Upper GI Tract

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

Many patients are receiving inadequate eradication therapy for Helicobacter pylori infection, according to analysis of a European registry.

In their analysis, published in the Journal of Clinical Gastroenterology, Olga P. Nyssen, BSc, PhD, of the Autonomous University of Madrid and colleagues discussed seven errors, which included prescribing a triple instead of quadruple regimen, prescribing therapy for too short of a duration, and prescribing a low dose of proton pump inhibitors (PPIs).

“[E]ven after more than 30 years of experience in H. pylori treatment, the ideal regimen to treat this infection remains undefined,” the investigators wrote. The European Registry on Helicobacter pylori management “represents a good mapping overview of the current situation regarding H. pylori management, allowing not only continuous assessment of the integration of clinical recommendations agreed on medical consensus, but also of the possible strategies for improvement.”

Patient data were drawn from registry-participating countries that each had more than 1,000 cases of H. pylori available; most came from Spain, followed by Russia, Italy, Slovenia, and Lithuania. Of these patients, data for 26,340 patients were analyzed, which ultimately represented 80% of the total registry from 2013 to 2019.

The first mistake discussed in the paper regarded use of less-effective triple therapies (typically PPI plus two antibiotics); one review showed that these regimens fail in 20%-40% of cases. Increasing antibiotic resistances have only worsened the success rate. According to this study, a triple regimen was given as first-line treatment in 46% of cases. Overall, frequency of triple-therapy prescriptions decreased from more than 50% in 2013 to about 40% in 2019. More significant improvements in this area were achieved in Spain, where use of triple therapies decreased from 24% in 2014 to 0% in 2019. According to the investigators, this finding serves as a “paradigmatic example of improvement with time.”

The authors pointed out that “overwhelming evidence” supports 14-day treatment; however, 69% of triple-therapy durations and 58% of quadruple therapy cases were for 7 or 10 days. Triple therapy at this duration showed only 81% cure rate, while it was 88% with 14 days, and quadruple therapy was only 80% effective at 7-10 days but 90% effective at 14 days.

“Fortunately,” the investigators wrote, “this mistake was progressively found less frequently and, at present, the prescription of 7-day standard triple therapy regimens has almost disappeared.”

The authors noted acid suppression via PPIs improves cure rates: In one meta-analysis, the cure rate of triple therapy regimens increased by 6%-10% with high doses of PPIs. However, the current study found that 48% of triple therapies included low-dose PPIs. This number decreased over time, the authors noted: from 67% in 2013 to 20% in 2019.

“From another perspective, the daily PPI dose has increased from a dose equivalent to 54 mg of omeprazole in 2013 to 104 mg in 2019,” they wrote.

The other four errors they discussed were failing to adequately consider penicillin allergies in prescription choices, failing to consider the importance of treatment compliance, repeating certain antibiotics after failures, and not checking eradication success after treatment.

Based on these findings, Dr. Nyssen and colleagues suggested that “penetration of recommendations in the participating European countries is still poor and delayed, even though some improvements from guidelines have been partially incorporated.”

According to Grigorios I. Leontiadis, MD, PhD, of McMaster University, Hamilton, Ont., who coauthored the 2017 American College of Gastroenterology H. pylori management guidelines and the Canadian Association of Gastroenterology “Toronto Consensus” in 2016, “This study is important and timely given the steadily increasing antibiotic resistance of H. pylori worldwide.”

Although Dr. Leontiadias described the results as “suboptimal,” he was partially reassured by the improvements over time, “especially following publication of the 2016 European clinical practice guidelines.” He also noted that some older clinical practice guidelines issued conditional recommendations, which could “justify the lower adherence seen in the early period of this study.”

“The unanswered question,” Dr. Leontiadias went on, “is whether the practice of gastroenterologists who volunteered to participate in this prospective registry is truly representative of how H. pylori is managed in Europe. Most likely it isn’t. Nonparticipating gastroenterologists and nongastroenterologist health care practitioners are probably less aware of and less adherent to clinical practice guidelines. This means that the actual situation in the real world is probably grimmer than what this study shows.”

William D. Chey, MD, Nostrant Collegiate Professor of Gastroenterology at the University of Michigan, Ann Arbor, considered the results “not entirely surprising, but nonetheless, noteworthy.”

Dr. Chey noted that the United States lacks a similar registry to compare real-world H. pylori management; even so, he suggested several findings that “bear reiteration” for clinicians in the United States.

“U.S. providers should consider regimens other than clarithromycin triple therapy when treating H. pylori infection,” Dr. Chey said. “Since U.S. providers do not have reliable data on H. pylori antimicrobial resistance, it is useful to ask about prior macrolide antibiotic exposure, and if a patient has received a macrolide for any reason, clarithromycin triple therapy should be avoided. Bismuth quadruple therapy remains a reliable first-line treatment option in the U.S. Another recently approved first-line treatment option is the combination of a proton pump inhibitor, rifabutin, and amoxicillin. Treatment regimens in the U.S. should be given for a minimum of 10 days and, preferably, for 14 days. Another point made by the article is that providers should be maximizing gastric acid suppression by using higher doses of proton pump inhibitors when treating H. pylori.”

Dr. Chey also noted an emerging treatment option that could soon be available. “Results from phase 3 trials in North America and Europe with the potassium-competitive acid blocker vonoprazan combined with amoxicillin, with and without clarithromycin, are expected in 2021 and may provide another novel first-line treatment option.”

Dr. Nyssen and colleagues disclosed relationships with Allergan, Mayoly, Janssen, and others. Dr. Chey is a consultant for Redhill, Phathom, and Takeda, which is developing vonoprazan. Dr. Leontiadias disclosed no conflicts of interest.

This article was updated 2/16/21.

Most patients with normal findings on functional luminal imaging probe (FLIP) showed no clinical evidence of a major esophageal motor disorder, even when their high-resolution manometry (HRM) test results were abnormal, according to the results of a single-center retrospective cohort study.

Among 111 study participants with normal FLIP findings, 79% also showed no evidence of a major esophageal motor disorder on esophageal high-resolution manometry (HRM), wrote Alexandra J. Baumann, DO, of Northwestern University, Chicago, and associates. “Among the remaining 21% with apparent disagreement with HRM, [those] with normal FLIP panometry carried overall clinical impressions of not having a major esophageal motor disorder and subsequently were treated conservatively without the need for surgical interventions,” they reported. For patients with normal upper endoscopy and normal FLIP panometry, “the initial clinical management strategy could be directed toward addressing gastroesophageal reflux or a functional syndrome,” they wrote in Clinical Gastroenterology and Hepatology.

FLIP uses high-resolution impedance planimetry to evaluate esophageal lumen parameters, distensibility, and contractility in response to distension. Although HRM is standard for evaluating esophageal motility, false negatives and positives can result from challenges with interpreting outflow obstructions and normal lower-esophageal sphincter relaxation pressures among patients with clinical achalasia.

Hence, the researchers evaluated correlations between FLIP and HRM in 111 patients with esophageal symptoms and nonobstructive endoscopy findings who were evaluated at the Esophageal Center of Northwestern University between 2012 and 2019. Gastroenterologists performed additional studies, such as barium esophagrams, at their discretion. By study design, all patients had normal FLIP results, defined as an esophagogastric junction distensibility index above 3.0 mm² per mm Hg and a normal contractile response (that is, normal repetitive retrograde contractions and a repetitive antegrade contraction pattern that met the Rule-of-6s). Three clinicians evaluated and reached consensus on each FLIP study. Esophageal HRM data were interpreted based on the Chicago classification system (version 3.0).

Patients with normal FLIP panometry findings “did not have a clinical impression of a major esophageal motor disorder,” the researchers reported. In all, 23 (21%) patients with normal FLIP results had discrepant (abnormal) HRM findings, most of which were false positives or equivocal.

