Receiving Proton Pump Inhibitor Therapy Research Articles

Laparoscopic repair of a perforated marginal ulcer 2 years after gastric bypass

The authors present the case of a 43-year-old women who underwent a laparoscopic gastric bypass in 2003 for morbid obesity. They report that 2 years later, she had maintained significant weight loss, but had developed acute abdominal pain, followed by nausea and emesis. In the emergency room, she had diffuse tenderness, tachycardia, and leukocytosis. After initial resuscitation, a computed tomography was performed, which showed free air above the liver and thickened small bowel loops. She was brought emergently to the operating room for laparoscopy. At surgery, turbid fluid and inflamed small bowel loops were seen. A perforated marginal ulcer was discovered in the Roux limb, approximately 2 cm distal to the gastrojejunal anastomosis. The perforation was oversewn primarily and patched with omentum. The repair was tested by intraoperative endoscopy. A gastrostomy tube also was placed within the gastric remnant for enteral access. The patient did extremely well postoperatively, and had an uneventful postoperative course. She was discharged on postoperative day 4. The gastrostomy tube was removed at 1 month, and at this writing, she remains well since surgery. An upper endoscopy at 2 months was completely normal, and the Helicobacter pylori test results were negative. The gastric pouch had not significantly enlarged since initial surgery, as indicated by both endoscopy and barium study. Marginal ulcer is reported to be 0.6% to 16% after laparoscopic gastric bypass. Etiologies include gastrogastric fistula, excessively large gastric pouch containing antral mucosa, H. pylori infection, nonsteroidal antiinflammatory use, and smoking. Unfortunately, none of these applied to the reported patient. Because her exact etiology remains unknown, she at this writing continues to receive proton pump inhibitor therapy.

Long-Term Proton Pump Inhibitor Use in Children: A Retrospective Review of Safety

The objective of this work was to assess the efficacy of continuous proton pump inhibitor (PPI) therapy in children and to evaluate changes in biochemical, endoscopic, and histologic parameters during such treatment. A retrospective review of children receiving PPI therapy continuously for 1 year or more with baseline and follow-up esophageal and gastric biopsies on treatment was conducted to assess type, frequency, and duration of PPI dosing, symptom relief, gastrin levels, histologic findings, and adverse events. A total of 113 children (59 male, median age 4.5 years) were identified. Of these, 31% (35/113) were neurologically impaired. The median treatment duration was 35.2 months. Elevated serum gastrin levels occurred in 73% of children with no statistically significant differences in gastrin level by PPI type, dose, and dosing frequency or treatment duration. Adverse events were reported by 12% of children: diarrhea (5%) and constipation (4%) were the most frequent. Long-term PPI therapy appears to be effective, safe and well tolerated in children despite some biochemical, endoscopic, and histologic changes.

Proton Pump Inhibitors Improve Acid-Related Dyspepsia in Gastroesophageal Reflux Disease Patients

It has been reported that proton pump inhibitors are more effective than H2 receptor antagonists in patients with functional dyspepsia. Dyspeptic symptoms that respond to proton pump inhibitors are classified as acid-related dyspepsia. A new questionnaire for assessing gastroesophageal reflux disease (GERD), the Frequency Scale for Symptoms of GERD, covers the 12 most common symptoms of GERD patients. A quantitative assessment of the changes of reflux symptoms and acid-related dyspepsia was made in GERD patients receiving proton pump inhibitor therapy. Sixty-eight GERD patients receiving proton pump inhibitor therapy completed the questionnaire before and after treatment for 8 weeks. There is a significant positive correlation between reflux symptoms and acid-related dyspepsia before and after therapy (r = 0.569 and r = 0.569; both P's < 0.001) and acid-related dyspepsia in patients with both nonerosive and erosive GERD. We conclude that GERD patients suffer not only from reflux symptoms, but also from acid-related dyspepsia, and proton pump inhibitors improve both types of symptoms.

Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy

To assess the prevalence of oesophagitis, Barrett's oesophagus (BE) and other oesophageal mucosal abnormalities in patients with systemic sclerosis (SSc) without prior selection on digestive clinical presentation. We also investigated the association between oesophageal endoscopic and manometric data with clinical manifestations of SSc. Oesophageal endoscopy and manometry were performed in 133 consecutive patients with SSc, receiving proton pump inhibitor (PPI) therapy since SSc diagnosis. Endoscopy revealed oesophagitis in 43 patients (32.3%), BE in 9 patients (6.8%), candidiasis in 7 patients (5.3%) and hyperplastic polyp arising in ectopic gastric mucosa in 1 patient. Patients with severe oesophageal motor impairment further exhibited a higher prevalence of interstitial lung disease (ILD) when compared with those without. Our study underlines the high frequency of oesophageal mucosal abnormalities in unselected SSc patients receiving long-term PPI therapy. A relationship between oesophagitis/BE and severe manometric motor disturbances was established; these patients may require a higher regimen of PPI. Finally, our series indicates a correlation between severe oesophageal motor disturbances and evidence for ILD in patients, suggesting that gastro-oesophageal reflux may be one of the contributing factors of ILD in SSc; this subgroup of patients may require close monitoring of lung parameters.

Adéquation aux recommandations des prescriptions des inhibiteurs de la pompe à protons dans un service de médecine interne

Introduction Proton pump inhibitors (PPIs) are an efficient therapy, being widely used by physicians. In 2004, cost of PPIs' therapy was as high as 748 millions of euros (for The Caisse primaire d'Assurance Maladie) in France. Although validated indications of PPIs are well known, numerous un-necessary prescriptions of PPIs are common. The aim of this prospective study was to evaluate PPIs' prescriptions of patients in a department of internal medicine. Patients and methods This is a 12-week assessment of medical charts of patients, receiving PPI therapy in patients in our Department of internal medicine. Data were collected by a standardized questionnaire, with regards to: PPIs' nature and regimen, PPIs' indications as well as duration of therapy. Results The medical charts of 729 consecutive patients, with a mean age of 67 years, were collected. Two hundred (and) twenty-four patients (30.7%) received PPI therapy; 157 of these patients were given PPI before admission in our department. Omeprazole was used in 71% of patients. Duration of PPI therapy was over one year in 45% of cases. Thirty-five per cent of family physicians' PPI prescription were validated and 23.8% of those of physicians working in the department of internal medicine. The main non-conform PPI's indications, by family physicians and internists were as follows: prevention of hemorrhagic risk of anti-platelet agent (21 vs 16.4%), anticoagulant (17.8 vs 16.4%), steroids (8.3 vs 13.4%) or non-steroid anti-inflammatory therapy without risk factor (1.9 vs 9%). Finally, in patients receiving PPI therapy before admission, this therapy was maintained in 76% of cases. Conclusion This prospective study confirms the frequent prescription of PPI therapy in a department of internal medicine (31% of patients). It also underscores the importance of PPIs' use by family physicians and physicians working in a department of internal medicine; this series further highlights the difficulties to interrupt this well tolerated therapy. To date, PPI therapy should be prescribed with a cautious reweighted cost/benefit consideration.

Pre‐endoscopic proton pump inhibitor therapy reduces recurrent adverse gastrointestinal outcomes in patients with acute non‐variceal upper gastrointestinal bleeding

Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.

The Extent of Abuse of Proton Pump Inhibitor Therapy and Its Potential Consequences for the Patient and Impact on Health Care Costs

Purpose: Proton Pump Inhibitor (PPI) agents are relatively safe and highly effective in offering symptomatic relief in patients with GERD, as part of triple therapy for H. Pylori and as gastric protective agents during NSAID therapy. A prescription for a PPI is often initially given without much thought on its need and renewed with much less scrutiny for months. Aim: To evaluate the extent of abuse of PPI therapy in a medical clinic of a teaching institution. To analyze the financial impact of the abusive use of PPI therapy. Methods: A chart review of 500 consecutive patients was conducted for the number of prescriptions for any one of the PPI agents (Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole and Rabeprazole) and for their indication or the lack of it. Patients receiving PPI therapy were classified into three groups –Group 1– those who had a valid indication, Group 2– those who had a questionable indication (the Gray Zone – patients with nausea, vomiting, decreased appetite, abdominal pain of unknown etiology, viral/candida esophagitis, chronic dry cough) and Group 3– those who had no indication or even had achlorhydria. Results: Total number of patients on a PPI = 131 (26%)/500 The misuse of PPI therapy is anywhere between 15% to 42% (15% + 27%) (See Table 1)Table 1: GROUP RESULTS.Cost Analysis: The cost of therapy in: Group 3 = 20 patients X $4.94/day*=$36,062.00/year Group 2 =35 patients X $4.94/day*=$63,108.50/year Group 1 is not calculated since it was medically indicated. (*Mean cost of the available PPIs used once-daily. Prices from Walgreens.com effective 6/14/06). Conclusions: Once PPI therapy is initiated, for any reason, it is seldom discontinued. The financial impact on healthcare is substantial due to the high cost of PPI therapy. Potential side effects of PPI therapy, including increased susceptibility to C. Difficile colitis, Community Acquired Pneumonia, Vit. B12 malabsorption and Acute Interstitial Nephritis (AIN), are rarely assessed because of the feeling that PPIs are safe. Patients may be spending their limited resources on PPI therapy at the expense of other life saving medications.

