User login
Increased risk of death seen in PPI users
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2-receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, MPH, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2-receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2-receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total had only a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
The authors declared no relevant financial conflicts of interest.
Review AGA’s “Guide to Conversations About the Latest PPI Research Results” for tips on talking with your patients about this research study.
Idarucizumab reversed dabigatran completely and rapidly in study
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
One IV 5-g dose of idarucizumab completely, rapidly, and safely reversed the anticoagulant effect of dabigatran, according to final results for 503 patients in the multicenter, prospective, open-label, uncontrolled RE-VERSE AD study.
Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group of 202 patients, 197 were able to undergo urgent procedures after a median of 1.6 hours, Charles V. Pollack Jr., MD, and his associates reported at the International Society on Thrombosis and Haemostasis congress. The report was simultaneously published in the New England Journal of Medicine.
Idarucizumab was specifically developed to reverse the anticoagulant effect of dabigatran. Many countries have already licensed the humanized monoclonal antibody fragment based on interim results for the first 90 patients enrolled in the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) study (NCT02104947), noted Dr. Pollack, of Thomas Jefferson University, Philadelphia.
The final RE-VERSE AD cohort included 301 patients with uncontrolled gastrointestinal, intracranial, or trauma-related bleeding and 202 patients who needed urgent procedures. Participants from both groups typically were white, in their late 70s (age range, 21-96 years), and receiving 110 mg (75-150 mg) dabigatran twice daily. The primary endpoint was maximum percentage reversal within 4 hours after patients received idarucizumab, based on diluted thrombin time and ecarin clotting time.
The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100% to 100%) in more than 98% of patients, and the effect usually lasted 24 hours. Among patients who underwent procedures, intraprocedural hemostasis was considered normal in 93% of cases, mildly abnormal in 5% of cases, and moderately abnormal in 2% of cases, the researchers noted. Seven patients received another dose of idarucizumab after developing recurrent or postoperative bleeding.
A total of 24 patients had an adjudicated thrombotic event within 30 days after receiving idarucizumab. These events included pulmonary embolism, systemic embolism, ischemic stroke, deep vein thrombosis, and myocardial infarction. The fact that many patients did not restart anticoagulation could have contributed to these thrombotic events, the researchers asserted. They noted that idarucizumab had no procoagulant activity in studies of animals and healthy human volunteers.
About 19% of patients in both groups died within 90 days. “Patients enrolled in this study were elderly, had numerous coexisting conditions, and presented with serious index events, such as intracranial hemorrhage, multiple trauma, sepsis, acute abdomen, or open fracture,” the investigators wrote. “Most of the deaths that occurred within 5 days after enrollment appeared to be related to the severity of the index event or to coexisting conditions, such as respiratory failure or multiple organ failure, whereas deaths that occurred after 30 days were more likely to be independent events or related to coexisting conditions.”
Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, Bristol-Myers Squibb/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators also disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
FROM 2017 ISTH CONGRESS
Key clinical point:
Major finding: Uncontrolled bleeding stopped a median of 2.5 hours after 134 patients received idarucizumab. In a separate group, 197 patients were able to undergo urgent procedures after a median of 1.6 hours.
Data source: A multicenter, prospective, open-label study of 503 patients (RE-VERSE AD).
Disclosures: Boehringer Ingelheim Pharmaceuticals provided funding. Dr. Pollack disclosed grant support from Boehringer Ingelheim during the course of the study and ties to Daiichi Sankyo, Portola, CSL Behring, BMS/Pfizer, Janssen Pharma, and AstraZeneca. Eighteen coinvestigators disclosed ties to Boehringer Ingelheim and a number of other pharmaceutical companies. Two coinvestigators had no relevant financial disclosures.
Persistently nondysplastic Barrett’s esophagus did not protect against progression
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Current practice guidelines recommend endoscopic surveillance in Barrett’s esophagus (BE) patients to detect esophageal adenocarcinoma (EAC) at an early and potentially curable stage.
As currently practiced, endoscopic surveillance of BE has numerous limitations and provides the impetus for improved risk-stratification and, ultimately, the effectiveness of current surveillance strategies. Persistence of nondysplastic BE (NDBE) has previously been shown to be an indicator of lower risk of progression to high-grade dysplasia (HGD)/EAC. However, outcomes studies on this topic have reported conflicting results.
