Upper GI Tract

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Six months of treatment with a proton pump inhibitor (PPI) is a safe way to cut the incidence of major gastrointestinal events in cardiovascular disease patients on dual-antiplatelet therapy regardless of whether they receive low-dose or high-dose aspirin, according to a post-hoc analysis of data from more than 3,700 patients enrolled in the multicenter, randomized COGENT trial.

“Short-term, prophylactic PPI therapy consistently reduced rates of adjudicated upper-gastrointestinal events without increasing cardiovascular events, regardless of the aspirin dose,” Dr. Muthiah Vaduganathan said while presenting his study at the annual meeting of the American College of Cardiology. “Gastroprotection with PPI therapy should be used in appropriately selected patients with coronary artery disease who require dual-antiplatelet therapy even if they are on low-dose aspirin.”

Mitchel L. Zoler/Frontline Medical News

In addition to documenting the safety and efficacy of 6 months of PPI treatment for patients at high risk for cardiovascular events and low or moderate risk for a GI event, the results from the analysis also documented how common GI events are in this population, even when patients receive low-dose aspirin. Nearly two-thirds of the 3,752 patients included in the analysis took low-dose aspirin, either 75 mg or 81 mg per day. Their incidence of an adjudicated upper GI bleed, the study’s primary GI endpoint, occurred in 3.1% of patients on placebo, and in 1.2% of patients taking a prophylactic PPI. Among the other 34% of patients on high-dose aspirin – a daily dosage of at least 150 mg – the rate of adjudicated upper-GI bleeds was 2.6% without a PPI and 0.9% in those on a PPI.

In other words, even among patients deemed to have a relatively low risk for upper GI complications from aspirin (because their entry into this study required no history of major GI bleeds or recent treatment with a gastroprotection agent), treatment with low-dose aspirin resulted in upper-GI bleeds at the same rate, about 3%, as high-dose aspirin. And in both of these aspirin subgroups 6 months of concurrent treatment with a PPI cut the incidence of major GI bleeds by more than half.

The findings are especially notable because the enrollment criteria stacked the deck toward patients with high cardiovascular disease risk and relatively low GI risk. The study enrolled “a unique population at high risk for cardiovascular disease – 71% had previously undergone a percutaneous coronary intervention, and 42% had a history of an acute coronary syndrome – and low GI risk, but even in this population enriched for cardiovascular disease risk, there was no increased rate of cardiovascular disease events” during a median follow-up while on PPI treatment of 110 days, Dr. Vaduganathan said.

Among patients on low-dose aspirin, the rate of cardiovascular death, MI, stroke, or coronary revascularization was 5.6% with PPI treatment and 5.5% without, and in the high-dose aspirin patients the rates were 4.2% with PPI treatment and 5.5% without. Neither of these differences between the subgroups taking or not taking a PPI were statistically significant.

Concurrent with Dr. Vaduganathan’s report at the meeting the results also appeared online (J Am Coll Cardiol. 2016 April 12;67[14]:661-71).

“There appeared to be no adverse clinical effect from PPI treatment. When used short-term, for up to 6 months, PPI treatment appears to be safe in patients with cardiovascular disease,” Dr. Vaduganathan concluded.

The analysis used data collected in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial), a phase 3 study designed to compare a single-pill formulation of 20 mg omeprazole and 75 mg clopidogrel taken orally once daily with 75 mg clopidogrel against a background of all patients taking aspirin. COGENT stopped prematurely in late 2008 as the company developing this formulation and sponsoring the trial, Cogentus Pharmaceuticals, filed for bankruptcy. Despite its abrupt conclusion, the trial had enrolled and followed enough patients to show that treatment with omeprazole plus clopidogrel and aspirin led to a significant reduction in upper GI bleeding without increasing the rate of cardiovascular disease events, compared with clopidogrel plus aspirin (N Engl J Med. 2010 Nov 11;363[20]:1909-17).

The new analysis focused on the greater than 99% of patients in the total COGENT cohort for whom information was available on whether they received high- or low-dose aspirin.

Although the primary findings from COGENT, reported in 2010, documented the safety and efficacy of concomitant PPI treatment during dual-antiplatelet therapy, and despite guidelines revised in 2010 that called for PPI treatment when appropriate, this strategy for preventing GI complications remains underused, Dr. Vaduganathan said. The most recent U.S. recommendations that address this issue called for assessing the potential risk and benefit from PPI treatment in patients receiving dual-antiplatelet therapy: “The risk reduction with PPIs is substantial in patients with risk factors for GI bleeding and may outweigh any potential reduction in the CV efficacy of antiplatelet treatment because of a drug-drug interaction (J Am Coll Cardiol. 2010 Dec;56[24]:2051-66).”

The only caveat Dr. Vaduganathan placed on PPI use was that the COGENT data addressed only 6 months of PPI use; the safety of longer-term use has not been studied. But “the trend is to use PPIs for as short a period as possible,” and the risk for adverse effects from PPI treatment on cardiovascular disease events is likely greatest during the first 6 months of PPI treatment, he noted. If PPI treatment needs to continue beyond 6 months, he suggested systematically reassessing the risk-benefit balance for individual patients from continued PPI treatment every 3 months.*

*Changes were made to this story on 4/20/2016.

[email protected]

On Twitter @mitchelzoler

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.

Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.

To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).

The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.

In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.

“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”

Dr. Freedberg also noted several key limitations of the study.

