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AGA CPU: Extraesophageal symptoms attributed to GERD
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
Barrett’s esophagus risk factor profile may predict progression
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Male sex, older age, smoking, greater segment length, and low-grade dysplasia separately predicted progression of Barrett’s esophagus.
Major finding: Pooled odds ratios for risk ranged from 4.3 (low-grade dysplasia) to 1.03 (older age).
Study details: Systematic review and meta-analysis of 20 studies published through May 2016.
Disclosures: The reviewers disclosed no external funding sources or conflicts of interest.
Source: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30.
Fundoplication works best for true PPI-refractory heartburn
WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.
Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week®.
“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.
The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.
This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.
The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.
The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.
Dr. Spechler had no disclosures to report.
WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.
Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week®.
“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.
The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.
This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.
The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.
The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.
Dr. Spechler had no disclosures to report.
WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.
Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week®.
“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.
The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.
This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.
The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.
The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.
Dr. Spechler had no disclosures to report.
REPORTING FROM DDW 2018
Key clinical point: Fundoplication produces the best outcomes in patients with true proton pump inhibitor–refractory heartburn.
Major finding: Two-thirds of patients treated with fundoplication had successful outcomes, compared with 28% in medical controls and 12% in placebo controls.
Study details: A multicenter, randomized study with 78 patients.
Disclosures: Dr. Spechler had no disclosures to report.
Barrett’s segment length, low-grade dysplasia tied to increased risk of neoplastic progression
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
REPORTING FROM DDW 2018
Key clinical point: Barrett’s segment length and low-grade dysplasia are associated with neoplastic progression.
Major finding: Low-grade dysplasia at baseline is associated with an increased risk of high-grade dysplasia or esophageal adenocarcinoma, hazard ratio of 2.38 (1.30 - 4.36).
Study details: This study was a prospective, multi-center cohort study involving 986 patients receiving treatment in six Dutch community-based hospitals from 2003 to 2017.
Disclosures: The study author did not report any financial disclosures.
Source: Klaver E et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
First reversal agent for apixaban and rivaroxaban gets fast-track approval
, according to a May 3 statement from Portola Pharmaceuticals.
It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.
Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.
“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.
The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.
Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.
He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”
The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.
The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.
Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*
The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.
*This article was updated on May 7, 2018.
, according to a May 3 statement from Portola Pharmaceuticals.
It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.
Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.
“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.
The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.
Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.
He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”
The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.
The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.
Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*
The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.
*This article was updated on May 7, 2018.
, according to a May 3 statement from Portola Pharmaceuticals.
It is approved for use in patients treated with these factor Xa inhibitors when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, according to the company.
Andexanet alfa (Andexxa, Portola) received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway.
“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, MD, professor of medicine and an electrophysiologist at McMaster University in Hamilton, Ont., who is chair of the ANNEXA-4 executive committee. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts,” he added in the statement.
The approval was supported by two phase 3 trials in the ANNEXA series, which showed acceptable change from baseline in anti-Factor Xa activity in healthy volunteers. But the strongest data came from interim results from ANNEXA-4, a single-arm cohort study with 227 patients who were receiving a factor Xa inhibitor and were experiencing an acute major bleeding event.
Clinicians administered andexanet alfa as a bolus followed by a 2-hour continuous infusion, with hemostatic efficacy assessed 12 hours after the start of treatment. The results showed that factor Xa inhibition fell by a median 90% for rivaroxaban and 93% for apixaban.
Andexanet alfa is a factor Xa “decoy” molecule that acts by latching onto the inhibitor molecules and thereby preventing them from interacting with actual factor Xa, but andexanet also has a short half life and hence the effect quickly reduces once treatment stops, Dr. Connelly reported at the American College of Cardiology annual meeting in March when presenting ANNEXA-4.
He noted at the time the results placed andexanet in the same ballpark for efficacy and safety as idarucizumab (Praxbind) approved in 2015 for reversing the anticoagulant dabigatran (Pradaxa)
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the Portola statement. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”
The prescribing information for andexanet states that treated patients should be monitored for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Further, anticoagulant therapy should be resumed as soon as medically appropriate following andexanet treatment to reduce thromboembolic risk.
The most common adverse reactions, occurring in at least 5% of patients, were urinary tract infections and pneumonia.
Portola intends to bring Andexxa to limited markets in early June; a broader commercial launch is anticipated in early 2019.*
The FDA is requiring a postmarketing clinical trial that randomizes patients to either andexanet or usual care. The study is scheduled to begin in 2019 and report outcomes in 2023.
*This article was updated on May 7, 2018.
AGA Clinical Practice Update: Screening for Barrett’s esophagus requires consideration for those most at risk
The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.
Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology.
Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.
Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.
Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.
Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.
Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.
Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.
Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.
A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.
Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).
With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.
While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.
“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”
The development of this commentary was supported solely by the American Gastroenterological Association Institute. No conflicts of interest were disclosed for this report.
SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).
AGA Resource
AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.
The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.
Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology.
Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.
Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.
Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.
Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.
Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.
Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.
Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.
A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.
Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).
With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.
While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.
“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”
The development of this commentary was supported solely by the American Gastroenterological Association Institute. No conflicts of interest were disclosed for this report.
SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).
AGA Resource
AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.
The evidence discussed in this article supports the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus be performed only in well-defined, high-risk populations. Alternative tests for screening are not now recommended; however, some of the alternative tests show great promise, and it is expected that they will soon find a useful place in clinical practice. At the same time, there should be a complementary focus on using demographic and clinical factors as well as noninvasive tools to further define populations for screening. All tests and tools should be balanced with the cost and potential risks of the screening proposed.
Stuart Spechler, MD, of the University of Texas and his colleagues looked at a variety of techniques, both conventional and novel, as well as the cost effectiveness of these strategies in a commentary published in the May issue of Gastroenterology.
Some studies have shown that endoscopic surveillance programs have identified early-stage cancer and provided better outcomes, compared with patients presenting after they already have cancer symptoms. One meta-analysis included 51 studies with 11,028 subjects and demonstrated that patients who had surveillance-detected esophageal adenocarcinoma (EAC) had a 61% reduction in their mortality risk. Other studies have shown similar results, but are susceptible to certain biases. Still other studies have refuted that the surveillance programs help at all. In fact, those with Barrett’s esophagus who died of EAC underwent similar surveillance, compared with controls, in those studies, showing that surveillance did very little to improve their outcomes.
Perhaps one of the most intriguing and cost-effective strategies is to identify patients with Barrett’s esophagus and develop a tool based on demographic and historical information. Tools like this have been developed, but have shown lukewarm results, with areas under the receiver operating characteristic curve (AUROC) ranging from 0.61 to 0.75. One study used information concerning obesity, smoking history, and increasing age, combined with weekly symptoms of gastroesophageal reflux and found that this improved results by nearly 25%. Modified versions of this model have also shown improved detection. When Thrift et al. added additional factors like education level, body mass index, smoking status, and more serious alarm symptoms like unexplained weight loss, the model was able to improve AUROC scores to 0.85 (95% confidence interval, 0.78-0.91). Of course, the clinical utility of these models is still unclear. Nonetheless, these models have influenced certain GI societies that only believe in endoscopic screening of patients with additional risk factors.
Although predictive models may assist in identifying at-risk patients, endoscopes are still needed to diagnose. Transnasal endoscopes (TNEs), the thinner cousins of the regular endoscope, tend to be better tolerated by patients and result in less gagging. One study showed that TNEs (45.7%) improved participation, compared with standard endoscopy (40.7%), and almost 80% of TNE patients were willing to undergo the procedure again. Despite the positives, TNEs provided significantly lower biopsy acquisitions than standard endoscopes (83% vs. 100%, P = .001) because of the sheathing on the endoscope. Other studies have demonstrated the strengths of TNEs, including a study in which 38% of patients had a finding that changed management of their disease. TNEs should be considered a reliable screening tool for Barrett’s esophagus.
Other advances in imaging technology like the advent of the high-resolution complementary metal oxide semiconductor (CMOS), which is small enough to fit into a pill capsule, have led researchers to look into its effectiveness as a screening tool for Barrett’s esophagus. One meta-analysis of 618 patients found that the pooled sensitivity and specificity for diagnosis were 77% and 86%, respectively. Despite its ability to produce high-quality images, the device remains difficult to control and lacks the ability to obtain biopsy samples.
Another example of a swallowed medical device, the Cytosponge-TFF3 is an ingestible capsule that degrades in stomach acid. After 5 minutes, the capsule dissolves and releases a mesh sponge that will be withdrawn through the mouth, scraping the esophagus and gathering a sample. The Cytosponge has proven effective in the Barrett’s Esophagus Screening Trials (BEST) 1. The BEST 2 looked at 463 control and 647 patients with Barrett’s esophagus across 11 United Kingdom hospitals. The trial showed that the Cytosponge exhibited sensitivity of 79.9%, which increased to 87.2% in patients with more than 3 cm of circumferential Barrett’s metaplasia.
Breaking from the invasive nature of imaging scopes and the Cytosponge, some researchers are looking to use “liquid biopsy” or blood tests to detect abnormalities in the blood like DNA or microRNA (miRNA) to identify precursors or presence of a disease. Much remains to be done to develop a clinically meaningful test, but the use of miRNAs to detect disease is an intriguing option. miRNAs control gene expression, and their dysregulation has been associated with the development of many diseases. One study found that patients with Barrett’s esophagus had increased levels of miRNA-194, 215, and 143 but these findings were not validated in a larger study. Other studies have demonstrated similar findings, but more research must be done to validate these findings in larger cohorts.
