From the AGA Journals

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.

Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.

Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.

IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.

In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.

Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).

Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.

The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
 

SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.

Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.

Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.

IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.

In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.

Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).

Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.

The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
 

SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.

Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.

Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.

IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.

In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.

Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).

Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.

The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
 

SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.

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

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

For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.

Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.

Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.

Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.

Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).

Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”

An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.

SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.

For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.

Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.

Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.

Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.

Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).

Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”

An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.

SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.

For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.

Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.

Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.

Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.

Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).

Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”

An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.

SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.

Middle-aged and older adults who closely followed a Mediterranean-style diet for 6 years were at significantly lower risk of developing fatty liver disease than others in a large prospective study.

Each 1-standard-deviation rise in Mediterranean-style Diet Score (MDS) correlated with significantly decreased hepatic fat accumulation and a 26% lower odds of new onset fatty liver disease (P = .002). “To our knowledge, ours is the first prospective study to examine the relations of long-term habitual diet to fatty liver,” Jiantao Ma, MBBS, PhD, and his associates wrote in Gastroenterology. “Our findings indicate that improved diet quality may be particularly important for those with high genetic risk for NAFLD.”

Lisovskaya/ThinkStock

SOURCE: Ma J, et al. Gastroenterology. 2018 Mar 28. doi: 10.1053/j.gastro.2018.03.038

Middle-aged and older adults who closely followed a Mediterranean-style diet for 6 years were at significantly lower risk of developing fatty liver disease than others in a large prospective study.

Each 1-standard-deviation rise in Mediterranean-style Diet Score (MDS) correlated with significantly decreased hepatic fat accumulation and a 26% lower odds of new onset fatty liver disease (P = .002). “To our knowledge, ours is the first prospective study to examine the relations of long-term habitual diet to fatty liver,” Jiantao Ma, MBBS, PhD, and his associates wrote in Gastroenterology. “Our findings indicate that improved diet quality may be particularly important for those with high genetic risk for NAFLD.”

Lisovskaya/ThinkStock

SOURCE: Ma J, et al. Gastroenterology. 2018 Mar 28. doi: 10.1053/j.gastro.2018.03.038

Middle-aged and older adults who closely followed a Mediterranean-style diet for 6 years were at significantly lower risk of developing fatty liver disease than others in a large prospective study.

Each 1-standard-deviation rise in Mediterranean-style Diet Score (MDS) correlated with significantly decreased hepatic fat accumulation and a 26% lower odds of new onset fatty liver disease (P = .002). “To our knowledge, ours is the first prospective study to examine the relations of long-term habitual diet to fatty liver,” Jiantao Ma, MBBS, PhD, and his associates wrote in Gastroenterology. “Our findings indicate that improved diet quality may be particularly important for those with high genetic risk for NAFLD.”

Lisovskaya/ThinkStock

SOURCE: Ma J, et al. Gastroenterology. 2018 Mar 28. doi: 10.1053/j.gastro.2018.03.038

Inflammatory bowel disease (IBD) and Crohn’s disease (CD), in particular, are characterized by an unusual ectopic extension of mesenteric adipose tissue. This intra-abdominal fat, also known as “creeping fat,” which wraps around the intestine during the onset of CD, is associated with inflammation and ulceration of the small or large intestine. The role of this fat in the development of CD, and whether it is protective or harmful, however, is not clear.

The current study demonstrates that adipose-derived stromal cells (ADSCs), the precursor cell population of adipose tissue, promote colonocyte proliferation and exhibit a differential gene expression profile in a disease-dependent manner. CD patient–derived ADSCs attenuated the severity of experimental colitis by releasing extracellular mediators, which exhibits a protective role for mesenteric adipose tissue during intestinal inflammation, according to Jill M. Hoffman, MD, and her colleagues at the University of California, Los Angeles. Increased expression and release of lactoferrin by ADSCs – an iron-binding glycoprotein and antimicrobial peptide usually found in large quantities in breast milk – was shown to be a likely mediator that could regulate inflammatory responses during CD. These results were published in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2018.02.001).

Intestinal inflammation is primarily mediated by cytokine production, and targeted anticytokine therapy is the current standard for IBD treatment. The cytokine profile from CD patient–derived mesenteric ADSCs and fat tissue was significantly different from that of these patients’ disease-free counterparts. The authors hypothesized that mesenteric ADSCs release adipokines in response to disease-associated signals; this release of adipokines results from differential gene expression of mesenteric ADSCs in CD versus control patients. To test this hypothesis, conditioned media from CD patient–derived ADSCs was used to study gene expression in colonic intestinal epithelial cells in vitro and in mice with experimental colitis in vivo.

Using the Human LncRNA Expression Microarray V4.0, expression of 20,730 protein-coding mRNA targets was analysed, and 992 mRNA transcripts were found to be differentially (less than or equal to twofold change) expressed in CD patient–derived ADSCs, compared with control patient–derived ADSCs. Subsequent pathway analysis suggested activation of cellular growth and proliferation pathways with caspase 8 and p42/44 as top predicted networks that are differentially regulated in CD patient–derived ADSCs with respect to those of control patients.

The investigators treated intestinal epithelial cells – specifically, NCM460 – with conditioned 233 media from the same CD or control patient–derived ADSCs; subsequent microarray profiling using the GeneChip Human Gene ST Array showed increased expression of interleukin-17A, CCL23, and VEGFA. Ingenuity Pathway Analysis of mRNA expression indicated convergence in injury and inflammation pathways with the SERPINE1 gene, which suggests it’s the central regulator of the differential gene expression network.

