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VIP an unwelcome contributor to eosinophilic esophagitis
Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.
Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.
“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.
Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.
They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.
To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.
When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.
They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.
The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.
To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.
“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.
Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.
They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).
The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.
SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.
The rapid increase in the incidence of pediatric and adult eosinophilic esophagitis (EoE) draws immediate attention to the importance of studying the mechanisms underlying this detrimental condition. The lack of preventive or curative therapies for EoE further underscores the importance of research that addresses gaps in our understanding of how eosinophilic inflammation of the esophagus is regulated on the molecular and cellular level. EoE is classified as an allergic immune disorder of the gastrointestinal tract and is characterized by eosinophil-rich, chronic Th2-type inflammation of the esophagus.
In this recent publication, the laboratory of Anil Mishra, PhD, showed that vasoactive intestinal peptide (VIP) serves as a potent chemoattractant for eosinophils and promotes accumulation of these innate immune cells adjacent to nerve cells in the muscular mucosa. Increased VIP expression was documented in EoE patients when compared to controls, and the authors identified the chemoattractant receptor homologous molecule expressed on Th2 lymphocytes (CRTH2) as a main binding receptor for VIP. Interestingly, CRTH2 was not only found to be expressed on eosinophils but also on tissue mast cells – another innate immune cell type that significantly contributes to the inflammatory tissue infiltrate in EoE patients. Based on the human findings, the authors tested whether VIP plays a major role in recruiting eosinophils and mast cells to the inflamed esophagus and whether CRTH2 blockade can modulate experimental EoE. Indeed, EoE pathology improved in animals that were treated with a CRTH2 antagonist.
In conclusion, these observations suggest that inhibiting the VIP-CRTH2 axis may serve as a therapeutic intervention pathway to ameliorate innate tissue inflammation in EoE patients.
Edda Fiebiger, PhD, is in the department of pediatrics in the division of gastroenterology, hepatology and nutrition at Boston Children’s Hospital, as well as in the department of medicine at Harvard Medical School, also in Boston. She had no disclosures.
The rapid increase in the incidence of pediatric and adult eosinophilic esophagitis (EoE) draws immediate attention to the importance of studying the mechanisms underlying this detrimental condition. The lack of preventive or curative therapies for EoE further underscores the importance of research that addresses gaps in our understanding of how eosinophilic inflammation of the esophagus is regulated on the molecular and cellular level. EoE is classified as an allergic immune disorder of the gastrointestinal tract and is characterized by eosinophil-rich, chronic Th2-type inflammation of the esophagus.
In this recent publication, the laboratory of Anil Mishra, PhD, showed that vasoactive intestinal peptide (VIP) serves as a potent chemoattractant for eosinophils and promotes accumulation of these innate immune cells adjacent to nerve cells in the muscular mucosa. Increased VIP expression was documented in EoE patients when compared to controls, and the authors identified the chemoattractant receptor homologous molecule expressed on Th2 lymphocytes (CRTH2) as a main binding receptor for VIP. Interestingly, CRTH2 was not only found to be expressed on eosinophils but also on tissue mast cells – another innate immune cell type that significantly contributes to the inflammatory tissue infiltrate in EoE patients. Based on the human findings, the authors tested whether VIP plays a major role in recruiting eosinophils and mast cells to the inflamed esophagus and whether CRTH2 blockade can modulate experimental EoE. Indeed, EoE pathology improved in animals that were treated with a CRTH2 antagonist.
In conclusion, these observations suggest that inhibiting the VIP-CRTH2 axis may serve as a therapeutic intervention pathway to ameliorate innate tissue inflammation in EoE patients.
Edda Fiebiger, PhD, is in the department of pediatrics in the division of gastroenterology, hepatology and nutrition at Boston Children’s Hospital, as well as in the department of medicine at Harvard Medical School, also in Boston. She had no disclosures.
The rapid increase in the incidence of pediatric and adult eosinophilic esophagitis (EoE) draws immediate attention to the importance of studying the mechanisms underlying this detrimental condition. The lack of preventive or curative therapies for EoE further underscores the importance of research that addresses gaps in our understanding of how eosinophilic inflammation of the esophagus is regulated on the molecular and cellular level. EoE is classified as an allergic immune disorder of the gastrointestinal tract and is characterized by eosinophil-rich, chronic Th2-type inflammation of the esophagus.
In this recent publication, the laboratory of Anil Mishra, PhD, showed that vasoactive intestinal peptide (VIP) serves as a potent chemoattractant for eosinophils and promotes accumulation of these innate immune cells adjacent to nerve cells in the muscular mucosa. Increased VIP expression was documented in EoE patients when compared to controls, and the authors identified the chemoattractant receptor homologous molecule expressed on Th2 lymphocytes (CRTH2) as a main binding receptor for VIP. Interestingly, CRTH2 was not only found to be expressed on eosinophils but also on tissue mast cells – another innate immune cell type that significantly contributes to the inflammatory tissue infiltrate in EoE patients. Based on the human findings, the authors tested whether VIP plays a major role in recruiting eosinophils and mast cells to the inflamed esophagus and whether CRTH2 blockade can modulate experimental EoE. Indeed, EoE pathology improved in animals that were treated with a CRTH2 antagonist.
In conclusion, these observations suggest that inhibiting the VIP-CRTH2 axis may serve as a therapeutic intervention pathway to ameliorate innate tissue inflammation in EoE patients.
Edda Fiebiger, PhD, is in the department of pediatrics in the division of gastroenterology, hepatology and nutrition at Boston Children’s Hospital, as well as in the department of medicine at Harvard Medical School, also in Boston. She had no disclosures.
Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.
Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.
“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.
Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.
They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.
To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.
When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.
They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.
The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.
To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.
“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.
Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.
They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).
The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.
SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.
Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.
Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.
“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.
Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.
They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.
To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.
When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.
They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.
The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.
To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.
“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.
Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.
They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).
The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.
SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: VIP appears to play an important role in the pathogenesis of eosinophilic esophagitis (EoE).
Major finding: Neurally derived VIP and its interaction with the CRTH2 receptor appear to recruit eosinophils and mast cells into the esophageal mucosa.
Data source: In vitro studies of human EoE biopsy samples and in vivo studies in mouse models of EoE.
Disclosures: The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.
Source: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.
Hiatal hernia repair more common at time of sleeve gastrectomy, compared with RYGB
SAN DIEGO – Concomitant hiatal hernia repair is significantly more common at the time of laparoscopic sleeve gastrectomy, compared with laparoscopic Roux-en-Y gastric bypass, according to a retrospective analysis.
“GERD [gastroesophageal reflux disease] is common in patients with a high body mass index,” lead study author Dino Spaniolas, MD, said at the annual clinical congress of the American College of Surgeons. “In fact, 35%-40% of patients who undergo bariatric surgery are diagnosed with a hiatal hernia, and the majority of them are diagnosed during surgery.”
In an effort to assess the differences in practice patterns in the performance of hiatal hernia repair during laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), the researchers evaluated the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program public use files from 2015. They limited the analysis to LSG and LRYGB and also excluded revision procedures and patients with a history of foregut surgery.
In all, 130,686 patients were included in the study. Their mean age was 45 years, 79% were female, 75% were Caucasian, and their mean body mass index was 45.7 kg/m2. Most (70%) underwent LSG, while the remainder underwent LRYGB.
At baseline, a greater proportion of the LRYGB patients had a history of GERD than did LSG patients (37.2% vs. 28.6%, respectively; P less than .0001). They were also more likely to have hypertension (54.1% vs. 47.9%; P less than .0001), hyperlipidemia (29.9% vs. 23.2%; P less than .0001), and diabetes (35.5% vs. 23.3%; P less than .0001). Overall, about 15% of patients had a concomitant hiatal hernia repair in addition to their bariatric surgery.
Next, the investigators found what Dr. Spaniolas termed “the GERD paradox”: Although the LRYGB patients were more likely to have GERD before surgery, they were much less likely to undergo a hiatal hernia repair in addition to their bariatric procedure. Specifically, concomitant hiatal hernia repair was performed in 21% of LSG patients, compared with only 10.8% of LRYGB patients (P less than .0001). After investigators controlled for baseline BMI, preoperative GERD, and other patient characteristics, they found that LSG patients were 2.14 times more likely to undergo concomitant hiatal hernia repair, compared with LRYGB patients.
“This is a retrospective review, but nevertheless, I think we can conclude that these findings suggest that concomitant hiatal hernia repair is significantly more common after LSG, compared with LRYGB, despite having less GERD preoperatively,” Dr. Spaniolas said. “This suggests that there is a nationwide difference in the intraoperative management of hiatal hernia based on the type of planned bariatric procedure. This practice pattern needs to be considered while retrospectively assessing GERD-related outcomes of bariatric surgery in the future.”
Dr. Spaniolas disclosed that he has received research support from Merck and that he is a consultant for Mallinckrodt.
