Digestive Disease Week (DDW)

SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

SAN DIEGO – Monitored anesthesia care (MAC) for outpatient endoscopy is on the rise in the United States, presumably because of financial incentives for fee-for-service gastroenterology (GI) practices. However, a new study found that use of MAC is increasing in Veteran’s Health Administration (VHA) facilities, an environment free of financial incentives.

The increase in VHA hospitals is much smaller than in the country as a whole, but the study suggests that there are additional drivers for use of MAC that need to be more fully explored.

Over the past two decades, the rate of MAC use for outpatient endoscopy in fee-for-service practices has increased by at least 30%. Over the study period, the rate of MAC use for endoscopy procedures doubled in VHA facilities from 5.7% in 2000 to 11.1% in 2013, with a larger proportion of increase between 2011 and 2013.

“The increase in MAC use in fee-for-service practices is thought to be driven by financial gain. With an anesthesiologist on hand for an endoscopy procedure, the practice can bill double [duplicative billing with separate billing codes], essentially getting double reimbursement. The VHA has little incentive to increase use of MAC for financial gain. We wanted to study use of MAC in the VHA environment to determine if there are other factors involved,” explained Dr. Megan A. Adams of the University of Michigan, Ann Arbor.

In an interview, Dr. Adams explained that American Society for Gastrointestinal Endoscopy guidelines for MAC use are relatively broad and diffuse. They state that MAC should be considered for patients with anticipated intolerance to standard sedatives, certain cardiopulmonary morbidities, and the potential for airway compromise.

“These will need to be more specific in the future,” she said.

The retrospective cohort study she reported on at the annual Digestive Disease Week was based on national VHA data from more than 1,700 sites of care, with about 300,000 endoscopies performed each year.

“A large variation of MAC use was observed across study facilities, particularly in the later years of the study period,” Dr. Adams explained.

The investigators developed a model based on 122 VHA facilities, 2.1 million patient encounters, and the time of event to analyze patient-level and provider-level predictors of MAC using multilevel random effects logistical regression analysis.

Patient-level factors associated with the increased use of MAC included female gender (35% increase), body mass index greater than 35 kg/m² (20% increase), obstructive sleep apnea (50% increase), opioid use (17% increase), and benzodiazepine use (13%). Charlson comorbidity scores were associated with a significant increase, compared with healthy patients, with a score of 3 having a 30% increased likelihood of MAC use.

Provider-level predictors of MAC use were related to facilities. Outside of the GI endoscopy suite, endoscopy procedures were about four times more likely to be performed with MAC, and surgeons were about 50% more likely to use MAC.

“The variation in MAC use is largely explained by facility factors. Potential facility factors could be academic versus nonacademic setting, differences in how sites triage care, and differences in local policy. Patient-level factors were relatively weak influences. We will need to explore provider-level [facility] factors more fully to understand the specifics,” she said.

“We will need to align incentives to promote more appropriate use of MAC tailored to patient factors,” Dr. Adams said.

“Payment reforms are looming. CMS will probably remove duplicative reimbursement for MAC. The country will follow CMS. This will affect the financial drivers of MAC, but not necessarily the nonfinancial drivers,” she predicted.

Dr. Adams had no financial disclosures.

SAN DIEGO – Monitored anesthesia care (MAC) for outpatient endoscopy is on the rise in the United States, presumably because of financial incentives for fee-for-service gastroenterology (GI) practices. However, a new study found that use of MAC is increasing in Veteran’s Health Administration (VHA) facilities, an environment free of financial incentives.

The increase in VHA hospitals is much smaller than in the country as a whole, but the study suggests that there are additional drivers for use of MAC that need to be more fully explored.

Over the past two decades, the rate of MAC use for outpatient endoscopy in fee-for-service practices has increased by at least 30%. Over the study period, the rate of MAC use for endoscopy procedures doubled in VHA facilities from 5.7% in 2000 to 11.1% in 2013, with a larger proportion of increase between 2011 and 2013.

“The increase in MAC use in fee-for-service practices is thought to be driven by financial gain. With an anesthesiologist on hand for an endoscopy procedure, the practice can bill double [duplicative billing with separate billing codes], essentially getting double reimbursement. The VHA has little incentive to increase use of MAC for financial gain. We wanted to study use of MAC in the VHA environment to determine if there are other factors involved,” explained Dr. Megan A. Adams of the University of Michigan, Ann Arbor.

In an interview, Dr. Adams explained that American Society for Gastrointestinal Endoscopy guidelines for MAC use are relatively broad and diffuse. They state that MAC should be considered for patients with anticipated intolerance to standard sedatives, certain cardiopulmonary morbidities, and the potential for airway compromise.

“These will need to be more specific in the future,” she said.

The retrospective cohort study she reported on at the annual Digestive Disease Week was based on national VHA data from more than 1,700 sites of care, with about 300,000 endoscopies performed each year.