In vivo, mice with active dextran sulfate sodium (DSS) colitis that were treated with daily injections of conditioned media from CD patients showed attenuation of colitis as compared with mice treated with vehicle or conditioned media from control patients. Furthermore, the mRNA expression of proinflammatory cytokines was reduced with increased proliferative response (as measured by Ki67 expression) in intestinal epithelial cells in the dextran sulfate sodium–treated mice receiving media from CD patients, compared with that in mice receiving media from control patients or vehicle-treated mice.

Cell proliferation was studied in real time (during a period of 120 hours) using the xCELLigence platform. The authors suggested that mesenteric adipose tissue–derived mediators may regulate proliferative responses in intestinal epithelial cells during intestinal inflammation, as observed by enhanced cell-doubling time in conditioned media from CD patient–derived ADSCs.

SOURCE: Hoffman J et al. Cell Molec Gastro Hepatol. doi: 10.1016/j.jcmgh.2018.02.001.

Inflammatory bowel disease (IBD) and Crohn’s disease (CD), in particular, are characterized by an unusual ectopic extension of mesenteric adipose tissue. This intra-abdominal fat, also known as “creeping fat,” which wraps around the intestine during the onset of CD, is associated with inflammation and ulceration of the small or large intestine. The role of this fat in the development of CD, and whether it is protective or harmful, however, is not clear.

The current study demonstrates that adipose-derived stromal cells (ADSCs), the precursor cell population of adipose tissue, promote colonocyte proliferation and exhibit a differential gene expression profile in a disease-dependent manner. CD patient–derived ADSCs attenuated the severity of experimental colitis by releasing extracellular mediators, which exhibits a protective role for mesenteric adipose tissue during intestinal inflammation, according to Jill M. Hoffman, MD, and her colleagues at the University of California, Los Angeles. Increased expression and release of lactoferrin by ADSCs – an iron-binding glycoprotein and antimicrobial peptide usually found in large quantities in breast milk – was shown to be a likely mediator that could regulate inflammatory responses during CD. These results were published in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2018.02.001).

Intestinal inflammation is primarily mediated by cytokine production, and targeted anticytokine therapy is the current standard for IBD treatment. The cytokine profile from CD patient–derived mesenteric ADSCs and fat tissue was significantly different from that of these patients’ disease-free counterparts. The authors hypothesized that mesenteric ADSCs release adipokines in response to disease-associated signals; this release of adipokines results from differential gene expression of mesenteric ADSCs in CD versus control patients. To test this hypothesis, conditioned media from CD patient–derived ADSCs was used to study gene expression in colonic intestinal epithelial cells in vitro and in mice with experimental colitis in vivo.

Using the Human LncRNA Expression Microarray V4.0, expression of 20,730 protein-coding mRNA targets was analysed, and 992 mRNA transcripts were found to be differentially (less than or equal to twofold change) expressed in CD patient–derived ADSCs, compared with control patient–derived ADSCs. Subsequent pathway analysis suggested activation of cellular growth and proliferation pathways with caspase 8 and p42/44 as top predicted networks that are differentially regulated in CD patient–derived ADSCs with respect to those of control patients.

The investigators treated intestinal epithelial cells – specifically, NCM460 – with conditioned 233 media from the same CD or control patient–derived ADSCs; subsequent microarray profiling using the GeneChip Human Gene ST Array showed increased expression of interleukin-17A, CCL23, and VEGFA. Ingenuity Pathway Analysis of mRNA expression indicated convergence in injury and inflammation pathways with the SERPINE1 gene, which suggests it’s the central regulator of the differential gene expression network.

In vivo, mice with active dextran sulfate sodium (DSS) colitis that were treated with daily injections of conditioned media from CD patients showed attenuation of colitis as compared with mice treated with vehicle or conditioned media from control patients. Furthermore, the mRNA expression of proinflammatory cytokines was reduced with increased proliferative response (as measured by Ki67 expression) in intestinal epithelial cells in the dextran sulfate sodium–treated mice receiving media from CD patients, compared with that in mice receiving media from control patients or vehicle-treated mice.

Cell proliferation was studied in real time (during a period of 120 hours) using the xCELLigence platform. The authors suggested that mesenteric adipose tissue–derived mediators may regulate proliferative responses in intestinal epithelial cells during intestinal inflammation, as observed by enhanced cell-doubling time in conditioned media from CD patient–derived ADSCs.

SOURCE: Hoffman J et al. Cell Molec Gastro Hepatol. doi: 10.1016/j.jcmgh.2018.02.001.

Inflammatory bowel disease (IBD) and Crohn’s disease (CD), in particular, are characterized by an unusual ectopic extension of mesenteric adipose tissue. This intra-abdominal fat, also known as “creeping fat,” which wraps around the intestine during the onset of CD, is associated with inflammation and ulceration of the small or large intestine. The role of this fat in the development of CD, and whether it is protective or harmful, however, is not clear.

The current study demonstrates that adipose-derived stromal cells (ADSCs), the precursor cell population of adipose tissue, promote colonocyte proliferation and exhibit a differential gene expression profile in a disease-dependent manner. CD patient–derived ADSCs attenuated the severity of experimental colitis by releasing extracellular mediators, which exhibits a protective role for mesenteric adipose tissue during intestinal inflammation, according to Jill M. Hoffman, MD, and her colleagues at the University of California, Los Angeles. Increased expression and release of lactoferrin by ADSCs – an iron-binding glycoprotein and antimicrobial peptide usually found in large quantities in breast milk – was shown to be a likely mediator that could regulate inflammatory responses during CD. These results were published in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2018.02.001).

