Upper GI Tract

Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

*This article was updated on May 7, 2018.

[email protected]

Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

*This article was updated on May 7, 2018.

[email protected]

Andexanet alfa, the first agent shown to reverse the anticoagulant effects of rivaroxaban and apixaban, has been approved by the FDA, according to a May 3 statement from Portola Pharmaceuticals.

It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.

Mitchel L. Zoler/MDedge News

Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.

The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.

Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.

Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.

*This article was updated on May 7, 2018.

[email protected]

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.

Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology. 

Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.

Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.

Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.

Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.

Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.

Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.

Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.

A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.

Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).

With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.

While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.

“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”

[email protected]

SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).

AGA Resource

AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.

Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology. 

Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.

Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.

Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.

Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.

Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.

Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.

Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.

A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.

Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).

With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.

While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.

“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”

[email protected]

SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).

AGA Resource

AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.

Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology. 

Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.

Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.

Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.

Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.

Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.

Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.

Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.

A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.

Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).

With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.

While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.

“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”

[email protected]

SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).

AGA Resource

AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.

Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.

“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.

Schnoodle/ThinkStock

Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.

To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.

In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.

The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).

Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.

“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”

Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.

SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.

Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.

“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.

Schnoodle/ThinkStock

Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.

To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.

In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.

The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).

Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.

“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”

Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.

SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.

Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.

“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.

Schnoodle/ThinkStock

Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.

To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.

In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.

The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).

Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.

“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”

Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.

SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.

Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.

The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.

The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.

Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:

• Is there a penicillin allergy?
• Has there been previous macrolide exposure?

“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.

“Bismuth quadruple therapy is never the wrong answer,” he added.

Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.

Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H₂ blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.

Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.

If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.

Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.

Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.

Global Academy and this news organization are owned by the same parent company.

Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.

Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.

The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.

The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.

Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:

• Is there a penicillin allergy?
• Has there been previous macrolide exposure?

“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.

“Bismuth quadruple therapy is never the wrong answer,” he added.

Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.

Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H₂ blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.

Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.

If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.

Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.

Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.

Global Academy and this news organization are owned by the same parent company.

Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.

Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.

The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.

The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.

Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:

• Is there a penicillin allergy?
• Has there been previous macrolide exposure?

“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.

“Bismuth quadruple therapy is never the wrong answer,” he added.

Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.

Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H₂ blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.

Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.

If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.

Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.

Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.

Global Academy and this news organization are owned by the same parent company.

Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.

Patients with drug-refractory gastroparesis with a high Cajal cell count who underwent neurostimulation showed symptomatic relief of one-hour gastric emptying and gastric electrical activity after the therapy, and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.

Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.

“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.

The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”

After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.

After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).

Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).

SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.

*This story was updated on 4/30/2018.

Patients with drug-refractory gastroparesis with a high Cajal cell count who underwent neurostimulation showed symptomatic relief of one-hour gastric emptying and gastric electrical activity after the therapy, and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.

Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.

“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.

The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”

After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.

After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).

Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).

SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.

*This story was updated on 4/30/2018.

Patients with drug-refractory gastroparesis with a high Cajal cell count who underwent neurostimulation showed symptomatic relief of one-hour gastric emptying and gastric electrical activity after the therapy, and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.

Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.

“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.

The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”

After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.

After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).

Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).

SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.

*This story was updated on 4/30/2018.

A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).

Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.

Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).

The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).

Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”

There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.

SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.

A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).

Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.

Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).

The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).

Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”

There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.

SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.

A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).

Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.

Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).

The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).

Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”

There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.

SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.

PHILADELPHIA – While traditional elimination diets for eosinophilic esophagitis are highly restrictive and endoscopically intensive, a new “step-up” approach may offer a superior empiric scheme for identifying food triggers, according to Stuart J. Spechler, MD.

The recently described step-up approach may be preferable to the standard empiric six-food elimination diet, which has a 72% success rate but is challenging to implement, according to Dr. Spechler, chief of the division of gastroenterology, Baylor University Medical Center at Dallas.

Andrew D. Bowser/MDedge News

[email protected]

PHILADELPHIA – While traditional elimination diets for eosinophilic esophagitis are highly restrictive and endoscopically intensive, a new “step-up” approach may offer a superior empiric scheme for identifying food triggers, according to Stuart J. Spechler, MD.

The recently described step-up approach may be preferable to the standard empiric six-food elimination diet, which has a 72% success rate but is challenging to implement, according to Dr. Spechler, chief of the division of gastroenterology, Baylor University Medical Center at Dallas.

Andrew D. Bowser/MDedge News

[email protected]

PHILADELPHIA – While traditional elimination diets for eosinophilic esophagitis are highly restrictive and endoscopically intensive, a new “step-up” approach may offer a superior empiric scheme for identifying food triggers, according to Stuart J. Spechler, MD.

The recently described step-up approach may be preferable to the standard empiric six-food elimination diet, which has a 72% success rate but is challenging to implement, according to Dr. Spechler, chief of the division of gastroenterology, Baylor University Medical Center at Dallas.