“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.

“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.

In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.

“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.

The researchers had no financial conflicts to disclose.

Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.

Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.

To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).

The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.

In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.

“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”

Dr. Freedberg also noted several key limitations of the study.

“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.

“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.

In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.

“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.

The researchers had no financial conflicts to disclose.

Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.

Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.

To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).

The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.

In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.

“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”

Dr. Freedberg also noted several key limitations of the study.

“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.

“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.

In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.

“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.

The researchers had no financial conflicts to disclose.

The use of endoscopic mucosal resection (EMR) before radiofrequency ablation significantly reduced the risk for treatment failure among patients with Barrett’s esophagus–associated intramucosal adenocarcinoma (IMC) and dysplasia, according to new data published in the American Journal of Surgical Pathology.

Complete eradication of IMC/dysplasia on the first follow-up endoscopy after treatment was achieved in 86% of patients, while durable eradication, defined as a complete recurrence that persisted until the last follow-up, was achieved in 78% of patients. However, there was significant variation between the different study sites (P = .03) and outcomes were significantly impacted by the baseline extent of IMC and the use of EMR prior to radiofrequency ablation (RFA) therapy.

In addition, almost a quarter of all patients developed treatment-related strictures, usually in the setting of multiple EMRs, and recurrence occurred as a malignant stricture in one patient.

Radiofrequency ablation used with or without EMR, is a safe, effective, and durable treatment option for the treatment of dysplasia associated with Barrett’s esophagus. However, studies that have assessed the predictors of treatment failure in Barrett’s esophagus-associated intramucosal adenocarcinoma (IMC) are limited.

In this study, Dr. Agoston T. Agoston of the department of pathology at Brigham and Women’s Hospital, Boston, and his colleagues investigated the rate of Barrett’s esophagus–associated IMC eradication when using RFA, with or without EMR, in a multicenter setting. In addition, they attempted to identify clinical and pathologic predictors of treatment failure.

“We anticipate that these data will have significant implications for a personalized treatment approach to patients with BE [Barrett’s esophagus]–associated IMC,” wrote the authors.

They conducted a retrospective review of medical records from four tertiary care academic medical centers, and identified 78 patients who underwent RFA with or without EMR as the primary treatment for biopsy-proven IMC.

Some notable baseline differences were observed in patient characteristics at the different study sites, including baseline Barrett’s esophagus segment length (P = .06), baseline nodularity (P = .08), and percentage of tissue involved by IMC at pretreatment endoscopy and biopsy (P = .01).

Over a mean follow-up time of 26.4 months (range, 2-116 months), 86% of patients achieved complete eradication and 78% durable eradication of IMC/dysplasia.

Within the cohort, 11 patients failed to achieve complete eradication, and of the 67 patients who initially did, 6 patients (9.0%) had a subsequent recurrence of neoplasia (3.91 recurrences per 100 patient-years). This extrapolated to an overall rate of 22% for treatment failure (17/78 patients). Of the 17 patients who failed the treatment, 3 subsequently underwent esophagectomy, 1 received palliative measures in the setting of advanced neurological disease, and 1 patient is currently undergoing a repeat ablation procedure with curative intent.

Dr. Agoston and his team also identified 2 clinicopathologic factors that were significantly associated with treatment failure, and both remained significant on univariate and multivariate analysis. The first was that the use of EMR prior to RFA was associated with a significantly reduced risk for treatment failure (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P = .001), and the second was that the extent of IMC involving at least 50% of the columnar metaplastic area was associated with a significantly increased risk for treatment failure (HR, 4.24; 95% CI, 1.53-11.7; P = .005).

They also observed similar results when the analysis of extent of IMC as a predictor was restricted to a subset of 43 cases in which the diagnosis of IMC was made on EMR specimens only (HR, 10.8; 95% CI, 2.30-50.8; P = .003).

“In conclusion, we have identified endoscopic and pathologic factors associated with treatment success in patients with BE-associated IMC treated with RFA with or without EMR,” they wrote. “Utilization of these predictors can help in identifying patients with a high probability of success and also those patients with a higher risk for treatment failure for whom a more aggressive initial approach may be justified” (Am J Surg Pathol. 2015 Dec 5. doi: 10.1097/PAS.0000000000000566).

Dr. Rothstein and Dr. Abrams have received research support previously from Barrx/ Covidien and C2 Therapeutics/Covidien, respectively. None of the other authors reported significant conflicts of interest.

[email protected]

The use of endoscopic mucosal resection (EMR) before radiofrequency ablation significantly reduced the risk for treatment failure among patients with Barrett’s esophagus–associated intramucosal adenocarcinoma (IMC) and dysplasia, according to new data published in the American Journal of Surgical Pathology.

Complete eradication of IMC/dysplasia on the first follow-up endoscopy after treatment was achieved in 86% of patients, while durable eradication, defined as a complete recurrence that persisted until the last follow-up, was achieved in 78% of patients. However, there was significant variation between the different study sites (P = .03) and outcomes were significantly impacted by the baseline extent of IMC and the use of EMR prior to radiofrequency ablation (RFA) therapy.

In addition, almost a quarter of all patients developed treatment-related strictures, usually in the setting of multiple EMRs, and recurrence occurred as a malignant stricture in one patient.

Radiofrequency ablation used with or without EMR, is a safe, effective, and durable treatment option for the treatment of dysplasia associated with Barrett’s esophagus. However, studies that have assessed the predictors of treatment failure in Barrett’s esophagus-associated intramucosal adenocarcinoma (IMC) are limited.