Intestinal inflammation is primarily mediated by cytokine production, and targeted anticytokine therapy is the current standard for IBD treatment. The cytokine profile from CD patient–derived mesenteric ADSCs and fat tissue was significantly different from that of these patients’ disease-free counterparts. The authors hypothesized that mesenteric ADSCs release adipokines in response to disease-associated signals; this release of adipokines results from differential gene expression of mesenteric ADSCs in CD versus control patients. To test this hypothesis, conditioned media from CD patient–derived ADSCs was used to study gene expression in colonic intestinal epithelial cells in vitro and in mice with experimental colitis in vivo.

Using the Human LncRNA Expression Microarray V4.0, expression of 20,730 protein-coding mRNA targets was analysed, and 992 mRNA transcripts were found to be differentially (less than or equal to twofold change) expressed in CD patient–derived ADSCs, compared with control patient–derived ADSCs. Subsequent pathway analysis suggested activation of cellular growth and proliferation pathways with caspase 8 and p42/44 as top predicted networks that are differentially regulated in CD patient–derived ADSCs with respect to those of control patients.

The investigators treated intestinal epithelial cells – specifically, NCM460 – with conditioned 233 media from the same CD or control patient–derived ADSCs; subsequent microarray profiling using the GeneChip Human Gene ST Array showed increased expression of interleukin-17A, CCL23, and VEGFA. Ingenuity Pathway Analysis of mRNA expression indicated convergence in injury and inflammation pathways with the SERPINE1 gene, which suggests it’s the central regulator of the differential gene expression network.

In vivo, mice with active dextran sulfate sodium (DSS) colitis that were treated with daily injections of conditioned media from CD patients showed attenuation of colitis as compared with mice treated with vehicle or conditioned media from control patients. Furthermore, the mRNA expression of proinflammatory cytokines was reduced with increased proliferative response (as measured by Ki67 expression) in intestinal epithelial cells in the dextran sulfate sodium–treated mice receiving media from CD patients, compared with that in mice receiving media from control patients or vehicle-treated mice.

Cell proliferation was studied in real time (during a period of 120 hours) using the xCELLigence platform. The authors suggested that mesenteric adipose tissue–derived mediators may regulate proliferative responses in intestinal epithelial cells during intestinal inflammation, as observed by enhanced cell-doubling time in conditioned media from CD patient–derived ADSCs.

SOURCE: Hoffman J et al. Cell Molec Gastro Hepatol. doi: 10.1016/j.jcmgh.2018.02.001.

Endoscopic surveillance of patients with Barrett’s esophagus led to significantly earlier detection of esophageal cancer in a systematic review and numerous meta-analyses.

Endoscopic surveillance also was associated with modest improvements in all-cause and cancer-specific mortality, said Don C. Codipilly, MD, of the Mayo Clinic in Rochester, Minn., with his associates. The Barrett’s esophagus community “eagerly” await results from the multicenter, randomized BOSS trial (Barrett’s Oesophagus Surveillance versus endoscopy at need Study), the reviewers wrote in the June issue of Gastroenterology.

Guidelines recommend endoscopic surveillance of patients with Barrett’s esophagus, but it is unclear whether this practice improves survival. Hence, the reviewers searched databases such as Ovid MEDLINE, Embase, PubMed, and Scopus for studies published since 1996 that evaluated outcomes of endoscopic surveillance in Barrett’s esophagus. Eligible studies included a case-control study of a large hospital database in northern California, 6 retrospective cohort studies of endoscopic Barrett’s esophagus surveillance, and 11 prospective and retrospective studies comparing patients with esophageal adenocarcinoma (EAC) with and without a history of Barrett’s esophagus.

The case-control study found no link between endoscopic surveillance and improved survival in Barrett’s esophagus, said the reviewers. However, the retrospective cohort studies linked regular Barrett’s esophagus endoscopic surveillance with a 40% lower risk of death from EAC, compared with incomplete or no endoscopic surveillance, which was statistically significant (risk ratio, 0.60; 95% confidence interval, 0.50-0.71). Individual results of these studies also were consistent with the results of their meta-analysis. A separate meta-analysis of the remaining studies also linked endoscopic surveillance with a significantly lower risk of EAC-related mortality (RR, 0.73; 95% CI, 0.57-0.94), but these studies had substantial heterogeneity, the investigators said.

Meta-analyses also supported endoscopic surveillance for earlier detection of EAC. Unadjusted data from four studies indicated that Barrett’s esophagus surveillance helped detect EAC while it was still early stage (stage 0 or 1) rather than later stage (RR, 2.1; 95% CI, 1.1-4.1). Similarly, patients who had already been diagnosed with Barrett’s esophagus were significantly more likely to present with early-stage EAC (RR, 5.5; 95% CI, 3.7-8.2). In contrast, enrollment in a Barrett’s esophagus surveillance program did not appear to affect the likelihood of esophagectomy.