For example, among 20 patients whose HRM suggested an esophagogastric junction outflow obstruction, 17 showed normal bolus transit on supine swallows and 16 showed normalization of integrated relaxation pressure after adjunctive maneuvers. Similarly, among 10 patients who underwent a barium esophagram, 8 showed normal emptying, 1 showed a temporary delay but no retention, and 1 had an incomplete study. “The overall clinical impression was not of an achalasia variant in any of these 20 patients with [esophagogastric junction outflow obstruction] on HRM, and thus none underwent botulinum toxin injection, pneumatic dilation, or lower-esophageal sphincter myotomy at our center,” the researchers wrote. Among 17 patients who were available for clinical follow-up, 4 underwent empiric dilation, of whom none had mucosal disruption. One patient was diagnosed with dysphagia lusoria based on cross-sectional imaging, while the rest were managed conservatively.

Similarly, among 10 patients with at least 50% ineffective swallows on HRM, 5 showed normal barium emptying and 9 were managed conservatively (the remaining patient underwent cricopharyngeal dilation for concurrent oropharyngeal dysphagia). The strong correlation between HRM and esophagrams in this study indicates that“[n]ormal findings from FLIP panometry can be used to exclude esophageal motility disorders at the time of endoscopy, possibly reducing the need for high-resolution manometry evaluation of some patients,” the investigators concluded. “However, further longitudinal studies are needed to support this approach.”

The work was supported by the Public Health Service and the American College of Gastroenterology. Dr. Baumann reported having no conflicts of interest. Four coinvestigators disclosed relevant ties to Crospon, Given Imaging, Ironwood, Medtronic, Sandhill Scientific, Torax, and other companies..

SOURCE: Baumann AJ et al. Clin Gastroenterol Hepatol 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.040.

Most patients with normal findings on functional luminal imaging probe (FLIP) showed no clinical evidence of a major esophageal motor disorder, even when their high-resolution manometry (HRM) test results were abnormal, according to the results of a single-center retrospective cohort study.

Among 111 study participants with normal FLIP findings, 79% also showed no evidence of a major esophageal motor disorder on esophageal high-resolution manometry (HRM), wrote Alexandra J. Baumann, DO, of Northwestern University, Chicago, and associates. “Among the remaining 21% with apparent disagreement with HRM, [those] with normal FLIP panometry carried overall clinical impressions of not having a major esophageal motor disorder and subsequently were treated conservatively without the need for surgical interventions,” they reported. For patients with normal upper endoscopy and normal FLIP panometry, “the initial clinical management strategy could be directed toward addressing gastroesophageal reflux or a functional syndrome,” they wrote in Clinical Gastroenterology and Hepatology.

FLIP uses high-resolution impedance planimetry to evaluate esophageal lumen parameters, distensibility, and contractility in response to distension. Although HRM is standard for evaluating esophageal motility, false negatives and positives can result from challenges with interpreting outflow obstructions and normal lower-esophageal sphincter relaxation pressures among patients with clinical achalasia.

Hence, the researchers evaluated correlations between FLIP and HRM in 111 patients with esophageal symptoms and nonobstructive endoscopy findings who were evaluated at the Esophageal Center of Northwestern University between 2012 and 2019. Gastroenterologists performed additional studies, such as barium esophagrams, at their discretion. By study design, all patients had normal FLIP results, defined as an esophagogastric junction distensibility index above 3.0 mm² per mm Hg and a normal contractile response (that is, normal repetitive retrograde contractions and a repetitive antegrade contraction pattern that met the Rule-of-6s). Three clinicians evaluated and reached consensus on each FLIP study. Esophageal HRM data were interpreted based on the Chicago classification system (version 3.0).

Patients with normal FLIP panometry findings “did not have a clinical impression of a major esophageal motor disorder,” the researchers reported. In all, 23 (21%) patients with normal FLIP results had discrepant (abnormal) HRM findings, most of which were false positives or equivocal.

For example, among 20 patients whose HRM suggested an esophagogastric junction outflow obstruction, 17 showed normal bolus transit on supine swallows and 16 showed normalization of integrated relaxation pressure after adjunctive maneuvers. Similarly, among 10 patients who underwent a barium esophagram, 8 showed normal emptying, 1 showed a temporary delay but no retention, and 1 had an incomplete study. “The overall clinical impression was not of an achalasia variant in any of these 20 patients with [esophagogastric junction outflow obstruction] on HRM, and thus none underwent botulinum toxin injection, pneumatic dilation, or lower-esophageal sphincter myotomy at our center,” the researchers wrote. Among 17 patients who were available for clinical follow-up, 4 underwent empiric dilation, of whom none had mucosal disruption. One patient was diagnosed with dysphagia lusoria based on cross-sectional imaging, while the rest were managed conservatively.

Similarly, among 10 patients with at least 50% ineffective swallows on HRM, 5 showed normal barium emptying and 9 were managed conservatively (the remaining patient underwent cricopharyngeal dilation for concurrent oropharyngeal dysphagia). The strong correlation between HRM and esophagrams in this study indicates that“[n]ormal findings from FLIP panometry can be used to exclude esophageal motility disorders at the time of endoscopy, possibly reducing the need for high-resolution manometry evaluation of some patients,” the investigators concluded. “However, further longitudinal studies are needed to support this approach.”

The work was supported by the Public Health Service and the American College of Gastroenterology. Dr. Baumann reported having no conflicts of interest. Four coinvestigators disclosed relevant ties to Crospon, Given Imaging, Ironwood, Medtronic, Sandhill Scientific, Torax, and other companies..

SOURCE: Baumann AJ et al. Clin Gastroenterol Hepatol 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.040.

Most patients with normal findings on functional luminal imaging probe (FLIP) showed no clinical evidence of a major esophageal motor disorder, even when their high-resolution manometry (HRM) test results were abnormal, according to the results of a single-center retrospective cohort study.

Among 111 study participants with normal FLIP findings, 79% also showed no evidence of a major esophageal motor disorder on esophageal high-resolution manometry (HRM), wrote Alexandra J. Baumann, DO, of Northwestern University, Chicago, and associates. “Among the remaining 21% with apparent disagreement with HRM, [those] with normal FLIP panometry carried overall clinical impressions of not having a major esophageal motor disorder and subsequently were treated conservatively without the need for surgical interventions,” they reported. For patients with normal upper endoscopy and normal FLIP panometry, “the initial clinical management strategy could be directed toward addressing gastroesophageal reflux or a functional syndrome,” they wrote in Clinical Gastroenterology and Hepatology.

FLIP uses high-resolution impedance planimetry to evaluate esophageal lumen parameters, distensibility, and contractility in response to distension. Although HRM is standard for evaluating esophageal motility, false negatives and positives can result from challenges with interpreting outflow obstructions and normal lower-esophageal sphincter relaxation pressures among patients with clinical achalasia.

Hence, the researchers evaluated correlations between FLIP and HRM in 111 patients with esophageal symptoms and nonobstructive endoscopy findings who were evaluated at the Esophageal Center of Northwestern University between 2012 and 2019. Gastroenterologists performed additional studies, such as barium esophagrams, at their discretion. By study design, all patients had normal FLIP results, defined as an esophagogastric junction distensibility index above 3.0 mm² per mm Hg and a normal contractile response (that is, normal repetitive retrograde contractions and a repetitive antegrade contraction pattern that met the Rule-of-6s). Three clinicians evaluated and reached consensus on each FLIP study. Esophageal HRM data were interpreted based on the Chicago classification system (version 3.0).

Patients with normal FLIP panometry findings “did not have a clinical impression of a major esophageal motor disorder,” the researchers reported. In all, 23 (21%) patients with normal FLIP results had discrepant (abnormal) HRM findings, most of which were false positives or equivocal.