Nonacid Reflux in Patients With Chronic Cough on Acid-Suppressive Therapy

It is generally accepted that extraesophageal gastroesophageal reflux disease (GERD) symptoms and their persistence despite acid-suppressive therapy are poor prognostic factors for antireflux surgery. Recent studies indicating that cough can be temporally associated with reflux episodes of pH 4 to 7 (ie, nonacid reflux) reinvigorates the need for a more careful workup in patients with cough suspected to be due to GERD. To evaluate the frequency of chronic cough associated with nonacid reflux and the response of these patients to laparoscopic Nissen fundoplication. We retrospectively reviewed data from patients with persistent cough despite twice-daily proton pump inhibitor (PPI) with or without the use of nighttime regimens of histamine-2 receptor antagonist (H2RA), who had undergone combined multichannel intraluminal impedance and pH monitoring. The association of cough and reflux was evaluated by calculating the symptom index (SI) [positive if > or = 50%]. A subset of patients with positive SI values for impedance-detected reflux with therapy was referred for laparoscopic Nissen fundoplication. Of 50 patients (38 female patients; mean age, 43 years; age range, 6 months to 84 years) who were monitored while receiving therapy, 13 patients (26%) had a positive SI for cough. The SI-positive group had a lower percentage of female patients and patients of younger age compared to the SI-negative group. Laparoscopic Nissen fundoplication was performed in six SI-positive patients who became asymptomatic and stopped receiving acid-suppressive therapy during follow-up evaluations (median time, 17 months; range, 12 to 27 months). Impedance pH monitoring should be performed while receiving therapy in patients with persistent symptoms who are receiving PPI therapy. A positive SI for nonacid reflux may be helpful in selecting patients who will benefit from antireflux surgery.

The Prevalence of Pantoprozole Associated Thrombocytopenia in a Community Hospital - A Retrospective Study.

Proton Pump Inhibitors (PPIs) are widely used in the treatment of peptic ulcer disease, Helicobacter pylori (H pylori) gastritis and gastro-esophageal reflux disease. PPIs are known to be relatively safe medications, with the most common adverse reactions reported as diarrhea, nausea, vomiting, abdominal pain and headache. Thrombocytopenia has not been found to be a significant side effect of PPI use. Furthermore, successful treatment of H pylori associated immune thrombocytopenic purpura (ITP) with PPI therapy has been reported in the literature. In clinical practice, however, PPI use has been thought to be associated with medication-induced thrombocytopenia, although the precise prevalence of this consequence has not been quantified. The purpose of this study is to determine the prevalence of thrombocytopenia in hospitalized patients treated with pantoprazole, a commonly prescribed PPI, compared to non-medicated controls. In this retrospective, case-controlled analysis, we analyzed the platelet counts of 626 patients between 18 and 80 years of age who were admitted to an urban, community-based hospital and were medicated with pantoprazole for at least three days during their hospital stay. Thrombocytopenia was defined as a drop in the platelet count to below 150,000/ml, or a drop of at least 50% from baseline. Patients who had a platelet count below 150,000/ml on admission or were hospitalized for less than 3 days were excluded from the study. A control group of 560 patients with the same inclusion criteria who had not been prescribed pantoprazole was analyzed for comparison. 626 patients were included in the study group and 560 patients in the control group. The median age was 67 years in study group, and 61 years in the control group. The mean platelet count on admission was 260,00/ml in the study group, and 257,000/ml in the control group. Of the subject group, 39 patients (6.2%) met our definition of thrombocytopenia, which was not statistically different from the 35 patients (6.2%) with thrombocytopenia in the control group (p=0.90). Our study compared patients who received PPI therapy with pantoprazole for at least three hospital days to patients without treatment. We found no difference in the rate of thrombocytopenia between hospitalized patients treated with pantoprazole and the non-medicated controls. The rate of thrombocytopenia that we observed is probably an estimate of the overall thrombocytopenia rate in hospitalized patients irrespective of specific medications. While our report did not control for variables such as concurrent medication use, comorbid illnesses, and patient demographics, we are confident that the sample size selected for this study is large enough to provide sufficient evidence that thrombocytopenia is not a significant side effect of pantoprazole therapy.