Additional meta-analyses suggested that endoscopic surveillance of Barrett’s esophagus might confer a “potentially small” overall survival benefit, the reviewers said. A meta-analysis of adjusted data from three studies linked surveillance with a 25% reduction in risk of all-cause mortality, compared with no surveillance (hazard ratio, 0.75; 95% CI, 0.58-0.94). Having a prior Barrett’s esophagus diagnosis also was associated with a 52% decrease in all-cause mortality, compared with having symptomatic cancer (RR, 0.48; 95% CI, 0.37-0.63) in a meta-analysis of unadjusted data from 12 studies. Five studies with adjusted data linked a prior Barrett’s esophagus diagnosis with a 41% lower risk of all-cause mortality (HR, 0.59; 95% CI, 0.45-0.76). However, individual findings varied substantially, and adjusting for lead time “almost eliminated this overall survival benefit,” the reviewers said.

The National Institutes of Health and a Public Health Service Award supported the study. Dr. Codipilly reported having no conflicts of interest. Five coinvestigators disclosed ties to Exact Sciences, C2 Therapeutics, and other companies.

SOURCE: Codipilly DC et al. Gastroenterology. 2018 Feb 17. doi: 10.1053/j.gastro.2018.02.022.

Endoscopic surveillance of patients with Barrett’s esophagus led to significantly earlier detection of esophageal cancer in a systematic review and numerous meta-analyses.

Endoscopic surveillance also was associated with modest improvements in all-cause and cancer-specific mortality, said Don C. Codipilly, MD, of the Mayo Clinic in Rochester, Minn., with his associates. The Barrett’s esophagus community “eagerly” await results from the multicenter, randomized BOSS trial (Barrett’s Oesophagus Surveillance versus endoscopy at need Study), the reviewers wrote in the June issue of Gastroenterology.

Guidelines recommend endoscopic surveillance of patients with Barrett’s esophagus, but it is unclear whether this practice improves survival. Hence, the reviewers searched databases such as Ovid MEDLINE, Embase, PubMed, and Scopus for studies published since 1996 that evaluated outcomes of endoscopic surveillance in Barrett’s esophagus. Eligible studies included a case-control study of a large hospital database in northern California, 6 retrospective cohort studies of endoscopic Barrett’s esophagus surveillance, and 11 prospective and retrospective studies comparing patients with esophageal adenocarcinoma (EAC) with and without a history of Barrett’s esophagus.

The case-control study found no link between endoscopic surveillance and improved survival in Barrett’s esophagus, said the reviewers. However, the retrospective cohort studies linked regular Barrett’s esophagus endoscopic surveillance with a 40% lower risk of death from EAC, compared with incomplete or no endoscopic surveillance, which was statistically significant (risk ratio, 0.60; 95% confidence interval, 0.50-0.71). Individual results of these studies also were consistent with the results of their meta-analysis. A separate meta-analysis of the remaining studies also linked endoscopic surveillance with a significantly lower risk of EAC-related mortality (RR, 0.73; 95% CI, 0.57-0.94), but these studies had substantial heterogeneity, the investigators said.

Meta-analyses also supported endoscopic surveillance for earlier detection of EAC. Unadjusted data from four studies indicated that Barrett’s esophagus surveillance helped detect EAC while it was still early stage (stage 0 or 1) rather than later stage (RR, 2.1; 95% CI, 1.1-4.1). Similarly, patients who had already been diagnosed with Barrett’s esophagus were significantly more likely to present with early-stage EAC (RR, 5.5; 95% CI, 3.7-8.2). In contrast, enrollment in a Barrett’s esophagus surveillance program did not appear to affect the likelihood of esophagectomy.

Additional meta-analyses suggested that endoscopic surveillance of Barrett’s esophagus might confer a “potentially small” overall survival benefit, the reviewers said. A meta-analysis of adjusted data from three studies linked surveillance with a 25% reduction in risk of all-cause mortality, compared with no surveillance (hazard ratio, 0.75; 95% CI, 0.58-0.94). Having a prior Barrett’s esophagus diagnosis also was associated with a 52% decrease in all-cause mortality, compared with having symptomatic cancer (RR, 0.48; 95% CI, 0.37-0.63) in a meta-analysis of unadjusted data from 12 studies. Five studies with adjusted data linked a prior Barrett’s esophagus diagnosis with a 41% lower risk of all-cause mortality (HR, 0.59; 95% CI, 0.45-0.76). However, individual findings varied substantially, and adjusting for lead time “almost eliminated this overall survival benefit,” the reviewers said.

The National Institutes of Health and a Public Health Service Award supported the study. Dr. Codipilly reported having no conflicts of interest. Five coinvestigators disclosed ties to Exact Sciences, C2 Therapeutics, and other companies.

SOURCE: Codipilly DC et al. Gastroenterology. 2018 Feb 17. doi: 10.1053/j.gastro.2018.02.022.

Endoscopic surveillance of patients with Barrett’s esophagus led to significantly earlier detection of esophageal cancer in a systematic review and numerous meta-analyses.

Endoscopic surveillance also was associated with modest improvements in all-cause and cancer-specific mortality, said Don C. Codipilly, MD, of the Mayo Clinic in Rochester, Minn., with his associates. The Barrett’s esophagus community “eagerly” await results from the multicenter, randomized BOSS trial (Barrett’s Oesophagus Surveillance versus endoscopy at need Study), the reviewers wrote in the June issue of Gastroenterology.