Other novel detection therapies have been investigated, including serum adipokine and electronic nose breathing tests. The serum adipokine test looks at the metabolically active adipokines secreted in obese patients and those with metabolic syndrome to see if they could predict the presence of Barrett’s esophagus. Unfortunately, the data appear to be conflicting, but these tests can be used in conjunction with other tools to detect Barrett’s esophagus. Electronic nose breathing tests also work by detecting metabolically active compounds from human and gut bacterial metabolism. One study found that analyzing these volatile compounds could delineate between Barrett’s and non-Barrett’s patients with 82% sensitivity, 80% specificity, and 81% accuracy. Both of these technologies need large prospective studies in primary care to validate their clinical utility.
A discussion of the effectiveness of these screening tools would be incomplete without a discussion of their costs. Currently, endoscopic screening costs are high. Therefore, it is important to reserve these tools for the patients who will benefit the most – in other words, patients with clear risk factors for Barrett’s esophagus. Even the capsule endoscope is quite expensive because of the cost of materials associated with the tool.
Cost-effectivenes calculations surrounding the Cytosponge are particularly complicated. One analysis found the computed incremental cost-effectiveness ratio (ICER) of endoscopy, compared with Cytosponge, to have a range of $107,583-$330,361. The potential benefit that Cytosponge offers comes at an ICER for Cytosponge screening, compared with no screening, that ranges from $26,358 to $33,307. The numbers skyrocket when you consider what society would be willing to pay (up to $50,000 per quality-adjusted life-year gained).
With all of this information in mind, it would be useful to look at Barrett’s esophagus and the tools used to diagnose it from a broader perspective.
While the adoption of a new screening strategy could succeed where others have failed, Dr. Spechler points out the potential harm.
“There also is potential for harm in identifying asymptomatic patients with Barrett’s esophagus. In addition to the high costs and small risks of standard endoscopy, the diagnosis of Barrett’s esophagus can cause psychological stress, have a negative impact on quality of life, result in higher premiums for health and life insurance, and might identify innocuous lesions that lead to potentially hazardous invasive treatments. Efforts should therefore be continued to combine biomarkers for Barrett’s with risk stratification. Overall, while these vexing uncertainties must temper enthusiasm for the unqualified endorsement of any screening test for Barrett’s esophagus, the alternative of making no attempt to stem the rapidly rising incidence of a lethal malignancy also is unpalatable.”
The development of this commentary was supported solely by the American Gastroenterological Association Institute. No conflicts of interest were disclosed for this report.
SOURCE: Spechler S et al. Gastroenterology. 2018 May doi: 10.1053/j.gastro.2018.03.031).
AGA Resource
AGA patient education on Barrett’s esophagus will help your patients better understand the disease and how to manage it. Learn more at gastro.org/patient-care.
FROM GASTROENTEROLOGY
PPI use not linked to cognitive decline
Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.
“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.
Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.
To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.
In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.
The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).
Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.
“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”
Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.
SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.
Over the last 20 years, there have been multiple retrospective studies which have shown associations between the use of proton pump inhibitors (PPIs) and a wide constellation of serious medical complications. However, detecting an association between a drug and a complication does not necessarily indicate that the drug was indeed responsible.
This well-done study by Wod et al, which shows no significant association between PPI use and decreased cognition and cognitive decline will, I hope, serve to allay any misplaced concerns that may exist among clinicians and patients about PPI use in this population. This paper has notable strengths, most importantly having access to results of a direct, unbiased assessment of changes in cognitive function over time and accurate assessment of PPI exposure. Short of performing a controlled, prospective trial, we are unlikely to see better evidence indicating a lack of a causal relationship between PPI use and changes in cognitive function. This provides assurance that patients with indications for PPI use can continue to use them.
Laura E. Targownik, MD, MSHS, FRCPC, is section head, section of gastroenterology, University of Manitoba, Winnipeg, Canada; Gastroenterology and Endoscopy Site Lead, Health Sciences Centre, Winnipeg; associate director, University of Manitoba Inflammatory Bowel Disease Research Centre; associate professor, department of internal medicine, section of gastroenterology, University of Manitoba. She has no conflicts of interest.
Over the last 20 years, there have been multiple retrospective studies which have shown associations between the use of proton pump inhibitors (PPIs) and a wide constellation of serious medical complications. However, detecting an association between a drug and a complication does not necessarily indicate that the drug was indeed responsible.
This well-done study by Wod et al, which shows no significant association between PPI use and decreased cognition and cognitive decline will, I hope, serve to allay any misplaced concerns that may exist among clinicians and patients about PPI use in this population. This paper has notable strengths, most importantly having access to results of a direct, unbiased assessment of changes in cognitive function over time and accurate assessment of PPI exposure. Short of performing a controlled, prospective trial, we are unlikely to see better evidence indicating a lack of a causal relationship between PPI use and changes in cognitive function. This provides assurance that patients with indications for PPI use can continue to use them.