Where do we stand with regard to persistence of NDBE and its impact on surveillance intervals? Future large cohort studies are required that address all potential confounders and include a large number of patients with progression to HGD/EAC (a challenge given the rarity of this outcome). At the present time, based on the available data, surveillance intervals cannot be lengthened in patients with persistent NDBE. Future studies also need to focus on the development and validation of prediction models that incorporate clinical, endoscopic, and histologic factors in risk stratification. Until then, meticulous examination techniques, cognitive knowledge and training, use of standardized grading systems, and use of high-definition white light endoscopy are critical in improving effectiveness of surveillance programs in BE patients.
Sachin Wani, MD, is associate professor of medicine and Medical codirector of the Esophageal and Gastric Center of Excellence, division of gastroenterology and hepatology, University of Colorado at Denver, Aurora. He is supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program and is a consultant for Medtronic and Boston Scientific.
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
Patients with at least five biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to high-grade dysplasia or esophageal adenocarcinoma as patients with a single such biopsy, according to a multicenter prospective registry study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: org/10.1016/j.cgh.2017.02.019).
The findings, which contradict those from another recent multicenter cohort study (Gastroenterology. 2013;145[3]:548-53), highlight the need for more studies before lengthening the time between surveillance biopsies in patients with nondysplastic Barrett’s esophagus, Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., wrote with his associates.
Barrett’s esophagus is the strongest predictor of esophageal adenocarcinoma, but studies have reported mixed results as to whether the risk of this cancer increases over time or wanes with consecutive biopsies that indicate nondysplasia, the researchers noted. Therefore, they studied the prospective, multicenter Mayo Clinic Esophageal Adenocarcinoma and Barrett’s Esophagus registry, excluding patients who progressed to adenocarcinoma within 12 months, had missing data, or had no follow-up biopsies. This approach left 480 subjects for analysis. Patients averaged 63 years of age, 78% were male, the mean length of Barrett’s esophagus was 5.7 cm, and the average time between biopsies was 1.8 years, with a standard deviation of 1.3 years.
A total of 16 patients progressed to high-grade dysplasia or esophageal adenocarcinoma over 1,832 patient-years of follow-up, for an overall annual risk of progression of 0.87%. Two patients progressed to esophageal adenocarcinoma (annual risk, 0.11%; 95% confidence interval, 0.03% to 0.44%), while 14 patients progressed to high-grade dysplasia (annual risk, 0.76%; 95% CI, 0.45% to 1.29%). Eight patients progressed to one of these two outcomes after a single nondysplastic biopsy, three progressed after two such biopsies, three progressed after three such biopsies, none progressed after four such biopsies, and two progressed after five such biopsies. Statistically, patients with at least five consecutive nondysplastic biopsies were no less likely to progress than were patients with only one nondysplastic biopsy (hazard ratio, 0.48; 95% CI, 0.07 to 1.92; P = .32). Hazard ratios for the other groups ranged between 0.0 and 0.85, with no significant difference in estimated risk between groups (P = .68) after controlling for age, sex, and length of Barrett’s esophagus.
The previous multicenter cohort study linked persistently nondysplastic Barrett’s esophagus with a lower rate of progression to esophageal adenocarcinoma, and, based on those findings, the authors suggested lengthening intervals between biopsy surveillance or even stopping surveillance, Dr. Krishnamoorthi and his associates noted. However, that study did not have mutually exclusive groups. “Additional data are required before increasing the interval between surveillance endoscopies based on persistence of nondysplastic Barrett’s esophagus,” they concluded.
The study lacked misclassification bias given long-segment Barrett’s esophagus, and specialized gastrointestinal pathologists interpreted all histology specimens, the researchers noted. “The small number of progressors is a potential limitation, reducing power to assess associations,” they added.
The investigators did not report funding sources. They reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Patients with multiple consecutive biopsies showing nondysplastic Barrett’s esophagus were statistically as likely to progress to esophageal adenocarcinoma or high-grade dysplasia as those with a single nondysplastic biopsy.