Andrew D. Bowser/MDedge News

[email protected]

PHILADELPHIA – When evaluating potential causes of gastroparesis, cannabis use is a “do not miss” diagnosis that is easy to overlook and likely on the rise, according to Anthony J. Lembo, MD.

“This is not an infrequent problem, and I’ve even missed it a couple of times,” said Dr. Lembo, director of the GI Motility Laboratory at Beth Israel Deaconess Medical Center, Boston.

The rate of U.S. emergency department visits for vomiting with cannabis use disorder rose from 2.3 to 13.3 per 100,000 visits from 2006 to 2013, according to an analysis recently published by Dr. Lembo and colleagues (J Clin Gastroenterol. 2017 Oct 31. doi: 10.1097/MCG.0000000000000944).

The study showed that men between 20 and 29 years were the most common group presenting for vomiting with cannabis use disorder.

“It was only after we managed to hospitalize him because he was losing so much weight that he came out and talked to one of the residents that he was an actually a daily pot smoker,” Dr. Lembo said. “Once we stopped it, the symptoms went away.”

PHILADELPHIA – When evaluating potential causes of gastroparesis, cannabis use is a “do not miss” diagnosis that is easy to overlook and likely on the rise, according to Anthony J. Lembo, MD.

“This is not an infrequent problem, and I’ve even missed it a couple of times,” said Dr. Lembo, director of the GI Motility Laboratory at Beth Israel Deaconess Medical Center, Boston.

The rate of U.S. emergency department visits for vomiting with cannabis use disorder rose from 2.3 to 13.3 per 100,000 visits from 2006 to 2013, according to an analysis recently published by Dr. Lembo and colleagues (J Clin Gastroenterol. 2017 Oct 31. doi: 10.1097/MCG.0000000000000944).

The study showed that men between 20 and 29 years were the most common group presenting for vomiting with cannabis use disorder.

“It was only after we managed to hospitalize him because he was losing so much weight that he came out and talked to one of the residents that he was an actually a daily pot smoker,” Dr. Lembo said. “Once we stopped it, the symptoms went away.”

PHILADELPHIA – When evaluating potential causes of gastroparesis, cannabis use is a “do not miss” diagnosis that is easy to overlook and likely on the rise, according to Anthony J. Lembo, MD.

“This is not an infrequent problem, and I’ve even missed it a couple of times,” said Dr. Lembo, director of the GI Motility Laboratory at Beth Israel Deaconess Medical Center, Boston.

The rate of U.S. emergency department visits for vomiting with cannabis use disorder rose from 2.3 to 13.3 per 100,000 visits from 2006 to 2013, according to an analysis recently published by Dr. Lembo and colleagues (J Clin Gastroenterol. 2017 Oct 31. doi: 10.1097/MCG.0000000000000944).

The study showed that men between 20 and 29 years were the most common group presenting for vomiting with cannabis use disorder.

“It was only after we managed to hospitalize him because he was losing so much weight that he came out and talked to one of the residents that he was an actually a daily pot smoker,” Dr. Lembo said. “Once we stopped it, the symptoms went away.”

Starting a prescription proton pump inhibitor (PPI) conferred no short-term increase in risk for myocardial infarction in a large retrospective insurance claims study.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Over a median follow-up of 2-3 months, estimated weighted risks of first-ever MI were low and similar regardless of whether patients started PPIs or histamine₂ receptor antagonists (H₂RAs), reported Suzanne N. Landi of the University of North Carolina at Chapel Hill, and her associates. “Contrary to prior literature, our analyses do not indicate increased risk of MI in PPI initiators compared to histamine₂-receptor antagonist initiators,” they wrote in the March issue of Gastroenterology.

Epidemiologic studies have produced mixed findings on PPI use and MI risk. Animal models and ex vivo studies of human tissue indicate that PPIs might harm coronary vessels by increasing plasma levels of asymmetrical dimethylarginine, which counteracts the vasoprotective activity of endothelial nitrous oxide synthase, the investigators noted. To further assess PPIs and risk of MI while minimizing potential confounding, they studied new users of either prescription PPIs or an active comparator, prescription H₂RAs. The dataset included administrative claims for more than 5 million patients with no MI history who were enrolled in commercial insurance plans or Medicare Supplemental Insurance plans. The study data spanned from 2001 to 2014, and patients were followed from their initial antacid prescription until they either developed a first-ever MI, stopped their medication, or left their insurance plan. Median follow-up times were 60 days in patients with commercial insurance and 96 days in patients with Medicare Supplemental Insurance, which employers provide for individuals who are at least 65 years old.

After controlling for numerous measurable clinical and demographic confounders, the estimated 12-month risk of MI was about 2 cases per 1,000 commercially insured patients and about 8 cases per 1,000 Medicare Supplemental Insurance enrollees. The estimated 12-month risk of MI did not significantly differ between users of PPIs and H₂RAs, regardless of whether they were enrolled in commercial insurance plans (weighted risk difference per 1,000 users, –0.08; 95% confidence interval, –0.51 to 0.36) or Medicare Supplemental Insurance (weighted risk difference per 1,000 users, –0.45; 95% CI, –1.53 to 0.58) plans.

