User login
GI Disorders Linked With Sleep Problems
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
“Emerging evidence suggests a bidirectional relationship between GI diseases and sleep disorders, whereby dysfunction in one domain may exacerbate the other,” wrote Shicheng Ye, PhD, of The Third Clinical Medical College of Guangzhou University of Chinese Medicine, and colleagues. However, previous studies on the association between GI and sleep problems have been small, and the role of depression as a mediator has not been well explored.
In the study, which was published online in BMC Gastroenterology, the researchers reviewed data from the US National Health and Nutrition Examination Survey between 2005 and 2014. The study population included 10,626 adults aged 20 years or older, with a mean age of 45.6 years, 50.8% of whom were women. Of these, 6444 were identified as having GI disease on the basis of a “yes” response to the question of whether they had a stomach or intestinal illness with vomiting or diarrhea within the past 30 days.
Researchers also examined responses to survey questions related to sleep duration, trouble sleeping, and diagnosis of a sleep disorder. Individuals with vs without GI diseases had a significantly higher prevalence of sleep trouble (37.99% vs 24.21%; P < .001) and a greater frequency of diagnosed sleep disorders (14.99% vs 8.08%; P < .001).
An analysis adjusted for demographic, lifestyle, and clinical factors found that individuals with vs without GI diseases were 70% more likely to have sleep trouble. Individuals with vs without GI diseases were also significantly more likely to have a diagnosed sleep disorder and a reduction in sleep duration (adjusted odds ratio, 1.8; adjusted beta, -0.15).
The association between GI diseases and sleep problems remained consistent across individuals of multiple subgroups, including those without hypertension, diabetes, or a history of smoking. It also remained significant among individuals with coronary heart disease and higher scores on the dietary index for gut microbiota. No significant interaction effects related to age, sex, or chronic disease appeared in any subgroup (P > .05).
An additional mediation analysis found that depression partly mediated the associations between GI diseases and sleep issues. Depression accounted for 21.29% of the total effect on sleep problems, 19.23% of the effect on sleep disorders, and 26.68% of the effect on sleep duration.
The mediating role of depression on the association between GI disease and sleep problems may not be exclusive, the researchers wrote. Other potential mechanisms may include systemic inflammation, visceral hypersensitivity, and metabolic dysfunction.
The findings were limited by several factors, including the possibly underpowered sample size for machine-learning models and the reliance on self-reports of GI diseases, sleep outcomes, and coronary heart disease, the researchers noted. Other limitations included the inability to adjust for confounding factors, including obstructive sleep apnea, chronic pain, and hypertension.
However, the results illustrate the need to address both psychological and GI factors in clinical practice to improve sleep health, the researchers wrote. More research is needed to identify causal pathways and develop targeted, multidimensional interventions for this interconnected trio of health problems.
Increasing Evidence for Gut-Brain Interaction
Both sleep disorders and disorders of GBI (DGBI) are highly prevalent worldwide, Jatin Roper, MD, gastroenterologist and associate professor of medicine at Duke University, Durham, North Carolina, told GI & Hepatology News.
“A growing body of evidence suggests that DGBI, including irritable bowel syndrome, are caused by imbalances in signaling between the brain and the intestine, which include the vagus nerve, hormonal signals, the gut microbiota, and immune system,” said Roper, who was not involved in the current study.
“Since many sleep disturbances are centrally mediated, it is plausible that sleep and gastrointestinal disorders could be mechanistically linked,” he said. Rigorous analysis of patient databases for a possible association between sleep and GI disorders, as was done in the current study, is an important step.
The current study findings were not unexpected, “particularly the finding that depression may mediate a link between sleep and GI disorders, because depression is well known to be associated to sleep disturbances and DGBI,” Roper said.
However, GI doctors often do not ask patients about problems with sleep, and pulmonary doctors or sleep specialists may not ask patients about GI symptoms, Roper noted. Similarly, patients may not bring up all their symptoms when seeing these specialists.
“The current study underscores the need for comprehensive, multisystem evaluations in specialty clinics for sleep and GI conditions and appropriate referrals to specialists, when necessary,” he said.
The research raised an important question of whether sleep and GI disorders are associated with each other because of other underlying medical conditions, which may be difficult to control for in cross-sectional studies, or whether sleep problems cause GI problems or vice versa, Roper said. Other uncertainties include whether the conditions are biologically linked, possibly through shared changes in the brain-gut axis.
Long-term observational studies would be useful to identify whether sleep disturbances precede DGBI or vice versa, Roper added.
The study received no outside funding. The researchers and Roper had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Elevated Serologic Markers Insufficient to Diagnose Celiac Disease
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.
, a large pediatric cohort study in North America found.
Because tTG-IgA assay performance varied widely across labs, diagnostic confirmation by a specialist is essential before gluten-targeted dietary changes are made, according to Denis Chang, MD, MS, of the Division of Gastroenterology and Nutrition at Boston Children’s Hospital in Boston, and colleagues reported in Pediatrics.
“Currently, small intestinal biopsy is the gold standard for diagnosing pediatric celiac disease, but recent European diagnostic criteria allow a nonbiopsy pathway for serologic diagnosis,” Chang told GI & Heaptology News. The European guidelines allow this pathway when a very high tTG-IgA is confirmed by a positive endomysial IgA antibody (EMA) in a second blood sample.
Those guidelines have not been adopted on this continent, however, so Chang’s group assessed the positive predictive value (PPV) of the North American tTG-IgA assay to identify histologic findings of celiac disease.
Another issue is the absence of a universal standard threshold across labs for a high antibody value. “Common assays used in North America differ in performance, and there are not many large multicenter studies looking at this issue. Hopefully, a standard will be developed in the near future. Before this serologic pathway can enter into our guidelines, this question needs to be addressed.”
Study Details
The multicenter retrospective study by Dr. Chang’s team looked at patients younger than 18 years from three pediatric hospitals in Canada and nine in the US who had an elevated tTG-IgA within 6 months of an esophagogastroduodenoscopy from January 2016 to December 2021. Biopsy-confirmed celiac disease was determined by the presence of intraepithelial lymphocytosis and villous atrophy. The primary outcomes were the PPV of an elevated tTG-IgA and a tTG-IgA at least 10 times the upper limit of normal (10x ULN).
The study cohort included 4019 children (63.3% female, 9% with type 1 diabetes, and 2% with Down syndrome). Histologic findings were consistent with celiac disease for 3321 children, for a PPV of 82.6% (95% CI, 81.4%-83.8%).
Among the 1739 (43.2%) children with tTG-IgA of at least 10x ULN, 1651 had biopsy-confirmed celiac disease, for a PPV 10x ULN of 94.9% (95% CI, 93.8%-95.9%). About 5% (n = 88) of positive-testing children did not have histologic findings of celiac disease, including 2% (n = 41) with normal histology.
Diagnostic accuracy of tTG-IgA varied widely among the assays used in North America, with a PPV range of 71.5%-88.8% and a PPV 10x ULN range of 89.3%-97.3%. Assays did not perform as well in children with type 1 diabetes: PPV 10x ULN of 89% (95% CI, 83.5%-92.8%).
In other notable findings, the EMA blood test only marginally improved specificity, as 76% of children without celiac disease, but with a tTG-IgA of at least 10x ULN had a positive EMA in the same sample.
While the study lends credence to the notion that a highly positive tTG-IgA correlates with enteropathy in most children, the 1 in 20 with a tTG-IgA greater than 10x ULN who did not have histologic findings diagnostic of celiac disease cannot be ignored. “This included 2% who had normal small intestinal biopsies on a gluten-containing unrestricted diet, highlighting the limitations of making a celiac disease diagnosis based solely upon a single, highly positive tTG-IgA level,” Chang and colleagues wrote.
Does this mean that substantial numbers of children with suspected celiac disease are being unnecessarily placed on gluten-restricted diets to no avail? “That’s a good question, but our retrospective data do not provide an answer to that,” Chang said. And what causes elevated autoantibodies in children who are not diagnosed with celiac disease? “That is also a question that will require further research,” he said.
Commenting on the study but not involved in it, Supriya Nair, MD, a pediatric gastroenterologist at UTHealth Houston, called it “very interesting because it highlights for primary care physicians that we may need endoscopic evaluation more than we thought.” This is particularly true given the lack of standardized laboratory values noted in the study.
Nair said that some children with high seromarker levels but no discernible lesions may develop celiac disease later. “It may be that the markers are not yet causing inflammation in the bowel. These patients must be monitored to see if levels stay high or come down.”
In her practice, she has seen some children who have been put on gluten-free diets prematurely. “But it’s very important to get an accurate, official confirmation with endoscopy because of the ramifications of a celiac diagnosis,” she said. “This is a lifelong condition, and the diet is not easy to follow, especially in North America.” And for children, especially, there are restrictive social impacts and the constant need to be aware of what they’re eating and the danger of cross-contamination in foods, she said.
Chang hopes these data will be pivotal in helping medical societies develop new North American guidelines. In the meantime, pediatricians and primary doctors need to be aware that a high number on a tTG-IgA test does not always mean the presence of celiac disease, although it could be a harbinger of its future development. “Further confirmation by a specialist is essential.”
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Chang and Nair reported having no competing interests. Several study authors reported receiving research support from and serving as consultants or members of data safety monitoring boards for pharmaceutical companies.
A version of this article appeared on Medscape.com.
Skip Antibiotic Prophylaxis for Upper GI Bleeding in Cirrhosis?
Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).
Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).
Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], -2.6% to 4.9%).
Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“Our findings re-open the discussion surrounding the long-standing and firmly held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
New trials for shorter duration and no antibiotic prophylaxis “should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
New Treatment Guidance Issued for Challenging Overlap of Hypermobility Syndromes and GI Symptoms
to help clinicians comprehend such cases.
“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.
Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.
“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”
Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.
With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.
“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”
Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”
With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.
In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:
- Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
- Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
- Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
- In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.
Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.
In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.
Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.
“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”
“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”
Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.
“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.
“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”
Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.
Deciphering Gut-Brain Disorder Challenges
Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.
“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.
“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”
Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.
“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.
The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.
Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.
A version of this article appeared on Medscape.com.
to help clinicians comprehend such cases.
“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.
Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.
“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”
Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.
With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.
“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”
Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”
With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.
In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:
- Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
- Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
- Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
- In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.
Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.
In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.
Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.
“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”
“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”
Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.
“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.
“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”
Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.
Deciphering Gut-Brain Disorder Challenges
Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.
“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.
“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”
Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.
“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.
The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.
Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.
A version of this article appeared on Medscape.com.
to help clinicians comprehend such cases.
“Recognizing and treating GI symptoms in patients with hEDS or hypermobility spectrum disorders and comorbid POTS or MCAS present major challenges for clinicians, who often feel under equipped to address their needs,” AGA reported in the update, published in Clinical Gastroenterology and Hepatology.
Importantly, “the poor understanding of these overlapping syndromes can lead to nonstandardized approaches to diagnostic evaluation and management,” the authors noted.
“Gastroenterology providers should be aware of the features of [these syndromes] to recognize the full complexity of patients presenting with multisystemic symptoms.”
Hypermobility spectrum disorders, which include hEDS, are typically genetic, and patients experience pain along with joint hypermobility, or extreme flexibility of joints beyond the normal range of motion.
With research showing that most of those patients — up to 98% — also experience GI symptoms, gastroenterologists may be encountering them more commonly than realized, Lucinda A. Harris, MD, AGAF, of the Mayo Clinic School of Medicine, in Scottsdale, Arizona, explained to GI & Hepatology News.
“As our knowledge in gastroenterology has progressed, we realize that hypermobility itself predisposes individuals to disorders of brain-gut interaction,” she said. “We may only be seeing the tip of the iceberg when it comes to diagnosing patients with hypermobility.”
Additionally, “many of these patients have POTS, which has also been increasingly diagnosed,” Harris added. “The strong overlap of these conditions prompted us to present this data.”
