Upper GI Tract

An online educational tool for endoscopists helped improve their detection of Barrett’s esophagus–related neoplasia (BORN), researchers reported in the April issue of Gastroenterology.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

In tests administered before and after training, endoscopists increased their rates of BORN detection by a median of 30% (P less than .001), reported J.J. Bergman, MD, PhD, of the University of Amsterdam, together with his associates. “To our knowledge, this is the first validated online, interactive endoscopic training program in our field,” they wrote. “Widespread use of this tool might improve management of Barrett’s esophagus by general endoscopists.”

To develop the program, the investigators recorded high-definition videos of upper endoscopies of patients with either BORN or nondysplastic Barrett’s esophagus. They sent these videos to three experts, who used special tools to superimpose their delineations of lesions.

Next, 68 general endoscopists (fellows, early-career general gastroenterologists, and senior general gastroenterologists) watched four batches of 20 videos each. The researchers compared the assessors’ interpretations with the experts’ to identify the 25 videos with the most educational impact. These were then shown in four batches of five to 121 new assessors (five videos were reserved for pre- and post testing).

From the first to the fourth batch of training videos, assessors sequentially improved their scores for detection, delineation, agreement delineation, and relative delineation of BORN, the researchers said. Among the 121 assessors in the second phase of development, median rates of detection of BORN rose by 30% after training. Furthermore, from baseline to the end of the study, scores rose by 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all P less than .001). These improvements did not depend on the country of origin of the assessors or their level of endoscopic experience.

This module requires the use of high-definition videos whose resolution is not lost during replay or when viewed on the web, the researchers emphasized. They noted that the module is active, not passive – learners select the video frame to position a biopsy mark and delineate the lesion, and the software then gives them tailored feedback on their choice. Learners also can add and remove the experts’ delineations as well as their own during feedback sessions at the end of each batch of videos. This enables them to “fully appreciate the subtle appearance of the lesion on the selected time frame,” the investigators wrote.

By completing the training module, “general endoscopists with a wide range of experience and from different countries of origin can substantially and conveniently increase their skills for detection and delineation of early BORN lesions,” they concluded. “Therefore, the module could provide training in an essential upper gastrointestinal endoscopic skill that is not otherwise readily available.”

The investigators disclosed no external funding sources. They reported having no conflicts of interest.

SOURCE: Bergman JJ et al. Gastroenterology. 2019 Jan 2. doi: 10.1053/j.gastro.2018.12.021.

An online educational tool for endoscopists helped improve their detection of Barrett’s esophagus–related neoplasia (BORN), researchers reported in the April issue of Gastroenterology.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

In tests administered before and after training, endoscopists increased their rates of BORN detection by a median of 30% (P less than .001), reported J.J. Bergman, MD, PhD, of the University of Amsterdam, together with his associates. “To our knowledge, this is the first validated online, interactive endoscopic training program in our field,” they wrote. “Widespread use of this tool might improve management of Barrett’s esophagus by general endoscopists.”

To develop the program, the investigators recorded high-definition videos of upper endoscopies of patients with either BORN or nondysplastic Barrett’s esophagus. They sent these videos to three experts, who used special tools to superimpose their delineations of lesions.

Next, 68 general endoscopists (fellows, early-career general gastroenterologists, and senior general gastroenterologists) watched four batches of 20 videos each. The researchers compared the assessors’ interpretations with the experts’ to identify the 25 videos with the most educational impact. These were then shown in four batches of five to 121 new assessors (five videos were reserved for pre- and post testing).

From the first to the fourth batch of training videos, assessors sequentially improved their scores for detection, delineation, agreement delineation, and relative delineation of BORN, the researchers said. Among the 121 assessors in the second phase of development, median rates of detection of BORN rose by 30% after training. Furthermore, from baseline to the end of the study, scores rose by 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all P less than .001). These improvements did not depend on the country of origin of the assessors or their level of endoscopic experience.