SAN DIEGO – Concomitant hiatal hernia repair is significantly more common at the time of laparoscopic sleeve gastrectomy, compared with laparoscopic Roux-en-Y gastric bypass, according to a retrospective analysis.
“GERD [gastroesophageal reflux disease] is common in patients with a high body mass index,” lead study author Dino Spaniolas, MD, said at the annual clinical congress of the American College of Surgeons. “In fact, 35%-40% of patients who undergo bariatric surgery are diagnosed with a hiatal hernia, and the majority of them are diagnosed during surgery.”
In an effort to assess the differences in practice patterns in the performance of hiatal hernia repair during laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), the researchers evaluated the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program public use files from 2015. They limited the analysis to LSG and LRYGB and also excluded revision procedures and patients with a history of foregut surgery.
In all, 130,686 patients were included in the study. Their mean age was 45 years, 79% were female, 75% were Caucasian, and their mean body mass index was 45.7 kg/m2. Most (70%) underwent LSG, while the remainder underwent LRYGB.
At baseline, a greater proportion of the LRYGB patients had a history of GERD than did LSG patients (37.2% vs. 28.6%, respectively; P less than .0001). They were also more likely to have hypertension (54.1% vs. 47.9%; P less than .0001), hyperlipidemia (29.9% vs. 23.2%; P less than .0001), and diabetes (35.5% vs. 23.3%; P less than .0001). Overall, about 15% of patients had a concomitant hiatal hernia repair in addition to their bariatric surgery.
Next, the investigators found what Dr. Spaniolas termed “the GERD paradox”: Although the LRYGB patients were more likely to have GERD before surgery, they were much less likely to undergo a hiatal hernia repair in addition to their bariatric procedure. Specifically, concomitant hiatal hernia repair was performed in 21% of LSG patients, compared with only 10.8% of LRYGB patients (P less than .0001). After investigators controlled for baseline BMI, preoperative GERD, and other patient characteristics, they found that LSG patients were 2.14 times more likely to undergo concomitant hiatal hernia repair, compared with LRYGB patients.
“This is a retrospective review, but nevertheless, I think we can conclude that these findings suggest that concomitant hiatal hernia repair is significantly more common after LSG, compared with LRYGB, despite having less GERD preoperatively,” Dr. Spaniolas said. “This suggests that there is a nationwide difference in the intraoperative management of hiatal hernia based on the type of planned bariatric procedure. This practice pattern needs to be considered while retrospectively assessing GERD-related outcomes of bariatric surgery in the future.”
Dr. Spaniolas disclosed that he has received research support from Merck and that he is a consultant for Mallinckrodt.
SAN DIEGO – Concomitant hiatal hernia repair is significantly more common at the time of laparoscopic sleeve gastrectomy, compared with laparoscopic Roux-en-Y gastric bypass, according to a retrospective analysis.
“GERD [gastroesophageal reflux disease] is common in patients with a high body mass index,” lead study author Dino Spaniolas, MD, said at the annual clinical congress of the American College of Surgeons. “In fact, 35%-40% of patients who undergo bariatric surgery are diagnosed with a hiatal hernia, and the majority of them are diagnosed during surgery.”
In an effort to assess the differences in practice patterns in the performance of hiatal hernia repair during laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB), the researchers evaluated the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program public use files from 2015. They limited the analysis to LSG and LRYGB and also excluded revision procedures and patients with a history of foregut surgery.
In all, 130,686 patients were included in the study. Their mean age was 45 years, 79% were female, 75% were Caucasian, and their mean body mass index was 45.7 kg/m2. Most (70%) underwent LSG, while the remainder underwent LRYGB.
At baseline, a greater proportion of the LRYGB patients had a history of GERD than did LSG patients (37.2% vs. 28.6%, respectively; P less than .0001). They were also more likely to have hypertension (54.1% vs. 47.9%; P less than .0001), hyperlipidemia (29.9% vs. 23.2%; P less than .0001), and diabetes (35.5% vs. 23.3%; P less than .0001). Overall, about 15% of patients had a concomitant hiatal hernia repair in addition to their bariatric surgery.
Next, the investigators found what Dr. Spaniolas termed “the GERD paradox”: Although the LRYGB patients were more likely to have GERD before surgery, they were much less likely to undergo a hiatal hernia repair in addition to their bariatric procedure. Specifically, concomitant hiatal hernia repair was performed in 21% of LSG patients, compared with only 10.8% of LRYGB patients (P less than .0001). After investigators controlled for baseline BMI, preoperative GERD, and other patient characteristics, they found that LSG patients were 2.14 times more likely to undergo concomitant hiatal hernia repair, compared with LRYGB patients.
“This is a retrospective review, but nevertheless, I think we can conclude that these findings suggest that concomitant hiatal hernia repair is significantly more common after LSG, compared with LRYGB, despite having less GERD preoperatively,” Dr. Spaniolas said. “This suggests that there is a nationwide difference in the intraoperative management of hiatal hernia based on the type of planned bariatric procedure. This practice pattern needs to be considered while retrospectively assessing GERD-related outcomes of bariatric surgery in the future.”
Dr. Spaniolas disclosed that he has received research support from Merck and that he is a consultant for Mallinckrodt.
AT THE ACS CLINICAL CONGRESS
Key clinical point: LSG patients are more likely to undergo concomitant hiatal hernia repair, compared with LRYGB patients.
Major finding: According to multivariate analysis, LSG patients were more likely to undergo concomitant HH repair (odds ratio, 2.14).
Study details: A retrospective analysis of 130,686 patients who underwent bariatric surgery in 2015.
Disclosures: Dr. Spaniolas disclosed that he has received research support from Merck and that he is a consultant for Mallinckrodt.
AGA Clinical Practice Update: Best practices for POEM in achalasia
Peroral endoscopic myotomy, or POEM, should be considered as primary therapy for type III achalasia and as a treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes – but only when physicians with expertise are available, according to a clinical practice update from the American Gastroenterological Association.
Further, post-POEM patients should be considered at high risk of developing reflux esophagitis and should be advised of the management considerations, including potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy, prior to undergoing the procedure, Peter J. Kahrilas, MD, of Northwestern University, Chicago, and his colleagues wrote in the update, which is published in the November issue of Gastroenterology (2017. doi: 10.1053/j.gastro.2017.10.001).
In an effort to describe the place for POEM among the currently available robust treatments for achalasia, the authors conducted a literature review – their “best practice” recommendations are based on the findings from relevant publications and on expert opinion.
Additionally, they said POEM should be performed by experienced physicians in high-volume centers since the procedure is complex and an estimated 20-30 procedures are needed to achieve competence.
The update and these proposed best practices follow the evolution of POEM over the last decade: it began as an exciting concept and is now a mainstream treatment option for achalasia, the authors said.
“Uncontrolled outcome data have been very promising comparing POEM with the standard surgical treatment for achalasia, laparoscopic Heller myotomy (LHM). However, concerns remain regarding post-POEM reflux, the durability of the procedure, and the learning curve for endoscopists adopting the technique,” they wrote, which, when coupled with recent randomized controlled study data showing excellent and equivalent 5-year outcomes with pneumatic dilation and LHM, make the role of POEM somewhat controversial.
As part of the review, they considered the strengths and weaknesses of both POEM and LHM. The data comparing POEM with LHM or pneumatic dilation remain very limited, but based on those that do exist, the authors concluded that “POEM appears to be a safe, effective, and minimally invasive management option in achalasia in the short term.”
Long-term durability data are not yet available, they noted.
Dr. Kahrilas received funding from the U.S. Public Health Service.
Peroral endoscopic myotomy, or POEM, should be considered as primary therapy for type III achalasia and as a treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes – but only when physicians with expertise are available, according to a clinical practice update from the American Gastroenterological Association.
Further, post-POEM patients should be considered at high risk of developing reflux esophagitis and should be advised of the management considerations, including potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy, prior to undergoing the procedure, Peter J. Kahrilas, MD, of Northwestern University, Chicago, and his colleagues wrote in the update, which is published in the November issue of Gastroenterology (2017. doi: 10.1053/j.gastro.2017.10.001).
In an effort to describe the place for POEM among the currently available robust treatments for achalasia, the authors conducted a literature review – their “best practice” recommendations are based on the findings from relevant publications and on expert opinion.
Additionally, they said POEM should be performed by experienced physicians in high-volume centers since the procedure is complex and an estimated 20-30 procedures are needed to achieve competence.
The update and these proposed best practices follow the evolution of POEM over the last decade: it began as an exciting concept and is now a mainstream treatment option for achalasia, the authors said.
“Uncontrolled outcome data have been very promising comparing POEM with the standard surgical treatment for achalasia, laparoscopic Heller myotomy (LHM). However, concerns remain regarding post-POEM reflux, the durability of the procedure, and the learning curve for endoscopists adopting the technique,” they wrote, which, when coupled with recent randomized controlled study data showing excellent and equivalent 5-year outcomes with pneumatic dilation and LHM, make the role of POEM somewhat controversial.