With a lack of evidence-based understanding of the overlapping syndromes, AGA’s guidance does not carry formal ratings but is drawn from a review of the published literature and expert opinion.
In addition to the key recommendation of being aware of the observed combination of syndromes, their recommendations include:
- Regarding testing: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of the disorders, but universal testing for POTS/MCAS in all patients with hEDS or hypermobility spectrum disorders is not currently supported by the evidence, the guidance advises.
- Gastroenterologists seeing patients with disorders of gut-brain interaction should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS or offer appropriate referral to a specialist where resources are available, the AGA recommends.
- Medical management: Management of GI symptoms in hEDS or hypermobility spectrum disorders and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results.
- In addition to general disorders of gut-brain interactions and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.
Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.
In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS or hypermobility spectrum disorders and disorders of gut-brain interaction with episodic symptoms that suggest a more generalized mast cell disorder involving two or more physiological systems. However, current data does not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS or hypermobility spectrum disorders without clinical or laboratory evidence of a primary or secondary mast cell disorder, the authors noted.
Harris explained that patients presenting with gut-brain disorders are often mistakenly classified as having irritable bowel syndrome or dyspepsia, whereas these conditions may be affecting the GI disorders they have.
“For example, a patient with Ehlers-Danlos syndrome might have problems with constipation, which is impacted by pelvic floor dysfunction,” she said. “Due to their hypermobility, they may experience more pelvic floor descent than usual.”
“If we do not recognize this, the patient risks developing rectal prolapse or not effectively addressing their constipation.”
Regarding patient characteristics, Harris said that those with hEDS and POTS appear to more likely be women and tend to present in younger patients, aged 18-50 years. Of note, there is no genetic test for hEDS.
“The take-home point for clinicians should be to consider POTS and Ehlers-Danlos syndrome when encountering young female patients with symptoms of palpitations, hypermobility, and orthostatic intolerance,” she said.
“Recognizing hypermobility is crucial, not only for GI symptoms but also to prevent joint dislocations, tendon ruptures, and other connective tissue issues.”
Clinicians are further urged to “offer informed counseling, and guide patients away from unreliable sources or fragmented care to foster therapeutic relationships and evidence-based care,” the authors added.
Deciphering Gut-Brain Disorder Challenges
Commenting to GI & Hepatology News, Clair Francomano, MD, a professor of medical and molecular genetics at the Indiana University School of Medicine, in Indianapolis, said the new guidance sheds important light on the syndromes.
“I’m delighted to see this guidance offered through the AGA as it will encourage gastroenterologists to think of EDS, POTS and MCAS when they are evaluating patients with disorders of gut-brain interaction,” Francomano said.
“This should allow patients to receive more accurate and timely diagnoses and appropriate management.”
Francomano noted that the Ehlers-Danlos Society, which provides information for clinicians and patients alike on the syndromes, and where she serves on the medical scientific board, has also been active in raising awareness.
“While co-occurrence of POTS and MCAS with EDS has in fact been recognized for many years, I do think awareness is increasing, in large part due to the advocacy and educational efforts of the Ehlers-Danlos Society,” she said.
The take-home message? “When clinicians see disorders of the gut-brain axis, POTS or MCAS, they should be thinking, ‘Could this be related to joint hypermobility or Ehlers-Danlos syndrome?’” Francomano said.
Harris reported serving as a consultant for AbbVie, Ardelyx, Salix, and Gemelli Biotech and reported receiving research support from Takeda and Anyx. Francomano did not report any relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Journal Highlights: May-July 2025
Esophagus/Motility
Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.
Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.
Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.
Stomach
Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.
Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.
Colon
Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.
Pancreas
Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.
Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.
Hepatology
Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.
Miscellaneous
Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.
Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.
Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.
Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.
Stomach
Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.
Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.
Colon
Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.
Pancreas
Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.
Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.
Hepatology
Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.
Miscellaneous
Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.
Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Esophagus/Motility
Nguyen AD, et al. AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review. Gastroenterology. 2025 Jul. doi: 10.1053/j.gastro.2025.05.011.
Hartnett DA, et al. Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.06.032.
Gyawali CP, et al. pH Impedance Monitoring on Proton Pump Inhibitor Therapy Impacts Management Decisions in Proven GERD but not in Unproven GERD. Clin Gastroenterol Hepatol. 2025 May. doi: 10.1016/j.cgh.2025.02.032.
Stomach
Wiklund AK, et al. Risk of Gastric Adenocarcinoma After Eradication of Helicobacter pylori. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.239.
Sonaiya S, et al. Over-the-Scope Clip versus Standard Endoscopic Therapy as First-Line Intervention for Nonvariceal Upper Gastrointestinal Bleeding: A Cost-Effectiveness Analysis. Tech Innov Gastrointest. 2025 Jun. doi: 10.1016/j.tige.2025.250935.
Colon
Hassan C, et al. Colon Cancer Screening, Surveillance, and Treatment: Novel Artificial Intelligence Driving Strategies in the Management of Colon Lesions. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.021.
Pancreas
Wilcox CM, et al; US Pancreatic Disease Study Group. Management of the Disconnected Pancreatic Duct in Pancreatic Necrosis. Clin Gastroenterol Hepatol. 2025 Jul. doi: 10.1016/j.cgh.2025.05.024.
Ghimire C, et al. The effect of advances in pancreatic cancer treatment in population mortality: A SEER-based study. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100739.
Hepatology
Canivet CM, et al. Validation of the AASLD/EASL Multi-Step Screening Strategies for MASLD. Gastro Hep Adv. 2025 Jul. doi: 10.1016/j.gastha.2025.100747.
Miscellaneous
Chang L, et al. Gut Feelings: The Critical Role of Interoception in Obesity and Disorders of Gut-Brain Interaction. Gastroenterology. 2025 Aug. doi: 10.1053/j.gastro.2025.04.002.
Bashiri K, et al. Advancing Hemostatic Powder Technologies for Management of Gastrointestinal Bleeding: Challenges and Solutions. Tech Innov Gastrointest. 2025 Jul. doi: 10.1016/j.tige.2025.250940.
Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.
Most GI Service Chiefs Support POCUS Training, But Uptake Is Slow
, according to a national survey.
Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.
“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”
To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.
Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.
Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.
Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.
Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.
Barriers to implementation were widespread and often multifactorial.
Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds.
Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them.
Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.
“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway.
They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.
The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
, according to a national survey.
Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.
“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”
To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.
Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.
Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.
Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.
Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.
Barriers to implementation were widespread and often multifactorial.
Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds.
Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them.
Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.
“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway.
They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.
The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
, according to a national survey.
Low POCUS uptake may be explained by substantial barriers to implementation, including lack of trained instructors, necessary equipment, and support staff, lead author Keerthi Thallapureddy, MD, of the University of Texas Health San Antonio, and colleagues, reported.
“POCUS is being increasingly used by gastroenterologists due to its portability and real-time diagnostic ability,” the investigators wrote in Gastro Hep Advances, but “there is limited understanding of how gastroenterologists use POCUS.”
To learn more, the investigators conducted a nationwide survey of the VA healthcare system. Separate questionnaires were sent to chiefs of staff (n = 130) and GI service chiefs (n = 117), yielding response rates of 100% and 79%, respectively.
Respondents represented a wide distribution of geographic regions and institutional complexity levels, with 80% of GI groups based at high-complexity centers and 92% in urban locations. A minority (8%) reported the presence of a liver transplant program.
Data collection focused on the prevalence of POCUS use, types of clinical applications, institutional policies and training processes, and perceived or actual barriers to wider adoption. Barriers were sorted into three categories: training, equipment, and infrastructure.
Of the 93 GI service chiefs who participated in the survey, 44% reported that at least 1 gastroenterologist at their facility currently uses POCUS. Most common procedural uses were paracentesis (23%) and liver biopsy (13%), while ascites assessment (19%) and biliary visualization (7%) were the most common diagnostic uses.
Among the same respondents, 69% said they would support sending clinicians to a POCUS training course, and 37% said their teams had expressed an active interest in pursuing such training. Only 17% of facilities had a formal process in place to obtain POCUS training, and an equal proportion had implemented a facility-wide policy to guide its use.
Barriers to implementation were widespread and often multifactorial.
Most challenges related to training: 48% of sites reported a lack of trained providers, 28% cited insufficient funding for training, 24% noted a lack of training opportunities, and 14% reported difficulty securing travel funds.
Equipment limitations were also common, with 41% of sites lacking ultrasound machines and 27% lacking funding to purchase them.
Institutional infrastructure posed further hurdles. Nearly a quarter of GI chiefs (23%) reported lacking a clinician champion to lead implementation, while others cited a lack of support staff, simulation space, privileging criteria, image archiving capabilities, or standardized reporting forms.
“Our findings on current POCUS use, training, barriers, and infrastructure can guide expansion of POCUS use and training among GI groups,” Dr. Thallapureddy and colleagues wrote, noting that early efforts to expand access to GI-specific POCUS training are already underway.
They cited growing interest from national organizations such as the American Gastroenterological Association and the American Association for the Study of Liver Diseases, the latter of which piloted training workshops at the 2024 Liver Meeting. Similarly, the International Bowel Ultrasound Group now offers a 3-part certification program in intestinal ultrasound and is developing additional online and interactive modules to improve training accessibility.
The study was supported by the US Department of Veterans Affairs, Quality Enhancement Research Initiative Partnered Evaluation Initiative Grant, and the VA National Center for Patient Safety. The investigators reported no conflicts of interest.
FROM GASTRO HEP ADVANCES
Evolving Standards of Practice: Esophageal Varices and Barrett’s Esophagus
Dear colleagues,
In the dynamic field of medicine, long-held practices are being reevaluated in light of new evidence and evolving standards of practice.
Dr. Anahita Rabiee discusses the importance of prioritizing non-selective beta blockers (NSBB) over endoscopic variceal ligation (EVL) in the primary prophylaxis of variceal bleeding in patients with compensated cirrhosis. Drawing on data from the PREDESCI trial and real-world experience, she argues that NSBB address the upstream driver—portal hypertension—more broadly and effectively than EVL. In a complementary piece, Dr. Tarek Sawas explores the nuanced landscape of screening and surveillance in Barrett’s esophagus. From how to manage irregular Z-lines, to rethinking the need for 1-year follow-up endoscopies and interpreting the implications of the BOSS trial, Dr. Sawas advocates for a more personalized, risk-based approach.
We hope these perspectives spark dialogue and reflection in your own practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Choose NSBBs, Not EVL, in Patients with Compensated Cirrhosis
BY ANAHITA RABIEE, MD, MHS
I strongly favor the use of non selective beta blockers (NSBBs) in patients with compensated cirrhosis, rather than endoscopy and esophageal variceal ligation (EVL) for primary prophylaxis.
Since the results of PREDESCI trial (β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (CSPH)) were published in 2019, there has been much debate on the role of screening endoscopy and EVL for primary prophylaxis. While many argue that a single randomized trial should not overturn long standing practice, several compelling reasons convince me to choose NSBBs, when possible.
Recent guidance from major liver societies now recommends NSBBs as first line therapy for CSPH. Yet, adoption in clinical practice remains inconsistent.
Here is why I believe NSBB represent a better solution:
Treating Upstream, Not Just a Local Treatment
NSBBs such as propranolol and nadolol decrease portal pressure by decreasing portal venous inflow through β1 and β2 adrenergic blockade. Carvedilol is often preferred given its additional α1 adrenergic blocking activity making it the most effective one in decreasing the portal pressure. Therefore, NSBBs address the upstream driver of decompensation by decreasing portal pressures.
EVL, in contrast, is a local fix that only prevents variceal bleeding. Ascites, not variceal bleeding, is the most common initial decompensating event and is associated with high mortality. Preventing all forms of decompensation is clearly preferable to preventing just one.
Broader Eligibility, More Patients Benefit
CSPH is defined as hepatic venous pressure gradient (HVPG)>10 mmHg, the threshold where increased portal venous inflow secondary to splanchnic vasodilation and hyperdynamic circulation drives the increase in portal hypertension. This threshold has been shown to strongly predict decompensation in patients with compensated disease.