“A large variation of MAC use was observed across study facilities, particularly in the later years of the study period,” Dr. Adams explained.

The investigators developed a model based on 122 VHA facilities, 2.1 million patient encounters, and the time of event to analyze patient-level and provider-level predictors of MAC using multilevel random effects logistical regression analysis.

Patient-level factors associated with the increased use of MAC included female gender (35% increase), body mass index greater than 35 kg/m² (20% increase), obstructive sleep apnea (50% increase), opioid use (17% increase), and benzodiazepine use (13%). Charlson comorbidity scores were associated with a significant increase, compared with healthy patients, with a score of 3 having a 30% increased likelihood of MAC use.

Provider-level predictors of MAC use were related to facilities. Outside of the GI endoscopy suite, endoscopy procedures were about four times more likely to be performed with MAC, and surgeons were about 50% more likely to use MAC.

“The variation in MAC use is largely explained by facility factors. Potential facility factors could be academic versus nonacademic setting, differences in how sites triage care, and differences in local policy. Patient-level factors were relatively weak influences. We will need to explore provider-level [facility] factors more fully to understand the specifics,” she said.

“We will need to align incentives to promote more appropriate use of MAC tailored to patient factors,” Dr. Adams said.

“Payment reforms are looming. CMS will probably remove duplicative reimbursement for MAC. The country will follow CMS. This will affect the financial drivers of MAC, but not necessarily the nonfinancial drivers,” she predicted.

Dr. Adams had no financial disclosures.

SAN DIEGO – Monitored anesthesia care (MAC) for outpatient endoscopy is on the rise in the United States, presumably because of financial incentives for fee-for-service gastroenterology (GI) practices. However, a new study found that use of MAC is increasing in Veteran’s Health Administration (VHA) facilities, an environment free of financial incentives.

The increase in VHA hospitals is much smaller than in the country as a whole, but the study suggests that there are additional drivers for use of MAC that need to be more fully explored.

Over the past two decades, the rate of MAC use for outpatient endoscopy in fee-for-service practices has increased by at least 30%. Over the study period, the rate of MAC use for endoscopy procedures doubled in VHA facilities from 5.7% in 2000 to 11.1% in 2013, with a larger proportion of increase between 2011 and 2013.

“The increase in MAC use in fee-for-service practices is thought to be driven by financial gain. With an anesthesiologist on hand for an endoscopy procedure, the practice can bill double [duplicative billing with separate billing codes], essentially getting double reimbursement. The VHA has little incentive to increase use of MAC for financial gain. We wanted to study use of MAC in the VHA environment to determine if there are other factors involved,” explained Dr. Megan A. Adams of the University of Michigan, Ann Arbor.

In an interview, Dr. Adams explained that American Society for Gastrointestinal Endoscopy guidelines for MAC use are relatively broad and diffuse. They state that MAC should be considered for patients with anticipated intolerance to standard sedatives, certain cardiopulmonary morbidities, and the potential for airway compromise.

“These will need to be more specific in the future,” she said.

The retrospective cohort study she reported on at the annual Digestive Disease Week was based on national VHA data from more than 1,700 sites of care, with about 300,000 endoscopies performed each year.

“A large variation of MAC use was observed across study facilities, particularly in the later years of the study period,” Dr. Adams explained.

The investigators developed a model based on 122 VHA facilities, 2.1 million patient encounters, and the time of event to analyze patient-level and provider-level predictors of MAC using multilevel random effects logistical regression analysis.

Patient-level factors associated with the increased use of MAC included female gender (35% increase), body mass index greater than 35 kg/m² (20% increase), obstructive sleep apnea (50% increase), opioid use (17% increase), and benzodiazepine use (13%). Charlson comorbidity scores were associated with a significant increase, compared with healthy patients, with a score of 3 having a 30% increased likelihood of MAC use.

Provider-level predictors of MAC use were related to facilities. Outside of the GI endoscopy suite, endoscopy procedures were about four times more likely to be performed with MAC, and surgeons were about 50% more likely to use MAC.

“The variation in MAC use is largely explained by facility factors. Potential facility factors could be academic versus nonacademic setting, differences in how sites triage care, and differences in local policy. Patient-level factors were relatively weak influences. We will need to explore provider-level [facility] factors more fully to understand the specifics,” she said.

“We will need to align incentives to promote more appropriate use of MAC tailored to patient factors,” Dr. Adams said.

“Payment reforms are looming. CMS will probably remove duplicative reimbursement for MAC. The country will follow CMS. This will affect the financial drivers of MAC, but not necessarily the nonfinancial drivers,” she predicted.

Dr. Adams had no financial disclosures.

SAN DIEGO – A first-in-human study suggests that a novel technique holds promise for the treatment of diabetes, reducing the complications, associated morbidity, and economic burden of this disease. Duodenal mucosal resurfacing (DMR) achieved a significant reduction in hemoglobin A1c (HbA1c) levels as well as a robust reduction in the liver enzymes aspartate aminotransferase and alanine aminotransferase in patients with poorly controlled type 2 diabetes.