Oesophageal and gastric pH profiles in patients with gastro-oesophageal reflux disease and Barrett's oesophagus treated with proton pump inhibitors.

Acid plays a significant role in the development of gastro-oesophageal reflux symptoms and tissue damage. It is generally assumed that acid suppressive therapy with proton pump inhibitors improves or eliminates symptoms of gastro-oesophageal reflux disease by normalizing intra-oesophageal pH. However, the degree of acid suppression induced by proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease and/or Barrett's oesophagus has not been adequately studied. To assess the efficacy of proton pump inhibitors in normalizing intra-oesophageal and intra-gastric pH in patients with gastro-oesophageal reflux disease with and without Barrett's oesophagus who have been rendered symptom-free by acid-suppressive therapy. Patients with gastro-oesophageal reflux disease and Barrett's oesophagus were prospectively evaluated by dual sensor 24-h pH monitoring while receiving proton pump inhibitor therapy for complete control of gastro-oesophageal reflux disease symptoms. Analyses and comparisons of intra-oesophageal and intra-gastric pH profiles on therapy were then made. One hundred and ten patients, 98 men and 12 women, with gastro-oesophageal reflux disease (n = 62) and/or Barrett's oesophagus (n = 48), were studied. All tolerated proton pump inhibitors well and were asymptomatic at the time of the study. Thirty-six (58%) patients with gastro-oesophageal reflux disease and 24 (50%) patients with Barrett's oesophagus (P = 0.4) normalized their intra-oesophageal pH profiles on proton pump inhibitors. Compared with patients with gastro-oesophageal reflux disease, patients with Barrett's oesophagus were more likely to have higher degree of pathologic acid reflux despite proton pump inhibitor therapy (DeMeester score 50.5 +/- 8.2 vs. 31.4 +/- 4.6, P = 0.03) and exhibited less intra-gastric acid suppression (% total pH < 4.0: 53.9 +/- 2.7 vs. 39.9 +/- 2.6, P = 0.0004), particularly supine (% pH < 4.0: 62.1 +/- 3.4 vs. 44.8 +/- 3.4, P = 0.0006). Gastro-oesophageal reflux disease patients with or without Barrett's oesophagus continue to exhibit pathologic gastro-oesophageal reflux disease and low intra-gastric pH despite proton pump inhibitor therapy that accomplishes complete reflux symptom control. Further, intra-oesophageal and intra-gastric pH control is significantly more difficult to achieve in patients with Barrett's oesophagus. These findings may have significant therapeutic implications.

Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal and intragastric pH in patients with gastroesophageal reflux disease (GERD).

Acid plays a significant role in the development of gastroesophageal reflux symptoms, such as heartburn and regurgitation. It is generally assumed that acid suppressive therapy improves or eliminates symptoms by normalizing intraesophageal pH. The aim of this article was to assess the efficacy of proton-pump inhibitors (PPIs) in normalizing intraesophageal and intragastric pH in patients with GERD without Barrett's esophagus (BE) rendered symptom free by therapy. Patients were evaluated by dual-sensor 24-h pH monitoring while receiving PPI therapy for complete control of GERD symptoms. Analyses of intraesophageal and intragastric pH profiles were then made. Fifty patients, 39 men and 11 women, with GERD, without BE, were studied. All tolerated PPIs well and were asymptomatic at the time of the study. Fifty percent of patients had abnormal intraesophageal pH profiles despite adequate symptom control on PPIs, which was associated with significant breakthrough of intraesophageal acid control in both the upright and supine positions. Low intragastric pH correlated highly with intraesophageal acid reflux only in patients with persistent abnormal esophageal acid exposure (p= 0.001). Fifty percent of patients with GERD without BE continue to exhibit pathologic GERD and low intragastric pH despite PPI therapy that achieves complete reflux symptom control.