While all patients with varices have CSPH, not all patients with CSPH have varices. They can be identified by other non invasive criteria such as cross sectional imaging showing collaterals, or liver stiffness and platelet thresholds that have been previously validated. By restricting intervention to those with large varices and offering only EVL, we miss the opportunity to intervene earlier and to a broader group that would benefit from this treatment.
Comprehensive Protection Without Repeated Endoscopies
Once on an appropriate NSBB dose, patients are protected against variceal bleeding (at least as effectively as EVL). This eliminates the need for repeated surveillance endoscopies to identify and treat large varices in otherwise compensated patients.
Better Tolerated and – In Many Cases – Overlaps With Existing Medication List!
While overtreatment is a concern, regular endoscopies every two years are also burdensome. Many patients already need beta blockers for cardiac conditions such as atrial fibrillation, ischemic heart disease or hypertension. Carvedilol, in particular, offers dual benefit for both hepatologists and cardiologists.
It is important to emphasize that these arguments apply to compensated cirrhosis. In decompensated disease, the approach changes. After a variceal bleed, both NSBBs and EVL are required for secondary prophylaxis. In patients with prior ascites but no variceal bleed, the benefit of NSBBs is less pronounced since decompensation has already occurred. In this setting, NSBBs can still be used selectively, but only if systolic blood pressure remains above 90 mmHg.
The evidence supporting NSBBs over EVL in compensated cirrhosis is not perfect, but few things in medicine are. Given current data, NSBBs should be the first line therapy in compensated cirrhosis with CSPH. Once a patient is on an appropriate and tolerated NSBB dose, routine endoscopic surveillance is unnecessary. Endoscopy should be reserved for those who cannot tolerate NSBBs, in whom EVL is then indicated if large varices are present.
Dr. Rabiee is based at the Yale School of Medicine, New Haven, Connecticut, and the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut. She has no disclosures in regard to this article.
Rethinking Screening and Surveillance in Barrett’s Esophagus: Navigating Controversies and Nuances
BY TAREK SAWAS, MD, MPH
Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Despite our comprehensive guidelines, many of the day-to-day decisions still rely on clinical judgment and honest conversations with patients. This article explores common scenarios in which management decisions are nuanced and the right answer remains debatable.
Irregular Z-Line/Ultrashort Segment BE: Leave Or Watch It?
Few findings provoke more confusion than irregular Z-line or intestinal metaplasia (IM) < 1 cm at the gastroesophageal junction (GEJ). For years, we have debated whether these subtle changes represent a precursor to EAC or simply a benign variant. We have wrestled with how to handle these cases from whether we should take biopsies to how to perform surveillance.
The American College of Gastroenterology (ACG) guideline suggests that irregular Z-lines should not be routinely biopsied or surveyed. Similarly, the upcoming American Gastroenterology Association (AGA) surveillance guideline suggests against surveillance of IM<1 cm citing the low individual annual risk of progression to high-grade dysplasia (HGD) and EAC of 0.23% per year which is lower than that of non-dysplastic Barrett’s esophagus (NDBE). However, this is not the entire picture.
Despite the low per-patient risk, IM<1cm is highly prevalent with columnar mucosa observed in approximately 15% of patients undergoing upper endoscopy. This paradox is unsettling. While any one patient with IM<1 cm is unlikely to progress to EAC, the group accounts for a meaningful share of the EAC burden. Some experts have argued that this justifies routine biopsy and surveillance in all patients with visible columnar mucosa regardless of length. However, this approach risks overwhelming our surveillance infrastructure.
A recent decision modeling analysis suggested that at the lowest progression rates, either no surveillance or one-time endoscopy can be considered. Based on these data, I do not regularly biopsy ultrashort segments unless the mucosa appears suspicious. In those with IM<1 cm detected during a high-quality endoscopic exam, no follow-up is needed. However, if the exam is suboptimal, I perform a 1-time high-quality repeat exam. If there is no evidence of dysplasia then I do not pursue any further surveillance.
The One-Year Follow-Up Endoscopy: Is It Necessary?
Another controversy is the one-year follow-up endoscopy after an initial diagnosis of NDBE. Proponents of this approach cite the high proportion of post endoscopy esophageal neoplasia and cancer (PEEN/PEEC) detected in the first year after diagnosis (missed HGD/EAC). In fact, PEEN account for about a quarter of all HGD/EAC cases diagnosed during surveillance.
While this approach might mitigate PEEN/PEEC risk, it may not be necessary if the index endoscopy is high quality. To ensure high quality exams, several best practices have been proposed including:
- Use of high-definition white light endoscopy (HD-WLE) with chromoendoscopy (virtual or dye based)
- Appropriate inspection time (1 minute per cm of circumferential BE)
- Accurate documentation using the Prague criteria
- Adherence to the Seattle protocol with additional targeted biopsies
If the index endoscopy meets these quality metrics, I typically do not bring the patient back at one year. However, if the exam quality is in question, then I repeat it at one year to establish a reliable baseline and rule out prevalent neoplasia.
Surveillance In NDBE: After BOSS, Do We Rethink Everything?
The recently published BOSS trial (Barrett’s Oesophagus Surveillance Study) has reignited the debate over the value of endoscopic surveillance in NDBE. In this study, 3,453 patients with NDBE across the UK were randomized to either surveillance endoscopy every two years or endoscopy only as clinically indicated. After a median follow-up of 12.8 years, the trial found no significant difference in all-cause mortality between the two groups.
While these findings are important, they should be interpreted with caution. First, the primary endpoint, all-cause mortality, is not optimal for evaluating surveillance for EAC. Surveillance is not intended to reduce all-cause mortality but rather to reduce EAC–related mortality. Second, a substantial number of patients in the no surveillance group still underwent endoscopy at intervals that were not meaningfully different from those in the surveillance group. If both groups receive similar exposure to endoscopy, the comparison loses power. Lastly, the trial was underpowered due to overestimation of progression risk during its initial design. As we have since learned, the risk of progression of NDBE is lower than originally assumed.
So where do we stand now? For me, the BOSS trial does not negate the value of surveillance. it reminds us that a one-size-fits-all approach is inefficient, and our strategy must be risk based. For low-risk individuals, particularly older adults with short-segment NDBE, surveillance may offer little benefit. But in healthier, younger patients with longer segments or additional risk factors, surveillance remains an essential tool for early neoplasia detection.
When to Stop Surveillance
Perhaps the most under-discussed point is when to stop surveillance. Existing guidelines do not account for competing mortality risks unrelated to EAC or provide specific recommendations regarding cessation of surveillance. The desired benefits of surveillance likely diminish with advanced age and greater comorbidity because of lower life expectancy and ineligibility for definitive therapy for EAC.
A recent modeling study found that the optimal ages for last surveillance were 81, 80, 77, and 73 years for men with no, mild, moderate, and severe comorbidity respectively and 75, 73, 73, and 69 years for women. In my practice, I discuss surveillance cessation in patients older than 75 based on their comorbidities. If the risk of progression is outweighed by the risk of the procedure or by the reality of limited life expectancy, we should not hesitate to consider surveillance cessation.
In summary, high-quality endoscopic exam in appropriately selected patients remains the cornerstone of BE surveillance. A more personalized, risk-based approach is needed taking into account competing comorbidities. Emerging technology through risk stratification tools such as biomarkers and artificial intelligence may refine our approach and help address the current limitations.
Dr. Sawas is based at the University of Texas Southwestern, Dallas, Texas. He has no disclosures in regard to this article.
Dear colleagues,
In the dynamic field of medicine, long-held practices are being reevaluated in light of new evidence and evolving standards of practice.
Dr. Anahita Rabiee discusses the importance of prioritizing non-selective beta blockers (NSBB) over endoscopic variceal ligation (EVL) in the primary prophylaxis of variceal bleeding in patients with compensated cirrhosis. Drawing on data from the PREDESCI trial and real-world experience, she argues that NSBB address the upstream driver—portal hypertension—more broadly and effectively than EVL. In a complementary piece, Dr. Tarek Sawas explores the nuanced landscape of screening and surveillance in Barrett’s esophagus. From how to manage irregular Z-lines, to rethinking the need for 1-year follow-up endoscopies and interpreting the implications of the BOSS trial, Dr. Sawas advocates for a more personalized, risk-based approach.
We hope these perspectives spark dialogue and reflection in your own practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Choose NSBBs, Not EVL, in Patients with Compensated Cirrhosis
BY ANAHITA RABIEE, MD, MHS
I strongly favor the use of non selective beta blockers (NSBBs) in patients with compensated cirrhosis, rather than endoscopy and esophageal variceal ligation (EVL) for primary prophylaxis.
Since the results of PREDESCI trial (β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (CSPH)) were published in 2019, there has been much debate on the role of screening endoscopy and EVL for primary prophylaxis. While many argue that a single randomized trial should not overturn long standing practice, several compelling reasons convince me to choose NSBBs, when possible.
Recent guidance from major liver societies now recommends NSBBs as first line therapy for CSPH. Yet, adoption in clinical practice remains inconsistent.
Here is why I believe NSBB represent a better solution:
Treating Upstream, Not Just a Local Treatment
NSBBs such as propranolol and nadolol decrease portal pressure by decreasing portal venous inflow through β1 and β2 adrenergic blockade. Carvedilol is often preferred given its additional α1 adrenergic blocking activity making it the most effective one in decreasing the portal pressure. Therefore, NSBBs address the upstream driver of decompensation by decreasing portal pressures.
EVL, in contrast, is a local fix that only prevents variceal bleeding. Ascites, not variceal bleeding, is the most common initial decompensating event and is associated with high mortality. Preventing all forms of decompensation is clearly preferable to preventing just one.
Broader Eligibility, More Patients Benefit
CSPH is defined as hepatic venous pressure gradient (HVPG)>10 mmHg, the threshold where increased portal venous inflow secondary to splanchnic vasodilation and hyperdynamic circulation drives the increase in portal hypertension. This threshold has been shown to strongly predict decompensation in patients with compensated disease.
While all patients with varices have CSPH, not all patients with CSPH have varices. They can be identified by other non invasive criteria such as cross sectional imaging showing collaterals, or liver stiffness and platelet thresholds that have been previously validated. By restricting intervention to those with large varices and offering only EVL, we miss the opportunity to intervene earlier and to a broader group that would benefit from this treatment.
Comprehensive Protection Without Repeated Endoscopies
Once on an appropriate NSBB dose, patients are protected against variceal bleeding (at least as effectively as EVL). This eliminates the need for repeated surveillance endoscopies to identify and treat large varices in otherwise compensated patients.
Better Tolerated and – In Many Cases – Overlaps With Existing Medication List!
While overtreatment is a concern, regular endoscopies every two years are also burdensome. Many patients already need beta blockers for cardiac conditions such as atrial fibrillation, ischemic heart disease or hypertension. Carvedilol, in particular, offers dual benefit for both hepatologists and cardiologists.
It is important to emphasize that these arguments apply to compensated cirrhosis. In decompensated disease, the approach changes. After a variceal bleed, both NSBBs and EVL are required for secondary prophylaxis. In patients with prior ascites but no variceal bleed, the benefit of NSBBs is less pronounced since decompensation has already occurred. In this setting, NSBBs can still be used selectively, but only if systolic blood pressure remains above 90 mmHg.
The evidence supporting NSBBs over EVL in compensated cirrhosis is not perfect, but few things in medicine are. Given current data, NSBBs should be the first line therapy in compensated cirrhosis with CSPH. Once a patient is on an appropriate and tolerated NSBB dose, routine endoscopic surveillance is unnecessary. Endoscopy should be reserved for those who cannot tolerate NSBBs, in whom EVL is then indicated if large varices are present.