Guidelines recommend endoscopic surveillance of patients with Barrett’s esophagus, but it is unclear whether this practice improves survival. Hence, the reviewers searched databases such as Ovid MEDLINE, Embase, PubMed, and Scopus for studies published since 1996 that evaluated outcomes of endoscopic surveillance in Barrett’s esophagus. Eligible studies included a case-control study of a large hospital database in northern California, 6 retrospective cohort studies of endoscopic Barrett’s esophagus surveillance, and 11 prospective and retrospective studies comparing patients with esophageal adenocarcinoma (EAC) with and without a history of Barrett’s esophagus.

The case-control study found no link between endoscopic surveillance and improved survival in Barrett’s esophagus, said the reviewers. However, the retrospective cohort studies linked regular Barrett’s esophagus endoscopic surveillance with a 40% lower risk of death from EAC, compared with incomplete or no endoscopic surveillance, which was statistically significant (risk ratio, 0.60; 95% confidence interval, 0.50-0.71). Individual results of these studies also were consistent with the results of their meta-analysis. A separate meta-analysis of the remaining studies also linked endoscopic surveillance with a significantly lower risk of EAC-related mortality (RR, 0.73; 95% CI, 0.57-0.94), but these studies had substantial heterogeneity, the investigators said.

Meta-analyses also supported endoscopic surveillance for earlier detection of EAC. Unadjusted data from four studies indicated that Barrett’s esophagus surveillance helped detect EAC while it was still early stage (stage 0 or 1) rather than later stage (RR, 2.1; 95% CI, 1.1-4.1). Similarly, patients who had already been diagnosed with Barrett’s esophagus were significantly more likely to present with early-stage EAC (RR, 5.5; 95% CI, 3.7-8.2). In contrast, enrollment in a Barrett’s esophagus surveillance program did not appear to affect the likelihood of esophagectomy.

Additional meta-analyses suggested that endoscopic surveillance of Barrett’s esophagus might confer a “potentially small” overall survival benefit, the reviewers said. A meta-analysis of adjusted data from three studies linked surveillance with a 25% reduction in risk of all-cause mortality, compared with no surveillance (hazard ratio, 0.75; 95% CI, 0.58-0.94). Having a prior Barrett’s esophagus diagnosis also was associated with a 52% decrease in all-cause mortality, compared with having symptomatic cancer (RR, 0.48; 95% CI, 0.37-0.63) in a meta-analysis of unadjusted data from 12 studies. Five studies with adjusted data linked a prior Barrett’s esophagus diagnosis with a 41% lower risk of all-cause mortality (HR, 0.59; 95% CI, 0.45-0.76). However, individual findings varied substantially, and adjusting for lead time “almost eliminated this overall survival benefit,” the reviewers said.

The National Institutes of Health and a Public Health Service Award supported the study. Dr. Codipilly reported having no conflicts of interest. Five coinvestigators disclosed ties to Exact Sciences, C2 Therapeutics, and other companies.

SOURCE: Codipilly DC et al. Gastroenterology. 2018 Feb 17. doi: 10.1053/j.gastro.2018.02.022.

Liver transplantation led to “excellent outcomes” when performed after downstaging hepatocellular carcinoma using the UNOS (United Network for Organ Sharing) Region 5 protocol, investigators reported.

Downstaging succeeded for 58% of patients, and an estimated 87% of transplantation recipients were alive and recurrence free at 5 years, said Neil Mehta, MD, of the University of California, San Francisco, and his associates. The findings support expanding priority access to liver transplantation to include patients whose hepatocellular carcinoma (HCC) has been successfully downstaged, they said. “In the meantime, UNOS has recently approved the Region 5 downstaging protocol for receiving automatic HCC-MELD exception listing,” they wrote. The report was published in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.11.037).

This is the first multicenter study of HCC downstaging according to a uniform protocol, the researchers noted. In multivariable analyses, downstaging was significantly more likely to fail in the setting of moderate to severe (Child Pugh B or C) hepatic impairment (hazard ratio, 3.3; 95% confidence interval, 3.0 to 3.6; P less than .001) or baseline alpha-fetoprotein level above 1,000 ng/mL (HR, 1.6; 95% CI, 1.4 to 1.9; P less than .001).

The incidence of HCC in the United States is expected to keep rising for at least another decade because of epidemic levels of fatty liver disease and chronic hepatitis C, the investigators noted. Downstaging HCC with local-regional therapy is a common bridge to transplantation, and successful treatment tends to reflect favorable tumor biology, which bodes well for transplantation. However, no multicenter study had evaluated these associations. Therefore, the investigators retrospectively studied 187 patients with HCC from three centers in California who underwent downstaging according to the UNOS Region 5 protocol between 2002 and 2012.

A total of 156 patients (83%) were successfully downstaged to within Milan criteria after a median of 2.7 months (interquartile range, 1.4 to 4.9 months), said the researchers. Among patients who were successfully downstaged but did not undergo transplantation, 37 patients had tumor progression or died from liver-related causes after a median of 6 months, while 10 patients remained on the transplant list. Among the 109 patients who underwent transplantation after a median of 13 months (interquartile range 6 to 19 months), median follow-up time was 4.3 years and estimated 5-year survival was 80%, and estimated recurrence-free survival was 87%.

Fully 68% of successfully downstaged patients required only one local-regional treatment, the researchers said. The Region 5 protocol considers patients eligible for downstaging if they have a single HCC lesion measuring up to 8 cm or multiple lesions whose combined diameters do not exceed 8 cm, and no evidence of extrahepatic disease or vascular invasion on multiphase computed tomography or magnetic resonance imaging.