In this study, Dr. Agoston T. Agoston of the department of pathology at Brigham and Women’s Hospital, Boston, and his colleagues investigated the rate of Barrett’s esophagus–associated IMC eradication when using RFA, with or without EMR, in a multicenter setting. In addition, they attempted to identify clinical and pathologic predictors of treatment failure.

“We anticipate that these data will have significant implications for a personalized treatment approach to patients with BE [Barrett’s esophagus]–associated IMC,” wrote the authors.

They conducted a retrospective review of medical records from four tertiary care academic medical centers, and identified 78 patients who underwent RFA with or without EMR as the primary treatment for biopsy-proven IMC.

Some notable baseline differences were observed in patient characteristics at the different study sites, including baseline Barrett’s esophagus segment length (P = .06), baseline nodularity (P = .08), and percentage of tissue involved by IMC at pretreatment endoscopy and biopsy (P = .01).

Over a mean follow-up time of 26.4 months (range, 2-116 months), 86% of patients achieved complete eradication and 78% durable eradication of IMC/dysplasia.

Within the cohort, 11 patients failed to achieve complete eradication, and of the 67 patients who initially did, 6 patients (9.0%) had a subsequent recurrence of neoplasia (3.91 recurrences per 100 patient-years). This extrapolated to an overall rate of 22% for treatment failure (17/78 patients). Of the 17 patients who failed the treatment, 3 subsequently underwent esophagectomy, 1 received palliative measures in the setting of advanced neurological disease, and 1 patient is currently undergoing a repeat ablation procedure with curative intent.

Dr. Agoston and his team also identified 2 clinicopathologic factors that were significantly associated with treatment failure, and both remained significant on univariate and multivariate analysis. The first was that the use of EMR prior to RFA was associated with a significantly reduced risk for treatment failure (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P = .001), and the second was that the extent of IMC involving at least 50% of the columnar metaplastic area was associated with a significantly increased risk for treatment failure (HR, 4.24; 95% CI, 1.53-11.7; P = .005).

They also observed similar results when the analysis of extent of IMC as a predictor was restricted to a subset of 43 cases in which the diagnosis of IMC was made on EMR specimens only (HR, 10.8; 95% CI, 2.30-50.8; P = .003).

“In conclusion, we have identified endoscopic and pathologic factors associated with treatment success in patients with BE-associated IMC treated with RFA with or without EMR,” they wrote. “Utilization of these predictors can help in identifying patients with a high probability of success and also those patients with a higher risk for treatment failure for whom a more aggressive initial approach may be justified” (Am J Surg Pathol. 2015 Dec 5. doi: 10.1097/PAS.0000000000000566).

Dr. Rothstein and Dr. Abrams have received research support previously from Barrx/ Covidien and C2 Therapeutics/Covidien, respectively. None of the other authors reported significant conflicts of interest.

[email protected]

The use of endoscopic mucosal resection (EMR) before radiofrequency ablation significantly reduced the risk for treatment failure among patients with Barrett’s esophagus–associated intramucosal adenocarcinoma (IMC) and dysplasia, according to new data published in the American Journal of Surgical Pathology.

Complete eradication of IMC/dysplasia on the first follow-up endoscopy after treatment was achieved in 86% of patients, while durable eradication, defined as a complete recurrence that persisted until the last follow-up, was achieved in 78% of patients. However, there was significant variation between the different study sites (P = .03) and outcomes were significantly impacted by the baseline extent of IMC and the use of EMR prior to radiofrequency ablation (RFA) therapy.

In addition, almost a quarter of all patients developed treatment-related strictures, usually in the setting of multiple EMRs, and recurrence occurred as a malignant stricture in one patient.

Radiofrequency ablation used with or without EMR, is a safe, effective, and durable treatment option for the treatment of dysplasia associated with Barrett’s esophagus. However, studies that have assessed the predictors of treatment failure in Barrett’s esophagus-associated intramucosal adenocarcinoma (IMC) are limited.

In this study, Dr. Agoston T. Agoston of the department of pathology at Brigham and Women’s Hospital, Boston, and his colleagues investigated the rate of Barrett’s esophagus–associated IMC eradication when using RFA, with or without EMR, in a multicenter setting. In addition, they attempted to identify clinical and pathologic predictors of treatment failure.

“We anticipate that these data will have significant implications for a personalized treatment approach to patients with BE [Barrett’s esophagus]–associated IMC,” wrote the authors.

They conducted a retrospective review of medical records from four tertiary care academic medical centers, and identified 78 patients who underwent RFA with or without EMR as the primary treatment for biopsy-proven IMC.

Some notable baseline differences were observed in patient characteristics at the different study sites, including baseline Barrett’s esophagus segment length (P = .06), baseline nodularity (P = .08), and percentage of tissue involved by IMC at pretreatment endoscopy and biopsy (P = .01).

Over a mean follow-up time of 26.4 months (range, 2-116 months), 86% of patients achieved complete eradication and 78% durable eradication of IMC/dysplasia.

Within the cohort, 11 patients failed to achieve complete eradication, and of the 67 patients who initially did, 6 patients (9.0%) had a subsequent recurrence of neoplasia (3.91 recurrences per 100 patient-years). This extrapolated to an overall rate of 22% for treatment failure (17/78 patients). Of the 17 patients who failed the treatment, 3 subsequently underwent esophagectomy, 1 received palliative measures in the setting of advanced neurological disease, and 1 patient is currently undergoing a repeat ablation procedure with curative intent.