Persistent acid and bile reflux in asymptomatic patients with Barrett esophagus receiving proton pump inhibitor therapy.

Symptom control does not reflect elimination of abnormal acid reflux or abnormal bile reflux in patients with long-segment Barrett esophagus receiving proton pump inhibitors (PPIs). Prospective survey. University hospital. Thirty-two patients with long-segment Barrett esophagus who were asymptomatic with PPIs. Twenty-four-hour ambulatory pH and bile reflux monitoring while continuing PPIs. Abnormal acid reflux (pH <4 for 11.9% [interquartile range, 6.8%-19.6%) of 24 hours] persisted in 15 patients (47%) who could not be distinguished from those with normal acid reflux (pH <4 for <4.5% of 24 hours) by any endoscopic, manometric, or therapeutic characteristic. Abnormal bile reflux (absorbance >0.14 for 8.7% [interquartile range, 3.9%-8.7%] of 24 hours) was detected in 11 (48%) of 23 patients, such that both normal bile reflux (absorbance >0.14 for <1.8% of 24 hours) and normal acid reflux were observed in only 8 patients (35%). There was no association between abnormal acid reflux and abnormal bile reflux. Despite symptom control with PPIs, both acid reflux and bile reflux were controlled in only one third of patients. Posttherapeutic monitoring of acid and bile reflux is recommended in future clinical trials of PPI treatment vs laparoscopic antireflux surgery.

Granular Cell Tumor of the Esophagus: Report of a Pediatric Case and Literature Review

Granular Cell Tumor of the Esophagus: Report of a Pediatric Case and Literature Review

What’s New

What’s New

Fundic gland polyps are not induced by proton pump inhibitor therapy.

It is still unclear whether proton pump inhibitors (PPIs) could cause fundic gland polyps (FGPs) in patients without Helicobacter pylori infection. The frequency of FGPs in patients during PPI therapy has not been compared, however with a control group of patients who did not have H. pylori infection and were not undergoing PPI treatment. In a retrospective 12-month study, the frequency of FGPs in 2,251 patients without H. pylori infection receiving PPI therapy (duration of treatment at least 4 weeks) was compared with a control group of 28,096 patients who did not have H. pylori infection and were not receiving PPI therapy. FGPs were identified with an identical frequency in both groups (5.0% in the control and 5.2% in the PPI group). No significant differences were present between the groups with respect to the presence of gastritis or age or sex. Our study shows that a causal pathogenetic relationship between PPI therapy and FGPs is unlikely.

Prevention of the neoplastic progression of Barrett's oesophagus by endoscopic argon beam plasma ablation.

Patients with Barrett's oesophagus have a risk of approximately 1 per 100 patient-years for the development of oesophageal adenocarcinoma. Endoscopic ablation of Barrett's oesophagus has been shown to lead to the regrowth of a 'neo' squamous epithelium if gastro-oesophageal reflux is controlled, but the incidence of subsequent tumour formation is unknown. The follow-up of 55 patients who underwent endoscopic ablation of Barrett's oesophagus by argon beam plasma coagulation (ABPC) is reported. Of the 55 patients, nine had low-grade dysplasia, nine had high-grade dysplasia and the remainder had non-dysplastic Barrett's metaplasia. Twelve patients had reflux control by antireflux surgery and the remainder received proton pump inhibitor therapy. Barrett's metaplasia was ablated by ABPC to within 2 cm of the gastro-oesophageal junction. To date, one patient has died and one patient was unable to complete treatment. The remaining patients were followed by regular endoscopic surveillance for a mean of 38.5 months to give a total follow-up of 173.5 patient-years. No malignancy has developed in any patient during follow-up. The absence of malignant complications in this study of prophylactic ablation of long-segment Barrett's oesophagus strengthens the argument for endoscopic ablation in the prevention of oesophageal adenocarcinoma.