Dr. Rabiee is based at the Yale School of Medicine, New Haven, Connecticut, and the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut. She has no disclosures in regard to this article.
Rethinking Screening and Surveillance in Barrett’s Esophagus: Navigating Controversies and Nuances
BY TAREK SAWAS, MD, MPH
Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Despite our comprehensive guidelines, many of the day-to-day decisions still rely on clinical judgment and honest conversations with patients. This article explores common scenarios in which management decisions are nuanced and the right answer remains debatable.
Irregular Z-Line/Ultrashort Segment BE: Leave Or Watch It?
Few findings provoke more confusion than irregular Z-line or intestinal metaplasia (IM) < 1 cm at the gastroesophageal junction (GEJ). For years, we have debated whether these subtle changes represent a precursor to EAC or simply a benign variant. We have wrestled with how to handle these cases from whether we should take biopsies to how to perform surveillance.
The American College of Gastroenterology (ACG) guideline suggests that irregular Z-lines should not be routinely biopsied or surveyed. Similarly, the upcoming American Gastroenterology Association (AGA) surveillance guideline suggests against surveillance of IM<1 cm citing the low individual annual risk of progression to high-grade dysplasia (HGD) and EAC of 0.23% per year which is lower than that of non-dysplastic Barrett’s esophagus (NDBE). However, this is not the entire picture.
Despite the low per-patient risk, IM<1cm is highly prevalent with columnar mucosa observed in approximately 15% of patients undergoing upper endoscopy. This paradox is unsettling. While any one patient with IM<1 cm is unlikely to progress to EAC, the group accounts for a meaningful share of the EAC burden. Some experts have argued that this justifies routine biopsy and surveillance in all patients with visible columnar mucosa regardless of length. However, this approach risks overwhelming our surveillance infrastructure.
A recent decision modeling analysis suggested that at the lowest progression rates, either no surveillance or one-time endoscopy can be considered. Based on these data, I do not regularly biopsy ultrashort segments unless the mucosa appears suspicious. In those with IM<1 cm detected during a high-quality endoscopic exam, no follow-up is needed. However, if the exam is suboptimal, I perform a 1-time high-quality repeat exam. If there is no evidence of dysplasia then I do not pursue any further surveillance.
The One-Year Follow-Up Endoscopy: Is It Necessary?
Another controversy is the one-year follow-up endoscopy after an initial diagnosis of NDBE. Proponents of this approach cite the high proportion of post endoscopy esophageal neoplasia and cancer (PEEN/PEEC) detected in the first year after diagnosis (missed HGD/EAC). In fact, PEEN account for about a quarter of all HGD/EAC cases diagnosed during surveillance.
While this approach might mitigate PEEN/PEEC risk, it may not be necessary if the index endoscopy is high quality. To ensure high quality exams, several best practices have been proposed including:
- Use of high-definition white light endoscopy (HD-WLE) with chromoendoscopy (virtual or dye based)
- Appropriate inspection time (1 minute per cm of circumferential BE)
- Accurate documentation using the Prague criteria
- Adherence to the Seattle protocol with additional targeted biopsies
If the index endoscopy meets these quality metrics, I typically do not bring the patient back at one year. However, if the exam quality is in question, then I repeat it at one year to establish a reliable baseline and rule out prevalent neoplasia.
Surveillance In NDBE: After BOSS, Do We Rethink Everything?
The recently published BOSS trial (Barrett’s Oesophagus Surveillance Study) has reignited the debate over the value of endoscopic surveillance in NDBE. In this study, 3,453 patients with NDBE across the UK were randomized to either surveillance endoscopy every two years or endoscopy only as clinically indicated. After a median follow-up of 12.8 years, the trial found no significant difference in all-cause mortality between the two groups.
While these findings are important, they should be interpreted with caution. First, the primary endpoint, all-cause mortality, is not optimal for evaluating surveillance for EAC. Surveillance is not intended to reduce all-cause mortality but rather to reduce EAC–related mortality. Second, a substantial number of patients in the no surveillance group still underwent endoscopy at intervals that were not meaningfully different from those in the surveillance group. If both groups receive similar exposure to endoscopy, the comparison loses power. Lastly, the trial was underpowered due to overestimation of progression risk during its initial design. As we have since learned, the risk of progression of NDBE is lower than originally assumed.
So where do we stand now? For me, the BOSS trial does not negate the value of surveillance. it reminds us that a one-size-fits-all approach is inefficient, and our strategy must be risk based. For low-risk individuals, particularly older adults with short-segment NDBE, surveillance may offer little benefit. But in healthier, younger patients with longer segments or additional risk factors, surveillance remains an essential tool for early neoplasia detection.
When to Stop Surveillance
Perhaps the most under-discussed point is when to stop surveillance. Existing guidelines do not account for competing mortality risks unrelated to EAC or provide specific recommendations regarding cessation of surveillance. The desired benefits of surveillance likely diminish with advanced age and greater comorbidity because of lower life expectancy and ineligibility for definitive therapy for EAC.
A recent modeling study found that the optimal ages for last surveillance were 81, 80, 77, and 73 years for men with no, mild, moderate, and severe comorbidity respectively and 75, 73, 73, and 69 years for women. In my practice, I discuss surveillance cessation in patients older than 75 based on their comorbidities. If the risk of progression is outweighed by the risk of the procedure or by the reality of limited life expectancy, we should not hesitate to consider surveillance cessation.
In summary, high-quality endoscopic exam in appropriately selected patients remains the cornerstone of BE surveillance. A more personalized, risk-based approach is needed taking into account competing comorbidities. Emerging technology through risk stratification tools such as biomarkers and artificial intelligence may refine our approach and help address the current limitations.
Dr. Sawas is based at the University of Texas Southwestern, Dallas, Texas. He has no disclosures in regard to this article.
Dear colleagues,
In the dynamic field of medicine, long-held practices are being reevaluated in light of new evidence and evolving standards of practice.
Dr. Anahita Rabiee discusses the importance of prioritizing non-selective beta blockers (NSBB) over endoscopic variceal ligation (EVL) in the primary prophylaxis of variceal bleeding in patients with compensated cirrhosis. Drawing on data from the PREDESCI trial and real-world experience, she argues that NSBB address the upstream driver—portal hypertension—more broadly and effectively than EVL. In a complementary piece, Dr. Tarek Sawas explores the nuanced landscape of screening and surveillance in Barrett’s esophagus. From how to manage irregular Z-lines, to rethinking the need for 1-year follow-up endoscopies and interpreting the implications of the BOSS trial, Dr. Sawas advocates for a more personalized, risk-based approach.
We hope these perspectives spark dialogue and reflection in your own practice. Join the conversation on X at @AGA_GIHN.
Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.
Choose NSBBs, Not EVL, in Patients with Compensated Cirrhosis
BY ANAHITA RABIEE, MD, MHS
I strongly favor the use of non selective beta blockers (NSBBs) in patients with compensated cirrhosis, rather than endoscopy and esophageal variceal ligation (EVL) for primary prophylaxis.
Since the results of PREDESCI trial (β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (CSPH)) were published in 2019, there has been much debate on the role of screening endoscopy and EVL for primary prophylaxis. While many argue that a single randomized trial should not overturn long standing practice, several compelling reasons convince me to choose NSBBs, when possible.
Recent guidance from major liver societies now recommends NSBBs as first line therapy for CSPH. Yet, adoption in clinical practice remains inconsistent.
Here is why I believe NSBB represent a better solution:
Treating Upstream, Not Just a Local Treatment
NSBBs such as propranolol and nadolol decrease portal pressure by decreasing portal venous inflow through β1 and β2 adrenergic blockade. Carvedilol is often preferred given its additional α1 adrenergic blocking activity making it the most effective one in decreasing the portal pressure. Therefore, NSBBs address the upstream driver of decompensation by decreasing portal pressures.
EVL, in contrast, is a local fix that only prevents variceal bleeding. Ascites, not variceal bleeding, is the most common initial decompensating event and is associated with high mortality. Preventing all forms of decompensation is clearly preferable to preventing just one.
Broader Eligibility, More Patients Benefit
CSPH is defined as hepatic venous pressure gradient (HVPG)>10 mmHg, the threshold where increased portal venous inflow secondary to splanchnic vasodilation and hyperdynamic circulation drives the increase in portal hypertension. This threshold has been shown to strongly predict decompensation in patients with compensated disease.
While all patients with varices have CSPH, not all patients with CSPH have varices. They can be identified by other non invasive criteria such as cross sectional imaging showing collaterals, or liver stiffness and platelet thresholds that have been previously validated. By restricting intervention to those with large varices and offering only EVL, we miss the opportunity to intervene earlier and to a broader group that would benefit from this treatment.
Comprehensive Protection Without Repeated Endoscopies
Once on an appropriate NSBB dose, patients are protected against variceal bleeding (at least as effectively as EVL). This eliminates the need for repeated surveillance endoscopies to identify and treat large varices in otherwise compensated patients.
Better Tolerated and – In Many Cases – Overlaps With Existing Medication List!
While overtreatment is a concern, regular endoscopies every two years are also burdensome. Many patients already need beta blockers for cardiac conditions such as atrial fibrillation, ischemic heart disease or hypertension. Carvedilol, in particular, offers dual benefit for both hepatologists and cardiologists.
It is important to emphasize that these arguments apply to compensated cirrhosis. In decompensated disease, the approach changes. After a variceal bleed, both NSBBs and EVL are required for secondary prophylaxis. In patients with prior ascites but no variceal bleed, the benefit of NSBBs is less pronounced since decompensation has already occurred. In this setting, NSBBs can still be used selectively, but only if systolic blood pressure remains above 90 mmHg.
The evidence supporting NSBBs over EVL in compensated cirrhosis is not perfect, but few things in medicine are. Given current data, NSBBs should be the first line therapy in compensated cirrhosis with CSPH. Once a patient is on an appropriate and tolerated NSBB dose, routine endoscopic surveillance is unnecessary. Endoscopy should be reserved for those who cannot tolerate NSBBs, in whom EVL is then indicated if large varices are present.
Dr. Rabiee is based at the Yale School of Medicine, New Haven, Connecticut, and the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut. She has no disclosures in regard to this article.
Rethinking Screening and Surveillance in Barrett’s Esophagus: Navigating Controversies and Nuances
BY TAREK SAWAS, MD, MPH
Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Despite our comprehensive guidelines, many of the day-to-day decisions still rely on clinical judgment and honest conversations with patients. This article explores common scenarios in which management decisions are nuanced and the right answer remains debatable.
Irregular Z-Line/Ultrashort Segment BE: Leave Or Watch It?
Few findings provoke more confusion than irregular Z-line or intestinal metaplasia (IM) < 1 cm at the gastroesophageal junction (GEJ). For years, we have debated whether these subtle changes represent a precursor to EAC or simply a benign variant. We have wrestled with how to handle these cases from whether we should take biopsies to how to perform surveillance.
The American College of Gastroenterology (ACG) guideline suggests that irregular Z-lines should not be routinely biopsied or surveyed. Similarly, the upcoming American Gastroenterology Association (AGA) surveillance guideline suggests against surveillance of IM<1 cm citing the low individual annual risk of progression to high-grade dysplasia (HGD) and EAC of 0.23% per year which is lower than that of non-dysplastic Barrett’s esophagus (NDBE). However, this is not the entire picture.
Despite the low per-patient risk, IM<1cm is highly prevalent with columnar mucosa observed in approximately 15% of patients undergoing upper endoscopy. This paradox is unsettling. While any one patient with IM<1 cm is unlikely to progress to EAC, the group accounts for a meaningful share of the EAC burden. Some experts have argued that this justifies routine biopsy and surveillance in all patients with visible columnar mucosa regardless of length. However, this approach risks overwhelming our surveillance infrastructure.