DMR entails thermal ablation of the duodenal mucosa via minimally invasive endoscopy. According to the pioneer behind this technique, Dr. Harith Rajagopalan, who is the founder and CEO of Fractyl Laboratories, in Waltham, Mass., DMR can be compared to laser resurfacing of the skin to remove actinic keratosis. The procedure removes the surface cells of the duodenum, which are insulin resistant, and they heal and become insulin sensitive.

The procedure does not involve surgery or implants, and takes about 60 minutes.

“We hope that once the procedure is done, patients will adopt lifestyle interventions. In the future, we plan to study whether DMR will have even greater potential if patients adapt to a healthy lifestyle,” he said.

Alice Goodman/Frontline Medical News

During the annual Digestive Disease Week, Dr. Rajagopalan detailed experience with the first 39 humans treated with DMR. All patients had poorly controlled type 2 diabetes and were taking at least one antidiabetic medication. The average age was 53 years, mean body mass index was 31 kg/m², and 50% were taking metformin. DMR was performed after 2 weeks of a low-calorie diet.

In this single-arm study, DMR reduced HbA_1c by 1.2%, reduced ALT from 40 to 27 IU/L, and reduced AST from 32 to 22 IU/L over a period of 6 months. Patients with the highest entry levels of AST and ALT had the greatest reductions.

Of the 39 patients, 28 had a 9-cm ablation of the duodenum, and in these patients, the metabolic benefits were even more robust. Thus, 9 cm was identified as the optimal surface area for ablation in future studies.

The procedure was well tolerated, with minimal gastrointestinal symptoms. Adverse events were mostly mild and mainly abdominal pain due to air for the first 2 days following DMR. Three episodes of duodenal stenosis were reported over the first 6 weeks post procedure.

“These resolved with endoscopic balloon dilatation. We have since improved the procedure, and have not seen subsequent events,” Dr Rajagopalan said.

“We know that bariatric surgeries, particularly those that prevent contact of nutrients with mucosa, improve metabolic measures of metabolism in type 2 diabetes, including indicators of fatty liver disease. Revita resurfaces the duodenal mucosa. We have shown in this first-in-human study that the procedure appears to be safe, that the optimal length of the segment to be resurfaced is 9 cm, and that the procedure is associated with metabolic benefits that persist through 6 months after the mucosa heals,” Dr Rajagopalan said.

Longer-term data are needed beyond 6 months, he noted. The investigators will have 12-month data from this study in a few months, and a multicenter trial is now being conducted in Europe in patients with type 2 diabetes treated with DMR and 9-cm resurfacing of the duodenal mucosa.

“These early results raise the intriguing possibility that our intervention might be used not only in type 2 diabetes, but also in patients with metabolic liver disease and other insulin resistance–mediated diseases,” he said.

Insulin resistance plays a central role across a range of disorders, affecting many different organs, including the liver and gastrointestinal tract. Insulin resistance leads to inherent complications and associated syndromes. Just as polycystic ovarian syndrome is now called metabolic reproductive syndrome, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis could be called metabolic liver disease, he suggested.

“Although some patients treated with DMR lost a modest amount of weight, the liver enzyme levels were still reduced. The weight really didn’t budge, yet the liver enzymes were reduced, which was surprising. This forces the question whether obesity really causes type 2 diabetes, or is the cause of insulin resistance independent of weight and are there other contributing factors than obesity,” he said.

“This study shows the potential for a single-point upper GI intervention that can exert broad metabolic effects in glycemia and fatty liver disease,” he commented.

“Even though the duodenal mucosa regenerates over months 1-3, there appears to be a sustained effect of DMR. However, we need controlled studies that prevent medication adjustments that affect glycemic signals,” Dr Rajagopalan noted.

SAN DIEGO – A first-in-human study suggests that a novel technique holds promise for the treatment of diabetes, reducing the complications, associated morbidity, and economic burden of this disease. Duodenal mucosal resurfacing (DMR) achieved a significant reduction in hemoglobin A1c (HbA1c) levels as well as a robust reduction in the liver enzymes aspartate aminotransferase and alanine aminotransferase in patients with poorly controlled type 2 diabetes.

DMR entails thermal ablation of the duodenal mucosa via minimally invasive endoscopy. According to the pioneer behind this technique, Dr. Harith Rajagopalan, who is the founder and CEO of Fractyl Laboratories, in Waltham, Mass., DMR can be compared to laser resurfacing of the skin to remove actinic keratosis. The procedure removes the surface cells of the duodenum, which are insulin resistant, and they heal and become insulin sensitive.

The procedure does not involve surgery or implants, and takes about 60 minutes.

“We hope that once the procedure is done, patients will adopt lifestyle interventions. In the future, we plan to study whether DMR will have even greater potential if patients adapt to a healthy lifestyle,” he said.