Laura E. Targownik, MD, MSHS, FRCPC, is section head, section of gastroenterology, University of Manitoba, Winnipeg, Canada; Gastroenterology and Endoscopy Site Lead, Health Sciences Centre, Winnipeg; associate director, University of Manitoba Inflammatory Bowel Disease Research Centre; associate professor, department of internal medicine, section of gastroenterology, University of Manitoba. She has no conflicts of interest.
Over the last 20 years, there have been multiple retrospective studies which have shown associations between the use of proton pump inhibitors (PPIs) and a wide constellation of serious medical complications. However, detecting an association between a drug and a complication does not necessarily indicate that the drug was indeed responsible.
This well-done study by Wod et al, which shows no significant association between PPI use and decreased cognition and cognitive decline will, I hope, serve to allay any misplaced concerns that may exist among clinicians and patients about PPI use in this population. This paper has notable strengths, most importantly having access to results of a direct, unbiased assessment of changes in cognitive function over time and accurate assessment of PPI exposure. Short of performing a controlled, prospective trial, we are unlikely to see better evidence indicating a lack of a causal relationship between PPI use and changes in cognitive function. This provides assurance that patients with indications for PPI use can continue to use them.
Laura E. Targownik, MD, MSHS, FRCPC, is section head, section of gastroenterology, University of Manitoba, Winnipeg, Canada; Gastroenterology and Endoscopy Site Lead, Health Sciences Centre, Winnipeg; associate director, University of Manitoba Inflammatory Bowel Disease Research Centre; associate professor, department of internal medicine, section of gastroenterology, University of Manitoba. She has no conflicts of interest.
Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.
“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.
Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.
To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.
In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.
The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).
Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.
“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”
Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.
SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.
Use of proton pump inhibitors (PPIs) is not associated with cognitive decline in two prospective, population-based studies of identical twins published in the May issue of Clinical Gastroenterology and Hepatology.
“No stated differences in [mean cognitive] scores between PPI users and nonusers were significant,” wrote Mette Wod, PhD, of the University of Southern Denmark, Odense, with her associates.
Past research has yielded mixed findings about whether using PPIs affects the risk of dementia. Preclinical data suggest that exposure to these drugs affects amyloid levels in mice, but “the evidence is equivocal, [and] the results of epidemiologic studies [of humans] have also been inconclusive, with more recent studies pointing toward a null association,” the investigators wrote. Furthermore, there are only “scant” data on whether long-term PPI use affects cognitive function, they noted.
To help clarify the issue, they analyzed prospective data from two studies of twins in Denmark: the Study of Middle-Aged Danish Twins, in which individuals underwent a five-part cognitive battery at baseline and then 10 years later, and the Longitudinal Study of Aging Danish Twins, in which participants underwent the same test at baseline and 2 years later. The cognitive test assessed verbal fluency, forward and backward digit span, and immediate and delayed recall of a 12-item list. Using data from a national prescription registry, the investigators also estimated individuals’ PPI exposure starting 2 years before study enrollment.
In the study of middle-aged twins, participants who used high-dose PPIs before study enrollment had cognitive scores that were slightly lower at baseline, compared with PPI nonusers. Mean baseline scores were 43.1 (standard deviation, 13.1) and 46.8 (SD, 10.2), respectively. However, after researchers adjusted for numerous clinical and demographic variables, the between-group difference in baseline scores narrowed to just 0.69 (95% confidence interval, –4.98 to 3.61), which was not statistically significant.
The longitudinal study of older twins yielded similar results. Individuals who used high doses of PPIs had slightly higher adjusted mean baseline cognitive score than did nonusers, but the difference did not reach statistical significance (0.95; 95% CI, –1.88 to 3.79).
Furthermore, prospective assessments of cognitive decline found no evidence of an effect. In the longitudinal aging study, high-dose PPI users had slightly less cognitive decline (based on a smaller change in test scores over time) than did nonusers, but the adjusted difference in decline between groups was not significant (1.22 points; 95% CI, –3.73 to 1.29). In the middle-aged twin study, individuals with the highest levels of PPI exposure (at least 1,600 daily doses) had slightly less cognitive decline than did nonusers, with an adjusted difference of 0.94 points (95% CI, –1.63 to 3.50) between groups, but this did not reach statistical significance.
“This study is the first to examine the association between long-term PPI use and cognitive decline in a population-based setting,” the researchers concluded. “Cognitive scores of more than 7,800 middle-aged and older Danish twins at baseline did not indicate an association with previous PPI use. Follow-up data on more than 4,000 of these twins did not indicate that use of this class of drugs was correlated to cognitive decline.”
Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.
SOURCE: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Use of proton pump inhibitors was not associated with cognitive decline.