A recent decision modeling analysis suggested that at the lowest progression rates, either no surveillance or one-time endoscopy can be considered. Based on these data, I do not regularly biopsy ultrashort segments unless the mucosa appears suspicious. In those with IM<1 cm detected during a high-quality endoscopic exam, no follow-up is needed. However, if the exam is suboptimal, I perform a 1-time high-quality repeat exam. If there is no evidence of dysplasia then I do not pursue any further surveillance.
The One-Year Follow-Up Endoscopy: Is It Necessary?
Another controversy is the one-year follow-up endoscopy after an initial diagnosis of NDBE. Proponents of this approach cite the high proportion of post endoscopy esophageal neoplasia and cancer (PEEN/PEEC) detected in the first year after diagnosis (missed HGD/EAC). In fact, PEEN account for about a quarter of all HGD/EAC cases diagnosed during surveillance.
While this approach might mitigate PEEN/PEEC risk, it may not be necessary if the index endoscopy is high quality. To ensure high quality exams, several best practices have been proposed including:
- Use of high-definition white light endoscopy (HD-WLE) with chromoendoscopy (virtual or dye based)
- Appropriate inspection time (1 minute per cm of circumferential BE)
- Accurate documentation using the Prague criteria
- Adherence to the Seattle protocol with additional targeted biopsies
If the index endoscopy meets these quality metrics, I typically do not bring the patient back at one year. However, if the exam quality is in question, then I repeat it at one year to establish a reliable baseline and rule out prevalent neoplasia.
Surveillance In NDBE: After BOSS, Do We Rethink Everything?
The recently published BOSS trial (Barrett’s Oesophagus Surveillance Study) has reignited the debate over the value of endoscopic surveillance in NDBE. In this study, 3,453 patients with NDBE across the UK were randomized to either surveillance endoscopy every two years or endoscopy only as clinically indicated. After a median follow-up of 12.8 years, the trial found no significant difference in all-cause mortality between the two groups.
While these findings are important, they should be interpreted with caution. First, the primary endpoint, all-cause mortality, is not optimal for evaluating surveillance for EAC. Surveillance is not intended to reduce all-cause mortality but rather to reduce EAC–related mortality. Second, a substantial number of patients in the no surveillance group still underwent endoscopy at intervals that were not meaningfully different from those in the surveillance group. If both groups receive similar exposure to endoscopy, the comparison loses power. Lastly, the trial was underpowered due to overestimation of progression risk during its initial design. As we have since learned, the risk of progression of NDBE is lower than originally assumed.
So where do we stand now? For me, the BOSS trial does not negate the value of surveillance. it reminds us that a one-size-fits-all approach is inefficient, and our strategy must be risk based. For low-risk individuals, particularly older adults with short-segment NDBE, surveillance may offer little benefit. But in healthier, younger patients with longer segments or additional risk factors, surveillance remains an essential tool for early neoplasia detection.
When to Stop Surveillance
Perhaps the most under-discussed point is when to stop surveillance. Existing guidelines do not account for competing mortality risks unrelated to EAC or provide specific recommendations regarding cessation of surveillance. The desired benefits of surveillance likely diminish with advanced age and greater comorbidity because of lower life expectancy and ineligibility for definitive therapy for EAC.
A recent modeling study found that the optimal ages for last surveillance were 81, 80, 77, and 73 years for men with no, mild, moderate, and severe comorbidity respectively and 75, 73, 73, and 69 years for women. In my practice, I discuss surveillance cessation in patients older than 75 based on their comorbidities. If the risk of progression is outweighed by the risk of the procedure or by the reality of limited life expectancy, we should not hesitate to consider surveillance cessation.
In summary, high-quality endoscopic exam in appropriately selected patients remains the cornerstone of BE surveillance. A more personalized, risk-based approach is needed taking into account competing comorbidities. Emerging technology through risk stratification tools such as biomarkers and artificial intelligence may refine our approach and help address the current limitations.
Dr. Sawas is based at the University of Texas Southwestern, Dallas, Texas. He has no disclosures in regard to this article.
GLP-1 Receptor Agonist Use in Gastrointestinal Endoscopy: A Review of Current Evidence and Guidelines
The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has increased over the past several years and has become a cornerstone in both diabetes and weight loss management, particularly because of its unique combination of glucose control, weight reduction potential, and cardiac and metabolic benefits. However, increased use of these agents presents a dilemma in gastrointestinal endoscopy as it pertains to their safety and management during the periprocedural period.
highlighting gaps and future directions.
Pharmacology and Mechanisms of Action
GLP-1 RAs have several mechanisms of action that make them relevant in gastrointestinal endoscopy. These medications modulate glucose control via enhancement of glucose-dependent insulin secretion and reduction of postprandial glucagon, which promotes satiety and delays gastric emptying. This delay in gastric emptying mediated by vagal pathways has been postulated to increase gastric residuals, posing a risk for aspiration during anesthesia.1
It is important to also consider the pharmacokinetics of GLP-1 RAs, as some have shorter half-lives on the order of several hours, like exenatide, while others, like semaglutide, are dosed weekly. Additionally, common side effects of GLP-1 RAs include nausea, vomiting, bloating, and early satiety, which pose challenges for patients undergoing endoscopic procedures.
Current Guidelines
Various societies have published guidelines on the periprocedural use of GLP-1 RAs. The American Society of Anesthesiologist (ASA) in 2023 presented early recommendations to hold GLP-1 RAs either day of procedure or week prior depending on pharmacokinetics, because of the risk of delayed gastric emptying and increased potential for aspiration.2 Soon thereafter, a multi-gastroenterology society guideline was released stating more data is needed to decide if GLP-1 RAs need to be held prior to endoscopic procedures.3
In early 2024, the American Gastroenterological Association (AGA) published a rapid clinical update that advocated for a more individualized approach, particularly in light of limited overall data for GLP-1 RAs and endoscopic procedures.4 In asymptomatic patients who follow typical fasting protocols for procedures, it is generally safe to proceed with endoscopy without holding GLP-1 RAs. In symptomatic patients (nausea, abdominal distension, etc), the AGA advises additional precautions, including performing transabdominal ultrasound if feasible to assess retained gastric contents. The AGA also suggests placing a patient on a clear liquid diet the day prior to the procedure — rather than holding GLP-1 RAs — as another reasonable strategy.
The guidelines continue to evolve with newer multi-society guidelines establishing best practices. While initially in 2023 the ASA did recommend holding these medications prior to endoscopy, the initial guidance was based on expert opinion with limited evidence. Newer multi-society guidance published jointly by the ASA along with various gastroenterology societies, including the AGA in December 2024, takes a more nuanced approach.5
The newer guidelines include two main recommendations:
1. Periprocedural management of GLP-1 RAs should be a joint decision among the procedural, anesthesia, and prescribing team balancing metabolic needs vs patient risks.
- In a low-risk patient, one that is asymptomatic and on standard dosing, among other factors, the guidance states that GLP-1 RAs can be continued.
- In higher-risk patients, the original guidance of holding a day or a week prior to endoscopic procedures should be followed.
2. Periprocedural management of GLP-1 RAs should attempt to minimize the aspiration risks loosely associated with delayed gastric emptying.
- Consider a 24-hour clear liquid diet a day prior to the procedure and transabdominal ultrasound to check gastric contents.
- It is acknowledged that this guidance is based on limited evidence and will be evolving as new medications and data are released.
Recent Clinical Studies
Although there is very little data to guide clinicians, several recent studies have been published that can direct clinical decision-making as guidelines continue to be refined and updated.
A multicenter trial of approximately 800 patients undergoing upper endoscopy found a significant difference in rates of retained gastric contents between those that underwent endoscopy who did and did not follow the ASA guidance on periprocedural management of GLP-1 RAs (12.7% vs 4.4%; P < .0001). However, there were no significant differences in rates of aborted procedures or unplanned intubations.
Furthermore, a multivariable analysis was performed controlling for GLP-1 RA type and other factors, which found the likelihood of gastric retention increased by 36% for every 1% increase in hemoglobin A1c. This study suggests that a more individualized approach to holding GLP-1 RA would be applicable rather than a universal periprocedural hold.6
More recently, a single-center study of nearly 600 patients undergoing upper endoscopy showed that while there were slightly increased rates of retained gastric contents (OR 3.80; P = .003) and aborted procedures (1.3% vs 0%; P = .02), the rates of adverse anesthesia events (hypoxia, etc) were similar between the groups and no cases of pulmonary aspiration were noted.7
One single-center study of 57 patients evaluated the safety of GLP-1 RAs in those undergoing endoscopic sleeve gastrectomy. GLP-1 RAs were continued on all patients, but all adhered to a liquid only diet for at least 24 hours prior to the procedure. There were no instances of retained gastric solids, aspiration, or hypoxia. This study suggests that with a 24-hour clear liquid diet and routine NPO recommendations prior to endoscopy, it would be safe to continue GLP-1 RAs. This study provides rationale for the AGA recommendation for a clear liquid diet 24 hours prior to endoscopic procedures for those on GLP-1 RAs.8
A study looking at those who underwent emergency surgery and endoscopy with claims data of use of GLP-1 RAs found an overall incidence of postoperative respiratory complications of 3.5% for those with GLP-1 RAs fill history vs 4.0% for those without (P = .12). Approximately 800 of the 24,000 patients identified had undergone endoscopic procedures for GI bleeding or food impaction. The study overall showed that preoperative use of GLP-1 RAs in patients undergoing surgery or endoscopy, evaluated as a combined group, was not associated with an increased risk of pulmonary complications.9
Lastly, a systematic review and meta-analysis that included 15 studies that quantified gastric emptying using various methods, including gastric emptying scintigraphy and acetaminophen absorption test, found that there was a quantifiable delay in gastric emptying of about 36 minutes, compared to placebo (P < .01), in patients using GLP-1 RAs. However, compared to standard periprocedural fasting, this delay is clinically insignificant and standard fasting protocols would still be appropriate for patients on GLP-1 RAs.10
These studies taken together suggest that while GLP-1 RAs can mildly increase the likelihood of retained gastric contents, there is no statistically significant increase in the risk of aspiration or other anesthesia complications. Furthermore, while decreased gastric emptying is a known effect of GLP-1 RAs, this effect may not be clinically significant in the context of standard periprocedural fasting protocols particularly when combined with a 24-hour clear liquid diet. These findings support at a minimum a more patient-specific strategy for periprocedural management of GLP-1 RAs.
Clinical Implications
These most recent studies, as well as prior studies and guidelines by various societies lead to a dilemma among endoscopists on proper patient counseling on GLP-1 RAs use before endoscopic procedures. Clinicians must balance the metabolic benefits of GLP-1 RAs with potential endoscopic complications and risks.
Holding therapy theoretically decreases aspiration risk and pulmonary complications, though evidence remains low to support this. Holding medication, however, affects glycemic control leading to potential rebound hyperglycemia which may impact and delay plans for endoscopy. With growing indications for the use of GLP-1 RAs, a more tailored patient-centered treatment plan may be required, especially with consideration of procedure indication and comorbidities.
Currently, practice patterns at different institutions vary widely, making standardization much more difficult. Some centers have opted to follow ASA guidelines of holding these medications up to 1 week prior to procedures, while others have continued therapy with no pre-procedural adjustments. This leaves endoscopists to deal with the downstream effects of inconvenience to patients, care delays, and financial considerations if procedures are postponed related to GLP-1 RAs use.
Future Directions
Future studies are needed to make further evidence-based recommendations. Studies should focus on stratifying risks and recommendations based on procedure type (EGD, colonoscopy, etc). More widespread implementation of gastric ultrasound can assist in real-time decision-making, albeit this would require expertise and dedicated time within the pre-procedural workflow. Randomized controlled trials comparing outcomes of patients who continue GLP-1 RAs vs those who discontinue stratified by baseline risk will be instrumental for making concrete guidelines that provide clarity on periprocedural management of GLP-1 RAs.