Alice Goodman/Frontline Medical News

During the annual Digestive Disease Week, Dr. Rajagopalan detailed experience with the first 39 humans treated with DMR. All patients had poorly controlled type 2 diabetes and were taking at least one antidiabetic medication. The average age was 53 years, mean body mass index was 31 kg/m², and 50% were taking metformin. DMR was performed after 2 weeks of a low-calorie diet.

In this single-arm study, DMR reduced HbA_1c by 1.2%, reduced ALT from 40 to 27 IU/L, and reduced AST from 32 to 22 IU/L over a period of 6 months. Patients with the highest entry levels of AST and ALT had the greatest reductions.

Of the 39 patients, 28 had a 9-cm ablation of the duodenum, and in these patients, the metabolic benefits were even more robust. Thus, 9 cm was identified as the optimal surface area for ablation in future studies.

The procedure was well tolerated, with minimal gastrointestinal symptoms. Adverse events were mostly mild and mainly abdominal pain due to air for the first 2 days following DMR. Three episodes of duodenal stenosis were reported over the first 6 weeks post procedure.

“These resolved with endoscopic balloon dilatation. We have since improved the procedure, and have not seen subsequent events,” Dr Rajagopalan said.

“We know that bariatric surgeries, particularly those that prevent contact of nutrients with mucosa, improve metabolic measures of metabolism in type 2 diabetes, including indicators of fatty liver disease. Revita resurfaces the duodenal mucosa. We have shown in this first-in-human study that the procedure appears to be safe, that the optimal length of the segment to be resurfaced is 9 cm, and that the procedure is associated with metabolic benefits that persist through 6 months after the mucosa heals,” Dr Rajagopalan said.

Longer-term data are needed beyond 6 months, he noted. The investigators will have 12-month data from this study in a few months, and a multicenter trial is now being conducted in Europe in patients with type 2 diabetes treated with DMR and 9-cm resurfacing of the duodenal mucosa.

“These early results raise the intriguing possibility that our intervention might be used not only in type 2 diabetes, but also in patients with metabolic liver disease and other insulin resistance–mediated diseases,” he said.

Insulin resistance plays a central role across a range of disorders, affecting many different organs, including the liver and gastrointestinal tract. Insulin resistance leads to inherent complications and associated syndromes. Just as polycystic ovarian syndrome is now called metabolic reproductive syndrome, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis could be called metabolic liver disease, he suggested.

“Although some patients treated with DMR lost a modest amount of weight, the liver enzyme levels were still reduced. The weight really didn’t budge, yet the liver enzymes were reduced, which was surprising. This forces the question whether obesity really causes type 2 diabetes, or is the cause of insulin resistance independent of weight and are there other contributing factors than obesity,” he said.

“This study shows the potential for a single-point upper GI intervention that can exert broad metabolic effects in glycemia and fatty liver disease,” he commented.

“Even though the duodenal mucosa regenerates over months 1-3, there appears to be a sustained effect of DMR. However, we need controlled studies that prevent medication adjustments that affect glycemic signals,” Dr Rajagopalan noted.

SAN DIEGO – A first-in-human study suggests that a novel technique holds promise for the treatment of diabetes, reducing the complications, associated morbidity, and economic burden of this disease. Duodenal mucosal resurfacing (DMR) achieved a significant reduction in hemoglobin A1c (HbA1c) levels as well as a robust reduction in the liver enzymes aspartate aminotransferase and alanine aminotransferase in patients with poorly controlled type 2 diabetes.

DMR entails thermal ablation of the duodenal mucosa via minimally invasive endoscopy. According to the pioneer behind this technique, Dr. Harith Rajagopalan, who is the founder and CEO of Fractyl Laboratories, in Waltham, Mass., DMR can be compared to laser resurfacing of the skin to remove actinic keratosis. The procedure removes the surface cells of the duodenum, which are insulin resistant, and they heal and become insulin sensitive.

The procedure does not involve surgery or implants, and takes about 60 minutes.

“We hope that once the procedure is done, patients will adopt lifestyle interventions. In the future, we plan to study whether DMR will have even greater potential if patients adapt to a healthy lifestyle,” he said.

Alice Goodman/Frontline Medical News

During the annual Digestive Disease Week, Dr. Rajagopalan detailed experience with the first 39 humans treated with DMR. All patients had poorly controlled type 2 diabetes and were taking at least one antidiabetic medication. The average age was 53 years, mean body mass index was 31 kg/m², and 50% were taking metformin. DMR was performed after 2 weeks of a low-calorie diet.

In this single-arm study, DMR reduced HbA_1c by 1.2%, reduced ALT from 40 to 27 IU/L, and reduced AST from 32 to 22 IU/L over a period of 6 months. Patients with the highest entry levels of AST and ALT had the greatest reductions.

