omeprazole, pantoprazole and lansoprazole. The development of AIN was evaluated after at least 6 months of PPI therapy. Patients on medications commonly implicated in AIN including NSAIDs, antibiotics, loop diuretic, H2 blockers, rifampin, and allopurinol were excluded from the study if prescribed within 30 days of development of AIN. Patients with systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, and Sjogren’s were also excluded. The control group was defined as patients on H2 blockers with the above exclusion criteria. AE were defined as ICU admission within 7 days, hemodialysis within 2 weeks, chronic kidney disease within 6 months, and end stage renal disease within 1 year. Odds ratios with 95% CI were calculated for risk of AIN for each PPI compared to the control group. Chi-squared test was used to compare the risk of AEs in the combined PPI group vs H2 blockers. RESULTS: The prevalence of AIN on chronic PPI therapy comprised 6.49% (n = 16130). Prevalence of AIN in lansoprazole was 28 (per 10,000), esomeprazole was 21 (per 10,000), omeprazole was 15 (per 10,000), and pantoprazole was 8 (per 10,000). Esomeprazole, omeprazole, and lansoprazole were associated with an increased risk of AIN when compared to the control. Lansoprazole had the highest associated risk for AIN (OR 2.53, 95% CI 2.38-2.70, followed by esomeprazole (OR 1.9, 95% CI 1.8-2.02), and then omeprazole (OR 1.32, 95% CI 1.26-1.39). Esomeprazole had a higher risk of ICU admission and new-onset CKD. Lansoprazole had a higher risk of ESRD. CONCLUSION: Most PPIs confer a higher risk of AIN compared to H2-blockers. Esomeprazole should be used with caution in patients at high risk for the development of CKD or ESRD. Future prospective studies are needed to validate these findings.Figure 1Figure 2

How to advise patients on the risk of chronic proton pump inhibitor therapy.

Proton pump inhibitors (PPIs) are widely prescribed and have excellent short-term tolerability. Administrative database studies have highlighted that many diseases are associated with PPI therapy including pneumonia, fracture, cardiovascular disease, and all-cause mortality. This review therefore reviews the evidence of the risks and benefits of these drugs. There is high-to-moderate quality evidence that PPIs are effective at treating many acid-related disorders. Recent randomized trials have suggested that the associations between PPIs and various diseases are likely to be related to bias and residual confounding and these drugs appear to be safe apart from a possible increased risk of enteric infections. PPIs should be used at the lowest dose and for the shortest duration possible. They are still relatively well-tolerated drugs but should only be prescribed for proven indications.

A Cross Sectional Clinical Study to Assess the Influence of Chronic Proton Pump Inhibitor Therapy on Serum Magnesium Levels

A Cross Sectional Clinical Study to Assess the Influence of Chronic Proton Pump Inhibitor Therapy on Serum Magnesium Levels

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study.

Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long‑term therapy. The effects of term PPI use have not been fully elucidated. We aimed to determine the association between long‑term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). We enrolled 37 patients on long‑ term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55] ×106/μl vs 4.7 [0.4] ×106/μl; P <0.001 and 6.13 [1.44] ×103/μl vs 7.3 [1.28] ×103/μl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g /dl vs 14.3 [0.8] g /dl; P <0.001 and 16.3 [5.4] μmol/l vs 23.4 [2.7] μmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. Long‑term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also aff ect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear.

Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients.

Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.

Effects of Chronic Proton-Pump Inhibitor Use on Kidney Function in Older Adults

OBJECTIVE: Proton-pump inhibitors (PPIs) have been associated with adverse renal outcomes in older adults; however, there are little data regarding the magnitude of the change in renal function in this population. The objective of this study was to quantify the change in kidney function associated with chronic PPI therapy at two years in older adults using estimated glomerular filtration rate (eGFR).<br/> DESIGN: The study was a retrospective, pre/post, observational cohort.<br/> SETTING/PATIENTS/INTERVENTIONS/MAIN OUTCOME MEASURE(S): The study included University of Colorado Health primary care patients 60 to 89 years of age who were newly initiated on a PPI between August 1, 2012, and March 1, 2015, and remained on therapy for at least two years. The primary outcome was the change in kidney function, measured by eGFR, two years after starting PPI therapy. Secondary outcomes included change in kidney function and incidence of reduction in eGFR to < 60 mL/min/1.73 m² two years post-index date between patients with and without diabetes mellitus.<br/> RESULTS: Of 877 electronic health records reviewed, 100 patients met inclusion criteria. The mean change in eGFR was -6.15 mL/min/1.73 m² (standard error of the mean = 1.03) at two years compared with baseline<br/> (95% confidence interval -8.20 to -4.10; P < 0.0001). There were no differences in the secondary outcomes based on concomitant diabetes mellitus.<br/> CONCLUSIONS: Chronic PPI use was associated with a significant reduction in eGFR in ambulatory older adults at two years, beyond that expected based on increased age alone. Prescribers should be aware of the potential adverse renal effects of chronic PPI use.