For example, among 20 patients whose HRM suggested an esophagogastric junction outflow obstruction, 17 showed normal bolus transit on supine swallows and 16 showed normalization of integrated relaxation pressure after adjunctive maneuvers. Similarly, among 10 patients who underwent a barium esophagram, 8 showed normal emptying, 1 showed a temporary delay but no retention, and 1 had an incomplete study. “The overall clinical impression was not of an achalasia variant in any of these 20 patients with [esophagogastric junction outflow obstruction] on HRM, and thus none underwent botulinum toxin injection, pneumatic dilation, or lower-esophageal sphincter myotomy at our center,” the researchers wrote. Among 17 patients who were available for clinical follow-up, 4 underwent empiric dilation, of whom none had mucosal disruption. One patient was diagnosed with dysphagia lusoria based on cross-sectional imaging, while the rest were managed conservatively.

Similarly, among 10 patients with at least 50% ineffective swallows on HRM, 5 showed normal barium emptying and 9 were managed conservatively (the remaining patient underwent cricopharyngeal dilation for concurrent oropharyngeal dysphagia). The strong correlation between HRM and esophagrams in this study indicates that“[n]ormal findings from FLIP panometry can be used to exclude esophageal motility disorders at the time of endoscopy, possibly reducing the need for high-resolution manometry evaluation of some patients,” the investigators concluded. “However, further longitudinal studies are needed to support this approach.”

The work was supported by the Public Health Service and the American College of Gastroenterology. Dr. Baumann reported having no conflicts of interest. Four coinvestigators disclosed relevant ties to Crospon, Given Imaging, Ironwood, Medtronic, Sandhill Scientific, Torax, and other companies..

SOURCE: Baumann AJ et al. Clin Gastroenterol Hepatol 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.040.

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

Cryoballoon and cryospray ablation were equivalent for eradicating dysplastic Barrett’s esophagus, according to the findings of a single-center retrospective study of 71 ablation-naive patients.

At 18 months, rates of complete eradication of dysplasia were 95.6% in patients who received cryoballoon therapy and 96% in recipients of cryospray, reported Mohammed Alshelleh, MD, of Northwell Health System, a tertiary care system in New Hyde Park, N.Y. Rates of complete eradication of intestinal metaplasia were 84.75% and 80%, respectively. However, selection bias was likely, and a post hoc power calculation suggested that the cryospray group was underpowered by four patients. “Prospective studies are needed to confirm [these] data,” Dr. Alshelleh and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

Cryotherapy is common for treating dysplastic Barrett’s esophagus when patients do not achieve remission with radiofrequency ablation. For treatment-naive individuals, prospective studies suggest that cryotherapy may be less painful and as effective as radiofrequency ablation, but no studies have directly compared the two commercially available systems: a cryogenic balloon catheter (C2 Cryoballoon, Pentax Medical, Montvale, N.J.) that delivers cryogenic nitrous oxide (–85° C) into an inflated balloon in direct contact with the esophageal mucosa, and a spray cryotherapy system (truFreeze, Steris Endoscopy, Mentor, Ohio), which flash-freezes the mucosa to –196° C by delivering liquid nitrogen through a low-pressure catheter that is not directly in contact with the esophagus.

For the study, the investigators retrospectively compared rates of complete eradication of dysplasia, and complete eradication of intestinal metaplasia, among ablation-naive patients at their institution who had received one of these two cryogenic modalities between 2015 and 2019. All patients were treated at least twice, at 3-month intervals, and were followed for least 12 months, or until complete eradication of intestinal metaplasia was confirmed by at least one endoscopic biopsy. In all, 46 patients received cryoballoon therapy and 25 received cryospray. Outcomes between the two modalities showed no significant differences in subgroups stratified by baseline histology, nor were there significant differences in rates of postprocedural stricture (8.7% in the cryoballoon group vs. 12% in the cryospray group). However, the investigators acknowledged that the study was underpowered. Overall, clinicians tended to prefer cryoballoon because it uses prefilled nitrous oxide cartridges, making it unnecessary to fill up a large nitrogen tank or use a “cumbersome decompression tube,” the investigators wrote. “However, in patients with a very large hiatal hernia or if there was a need to treat in a retroflexed position, spray cryotherapy was used given its ease of use over cryoballoon in these scenarios. Finally, cryospray is more amenable to treat larger surface areas of Barrett’s versus the focal cryoballoon that treats focal areas, and thus was the cryotherapy choice for a long segment of Barrett’s.”

The investigators reported receiving no grant support. One investigator disclosed ties to Olympus America, Pentax Medical Research, and Ninepoint Medical.

SOURCE: Alshelleh M et al. Tech Innov Gastrointest Endosc. 2020 Jul 26. doi: 10.1016/j.tige.2020.07.004.

Cryoballoon and cryospray ablation were equivalent for eradicating dysplastic Barrett’s esophagus, according to the findings of a single-center retrospective study of 71 ablation-naive patients.

At 18 months, rates of complete eradication of dysplasia were 95.6% in patients who received cryoballoon therapy and 96% in recipients of cryospray, reported Mohammed Alshelleh, MD, of Northwell Health System, a tertiary care system in New Hyde Park, N.Y. Rates of complete eradication of intestinal metaplasia were 84.75% and 80%, respectively. However, selection bias was likely, and a post hoc power calculation suggested that the cryospray group was underpowered by four patients. “Prospective studies are needed to confirm [these] data,” Dr. Alshelleh and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

Cryotherapy is common for treating dysplastic Barrett’s esophagus when patients do not achieve remission with radiofrequency ablation. For treatment-naive individuals, prospective studies suggest that cryotherapy may be less painful and as effective as radiofrequency ablation, but no studies have directly compared the two commercially available systems: a cryogenic balloon catheter (C2 Cryoballoon, Pentax Medical, Montvale, N.J.) that delivers cryogenic nitrous oxide (–85° C) into an inflated balloon in direct contact with the esophageal mucosa, and a spray cryotherapy system (truFreeze, Steris Endoscopy, Mentor, Ohio), which flash-freezes the mucosa to –196° C by delivering liquid nitrogen through a low-pressure catheter that is not directly in contact with the esophagus.

For the study, the investigators retrospectively compared rates of complete eradication of dysplasia, and complete eradication of intestinal metaplasia, among ablation-naive patients at their institution who had received one of these two cryogenic modalities between 2015 and 2019. All patients were treated at least twice, at 3-month intervals, and were followed for least 12 months, or until complete eradication of intestinal metaplasia was confirmed by at least one endoscopic biopsy. In all, 46 patients received cryoballoon therapy and 25 received cryospray. Outcomes between the two modalities showed no significant differences in subgroups stratified by baseline histology, nor were there significant differences in rates of postprocedural stricture (8.7% in the cryoballoon group vs. 12% in the cryospray group). However, the investigators acknowledged that the study was underpowered. Overall, clinicians tended to prefer cryoballoon because it uses prefilled nitrous oxide cartridges, making it unnecessary to fill up a large nitrogen tank or use a “cumbersome decompression tube,” the investigators wrote. “However, in patients with a very large hiatal hernia or if there was a need to treat in a retroflexed position, spray cryotherapy was used given its ease of use over cryoballoon in these scenarios. Finally, cryospray is more amenable to treat larger surface areas of Barrett’s versus the focal cryoballoon that treats focal areas, and thus was the cryotherapy choice for a long segment of Barrett’s.”

The investigators reported receiving no grant support. One investigator disclosed ties to Olympus America, Pentax Medical Research, and Ninepoint Medical.

SOURCE: Alshelleh M et al. Tech Innov Gastrointest Endosc. 2020 Jul 26. doi: 10.1016/j.tige.2020.07.004.

Cryoballoon and cryospray ablation were equivalent for eradicating dysplastic Barrett’s esophagus, according to the findings of a single-center retrospective study of 71 ablation-naive patients.