Conclusion
The periprocedural management of GLP-1 RAs remains a controversial topic that presents unique challenges in endoscopy. Several guidelines have been released by various stakeholders including anesthesiologists, gastroenterologists, and other prescribing providers. Clinical data remains limited with no robust evidence available to suggest that gastric emptying delays caused by GLP-1 RAs prior to endoscopic procedures significantly increases risk of aspiration, pulmonary complications, or other comorbidities. Evolving multi-society guidelines will be important to establish more consistent practices with reassessment of the data as new studies emerge. A multidisciplinary, individualized patient approach may be the best strategy for managing GLP-1 RAs for patients undergoing endoscopic procedures.
Dr. Sekar and Dr. Asamoah are based in the department of gastroenterology at MedStar Georgetown University Hospital, Washington, D.C. Dr. Sekar reports no conflicts of interest in regard to this article. Dr. Asamoah serves on the Johnson & Johnson advisory board for inflammatory bowel disease–related therapies.
References
1. Halim MA et al. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. J Clin Endocrinol Metab. 2018 Feb. doi: 10.1210/jc.2017-02006.
2. American Society of Anesthesiologists. American Society of Anesthesiologists releases consensus-based guidance on preoperative use of GLP-1 receptor agonists. 2023 Jun 20. www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative
3. American Gastroenterological Association. GI multi-society statement regarding GLP-1 agonists and endoscopy. 2023 Jul 25. gastro.org/news/gi-multi-society-statement-regarding-glp-1-agonists-and-endoscopy/.
4. Hashash JG et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr. doi: 10.1016/j.cgh.2023.11.002.
5. Kindel TL et al; American Gastroenterological Association; American Society for Metabolic and Bariatric Surgery; American Society of Anesthesiologists; International Society of Perioperative Care of Patients with Obesity; Society of American Gastrointestinal and Endoscopic Surgeons. Multi-society Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.10.003.
6. Phan J et al. Glucagon-Like Peptide Receptor Agonists Use Before Endoscopy Is Associated With Low Retained Gastric Contents: A Multicenter Cross-Sectional Analysis. Am J Gastroenterol. 2025 Mar. doi: 10.14309/ajg.0000000000002969.
7. Panchal S et al. Endoscopy and Anesthesia Outcomes Associated With Glucagon-like Peptide-1 Receptor Agonist use in Patients Undergoing Outpatient Upper Endoscopy. Gastrointest Endosc. 2025 Aug. doi:10.1016/j.gie.2025.01.004.
8. Maselli DB et al. Safe Continuation of glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty. Obes Surg. 2024 Jul. doi: 10.1007/s11695-024-07278-2.
9. Dixit AA et al. Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA. 2024 Apr. doi: 10.1001/jama.2024.5003.
10. Hiramoto B et al. Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A systematic review and meta-analysis with insights for periprocedural management. Am J Gastroenterol. 2024 Jun. doi: 10.14309/ajg.0000000000002820.
The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has increased over the past several years and has become a cornerstone in both diabetes and weight loss management, particularly because of its unique combination of glucose control, weight reduction potential, and cardiac and metabolic benefits. However, increased use of these agents presents a dilemma in gastrointestinal endoscopy as it pertains to their safety and management during the periprocedural period.
highlighting gaps and future directions.
Pharmacology and Mechanisms of Action
GLP-1 RAs have several mechanisms of action that make them relevant in gastrointestinal endoscopy. These medications modulate glucose control via enhancement of glucose-dependent insulin secretion and reduction of postprandial glucagon, which promotes satiety and delays gastric emptying. This delay in gastric emptying mediated by vagal pathways has been postulated to increase gastric residuals, posing a risk for aspiration during anesthesia.1
It is important to also consider the pharmacokinetics of GLP-1 RAs, as some have shorter half-lives on the order of several hours, like exenatide, while others, like semaglutide, are dosed weekly. Additionally, common side effects of GLP-1 RAs include nausea, vomiting, bloating, and early satiety, which pose challenges for patients undergoing endoscopic procedures.
Current Guidelines
Various societies have published guidelines on the periprocedural use of GLP-1 RAs. The American Society of Anesthesiologist (ASA) in 2023 presented early recommendations to hold GLP-1 RAs either day of procedure or week prior depending on pharmacokinetics, because of the risk of delayed gastric emptying and increased potential for aspiration.2 Soon thereafter, a multi-gastroenterology society guideline was released stating more data is needed to decide if GLP-1 RAs need to be held prior to endoscopic procedures.3
In early 2024, the American Gastroenterological Association (AGA) published a rapid clinical update that advocated for a more individualized approach, particularly in light of limited overall data for GLP-1 RAs and endoscopic procedures.4 In asymptomatic patients who follow typical fasting protocols for procedures, it is generally safe to proceed with endoscopy without holding GLP-1 RAs. In symptomatic patients (nausea, abdominal distension, etc), the AGA advises additional precautions, including performing transabdominal ultrasound if feasible to assess retained gastric contents. The AGA also suggests placing a patient on a clear liquid diet the day prior to the procedure — rather than holding GLP-1 RAs — as another reasonable strategy.
The guidelines continue to evolve with newer multi-society guidelines establishing best practices. While initially in 2023 the ASA did recommend holding these medications prior to endoscopy, the initial guidance was based on expert opinion with limited evidence. Newer multi-society guidance published jointly by the ASA along with various gastroenterology societies, including the AGA in December 2024, takes a more nuanced approach.5
The newer guidelines include two main recommendations:
1. Periprocedural management of GLP-1 RAs should be a joint decision among the procedural, anesthesia, and prescribing team balancing metabolic needs vs patient risks.
- In a low-risk patient, one that is asymptomatic and on standard dosing, among other factors, the guidance states that GLP-1 RAs can be continued.
- In higher-risk patients, the original guidance of holding a day or a week prior to endoscopic procedures should be followed.
2. Periprocedural management of GLP-1 RAs should attempt to minimize the aspiration risks loosely associated with delayed gastric emptying.
- Consider a 24-hour clear liquid diet a day prior to the procedure and transabdominal ultrasound to check gastric contents.
- It is acknowledged that this guidance is based on limited evidence and will be evolving as new medications and data are released.
Recent Clinical Studies
Although there is very little data to guide clinicians, several recent studies have been published that can direct clinical decision-making as guidelines continue to be refined and updated.
A multicenter trial of approximately 800 patients undergoing upper endoscopy found a significant difference in rates of retained gastric contents between those that underwent endoscopy who did and did not follow the ASA guidance on periprocedural management of GLP-1 RAs (12.7% vs 4.4%; P < .0001). However, there were no significant differences in rates of aborted procedures or unplanned intubations.
Furthermore, a multivariable analysis was performed controlling for GLP-1 RA type and other factors, which found the likelihood of gastric retention increased by 36% for every 1% increase in hemoglobin A1c. This study suggests that a more individualized approach to holding GLP-1 RA would be applicable rather than a universal periprocedural hold.6
More recently, a single-center study of nearly 600 patients undergoing upper endoscopy showed that while there were slightly increased rates of retained gastric contents (OR 3.80; P = .003) and aborted procedures (1.3% vs 0%; P = .02), the rates of adverse anesthesia events (hypoxia, etc) were similar between the groups and no cases of pulmonary aspiration were noted.7
One single-center study of 57 patients evaluated the safety of GLP-1 RAs in those undergoing endoscopic sleeve gastrectomy. GLP-1 RAs were continued on all patients, but all adhered to a liquid only diet for at least 24 hours prior to the procedure. There were no instances of retained gastric solids, aspiration, or hypoxia. This study suggests that with a 24-hour clear liquid diet and routine NPO recommendations prior to endoscopy, it would be safe to continue GLP-1 RAs. This study provides rationale for the AGA recommendation for a clear liquid diet 24 hours prior to endoscopic procedures for those on GLP-1 RAs.8
A study looking at those who underwent emergency surgery and endoscopy with claims data of use of GLP-1 RAs found an overall incidence of postoperative respiratory complications of 3.5% for those with GLP-1 RAs fill history vs 4.0% for those without (P = .12). Approximately 800 of the 24,000 patients identified had undergone endoscopic procedures for GI bleeding or food impaction. The study overall showed that preoperative use of GLP-1 RAs in patients undergoing surgery or endoscopy, evaluated as a combined group, was not associated with an increased risk of pulmonary complications.9
Lastly, a systematic review and meta-analysis that included 15 studies that quantified gastric emptying using various methods, including gastric emptying scintigraphy and acetaminophen absorption test, found that there was a quantifiable delay in gastric emptying of about 36 minutes, compared to placebo (P < .01), in patients using GLP-1 RAs. However, compared to standard periprocedural fasting, this delay is clinically insignificant and standard fasting protocols would still be appropriate for patients on GLP-1 RAs.10
These studies taken together suggest that while GLP-1 RAs can mildly increase the likelihood of retained gastric contents, there is no statistically significant increase in the risk of aspiration or other anesthesia complications. Furthermore, while decreased gastric emptying is a known effect of GLP-1 RAs, this effect may not be clinically significant in the context of standard periprocedural fasting protocols particularly when combined with a 24-hour clear liquid diet. These findings support at a minimum a more patient-specific strategy for periprocedural management of GLP-1 RAs.
Clinical Implications
These most recent studies, as well as prior studies and guidelines by various societies lead to a dilemma among endoscopists on proper patient counseling on GLP-1 RAs use before endoscopic procedures. Clinicians must balance the metabolic benefits of GLP-1 RAs with potential endoscopic complications and risks.
Holding therapy theoretically decreases aspiration risk and pulmonary complications, though evidence remains low to support this. Holding medication, however, affects glycemic control leading to potential rebound hyperglycemia which may impact and delay plans for endoscopy. With growing indications for the use of GLP-1 RAs, a more tailored patient-centered treatment plan may be required, especially with consideration of procedure indication and comorbidities.
Currently, practice patterns at different institutions vary widely, making standardization much more difficult. Some centers have opted to follow ASA guidelines of holding these medications up to 1 week prior to procedures, while others have continued therapy with no pre-procedural adjustments. This leaves endoscopists to deal with the downstream effects of inconvenience to patients, care delays, and financial considerations if procedures are postponed related to GLP-1 RAs use.
Future Directions
Future studies are needed to make further evidence-based recommendations. Studies should focus on stratifying risks and recommendations based on procedure type (EGD, colonoscopy, etc). More widespread implementation of gastric ultrasound can assist in real-time decision-making, albeit this would require expertise and dedicated time within the pre-procedural workflow. Randomized controlled trials comparing outcomes of patients who continue GLP-1 RAs vs those who discontinue stratified by baseline risk will be instrumental for making concrete guidelines that provide clarity on periprocedural management of GLP-1 RAs.
Conclusion
The periprocedural management of GLP-1 RAs remains a controversial topic that presents unique challenges in endoscopy. Several guidelines have been released by various stakeholders including anesthesiologists, gastroenterologists, and other prescribing providers. Clinical data remains limited with no robust evidence available to suggest that gastric emptying delays caused by GLP-1 RAs prior to endoscopic procedures significantly increases risk of aspiration, pulmonary complications, or other comorbidities. Evolving multi-society guidelines will be important to establish more consistent practices with reassessment of the data as new studies emerge. A multidisciplinary, individualized patient approach may be the best strategy for managing GLP-1 RAs for patients undergoing endoscopic procedures.
Dr. Sekar and Dr. Asamoah are based in the department of gastroenterology at MedStar Georgetown University Hospital, Washington, D.C. Dr. Sekar reports no conflicts of interest in regard to this article. Dr. Asamoah serves on the Johnson & Johnson advisory board for inflammatory bowel disease–related therapies.
References
1. Halim MA et al. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. J Clin Endocrinol Metab. 2018 Feb. doi: 10.1210/jc.2017-02006.