Major finding: Hazard ratios for progression ranged between 0.00 and 0.85, with no significant difference in estimated risk among groups stratified by number of consecutive nondysplastic biopsies (P = .68), after controlling for age, sex, and length of Barrett’s esophagus.
Data source: A prospective multicenter registry of 480 patients with nondysplastic Barrett’s esophagus and multiple surveillance biopsies.
Disclosures: The investigators did not report funding sources. They reported having no conflicts of interest.
VIDEO: LINX magnetic band beats omeprazole for GERD regurgitation
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
CHICAGO – Persistent reflux symptoms resolved in 93% of patients who underwent laparoscopic deployment of a circlet of magnet beads to the lower esophageal juncture, but in just 9% of those who doubled their dose of omeprazole, Reginald Bell, MD, said at the annual Digestive Disease Week®.
In addition to bolstering positive device data, the results of this ongoing randomized study suggest that it may be time to rethink the treatment algorithm for patients who don’t respond optimally to medical therapy, Dr. Bell said in an interview.
“We found that relatively few patients respond well to the typical doubling of PPIs,” said Dr. Bell of the SOFI SurgOne Foregut Institute, Englewood, Colo. “In light of these strong results, it’s my opinion that we should consider going straight to surgery for at least some of these patients”
The LINX Reflux Management System (TORAX Medical; Shoreview, Minn.) is a small, flexible band of interlinked titanium beads with magnetic cores. The magnetic attraction between the beads keeps them joined when the lower esophageal sphincter is at rest. It exerts just enough resistance, however, to keep the sphincter from opening under gastric pressures of less than about 20 mm Hg, preventing reflux into the esophagus. Reflux typically occurs at an opening pressure of 10-12 mm Hg. Swallowing pressures, however, generally exceed 20 mm Hg, Dr. Bell said, allowing the circlet to expand enough to allow free passage of the bolus. The magnetic forces then bring the beads back together, again keeping the sphincter in a closed position.
This variable pressure is a big advantage over the Nissen fundoplication, which creates a pseudoflap that isn’t as yielding to intragastric pressure, Dr. Bell said. Nissen patients frequently have trouble belching or vomiting, and can experience bloating and distention from a reduced ability to vent gases. That is generally not a problem with LINX patients. And while some do initially experience dysphagia, this is typically transient. In the pivotal trial, bloating occurred in 7% of patients by 24 months.
The study comprised 150 patients with persistent symptoms of gastroesophageal reflux disease (GERD), despite at least 8 weeks of taking 20 mg omeprazole daily. These patients were randomized on a 2:1 scheme to either a doubling of omeprazole (20 mg twice a day) or surgery with LINX. Dr. Bell reported 6-month outcomes on 80 patients, 25 of whom had the LINX procedure and 55 of whom began double-dose omeprazole.
These patients were a mean of 47 years old, and had used a proton pump inhibitor (PPI) for a mean of 8 years. Baseline work-ups confirmed moderate to severe GERD, with about 12% of gastric measurement times at less than pH 4. The mean DeMeester Score was about 40. On the GERD Health-Related Quality of Life Questionnaire, patients scored about 24 while on medical therapy and 31 while off. They reported moderate to severe heartburn and regurgitation.
The study’s primary endpoint was relief of moderate to severe regurgitation. This was reached in 93% of the LINX group and 9% of the double-dose PPI group – a significant difference. Significantly more LINX patients also achieved at least a 50% reduction in their baseline GERD-HRQL score (90% vs.7%). The mean score dropped from about 32-5 in the LINX group and 30-24 in the PPI group.
Mean scores on the Reflux Disease Questionnaire improved significantly more in the LINX group than in the PPI group, including regurgitation (4.2.-1.4; 4.4 at both time points), and heartburn (3.4-1.6; 3.6-3.9).
An independent, blinded laboratory conducted pH/impedance testing on the cohort; the normal values were less than 57 reflux episodes/24 hours. At 6 months, the LINX group experienced a mean of 30 episodes vs. 70 in the PPI group.
When the investigators examined a combined measure of the number of reflux episodes and the change in DeMeester scores, they found normal reflux in 92% of the LINX group and 36% of the PPI group.