Of the 39 patients, 28 had a 9-cm ablation of the duodenum, and in these patients, the metabolic benefits were even more robust. Thus, 9 cm was identified as the optimal surface area for ablation in future studies.

The procedure was well tolerated, with minimal gastrointestinal symptoms. Adverse events were mostly mild and mainly abdominal pain due to air for the first 2 days following DMR. Three episodes of duodenal stenosis were reported over the first 6 weeks post procedure.

“These resolved with endoscopic balloon dilatation. We have since improved the procedure, and have not seen subsequent events,” Dr Rajagopalan said.

“We know that bariatric surgeries, particularly those that prevent contact of nutrients with mucosa, improve metabolic measures of metabolism in type 2 diabetes, including indicators of fatty liver disease. Revita resurfaces the duodenal mucosa. We have shown in this first-in-human study that the procedure appears to be safe, that the optimal length of the segment to be resurfaced is 9 cm, and that the procedure is associated with metabolic benefits that persist through 6 months after the mucosa heals,” Dr Rajagopalan said.

Longer-term data are needed beyond 6 months, he noted. The investigators will have 12-month data from this study in a few months, and a multicenter trial is now being conducted in Europe in patients with type 2 diabetes treated with DMR and 9-cm resurfacing of the duodenal mucosa.

“These early results raise the intriguing possibility that our intervention might be used not only in type 2 diabetes, but also in patients with metabolic liver disease and other insulin resistance–mediated diseases,” he said.

Insulin resistance plays a central role across a range of disorders, affecting many different organs, including the liver and gastrointestinal tract. Insulin resistance leads to inherent complications and associated syndromes. Just as polycystic ovarian syndrome is now called metabolic reproductive syndrome, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis could be called metabolic liver disease, he suggested.

“Although some patients treated with DMR lost a modest amount of weight, the liver enzyme levels were still reduced. The weight really didn’t budge, yet the liver enzymes were reduced, which was surprising. This forces the question whether obesity really causes type 2 diabetes, or is the cause of insulin resistance independent of weight and are there other contributing factors than obesity,” he said.

“This study shows the potential for a single-point upper GI intervention that can exert broad metabolic effects in glycemia and fatty liver disease,” he commented.

“Even though the duodenal mucosa regenerates over months 1-3, there appears to be a sustained effect of DMR. However, we need controlled studies that prevent medication adjustments that affect glycemic signals,” Dr Rajagopalan noted.

SAN DIEGO – Statin use, but not aspirin use, showed a protective effect against pancreatic ductal adenocarcinoma in a large prospective case-control study.

“There also appears to be no chemoenhancing effect from combining the two drugs,” Dr. Livia Archibugi of Hospital Sant’Andrea in Rome, Italy, said at the annual Digestive Disease Week. The study also confirmed known risk factors for pancreatic cancer, “supporting the genuineness of our population,” she and her associates said.

Louise Koenig/Frontline Medical News

This is the first epidemiologic study to look at both aspirin and statins in relationship to pancreatic cancer. Both types of drugs have shown anticarcinogenic effects in laboratory and epidemiologic studies, Dr. Archibugi noted. For example, aspirin blocks mTOR, NF-kappa B and Wnt signaling, which inhibits carcinogenesis and angiogenesis and promotes apoptosis and DNA mismatch repair. A recent meta-analysis, found a 23% lower risk of pancreatic cancer among aspirin users than nonusers, but the study did not assess concurrent statin use.

Statins, for their part, are both immunomodulatory and anti-inflammatory, and inhibit angiogenesis at low doses, said Dr. Archibugi. However, studies have yielded mixed results about whether they reduce the risk of pancreatic cancer, she noted.

Therefore, between 2005 and 2016, she and her colleagues used questionnaires to study environmental exposures and the family and individual health histories of 408 consecutive patients with pancreatic ductal adenocarcinoma and 816 age- and sex-matched controls. The controls were gastroenterology patients at the same hospital and did not have chronic obstructive pulmonary disease, cirrhosis, chronic kidney failure, acute bleeding, inflammatory bowel disease, or a history of cancer in the past 5 years. The study was large enough to have an 80% power to detect an odds ratio of 0.65 for the relationship between incident pancreatic cancer and either aspirin or statin exposure, and an odds ratio of 0.5 for dual exposure, Dr. Archibugi noted.

Reported statin use was significantly more common among controls (24%) than cases (18%; P = .03), and controls were more likely than cases to report taking either low-dose (less than 20 mg) or high-dose (greater than 20 mg) statins, the investigators found. Proportionally more controls also reported at least a 5-year history of statin use. After controlling for age, sex, and known risk factors, only statin use was significantly associated with incident pancreatic cancer in the multivariate analysis (OR, 0.59; 95% confidence interval, 0.42-0.85; P = .004). The protective effect of statins held up in subgroups stratified by gender, age, and statin type, Dr. Archibugi said.