As part of the review, they considered the strengths and weaknesses of both POEM and LHM. The data comparing POEM with LHM or pneumatic dilation remain very limited, but based on those that do exist, the authors concluded that “POEM appears to be a safe, effective, and minimally invasive management option in achalasia in the short term.”
Long-term durability data are not yet available, they noted.
Dr. Kahrilas received funding from the U.S. Public Health Service.
Peroral endoscopic myotomy, or POEM, should be considered as primary therapy for type III achalasia and as a treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes – but only when physicians with expertise are available, according to a clinical practice update from the American Gastroenterological Association.
Further, post-POEM patients should be considered at high risk of developing reflux esophagitis and should be advised of the management considerations, including potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy, prior to undergoing the procedure, Peter J. Kahrilas, MD, of Northwestern University, Chicago, and his colleagues wrote in the update, which is published in the November issue of Gastroenterology (2017. doi: 10.1053/j.gastro.2017.10.001).
In an effort to describe the place for POEM among the currently available robust treatments for achalasia, the authors conducted a literature review – their “best practice” recommendations are based on the findings from relevant publications and on expert opinion.
Additionally, they said POEM should be performed by experienced physicians in high-volume centers since the procedure is complex and an estimated 20-30 procedures are needed to achieve competence.
The update and these proposed best practices follow the evolution of POEM over the last decade: it began as an exciting concept and is now a mainstream treatment option for achalasia, the authors said.
“Uncontrolled outcome data have been very promising comparing POEM with the standard surgical treatment for achalasia, laparoscopic Heller myotomy (LHM). However, concerns remain regarding post-POEM reflux, the durability of the procedure, and the learning curve for endoscopists adopting the technique,” they wrote, which, when coupled with recent randomized controlled study data showing excellent and equivalent 5-year outcomes with pneumatic dilation and LHM, make the role of POEM somewhat controversial.
As part of the review, they considered the strengths and weaknesses of both POEM and LHM. The data comparing POEM with LHM or pneumatic dilation remain very limited, but based on those that do exist, the authors concluded that “POEM appears to be a safe, effective, and minimally invasive management option in achalasia in the short term.”
Long-term durability data are not yet available, they noted.
Dr. Kahrilas received funding from the U.S. Public Health Service.
FROM GASTROENTEROLOGY
Intubation for upper GI bleeding may increase cardiopulmonary risk
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: Although many advocate prophylactic endotracheal intubation in critically ill patients presenting with brisk upper GI bleeding, doing so may actually increase, rather than decrease, risk of cardiopulmonary events.
Major finding: The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008), with the difference remaining significant even after adjusting for the presence of esophageal varices.
Data source: Retrospective cohort study including data on 365 adult patients who presented with brisk upper GI bleeding at a tertiary care center.
Disclosures: The authors disclosed no financial relationships relevant to the current study.
Pilot study: Novel spray powder stops GI bleeding
ORLANDO – TC-325 (Hemospray), a proprietary mineral powder blend developed for endoscopic hemostasis, promoted immediate hemostasis and prevented rebleeding in patients with malignant gastrointestinal bleeding in a randomized pilot trial.
Nine of 10 patients randomized to receive treatment with TC-325 experienced immediate hemostasis, compared with 4 of 10 patients randomized to receive standard of care (usually argon plasma coagulation, sometimes with radiation therapy), Alan Barkun, MD, of McGill University, Montreal reported at the World Congress of Gastroenterology at ACG 2017.
Five of six patients in the standard of care group who did not achieve immediate hemostasis crossed over to TC-325. Hemostasis was then achieved at index endoscopy in 80% of these crossovers, said Dr. Barkun, whose work received the 2017 GI Bleeding Category Award at the congress.
“So a total of 15 patients were treated with Hemospray among both groups, and 100% of them achieved immediate hemostasis,” he said. “We also assessed feasibility of recruitment and randomization, and it was indeed demonstrated in the context of this feasibility trial.”
Secondary measures, including the use of additional hemostatic approaches, blood transfusions, length of stay, and mortality, among others, did not differ between the two groups.
“This pilot trial is the first to assess TC-325 in patients with malignant bleeding, allowing us to plan for adequate powering and demonstrating feasibility for a larger multicenter, randomized, controlled trial,” he said. “Although this trial was not powered to seek statistically significant differences, the observed results suggest that TC-325 may indeed be a promising hemostatic modality in managing patients with malignant bleeding in achieving both immediate hemostasis and in our minds, surprisingly, perhaps delayed rebleeding.”
Hemospray, which is approved in Canada for upper/lower gastrointestinal bleeding of any etiology, as well as in Mexico and in some countries in Europe, Asia, and South America, works by forming a mechanical barrier over the bleeding site. The powder absorbs water, then acts both cohesively and adhesively to form that barrier, according to information from Cook Medical, which developed the product. It is not currently approved for this indication in the United States.
“An adequately powered randomized, controlled trial is now needed to better determine any beneficial downstream effect on subsequent rebleeding and health care resource use when compared to existing standard of care,” he concluded.
Dr. Barkun is an advisory committee/board member and consultant for Cook Medical and has received grant/research support from the company.
ORLANDO – TC-325 (Hemospray), a proprietary mineral powder blend developed for endoscopic hemostasis, promoted immediate hemostasis and prevented rebleeding in patients with malignant gastrointestinal bleeding in a randomized pilot trial.
Nine of 10 patients randomized to receive treatment with TC-325 experienced immediate hemostasis, compared with 4 of 10 patients randomized to receive standard of care (usually argon plasma coagulation, sometimes with radiation therapy), Alan Barkun, MD, of McGill University, Montreal reported at the World Congress of Gastroenterology at ACG 2017.
Five of six patients in the standard of care group who did not achieve immediate hemostasis crossed over to TC-325. Hemostasis was then achieved at index endoscopy in 80% of these crossovers, said Dr. Barkun, whose work received the 2017 GI Bleeding Category Award at the congress.
“So a total of 15 patients were treated with Hemospray among both groups, and 100% of them achieved immediate hemostasis,” he said. “We also assessed feasibility of recruitment and randomization, and it was indeed demonstrated in the context of this feasibility trial.”
Secondary measures, including the use of additional hemostatic approaches, blood transfusions, length of stay, and mortality, among others, did not differ between the two groups.
“This pilot trial is the first to assess TC-325 in patients with malignant bleeding, allowing us to plan for adequate powering and demonstrating feasibility for a larger multicenter, randomized, controlled trial,” he said. “Although this trial was not powered to seek statistically significant differences, the observed results suggest that TC-325 may indeed be a promising hemostatic modality in managing patients with malignant bleeding in achieving both immediate hemostasis and in our minds, surprisingly, perhaps delayed rebleeding.”
Hemospray, which is approved in Canada for upper/lower gastrointestinal bleeding of any etiology, as well as in Mexico and in some countries in Europe, Asia, and South America, works by forming a mechanical barrier over the bleeding site. The powder absorbs water, then acts both cohesively and adhesively to form that barrier, according to information from Cook Medical, which developed the product. It is not currently approved for this indication in the United States.
“An adequately powered randomized, controlled trial is now needed to better determine any beneficial downstream effect on subsequent rebleeding and health care resource use when compared to existing standard of care,” he concluded.
Dr. Barkun is an advisory committee/board member and consultant for Cook Medical and has received grant/research support from the company.
ORLANDO – TC-325 (Hemospray), a proprietary mineral powder blend developed for endoscopic hemostasis, promoted immediate hemostasis and prevented rebleeding in patients with malignant gastrointestinal bleeding in a randomized pilot trial.
Nine of 10 patients randomized to receive treatment with TC-325 experienced immediate hemostasis, compared with 4 of 10 patients randomized to receive standard of care (usually argon plasma coagulation, sometimes with radiation therapy), Alan Barkun, MD, of McGill University, Montreal reported at the World Congress of Gastroenterology at ACG 2017.
Five of six patients in the standard of care group who did not achieve immediate hemostasis crossed over to TC-325. Hemostasis was then achieved at index endoscopy in 80% of these crossovers, said Dr. Barkun, whose work received the 2017 GI Bleeding Category Award at the congress.
“So a total of 15 patients were treated with Hemospray among both groups, and 100% of them achieved immediate hemostasis,” he said. “We also assessed feasibility of recruitment and randomization, and it was indeed demonstrated in the context of this feasibility trial.”
Secondary measures, including the use of additional hemostatic approaches, blood transfusions, length of stay, and mortality, among others, did not differ between the two groups.
“This pilot trial is the first to assess TC-325 in patients with malignant bleeding, allowing us to plan for adequate powering and demonstrating feasibility for a larger multicenter, randomized, controlled trial,” he said. “Although this trial was not powered to seek statistically significant differences, the observed results suggest that TC-325 may indeed be a promising hemostatic modality in managing patients with malignant bleeding in achieving both immediate hemostasis and in our minds, surprisingly, perhaps delayed rebleeding.”