There was one adverse event related to the LINX procedure. A 66-year-old man was hospitalized and medically treated for esophageal spasms. The incident resolved with no sequelae, Dr. Bell said. So far, one LINX patient has needed to add PPI therapy; other studies typically show that 2%-3% of patients with the device do so.
Dr. Bell disclosed that he is a consultant for TORAX.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_gal
AT DDW 2017
Key clinical point:
Major finding: Symptoms resolved in 93% of patients, compared to 9% of those who took the proton pump inhibitor.
Data source: An ongoing randomized study of 150 patients; Dr. Bell reported 6-month outcomes on 80.
Disclosures: Dr. Bell is a consultant for TORAX Medical, which developed and manufactures the device.
Misoprostol effective in healing aspirin-induced small bowel bleeding
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
AT DDW
Key clinical point: Misoprostol was more effective than placebo in healing small bowel ulcers in patients who used daily low-dose aspirin.
Major finding: 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
Data source: An 8-week, double-blind, randomized placebo-controlled trial of 72 patients that assessed misoprostol vs. placebo for healing small bowel ulcers.
Disclosures: The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
Three clinical disorders confound diagnosis of gastroparesis
PHILADELPHIA – Particularly in adults, there are three conditions that produce symptoms consistent with idiopathic gastroparesis and should be specifically considered in a detailed history conducted before advanced diagnostic tests, according to a clinical update at the Fourth Annual Digestive Diseases: New Advances meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.
The three disorders “are very important, because we see them missed all the time,” reported Anthony J. Lembo, MD, director of the GI Motility Laboratory, Beth Israel Deaconess Medical Center, Boston.
“If you do not take a detailed enough history or if the patient is not willing to tell you about their past history, there is a good chance that these will go undetected,” Dr. Lembo explained. In his update on gastroparesis, he identified the recognition of these disorders as the most important clinical pearl of his overview of the challenges faced when evaluating the highly nonspecific symptoms of delayed–bowel transit time.
“Rumination syndrome has a very classic set of symptoms. When the patient swallows food, it will almost immediately or very quickly come back up. Sometimes the food is vomited. Often, it gets swallowed back down. That is not gastroparesis,” Dr. Lembo explained. Although vomiting after eating is a common symptom of gastroparesis, it is typically delayed by hours.
Cyclical vomiting syndrome, perhaps more readily recognized in children, does occur in adults more than many clinicians appreciate, according to Dr. Lembo. He said that there is one key giveaway for this condition: patients are asymptomatic between episodes. He also said that episodes are separated by substantial intervals of weeks to months.
Symptoms associated with cannabinoids are most commonly observed in young men frequently using marijuana over an extended period, according to Dr. Lembo. He said reports that symptoms are improved with hot showers may be a clue that marijuana is involved in the etiology. Urine tests are useful when patients suspected of marijuana use deny this history.
The problem is that, even when cannabinoid use is isolated as the cause of bowel symptoms, many patients are convinced that their symptoms improve, rather than get worse, with marijuana use. This is a common obstacle to the abstention needed to evaluate benefit, according to Dr. Lembo.
As for other possible etiologies, Dr. Lembo advised upper endoscopy to rule out mechanical causes of gastroparesis, such as peptic ulcer disease, proximal bowel obstruction, or gastrointestinal cancer. He specifically recommended scoping to the “third portion of the duodenum” when obstruction is being considered in the differential diagnosis.
When gastroparesis is considered the most likely cause of symptoms, Dr. Lembo recommended a gastric-emptying study to increase confidence in the diagnosis. He identified 4-hour scintigraphy as the standard of care, as defined by current guidelines. However, he warned that even well-regarded centers do not always follow this standard. Based on the lower sensitivity and specificity of shorter duration tests and of other options such as breath tests or wireless motility capsules, clinicians “should really insist” on the 4-hour gastric-emptying test when they are concerned about documentation, he said.
Once the diagnosis has been made, there are numerous therapeutic options, but the top three are “diet, diet, and diet,” according to Dr. Lembo. In his review of prokinetic drugs, such as metoclopramide and motilin agonists, he cautioned that there is often a delicate balance between risk and benefit. New options on the horizon include a ghrelin agonist that showed promise in a phase III trial, but he noted that many patients with severe unremitting symptoms are prepared to try almost anything.