At 18 months, rates of complete eradication of dysplasia were 95.6% in patients who received cryoballoon therapy and 96% in recipients of cryospray, reported Mohammed Alshelleh, MD, of Northwell Health System, a tertiary care system in New Hyde Park, N.Y. Rates of complete eradication of intestinal metaplasia were 84.75% and 80%, respectively. However, selection bias was likely, and a post hoc power calculation suggested that the cryospray group was underpowered by four patients. “Prospective studies are needed to confirm [these] data,” Dr. Alshelleh and associates wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

Cryotherapy is common for treating dysplastic Barrett’s esophagus when patients do not achieve remission with radiofrequency ablation. For treatment-naive individuals, prospective studies suggest that cryotherapy may be less painful and as effective as radiofrequency ablation, but no studies have directly compared the two commercially available systems: a cryogenic balloon catheter (C2 Cryoballoon, Pentax Medical, Montvale, N.J.) that delivers cryogenic nitrous oxide (–85° C) into an inflated balloon in direct contact with the esophageal mucosa, and a spray cryotherapy system (truFreeze, Steris Endoscopy, Mentor, Ohio), which flash-freezes the mucosa to –196° C by delivering liquid nitrogen through a low-pressure catheter that is not directly in contact with the esophagus.

For the study, the investigators retrospectively compared rates of complete eradication of dysplasia, and complete eradication of intestinal metaplasia, among ablation-naive patients at their institution who had received one of these two cryogenic modalities between 2015 and 2019. All patients were treated at least twice, at 3-month intervals, and were followed for least 12 months, or until complete eradication of intestinal metaplasia was confirmed by at least one endoscopic biopsy. In all, 46 patients received cryoballoon therapy and 25 received cryospray. Outcomes between the two modalities showed no significant differences in subgroups stratified by baseline histology, nor were there significant differences in rates of postprocedural stricture (8.7% in the cryoballoon group vs. 12% in the cryospray group). However, the investigators acknowledged that the study was underpowered. Overall, clinicians tended to prefer cryoballoon because it uses prefilled nitrous oxide cartridges, making it unnecessary to fill up a large nitrogen tank or use a “cumbersome decompression tube,” the investigators wrote. “However, in patients with a very large hiatal hernia or if there was a need to treat in a retroflexed position, spray cryotherapy was used given its ease of use over cryoballoon in these scenarios. Finally, cryospray is more amenable to treat larger surface areas of Barrett’s versus the focal cryoballoon that treats focal areas, and thus was the cryotherapy choice for a long segment of Barrett’s.”

The investigators reported receiving no grant support. One investigator disclosed ties to Olympus America, Pentax Medical Research, and Ninepoint Medical.

SOURCE: Alshelleh M et al. Tech Innov Gastrointest Endosc. 2020 Jul 26. doi: 10.1016/j.tige.2020.07.004.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

A new analysis of a U.S. national database suggests that surveillance endoscopies are being initiated unnecessarily in patients without a diagnosis of Barrett’s esophagus, and sooner than the recommended interval in patients with nondysplastic Barrett’s esophagus. The study, published in the American Journal of Gastroenterology, found some improvements, suggesting that 2016 recommendations from the American College of Gastroenterology and the American Board of Internal Medicine have had some impact in reducing unnecessary surveillance, but more work may need to be done. The guidelines recommend surveillance of nondysplastic Barrett’s esophagus every 3-5 years, and no biopsy for normal or irregular Z-line (<1 cm of variability).

“There was a notable change in practice after the 2016 ACG guidelines,” said Ziad Gellad, MD, an associate professor of medicine at Duke University, Durham, N.C., in an interview. He noted that fewer providers were recommending 1-2-year surveillance intervals for nondysplastic Barrett’s esophagus and an increase in those who recommended a 3-year interval.

But the study also found frequent biopsies of irregular Z-line. Whether that’s a clear signal of overuse of biopsy is unclear, since the researchers couldn’t determine if other macroscopic or endoscopically visible abnormalities may have been present and driven a decision. “We can’t assume that there wasn’t any other abnormality in the esophagus that deserved to be biopsied,” said Dr. Gellad, who was not involved in the study.

The authors, led by Sachin Wani, MD, of the University of Colorado at Denver, Aurora, and Nicholas J. Shaheen, MD, MPH, of the University of North Carolina at Chapel Hill, analyzed data from the GI Quality Improvement Consortium Registry on 135,704 endoscopies in 114,894 patients, performed between January 2013 and December 2019. Analyzed data included procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy.

Just over 61% of subjects were men, and 91.0% were White. The mean age at time of endoscopy was 61.7 years. 50.2% of procedures produced a pathology-confirmed diagnosis of intestinal metaplasia (IM). Of these, 5.9% were indefinite for dysplasia or low-grade dysplasia (LGD), and 1.5% were high-grade dysplasia (HGD).

In 81.4% of cases with IM and a normal Z-line, the endoscopist recommended surveillance endoscopy. In 44.2%, the repeat was recommended in 3 years. 26.1% were recommended for surveillance in 1-2 years. Surveillance was recommended in 80.7% of cases with IM and an irregular Z-line; 51.5% in 3 years and 19.5% in 1-2 years. Almost 20% of subjects with normal Z-line and no IM were recommended for surveillance endoscopy, most often in 3 years (8.6%). 24% of those with irregular Z-line and no IM were recommended for surveillance endoscopy (15.8% in 3 years). Overall, between 2016 and 2019, compared with 2013-2015, the researchers found an increase in the frequency of recommendation of 3-year intervals, and a decrease in recommendation of 1-2-year intervals.

Among patients with columnar-lined esophagus and confirmed Barrett’s esophagus, 53.4% of the 1- to 3-cm group and 41.8% of the >3-cm group were recommended surveillance endoscopy at 3 years. 21.9% of the 1- to 3-cm group and 30.3% of the >3-cm group were recommended for surveillance endoscopy sooner than 3 years.

“It confirms overuse of upper endoscopy in the management of Barrett’s. However, there is also a nagging question in my mind about what to do about an irregular Z-line,” said Dr. Gellad. He noted that 33.8% of individuals with irregular Z-line had IM, while 3.8% had LGD and 0.7% had HGD. Those patients would have been missed if biopsies had not been taken, which would have been consistent with the new guidelines. However, he noted that pathology findings were not reviewed by an expert pathologist. “Does this data suggest because you find HGD in irregular Z-line, should we now in fact biopsy irregular Z-line? That’s one of the interesting pieces of this,” said Dr. Gellad.

He also believes that there is much more to be learned about what drives the decisions and timing surrounding surveillance endoscopy. “I think that’s an area that’s ripe for research,” said Dr. Gellad.

The study was funded by the University of Colorado department of medicine. The article authors have consulted for various companies. Dr. Gellad has no relevant financial disclosures.

SOURCE: Wani S et al. Am J Gastroenterol. 2020 Oct 11. doi: 10.14309/ajg.0000000000000960.

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

In a phase 2 trial in eosinophilic gastritis and duodenitis, an anti–Siglec-8 antibody greatly reduced populations of eosinophilic cells, and also led to improved symptoms. The sponsoring company, Alkalos, is currently conducting a phase 3 trial in eosinophilic gastritis or duodenitis and a phase 2-3 trial in eosinophilic esophagitis.

The news is welcome to clinicians who treat these rare conditions, since the only current treatment option is steroids. This is particularly challenging because most patients with these conditions present in their 30s and 40s, according to Carol Semrad, MD, professor of medicine at the University of Chicago, who was asked to comment on the study. She noted that the study’s results were impressive, but it will take a phase 3 trial to convince. It’s also unclear if the clinical benefit tracks with the impressive reduction seen in eosinophil count. “There’s somewhat of a disconnect between symptom reduction and reduction of the eosinophil counts. Sometimes just blocking the inflammation [isn’t enough]. Maybe there is other damage to the bowel.”