Hemospray, which is approved in Canada for upper/lower gastrointestinal bleeding of any etiology, as well as in Mexico and in some countries in Europe, Asia, and South America, works by forming a mechanical barrier over the bleeding site. The powder absorbs water, then acts both cohesively and adhesively to form that barrier, according to information from Cook Medical, which developed the product. It is not currently approved for this indication in the United States.
“An adequately powered randomized, controlled trial is now needed to better determine any beneficial downstream effect on subsequent rebleeding and health care resource use when compared to existing standard of care,” he concluded.
Dr. Barkun is an advisory committee/board member and consultant for Cook Medical and has received grant/research support from the company.
AT THE WORLD CONGRESS OF GASTROENTEROLOGY
Key clinical point:
Major finding: All 15 patients treated with Hemospray achieved immediate hemostasis.
Data source: A randomized pilot study of 20 patients.
Disclosures: Dr. Barkun is an advisory committee/board member and consultant for Cook Medical and has received grant/research support from the company.
GERD postop relapse rates highest in women, older adults
Healthy men younger than 45 years have the lowest risk of relapse after reflux surgery compared with other demographic subgroups, according to data from a population-based study of 2,655 adults in Sweden. The findings were published online in JAMA.
“Cohort studies have shown a high risk of recurrent symptoms of GERD after surgery, which may have contributed to the decline in the use of antireflux surgery,” but long-term reflux recurrence rates and potential risk factors have not been well studied, wrote John Maret-Ouda, MD, and colleagues at the Karolinska Institutet in Stockholm, Sweden.
Overall, 18% of the patients suffered a reflux relapse; 84% of these were prescribed long-term medication, and 16% underwent additional surgery.
The highest relapse rates occurred among women, older patients, and those with comorbid conditions. Reflux occurred in 22% of women vs. 14% of men (hazard ratio 1.57), and the hazard ratio was 1.41 for patients aged 61 years and older compared with those aged 45 years and younger. Patients with one or more comorbidities were approximately one-third more likely to have a recurrence of reflux, compared with those who had no comorbidities (hazard ratio 1.36).
Approximately 4% of patients reported complications; the most common complication was infection (1.1%), followed by bleeding (0.9%), and esophageal perforation (0.9%).
The recurrence rate of 18% is low compared with other studies, the researchers noted. Possible reasons for the difference include the population-based design of the current study, which meant that no patients were lost to follow-up, as well as the recent time period, “in which laparoscopic antireflux surgery has become more centralized to expert centers where selection of patients might be stricter and the quality of surgery might be higher,” they wrote.
The study findings were limited by several factors including clinical variations on coding, lack of data on certain confounding variables including body mass index and smoking, and a lack of control GERD patients who did not undergo antireflux surgery, the researchers said. The results suggest that the benefits of laparoscopic antireflux surgery may be diminished by the potential for recurrent GERD, they added.
The Swedish Research Council funded the study. The researchers had no financial conflicts to disclose.
“The operation can be performed with a relatively low rate of morbidity and a very low mortality rate,” Stuart J. Spechler, MD, wrote in an editorial. “Although findings regarding GERD symptom relief and patient satisfaction based on medication usage data should be interpreted with caution, the observation that more than 80% of patients did not restart antireflux medications after laparoscopic antireflux surgery suggests that the operation provided long-lasting relief of GERD symptoms for most patients,” he said. Although surgery is not a permanent cure for all patients with GERD, “the ever-increasing number of proposed [proton pump inhibitor] risks has caused the greatest concern among clinicians and their patients,” said Dr. Spechler. “Whether the greater than 80% possibility of long-term freedom from PPIs and their associated risks warrants the 4% risk of acute surgical complications and the 17.7% risk of GERD recurrence is a decision that individual patients should make after a detailed discussion of these risks and benefits with their physicians,” he said. However, the study findings suggest “that laparoscopic antireflux surgery might be an especially appealing option for young and otherwise healthy men, who seem to have the lowest rate of GERD recurrence after antireflux surgery and who otherwise would likely require decades of PPI treatment without the operation,” he wrote (JAMA 2017;318:913-5).
Dr. Spechler is affiliated with Baylor University in Dallas. He disclosed serving as a consultant for Ironwood Pharmaceuticals and Takeda Pharmaceuticals, and funding support from the National Institutes of Health.
“The operation can be performed with a relatively low rate of morbidity and a very low mortality rate,” Stuart J. Spechler, MD, wrote in an editorial. “Although findings regarding GERD symptom relief and patient satisfaction based on medication usage data should be interpreted with caution, the observation that more than 80% of patients did not restart antireflux medications after laparoscopic antireflux surgery suggests that the operation provided long-lasting relief of GERD symptoms for most patients,” he said. Although surgery is not a permanent cure for all patients with GERD, “the ever-increasing number of proposed [proton pump inhibitor] risks has caused the greatest concern among clinicians and their patients,” said Dr. Spechler. “Whether the greater than 80% possibility of long-term freedom from PPIs and their associated risks warrants the 4% risk of acute surgical complications and the 17.7% risk of GERD recurrence is a decision that individual patients should make after a detailed discussion of these risks and benefits with their physicians,” he said. However, the study findings suggest “that laparoscopic antireflux surgery might be an especially appealing option for young and otherwise healthy men, who seem to have the lowest rate of GERD recurrence after antireflux surgery and who otherwise would likely require decades of PPI treatment without the operation,” he wrote (JAMA 2017;318:913-5).
Dr. Spechler is affiliated with Baylor University in Dallas. He disclosed serving as a consultant for Ironwood Pharmaceuticals and Takeda Pharmaceuticals, and funding support from the National Institutes of Health.
“The operation can be performed with a relatively low rate of morbidity and a very low mortality rate,” Stuart J. Spechler, MD, wrote in an editorial. “Although findings regarding GERD symptom relief and patient satisfaction based on medication usage data should be interpreted with caution, the observation that more than 80% of patients did not restart antireflux medications after laparoscopic antireflux surgery suggests that the operation provided long-lasting relief of GERD symptoms for most patients,” he said. Although surgery is not a permanent cure for all patients with GERD, “the ever-increasing number of proposed [proton pump inhibitor] risks has caused the greatest concern among clinicians and their patients,” said Dr. Spechler. “Whether the greater than 80% possibility of long-term freedom from PPIs and their associated risks warrants the 4% risk of acute surgical complications and the 17.7% risk of GERD recurrence is a decision that individual patients should make after a detailed discussion of these risks and benefits with their physicians,” he said. However, the study findings suggest “that laparoscopic antireflux surgery might be an especially appealing option for young and otherwise healthy men, who seem to have the lowest rate of GERD recurrence after antireflux surgery and who otherwise would likely require decades of PPI treatment without the operation,” he wrote (JAMA 2017;318:913-5).
Dr. Spechler is affiliated with Baylor University in Dallas. He disclosed serving as a consultant for Ironwood Pharmaceuticals and Takeda Pharmaceuticals, and funding support from the National Institutes of Health.
Healthy men younger than 45 years have the lowest risk of relapse after reflux surgery compared with other demographic subgroups, according to data from a population-based study of 2,655 adults in Sweden. The findings were published online in JAMA.
“Cohort studies have shown a high risk of recurrent symptoms of GERD after surgery, which may have contributed to the decline in the use of antireflux surgery,” but long-term reflux recurrence rates and potential risk factors have not been well studied, wrote John Maret-Ouda, MD, and colleagues at the Karolinska Institutet in Stockholm, Sweden.
Overall, 18% of the patients suffered a reflux relapse; 84% of these were prescribed long-term medication, and 16% underwent additional surgery.
The highest relapse rates occurred among women, older patients, and those with comorbid conditions. Reflux occurred in 22% of women vs. 14% of men (hazard ratio 1.57), and the hazard ratio was 1.41 for patients aged 61 years and older compared with those aged 45 years and younger. Patients with one or more comorbidities were approximately one-third more likely to have a recurrence of reflux, compared with those who had no comorbidities (hazard ratio 1.36).
Approximately 4% of patients reported complications; the most common complication was infection (1.1%), followed by bleeding (0.9%), and esophageal perforation (0.9%).
The recurrence rate of 18% is low compared with other studies, the researchers noted. Possible reasons for the difference include the population-based design of the current study, which meant that no patients were lost to follow-up, as well as the recent time period, “in which laparoscopic antireflux surgery has become more centralized to expert centers where selection of patients might be stricter and the quality of surgery might be higher,” they wrote.
The study findings were limited by several factors including clinical variations on coding, lack of data on certain confounding variables including body mass index and smoking, and a lack of control GERD patients who did not undergo antireflux surgery, the researchers said. The results suggest that the benefits of laparoscopic antireflux surgery may be diminished by the potential for recurrent GERD, they added.
The Swedish Research Council funded the study. The researchers had no financial conflicts to disclose.