Major finding: Mean baseline cognitive scores did not significantly differ between PPI users and nonusers, nor did changes in cognitive scores over time.
Study details: Two population-based studies of twins in Denmark.
Disclosures: Odense University Hospital provided partial funding. Dr. Wod had no disclosures. Three coinvestigators disclosed ties to AstraZeneca and Bayer AG.
Source: Wod M et al. Clin Gastro Hepatol. 2018 Feb 3. doi: 10.1016/j.cgh.2018.01.034.
Use these two questions to simplify H. pylori treatment choice
Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.
The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.
The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.
Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:
- Is there a penicillin allergy?
- Has there been previous macrolide exposure?
“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.
“Bismuth quadruple therapy is never the wrong answer,” he added.
Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.
Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H2 blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.
Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.
If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.
Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.
Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.
Global Academy and this news organization are owned by the same parent company.
Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.
Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.
The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.
The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.
Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:
- Is there a penicillin allergy?
- Has there been previous macrolide exposure?
“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.
“Bismuth quadruple therapy is never the wrong answer,” he added.
Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.
Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H2 blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.
Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.
If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.
Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.
Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.
Global Academy and this news organization are owned by the same parent company.
Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.
Recent clinical guidelines have expanded not only the pool of patients who should be tested for Helicobacter pylori infection, but also the number of first-line treatment strategies clinicians should consider.
The American College of Gastroenterology guidelines from 2007 recommended just two treatments: clarithromycin-based triple therapy or bismuth-based quadruple therapy.
The 2017 update to ACG guidelines adds five additional recommended treatment possibilities, not all of which have been well studied in U.S. clinical practice, Colin W. Howden, MD, AGAF, said in a presentation at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.
“There are a variety of options, and unfortunately for us as practitioners, antibiotic sensitivity testing is not routinely or easily available in contemporary U.S. practice,” said Dr. Howden, professor of medicine–gastroenterology at the University of Tennessee Health Sciences Center, Memphis.
Dr. Howden, a coauthor of the latest ACG guidelines, said asking two pointed questions outlined in the document can help simplify the treatment decision:
- Is there a penicillin allergy?
- Has there been previous macrolide exposure?
“The ideal situation is that the patient is not penicillin allergic, and they’ve never had a macrolide before,” Dr. Howden said. In that case, bismuth-based quadruple therapy would be an appropriate choice.
“Bismuth quadruple therapy is never the wrong answer,” he added.
Clarithromycin-based triple therapy might be considered, according to Dr. Howden, if the local rate of resistance to H. pylori is known to be low.
Bismuth-based quadruple therapy consists of a proton pump inhibitor (PPI) or H2 blocker, bismuth, tetracycline, and metronidazole for 10-14 days, while clarithromycin triple therapy consists of a PPI, clarithromycin, and amoxicillin or metronidazole for 10-14 days.
Several other options recently added to the guidelines have been tried in this scenario, he noted, including concomitant therapy, which consists of a PPI, clarithromycin, amoxicillin, and metronidazole for 10-14 days.
If there has been previous macrolide use but the patient is not penicillin allergic, bismuth quadruple therapy is again recommended, Dr. Howden said, and an additional approach might be the introduction of a levofloxacin-based regimen, as outlined in the guidelines.
Conversely, if there has been no previous macrolide use but the patient is confirmed to be penicillin allergic, the current guideline-recommended options are limited to bismuth quadruple therapy, or clarithromycin triple therapy with metronidazole instead of amoxicillin, Dr. Howden said at the meeting.
Finally, for penicillin-allergic patients with previous macrolide use, recommended options are whittled down to just bismuth-based quadruple therapy. “Again, it’s never the wrong answer,” Dr. Howden said.
Global Academy and this news organization are owned by the same parent company.
Dr. Howden reported disclosures related to Horizon, Otsuka, Allergan, Aralaez, EndoStim, Ironwood, Pfizer, and SynteractHCR.
EXPERT ANALYSIS FROM PERSPECTIVES IN DIGESTIVE DISEASES
High Cajal cell count with gastric electrical stimulation improves symptoms for refractory gastroparesis patients
and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.
Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.
“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.
The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”
After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.
After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).
Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).
Nausea and vomiting symptoms significantly improved in the group with ICC greater than or equal to 2.00 (vomiting change, –2.07; P less than .001 and bloating change, –1.80; P less than .001) with a weaker association with symptom improvement in the group with ICC less than 2.00 (vomiting change, –1.65; P =.035 and bloating change, –1.00; P = 0.86). TSS improved by 52% in the ICC group with greater than or equal to 2.00 (P = .002) and by 29.6% in the ICC less than 2.00 group (P = .047).
“The observation that some patients with severe depletion of ICC showed improvement in symptoms might indicate differential loss of specific type of ICC cells,” Dr. Abell and his colleagues wrote. “Better understanding of response to GES in patients with particular type of ICC loss might shed light on the mechanism of GES, as well as predicting and selecting patients who respond better. Future studies should focus on stratifying patients based on predominant type of ICC loss as it relates to severity of symptoms and response to GES.”