The protocol considers downstaging successful if it results in one lesion measuring up to 5 cm or no more than three lesions of up to 3 cm each. Thus, patients who start out with four or five lesions must have complete necrosis of at least one to two tumors. Successfully downstaged patients must remain free of acute hepatic decompensation for at least 3 consecutive months before undergoing transplantation, according to the protocol.

SOURCE: Mehta N, et al. Clin Gastroenterol Hepatol. 2017 Nov 23. doi: 10.1016/j.cgh.2017.11.037.

Liver transplantation led to “excellent outcomes” when performed after downstaging hepatocellular carcinoma using the UNOS (United Network for Organ Sharing) Region 5 protocol, investigators reported.

Downstaging succeeded for 58% of patients, and an estimated 87% of transplantation recipients were alive and recurrence free at 5 years, said Neil Mehta, MD, of the University of California, San Francisco, and his associates. The findings support expanding priority access to liver transplantation to include patients whose hepatocellular carcinoma (HCC) has been successfully downstaged, they said. “In the meantime, UNOS has recently approved the Region 5 downstaging protocol for receiving automatic HCC-MELD exception listing,” they wrote. The report was published in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.11.037).

This is the first multicenter study of HCC downstaging according to a uniform protocol, the researchers noted. In multivariable analyses, downstaging was significantly more likely to fail in the setting of moderate to severe (Child Pugh B or C) hepatic impairment (hazard ratio, 3.3; 95% confidence interval, 3.0 to 3.6; P less than .001) or baseline alpha-fetoprotein level above 1,000 ng/mL (HR, 1.6; 95% CI, 1.4 to 1.9; P less than .001).

The incidence of HCC in the United States is expected to keep rising for at least another decade because of epidemic levels of fatty liver disease and chronic hepatitis C, the investigators noted. Downstaging HCC with local-regional therapy is a common bridge to transplantation, and successful treatment tends to reflect favorable tumor biology, which bodes well for transplantation. However, no multicenter study had evaluated these associations. Therefore, the investigators retrospectively studied 187 patients with HCC from three centers in California who underwent downstaging according to the UNOS Region 5 protocol between 2002 and 2012.

A total of 156 patients (83%) were successfully downstaged to within Milan criteria after a median of 2.7 months (interquartile range, 1.4 to 4.9 months), said the researchers. Among patients who were successfully downstaged but did not undergo transplantation, 37 patients had tumor progression or died from liver-related causes after a median of 6 months, while 10 patients remained on the transplant list. Among the 109 patients who underwent transplantation after a median of 13 months (interquartile range 6 to 19 months), median follow-up time was 4.3 years and estimated 5-year survival was 80%, and estimated recurrence-free survival was 87%.

Fully 68% of successfully downstaged patients required only one local-regional treatment, the researchers said. The Region 5 protocol considers patients eligible for downstaging if they have a single HCC lesion measuring up to 8 cm or multiple lesions whose combined diameters do not exceed 8 cm, and no evidence of extrahepatic disease or vascular invasion on multiphase computed tomography or magnetic resonance imaging.

The protocol considers downstaging successful if it results in one lesion measuring up to 5 cm or no more than three lesions of up to 3 cm each. Thus, patients who start out with four or five lesions must have complete necrosis of at least one to two tumors. Successfully downstaged patients must remain free of acute hepatic decompensation for at least 3 consecutive months before undergoing transplantation, according to the protocol.

SOURCE: Mehta N, et al. Clin Gastroenterol Hepatol. 2017 Nov 23. doi: 10.1016/j.cgh.2017.11.037.

Liver transplantation led to “excellent outcomes” when performed after downstaging hepatocellular carcinoma using the UNOS (United Network for Organ Sharing) Region 5 protocol, investigators reported.

Downstaging succeeded for 58% of patients, and an estimated 87% of transplantation recipients were alive and recurrence free at 5 years, said Neil Mehta, MD, of the University of California, San Francisco, and his associates. The findings support expanding priority access to liver transplantation to include patients whose hepatocellular carcinoma (HCC) has been successfully downstaged, they said. “In the meantime, UNOS has recently approved the Region 5 downstaging protocol for receiving automatic HCC-MELD exception listing,” they wrote. The report was published in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.11.037).

This is the first multicenter study of HCC downstaging according to a uniform protocol, the researchers noted. In multivariable analyses, downstaging was significantly more likely to fail in the setting of moderate to severe (Child Pugh B or C) hepatic impairment (hazard ratio, 3.3; 95% confidence interval, 3.0 to 3.6; P less than .001) or baseline alpha-fetoprotein level above 1,000 ng/mL (HR, 1.6; 95% CI, 1.4 to 1.9; P less than .001).

The incidence of HCC in the United States is expected to keep rising for at least another decade because of epidemic levels of fatty liver disease and chronic hepatitis C, the investigators noted. Downstaging HCC with local-regional therapy is a common bridge to transplantation, and successful treatment tends to reflect favorable tumor biology, which bodes well for transplantation. However, no multicenter study had evaluated these associations. Therefore, the investigators retrospectively studied 187 patients with HCC from three centers in California who underwent downstaging according to the UNOS Region 5 protocol between 2002 and 2012.

A total of 156 patients (83%) were successfully downstaged to within Milan criteria after a median of 2.7 months (interquartile range, 1.4 to 4.9 months), said the researchers. Among patients who were successfully downstaged but did not undergo transplantation, 37 patients had tumor progression or died from liver-related causes after a median of 6 months, while 10 patients remained on the transplant list. Among the 109 patients who underwent transplantation after a median of 13 months (interquartile range 6 to 19 months), median follow-up time was 4.3 years and estimated 5-year survival was 80%, and estimated recurrence-free survival was 87%.