Still, “it looks like they have a proof of concept that it’s very effective at blocking the eosinophils and mast cells that are thought to be causing eosinophilic gastritis and duodenitis in human disease. That, along with improvement in symptoms, is highly promising, given that we have no other treatment beside steroids,” said Dr. Semrad.

The research, led by Evan S. Dellon, MD, MPH, of the University of North Carolina at Chapel Hill, and Ikuo Hirano, MD, of Northwestern University, Chicago, appeared in the New England Journal of Medicine.

The antibody (lirentelimab) targets sialic acid–binding immunoglobulin-like lectin 8 (Siglec-8), which is an inhibitory receptor found on mature eosinophils and mast cells, and expressed at low levels on basophils. The antibody reduces eosinophil population through natural killer cell-mediated cellular cytotoxicity and apoptosis, and other antibodies against the same target have been shown to inhibit activation of mast cells.

At 22 sites across the United States, researchers randomized 65 adults with active, uncontrolled eosinophilic gastritis or eosinophilic duodenitis, or both, to receive four monthly low doses (0.3, 1, 1, and 1 mg/kg) or high-dose lirentelimab (0.3, 1, 3, and 3 mg/kg), or placebo. A total of 10 patients had gastritis, 25 had duodenitis, and 30 had both.

In the intention-to-treat analysis, there was a mean 86% reduction in eosinophil count in patients in the treatment groups, compared with a 9% increase in controls (P < .001). In the per-protocol analysis, there was a 95% reduction versus a 10% increase (P < .001). Of treated patients, 95% had a gastrointestinal eosinophil count of 6 or fewer per high-powered field, compared with 0% in the placebo group.

In the intention-to-treat analysis, 63% of treated patients experienced a treatment response, defined as at least a 30% reduction in total symptom score and at least a 75% reduction in eosinophil count. About 5% of patients had a response in the placebo group (P < .001). The mean percentage change in total symptom score was –48 versus –22 in the placebo group (P = .004). In the per-protocol analysis, 69% responded versus 5% (P < .001). The mean percentage change in total symptom score was –53 versus –24 (P = .001).

91% of patients in the treatment groups experienced at least one adverse event, compared with 82% in the placebo group. About 60% in the treatment group had an infusion-related reaction versus 23% who received placebo; 93% of reactions were mild to moderate. Serious adverse events occurred in 9% of the treatment group and 14% of patients on placebo. The only serious adverse event thought to be related to the drug was a single grade 4 infusion-related event in the high-dose treatment group, which led to discontinuation of the drug and withdrawal from the trial. 86% of patients in the treatment group experienced transient lymphopenia, as did 47% of the placebo group, but there were no clinical consequences.

One potential concern with the therapy is the effect that long-term suppression of eosinophils and mast cells, and to a lesser extent basophils, could have on the immune system. Eosinophils are key to defenses against parasites, so that will need to be looked at in further studies, according to Dr. Semrad: “How is blocking those inflammatory cells going to impact gut function and the ability to fight off certain organisms? That’s going to be one of the real questions.”

The study was funded by Alkalos. Dr. Semrad has no relevant financial disclosures.

SOURCE: Dellon ES et al. N Engl J Med. 2020 Oct 22. doi: 10.1056/NEJMoa2012047.

In a phase 2 trial in eosinophilic gastritis and duodenitis, an anti–Siglec-8 antibody greatly reduced populations of eosinophilic cells, and also led to improved symptoms. The sponsoring company, Alkalos, is currently conducting a phase 3 trial in eosinophilic gastritis or duodenitis and a phase 2-3 trial in eosinophilic esophagitis.

The news is welcome to clinicians who treat these rare conditions, since the only current treatment option is steroids. This is particularly challenging because most patients with these conditions present in their 30s and 40s, according to Carol Semrad, MD, professor of medicine at the University of Chicago, who was asked to comment on the study. She noted that the study’s results were impressive, but it will take a phase 3 trial to convince. It’s also unclear if the clinical benefit tracks with the impressive reduction seen in eosinophil count. “There’s somewhat of a disconnect between symptom reduction and reduction of the eosinophil counts. Sometimes just blocking the inflammation [isn’t enough]. Maybe there is other damage to the bowel.”

Still, “it looks like they have a proof of concept that it’s very effective at blocking the eosinophils and mast cells that are thought to be causing eosinophilic gastritis and duodenitis in human disease. That, along with improvement in symptoms, is highly promising, given that we have no other treatment beside steroids,” said Dr. Semrad.

The research, led by Evan S. Dellon, MD, MPH, of the University of North Carolina at Chapel Hill, and Ikuo Hirano, MD, of Northwestern University, Chicago, appeared in the New England Journal of Medicine.

The antibody (lirentelimab) targets sialic acid–binding immunoglobulin-like lectin 8 (Siglec-8), which is an inhibitory receptor found on mature eosinophils and mast cells, and expressed at low levels on basophils. The antibody reduces eosinophil population through natural killer cell-mediated cellular cytotoxicity and apoptosis, and other antibodies against the same target have been shown to inhibit activation of mast cells.

At 22 sites across the United States, researchers randomized 65 adults with active, uncontrolled eosinophilic gastritis or eosinophilic duodenitis, or both, to receive four monthly low doses (0.3, 1, 1, and 1 mg/kg) or high-dose lirentelimab (0.3, 1, 3, and 3 mg/kg), or placebo. A total of 10 patients had gastritis, 25 had duodenitis, and 30 had both.

In the intention-to-treat analysis, there was a mean 86% reduction in eosinophil count in patients in the treatment groups, compared with a 9% increase in controls (P < .001). In the per-protocol analysis, there was a 95% reduction versus a 10% increase (P < .001). Of treated patients, 95% had a gastrointestinal eosinophil count of 6 or fewer per high-powered field, compared with 0% in the placebo group.

In the intention-to-treat analysis, 63% of treated patients experienced a treatment response, defined as at least a 30% reduction in total symptom score and at least a 75% reduction in eosinophil count. About 5% of patients had a response in the placebo group (P < .001). The mean percentage change in total symptom score was –48 versus –22 in the placebo group (P = .004). In the per-protocol analysis, 69% responded versus 5% (P < .001). The mean percentage change in total symptom score was –53 versus –24 (P = .001).

91% of patients in the treatment groups experienced at least one adverse event, compared with 82% in the placebo group. About 60% in the treatment group had an infusion-related reaction versus 23% who received placebo; 93% of reactions were mild to moderate. Serious adverse events occurred in 9% of the treatment group and 14% of patients on placebo. The only serious adverse event thought to be related to the drug was a single grade 4 infusion-related event in the high-dose treatment group, which led to discontinuation of the drug and withdrawal from the trial. 86% of patients in the treatment group experienced transient lymphopenia, as did 47% of the placebo group, but there were no clinical consequences.

One potential concern with the therapy is the effect that long-term suppression of eosinophils and mast cells, and to a lesser extent basophils, could have on the immune system. Eosinophils are key to defenses against parasites, so that will need to be looked at in further studies, according to Dr. Semrad: “How is blocking those inflammatory cells going to impact gut function and the ability to fight off certain organisms? That’s going to be one of the real questions.”

The study was funded by Alkalos. Dr. Semrad has no relevant financial disclosures.

SOURCE: Dellon ES et al. N Engl J Med. 2020 Oct 22. doi: 10.1056/NEJMoa2012047.

In a phase 2 trial in eosinophilic gastritis and duodenitis, an anti–Siglec-8 antibody greatly reduced populations of eosinophilic cells, and also led to improved symptoms. The sponsoring company, Alkalos, is currently conducting a phase 3 trial in eosinophilic gastritis or duodenitis and a phase 2-3 trial in eosinophilic esophagitis.