Dr. Abell is the founder of ADEPT-GI and has intellectual property rights related to the technology in this study. The other authors declare no relevant financial disclosures.
SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.
*This story was updated on 4/30/2018.
and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.
Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.
“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.
The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”
After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.
After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).
Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).
Nausea and vomiting symptoms significantly improved in the group with ICC greater than or equal to 2.00 (vomiting change, –2.07; P less than .001 and bloating change, –1.80; P less than .001) with a weaker association with symptom improvement in the group with ICC less than 2.00 (vomiting change, –1.65; P =.035 and bloating change, –1.00; P = 0.86). TSS improved by 52% in the ICC group with greater than or equal to 2.00 (P = .002) and by 29.6% in the ICC less than 2.00 group (P = .047).
“The observation that some patients with severe depletion of ICC showed improvement in symptoms might indicate differential loss of specific type of ICC cells,” Dr. Abell and his colleagues wrote. “Better understanding of response to GES in patients with particular type of ICC loss might shed light on the mechanism of GES, as well as predicting and selecting patients who respond better. Future studies should focus on stratifying patients based on predominant type of ICC loss as it relates to severity of symptoms and response to GES.”
Dr. Abell is the founder of ADEPT-GI and has intellectual property rights related to the technology in this study. The other authors declare no relevant financial disclosures.
SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.
*This story was updated on 4/30/2018.
and researchers suggested patients with depleted Cajal cells who did not improve could have lost certain Cajal cells.
Thomas L. Abell, MD, from the department of medicine and division of gastroenterology, hepatology and nutrition at the University of Louisville (Ky.) and his colleagues recruited 23 patients with drug-refractory gastroparesis to undergo gastric electrical stimulation (GES) therapy for 12 months. Patients were white females with a mean age of 45.7 years. They performed a gastric-emptying test before therapy; the composite symptom scores were 23.89 plus or minus 34.10 for 4-hour gastric emptying in the group with interstitial cells of Cajal (ICC) less than 2.00 and a 22.62 plus or minus 25.51 in the group with ICC greater than or equal to 2.00.
“We believe neurostimulation might modify or augment the function of ICC cells. However, in patients with severe depletion, the ICC density might be too sparse to be augmented and hence contribute to suboptimal response to GES,” Dr. Abell and colleagues wrote in their study.
The GES system consisted of an “implanted pulse generator, two leads, and the stimulator programmer.” Patients used a trial GES system for 1-2 weeks, in which a “temporary lead is placed endoscopically through the nose and inserted into the gastric mucosa in the middle of the stomach.”
After the trial GES system, the researchers performed a gastric wall biopsy to determine ICC counts to divide the patients into two groups: those with less than 2 ICC and those with greater than or equal to 2 ICC (per high power field). Following the trial, a more permanent system was implanted and researchers analyzed results after 12 months with the Student t test, patient-reported symptom assessment, and Total Symptom Score (TSS) using a Likert scale.
After GES, 1-hour gastric emptying improved in the group with ICC greater than or equal to 2.00 from pretreatment (75.47 plus or minus 13.80) to posttreatment (57.97 plus or minus 21.34) with a mean between-group difference of 17.5% (95% confidence interval, 1.41-33.58; P = .035). Dr. Abell and colleagues noted a nonstatistically significant improvement in 2-hour (mean between-group difference, 8%) and 4-hour (4%) gastric emptying (P = .032). Compared with pretreatment, patients with an ICC count less that 2 showed no significant change at 1-hour (63.78 plus or minus 26.01 vs. 68.86 plus or minus 33.14; P = .646), 7% worsening at 2-hour (41.22 plus or minus 33.44 vs. 49.37 plus or minus 34.21; P = .343) and 7% worsening at 4-hour gastric emptying (23.89 plus or minus 34.10 vs. 30.82 plus or minus 30.82; P = .166).
Researchers found patients with “normal to moderate depletion of ICC counts” had a significantly higher change in serosal amplitude, with a mean amplitude change of 0.19 (P = .05). Patients with “severe depletion of ICC” showed no significant change in amplitude (mean amplitude change, 0.01; P = .79). Among patients with normal or moderate depletion of ICC, the pre-GES serosal frequency was 3.96 plus or minus 1.02 and the post-GES frequency was 3.83 plus or minus 1.36 (P = .79), while the patients with severe depletion of ICC had a pre-GES frequency of 4.67 plus or minus 1.57 and a post-GES frequency of 4.23 plus or minus 1.30 (P = .54).