2. American Society of Anesthesiologists. American Society of Anesthesiologists releases consensus-based guidance on preoperative use of GLP-1 receptor agonists. 2023 Jun 20. www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative
3. American Gastroenterological Association. GI multi-society statement regarding GLP-1 agonists and endoscopy. 2023 Jul 25. gastro.org/news/gi-multi-society-statement-regarding-glp-1-agonists-and-endoscopy/.
4. Hashash JG et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr. doi: 10.1016/j.cgh.2023.11.002.
5. Kindel TL et al; American Gastroenterological Association; American Society for Metabolic and Bariatric Surgery; American Society of Anesthesiologists; International Society of Perioperative Care of Patients with Obesity; Society of American Gastrointestinal and Endoscopic Surgeons. Multi-society Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.10.003.
6. Phan J et al. Glucagon-Like Peptide Receptor Agonists Use Before Endoscopy Is Associated With Low Retained Gastric Contents: A Multicenter Cross-Sectional Analysis. Am J Gastroenterol. 2025 Mar. doi: 10.14309/ajg.0000000000002969.
7. Panchal S et al. Endoscopy and Anesthesia Outcomes Associated With Glucagon-like Peptide-1 Receptor Agonist use in Patients Undergoing Outpatient Upper Endoscopy. Gastrointest Endosc. 2025 Aug. doi:10.1016/j.gie.2025.01.004.
8. Maselli DB et al. Safe Continuation of glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty. Obes Surg. 2024 Jul. doi: 10.1007/s11695-024-07278-2.
9. Dixit AA et al. Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA. 2024 Apr. doi: 10.1001/jama.2024.5003.
10. Hiramoto B et al. Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A systematic review and meta-analysis with insights for periprocedural management. Am J Gastroenterol. 2024 Jun. doi: 10.14309/ajg.0000000000002820.
The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has increased over the past several years and has become a cornerstone in both diabetes and weight loss management, particularly because of its unique combination of glucose control, weight reduction potential, and cardiac and metabolic benefits. However, increased use of these agents presents a dilemma in gastrointestinal endoscopy as it pertains to their safety and management during the periprocedural period.
highlighting gaps and future directions.
Pharmacology and Mechanisms of Action
GLP-1 RAs have several mechanisms of action that make them relevant in gastrointestinal endoscopy. These medications modulate glucose control via enhancement of glucose-dependent insulin secretion and reduction of postprandial glucagon, which promotes satiety and delays gastric emptying. This delay in gastric emptying mediated by vagal pathways has been postulated to increase gastric residuals, posing a risk for aspiration during anesthesia.1
It is important to also consider the pharmacokinetics of GLP-1 RAs, as some have shorter half-lives on the order of several hours, like exenatide, while others, like semaglutide, are dosed weekly. Additionally, common side effects of GLP-1 RAs include nausea, vomiting, bloating, and early satiety, which pose challenges for patients undergoing endoscopic procedures.
Current Guidelines
Various societies have published guidelines on the periprocedural use of GLP-1 RAs. The American Society of Anesthesiologist (ASA) in 2023 presented early recommendations to hold GLP-1 RAs either day of procedure or week prior depending on pharmacokinetics, because of the risk of delayed gastric emptying and increased potential for aspiration.2 Soon thereafter, a multi-gastroenterology society guideline was released stating more data is needed to decide if GLP-1 RAs need to be held prior to endoscopic procedures.3
In early 2024, the American Gastroenterological Association (AGA) published a rapid clinical update that advocated for a more individualized approach, particularly in light of limited overall data for GLP-1 RAs and endoscopic procedures.4 In asymptomatic patients who follow typical fasting protocols for procedures, it is generally safe to proceed with endoscopy without holding GLP-1 RAs. In symptomatic patients (nausea, abdominal distension, etc), the AGA advises additional precautions, including performing transabdominal ultrasound if feasible to assess retained gastric contents. The AGA also suggests placing a patient on a clear liquid diet the day prior to the procedure — rather than holding GLP-1 RAs — as another reasonable strategy.
The guidelines continue to evolve with newer multi-society guidelines establishing best practices. While initially in 2023 the ASA did recommend holding these medications prior to endoscopy, the initial guidance was based on expert opinion with limited evidence. Newer multi-society guidance published jointly by the ASA along with various gastroenterology societies, including the AGA in December 2024, takes a more nuanced approach.5
The newer guidelines include two main recommendations:
1. Periprocedural management of GLP-1 RAs should be a joint decision among the procedural, anesthesia, and prescribing team balancing metabolic needs vs patient risks.
- In a low-risk patient, one that is asymptomatic and on standard dosing, among other factors, the guidance states that GLP-1 RAs can be continued.
- In higher-risk patients, the original guidance of holding a day or a week prior to endoscopic procedures should be followed.
2. Periprocedural management of GLP-1 RAs should attempt to minimize the aspiration risks loosely associated with delayed gastric emptying.
- Consider a 24-hour clear liquid diet a day prior to the procedure and transabdominal ultrasound to check gastric contents.
- It is acknowledged that this guidance is based on limited evidence and will be evolving as new medications and data are released.
Recent Clinical Studies
Although there is very little data to guide clinicians, several recent studies have been published that can direct clinical decision-making as guidelines continue to be refined and updated.
A multicenter trial of approximately 800 patients undergoing upper endoscopy found a significant difference in rates of retained gastric contents between those that underwent endoscopy who did and did not follow the ASA guidance on periprocedural management of GLP-1 RAs (12.7% vs 4.4%; P < .0001). However, there were no significant differences in rates of aborted procedures or unplanned intubations.
Furthermore, a multivariable analysis was performed controlling for GLP-1 RA type and other factors, which found the likelihood of gastric retention increased by 36% for every 1% increase in hemoglobin A1c. This study suggests that a more individualized approach to holding GLP-1 RA would be applicable rather than a universal periprocedural hold.6
More recently, a single-center study of nearly 600 patients undergoing upper endoscopy showed that while there were slightly increased rates of retained gastric contents (OR 3.80; P = .003) and aborted procedures (1.3% vs 0%; P = .02), the rates of adverse anesthesia events (hypoxia, etc) were similar between the groups and no cases of pulmonary aspiration were noted.7
One single-center study of 57 patients evaluated the safety of GLP-1 RAs in those undergoing endoscopic sleeve gastrectomy. GLP-1 RAs were continued on all patients, but all adhered to a liquid only diet for at least 24 hours prior to the procedure. There were no instances of retained gastric solids, aspiration, or hypoxia. This study suggests that with a 24-hour clear liquid diet and routine NPO recommendations prior to endoscopy, it would be safe to continue GLP-1 RAs. This study provides rationale for the AGA recommendation for a clear liquid diet 24 hours prior to endoscopic procedures for those on GLP-1 RAs.8
A study looking at those who underwent emergency surgery and endoscopy with claims data of use of GLP-1 RAs found an overall incidence of postoperative respiratory complications of 3.5% for those with GLP-1 RAs fill history vs 4.0% for those without (P = .12). Approximately 800 of the 24,000 patients identified had undergone endoscopic procedures for GI bleeding or food impaction. The study overall showed that preoperative use of GLP-1 RAs in patients undergoing surgery or endoscopy, evaluated as a combined group, was not associated with an increased risk of pulmonary complications.9
Lastly, a systematic review and meta-analysis that included 15 studies that quantified gastric emptying using various methods, including gastric emptying scintigraphy and acetaminophen absorption test, found that there was a quantifiable delay in gastric emptying of about 36 minutes, compared to placebo (P < .01), in patients using GLP-1 RAs. However, compared to standard periprocedural fasting, this delay is clinically insignificant and standard fasting protocols would still be appropriate for patients on GLP-1 RAs.10
These studies taken together suggest that while GLP-1 RAs can mildly increase the likelihood of retained gastric contents, there is no statistically significant increase in the risk of aspiration or other anesthesia complications. Furthermore, while decreased gastric emptying is a known effect of GLP-1 RAs, this effect may not be clinically significant in the context of standard periprocedural fasting protocols particularly when combined with a 24-hour clear liquid diet. These findings support at a minimum a more patient-specific strategy for periprocedural management of GLP-1 RAs.
Clinical Implications
These most recent studies, as well as prior studies and guidelines by various societies lead to a dilemma among endoscopists on proper patient counseling on GLP-1 RAs use before endoscopic procedures. Clinicians must balance the metabolic benefits of GLP-1 RAs with potential endoscopic complications and risks.
Holding therapy theoretically decreases aspiration risk and pulmonary complications, though evidence remains low to support this. Holding medication, however, affects glycemic control leading to potential rebound hyperglycemia which may impact and delay plans for endoscopy. With growing indications for the use of GLP-1 RAs, a more tailored patient-centered treatment plan may be required, especially with consideration of procedure indication and comorbidities.
Currently, practice patterns at different institutions vary widely, making standardization much more difficult. Some centers have opted to follow ASA guidelines of holding these medications up to 1 week prior to procedures, while others have continued therapy with no pre-procedural adjustments. This leaves endoscopists to deal with the downstream effects of inconvenience to patients, care delays, and financial considerations if procedures are postponed related to GLP-1 RAs use.
Future Directions
Future studies are needed to make further evidence-based recommendations. Studies should focus on stratifying risks and recommendations based on procedure type (EGD, colonoscopy, etc). More widespread implementation of gastric ultrasound can assist in real-time decision-making, albeit this would require expertise and dedicated time within the pre-procedural workflow. Randomized controlled trials comparing outcomes of patients who continue GLP-1 RAs vs those who discontinue stratified by baseline risk will be instrumental for making concrete guidelines that provide clarity on periprocedural management of GLP-1 RAs.
Conclusion
The periprocedural management of GLP-1 RAs remains a controversial topic that presents unique challenges in endoscopy. Several guidelines have been released by various stakeholders including anesthesiologists, gastroenterologists, and other prescribing providers. Clinical data remains limited with no robust evidence available to suggest that gastric emptying delays caused by GLP-1 RAs prior to endoscopic procedures significantly increases risk of aspiration, pulmonary complications, or other comorbidities. Evolving multi-society guidelines will be important to establish more consistent practices with reassessment of the data as new studies emerge. A multidisciplinary, individualized patient approach may be the best strategy for managing GLP-1 RAs for patients undergoing endoscopic procedures.
Dr. Sekar and Dr. Asamoah are based in the department of gastroenterology at MedStar Georgetown University Hospital, Washington, D.C. Dr. Sekar reports no conflicts of interest in regard to this article. Dr. Asamoah serves on the Johnson & Johnson advisory board for inflammatory bowel disease–related therapies.
References
1. Halim MA et al. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. J Clin Endocrinol Metab. 2018 Feb. doi: 10.1210/jc.2017-02006.
2. American Society of Anesthesiologists. American Society of Anesthesiologists releases consensus-based guidance on preoperative use of GLP-1 receptor agonists. 2023 Jun 20. www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative
3. American Gastroenterological Association. GI multi-society statement regarding GLP-1 agonists and endoscopy. 2023 Jul 25. gastro.org/news/gi-multi-society-statement-regarding-glp-1-agonists-and-endoscopy/.
4. Hashash JG et al. AGA Rapid Clinical Practice Update on the Management of Patients Taking GLP-1 Receptor Agonists Prior to Endoscopy: Communication. Clin Gastroenterol Hepatol. 2024 Apr. doi: 10.1016/j.cgh.2023.11.002.
5. Kindel TL et al; American Gastroenterological Association; American Society for Metabolic and Bariatric Surgery; American Society of Anesthesiologists; International Society of Perioperative Care of Patients with Obesity; Society of American Gastrointestinal and Endoscopic Surgeons. Multi-society Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2024 Oct. doi: 10.1016/j.cgh.2024.10.003.
6. Phan J et al. Glucagon-Like Peptide Receptor Agonists Use Before Endoscopy Is Associated With Low Retained Gastric Contents: A Multicenter Cross-Sectional Analysis. Am J Gastroenterol. 2025 Mar. doi: 10.14309/ajg.0000000000002969.