Healthy men younger than 45 years have the lowest risk of relapse after reflux surgery compared with other demographic subgroups, according to data from a population-based study of 2,655 adults in Sweden. The findings were published online in JAMA.
“Cohort studies have shown a high risk of recurrent symptoms of GERD after surgery, which may have contributed to the decline in the use of antireflux surgery,” but long-term reflux recurrence rates and potential risk factors have not been well studied, wrote John Maret-Ouda, MD, and colleagues at the Karolinska Institutet in Stockholm, Sweden.
Overall, 18% of the patients suffered a reflux relapse; 84% of these were prescribed long-term medication, and 16% underwent additional surgery.
The highest relapse rates occurred among women, older patients, and those with comorbid conditions. Reflux occurred in 22% of women vs. 14% of men (hazard ratio 1.57), and the hazard ratio was 1.41 for patients aged 61 years and older compared with those aged 45 years and younger. Patients with one or more comorbidities were approximately one-third more likely to have a recurrence of reflux, compared with those who had no comorbidities (hazard ratio 1.36).
Approximately 4% of patients reported complications; the most common complication was infection (1.1%), followed by bleeding (0.9%), and esophageal perforation (0.9%).
The recurrence rate of 18% is low compared with other studies, the researchers noted. Possible reasons for the difference include the population-based design of the current study, which meant that no patients were lost to follow-up, as well as the recent time period, “in which laparoscopic antireflux surgery has become more centralized to expert centers where selection of patients might be stricter and the quality of surgery might be higher,” they wrote.
The study findings were limited by several factors including clinical variations on coding, lack of data on certain confounding variables including body mass index and smoking, and a lack of control GERD patients who did not undergo antireflux surgery, the researchers said. The results suggest that the benefits of laparoscopic antireflux surgery may be diminished by the potential for recurrent GERD, they added.
The Swedish Research Council funded the study. The researchers had no financial conflicts to disclose.
FROM JAMA
Key clinical point: Young men were less likely than were other demographic groups to experience recurrence of gastroesophageal reflux after surgery.
Major finding: Overall, 18% of 2,655 adults who underwent reflux surgery experienced recurrent reflux requiring long-term medication or additional surgery.
Data source: A population-based, retrospective cohort study of reflux surgery patients in Sweden.
Disclosures: The Swedish Research Council supported the study.
Study linked H2 receptor antagonists, but not PPIs, to dementia
A large prospective study of middle-aged and older women found no convincing evidence that using proton pump inhibitors increased their risk of dementia, investigators reported.
However, using H2 receptor antagonists for at least 9 years was associated with a slight decrease in scores of learning and working memory (mean decrease, –0.2; 95% confidence interval, –0.3 to –0.08; P less than .001), Paul Lochhead, MBChB, PhD, and his associates wrote in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2017.06.061). “Since our primary hypothesis related to PPI [proton pump inhibitor] use, our findings for [H2 receptor antagonists] should be interpreted with caution,” they said.
Source: American Gastroenterological Association
In a recent German study of a medical claims database, use of PPIs was associated with a 44% increase in the likelihood of incident dementia (JAMA Neurol. 2016;73:410-6). “The existence of a causal mechanism linking PPI use to dementia is suggested by observations from cellular and animal models of Alzheimer’s disease, where PPI exposure appears to influence amyloid-beta metabolism,” Dr. Lochhead and his associates wrote. “However, other preclinical data on PPIs and Alzheimer’s disease are conflicting.” Noting that cognitive function predicts dementia later in life, they analyzed prospective data on medications and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed Cogstate, a computerized, self-administered neuropsychological battery.
Study participants averaged 61 years old when they underwent cognitive testing, ranging in age from 50 to 70 years. Users of PPIs tended to be older, had more comorbidities, were less physically active, had higher body mass indexes, had less education, and ate a lower-quality diet than women who did not use PPIs. After adjusting for such confounders, using PPIs for 9-14 years was associated with a modest decrease in scores for psychomotor speed and attention (mean score difference, compared with never users, –0.06; 95% CI, –0.11 to 0.00; P = .03). “For comparison, in multivariable models, a 1-year increase in age was associated with mean score decreases of 0.03 for psychomotor speed and attention, 0.02 for learning and working memory, and 0.03 for overall cognition,” the researchers wrote.
Next, they examined links between use of H2 receptor antagonists and cognitive scores among 10,778 study participants who had used PPIs for 2 years or less. Use of H2 receptor antagonists for 9-14 years predicted poorer scores on learning, working memory, and overall cognition, even after controlling for potential confounders (P less than or equal to .002). “The magnitudes of mean score differences were larger than those observed in the analysis of PPI use, particularly for learning and working memory,” the researchers noted. Additionally, PPI use did not predict lower cognitive scores among individuals who had never used H2 receptor antagonists.
On the other hand, using PPIs for 9-14 years was associated with the equivalent of about 2 years of age-related cognitive decline, and controlling for exposure to H2 receptor antagonists weakened even this modest effect, the investigators said. Users and nonusers of PPIs tend to differ on many measures, and analyses of claims data, such as the German study above, are less able to account for these potential confounders, they noted. “Nonjudicious PPI prescribing is especially frequent among the elderly and those with cognitive impairment,” they added. “Therefore, elderly individuals who have frequent contact with health providers are at increased risk of both PPI prescription and dementia diagnosis. This bias may not be completely mitigated by adjustment for comorbidities or polypharmacy.”
The findings regarding H2 receptor antagonists reflect those of three smaller cohort studies, and these medications are known to cause central nervous system effects in the elderly, including delirium, the researchers said. Ranitidine and cimetidine have anticholinergic effects that also could “pose a risk for adverse cognitive effects with long-term use.”
Dr. Lochhead reported having no conflicts. Two coinvestigators disclosed ties to Bayer Healthcare, Pfizer, Aralez Pharmaceuticals, AbbVie, Samsung Bioepis, and Takeda.
Numerous possible PPI-related adverse events have been reported within the past few years; some resultant media attention has caused anxiety for patients. Dementia is a dreaded diagnosis. Therefore, initial reports that PPI treatment might be associated with an increased risk of dementia attracted considerable media attention, much of which was unbalanced and uninformed. There is no obvious biological rationale for such an association, and the risks reported initially were of small magnitude (for example, hazard ratios of approximately 1.4). However, patients cannot reliably assess levels of risk from media coverage that often veers toward sensationalism.
The study by Lochhead et al. is a welcome contribution to the topic of PPI safety. Using the Nurses’ Health Study II database, the investigators measured cognitive function in a large group of female PPI users and nonusers. Unsurprisingly, PPI users were older and sicker than nonusers. There were quantitatively small changes in some measures of cognitive function among PPI users. However, learning and working memory scores, which are more predictive of Alzheimer’s-type cognitive decline, were unaffected by PPI use.
For those prescribers with residual concerns about any association between PPIs and dementia, these prospectively collected data on cognitive function should provide further reassurance. It is appropriate that this study should have been highlighted in GI & Hepatology News, but since it lacks the potential sensationalism of studies that report a putative association, we should not expect it to be discussed on the TV evening news anytime soon!
Colin W. Howden, MD, AGAF, is chief of gastroenterology at University of Tennessee Health Science Center, Memphis. He has been a consultant, investigator, and/or speaker for all PPI manufacturers at some time. He is currently a consultant for Takeda, Aralez, and Pfizer Consumer Health.
Numerous possible PPI-related adverse events have been reported within the past few years; some resultant media attention has caused anxiety for patients. Dementia is a dreaded diagnosis. Therefore, initial reports that PPI treatment might be associated with an increased risk of dementia attracted considerable media attention, much of which was unbalanced and uninformed. There is no obvious biological rationale for such an association, and the risks reported initially were of small magnitude (for example, hazard ratios of approximately 1.4). However, patients cannot reliably assess levels of risk from media coverage that often veers toward sensationalism.
The study by Lochhead et al. is a welcome contribution to the topic of PPI safety. Using the Nurses’ Health Study II database, the investigators measured cognitive function in a large group of female PPI users and nonusers. Unsurprisingly, PPI users were older and sicker than nonusers. There were quantitatively small changes in some measures of cognitive function among PPI users. However, learning and working memory scores, which are more predictive of Alzheimer’s-type cognitive decline, were unaffected by PPI use.
For those prescribers with residual concerns about any association between PPIs and dementia, these prospectively collected data on cognitive function should provide further reassurance. It is appropriate that this study should have been highlighted in GI & Hepatology News, but since it lacks the potential sensationalism of studies that report a putative association, we should not expect it to be discussed on the TV evening news anytime soon!
Colin W. Howden, MD, AGAF, is chief of gastroenterology at University of Tennessee Health Science Center, Memphis. He has been a consultant, investigator, and/or speaker for all PPI manufacturers at some time. He is currently a consultant for Takeda, Aralez, and Pfizer Consumer Health.