Nausea and vomiting symptoms significantly improved in the group with ICC greater than or equal to 2.00 (vomiting change, –2.07; P less than .001 and bloating change, –1.80; P less than .001) with a weaker association with symptom improvement in the group with ICC less than 2.00 (vomiting change, –1.65; P =.035 and bloating change, –1.00; P = 0.86). TSS improved by 52% in the ICC group with greater than or equal to 2.00 (P = .002) and by 29.6% in the ICC less than 2.00 group (P = .047).
“The observation that some patients with severe depletion of ICC showed improvement in symptoms might indicate differential loss of specific type of ICC cells,” Dr. Abell and his colleagues wrote. “Better understanding of response to GES in patients with particular type of ICC loss might shed light on the mechanism of GES, as well as predicting and selecting patients who respond better. Future studies should focus on stratifying patients based on predominant type of ICC loss as it relates to severity of symptoms and response to GES.”
Dr. Abell is the founder of ADEPT-GI and has intellectual property rights related to the technology in this study. The other authors declare no relevant financial disclosures.
SOURCE: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.
*This story was updated on 4/30/2018.
FROM JOURNAL OF CLINICAL GASTROENTEROLOGY
Key clinical point: Higher Cajal cell counts were linked to improved symptoms and gastric electrical activity in patients with drug-refractory gastroparesis who underwent neurostimulation.
Major finding: The rate of 1-hour gastric emptying significantly improved in patients with interstitial cells of Cajal greater than or equal to two after gastric electrical stimulation with a mean group difference of 17.5%, as well as a mean serosal amplitude change of 0.19.
Study details: A single-center study of 23 women with drug-refractory gastroparesis recruited from the gastric motility clinic at the University of Mississippi.
Disclosures: Dr. Abell is the founder of ADEPT-GI and has intellectual property rights related to the technology in this study. The other authors declare no relevant financial disclosures.
Source: Omer E et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001025.
Model predicted Barrett’s esophagus progression
A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).
Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.
Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).
The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).
Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”
There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.
SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma (EAC), a rapidly rising cancer in the Western world, which has a poor 5-year survival rate of less than 20%. Management strategies to affect EAC incidence include screening and surveillance, with current guidelines recommending surveillance for all patients with a diagnosis of BE.
However, there are several challenges associated with adopting BE surveillance for all patients: It is estimated that anywhere from 2 million to 5 million U.S. adults may harbor BE, and the overall risk of BE progression to EAC is low (approximately 0.2%-0.4% annually). Both of these factors influence the cost-effectiveness of a global BE surveillance program.
Hence, a risk-stratification score that can distinguish BE patients who are at high risk for progression to high-grade dysplasia (HGD) and/or EAC from those whose disease will not progress will be extremely useful. This concept would be similar to other risk-scoring mechanisms, such as the MELD score for progression in liver disease.
With use of a large multicenter cohort of patients with BE (more than 4,500 patients), this is the first risk-prediction score developed and validated using baseline demographic and endoscopy information to determine risk of progression. Readily available factors such as patient sex, smoking status, BE length, and confirmed histology were identified as risk factors for progression, which could then generate a score determining the individual patient’s risk of progression. Such a simple scoring system has the potential of tailoring management based on the risk factors. In the future, inclusion of molecular biomarkers along with this score may further enhance its potential for personalized medicine in BE patients.
Prateek Sharma, MD, is a professor of medicine of University of Kansas, Kansas City. He has no conflicts of interest.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma (EAC), a rapidly rising cancer in the Western world, which has a poor 5-year survival rate of less than 20%. Management strategies to affect EAC incidence include screening and surveillance, with current guidelines recommending surveillance for all patients with a diagnosis of BE.
However, there are several challenges associated with adopting BE surveillance for all patients: It is estimated that anywhere from 2 million to 5 million U.S. adults may harbor BE, and the overall risk of BE progression to EAC is low (approximately 0.2%-0.4% annually). Both of these factors influence the cost-effectiveness of a global BE surveillance program.
Hence, a risk-stratification score that can distinguish BE patients who are at high risk for progression to high-grade dysplasia (HGD) and/or EAC from those whose disease will not progress will be extremely useful. This concept would be similar to other risk-scoring mechanisms, such as the MELD score for progression in liver disease.
With use of a large multicenter cohort of patients with BE (more than 4,500 patients), this is the first risk-prediction score developed and validated using baseline demographic and endoscopy information to determine risk of progression. Readily available factors such as patient sex, smoking status, BE length, and confirmed histology were identified as risk factors for progression, which could then generate a score determining the individual patient’s risk of progression. Such a simple scoring system has the potential of tailoring management based on the risk factors. In the future, inclusion of molecular biomarkers along with this score may further enhance its potential for personalized medicine in BE patients.
Prateek Sharma, MD, is a professor of medicine of University of Kansas, Kansas City. He has no conflicts of interest.
Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma (EAC), a rapidly rising cancer in the Western world, which has a poor 5-year survival rate of less than 20%. Management strategies to affect EAC incidence include screening and surveillance, with current guidelines recommending surveillance for all patients with a diagnosis of BE.