This module requires the use of high-definition videos whose resolution is not lost during replay or when viewed on the web, the researchers emphasized. They noted that the module is active, not passive – learners select the video frame to position a biopsy mark and delineate the lesion, and the software then gives them tailored feedback on their choice. Learners also can add and remove the experts’ delineations as well as their own during feedback sessions at the end of each batch of videos. This enables them to “fully appreciate the subtle appearance of the lesion on the selected time frame,” the investigators wrote.

By completing the training module, “general endoscopists with a wide range of experience and from different countries of origin can substantially and conveniently increase their skills for detection and delineation of early BORN lesions,” they concluded. “Therefore, the module could provide training in an essential upper gastrointestinal endoscopic skill that is not otherwise readily available.”

The investigators disclosed no external funding sources. They reported having no conflicts of interest.

SOURCE: Bergman JJ et al. Gastroenterology. 2019 Jan 2. doi: 10.1053/j.gastro.2018.12.021.

An online educational tool for endoscopists helped improve their detection of Barrett’s esophagus–related neoplasia (BORN), researchers reported in the April issue of Gastroenterology.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

In tests administered before and after training, endoscopists increased their rates of BORN detection by a median of 30% (P less than .001), reported J.J. Bergman, MD, PhD, of the University of Amsterdam, together with his associates. “To our knowledge, this is the first validated online, interactive endoscopic training program in our field,” they wrote. “Widespread use of this tool might improve management of Barrett’s esophagus by general endoscopists.”

To develop the program, the investigators recorded high-definition videos of upper endoscopies of patients with either BORN or nondysplastic Barrett’s esophagus. They sent these videos to three experts, who used special tools to superimpose their delineations of lesions.

Next, 68 general endoscopists (fellows, early-career general gastroenterologists, and senior general gastroenterologists) watched four batches of 20 videos each. The researchers compared the assessors’ interpretations with the experts’ to identify the 25 videos with the most educational impact. These were then shown in four batches of five to 121 new assessors (five videos were reserved for pre- and post testing).

From the first to the fourth batch of training videos, assessors sequentially improved their scores for detection, delineation, agreement delineation, and relative delineation of BORN, the researchers said. Among the 121 assessors in the second phase of development, median rates of detection of BORN rose by 30% after training. Furthermore, from baseline to the end of the study, scores rose by 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all P less than .001). These improvements did not depend on the country of origin of the assessors or their level of endoscopic experience.

This module requires the use of high-definition videos whose resolution is not lost during replay or when viewed on the web, the researchers emphasized. They noted that the module is active, not passive – learners select the video frame to position a biopsy mark and delineate the lesion, and the software then gives them tailored feedback on their choice. Learners also can add and remove the experts’ delineations as well as their own during feedback sessions at the end of each batch of videos. This enables them to “fully appreciate the subtle appearance of the lesion on the selected time frame,” the investigators wrote.

By completing the training module, “general endoscopists with a wide range of experience and from different countries of origin can substantially and conveniently increase their skills for detection and delineation of early BORN lesions,” they concluded. “Therefore, the module could provide training in an essential upper gastrointestinal endoscopic skill that is not otherwise readily available.”

The investigators disclosed no external funding sources. They reported having no conflicts of interest.

SOURCE: Bergman JJ et al. Gastroenterology. 2019 Jan 2. doi: 10.1053/j.gastro.2018.12.021.

Uncomplicated gastroesophageal reflux disease (GERD) accounted for 13.5% of esophagogastroduodenoscopies, but 5.6% of these patients had suspected Barrett’s esophagus and only 1.4% had suspected long-segment Barrett’s esophagus, researchers reported. The study appears in the April issue of Clinical Gastroenterology and Hepatology.

“The prevalence of suspected Barrett’s esophagus is lower than in prior time periods. This raises questions about the utility of esophagogastroduodenoscopies to detect Barrett’s esophagus in patients with uncomplicated GERD,” wrote Emery C. Lin, MD, of Oregon Health and Science University, Portland, and his associates there and at Massachusetts General Hospital, Boston.