In contrast, statistically similar proportions of cases (19%) and controls (23%) reported using aspirin, and although aspirin use was inversely linked to incident pancreatic cancer in the univariate analysis, the effect lost significance in the multivariable analysis (OR, 0.78; 95% CI, 0.54-1.11). Moreover, patients who took both aspirin and statins were no less likely to develop pancreatic cancer than those who took only statins.

Like all case-control studies, recall bias could have affected the associations, she noted. However, the same analyses correlated pancreatic cancer with several known risk factors, including smoking (OR, 1.8), heavy drinking (OR, 1.7), diabetes (OR, 1.8), chronic pancreatitis (OR, 14.3), and first-degree family history of pancreatic cancer (OR, 3.1).

Dr. Archibugi and her associates had no disclosures.

SAN DIEGO – Statin use, but not aspirin use, showed a protective effect against pancreatic ductal adenocarcinoma in a large prospective case-control study.

“There also appears to be no chemoenhancing effect from combining the two drugs,” Dr. Livia Archibugi of Hospital Sant’Andrea in Rome, Italy, said at the annual Digestive Disease Week. The study also confirmed known risk factors for pancreatic cancer, “supporting the genuineness of our population,” she and her associates said.

Louise Koenig/Frontline Medical News

This is the first epidemiologic study to look at both aspirin and statins in relationship to pancreatic cancer. Both types of drugs have shown anticarcinogenic effects in laboratory and epidemiologic studies, Dr. Archibugi noted. For example, aspirin blocks mTOR, NF-kappa B and Wnt signaling, which inhibits carcinogenesis and angiogenesis and promotes apoptosis and DNA mismatch repair. A recent meta-analysis, found a 23% lower risk of pancreatic cancer among aspirin users than nonusers, but the study did not assess concurrent statin use.

Statins, for their part, are both immunomodulatory and anti-inflammatory, and inhibit angiogenesis at low doses, said Dr. Archibugi. However, studies have yielded mixed results about whether they reduce the risk of pancreatic cancer, she noted.

Therefore, between 2005 and 2016, she and her colleagues used questionnaires to study environmental exposures and the family and individual health histories of 408 consecutive patients with pancreatic ductal adenocarcinoma and 816 age- and sex-matched controls. The controls were gastroenterology patients at the same hospital and did not have chronic obstructive pulmonary disease, cirrhosis, chronic kidney failure, acute bleeding, inflammatory bowel disease, or a history of cancer in the past 5 years. The study was large enough to have an 80% power to detect an odds ratio of 0.65 for the relationship between incident pancreatic cancer and either aspirin or statin exposure, and an odds ratio of 0.5 for dual exposure, Dr. Archibugi noted.

Reported statin use was significantly more common among controls (24%) than cases (18%; P = .03), and controls were more likely than cases to report taking either low-dose (less than 20 mg) or high-dose (greater than 20 mg) statins, the investigators found. Proportionally more controls also reported at least a 5-year history of statin use. After controlling for age, sex, and known risk factors, only statin use was significantly associated with incident pancreatic cancer in the multivariate analysis (OR, 0.59; 95% confidence interval, 0.42-0.85; P = .004). The protective effect of statins held up in subgroups stratified by gender, age, and statin type, Dr. Archibugi said.

In contrast, statistically similar proportions of cases (19%) and controls (23%) reported using aspirin, and although aspirin use was inversely linked to incident pancreatic cancer in the univariate analysis, the effect lost significance in the multivariable analysis (OR, 0.78; 95% CI, 0.54-1.11). Moreover, patients who took both aspirin and statins were no less likely to develop pancreatic cancer than those who took only statins.

Like all case-control studies, recall bias could have affected the associations, she noted. However, the same analyses correlated pancreatic cancer with several known risk factors, including smoking (OR, 1.8), heavy drinking (OR, 1.7), diabetes (OR, 1.8), chronic pancreatitis (OR, 14.3), and first-degree family history of pancreatic cancer (OR, 3.1).

Dr. Archibugi and her associates had no disclosures.

SAN DIEGO – Statin use, but not aspirin use, showed a protective effect against pancreatic ductal adenocarcinoma in a large prospective case-control study.

“There also appears to be no chemoenhancing effect from combining the two drugs,” Dr. Livia Archibugi of Hospital Sant’Andrea in Rome, Italy, said at the annual Digestive Disease Week. The study also confirmed known risk factors for pancreatic cancer, “supporting the genuineness of our population,” she and her associates said.

Louise Koenig/Frontline Medical News

This is the first epidemiologic study to look at both aspirin and statins in relationship to pancreatic cancer. Both types of drugs have shown anticarcinogenic effects in laboratory and epidemiologic studies, Dr. Archibugi noted. For example, aspirin blocks mTOR, NF-kappa B and Wnt signaling, which inhibits carcinogenesis and angiogenesis and promotes apoptosis and DNA mismatch repair. A recent meta-analysis, found a 23% lower risk of pancreatic cancer among aspirin users than nonusers, but the study did not assess concurrent statin use.