The researchers received no grant support for this study. Ms. Landi disclosed a student fellowship from UCB Biosciences.

SOURCE: Source: Landi SN et al. Gastroenterology. 2017 Nov 6. doi: 10.1053/j.gastro.2017.10.042.

Starting a prescription proton pump inhibitor (PPI) conferred no short-term increase in risk for myocardial infarction in a large retrospective insurance claims study.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Over a median follow-up of 2-3 months, estimated weighted risks of first-ever MI were low and similar regardless of whether patients started PPIs or histamine₂ receptor antagonists (H₂RAs), reported Suzanne N. Landi of the University of North Carolina at Chapel Hill, and her associates. “Contrary to prior literature, our analyses do not indicate increased risk of MI in PPI initiators compared to histamine₂-receptor antagonist initiators,” they wrote in the March issue of Gastroenterology.

Epidemiologic studies have produced mixed findings on PPI use and MI risk. Animal models and ex vivo studies of human tissue indicate that PPIs might harm coronary vessels by increasing plasma levels of asymmetrical dimethylarginine, which counteracts the vasoprotective activity of endothelial nitrous oxide synthase, the investigators noted. To further assess PPIs and risk of MI while minimizing potential confounding, they studied new users of either prescription PPIs or an active comparator, prescription H₂RAs. The dataset included administrative claims for more than 5 million patients with no MI history who were enrolled in commercial insurance plans or Medicare Supplemental Insurance plans. The study data spanned from 2001 to 2014, and patients were followed from their initial antacid prescription until they either developed a first-ever MI, stopped their medication, or left their insurance plan. Median follow-up times were 60 days in patients with commercial insurance and 96 days in patients with Medicare Supplemental Insurance, which employers provide for individuals who are at least 65 years old.

After controlling for numerous measurable clinical and demographic confounders, the estimated 12-month risk of MI was about 2 cases per 1,000 commercially insured patients and about 8 cases per 1,000 Medicare Supplemental Insurance enrollees. The estimated 12-month risk of MI did not significantly differ between users of PPIs and H₂RAs, regardless of whether they were enrolled in commercial insurance plans (weighted risk difference per 1,000 users, –0.08; 95% confidence interval, –0.51 to 0.36) or Medicare Supplemental Insurance (weighted risk difference per 1,000 users, –0.45; 95% CI, –1.53 to 0.58) plans.

The researchers received no grant support for this study. Ms. Landi disclosed a student fellowship from UCB Biosciences.

SOURCE: Source: Landi SN et al. Gastroenterology. 2017 Nov 6. doi: 10.1053/j.gastro.2017.10.042.

Starting a prescription proton pump inhibitor (PPI) conferred no short-term increase in risk for myocardial infarction in a large retrospective insurance claims study.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Over a median follow-up of 2-3 months, estimated weighted risks of first-ever MI were low and similar regardless of whether patients started PPIs or histamine₂ receptor antagonists (H₂RAs), reported Suzanne N. Landi of the University of North Carolina at Chapel Hill, and her associates. “Contrary to prior literature, our analyses do not indicate increased risk of MI in PPI initiators compared to histamine₂-receptor antagonist initiators,” they wrote in the March issue of Gastroenterology.

Epidemiologic studies have produced mixed findings on PPI use and MI risk. Animal models and ex vivo studies of human tissue indicate that PPIs might harm coronary vessels by increasing plasma levels of asymmetrical dimethylarginine, which counteracts the vasoprotective activity of endothelial nitrous oxide synthase, the investigators noted. To further assess PPIs and risk of MI while minimizing potential confounding, they studied new users of either prescription PPIs or an active comparator, prescription H₂RAs. The dataset included administrative claims for more than 5 million patients with no MI history who were enrolled in commercial insurance plans or Medicare Supplemental Insurance plans. The study data spanned from 2001 to 2014, and patients were followed from their initial antacid prescription until they either developed a first-ever MI, stopped their medication, or left their insurance plan. Median follow-up times were 60 days in patients with commercial insurance and 96 days in patients with Medicare Supplemental Insurance, which employers provide for individuals who are at least 65 years old.

After controlling for numerous measurable clinical and demographic confounders, the estimated 12-month risk of MI was about 2 cases per 1,000 commercially insured patients and about 8 cases per 1,000 Medicare Supplemental Insurance enrollees. The estimated 12-month risk of MI did not significantly differ between users of PPIs and H₂RAs, regardless of whether they were enrolled in commercial insurance plans (weighted risk difference per 1,000 users, –0.08; 95% confidence interval, –0.51 to 0.36) or Medicare Supplemental Insurance (weighted risk difference per 1,000 users, –0.45; 95% CI, –1.53 to 0.58) plans.

The researchers received no grant support for this study. Ms. Landi disclosed a student fellowship from UCB Biosciences.

SOURCE: Source: Landi SN et al. Gastroenterology. 2017 Nov 6. doi: 10.1053/j.gastro.2017.10.042.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.