The news is welcome to clinicians who treat these rare conditions, since the only current treatment option is steroids. This is particularly challenging because most patients with these conditions present in their 30s and 40s, according to Carol Semrad, MD, professor of medicine at the University of Chicago, who was asked to comment on the study. She noted that the study’s results were impressive, but it will take a phase 3 trial to convince. It’s also unclear if the clinical benefit tracks with the impressive reduction seen in eosinophil count. “There’s somewhat of a disconnect between symptom reduction and reduction of the eosinophil counts. Sometimes just blocking the inflammation [isn’t enough]. Maybe there is other damage to the bowel.”

Still, “it looks like they have a proof of concept that it’s very effective at blocking the eosinophils and mast cells that are thought to be causing eosinophilic gastritis and duodenitis in human disease. That, along with improvement in symptoms, is highly promising, given that we have no other treatment beside steroids,” said Dr. Semrad.

The research, led by Evan S. Dellon, MD, MPH, of the University of North Carolina at Chapel Hill, and Ikuo Hirano, MD, of Northwestern University, Chicago, appeared in the New England Journal of Medicine.

The antibody (lirentelimab) targets sialic acid–binding immunoglobulin-like lectin 8 (Siglec-8), which is an inhibitory receptor found on mature eosinophils and mast cells, and expressed at low levels on basophils. The antibody reduces eosinophil population through natural killer cell-mediated cellular cytotoxicity and apoptosis, and other antibodies against the same target have been shown to inhibit activation of mast cells.

At 22 sites across the United States, researchers randomized 65 adults with active, uncontrolled eosinophilic gastritis or eosinophilic duodenitis, or both, to receive four monthly low doses (0.3, 1, 1, and 1 mg/kg) or high-dose lirentelimab (0.3, 1, 3, and 3 mg/kg), or placebo. A total of 10 patients had gastritis, 25 had duodenitis, and 30 had both.

In the intention-to-treat analysis, there was a mean 86% reduction in eosinophil count in patients in the treatment groups, compared with a 9% increase in controls (P < .001). In the per-protocol analysis, there was a 95% reduction versus a 10% increase (P < .001). Of treated patients, 95% had a gastrointestinal eosinophil count of 6 or fewer per high-powered field, compared with 0% in the placebo group.

In the intention-to-treat analysis, 63% of treated patients experienced a treatment response, defined as at least a 30% reduction in total symptom score and at least a 75% reduction in eosinophil count. About 5% of patients had a response in the placebo group (P < .001). The mean percentage change in total symptom score was –48 versus –22 in the placebo group (P = .004). In the per-protocol analysis, 69% responded versus 5% (P < .001). The mean percentage change in total symptom score was –53 versus –24 (P = .001).

91% of patients in the treatment groups experienced at least one adverse event, compared with 82% in the placebo group. About 60% in the treatment group had an infusion-related reaction versus 23% who received placebo; 93% of reactions were mild to moderate. Serious adverse events occurred in 9% of the treatment group and 14% of patients on placebo. The only serious adverse event thought to be related to the drug was a single grade 4 infusion-related event in the high-dose treatment group, which led to discontinuation of the drug and withdrawal from the trial. 86% of patients in the treatment group experienced transient lymphopenia, as did 47% of the placebo group, but there were no clinical consequences.

One potential concern with the therapy is the effect that long-term suppression of eosinophils and mast cells, and to a lesser extent basophils, could have on the immune system. Eosinophils are key to defenses against parasites, so that will need to be looked at in further studies, according to Dr. Semrad: “How is blocking those inflammatory cells going to impact gut function and the ability to fight off certain organisms? That’s going to be one of the real questions.”

The study was funded by Alkalos. Dr. Semrad has no relevant financial disclosures.

SOURCE: Dellon ES et al. N Engl J Med. 2020 Oct 22. doi: 10.1056/NEJMoa2012047.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.

Budesonide orodispersible tablets maintained remissions of eosinophilic esophagitis for 48 weeks in approximately 75% of patients and did not increase the risk for most adverse events, compared with placebo, according to the findings of a multicenter, randomized, double-blind trial.

While prior studies have shown that swallowed topical corticosteroids such as budesonide or fluticasone induce remission in EoE, this is the first multicenter phase 3 study of budesonide orodispersible tablets (BOTs) for maintaining remissions over the long term, wrote Alex Straumann, MD, of the Swiss EoE Research Group and University Hospital Zurich, and associates in Gastroenterology.

Eosinophilic esophagitis is the most common cause of esophageal dysphagia and food impaction. Swallowed topical corticosteroids improve symptoms and inflammation, but the off-label use of formulations developed for airway administration in asthma shows “suboptimal esophageal targeting and efficacy,” the researchers wrote. In the phase 3 EOS-2 trial, twice-daily treatment with 1.0 mg BOTs had induced clinicohistologic remissions in 58% of adults with EoE at 6 weeks and in 85% at 12 weeks.

To study long-term maintenance BOT therapy, the researchers randomly assigned 204 of the remitted patients to 48 weeks of twice-daily BOT 0.5 mg, BOT 1.0 mg, or placebo. There were 68 patients per group. A total of 141 patients completed this double-blind phase, but all 204 were evaluable for the primary analysis. The primary outcome was remission at week 48, defined as freedom from relapse (dysphagia or odynophagia rated as 4 or higher on a 10-point numeric rating scale), histologic relapse (≥48 eosinophils per mm² high-power field), food impaction requiring endoscopic intervention, and dilation.

After 48 weeks, 51 patients in the 1-mg group (75%) and 50 patients in the 0.5-mg group (73.5%) remained in remission, compared with only three patients in the placebo group (4.4%; both P less than .0001). Patients in the placebo group relapsed after a median of 87 days off BOTs. Overall, BOT therapy was similarly efficacious regardless of factors such as history of allergic diseases, location of inflammation at the start of induction, or concomitant use of proton pump inhibitors. However, patients with inflammation of all three esophageal segments achieved “clinically relevant” greater rates of remission with twice-daily 1.0-mg BOT, compared with twice-daily 0.5-mg BOT (80% vs. 68%). In secondary analyses, rates of histologic relapse were 13.2% with 0.5-mg BOT twice daily, 10.3% with 1.0-mg BOT twice daily, and 90% with placebo, and rates of clinical relapse were 10.3%, 7.4%, and 60.3%, respectively. “Histological remission in the BOT 0.5 and 1.0mg twice daily group was independently maintained in all esophageal segments,” the researchers reported.

Rates of most adverse events were similar across treatment groups, and no serious treatment-emergent adverse events were reported. Average morning serum cortisol levels were similar among groups and did not change after treatment ended, but four patients on BOT therapy developed asymptomatic subnormal levels of morning cortisol. “Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5mg group and in 11.8% of patients in the BOT 1.0mg group; all infections resolved with treatment,” the researchers wrote.

The study and editorial support were funded by Dr. Falk Pharma GmbH, a pharmaceutical company in Germany. Dr. Falk Pharma was involved in the study design and data collection, analysis, and interpretation. Dr. Straumann disclosed fees from several pharmaceutical companies, including Dr. Falk Pharma and AstraZeneca, which makes budesonide. Several other coinvestigators also disclosed ties to Dr. Falk Pharma, AstraZeneca, and other pharmaceutical companies.

SOURCE: Straumann A et al. Gastroenterology. 2020 July 25. doi: 10.1053/j.gastro.2020.07.039.

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

Regular use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes, according to a large prospective analysis of the Nurses’ Health Study. The results follow on other studies suggesting other potential adverse effects of PPIs such as dementia, kidney damage, and micronutrient deficiencies.

The authors, led by Jinqiu Yuan and Changhua Zhang of Sun Yat-sen University (Guangdong, China), call for regular blood glucose testing and diabetes screening for patients on long-term PPIs. But not all are convinced. “I think that’s a strong recommendation from the available data and it’s unclear how oe who would implement that in practice. I think instead practitioners should adhere to best practices, which emphasize using the lowest effective dose of PPIs for patients with appropriate indications,” David Leiman, MD, MSHP, assistant professor of medicine at Duke University, Durham, N.C. said in an interview.