Statins, for their part, are both immunomodulatory and anti-inflammatory, and inhibit angiogenesis at low doses, said Dr. Archibugi. However, studies have yielded mixed results about whether they reduce the risk of pancreatic cancer, she noted.

Therefore, between 2005 and 2016, she and her colleagues used questionnaires to study environmental exposures and the family and individual health histories of 408 consecutive patients with pancreatic ductal adenocarcinoma and 816 age- and sex-matched controls. The controls were gastroenterology patients at the same hospital and did not have chronic obstructive pulmonary disease, cirrhosis, chronic kidney failure, acute bleeding, inflammatory bowel disease, or a history of cancer in the past 5 years. The study was large enough to have an 80% power to detect an odds ratio of 0.65 for the relationship between incident pancreatic cancer and either aspirin or statin exposure, and an odds ratio of 0.5 for dual exposure, Dr. Archibugi noted.

Reported statin use was significantly more common among controls (24%) than cases (18%; P = .03), and controls were more likely than cases to report taking either low-dose (less than 20 mg) or high-dose (greater than 20 mg) statins, the investigators found. Proportionally more controls also reported at least a 5-year history of statin use. After controlling for age, sex, and known risk factors, only statin use was significantly associated with incident pancreatic cancer in the multivariate analysis (OR, 0.59; 95% confidence interval, 0.42-0.85; P = .004). The protective effect of statins held up in subgroups stratified by gender, age, and statin type, Dr. Archibugi said.

In contrast, statistically similar proportions of cases (19%) and controls (23%) reported using aspirin, and although aspirin use was inversely linked to incident pancreatic cancer in the univariate analysis, the effect lost significance in the multivariable analysis (OR, 0.78; 95% CI, 0.54-1.11). Moreover, patients who took both aspirin and statins were no less likely to develop pancreatic cancer than those who took only statins.

Like all case-control studies, recall bias could have affected the associations, she noted. However, the same analyses correlated pancreatic cancer with several known risk factors, including smoking (OR, 1.8), heavy drinking (OR, 1.7), diabetes (OR, 1.8), chronic pancreatitis (OR, 14.3), and first-degree family history of pancreatic cancer (OR, 3.1).

Dr. Archibugi and her associates had no disclosures.

SAN DIEGO – A colonoscopy capsule that requires no bowel preparation safely detected pedunculated and sessile polyps as small as 7 mm in a feasibility study of 54 volunteers.

The capsule scans the colon with very-low-dose X-rays, and the images are converted to high-resolution three-dimensional reconstructions that physicians can review remotely in about 10 minutes, said Dr. Nadir Arber of the Integrated Cancer Prevention Center at Tel Aviv Sourasky Medical Center. “All 54 capsules were excreted naturally, without discomfort or side effects,” he reported at the annual Digestive Disease Week.

Amy Karon

Bowel preparation is the most common reason for skipping a colonoscopy, and poor preparation leads to missed adenomas on conventional screens, Dr. Arber noted. “A colorectal cancer screening method that would generate structural data of the colon, without cathartic cleansing or diet restrictions, would offer an attractive alternative for many patients,” he said.

This capsule is no larger than others that have been approved, but it uses low-dose X-rays to circumvent the need for bowel preparation. Patients swallow the capsules and go about their day while wearing tracking patches on their lower backs that transmit (nonionizing) radiofrequency data to a localization system. This system determines when a capsule has reached the colon. At this point, the capsule is activated and begins emitting X-rays, but only when it is moving, Dr. Arber said. Because the capsule usually is not moving, radiation exposure is minimized. Also, an axis-positioning system reconciles the location of the capsule with the colonic wall to prevent movement artifacts.

The 54 volunteers in the study were 45-75 years old. The capsules took an average of 66 hours to move through the entire alimentary tract, with a standard deviation of 37 hours. If swallowed before the first meal of the day, the transit time averaged 51 hours, with a standard deviation of 25 hours. The total radiation dose per procedure averaged 0.03 mSv (standard deviation, 0.0007 mSv), which is equivalent to one dental or chest X-ray, Dr. Arber said.

Examples of reconstructed lesions included a 12 × 4 mm flat sessile polyp, a double-headed polyp with heads measuring 7 and 15 mm, and a 25-mm polyp in the sigmoid colon. “In humans, 7-mm polyps are well within the detection capability of the system,” he said.

He and his associates are planning multicenter studies to compare adenoma detection by the capsule with traditional colonoscopy. Reconstructing long pedunculated polyps might be difficult because of image distortion, Dr. Arber acknowledged.

He reported that his spouse or partner has received consulting fees from Check-Cap Ltd., the maker of the capsule.

SAN DIEGO – A colonoscopy capsule that requires no bowel preparation safely detected pedunculated and sessile polyps as small as 7 mm in a feasibility study of 54 volunteers.