7. Panchal S et al. Endoscopy and Anesthesia Outcomes Associated With Glucagon-like Peptide-1 Receptor Agonist use in Patients Undergoing Outpatient Upper Endoscopy. Gastrointest Endosc. 2025 Aug. doi:10.1016/j.gie.2025.01.004.
8. Maselli DB et al. Safe Continuation of glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty. Obes Surg. 2024 Jul. doi: 10.1007/s11695-024-07278-2.
9. Dixit AA et al. Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA. 2024 Apr. doi: 10.1001/jama.2024.5003.
10. Hiramoto B et al. Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A systematic review and meta-analysis with insights for periprocedural management. Am J Gastroenterol. 2024 Jun. doi: 10.14309/ajg.0000000000002820.
Less Invasive Sponge Test Stratifies Risk in Patients With Barrett’s Esophagus
The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy.
Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet.
“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.
Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.
In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”
The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.
“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.
The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.
Study Details
Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.
Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.
In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.
The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group.
The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.
Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”
“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”
Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”
Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”
One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”
This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health.
Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.
A version of this article appeared on Medscape.com.
The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy.
Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet.
“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.
Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.
In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”
The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.
“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.
The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.
Study Details
Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.
Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.
In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.
The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group.
The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.
Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”
“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”
Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”
Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”
One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”
This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health.
Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.
A version of this article appeared on Medscape.com.
The biomarker risk panel collected by the panesophageal Cytosponge-on-a-string in more than 900 UK patients helped identify those at highest risk for dysplasia or cancer and needing endoscopy. It was found safe for following low-risk patients who did not need endoscopy.
Endoscopic surveillance is the clinical standard for BE, but its effectiveness is inconsistent, wrote Rebecca C. Fitzgerald, MD, AGAF, professor in the Early Cancer Institute at the University of Cambridge in Cambridge, England, and colleagues in The Lancet.
“It is often performed by nonspecialists, and recent trials show that around 10% of cases of dysplasia and cancer are missed, which means some patients re-present within a year of their surveillance procedure with a symptomatic cancer that should have been diagnosed earlier,” Fitzgerald told GI & Hepatology News.
Moreover, repeated endoscopy monitoring is stressful. “A simple nonendoscopic capsule sponge test done nearer to home is less scary and could be less operator-dependent. By reducing the burden of endoscopy in patients at very low risk we can focus more on the patients at higher risk,” she said.
In 2022, her research group had reported that the capsule sponge test, coupled with a centralized lab test for p53 and atypia, can risk-stratify patients into low-, moderate-, and high-risk groups. “In the current study, we wanted to check this risk stratification capsule sponge test in the real world. Our main aim was to see if we could conform the 2022 results with the hypothesis that the low-risk patients — more than 50% of patients in surveillance — would have a risk of high-grade dysplasia or cancer that was sufficiently low — that is, less than from 3% — and could therefore have follow-up with the capsule sponge without requiring endoscopy.”
The investigators hypothesized that the 15% at high risk would have a significant chance of dysplasia warranting endoscopy in a specialist center.
“Our results showed that in the low-risk group the risk of high-grade dysplasia or cancer was 0.4%, suggesting these patients could be offered follow-up with the capsule sponge test,” Fitzgerald said.
The high-risk group with a double biomarker positive (p53 and atypia) had an 85% risk for dysplasia or cancer. “We call this a tier 1 or ultra-high risk, and this suggests these cases merit a specialist endoscopy in a center that could treat the dysplasia/cancer,” she said.
Study Details
Adult participants (n = 910) were recruited from August 2020 to December 2024 in two multicenter, prospective, pragmatic implementation studies from 13 hospitals. Patients with nondysplastic BE on last endoscopy had a capsule sponge test.
Patient risk was assigned as low (clinical and capsule sponge biomarkers negative), moderate (negative for capsule sponge biomarkers, positive clinical biomarkers: age, sex, and segment length), or high risk (p53 abnormality, glandular atypia regardless of clinical biomarkers, or both). The primary outcome was a diagnosis of high-grade dysplasia or cancer necessitating treatment, according to the risk group.
In the cohort, 138 (15%) were classified as having high risk, 283 (31%) had moderate risk, and 489 (54%) had low risk.
The positive predictive value for any dysplasia or worse in the high-risk group was 37.7% (95% CI, 29.7-46.4). Patients with both atypia and aberrant p53 had the highest risk for high-grade dysplasia or cancer with a relative risk of 135.8 (95% CI, 32.7-564.0) vs the low-risk group.
The prevalence of high-grade dysplasia or cancer in the low-risk group was, as mentioned, just 0.4% (95% CI, 0.1-1.6), while the negative predictive value for any dysplasia or cancer was 97.8% (95% CI, 95.9-98.8). Applying a machine learning algorithm reduced the proportion needing p53 pathology review to 32% without missing any positive cases.
Offering a US perspective on the study, Nicholas J. Shaheen, MD, MPH, AGAF, professor of medicine and director of the NC Translational & Clinical Sciences Institute at the University of North Carolina School of Medicine in Chapel Hill, called the findings “very provocative.”
“We have known for some time that nonendoscopic techniques could be used to screen for Barrett’s esophagus and esophageal cancer, allowing us to screen larger groups of patients in a more cost-effective manner compared to traditional upper endoscopy,” he told GI & Hepatology News. “This study suggests that, in addition to case-finding for Barrett’s [esophagus], a nonendoscopic sponge-based technique can also help us stratify risk, finding cases that either already harbor cancer or are at high risk to do so.”
Shaheen said these cases deserve immediate attention since they are most likely to benefit from timely endoscopic intervention. “The study also suggests that a nonendoscopic result could someday be used to decide subsequent follow-up, with low-risk patients undergoing further nonendoscopic surveillance, while higher-risk patients would move on to endoscopy. Such a paradigm could unburden our endoscopy units from low-risk patients unlikely to benefit from endoscopy as well as increase the numbers of patients who are able to be screened.”
Fitzgerald added, “The GI community is realizing that we need a better approach to managing patients with Barrett’s [esophagus]. In the UK this evidence is being considered by our guideline committee, and it would influence the upcoming guidelines in 2025 with a requirement to continue to audit the results. Outside of the UK we hope this will pave the way for nonendoscopic approaches to Barrett’s [esophagus] surveillance.”
One ongoing goal is to optimize the biomarkers, Fitzgerald said. “For patients with longer segments we would like to add additional genomic biomarkers to refine the risk predictions,” she said. “We need a more operator-independent, consistent method for monitoring Barrett’s [esophagus]. This large real-world study is highly encouraging for a more personalized and patient-friendly approach to Barrett’s [esophagus] surveillance.”
This study was funded by Innovate UK, Cancer Research UK, National Health Service England Cancer Alliance. Cytosponge technology is licensed by the Medical Research Council to Medtronic. Fitzgerald declared holding patents related to this test. Fitzgerald reported being a shareholder in Cyted Health.
Shaheen reported receiving research funding from Lucid Diagnostics and Cyted Health, both of which are manufacturers of nonendoscopic screening devices for BE.
A version of this article appeared on Medscape.com.
Hypothyroidism Linked to Gut Microbiome Disturbances
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.
, according to results of a study.
“[The research] supports the idea that improving gut health could have far-reaching effects beyond digestion, possibly even helping to prevent autoimmune diseases, such as Hashimoto thyroiditis,” said senior author Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education Center and director of Clinical Operations of Medically Associated Science and Technology, at Cedars-Sinai in Los Angeles, in a press statement for the study, which was presented at ENDO 2025: The Endocrine Society Annual Meeting.
“These findings open the door to new screening and prevention strategies,” Mathur added. “For example, doctors may begin to monitor thyroid health more closely in patients with SIBO, and vice versa.”
With some small studies previously suggesting an association between the gut microbiome and hypothyroidism, Mathur and colleagues further explored the relationship in two analyses.
Assessing the Role of the Small Bowel
For the first, they evaluated data on 49 patients with Hashimoto thyroiditis (HT) and 323 controls without the condition from their REIMAGINE trial, which included small bowel fluid samples from upper endoscopies and DNA sequencing.
In the study, all patients with HT were treated with thyroid replacement (levothyroxine), hence, there were notably no significant differences between the two groups in terms of thyroid stimulating hormone (TSH) levels.
Despite the lack of those differences, patients with HT had a prevalence of SIBO more than twice that of the control group, independent of gender (33% vs 15%; odds ratio, 2.71; P = .005).
When the two groups were further subdivided into two groups each — those with and without SIBO — significant further variations of microbial diversity were observed between those with and without HT, Mathur told GI & Hepatology News.
“Interestingly, we saw the small bowel microbiome was not only different in SIBO-positive patients, including higher gram negatives, which is to be expected, but that the presence or absence of hypothyroidism itself was associated with specific patterns of these gram-negative bacteria,” she explained.
“In addition, when we looked at hypothyroidism without SIBO present, there were also changes between groups, such as higher Neisseria in the hypothyroid group.”
“All these findings are novel as this is the first paper to look specifically at the small bowel,” she added, noting that previous smaller studies have focused more on evaluation of stool samples.
“We believe the small bowel is the most metabolically active area of the intestine and plays an important role in metabolism,” Mathur noted. “Thus, the microbial changes here are likely more physiologically significant than the patterns seen in stool.”
Further Findings from a Large Population
In a separate analysis, the team evaluated data from the TriNetX database on the 10-year incidence of developing SIBO among 1.1 million subjects with hypothyroidism in the US compared with 1 million controls.
They found that people with hypothyroidism were approximately twice as likely to develop SIBO compared with those without hypothyroidism (relative risk [RR], 2.20).
Furthermore, those with HT, in particular, had an even higher risk, at 2.4 times the controls (RR, 2.40).
Treatment with levothyroxine decreased the risk of developing SIBO in hypothyroidism (RR, 0.33) and HT (RR, 0.78) vs those who did not receive treatment.
Mechanisms?
However, the fact that differences in SIBO were observed even between people who were treated for HT and those without the condition in the first analysis, and hence had similar TSH levels, was notable, Mathur said.
“This suggests that perhaps there are other factors aside from TSH levels and free T4 that are at play here,” she said. “Some people have theorized that perhaps delayed gut motility in hypothyroidism promotes the development of SIBO; however, there are many other factors within this complex interplay between the microbiome and the thyroid that could also be playing a role.”
“For example, SIBO leads to inflammation and weakening of the gut barrier,” Mathur explained.
Furthermore, “levothyroxine absorption and cycling of the thyroid hormone occurs predominantly in the small bowel, [while the] microbiome plays a key role in the absorption of iron, selenium, iodine, and zinc, which are critical for thyroid function.”
Overall, “further research is needed to understand how the mechanisms are affected during the development of SIBO and hypothyroidism,” Mathur said.
Assessment of Changes Over Time Anticipated
Commenting on the research, Gregory A. Brent, MD, senior executive academic vice-chair of the Department of Medicine and professor of medicine and physiology at the David Geffen School of Medicine at University of California Los Angeles said the study is indeed novel.
“This, to my knowledge, is the first investigation to link characteristics of the small bowel microbiome with hypothyroidism,” Brent told GI & Hepatology News.
While any clinical significance has yet to be determined, “the association of these small bowel microbiome changes with hypothyroidism may have implications for contributing to the onset of autoimmune hypothyroidism in susceptible populations as well as influences on levothyroxine absorption in hypothyroid patients on levothyroxine therapy,” Brent said.
With the SIBO differences observed even among treated patients with vs without HT, “it seems less likely that the microbiome changes are the result of reduced thyroid hormone signaling,” Brent noted.
Furthermore, a key piece of the puzzle will be to observe the microbiome changes over time, he added.
“These studies were at a single time point [and] longitudinal studies will be especially important to see how the association changes over time and are influenced by the treatment of hypothyroidism and of SIBO,” Brent said.
The authors and Brent had no disclosures to report.
A version of this article appeared on Medscape.com.