“Overall, the data from the study can be classified as provocative results that I think may warrant further study,” he added. Consistent and strongly positive findings from more observationsal studies would be required to establish causality between PPI use and diabetes risk, and in any case the findings of the surrent study don't warrant a change in practice, Dr. Leiman said, noting that the study’s design makes it likely that much or all of the observed associations were due to unmeasured confounding.

The study appeared online Sept. 28 in Gut.

The researchers analyzed data from 80,500 women from the Nurses’ Health Study, 95,550 women from the Nurses’ Health Study II, and 28,639 men from the Health Professionals Follow-up Study (HPFS), with a median follow-up time of 12 years in NHS and NHS2 and 9.8 years in HPFS.

The absolute risk of diabetes was 7.44 per 1,000 person-years in PPI users versus 4.32 among nonusers. After adjustment for lagging PPI use for 2 years and stratification by age and study period, PPI use was associated with a 74% increased risk of diabetes (hazard ratio , 1.74; 95% confidence interval, 1.37-2.20). Multivariable adjustment for demographic factors, lifestyle habits, comorbidities, and use of other medications and clinical indications for PPI use attenuated the association but did not eliminate it (HR, 1.24; 95% CI, 1.17-1.31).

There was no statistically significant association in the HPFS group (HR, 1.12; 95% CI, 0.91-1.38), possibly because of the smaller sample size.

At 1 year, the number needed to harm with PPIs was 318.9 (95% CI, 285.2-385.0). At 2 years it was 170.8 (95% CI, 150.8-209.7) and at 3 years it was 77.3 (95% CI, 66.8-97.0).

At 0-2 years, PPI use was associated with a 5% increase in diabetes risk (HR, 1.05; 95% CI, 0.93-1.19). More than 2 years of use was associated with higher risk (HR, 1.26; 95% CI, 1.18-1.35).

There was also an association between stopping PPI use and a decreased risk of diabetes: Compared with current PPI users, those who had stopped within the past 2 years had a 17% reduction in risk (HR, 0.83; 95% CI, 0.70-0.98), and those who had stopped more than 2 years previously had a 19% reduction (HR, 0.81; 95% CI, 0.76-0.86).

The researchers also examined diabetes risk associated with use of H₂ receptor agonists (H₂RAs), since the drugs share clinical indications with PPIs. H₂RA use was also associated with a higher risk of diabetes (adjusted HR, 1.14; 95% CI, 1.07-1.23).

The researchers suggested that the fact that the less potent H₂RA inhibitors had a less pronounced association with diabetes risk supports the idea that acid suppression may be related to diabetes pathogenesis.

The authors also suggest that changes to the gut microbiota may underlie increased risk. PPI use has been shown to reduce gut microbiome diversity and alter its phenotype. Such changes could lead to weight gain, metabolic syndrome, and chronic liver disease, which could in turn heighten risk.

The study is limited by its observational nature, and lacked detailed information on dosage, frequency, and indications for PPI use.

SOURCE: Yuan J et al. Gut. 2020 Sep 28. doi: 10.1136/gutjnl-2020-322557.

This story was updated on 11/24/2020.

Help your patients understand the risks and benefits of long-term PPI use by sharing the AGA Clinical Practice Update patient companion at http://ow.ly/N1 

For patients with gastroesophageal reflux disease (GERD), endoscopic and minimally invasive surgical techniques may be viable alternatives to proton pump inhibitor (PPI) therapy, according to investigators.

Still, their exact role in the treatment process remains undetermined, reported Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues.

“The frequent incomplete response to PPI therapy, in addition to recent studies suggesting chronic complications with PPI therapy, have fueled discussion of alternative strategies for treating patients with GERD,” the investigators wrote in Gastroenterology. “For a substantial number of patients and providers with the above concerns who are unwilling to pursue the traditional surgical gastric fundoplication, endoscopic or less invasive surgical strategies have gained some traction.”

Dr. Vaezi and colleagues noted that they conducted the scoping review with intentions of being more descriptive than prescriptive.

“Our goal is not to recommend the utility of any of the discussed techniques in specific clinical scenarios,” they wrote. “Rather, it is to summarize the currently available evidence and identify where more research may be helpful.”

Across 22 randomized, controlled trials and observational studies, objective and symptomatic improvement varied between modalities. Measured outcomes also varied; most studies reported symptoms, health-related quality of life, and PPI use; fewer studies (but still a majority) reported intraesophageal acid exposure and/or lower esophageal sphincter (LES) pressure. Conclusions drawn by Dr. Vaezi and colleagues are summarized below.
 

Magnetic sphincter augmentation of the LES

In multiple trials, magnetic sphincter augmentation demonstrated a “high degree of efficacy” in the short or midterm, and a favorable safety profile. Dr. Vaezi and colleagues highlighted significant improvements in disease-related quality of life, with “a substantial proportion” of patients achieving normalization or at least 50% improvement in acid exposure. While some patients required esophageal dilation after the procedure, this was not needed any more frequently than after surgical fundoplication.

Radiofrequency ablation

Across five trials, radiofrequency ablation, which involves delivery of energy to the LES and gastric cardia, improved GERD-related quality of life, and reduced, but did not normalize, acid exposure. The technique lessened short-term need for PPIs, but long-term relief was not observed. Compared with observational studies, efficacy signals were weaker in randomized, controlled trials. The procedure was generally safe.

Surgical implantation of LES pacemaker

Limited data were available for LES sphincter stimulation among patients with GERD, and the most recent study, involving a comparison of device placement with or without stimulation, was terminated early. Still, available data suggest that the technique is generally well tolerated, with reduced need for PPIs, improved symptoms, and lessened acid exposure. Dr. Vaezi and colleagues noted that the manufacturing company, EndoStim, is in receivership, putting U.S. availability in question.

Full-thickness fundoplication

Endoscopic full-thickness fundoplication was associated with improvement of symptoms and quality of life, and a favorable safety profile. Although the procedure generally reduced PPI use, most patients still needed PPIs long-term. Reflux improved after the procedure, but not to the same degree as laparoscopic plication.

Transoral incisionless fundoplication

Based on a number of studies, including five randomized, controlled trials, transoral incisionless fundoplication appears safe and effective, with reduced need for PPIs up to 5 years. According to Dr. Vaezi and colleagues, variable results across studies are likely explained by variations in the technique over time and heterogeneous patient populations. Recent studies in which the “TIF 2.0 technique” has been performed on patients with hiatal hernias less than 2 cm have met objective efficacy outcomes.

Incisionless fundoplication with magnetic ultrasonic surgical endostapler

The magnetic ultrasonic surgical endostapler, which allows for incisionless fundoplication, had more limited data. Only two studies have been conducted, and neither had sham-controlled nor comparative-trial data. Furthermore, multiple safety signals have been encountered, with “substantial” complication rates and serious adverse events that were “noticeable and concerning,” according to Dr. Vaezi and colleagues.

Concluding their discussion, the investigators suggested that some endoscopic and minimally invasive approaches to GERD are “promising” alternatives to PPI therapy.

“However, their place in the treatment algorithm for GERD will be better defined when important clinical parameters, especially the durability of their effect, are understood,” they wrote.

The investigators reported no conflicts of interest.

SOURCE: Vaezi MF et al. Gastroenterology. 2020 Jul 1. doi: 10.1053/j.gastro.2020.05.097.

For patients with gastroesophageal reflux disease (GERD), endoscopic and minimally invasive surgical techniques may be viable alternatives to proton pump inhibitor (PPI) therapy, according to investigators.

Still, their exact role in the treatment process remains undetermined, reported Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues.