Symptoms of GERD affect more than one in four U.S. adults and are a risk factor for Barrett’s esophagus. However, the prevalence of Barrett’s esophagus is unclear in patients with dysphagia and in the era of proton pump inhibitors, the researchers said. The American Gastroenterological Association strongly discourages reflexively screening patients with GERD for Barrett’s esophagus, but “weakly recommends” screening GERD patients with multiple risk factors for Barrett’s esophagus, including chronic GERD, hiatal hernia, older age (50 years and up), white race, male sex, increased body mass index, and intra-abdominal adiposity.

To understand the prevalence and findings of esophagogastroduodenoscopy in patients with GERD without alarm symptoms (including weight loss, dysphagia, and bleeding), the investigators studied 543,103 of these procedures performed at 82 sites in the United States between 2003 and 2013. The data came from the National Endoscopic Database, which generates endoscopy reports using a structured computer form.

A total of 73,535 esophagogastroduodenoscopies (13.5%) were performed for GERD without alarm symptoms. Among these patients, 4,122 (5.6%) had suspected Barrett’s esophagus, of which 24.2% had suspected long-segment Barrett’s esophagus (3 cm or longer). Among patients with uncomplicated GERD, the prevalence of suspected Barrett’s esophagus was 5.6%, and the prevalence of long-segment disease was 1.4%.

Although male sex, older age, and white race were significant risk factors for suspected Barrett’s esophagus and suspected long-segment disease, 23.6% of esophagogastroduodenoscopies were performed in white men older than 50 years. “We find that low-risk populations with uncomplicated GERD make up a significant number of esophagogastroduodenoscopies done for uncomplicated GERD,” the investigators wrote. “If esophagogastroduodenoscopies were limited to patients that met the AGA criteria of being male, white, and age over 50, we would have detected 34 of 47 (72.3%) of esophageal tumors and found suspected Barrett’s esophagus in nearly 10%, while reducing the burden of endoscopy by more than 75%.”

Hiatal hernia was a significant correlate of suspected Barrett’s esophagus (odds ratio, 1.6), the researchers noted. Esophagitis was not associated with suspected Barrett’s esophagus overall but did correlate with long-segment disease. Esophagitis might mask underlying short-segment Barrett’s esophagus, and short-segment Barrett’s esophagus might be milder in nature and more responsive to antisecretory therapy, the researchers said. They noted that severe (grade C/D) esophagitis was strongly linked with both short-segment and long-segment Barrett’s esophagus.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The researchers reported having no conflicts of interest.

SOURCE: Lin EC et al. Clin Gastroenterol Hepatol. 2019 Apr. doi: 10.1016/j.cgh.2018.08.066.

Uncomplicated gastroesophageal reflux disease (GERD) accounted for 13.5% of esophagogastroduodenoscopies, but 5.6% of these patients had suspected Barrett’s esophagus and only 1.4% had suspected long-segment Barrett’s esophagus, researchers reported. The study appears in the April issue of Clinical Gastroenterology and Hepatology.

“The prevalence of suspected Barrett’s esophagus is lower than in prior time periods. This raises questions about the utility of esophagogastroduodenoscopies to detect Barrett’s esophagus in patients with uncomplicated GERD,” wrote Emery C. Lin, MD, of Oregon Health and Science University, Portland, and his associates there and at Massachusetts General Hospital, Boston.

Symptoms of GERD affect more than one in four U.S. adults and are a risk factor for Barrett’s esophagus. However, the prevalence of Barrett’s esophagus is unclear in patients with dysphagia and in the era of proton pump inhibitors, the researchers said. The American Gastroenterological Association strongly discourages reflexively screening patients with GERD for Barrett’s esophagus, but “weakly recommends” screening GERD patients with multiple risk factors for Barrett’s esophagus, including chronic GERD, hiatal hernia, older age (50 years and up), white race, male sex, increased body mass index, and intra-abdominal adiposity.

To understand the prevalence and findings of esophagogastroduodenoscopy in patients with GERD without alarm symptoms (including weight loss, dysphagia, and bleeding), the investigators studied 543,103 of these procedures performed at 82 sites in the United States between 2003 and 2013. The data came from the National Endoscopic Database, which generates endoscopy reports using a structured computer form.