“These can be desperate people when they have failed everything that is out there,” Dr. Lembo noted. He acknowledged that such patients express interest even in strategies that have failed to show convincing benefit in controlled trials, such as botulism toxin injection and neuroenteric gastric stimulators. When all other options have been exhausted, a referral to a specialist for experimental therapies may be appropriate because of the major adverse impact of unremitting symptoms on quality of life.
Dr. Lembo reported financial relationships with Alkermes, Allergan, Forest, Ironwood, Prometheus, and Salix.
PHILADELPHIA – Particularly in adults, there are three conditions that produce symptoms consistent with idiopathic gastroparesis and should be specifically considered in a detailed history conducted before advanced diagnostic tests, according to a clinical update at the Fourth Annual Digestive Diseases: New Advances meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.
The three disorders “are very important, because we see them missed all the time,” reported Anthony J. Lembo, MD, director of the GI Motility Laboratory, Beth Israel Deaconess Medical Center, Boston.
“If you do not take a detailed enough history or if the patient is not willing to tell you about their past history, there is a good chance that these will go undetected,” Dr. Lembo explained. In his update on gastroparesis, he identified the recognition of these disorders as the most important clinical pearl of his overview of the challenges faced when evaluating the highly nonspecific symptoms of delayed–bowel transit time.
“Rumination syndrome has a very classic set of symptoms. When the patient swallows food, it will almost immediately or very quickly come back up. Sometimes the food is vomited. Often, it gets swallowed back down. That is not gastroparesis,” Dr. Lembo explained. Although vomiting after eating is a common symptom of gastroparesis, it is typically delayed by hours.
Cyclical vomiting syndrome, perhaps more readily recognized in children, does occur in adults more than many clinicians appreciate, according to Dr. Lembo. He said that there is one key giveaway for this condition: patients are asymptomatic between episodes. He also said that episodes are separated by substantial intervals of weeks to months.
Symptoms associated with cannabinoids are most commonly observed in young men frequently using marijuana over an extended period, according to Dr. Lembo. He said reports that symptoms are improved with hot showers may be a clue that marijuana is involved in the etiology. Urine tests are useful when patients suspected of marijuana use deny this history.
The problem is that, even when cannabinoid use is isolated as the cause of bowel symptoms, many patients are convinced that their symptoms improve, rather than get worse, with marijuana use. This is a common obstacle to the abstention needed to evaluate benefit, according to Dr. Lembo.
As for other possible etiologies, Dr. Lembo advised upper endoscopy to rule out mechanical causes of gastroparesis, such as peptic ulcer disease, proximal bowel obstruction, or gastrointestinal cancer. He specifically recommended scoping to the “third portion of the duodenum” when obstruction is being considered in the differential diagnosis.
When gastroparesis is considered the most likely cause of symptoms, Dr. Lembo recommended a gastric-emptying study to increase confidence in the diagnosis. He identified 4-hour scintigraphy as the standard of care, as defined by current guidelines. However, he warned that even well-regarded centers do not always follow this standard. Based on the lower sensitivity and specificity of shorter duration tests and of other options such as breath tests or wireless motility capsules, clinicians “should really insist” on the 4-hour gastric-emptying test when they are concerned about documentation, he said.
Once the diagnosis has been made, there are numerous therapeutic options, but the top three are “diet, diet, and diet,” according to Dr. Lembo. In his review of prokinetic drugs, such as metoclopramide and motilin agonists, he cautioned that there is often a delicate balance between risk and benefit. New options on the horizon include a ghrelin agonist that showed promise in a phase III trial, but he noted that many patients with severe unremitting symptoms are prepared to try almost anything.
“These can be desperate people when they have failed everything that is out there,” Dr. Lembo noted. He acknowledged that such patients express interest even in strategies that have failed to show convincing benefit in controlled trials, such as botulism toxin injection and neuroenteric gastric stimulators. When all other options have been exhausted, a referral to a specialist for experimental therapies may be appropriate because of the major adverse impact of unremitting symptoms on quality of life.