Use and Incidence of Adverse Effects of Proton Pump Inhibitors in Patients with Cystic Fibrosis.

To evaluate the incidence of adverse effects associated with chronic proton pump inhibitor (PPI) use as well as the dosing, indication, and duration of use of PPIs in the cystic fibrosis (CF) population at a pediatric academic medical center. Study design was a retrospective chart review evaluating patients with CF who were prescribed a PPI for at least 6months (PPI group) or patients with CF who had never been prescribed a PPI (control group) from June 1, 2014, to May 31, 2015. The study enrolled 126 patients in the PPI group and 49 patients in the control group. Forty-four patients (34.9%) had an indication for both gastroesophageal reflux and enzyme enhancement, with an average PPI daily dose of 1mg/kg/day. Twenty-one patients (16.7%) in the PPI group had an incidence of hypomagnesemia compared with one patient (2%) in the control group (p=0.097). Overall, 75 patients (59.6%) receiving chronic PPI therapy had at least one pulmonary exacerbation compared with 12 patients (24.5%) in the control group (p<0.001). No significant difference was noted in the incidence of hypocalcemia, low bone mineral density, or positive Clostridium difficile toxin between the two groups. The PPI group had a higher risk of pulmonary exacerbation compared with the control group. Further studies are needed to assess adverse effects associated with chronic PPI use in patients with CF.

Discontinuing Long-Term PPI Therapy: Why, With Whom, and How?

Proton pump inhibitors (PPIs) are among the most widely used class of drugs prescribed over the long term in all of clinical medicine with 8-10% of ambulatory adults have been prescribed a PPI in the past 30 days. However, numerous studies have raised doubts about the long term safety of PPI use. The purpose of this review is threefold: (i) To provide an overview of the current evidence demonstrating associations between PPI use and adverse health outcomes and the likelihood of the associations being causal (Why?); (ii) To be able to identify long-term PPI users in whom the intensity of PPI therapy could be reduced or in whom PPIs could be eliminated outright (Who?); and (iii) To provide strategies on how to reduce or stop chronic PPI therapy while maintaining symptom control and reducing the risk for symptom or upper GI disease recurrence (How?).

Abstract No. 627 Proton pump inhibitors are associated with increased risk of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt creation

Hepatic encephalopathy is the most common complication after transjugular intrahepatic portosystemic shunt (TIPS) creation. Although proton pump inhibitors (PPIs) are regarded as a class of medications with an excellent safety profile, recent data suggests that in cirrhotic patients PPIs may be associated with an increased risk of hepatic encephalopathy (HE), perhaps by altering microbial flora in the gastrointestinal tract with resultant changes in metabolites in portal blood. The purpose of this study was to determine whether PPI usage was associated with an increased risk of HE exacerbations after TIPS. In this single-institution retrospective study, 199 patients (58 females, mean age = 56) underwent TIPS creation between 1/1/2005 and 4/1/2012 for ascites or hydrothorax (129), variceal hemorrhage (61), or both (9). The medical record was reviewed to determine dates of postprocedure PPI usage and HE exacerbations, as defined by hospital admission for HE or escalation in outpatient medical management. Negative binomial regression was used to analyze the rate of HE exacerbations per person-day following TIPS. Among 105 patients on chronic PPI therapy from the time of TIPS until death, transplant, or loss to follow-up, 73 patients experienced 135 HE exacerbations in 56207 person-days. Among 51 patients never on PPIs after TIPS, 15 experienced 16 HE exacerbations in 19517 person-days, a significantly lower rate of HE exacerbations per person-day compared to PPI users (p<0.001). In multivariate regression, older age (p = 0.04), higher pre-TIPS MELD (p<0.001), and PPI usage (p<0.001) were independent predictors of HE exacerbations. The remaining 43 patients had intermittent PPI usage after TIPS. This independent crossover sample experienced 48 HE exacerbations during 32387 days on PPIs and 25 HE exacerbations during 26836 days off PPIs, a non-significant trend toward increased risk while on PPIs (p = 0.08). In this study PPI use was associated with more frequent HE exacerbations after TIPS creation. These results raise the possibility that discontinuation of non-essential PPIs may reduce the risk of HE following TIPS.

Chronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis

Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship. Several mechanisms have been suggested through in vitro studies (endothelial dysfunction, endothelial senescence, hypomagnesemia, increase of chromogranin A levels, decrease of nitric oxide in endothelial cells) leading to the impairment of vascular homesostasis, paving the way to these complications. Evidence that PPIs may have off-targets and pleiotropic effects are mounting and may impose a cautious attitude in the prescription of PPI's, especially in elderly and/or in the context of chronic use.