“The frequent incomplete response to PPI therapy, in addition to recent studies suggesting chronic complications with PPI therapy, have fueled discussion of alternative strategies for treating patients with GERD,” the investigators wrote in Gastroenterology. “For a substantial number of patients and providers with the above concerns who are unwilling to pursue the traditional surgical gastric fundoplication, endoscopic or less invasive surgical strategies have gained some traction.”

Dr. Vaezi and colleagues noted that they conducted the scoping review with intentions of being more descriptive than prescriptive.

“Our goal is not to recommend the utility of any of the discussed techniques in specific clinical scenarios,” they wrote. “Rather, it is to summarize the currently available evidence and identify where more research may be helpful.”

Across 22 randomized, controlled trials and observational studies, objective and symptomatic improvement varied between modalities. Measured outcomes also varied; most studies reported symptoms, health-related quality of life, and PPI use; fewer studies (but still a majority) reported intraesophageal acid exposure and/or lower esophageal sphincter (LES) pressure. Conclusions drawn by Dr. Vaezi and colleagues are summarized below.
 

Magnetic sphincter augmentation of the LES

In multiple trials, magnetic sphincter augmentation demonstrated a “high degree of efficacy” in the short or midterm, and a favorable safety profile. Dr. Vaezi and colleagues highlighted significant improvements in disease-related quality of life, with “a substantial proportion” of patients achieving normalization or at least 50% improvement in acid exposure. While some patients required esophageal dilation after the procedure, this was not needed any more frequently than after surgical fundoplication.

Radiofrequency ablation

Across five trials, radiofrequency ablation, which involves delivery of energy to the LES and gastric cardia, improved GERD-related quality of life, and reduced, but did not normalize, acid exposure. The technique lessened short-term need for PPIs, but long-term relief was not observed. Compared with observational studies, efficacy signals were weaker in randomized, controlled trials. The procedure was generally safe.

Surgical implantation of LES pacemaker

Limited data were available for LES sphincter stimulation among patients with GERD, and the most recent study, involving a comparison of device placement with or without stimulation, was terminated early. Still, available data suggest that the technique is generally well tolerated, with reduced need for PPIs, improved symptoms, and lessened acid exposure. Dr. Vaezi and colleagues noted that the manufacturing company, EndoStim, is in receivership, putting U.S. availability in question.

Full-thickness fundoplication

Endoscopic full-thickness fundoplication was associated with improvement of symptoms and quality of life, and a favorable safety profile. Although the procedure generally reduced PPI use, most patients still needed PPIs long-term. Reflux improved after the procedure, but not to the same degree as laparoscopic plication.

Transoral incisionless fundoplication

Based on a number of studies, including five randomized, controlled trials, transoral incisionless fundoplication appears safe and effective, with reduced need for PPIs up to 5 years. According to Dr. Vaezi and colleagues, variable results across studies are likely explained by variations in the technique over time and heterogeneous patient populations. Recent studies in which the “TIF 2.0 technique” has been performed on patients with hiatal hernias less than 2 cm have met objective efficacy outcomes.

Incisionless fundoplication with magnetic ultrasonic surgical endostapler

The magnetic ultrasonic surgical endostapler, which allows for incisionless fundoplication, had more limited data. Only two studies have been conducted, and neither had sham-controlled nor comparative-trial data. Furthermore, multiple safety signals have been encountered, with “substantial” complication rates and serious adverse events that were “noticeable and concerning,” according to Dr. Vaezi and colleagues.

Concluding their discussion, the investigators suggested that some endoscopic and minimally invasive approaches to GERD are “promising” alternatives to PPI therapy.

“However, their place in the treatment algorithm for GERD will be better defined when important clinical parameters, especially the durability of their effect, are understood,” they wrote.

The investigators reported no conflicts of interest.

SOURCE: Vaezi MF et al. Gastroenterology. 2020 Jul 1. doi: 10.1053/j.gastro.2020.05.097.

For patients with gastroesophageal reflux disease (GERD), endoscopic and minimally invasive surgical techniques may be viable alternatives to proton pump inhibitor (PPI) therapy, according to investigators.

Still, their exact role in the treatment process remains undetermined, reported Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues.

“The frequent incomplete response to PPI therapy, in addition to recent studies suggesting chronic complications with PPI therapy, have fueled discussion of alternative strategies for treating patients with GERD,” the investigators wrote in Gastroenterology. “For a substantial number of patients and providers with the above concerns who are unwilling to pursue the traditional surgical gastric fundoplication, endoscopic or less invasive surgical strategies have gained some traction.”

Dr. Vaezi and colleagues noted that they conducted the scoping review with intentions of being more descriptive than prescriptive.

“Our goal is not to recommend the utility of any of the discussed techniques in specific clinical scenarios,” they wrote. “Rather, it is to summarize the currently available evidence and identify where more research may be helpful.”

Across 22 randomized, controlled trials and observational studies, objective and symptomatic improvement varied between modalities. Measured outcomes also varied; most studies reported symptoms, health-related quality of life, and PPI use; fewer studies (but still a majority) reported intraesophageal acid exposure and/or lower esophageal sphincter (LES) pressure. Conclusions drawn by Dr. Vaezi and colleagues are summarized below.
 

Magnetic sphincter augmentation of the LES

In multiple trials, magnetic sphincter augmentation demonstrated a “high degree of efficacy” in the short or midterm, and a favorable safety profile. Dr. Vaezi and colleagues highlighted significant improvements in disease-related quality of life, with “a substantial proportion” of patients achieving normalization or at least 50% improvement in acid exposure. While some patients required esophageal dilation after the procedure, this was not needed any more frequently than after surgical fundoplication.

Radiofrequency ablation

Across five trials, radiofrequency ablation, which involves delivery of energy to the LES and gastric cardia, improved GERD-related quality of life, and reduced, but did not normalize, acid exposure. The technique lessened short-term need for PPIs, but long-term relief was not observed. Compared with observational studies, efficacy signals were weaker in randomized, controlled trials. The procedure was generally safe.

Surgical implantation of LES pacemaker

Limited data were available for LES sphincter stimulation among patients with GERD, and the most recent study, involving a comparison of device placement with or without stimulation, was terminated early. Still, available data suggest that the technique is generally well tolerated, with reduced need for PPIs, improved symptoms, and lessened acid exposure. Dr. Vaezi and colleagues noted that the manufacturing company, EndoStim, is in receivership, putting U.S. availability in question.

Full-thickness fundoplication

Endoscopic full-thickness fundoplication was associated with improvement of symptoms and quality of life, and a favorable safety profile. Although the procedure generally reduced PPI use, most patients still needed PPIs long-term. Reflux improved after the procedure, but not to the same degree as laparoscopic plication.

Transoral incisionless fundoplication

Based on a number of studies, including five randomized, controlled trials, transoral incisionless fundoplication appears safe and effective, with reduced need for PPIs up to 5 years. According to Dr. Vaezi and colleagues, variable results across studies are likely explained by variations in the technique over time and heterogeneous patient populations. Recent studies in which the “TIF 2.0 technique” has been performed on patients with hiatal hernias less than 2 cm have met objective efficacy outcomes.

Incisionless fundoplication with magnetic ultrasonic surgical endostapler

The magnetic ultrasonic surgical endostapler, which allows for incisionless fundoplication, had more limited data. Only two studies have been conducted, and neither had sham-controlled nor comparative-trial data. Furthermore, multiple safety signals have been encountered, with “substantial” complication rates and serious adverse events that were “noticeable and concerning,” according to Dr. Vaezi and colleagues.

Concluding their discussion, the investigators suggested that some endoscopic and minimally invasive approaches to GERD are “promising” alternatives to PPI therapy.

“However, their place in the treatment algorithm for GERD will be better defined when important clinical parameters, especially the durability of their effect, are understood,” they wrote.

The investigators reported no conflicts of interest.

SOURCE: Vaezi MF et al. Gastroenterology. 2020 Jul 1. doi: 10.1053/j.gastro.2020.05.097.