However, there are several challenges associated with adopting BE surveillance for all patients: It is estimated that anywhere from 2 million to 5 million U.S. adults may harbor BE, and the overall risk of BE progression to EAC is low (approximately 0.2%-0.4% annually). Both of these factors influence the cost-effectiveness of a global BE surveillance program.
Hence, a risk-stratification score that can distinguish BE patients who are at high risk for progression to high-grade dysplasia (HGD) and/or EAC from those whose disease will not progress will be extremely useful. This concept would be similar to other risk-scoring mechanisms, such as the MELD score for progression in liver disease.
With use of a large multicenter cohort of patients with BE (more than 4,500 patients), this is the first risk-prediction score developed and validated using baseline demographic and endoscopy information to determine risk of progression. Readily available factors such as patient sex, smoking status, BE length, and confirmed histology were identified as risk factors for progression, which could then generate a score determining the individual patient’s risk of progression. Such a simple scoring system has the potential of tailoring management based on the risk factors. In the future, inclusion of molecular biomarkers along with this score may further enhance its potential for personalized medicine in BE patients.
Prateek Sharma, MD, is a professor of medicine of University of Kansas, Kansas City. He has no conflicts of interest.
A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).
Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.
Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).
The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).
Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”
There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.
SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.
A scoring model encompassing just four traits accurately predicted which patients with Barrett’s esophagus were most likely to develop high-grade dysplasia or esophageal adenocarcinoma, researchers reported in the April issue of Gastroenterology (2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009).
Those risk factors included sex, smoking, length of Barrett’s esophagus, and the presence of baseline low-grade dysplasia, said Sravanthi Parasa, MD, of Swedish Medical Center, Seattle, and her associates. For example, a male with a history of smoking found to have a 5-cm, nondysplastic Barrett’s esophagus on histology during his index endoscopy would fall into the model’s intermediate risk category, with a 0.7% annual risk of progression to high-grade dysplasia or esophageal adenocarcinoma, they explained. “This model has the potential to complement molecular biomarker panels currently in development,” they wrote.
Barrett’s esophagus increases the risk of esophageal adenocarcinoma by anywhere from 30 to 125 times, a range that reflects the multifactorial nature of progression and the hypothesis that not all patients with Barrett’s esophagus should undergo the same frequency of endoscopic surveillance, said the researchers. To incorporate predictors of progression into a single model, they analyzed prospective data from nearly 3,000 patients with Barrett’s esophagus who were followed for a median of 6 years at five centers in the United States and one center in the Netherlands. At baseline, patients were an average of 55 years old (standard deviation, 20 years), 84% were men, 88% were white, and the average Barrett’s esophagus length was 3.7 cm (SD, 3.2 cm).
The researchers created the model by starting with many demographic and clinical candidate variables and then using backward selection to eliminate those that did not predict progression with a P value of .05 or less. This is the same method used in the Framingham Heart Study, they noted. In all, 154 (6%) patients with Barrett’s esophagus developed high-grade dysplasia or esophageal adenocarcinoma, with an annual progression rate of about 1%. The significant predictors of progression included male sex, smoking, length of Barrett’s esophagus, and low-grade dysplasia at baseline. A model that included only these four variables distinguished progressors from nonprogressors with a c statistic of 0.76 (95% confidence interval, 0.72 to 0.80; P less than .001). Using 30% of patients as an internal validation cohort, the model’s calibration slope was 0.99 and its calibration intercept was -0.09 cohort (perfectly calibrated models have a slope of 1.0 and an intercept of 0.0).
Therefore, the model was well calibrated and did an appropriate job of identifying risk groups, the investigators concluded. Considering that the overall risk of Barrett’s esophagus progression is low, using this model could help avoid excess costs and burdens of unnecessary surveillance, they added. “We recognize that there is a key interest in contemporary medical research whether a marker (e.g. molecular, genetic) could add to incremental value of a risk progression score,” they wrote. “This can be an area of future research.”
There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.
SOURCE: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.
FROM GASTROENTEROLOGY
Key clinical point: A model containing four risk factors identified patients with Barrett’s esophagus at significantly increased risk of progression to high-grade dysplasia or esophageal adenocarcinoma.
Major finding: Scores assigned identified patients with BE that progressed to HGD or EAC with a c statistic of 0.76 (95% CI, 0.72 to 0.80; P less than .001).
Data source: A multicenter, longitudinal study of 2,697 patients with Barrett’s esophagus.
Disclosures: There were no funding sources. Dr. Parasa had no disclosures. One coinvestigator disclosed ties to Cook Medical, CDx Diagnostics, and Cosmo Pharmaceuticals.
Source: Parasa S et al. Gastroenterology. 2017 Dec 19. doi: 10.1053/j.gastro.2017.12.009.