Dr. Agoston and his team also identified 2 clinicopathologic factors that were significantly associated with treatment failure, and both remained significant on univariate and multivariate analysis. The first was that the use of EMR prior to RFA was associated with a significantly reduced risk for treatment failure (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P = .001), and the second was that the extent of IMC involving at least 50% of the columnar metaplastic area was associated with a significantly increased risk for treatment failure (HR, 4.24; 95% CI, 1.53-11.7; P = .005).

They also observed similar results when the analysis of extent of IMC as a predictor was restricted to a subset of 43 cases in which the diagnosis of IMC was made on EMR specimens only (HR, 10.8; 95% CI, 2.30-50.8; P = .003).

“In conclusion, we have identified endoscopic and pathologic factors associated with treatment success in patients with BE-associated IMC treated with RFA with or without EMR,” they wrote. “Utilization of these predictors can help in identifying patients with a high probability of success and also those patients with a higher risk for treatment failure for whom a more aggressive initial approach may be justified” (Am J Surg Pathol. 2015 Dec 5. doi: 10.1097/PAS.0000000000000566).

Dr. Rothstein and Dr. Abrams have received research support previously from Barrx/ Covidien and C2 Therapeutics/Covidien, respectively. None of the other authors reported significant conflicts of interest.

[email protected]

The use of proton pump inhibitors increased the risk of chronic kidney disease by 20%-50%, said the authors of two large population-based cohort analyses published online Jan. 11 in JAMA Internal Medicine.

These are the first such studies to link PPI use to chronic kidney disease (CKD), and the association held up after controlling for multiple potential confounders, said Dr. Benjamin Lazarus of Johns Hopkins University, Baltimore, and his associates. “Further research is required to investigate whether PPI use itself causes kidney damage and, if so, the underlying mechanisms of this association,” they wrote.

Proton pump inhibitors have been linked to other adverse health effects but remain among the most frequently prescribed medications in the United States. To further explore the risk of PPI use, the researchers analyzed data for 10,482 adults from the Atherosclerosis Risk in Communities (ARIC) study who were followed for a median of 13.9 years, and a replication cohort of 248,751 patients from a large rural health care system who were followed for a median of 6.2 years.

©decade3d/thinkstockphotos.com

Incident CKD was defined based on hospital discharge diagnosis codes, reports of end-stage renal disease from the United States Renal Data System Registry, or a glomerular filtration rate of less than 60 mL/min per 1.73 m² that persisted at follow-up visits (JAMA Intern Med. 2016 Jan 11. doi: 0.1001/jamainternmed.2015.7193).

In the ARIC study, there were 56 cases of CKD among 322 self-reported baseline PPI users, for an incidence of 14.2 cases per 1,000 person-years – significantly higher than the rate of 10.7 cases per 1,000 person-years among self-reported baseline nonusers. The 10-year estimated absolute risk of CKD among baseline users was 11.8% – 3.3% higher than the expected risk had they not used PPIs. Furthermore, PPI users were at significantly higher risk of CKD after demographic, socioeconomic, and clinical variables were accounted for (hazard ratio, 1.50; 95% confidence interval, 1.1-2.0), after modeling varying use of PPIs over time (adjusted HR, 1.3; 95% CI, 1.2-1.5), after directly comparing PPI users with H₂ receptor antagonist users (adjusted HR, 1.4; 95% CI, 1.01-1.9), and after comparing baseline PPI users with propensity score–matched nonusers (HR, 1.8; 95% CI, 1.1-2.7).

In the replication cohort, there were 1,921 new cases of CKD among 16,900 patients with an outpatient PPI prescription (incidence of 20.1 cases per 1,000 person-years). The incidence of CKD among the other patients was lower: 18.3 cases per 1,000 person-years. The use of PPIs was significantly associated with incident CKD in all analyses, and the 10-year absolute risk of CKD among baseline PPI users was 15.6% – 1.7% higher than the expected risk had they not used PPIs.

These observational analyses cannot show causality, but a causal relationship between PPIs and CKD “could have a considerable public health impact, give the widespread extent of use,” the researchers emphasized. “More than 15 million Americans used prescription PPIs in 2013, costing more than $10 billion. Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs (BMJ. 2008;336:2-3).”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, both of which are part of the National Institutes of Health. The researchers had no disclosures.

The use of proton pump inhibitors increased the risk of chronic kidney disease by 20%-50%, said the authors of two large population-based cohort analyses published online Jan. 11 in JAMA Internal Medicine.

These are the first such studies to link PPI use to chronic kidney disease (CKD), and the association held up after controlling for multiple potential confounders, said Dr. Benjamin Lazarus of Johns Hopkins University, Baltimore, and his associates. “Further research is required to investigate whether PPI use itself causes kidney damage and, if so, the underlying mechanisms of this association,” they wrote.

Proton pump inhibitors have been linked to other adverse health effects but remain among the most frequently prescribed medications in the United States. To further explore the risk of PPI use, the researchers analyzed data for 10,482 adults from the Atherosclerosis Risk in Communities (ARIC) study who were followed for a median of 13.9 years, and a replication cohort of 248,751 patients from a large rural health care system who were followed for a median of 6.2 years.