Fully 68% of successfully downstaged patients required only one local-regional treatment, the researchers said. The Region 5 protocol considers patients eligible for downstaging if they have a single HCC lesion measuring up to 8 cm or multiple lesions whose combined diameters do not exceed 8 cm, and no evidence of extrahepatic disease or vascular invasion on multiphase computed tomography or magnetic resonance imaging.

The protocol considers downstaging successful if it results in one lesion measuring up to 5 cm or no more than three lesions of up to 3 cm each. Thus, patients who start out with four or five lesions must have complete necrosis of at least one to two tumors. Successfully downstaged patients must remain free of acute hepatic decompensation for at least 3 consecutive months before undergoing transplantation, according to the protocol.

SOURCE: Mehta N, et al. Clin Gastroenterol Hepatol. 2017 Nov 23. doi: 10.1016/j.cgh.2017.11.037.

Colonic diverticulosis was not associated with mucosal inflammation or gastrointestinal symptoms in a single-center, prospective study of adults undergoing their first screening colonoscopy.

After adjustment for age, sex, and body mass index, there were no significant links between diverticulosis and tumor necrosis factor, CD4+ cells, CD8+ cells, CD57+ cells, irritable bowel syndrome, or chronic abdominal pain, reported Anne F. Peery, MD, with her associates at the University of North Carolina at Chapel Hill. “Our findings strongly question the rationale for treating symptomatic uncomplicated diverticular disease with mesalamine,” they wrote in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.05.051).

Colonic diverticula affect more than half of individuals in the United States over the age of 60 years, according to the results of past studies. “Although colonic diverticulosis can be complicated by the overt inflammation of acute diverticulitis, there is some thought that colonic diverticulosis is associated with low-grade mucosal inflammation,” the researchers said. “Moreover, this low-grade diverticular inflammation is believed to contribute to chronic gastrointestinal symptoms.” However, no rigorous prospective study had tested these assertions.

Accordingly, the researchers evaluated prospective data from 619 outpatients aged 30 years and older who underwent screening colonoscopies for the first time during 2013-2015. These patients had consented to participate in a study of risk factors for colonic diverticulosis. Most were white (76%) or black (21%), and most were aged 50-59 years.

A total of 255 individuals had diverticula while 364 controls did not. Patients with diverticula tended to be older and were more often male (47% vs. 41% of controls) and overweight or obese (72% vs. 62%). After adjustment for age, sex, and body mass index, there was no evidence linking diverticulosis with tumor necrosis factor alpha expression (odds ratio, 0.9; 95% confidence interval, 0.6-1.2), CD4+ cells (OR, 1.2; 95% CI, 0.9-1.6), CD8+ cells (OR, 1.0; 95% CI, 0.7-1.3), or CD57+ cells (OR, 0.8; 95% CI, 0.6-1.1).

Among 42 patients who met Rome III criteria for irritable bowel syndrome, 11 had diverticulosis. Diverticulosis in IBS was not associated with changes in expression of the mucosal inflammatory markers interleukin-6, interleukin-10, tumor necrosis factor, CD4, CD8, or mast cell tryptase, said the researchers. A total of 63 patients had chronic abdominal pain, of whom 22 also had diverticulosis. There were no significant differences in mucosal inflammatory markers between symptomatic patients with diverticula and those without. Adjusted analysis found no association between number of diverticula and chronic abdominal pain (OR, 0.7; 95% CI, 0.4-1.2) or IBS (OR, 0.5; 95% CI, 0.3-1.1).

The number of patients with IBS in this study was small, and the researchers did not ascertain IBS symptom severity, they noted. “Although we studied several immune markers and cytokines, there are other potential markers that may be associated with chronic inflammation,” they added. “Multianalyte profiling could be used to assess an array of cytokines, and markers for macrophages (CD68), global T cells (CD3), and B cells (CD19). Whether there is utility in further studies given our negative results is debatable.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Peery AF et al. Clin Gastroenterol Hepatol. 2017 Jun 8. doi: 10.1016/j.cgh.2017.05.051.

Colonic diverticulosis was not associated with mucosal inflammation or gastrointestinal symptoms in a single-center, prospective study of adults undergoing their first screening colonoscopy.

After adjustment for age, sex, and body mass index, there were no significant links between diverticulosis and tumor necrosis factor, CD4+ cells, CD8+ cells, CD57+ cells, irritable bowel syndrome, or chronic abdominal pain, reported Anne F. Peery, MD, with her associates at the University of North Carolina at Chapel Hill. “Our findings strongly question the rationale for treating symptomatic uncomplicated diverticular disease with mesalamine,” they wrote in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.05.051).

Colonic diverticula affect more than half of individuals in the United States over the age of 60 years, according to the results of past studies. “Although colonic diverticulosis can be complicated by the overt inflammation of acute diverticulitis, there is some thought that colonic diverticulosis is associated with low-grade mucosal inflammation,” the researchers said. “Moreover, this low-grade diverticular inflammation is believed to contribute to chronic gastrointestinal symptoms.” However, no rigorous prospective study had tested these assertions.