A total of 73,535 esophagogastroduodenoscopies (13.5%) were performed for GERD without alarm symptoms. Among these patients, 4,122 (5.6%) had suspected Barrett’s esophagus, of which 24.2% had suspected long-segment Barrett’s esophagus (3 cm or longer). Among patients with uncomplicated GERD, the prevalence of suspected Barrett’s esophagus was 5.6%, and the prevalence of long-segment disease was 1.4%.

Although male sex, older age, and white race were significant risk factors for suspected Barrett’s esophagus and suspected long-segment disease, 23.6% of esophagogastroduodenoscopies were performed in white men older than 50 years. “We find that low-risk populations with uncomplicated GERD make up a significant number of esophagogastroduodenoscopies done for uncomplicated GERD,” the investigators wrote. “If esophagogastroduodenoscopies were limited to patients that met the AGA criteria of being male, white, and age over 50, we would have detected 34 of 47 (72.3%) of esophageal tumors and found suspected Barrett’s esophagus in nearly 10%, while reducing the burden of endoscopy by more than 75%.”

Hiatal hernia was a significant correlate of suspected Barrett’s esophagus (odds ratio, 1.6), the researchers noted. Esophagitis was not associated with suspected Barrett’s esophagus overall but did correlate with long-segment disease. Esophagitis might mask underlying short-segment Barrett’s esophagus, and short-segment Barrett’s esophagus might be milder in nature and more responsive to antisecretory therapy, the researchers said. They noted that severe (grade C/D) esophagitis was strongly linked with both short-segment and long-segment Barrett’s esophagus.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The researchers reported having no conflicts of interest.

SOURCE: Lin EC et al. Clin Gastroenterol Hepatol. 2019 Apr. doi: 10.1016/j.cgh.2018.08.066.

Uncomplicated gastroesophageal reflux disease (GERD) accounted for 13.5% of esophagogastroduodenoscopies, but 5.6% of these patients had suspected Barrett’s esophagus and only 1.4% had suspected long-segment Barrett’s esophagus, researchers reported. The study appears in the April issue of Clinical Gastroenterology and Hepatology.

“The prevalence of suspected Barrett’s esophagus is lower than in prior time periods. This raises questions about the utility of esophagogastroduodenoscopies to detect Barrett’s esophagus in patients with uncomplicated GERD,” wrote Emery C. Lin, MD, of Oregon Health and Science University, Portland, and his associates there and at Massachusetts General Hospital, Boston.

Symptoms of GERD affect more than one in four U.S. adults and are a risk factor for Barrett’s esophagus. However, the prevalence of Barrett’s esophagus is unclear in patients with dysphagia and in the era of proton pump inhibitors, the researchers said. The American Gastroenterological Association strongly discourages reflexively screening patients with GERD for Barrett’s esophagus, but “weakly recommends” screening GERD patients with multiple risk factors for Barrett’s esophagus, including chronic GERD, hiatal hernia, older age (50 years and up), white race, male sex, increased body mass index, and intra-abdominal adiposity.

To understand the prevalence and findings of esophagogastroduodenoscopy in patients with GERD without alarm symptoms (including weight loss, dysphagia, and bleeding), the investigators studied 543,103 of these procedures performed at 82 sites in the United States between 2003 and 2013. The data came from the National Endoscopic Database, which generates endoscopy reports using a structured computer form.

A total of 73,535 esophagogastroduodenoscopies (13.5%) were performed for GERD without alarm symptoms. Among these patients, 4,122 (5.6%) had suspected Barrett’s esophagus, of which 24.2% had suspected long-segment Barrett’s esophagus (3 cm or longer). Among patients with uncomplicated GERD, the prevalence of suspected Barrett’s esophagus was 5.6%, and the prevalence of long-segment disease was 1.4%.