©decade3d/thinkstockphotos.com

Incident CKD was defined based on hospital discharge diagnosis codes, reports of end-stage renal disease from the United States Renal Data System Registry, or a glomerular filtration rate of less than 60 mL/min per 1.73 m² that persisted at follow-up visits (JAMA Intern Med. 2016 Jan 11. doi: 0.1001/jamainternmed.2015.7193).

In the ARIC study, there were 56 cases of CKD among 322 self-reported baseline PPI users, for an incidence of 14.2 cases per 1,000 person-years – significantly higher than the rate of 10.7 cases per 1,000 person-years among self-reported baseline nonusers. The 10-year estimated absolute risk of CKD among baseline users was 11.8% – 3.3% higher than the expected risk had they not used PPIs. Furthermore, PPI users were at significantly higher risk of CKD after demographic, socioeconomic, and clinical variables were accounted for (hazard ratio, 1.50; 95% confidence interval, 1.1-2.0), after modeling varying use of PPIs over time (adjusted HR, 1.3; 95% CI, 1.2-1.5), after directly comparing PPI users with H₂ receptor antagonist users (adjusted HR, 1.4; 95% CI, 1.01-1.9), and after comparing baseline PPI users with propensity score–matched nonusers (HR, 1.8; 95% CI, 1.1-2.7).

In the replication cohort, there were 1,921 new cases of CKD among 16,900 patients with an outpatient PPI prescription (incidence of 20.1 cases per 1,000 person-years). The incidence of CKD among the other patients was lower: 18.3 cases per 1,000 person-years. The use of PPIs was significantly associated with incident CKD in all analyses, and the 10-year absolute risk of CKD among baseline PPI users was 15.6% – 1.7% higher than the expected risk had they not used PPIs.

These observational analyses cannot show causality, but a causal relationship between PPIs and CKD “could have a considerable public health impact, give the widespread extent of use,” the researchers emphasized. “More than 15 million Americans used prescription PPIs in 2013, costing more than $10 billion. Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs (BMJ. 2008;336:2-3).”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, both of which are part of the National Institutes of Health. The researchers had no disclosures.

The use of proton pump inhibitors increased the risk of chronic kidney disease by 20%-50%, said the authors of two large population-based cohort analyses published online Jan. 11 in JAMA Internal Medicine.

These are the first such studies to link PPI use to chronic kidney disease (CKD), and the association held up after controlling for multiple potential confounders, said Dr. Benjamin Lazarus of Johns Hopkins University, Baltimore, and his associates. “Further research is required to investigate whether PPI use itself causes kidney damage and, if so, the underlying mechanisms of this association,” they wrote.

Proton pump inhibitors have been linked to other adverse health effects but remain among the most frequently prescribed medications in the United States. To further explore the risk of PPI use, the researchers analyzed data for 10,482 adults from the Atherosclerosis Risk in Communities (ARIC) study who were followed for a median of 13.9 years, and a replication cohort of 248,751 patients from a large rural health care system who were followed for a median of 6.2 years.

©decade3d/thinkstockphotos.com

Incident CKD was defined based on hospital discharge diagnosis codes, reports of end-stage renal disease from the United States Renal Data System Registry, or a glomerular filtration rate of less than 60 mL/min per 1.73 m² that persisted at follow-up visits (JAMA Intern Med. 2016 Jan 11. doi: 0.1001/jamainternmed.2015.7193).

In the ARIC study, there were 56 cases of CKD among 322 self-reported baseline PPI users, for an incidence of 14.2 cases per 1,000 person-years – significantly higher than the rate of 10.7 cases per 1,000 person-years among self-reported baseline nonusers. The 10-year estimated absolute risk of CKD among baseline users was 11.8% – 3.3% higher than the expected risk had they not used PPIs. Furthermore, PPI users were at significantly higher risk of CKD after demographic, socioeconomic, and clinical variables were accounted for (hazard ratio, 1.50; 95% confidence interval, 1.1-2.0), after modeling varying use of PPIs over time (adjusted HR, 1.3; 95% CI, 1.2-1.5), after directly comparing PPI users with H₂ receptor antagonist users (adjusted HR, 1.4; 95% CI, 1.01-1.9), and after comparing baseline PPI users with propensity score–matched nonusers (HR, 1.8; 95% CI, 1.1-2.7).

In the replication cohort, there were 1,921 new cases of CKD among 16,900 patients with an outpatient PPI prescription (incidence of 20.1 cases per 1,000 person-years). The incidence of CKD among the other patients was lower: 18.3 cases per 1,000 person-years. The use of PPIs was significantly associated with incident CKD in all analyses, and the 10-year absolute risk of CKD among baseline PPI users was 15.6% – 1.7% higher than the expected risk had they not used PPIs.

These observational analyses cannot show causality, but a causal relationship between PPIs and CKD “could have a considerable public health impact, give the widespread extent of use,” the researchers emphasized. “More than 15 million Americans used prescription PPIs in 2013, costing more than $10 billion. Study findings suggest that up to 70% of these prescriptions are without indication and that 25% of long-term PPI users could discontinue therapy without developing symptoms. Indeed, there are already calls for the reduction of unnecessary use of PPIs (BMJ. 2008;336:2-3).”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, both of which are part of the National Institutes of Health. The researchers had no disclosures.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

About half of patients with symptomatic esophageal eosinophilia achieved complete clinical and histologic remission on proton pump inhibitors (PPIs), according to a systematic review and meta-analysis of 33 studies.