Dr. Lembo reported financial relationships with Alkermes, Allergan, Forest, Ironwood, Prometheus, and Salix.
PHILADELPHIA – Particularly in adults, there are three conditions that produce symptoms consistent with idiopathic gastroparesis and should be specifically considered in a detailed history conducted before advanced diagnostic tests, according to a clinical update at the Fourth Annual Digestive Diseases: New Advances meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.
The three disorders “are very important, because we see them missed all the time,” reported Anthony J. Lembo, MD, director of the GI Motility Laboratory, Beth Israel Deaconess Medical Center, Boston.
“If you do not take a detailed enough history or if the patient is not willing to tell you about their past history, there is a good chance that these will go undetected,” Dr. Lembo explained. In his update on gastroparesis, he identified the recognition of these disorders as the most important clinical pearl of his overview of the challenges faced when evaluating the highly nonspecific symptoms of delayed–bowel transit time.
“Rumination syndrome has a very classic set of symptoms. When the patient swallows food, it will almost immediately or very quickly come back up. Sometimes the food is vomited. Often, it gets swallowed back down. That is not gastroparesis,” Dr. Lembo explained. Although vomiting after eating is a common symptom of gastroparesis, it is typically delayed by hours.
Cyclical vomiting syndrome, perhaps more readily recognized in children, does occur in adults more than many clinicians appreciate, according to Dr. Lembo. He said that there is one key giveaway for this condition: patients are asymptomatic between episodes. He also said that episodes are separated by substantial intervals of weeks to months.
Symptoms associated with cannabinoids are most commonly observed in young men frequently using marijuana over an extended period, according to Dr. Lembo. He said reports that symptoms are improved with hot showers may be a clue that marijuana is involved in the etiology. Urine tests are useful when patients suspected of marijuana use deny this history.
The problem is that, even when cannabinoid use is isolated as the cause of bowel symptoms, many patients are convinced that their symptoms improve, rather than get worse, with marijuana use. This is a common obstacle to the abstention needed to evaluate benefit, according to Dr. Lembo.
As for other possible etiologies, Dr. Lembo advised upper endoscopy to rule out mechanical causes of gastroparesis, such as peptic ulcer disease, proximal bowel obstruction, or gastrointestinal cancer. He specifically recommended scoping to the “third portion of the duodenum” when obstruction is being considered in the differential diagnosis.
When gastroparesis is considered the most likely cause of symptoms, Dr. Lembo recommended a gastric-emptying study to increase confidence in the diagnosis. He identified 4-hour scintigraphy as the standard of care, as defined by current guidelines. However, he warned that even well-regarded centers do not always follow this standard. Based on the lower sensitivity and specificity of shorter duration tests and of other options such as breath tests or wireless motility capsules, clinicians “should really insist” on the 4-hour gastric-emptying test when they are concerned about documentation, he said.
Once the diagnosis has been made, there are numerous therapeutic options, but the top three are “diet, diet, and diet,” according to Dr. Lembo. In his review of prokinetic drugs, such as metoclopramide and motilin agonists, he cautioned that there is often a delicate balance between risk and benefit. New options on the horizon include a ghrelin agonist that showed promise in a phase III trial, but he noted that many patients with severe unremitting symptoms are prepared to try almost anything.
“These can be desperate people when they have failed everything that is out there,” Dr. Lembo noted. He acknowledged that such patients express interest even in strategies that have failed to show convincing benefit in controlled trials, such as botulism toxin injection and neuroenteric gastric stimulators. When all other options have been exhausted, a referral to a specialist for experimental therapies may be appropriate because of the major adverse impact of unremitting symptoms on quality of life.
Dr. Lembo reported financial relationships with Alkermes, Allergan, Forest, Ironwood, Prometheus, and Salix.
PPI-responsive eosinophilic esophagitis may be misnomer
PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.
“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.
Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.
“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.
“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.
The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.
Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.
The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.
“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”
In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.
Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.
PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.
“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.
Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.
“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.
“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.
The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.
Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.
The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.
“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”
In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.
Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.
PHILADELPHIA – Eosinophilic esophagitis (EoE) responsive to a proton pump inhibitor (PPI) has been characterized as PPI-responsive esophageal eosinophilia (PPI-REE), but there is no compelling evidence that it is a distinct EoE subgroup, according to an expert who updated current thinking about this disease at Digestive Diseases: New Advances.