A Wolf in Sheepʼs Clothing: A Unique Case of Zollinger-Ellison Syndrome Masquerading as Ileal Crohnʼs Disease

Zollinger-Ellison Syndrome (ZES) often presents with peptic ulcer disease, symptoms of gastroesophageal reflux disease (GERD) and chronic diarrhea. This is the result of gastric acid hypersecretion secondary to ectopic gastrin production, typically, from a pancreatic or duodenal neuroendocrine tumour (NET). This report presents a unique case of a patient initially thought to have small bowel Crohn's disease (CD). Incidental discovery of a gastrinoma led to a diagnosis of ZES. A 57 year old male was referred to an outside gastroenterology clinic for evaluation and management of a longstanding history of dyspeptic symptoms and diarrhea. On review of his history, he had a repair of a perforated jejunal ulcer 3 years prior, presumed to have been related to intermittent use of non-steroidal anti-inflammatory drugs. He remained on chronic proton-pump inhibitor therapy, with adequate control of his dyspepsia. As part of his work-up for chronic diarrhea, he underwent upper endoscopy and colonoscopy. The upper tract was grossly normal, and biopsies showed mild chronic gastritis. Colonoscopy showed a grossly and histologically normal colon, but the terminal ileum could not be intubated. Subsequent CT enterography showed 2 fibrotic strictures of the distal ileum, leading to a diagnosis of Crohn's disease, and prompting referral to our Inflammatory Bowel Diseases Clinic. Incidental note was made of a 5cm mass at the tail of the pancreas, consistent with a probable NET, prompting immediate surgical referral. By the time of his presentation to our clinic, he was 2 months post the resection of his tumour, which was proven histologically to be a gastrin-producing NET. He reported complete resolution of his chronic diarrhea and dyspepsia. A diagnosis of ZES was entertained and a work-up for MEN-1 was initiated. Brain MRI demonstrated a 2 mm pituitary microadenoma, consistent with possible MEN-1. In the literature, 75% of gastrointestinal ulceration in ZES occur in the first portion of the duodenum with ulcers less likely in the distal duodenum and jejunum. There are no reports of ZES associated ulceration occurring in the ileum. This patient's ileal strictures are hypothesized to be secondary to ulcers due to the gastrinoma. This would offer a unifying diagnosis for this patient's findings and would explain the resolution of his symptoms with resection of his tumour.

Potential adverse effects of long term use of Proton Pump Inhibitors

Proton-Pump Inhibitors (PPIs) have changed the therapy of numerous upper gastrointestinal tract disorders; but their use is not without risk of adverse effects. Recent studies suggest more serious adverse events with chronic use of PPIs. Because of these risks, clinicians should reassess individual patient’s needs for chronic PPI therapy.

Effect of the Prophylactic Use of Proton-Pump Inhibitors on the Pattern of Gastrointestinal Symptoms in Patients Late After Kidney Transplant.

Although immunosuppressive drugs have been recognized as leading causes of gastrointestinal symptoms after kidney transplant, other widely used medications such as proton-pump inhibitors recently have been implicated. Our aim was to study the effects of chronic proton-pump inhibitor therapy on gastrointestinal symptoms in clinically stable patients late after kidney transplant. The study comprised 100 kidney transplant recipients (66 men and 34 women, mean age of 49 ± 12 y, mean time after transplant of 56 ± 46 mo). All patients completed the Gastrointestinal Symptoms Rating Scale and the Quality of Life Questionnaire SF-8 surveys. The most commonly reported symptoms included borborygmus (27%), flatulence (23%), abdominal distension (18%), urgent need of defecation (17%), and heartburn, acid reflux, and eructation (13%). Proton-pump inhibitors were chronically used by 50% of patients and sporadically by 33%. Gastrointestinal Symptoms Rating Scale scores were higher in patients who used proton-pump inhibitors (mean score of 7.8 ± 5.5 vs 4.6 ± 3.0; P = .013). Total score of items representing diarrhea in the Gastrointestinal Symptoms Rating Scale (increased passage of stools, loose stools, urgent need of defecation, incomplete evacuation) was higher in patients treated with proton-pump inhibitors than in those not treated (2.3 ± 2.2 vs 1.3 ± 1.9; P = .04). Chronic use of proton-pump inhibitors may increase the prevalence of gastrointestinal symptoms, particularly diarrhea, in patients late after kidney transplant.

A Gastric Carcinoid and Fundic Polyps in a Patient on Chronic Proton Pump Inhibitor Therapy: A Diagnostic Challenge

A Gastric Carcinoid and Fundic Polyps in a Patient on Chronic Proton Pump Inhibitor Therapy: A Diagnostic Challenge