Although male sex, older age, and white race were significant risk factors for suspected Barrett’s esophagus and suspected long-segment disease, 23.6% of esophagogastroduodenoscopies were performed in white men older than 50 years. “We find that low-risk populations with uncomplicated GERD make up a significant number of esophagogastroduodenoscopies done for uncomplicated GERD,” the investigators wrote. “If esophagogastroduodenoscopies were limited to patients that met the AGA criteria of being male, white, and age over 50, we would have detected 34 of 47 (72.3%) of esophageal tumors and found suspected Barrett’s esophagus in nearly 10%, while reducing the burden of endoscopy by more than 75%.”

Hiatal hernia was a significant correlate of suspected Barrett’s esophagus (odds ratio, 1.6), the researchers noted. Esophagitis was not associated with suspected Barrett’s esophagus overall but did correlate with long-segment disease. Esophagitis might mask underlying short-segment Barrett’s esophagus, and short-segment Barrett’s esophagus might be milder in nature and more responsive to antisecretory therapy, the researchers said. They noted that severe (grade C/D) esophagitis was strongly linked with both short-segment and long-segment Barrett’s esophagus.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The researchers reported having no conflicts of interest.

SOURCE: Lin EC et al. Clin Gastroenterol Hepatol. 2019 Apr. doi: 10.1016/j.cgh.2018.08.066.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.

Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.

Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.

The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.

In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.

Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.

*This story was updated on Feb. 7, 2019.

SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

For adults with eosinophilic esophagitis, maintenance treatment with swallowed topical steroids was associated with significantly higher remission rates when compared with “steroid holidays” in a single-center retrospective observational study presented in the February issue of Clinical Gastroenterology and Hepatology.

At a median follow-up time of 5 years, the rate of complete (including clinical, endoscopic, and histologic) remission was 16.1% when patients were receiving swallowed topical steroids but only 1.3% when they were not on these or other maintenance therapies (that is, on “drug holidays”), reported Thomas Greuter, MD, of University Hospital Zürich and the Mayo Clinic in Rochester, Minn., and his associates. Swallowed topical steroids also were associated with significantly higher rates of each individual endpoint (P less than .001). Swallowed topical steroid therapy did not appear to cause dysplasia or mucosal atrophy, although esophageal candidiasis was confirmed in 2.7% of visits when patients were on treatment. “Given the good safety profile of low-dose swallowed topical steroid therapy, we advocate for prolonged treatment. Dose-finding trials are needed to achieve higher remission rates,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Several studies have confirmed the efficacy of short-term swallowed topical steroids for treating eosinophilic esophagitis, but only one small randomized trial has evaluated longer-term treatment, and participants were followed for only 1 year. Dr. Greuter and his associates therefore analyzed retrospective data from 229 adults in Switzerland who received swallowed topical steroids for eosinophilic esophagitis between 2000 and 2014. Induction therapy consisted of 1 mg swallowed topical steroids twice daily, allowing 2-4 weeks for a clinical response. Patients then received infinite maintenance therapy with 0.25 mg swallowed topical steroids twice daily. Patients tended to be male and diagnosed in their late 30s. Endoscopy commonly showed corrugated rings, white exudates, edema, and furrows, and 35% of patients had strictures. Peak eosinophil count typically was 25 cells per high-power frame.

Among 819 follow-up visits, 336 (41%) occurred when patients were on maintenance swallowed topical steroid therapy. The median duration of maintenance therapy prior to a follow-up visit was 347 days (interquartile range, 90-750 days) or 677 doses (IQR, 280-1413 doses). The rate of clinical remission was 31% when patients were on maintenance treatment but only 4.5% when they were not (P less than .001). Respective rates of endoscopic and histologic remission were 48.8% versus 17.8% (P less than .001) and 44.8% versus 10.1% (P less than .001). After accounting for numerous demographic and clinical variables, the only significant predictors of clinical remission were treatment with swallowed topical steroids (odds ratio, 16.98; 95% confidence interval, 6.69-43.09) and a negative family history of esophageal eosinophilia (OR, 4.02; 95% CI, 1.41-11.47).