“Our results support the concept of PPIs as first-line therapy in both children and adults,” Dr. Alfredo Lucendo of the Servicio de Salud de Castillo–La Mancha, Hospital General de Tomelloso, Albacete, Spain, and his associates wrote in the January issue of Clinical Gastroenterology and Hepatology. “Other effective alternatives, such as dietary or topical steroid therapy, likely might be set aside as second-line treatment, owing to long-term safety concerns (topical steroid therapy) and impairment of quality of life and nutritional inadequacy (dietary interventions).”

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The study also confirmed that esophageal pH monitoring does not accurately predict therapeutic response to PPI therapy. “The performance of this test before histologic reevaluation on PPI therapy should be discouraged,” according to the researchers (Clin Gastroenterol Hepatol. 2015. [doi:10.1016/j.cgh.2015.07.041]). Eosinophilic esophagitis was first described as a distinct disorder about 20 years ago, but only recently was understood to be the most common cause of chronic esophageal symptoms among children and young adults. Some cases are now known to respond to PPI therapy, but reported remission rates have varied depending on study design and patient population, the investigators said. In addition, no one had systematically reviewed studies of PPI-responsive esophageal eosinophilia for quality or to determine the optimal type of PPI, dose, or treatment duration.

Therefore, the investigators searched MEDLINE, EMBASE, SCOPUS, and abstracts from the annual meetings of the American Gastroenterological Association, the American College of Gastroenterology, and United European Gastroenterology, identifying 33 studies of 619 patients with symptomatic esophageal eosinophilia. Eleven of the studies were prospective, of which only two were randomized controlled trials. The researchers defined a histologic response as less than 15 eosinophils per high-powered frame after PPI therapy. “Missing data regarding PPI therapy were common and prevented us from drawing conclusions on the most effective PPI drug and doses,” they said. In addition, most studies lacked structured or objective survey tools or other measures of clinical improvement, making it impossible to rule out self-adapted coping strategies as a main cause of improvement over time.

With those caveats in mind, about 61% of patients in the pooled analysis had a clinical response to PPI therapy (95% confidence interval, 48%-72%), and half achieved clinical and histologic remission (95% CI, 42%-59%), the investigators reported. Therapy was somewhat more effective when administered twice a day instead of once daily, when clinicians used esophageal pH monitoring, and when studies were prospective instead of retrospective, but the differences were not significant. Nor did therapeutic response significantly differ based on the age of patients, type of report, or quality of the study.

The overall findings “should be interpreted with caution because of poor-quality evidence, heterogeneity, and publication bias,” the researchers said. Prospective studies are needed to examine the best PPI, dose, and dosing interval to use in an initial trial in the clinic; to clarify long-term effects and dosing strategies; to assess the ability of PPIs to reverse fibrotic esophageal remodeling; and to examine the effects of the CYP2C19 genotype on clinical and histologic response, they added. “More quality evidence on pediatric PPI-responsive eosinophilic esophagitis is needed urgently,” they emphasized.

The authors reported no funding sources and had no disclosures.

The Eosinophilic Esophagitis Endoscopic Reference Score, or EREFS, is not only highly predictive of eosinophilic esophagitis (EoE) but also its responsiveness to treatment, which suggests it may be used as an outcome measure, researchers say.

A prospective study of 211 adults undergoing upper endoscopy to investigate symptoms of esophageal dysfunction compared the EREFS with consensus guidelines for diagnosis of eosinophilic esophagitis.

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The guidelines approach identified 67 cases of eosinophilic esophagitis and 144 control subjects without eosinophilic esophagitis. When these patients were assessed via the EREFS, researchers found multiple, highly significant differences between the cases and controls, with a mean total EREFS of 3.88 for cases and 0.42 for controls, according to a paper published online in Clinical Gastroenterology and Hepatology.

“On ROC [receiver operator characteristic] analysis, a model that contained all 5 components of the EREFS system as categorical variables had an AUC [area under the curve] of 0.946, indicating an excellent ability to predict EoE case status based on endoscopic findings alone,” wrote Dr. Evan S. Dellon and colleagues of the University of North Carolina at Chapel Hill.

In this model, a score of 2.0 or above showed a sensitivity of 88%, specificity of 92%, positive predictive value of 84%, negative predictive value of 94%, and accuracy of 91%.

Most of the score’s predictive ability was attributed to its inflammatory component, and less from the fibrostenotic score, which the authors suggested was due to the high prevalence of strictures in the control group.

The EREFS also improved significantly after treatment, in conjunction with endoscopic findings.

Total EREFS significantly decreased from 3.88 to 2.01, the inflammatory score decreased from 2.41 to 1.22, and the fibrostenotic score decreased from 1.46 to 0.89.

Histologic responders to treatment showed much more significant decreases in EREFS compared with nonresponders (Clin Gastro Hepatol. 2015, Sept. 12 [http://dx.doi.org/10.1016/j.cgh.2015.08.040]).

Researchers also examined the impact of weighing the various features of EREFS differently.

“The iterative analysis investigating weighing the EREFS features differently showed that increasing the weight of the exudate, rings, and edema score modestly increased the predictive power when the change in eosinophil counts was treated continuously and that increasing the weight of exudates and rings was beneficial with a threshold eosinophil count (less than 15 eosinophil/hpf) for response,” they reported.