Numerous possible PPI-related adverse events have been reported within the past few years; some resultant media attention has caused anxiety for patients. Dementia is a dreaded diagnosis. Therefore, initial reports that PPI treatment might be associated with an increased risk of dementia attracted considerable media attention, much of which was unbalanced and uninformed. There is no obvious biological rationale for such an association, and the risks reported initially were of small magnitude (for example, hazard ratios of approximately 1.4). However, patients cannot reliably assess levels of risk from media coverage that often veers toward sensationalism.
The study by Lochhead et al. is a welcome contribution to the topic of PPI safety. Using the Nurses’ Health Study II database, the investigators measured cognitive function in a large group of female PPI users and nonusers. Unsurprisingly, PPI users were older and sicker than nonusers. There were quantitatively small changes in some measures of cognitive function among PPI users. However, learning and working memory scores, which are more predictive of Alzheimer’s-type cognitive decline, were unaffected by PPI use.
For those prescribers with residual concerns about any association between PPIs and dementia, these prospectively collected data on cognitive function should provide further reassurance. It is appropriate that this study should have been highlighted in GI & Hepatology News, but since it lacks the potential sensationalism of studies that report a putative association, we should not expect it to be discussed on the TV evening news anytime soon!
Colin W. Howden, MD, AGAF, is chief of gastroenterology at University of Tennessee Health Science Center, Memphis. He has been a consultant, investigator, and/or speaker for all PPI manufacturers at some time. He is currently a consultant for Takeda, Aralez, and Pfizer Consumer Health.
A large prospective study of middle-aged and older women found no convincing evidence that using proton pump inhibitors increased their risk of dementia, investigators reported.
However, using H2 receptor antagonists for at least 9 years was associated with a slight decrease in scores of learning and working memory (mean decrease, –0.2; 95% confidence interval, –0.3 to –0.08; P less than .001), Paul Lochhead, MBChB, PhD, and his associates wrote in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2017.06.061). “Since our primary hypothesis related to PPI [proton pump inhibitor] use, our findings for [H2 receptor antagonists] should be interpreted with caution,” they said.
Source: American Gastroenterological Association
In a recent German study of a medical claims database, use of PPIs was associated with a 44% increase in the likelihood of incident dementia (JAMA Neurol. 2016;73:410-6). “The existence of a causal mechanism linking PPI use to dementia is suggested by observations from cellular and animal models of Alzheimer’s disease, where PPI exposure appears to influence amyloid-beta metabolism,” Dr. Lochhead and his associates wrote. “However, other preclinical data on PPIs and Alzheimer’s disease are conflicting.” Noting that cognitive function predicts dementia later in life, they analyzed prospective data on medications and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed Cogstate, a computerized, self-administered neuropsychological battery.
Study participants averaged 61 years old when they underwent cognitive testing, ranging in age from 50 to 70 years. Users of PPIs tended to be older, had more comorbidities, were less physically active, had higher body mass indexes, had less education, and ate a lower-quality diet than women who did not use PPIs. After adjusting for such confounders, using PPIs for 9-14 years was associated with a modest decrease in scores for psychomotor speed and attention (mean score difference, compared with never users, –0.06; 95% CI, –0.11 to 0.00; P = .03). “For comparison, in multivariable models, a 1-year increase in age was associated with mean score decreases of 0.03 for psychomotor speed and attention, 0.02 for learning and working memory, and 0.03 for overall cognition,” the researchers wrote.
Next, they examined links between use of H2 receptor antagonists and cognitive scores among 10,778 study participants who had used PPIs for 2 years or less. Use of H2 receptor antagonists for 9-14 years predicted poorer scores on learning, working memory, and overall cognition, even after controlling for potential confounders (P less than or equal to .002). “The magnitudes of mean score differences were larger than those observed in the analysis of PPI use, particularly for learning and working memory,” the researchers noted. Additionally, PPI use did not predict lower cognitive scores among individuals who had never used H2 receptor antagonists.
On the other hand, using PPIs for 9-14 years was associated with the equivalent of about 2 years of age-related cognitive decline, and controlling for exposure to H2 receptor antagonists weakened even this modest effect, the investigators said. Users and nonusers of PPIs tend to differ on many measures, and analyses of claims data, such as the German study above, are less able to account for these potential confounders, they noted. “Nonjudicious PPI prescribing is especially frequent among the elderly and those with cognitive impairment,” they added. “Therefore, elderly individuals who have frequent contact with health providers are at increased risk of both PPI prescription and dementia diagnosis. This bias may not be completely mitigated by adjustment for comorbidities or polypharmacy.”
The findings regarding H2 receptor antagonists reflect those of three smaller cohort studies, and these medications are known to cause central nervous system effects in the elderly, including delirium, the researchers said. Ranitidine and cimetidine have anticholinergic effects that also could “pose a risk for adverse cognitive effects with long-term use.”
Dr. Lochhead reported having no conflicts. Two coinvestigators disclosed ties to Bayer Healthcare, Pfizer, Aralez Pharmaceuticals, AbbVie, Samsung Bioepis, and Takeda.
A large prospective study of middle-aged and older women found no convincing evidence that using proton pump inhibitors increased their risk of dementia, investigators reported.
However, using H2 receptor antagonists for at least 9 years was associated with a slight decrease in scores of learning and working memory (mean decrease, –0.2; 95% confidence interval, –0.3 to –0.08; P less than .001), Paul Lochhead, MBChB, PhD, and his associates wrote in the October issue of Gastroenterology (doi: 10.1053/j.gastro.2017.06.061). “Since our primary hypothesis related to PPI [proton pump inhibitor] use, our findings for [H2 receptor antagonists] should be interpreted with caution,” they said.
Source: American Gastroenterological Association
In a recent German study of a medical claims database, use of PPIs was associated with a 44% increase in the likelihood of incident dementia (JAMA Neurol. 2016;73:410-6). “The existence of a causal mechanism linking PPI use to dementia is suggested by observations from cellular and animal models of Alzheimer’s disease, where PPI exposure appears to influence amyloid-beta metabolism,” Dr. Lochhead and his associates wrote. “However, other preclinical data on PPIs and Alzheimer’s disease are conflicting.” Noting that cognitive function predicts dementia later in life, they analyzed prospective data on medications and other potential risk factors from 13,864 participants in the Nurses’ Health Study II who had completed Cogstate, a computerized, self-administered neuropsychological battery.
Study participants averaged 61 years old when they underwent cognitive testing, ranging in age from 50 to 70 years. Users of PPIs tended to be older, had more comorbidities, were less physically active, had higher body mass indexes, had less education, and ate a lower-quality diet than women who did not use PPIs. After adjusting for such confounders, using PPIs for 9-14 years was associated with a modest decrease in scores for psychomotor speed and attention (mean score difference, compared with never users, –0.06; 95% CI, –0.11 to 0.00; P = .03). “For comparison, in multivariable models, a 1-year increase in age was associated with mean score decreases of 0.03 for psychomotor speed and attention, 0.02 for learning and working memory, and 0.03 for overall cognition,” the researchers wrote.
Next, they examined links between use of H2 receptor antagonists and cognitive scores among 10,778 study participants who had used PPIs for 2 years or less. Use of H2 receptor antagonists for 9-14 years predicted poorer scores on learning, working memory, and overall cognition, even after controlling for potential confounders (P less than or equal to .002). “The magnitudes of mean score differences were larger than those observed in the analysis of PPI use, particularly for learning and working memory,” the researchers noted. Additionally, PPI use did not predict lower cognitive scores among individuals who had never used H2 receptor antagonists.
On the other hand, using PPIs for 9-14 years was associated with the equivalent of about 2 years of age-related cognitive decline, and controlling for exposure to H2 receptor antagonists weakened even this modest effect, the investigators said. Users and nonusers of PPIs tend to differ on many measures, and analyses of claims data, such as the German study above, are less able to account for these potential confounders, they noted. “Nonjudicious PPI prescribing is especially frequent among the elderly and those with cognitive impairment,” they added. “Therefore, elderly individuals who have frequent contact with health providers are at increased risk of both PPI prescription and dementia diagnosis. This bias may not be completely mitigated by adjustment for comorbidities or polypharmacy.”
The findings regarding H2 receptor antagonists reflect those of three smaller cohort studies, and these medications are known to cause central nervous system effects in the elderly, including delirium, the researchers said. Ranitidine and cimetidine have anticholinergic effects that also could “pose a risk for adverse cognitive effects with long-term use.”
Dr. Lochhead reported having no conflicts. Two coinvestigators disclosed ties to Bayer Healthcare, Pfizer, Aralez Pharmaceuticals, AbbVie, Samsung Bioepis, and Takeda.
FROM GASTROENTEROLOGY
Key clinical point: A large prospective cohort study linked long-term use of H2 receptor antagonists, but not PPIs, to dementia.
Major finding: Use of PPIs did not significantly predict incident dementia in the adjusted analysis. However, using H2 receptor antagonists for at least 9 years was associated with a slight decrease in scores of learning and working memory (mean decrease, –0.2; P less than .001).