“Multivariate analyses have not identified any feature that distinguishes PPI-REE from EoE. Why? Because they are probably the same disorder,” reported Stuart J. Spechler, MD, AGAF, codirector of the center for esophageal diseases at Baylor University Medical Center at Dallas.
Although it is true that only a subset of EoE patients respond to PPIs, few therapies are effective for all patients in any disease Dr. Spechler observed. As an example, he noted that ulcerative colitis patients who respond to sulfasalazine are not subclassified as sulfasalazine-responsive ulcerative colitis.
“I do think the term PPI-REE should be retired, although I acknowledge that not everyone in this field is ready to agree,” Dr. Spechler said at the meeting, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.
The confusion regarding PPI responsiveness in EoE has been driven by the fact that acid control has been widely regarded as the only pertinent mechanism of action from PPIs. Although coexisting gastroesophageal reflux disease could explain symptom relief in some patients with EoE, no evidence of excess acid is found in many responders. Detailed evaluations of the PPI-REE subgroup relative to EOE overall emphasize this point, according to Dr. Spechler.
“Studies have shown that the clinical, endoscopic, histologic, and gene expression features of these two disorders are identical,” he reported.
The lack of distinction is now easier to understand with a growing body of evidence that PPIs have acid-independent effects relevant to benefit in EoE, according to Dr. Spechler. Tracing the advances in understanding the pathogenesis in EoE since it was first described in 1978, Dr. Spechler explained that EoE is now understood to be an antigen-driven expression of food allergy related to up-regulation of the Th2 helper adaptive response. After briefly reviewing several potential anti-inflammatory effects of PPIs, Dr. Spechler focused on evidence that PPIs inhibit the adhesion molecule eotaxin-3.
Specifically, when squamous cells from EoE patients are exposed to the cytokine interleukin-4 (IL-4), “production of eotaxin-3 is increased dramatically but you can block that cytokine Th2 stimulation with [the PPI] omeprazole,” said Dr. Spechler, citing published work by Edaire Cheng, MD, a researcher with whom he has collaborated at the University of Texas Southwestern Medical School, Dallas. This is a potentially important observation, because up-regulation of eotaxin-3 is considered a critical molecular event for the activation of eosinophils and their migration.
The relative importance of this specific mechanism for explaining the benefits of PPIs in EoE requires additional confirmation, but Dr. Spechler indicated that there is strong evidence of acid-independent effects from PPIs. In fact, in outlining an algorithm for treatment of EoE, he listed a trial of PPIs as a reasonable first choice.
“In my opinion, the major reason that we created an arbitrary distinction is this persistent notion that acid inhibition is the only possible therapeutic effect of PPIs,” Dr. Spechler reported. “I hope I have convinced you otherwise.”
In his brief update of EoE treatment in 2017, Dr. Spechler identified a trial of PPIs as first line “simply because they work.” However PPIs have been rendered even more attractive by the evidence of a plausible mechanism of action in EoE. Conversely, he cautioned that steroids are “just a band-aid” because “they cover up the allergy but the allergy remains.” Ultimately, while PPIs are a reasonable first-line therapy to control symptoms, Dr. Spechler suggested that elimination diets are ultimately the best strategy for treating the underlying cause of EoE.
Dr. Spechler reported a financial relationship with Ironwood Pharmaceuticals.
EXPERT ANALYSIS FROM DIGESTIVE DISEASES: NEW ADVANCES
Open-capsule PPIs linked to faster ulcer healing after Roux-en-Y
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules. 
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed ulcers at the gastrojejunal anastomosis after Roux-en-Y gastric bypass.
Major finding: The median time to ulcer healing was 91.0 versus 342.0 days for the open- and closed-capsule groups, respectively (P less than .001).
Data source: A single-center retrospective study of 162 patients.
Disclosures: The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
AGA Clinical Practice Update: Using FLIP to assess upper GI tract still murky territory
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Clinical Practice Update: PPIs should be prescribed sparingly, carefully
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
FROM GASTROENTEROLOGY