Based on this finding, the researchers created a set of EREFS scores using these varied weights, and showed that doubling the exudates, rings, and edema scores achieved the score’s maximum responsiveness while still keeping the weighting system simple, although these changes did not alter the score’s overall predictive ability.

The EREFS score was developed as a way to standardize the description, recognition, and reporting of eosinophilic esophagitis, but its diagnostic utility and responsiveness to treatment were unknown, the authors said.

“This prospective study found that the EREFS classification has diagnostic utility for EoE,” they wrote. “Moreover, the score is responsive to treatment, decreasing significantly in histologic responders, and can be used as an outcome measure.”

The National Institutes of Health and the University of North Carolina Center for Gastrointestinal Biology and Disease funded the study. No conflicts of interest were declared.

The Eosinophilic Esophagitis Endoscopic Reference Score, or EREFS, is not only highly predictive of eosinophilic esophagitis (EoE) but also its responsiveness to treatment, which suggests it may be used as an outcome measure, researchers say.

A prospective study of 211 adults undergoing upper endoscopy to investigate symptoms of esophageal dysfunction compared the EREFS with consensus guidelines for diagnosis of eosinophilic esophagitis.

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The guidelines approach identified 67 cases of eosinophilic esophagitis and 144 control subjects without eosinophilic esophagitis. When these patients were assessed via the EREFS, researchers found multiple, highly significant differences between the cases and controls, with a mean total EREFS of 3.88 for cases and 0.42 for controls, according to a paper published online in Clinical Gastroenterology and Hepatology.

“On ROC [receiver operator characteristic] analysis, a model that contained all 5 components of the EREFS system as categorical variables had an AUC [area under the curve] of 0.946, indicating an excellent ability to predict EoE case status based on endoscopic findings alone,” wrote Dr. Evan S. Dellon and colleagues of the University of North Carolina at Chapel Hill.

In this model, a score of 2.0 or above showed a sensitivity of 88%, specificity of 92%, positive predictive value of 84%, negative predictive value of 94%, and accuracy of 91%.

Most of the score’s predictive ability was attributed to its inflammatory component, and less from the fibrostenotic score, which the authors suggested was due to the high prevalence of strictures in the control group.

The EREFS also improved significantly after treatment, in conjunction with endoscopic findings.

Total EREFS significantly decreased from 3.88 to 2.01, the inflammatory score decreased from 2.41 to 1.22, and the fibrostenotic score decreased from 1.46 to 0.89.

Histologic responders to treatment showed much more significant decreases in EREFS compared with nonresponders (Clin Gastro Hepatol. 2015, Sept. 12 [http://dx.doi.org/10.1016/j.cgh.2015.08.040]).

Researchers also examined the impact of weighing the various features of EREFS differently.

“The iterative analysis investigating weighing the EREFS features differently showed that increasing the weight of the exudate, rings, and edema score modestly increased the predictive power when the change in eosinophil counts was treated continuously and that increasing the weight of exudates and rings was beneficial with a threshold eosinophil count (less than 15 eosinophil/hpf) for response,” they reported.

Based on this finding, the researchers created a set of EREFS scores using these varied weights, and showed that doubling the exudates, rings, and edema scores achieved the score’s maximum responsiveness while still keeping the weighting system simple, although these changes did not alter the score’s overall predictive ability.

The EREFS score was developed as a way to standardize the description, recognition, and reporting of eosinophilic esophagitis, but its diagnostic utility and responsiveness to treatment were unknown, the authors said.

“This prospective study found that the EREFS classification has diagnostic utility for EoE,” they wrote. “Moreover, the score is responsive to treatment, decreasing significantly in histologic responders, and can be used as an outcome measure.”

The National Institutes of Health and the University of North Carolina Center for Gastrointestinal Biology and Disease funded the study. No conflicts of interest were declared.

The Eosinophilic Esophagitis Endoscopic Reference Score, or EREFS, is not only highly predictive of eosinophilic esophagitis (EoE) but also its responsiveness to treatment, which suggests it may be used as an outcome measure, researchers say.

A prospective study of 211 adults undergoing upper endoscopy to investigate symptoms of esophageal dysfunction compared the EREFS with consensus guidelines for diagnosis of eosinophilic esophagitis.

©Magnus Manske/Wikimedia Commons/CC SA 3.0

The guidelines approach identified 67 cases of eosinophilic esophagitis and 144 control subjects without eosinophilic esophagitis. When these patients were assessed via the EREFS, researchers found multiple, highly significant differences between the cases and controls, with a mean total EREFS of 3.88 for cases and 0.42 for controls, according to a paper published online in Clinical Gastroenterology and Hepatology.

“On ROC [receiver operator characteristic] analysis, a model that contained all 5 components of the EREFS system as categorical variables had an AUC [area under the curve] of 0.946, indicating an excellent ability to predict EoE case status based on endoscopic findings alone,” wrote Dr. Evan S. Dellon and colleagues of the University of North Carolina at Chapel Hill.

In this model, a score of 2.0 or above showed a sensitivity of 88%, specificity of 92%, positive predictive value of 84%, negative predictive value of 94%, and accuracy of 91%.

Most of the score’s predictive ability was attributed to its inflammatory component, and less from the fibrostenotic score, which the authors suggested was due to the high prevalence of strictures in the control group.

The EREFS also improved significantly after treatment, in conjunction with endoscopic findings.

Total EREFS significantly decreased from 3.88 to 2.01, the inflammatory score decreased from 2.41 to 1.22, and the fibrostenotic score decreased from 1.46 to 0.89.