Data source: A population-based cohort study of 13,864 middle-aged and older women.
Disclosures: Dr. Lochhead reported having no conflicts. Two coinvestigators disclosed ties to Bayer Healthcare, Pfizer, Aralez Pharmaceuticals, AbbVie, Samsung Bioepis, and Takeda.
All guts and glory – esophagus, stomach, small intestine
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Prakash Gyawali, MD, led off the session with a lecture on functional heartburn, which he defined as burning retrosternal discomfort not relieved by antisecretory therapy, in a patient for whom endoscopy, esophageal pH monitoring, and manometry have revealed no evidence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), or major esophageal motility disorders. When performing pH monitoring to assess for functional heartburn, Dr. Gyawali advised that the test be done with patients off of proton pump inhibitors (PPIs). Despite similarity to the heartburn sensation of GERD, Dr. Gyawali pointed out how functional heartburn has features resembling irritable bowel syndrome, such as its association with anxiety and depression, and its response to neuromodulators (e.g., antidepressants). He discussed how new impedance-based esophageal metrics such as the postswallow-induced peristaltic wave index and measurement of mean nocturnal baseline impedance might be used to confirm a diagnosis of functional heartburn. Although neuromodulators remain the mainstay of management for functional heartburn, Dr. Gyawali discussed encouraging preliminary results of studies on psychotherapy, hypnotherapy, and alternative therapies such as acupuncture.
Rhonda Souza, MD, AGAF, discussed EoE, focusing especially on the controversial condition of PPI-responsive esophageal eosinophilia (PPI-REE) in which patients have typical EoE symptoms and histology, with no evidence of GERD by endoscopy or esophageal pH monitoring, yet they respond to PPI therapy. She discussed two possible explanations for PPI-REE: 1) the patients have subclinical GERD that responds to PPI antisecretory effects, or 2) the patients have EoE that responds to PPI anti-inflammatory effects. Dr. Souza reviewed data from her laboratory showing that omeprazole can block the secretion of eotaxin-3, a potent eosinophil chemoattractant in esophageal epithelial cells stimulated with allergic (Th2) cytokines in vitro. This potential anti-inflammatory PPI effect is entirely independent of any effect on gastric acid inhibition. After reviewing recent clinical and esophageal transcriptome data, Dr. Souza concluded that PPI-REE is probably just a subset of EoE, not an independent disorder.
John Inadomi, MD, AGAF, discussed Barrett’s esophagus and esophageal adenocarcinoma. He pointed out the inadequacy of current screening programs, noting studies showing that less than 10% of patients found to have esophageal adenocarcinoma had a prior diagnosis of Barrett’s esophagus. He estimated the annual incidence of adenocarcinoma at 0.12%-0.5% for patients with nondysplastic Barrett’s metaplasia. He discussed how current American College of Gastroenterology guidelines call for screening men who have chronic GERD symptoms with at least two other Barrett’s cancer risk factors (age greater than 50 years, white race, central obesity, cigarette smoking, family history of Barrett’s esophagus), and noted how the very low risk of esophageal adenocarcinoma in women (similar to the risk of breast cancer in men) supports the ACG recommendation not to screen women routinely for Barrett’s esophagus. Dr. Inadomi recommended endoscopic eradication as the preferred treatment for patients with confirmed dysplasia of any grade. He also noted that the removal of nodular lesions by endoscopic mucosal resection or endoscopic submucosal dissection is a crucial part of endoscopic eradication therapy.
In a lecture titled “The truth about PPIs,” Byron Cryer, MD, reviewed a number of potential adverse effects of PPIs, including Clostridium difficile–associated diarrhea, bone fractures, kidney disease, dementia, myocardial infarction, and interactions with clopidogrel. He pointed out that most of these putative adverse effects have been identified as modest increases in risks noted in observational studies, and the quality of this evidence is considered low or very low. In contrast, the benefits of PPIs for patients with complicated GERD and for patients at risk for NSAID complications have been established in high-quality, randomized controlled trials. Dr. Cryer concluded that, when PPIs are prescribed appropriately, their benefits likely outweigh their risks. However, he also noted that PPIs frequently are prescribed inappropriately, in which case they have no benefit and their potential for risk assumes greater importance.
Sheila Crowe, MD, AGAF, delivered the last lecture of the session, discussing celiac disease and gluten sensitivity. She reviewed recent data suggesting a role for infection with reovirus in triggering the development of celiac disease, and she noted that tissue transglutaminase IgA remains the best test to screen for the condition. She discussed the controversial topic of nonceliac gluten sensitivity, in which patients report symptoms or health alterations that they perceive to be the result of gluten ingestion. She pointed out difficulties in establishing an unequivocal diagnosis of nonceliac gluten sensitivity and, for patients without celiac disease, she highlighted a number of potential drawbacks of a gluten-free diet, including its expense, higher fat and sugar content, and increased levels of toxic metals such as arsenic and mercury.
Dr. Spechler is chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases, Baylor University Medical Center at Dallas; he is an investigator/professor and co-director of the Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2017.
Minimally invasive screening for Barrett’s esophagus offers cost-effective alternative
The high costs of endoscopy make screening patients with gastroesophageal reflux disease (GERD) for Barrett’s esophagus a costly endeavor. But using a minimally invasive test followed by endoscopy only if results are positive could cut costs by up to 41%, according to investigators.
The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.017).
The findings mirror those from a prior study (Gastroenterology. 2013 Jan;144[1]:62-73.e60) of the new cytosponge device, which tests surface esophageal tissue for trefoil factor 3, a biomarker for Barrett’s esophagus, said Curtis R. Heberle, of Massachusetts General Hospital in Boston, and his associates. In addition, two separate models found the cytosponge strategy cost effective compared with no screening (incremental cost-effectiveness ratios [ICERs], about $26,000-$33,000). However, using the cytosponge instead of screening all GERD patients with endoscopy would reduce quality-adjusted life-years (QALYs) by about 1.8-5.5 years for every 1,000 patients.
Rates of esophageal adenocarcinoma have climbed more than sixfold in the United States in 4 decades, and 5-year survival rates remain below 20%. Nonetheless, the high cost of endoscopy and 10%-20% prevalence of GERD makes screening all patients for Barrett’s esophagus infeasible. To evaluate the cytosponge strategy, the researchers fit data from the multicenter BEST2 study (PLoS Med. 2015 Jan; 12[1]: e1001780) into two validated models calibrated to high-quality Surveillance, Epidemiology and End Results (SEER) data on esophageal cancer. Both models compared no screening with a one-time screen by either endoscopy alone or cytosponge with follow-up endoscopy in the event of a positive test. The models assumed patients were male, were 60 years old, and had GERD but not esophageal adenocarcinoma.
Without screening, there were about 14-16 cancer cases and about 15,077 quality-adjusted life years (QALYs) for every 1,000 patients. The cytosponge strategy was associated with about 8-13 cancer cases and about 15,105 QALYs. Endoscopic screening produced the most benefit overall – only about 7-12 cancer cases, with more than 15,100 QALYs. “However, greater benefits were accompanied by higher total costs,” the researchers said. For every 1,000 patients, no screening cost about $704,000 to $762,000, the cytosponge strategy cost about $1.5 to $1.6 million, and population-wide endoscopy cost about $2.1 to $2.2 million. Thus, the cytosponge method would lower the cost of screening by 37%-41% compared with endoscopically screening all men with GERD. The cytosponge was also cost effective in a model of 60-year-old women with GERD.
Using only endoscopic screening was not cost effective in either model, exceeding a $100,000 threshold of willingness to pay by anywhere from $107,000 to $330,000. The cytosponge is not yet available commercially, but the investigators assumed it cost $182 based on information from the manufacturer (Medtronic) and Medicare payments for similar devices. Although the findings withstood variations in indirect costs and age at initial screening, they were “somewhat sensitive” to variations in costs of the cytosponge and its presumed sensitivity and specificity in clinical settings. However, endoscopic screening only became cost effective when the cytosponge test cost at least $225.
The models assumed perfect adherence to screening, which probably exaggerated the effectiveness of the cytosponge and endoscopic screening, the investigators said. They noted that cytosponge screening can be performed without sedation during a short outpatient visit.
The National Institutes of Health provided funding. The investigators had no relevant disclosures.
The high costs of endoscopy make screening patients with gastroesophageal reflux disease (GERD) for Barrett’s esophagus a costly endeavor. But using a minimally invasive test followed by endoscopy only if results are positive could cut costs by up to 41%, according to investigators.
The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.017).
The findings mirror those from a prior study (Gastroenterology. 2013 Jan;144[1]:62-73.e60) of the new cytosponge device, which tests surface esophageal tissue for trefoil factor 3, a biomarker for Barrett’s esophagus, said Curtis R. Heberle, of Massachusetts General Hospital in Boston, and his associates. In addition, two separate models found the cytosponge strategy cost effective compared with no screening (incremental cost-effectiveness ratios [ICERs], about $26,000-$33,000). However, using the cytosponge instead of screening all GERD patients with endoscopy would reduce quality-adjusted life-years (QALYs) by about 1.8-5.5 years for every 1,000 patients.