This study excluded patients whose eosinophilic esophagitis had responded to proton pump inhibitor therapy. Also, the maintenance dose of swallowed topical steroid dose (0.25 mg twice daily) probably was too low to achieve efficacious drug levels in the esophageal mucosa, which could explain the high proportion of treatment-refractory cases, according to the researchers. Evaluating a higher maintenance dose “would be of particular interest in the future,” they added.

The Swiss National Science Foundation provided partial funding. Dr. Greuter disclosed a travel grant from Falk Pharma GmbH and Vifor and an unrestricted research grant from Novartis.

SOURCE: Greuter T et al. Clin Gastroenterol Hepatol. 2018 Jun 11.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.

The diagnosis of eosinophilic esophagitis no longer needs to include a trial of proton pump inhibitor (PPI) therapy, according to an updated international consensus statement published in the October issue of Gastroenterology.

Dr. Graham Beards/Wikimedia Commons/CC ASA 3.0

“An initial rationale for the PPI trial was to distinguish eosinophilic esophagitis from gastroesophageal reflux disease, but it is now known that these conditions have a complex relationship and are not necessarily mutually exclusive,” wrote Evan S. Dellon, MD, of the University of North Carolina at Chapel Hill, and his associates. According to current evidence, “PPIs are better classified as a treatment for esophageal eosinophilia that may be due to eosinophilic esophagitis than as a diagnostic criterion,” they said.

Diagnostic guidelines for eosinophilic esophagitis were published first in 2007 and were updated in 2011. The guideline authors recommended either pH monitoring or an 8-week trial of high-dose PPI therapy to rule out inflammation from gastroesophageal reflux disease (GERD).

But subsequent publications described patients with symptomatic esophageal eosinophilia who responded to PPIs and lacked classic GERD symptoms. Guidelines called this condition “PPI-responsive esophageal eosinophilia” and considered it a separate entity from GERD.

However, an “evolving body of research” shows that eosinophilic esophagitis can overlap with GERD, Dr. Dellon and his associates wrote. Furthermore, each of these conditions can trigger the other. Eosinophilic esophagitis can decrease esophageal compliance, leading to secondary reflux, while gastroesophageal reflux can erode the esophageal epithelium, triggering antigen exposure and eosinophilia.

Therefore, Dr. Dellon and his associates recommended defining eosinophilic esophagitis as signs and symptoms of esophageal dysfunction and an esophageal biopsy showing at least 15 eosinophils per high-power field, or approximately 60 eosinophils per millimeter, with infiltration limited to the esophagus. They stressed the importance of esophageal biopsy even if endoscopy shows normal mucosa. “As per prior guidelines, multiple biopsies from two or more esophageal levels, targeting areas of apparent inflammation, are recommended to increase the diagnostic yield,” they added. “Gastric and duodenal biopsies should be obtained as clinically indicated by symptoms, endoscopic findings in the stomach or duodenum, or high index of suspicion for a mucosal process.”

Physicians should increase their suspicion of eosinophilic esophagitis if patients have other types of atopy or endoscopic findings of “rings, furrows, exudates, edema, stricture, narrowing, and crepe-paper mucosa,” they added. In addition to GERD, they recommended looking carefully for other conditions that can trigger esophageal eosinophilia, such as pemphigus, drug hypersensitivity reactions, achalasia, and Crohn’s disease with esophageal involvement.

To create the guideline, Dr. Dellon and his associates searched PubMed for studies of all designs and sizes published from 1966 through December 2016. Teams of experts on specific topics then reviewed and discussed relevant literature. In May 2017, 43 reviewers met for 8 hours to present and discuss conclusions. There was 100% agreement to remove the PPI trial from the diagnostic criteria, the experts noted.

The authors disclosed financial support from the International Gastrointestinal Eosinophilic Diseases Researchers (TIGERS), The David and Denise Bunning Family, and the Rare Disease Clinical Research Network. Dr. Dellon disclosed consulting relationships and receiving research funding from Adare, Celgene/Receptos, Regeneron, and Shire among others. The majority of his coauthors also disclosed relationships with numerous medical companies.

SOURCE: Dellon ES et al. Gastroenterology. 2018 Jul 12. doi: 10.1053/j.gastro.2018.07.009.