Histologic responders to treatment showed much more significant decreases in EREFS compared with nonresponders (Clin Gastro Hepatol. 2015, Sept. 12 [http://dx.doi.org/10.1016/j.cgh.2015.08.040]).

Researchers also examined the impact of weighing the various features of EREFS differently.

“The iterative analysis investigating weighing the EREFS features differently showed that increasing the weight of the exudate, rings, and edema score modestly increased the predictive power when the change in eosinophil counts was treated continuously and that increasing the weight of exudates and rings was beneficial with a threshold eosinophil count (less than 15 eosinophil/hpf) for response,” they reported.

Based on this finding, the researchers created a set of EREFS scores using these varied weights, and showed that doubling the exudates, rings, and edema scores achieved the score’s maximum responsiveness while still keeping the weighting system simple, although these changes did not alter the score’s overall predictive ability.

The EREFS score was developed as a way to standardize the description, recognition, and reporting of eosinophilic esophagitis, but its diagnostic utility and responsiveness to treatment were unknown, the authors said.

“This prospective study found that the EREFS classification has diagnostic utility for EoE,” they wrote. “Moreover, the score is responsive to treatment, decreasing significantly in histologic responders, and can be used as an outcome measure.”

The National Institutes of Health and the University of North Carolina Center for Gastrointestinal Biology and Disease funded the study. No conflicts of interest were declared.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

High serum insulin and leptin levels were significantly associated with Barrett’s esophagus, according to authors of a meta-analysis of nine observational studies published in the December issue of Clinical Gastroenterology and Hepatology.

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels, and were 1.74 times as likely to have hyperinsulinemia, said Dr. Apoorva Chandar of Case Western Reserve University (Cleveland) and his associates.

©Nephron/Wikimedia Commons/Creative Commons ASA 3.0

Central obesity was known to increase the risk of esophageal inflammation, metaplasia, and adenocarcinoma (Clin Gastroenterol Hepatol 2013 [doi: 10.1016/j.cgh.2013.05.009]), but this meta-analysis helped pinpoint the hormones that might mediate the relationship, the investigators said. However, the link between obesity and Barrett’s esophagus “is likely complex,” meriting additional longitudinal analyses, they added.

Metabolically active fat produces leptin and other adipokines. Elevated serum leptin has anti-apoptotic and angiogenic effects and also is a marker for insulin resistance, the researchers noted. “Several observational studies have examined the association of serum adipokines and insulin with Barrett’s esophagus, but evidence regarding this association remains inconclusive,” they said. Therefore, they reviewed observational studies published through April 2015 that examined relationships between Barrett’s esophagus, adipokines, and insulin. The studies included 10 separate cohorts of 1,432 patients with Barrett’s esophagus and 3,550 controls, enabling the researchers to estimate summary adjusted odds ratios (Clin Gastroenterol Hepatol. 2015 [doi: 10.1016/j.cgh.2015.06.041]).

Compared with population controls, patients with Barrett’s esophagus were twice as likely to have high serum leptin levels (adjusted OR, 2.23; 95% confidence interval [CI], 1.31-3.78) and 1.74 times as likely to have elevated serum insulin levels (95% CI, 1.14 to 2.65). Total serum adiponectin was not linked to risk of Barrett’s esophagus, but increased serum levels of high molecular weight (HMW) adiponectin were (aOR, 1.75; 95% CI, 1.16-2.63), and one study reported an inverse correlation between levels of low molecular weight leptin and Barrett’s esophagus risk. Low molecular weight adiponectin has anti-inflammatory effects, while HMW adiponectin is proinflammatory, the researchers noted.

“It is simplistic to assume that the effects of obesity on the development of Barrett’s esophagus are mediated by one single adipokine,” the researchers said. “Leptin and adiponectin seem to crosstalk, and both of these adipokines also affect insulin-signaling pathways.” Obesity is a chronic inflammatory state characterized by increases in other circulating cytokines, such as interleukin-6 and tumor necrosis factor–alpha, they noted. Their findings do not solely implicate leptin among the adipokines, but show that it “might be an important contributor, and support further studies on the effects of leptin on the leptin receptor in the proliferation of Barrett’s epithelium.” They also noted that although women have higher leptin levels than men, men are at much greater risk of Barrett’s esophagus, which their review could not explain. Studies to date are “not adequate” to assess gender-specific relationships between insulin, adipokines, and Barrett’s esophagus, they said.

Other evidence has linked insulin to Barrett’s esophagus, according to the researchers. Insulin and related signaling pathways are upregulated in tissue specimens of Barrett’s esophagus and esophageal adenocarcinoma, and Barrett’s esophagus is more likely to progress to esophageal adenocarcinoma in the setting of insulin resistance, they noted. “Given that recent studies have shown an association between Barrett’s esophagus and measures of central obesity and diabetes mellitus type 2, it is conceivable that hyperinsulinemia and insulin resistance, which are known consequences of central obesity, are associated with Barrett’s esophagus pathogenesis,” they said.

However, their study did not link hyperinsulinemia to Barrett’s esophagus among subjects with GERD, possibly because of confounding or overmatching, they noted. More rigorous studies would be needed to fairly evaluate any relationship between insulin resistance and risk of Barrett’s esophagus, they concluded.

The National Cancer Institute funded the study. The investigators had no conflicts of interest.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.