Rates of esophageal adenocarcinoma have climbed more than sixfold in the United States in 4 decades, and 5-year survival rates remain below 20%. Nonetheless, the high cost of endoscopy and 10%-20% prevalence of GERD makes screening all patients for Barrett’s esophagus infeasible. To evaluate the cytosponge strategy, the researchers fit data from the multicenter BEST2 study (PLoS Med. 2015 Jan; 12[1]: e1001780) into two validated models calibrated to high-quality Surveillance, Epidemiology and End Results (SEER) data on esophageal cancer. Both models compared no screening with a one-time screen by either endoscopy alone or cytosponge with follow-up endoscopy in the event of a positive test. The models assumed patients were male, were 60 years old, and had GERD but not esophageal adenocarcinoma.
Without screening, there were about 14-16 cancer cases and about 15,077 quality-adjusted life years (QALYs) for every 1,000 patients. The cytosponge strategy was associated with about 8-13 cancer cases and about 15,105 QALYs. Endoscopic screening produced the most benefit overall – only about 7-12 cancer cases, with more than 15,100 QALYs. “However, greater benefits were accompanied by higher total costs,” the researchers said. For every 1,000 patients, no screening cost about $704,000 to $762,000, the cytosponge strategy cost about $1.5 to $1.6 million, and population-wide endoscopy cost about $2.1 to $2.2 million. Thus, the cytosponge method would lower the cost of screening by 37%-41% compared with endoscopically screening all men with GERD. The cytosponge was also cost effective in a model of 60-year-old women with GERD.
Using only endoscopic screening was not cost effective in either model, exceeding a $100,000 threshold of willingness to pay by anywhere from $107,000 to $330,000. The cytosponge is not yet available commercially, but the investigators assumed it cost $182 based on information from the manufacturer (Medtronic) and Medicare payments for similar devices. Although the findings withstood variations in indirect costs and age at initial screening, they were “somewhat sensitive” to variations in costs of the cytosponge and its presumed sensitivity and specificity in clinical settings. However, endoscopic screening only became cost effective when the cytosponge test cost at least $225.
The models assumed perfect adherence to screening, which probably exaggerated the effectiveness of the cytosponge and endoscopic screening, the investigators said. They noted that cytosponge screening can be performed without sedation during a short outpatient visit.
The National Institutes of Health provided funding. The investigators had no relevant disclosures.
The high costs of endoscopy make screening patients with gastroesophageal reflux disease (GERD) for Barrett’s esophagus a costly endeavor. But using a minimally invasive test followed by endoscopy only if results are positive could cut costs by up to 41%, according to investigators.
The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.017).
The findings mirror those from a prior study (Gastroenterology. 2013 Jan;144[1]:62-73.e60) of the new cytosponge device, which tests surface esophageal tissue for trefoil factor 3, a biomarker for Barrett’s esophagus, said Curtis R. Heberle, of Massachusetts General Hospital in Boston, and his associates. In addition, two separate models found the cytosponge strategy cost effective compared with no screening (incremental cost-effectiveness ratios [ICERs], about $26,000-$33,000). However, using the cytosponge instead of screening all GERD patients with endoscopy would reduce quality-adjusted life-years (QALYs) by about 1.8-5.5 years for every 1,000 patients.
Rates of esophageal adenocarcinoma have climbed more than sixfold in the United States in 4 decades, and 5-year survival rates remain below 20%. Nonetheless, the high cost of endoscopy and 10%-20% prevalence of GERD makes screening all patients for Barrett’s esophagus infeasible. To evaluate the cytosponge strategy, the researchers fit data from the multicenter BEST2 study (PLoS Med. 2015 Jan; 12[1]: e1001780) into two validated models calibrated to high-quality Surveillance, Epidemiology and End Results (SEER) data on esophageal cancer. Both models compared no screening with a one-time screen by either endoscopy alone or cytosponge with follow-up endoscopy in the event of a positive test. The models assumed patients were male, were 60 years old, and had GERD but not esophageal adenocarcinoma.
Without screening, there were about 14-16 cancer cases and about 15,077 quality-adjusted life years (QALYs) for every 1,000 patients. The cytosponge strategy was associated with about 8-13 cancer cases and about 15,105 QALYs. Endoscopic screening produced the most benefit overall – only about 7-12 cancer cases, with more than 15,100 QALYs. “However, greater benefits were accompanied by higher total costs,” the researchers said. For every 1,000 patients, no screening cost about $704,000 to $762,000, the cytosponge strategy cost about $1.5 to $1.6 million, and population-wide endoscopy cost about $2.1 to $2.2 million. Thus, the cytosponge method would lower the cost of screening by 37%-41% compared with endoscopically screening all men with GERD. The cytosponge was also cost effective in a model of 60-year-old women with GERD.
Using only endoscopic screening was not cost effective in either model, exceeding a $100,000 threshold of willingness to pay by anywhere from $107,000 to $330,000. The cytosponge is not yet available commercially, but the investigators assumed it cost $182 based on information from the manufacturer (Medtronic) and Medicare payments for similar devices. Although the findings withstood variations in indirect costs and age at initial screening, they were “somewhat sensitive” to variations in costs of the cytosponge and its presumed sensitivity and specificity in clinical settings. However, endoscopic screening only became cost effective when the cytosponge test cost at least $225.
The models assumed perfect adherence to screening, which probably exaggerated the effectiveness of the cytosponge and endoscopic screening, the investigators said. They noted that cytosponge screening can be performed without sedation during a short outpatient visit.
The National Institutes of Health provided funding. The investigators had no relevant disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Using a minimally invasive screen for Barrett’s esophagus and following up with endoscopy if results are positive is a cost-effective alternative to endoscopy alone in patients with gastroesophageal reflux disease.
Major finding: The two-step screening strategy cut screening costs by 37%-41% but was associated with 1.8-5.5 fewer quality-adjusted life years for every 1,000 patients with GERD.
Data source: Two validated models based on Surveillance, Epidemiology, and End Results data, and data from the multicenter BEST2 trial.
Disclosures: The National Institutes of Health provided funding. The investigators had no relevant disclosures.
Relamorelin for diabetic gastroparesis: Trial results
Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT4 receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.
The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.
A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.
Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.
Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT4 receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.
The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.
A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.
Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.
Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.
Gastroparesis is defined as delayed gastric emptying with associated symptoms in the absence of mechanical obstruction. The cardinal symptoms are upper abdominal pain, postprandial fullness, bloating, early satiety, nausea, and, with more severe disease, vomiting. Weight loss, malnutrition, dehydration, electrolyte imbalance, bezoar formation, and aspiration pneumonia may occur in advanced cases. Unfortunately, there are few approved or efficacious treatment options for diabetic gastroparesis. The 5-HT4 receptor agonist, cisapride, has been withdrawn from the prescription markets in most countries.
The study aim was to evaluate the efficacy of relamorelin on disease symptoms and gastric emptying in moderate to severe diabetic gastroparesis. In a 12-week, double-blind, placebo-controlled, parallel-group, randomized, controlled trial, with a 2-week, single-blind placebo run-in, patients were randomized to 10 microg b.i.d., 30 microg b.i.d., 100 microg b.i.d., or placebo b.i.d. Patients completed a daily e-diary of symptoms (Diabetic Gastroparesis Symptom Severity Diary [DGSSD]: nausea, abdominal pain, postprandial fullness, and bloating on a 0–10 scale) and vomiting episodes, which were summarized by treatment week. The primary endpoint was a change from baseline in vomiting frequency; a key secondary endpoint was change from baseline in a four-symptom composite of DGSSD symptoms.
A longitudinal analysis over the 12-week trial showed there were reductions in nausea, postprandial fullness, abdominal pain, and bloating individually and as a composite score. Relamorelin accelerated gastric emptying T1/2 at all three doses compared with placebo. However, there were no effects on vomiting frequency, which showed a high placebo response. More hyperglycemia events and diarrhea events were observed with relamorelin treatment compared with placebo. The diarrhea reflects the previously demonstrated stimulation of colonic transit and motility and reduction of symptoms of constipation in patients with chronic constipation. The hyperglycemia likely resulted from accelerated gastric emptying rather than potential inhibition of insulin production, which has been reported with high levels of ghrelin in animal studies or with high levels of ghrelin associated with starvation.
Thus, relamorelin demonstrated substantially improved core symptoms of diabetic gastroparesis, was generally safe and well tolerated, and should be further assessed in pivotal phase 3 trials. The results in this trial suggest that there is no dose-response relationship between the three doses of relamorelin tested and that future trials of relamorelin might not need to include the 100-microg b.i.d. dose. Importantly, this study also suggests the importance to prospectively manage the hyperglycemia in future trials.
Dr. Camilleri is a faculty member in the department of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. His comments were made during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.