Accordingly, the researchers evaluated prospective data from 619 outpatients aged 30 years and older who underwent screening colonoscopies for the first time during 2013-2015. These patients had consented to participate in a study of risk factors for colonic diverticulosis. Most were white (76%) or black (21%), and most were aged 50-59 years.

A total of 255 individuals had diverticula while 364 controls did not. Patients with diverticula tended to be older and were more often male (47% vs. 41% of controls) and overweight or obese (72% vs. 62%). After adjustment for age, sex, and body mass index, there was no evidence linking diverticulosis with tumor necrosis factor alpha expression (odds ratio, 0.9; 95% confidence interval, 0.6-1.2), CD4+ cells (OR, 1.2; 95% CI, 0.9-1.6), CD8+ cells (OR, 1.0; 95% CI, 0.7-1.3), or CD57+ cells (OR, 0.8; 95% CI, 0.6-1.1).

Among 42 patients who met Rome III criteria for irritable bowel syndrome, 11 had diverticulosis. Diverticulosis in IBS was not associated with changes in expression of the mucosal inflammatory markers interleukin-6, interleukin-10, tumor necrosis factor, CD4, CD8, or mast cell tryptase, said the researchers. A total of 63 patients had chronic abdominal pain, of whom 22 also had diverticulosis. There were no significant differences in mucosal inflammatory markers between symptomatic patients with diverticula and those without. Adjusted analysis found no association between number of diverticula and chronic abdominal pain (OR, 0.7; 95% CI, 0.4-1.2) or IBS (OR, 0.5; 95% CI, 0.3-1.1).

The number of patients with IBS in this study was small, and the researchers did not ascertain IBS symptom severity, they noted. “Although we studied several immune markers and cytokines, there are other potential markers that may be associated with chronic inflammation,” they added. “Multianalyte profiling could be used to assess an array of cytokines, and markers for macrophages (CD68), global T cells (CD3), and B cells (CD19). Whether there is utility in further studies given our negative results is debatable.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Peery AF et al. Clin Gastroenterol Hepatol. 2017 Jun 8. doi: 10.1016/j.cgh.2017.05.051.

Colonic diverticulosis was not associated with mucosal inflammation or gastrointestinal symptoms in a single-center, prospective study of adults undergoing their first screening colonoscopy.

After adjustment for age, sex, and body mass index, there were no significant links between diverticulosis and tumor necrosis factor, CD4+ cells, CD8+ cells, CD57+ cells, irritable bowel syndrome, or chronic abdominal pain, reported Anne F. Peery, MD, with her associates at the University of North Carolina at Chapel Hill. “Our findings strongly question the rationale for treating symptomatic uncomplicated diverticular disease with mesalamine,” they wrote in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.05.051).

Colonic diverticula affect more than half of individuals in the United States over the age of 60 years, according to the results of past studies. “Although colonic diverticulosis can be complicated by the overt inflammation of acute diverticulitis, there is some thought that colonic diverticulosis is associated with low-grade mucosal inflammation,” the researchers said. “Moreover, this low-grade diverticular inflammation is believed to contribute to chronic gastrointestinal symptoms.” However, no rigorous prospective study had tested these assertions.

Accordingly, the researchers evaluated prospective data from 619 outpatients aged 30 years and older who underwent screening colonoscopies for the first time during 2013-2015. These patients had consented to participate in a study of risk factors for colonic diverticulosis. Most were white (76%) or black (21%), and most were aged 50-59 years.

A total of 255 individuals had diverticula while 364 controls did not. Patients with diverticula tended to be older and were more often male (47% vs. 41% of controls) and overweight or obese (72% vs. 62%). After adjustment for age, sex, and body mass index, there was no evidence linking diverticulosis with tumor necrosis factor alpha expression (odds ratio, 0.9; 95% confidence interval, 0.6-1.2), CD4+ cells (OR, 1.2; 95% CI, 0.9-1.6), CD8+ cells (OR, 1.0; 95% CI, 0.7-1.3), or CD57+ cells (OR, 0.8; 95% CI, 0.6-1.1).

Among 42 patients who met Rome III criteria for irritable bowel syndrome, 11 had diverticulosis. Diverticulosis in IBS was not associated with changes in expression of the mucosal inflammatory markers interleukin-6, interleukin-10, tumor necrosis factor, CD4, CD8, or mast cell tryptase, said the researchers. A total of 63 patients had chronic abdominal pain, of whom 22 also had diverticulosis. There were no significant differences in mucosal inflammatory markers between symptomatic patients with diverticula and those without. Adjusted analysis found no association between number of diverticula and chronic abdominal pain (OR, 0.7; 95% CI, 0.4-1.2) or IBS (OR, 0.5; 95% CI, 0.3-1.1).

The number of patients with IBS in this study was small, and the researchers did not ascertain IBS symptom severity, they noted. “Although we studied several immune markers and cytokines, there are other potential markers that may be associated with chronic inflammation,” they added. “Multianalyte profiling could be used to assess an array of cytokines, and markers for macrophages (CD68), global T cells (CD3), and B cells (CD19). Whether there is utility in further studies given our negative results is debatable.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SOURCE: Peery AF et al. Clin Gastroenterol Hepatol. 2017 Jun 8. doi: 10.1016/j.cgh.2017.05.051.

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

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.”

[email protected]

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.

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

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.”

[email protected]

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.

Screening and surveillance practices for Barrett’s esophagus are varied, but there are a variety of approaches researchers have taken to find the best strategy.

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.”

[email protected]

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.