The capsule scans the colon with very-low-dose X-rays, and the images are converted to high-resolution three-dimensional reconstructions that physicians can review remotely in about 10 minutes, said Dr. Nadir Arber of the Integrated Cancer Prevention Center at Tel Aviv Sourasky Medical Center. “All 54 capsules were excreted naturally, without discomfort or side effects,” he reported at the annual Digestive Disease Week.

Amy Karon

Bowel preparation is the most common reason for skipping a colonoscopy, and poor preparation leads to missed adenomas on conventional screens, Dr. Arber noted. “A colorectal cancer screening method that would generate structural data of the colon, without cathartic cleansing or diet restrictions, would offer an attractive alternative for many patients,” he said.

This capsule is no larger than others that have been approved, but it uses low-dose X-rays to circumvent the need for bowel preparation. Patients swallow the capsules and go about their day while wearing tracking patches on their lower backs that transmit (nonionizing) radiofrequency data to a localization system. This system determines when a capsule has reached the colon. At this point, the capsule is activated and begins emitting X-rays, but only when it is moving, Dr. Arber said. Because the capsule usually is not moving, radiation exposure is minimized. Also, an axis-positioning system reconciles the location of the capsule with the colonic wall to prevent movement artifacts.

The 54 volunteers in the study were 45-75 years old. The capsules took an average of 66 hours to move through the entire alimentary tract, with a standard deviation of 37 hours. If swallowed before the first meal of the day, the transit time averaged 51 hours, with a standard deviation of 25 hours. The total radiation dose per procedure averaged 0.03 mSv (standard deviation, 0.0007 mSv), which is equivalent to one dental or chest X-ray, Dr. Arber said.

Examples of reconstructed lesions included a 12 × 4 mm flat sessile polyp, a double-headed polyp with heads measuring 7 and 15 mm, and a 25-mm polyp in the sigmoid colon. “In humans, 7-mm polyps are well within the detection capability of the system,” he said.

He and his associates are planning multicenter studies to compare adenoma detection by the capsule with traditional colonoscopy. Reconstructing long pedunculated polyps might be difficult because of image distortion, Dr. Arber acknowledged.

He reported that his spouse or partner has received consulting fees from Check-Cap Ltd., the maker of the capsule.

SAN DIEGO – A colonoscopy capsule that requires no bowel preparation safely detected pedunculated and sessile polyps as small as 7 mm in a feasibility study of 54 volunteers.

The capsule scans the colon with very-low-dose X-rays, and the images are converted to high-resolution three-dimensional reconstructions that physicians can review remotely in about 10 minutes, said Dr. Nadir Arber of the Integrated Cancer Prevention Center at Tel Aviv Sourasky Medical Center. “All 54 capsules were excreted naturally, without discomfort or side effects,” he reported at the annual Digestive Disease Week.

Amy Karon

Bowel preparation is the most common reason for skipping a colonoscopy, and poor preparation leads to missed adenomas on conventional screens, Dr. Arber noted. “A colorectal cancer screening method that would generate structural data of the colon, without cathartic cleansing or diet restrictions, would offer an attractive alternative for many patients,” he said.

This capsule is no larger than others that have been approved, but it uses low-dose X-rays to circumvent the need for bowel preparation. Patients swallow the capsules and go about their day while wearing tracking patches on their lower backs that transmit (nonionizing) radiofrequency data to a localization system. This system determines when a capsule has reached the colon. At this point, the capsule is activated and begins emitting X-rays, but only when it is moving, Dr. Arber said. Because the capsule usually is not moving, radiation exposure is minimized. Also, an axis-positioning system reconciles the location of the capsule with the colonic wall to prevent movement artifacts.

The 54 volunteers in the study were 45-75 years old. The capsules took an average of 66 hours to move through the entire alimentary tract, with a standard deviation of 37 hours. If swallowed before the first meal of the day, the transit time averaged 51 hours, with a standard deviation of 25 hours. The total radiation dose per procedure averaged 0.03 mSv (standard deviation, 0.0007 mSv), which is equivalent to one dental or chest X-ray, Dr. Arber said.

Examples of reconstructed lesions included a 12 × 4 mm flat sessile polyp, a double-headed polyp with heads measuring 7 and 15 mm, and a 25-mm polyp in the sigmoid colon. “In humans, 7-mm polyps are well within the detection capability of the system,” he said.

He and his associates are planning multicenter studies to compare adenoma detection by the capsule with traditional colonoscopy. Reconstructing long pedunculated polyps might be difficult because of image distortion, Dr. Arber acknowledged.

He reported that his spouse or partner has received consulting fees from Check-Cap Ltd., the maker of the capsule.

SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.

The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.

Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.

However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.

Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.

After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).

“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”

Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”

During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”

The research is hospital-funded. Dr. Laursen had no financial disclosures to report.

SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.

The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.

Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.

However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.

Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.

After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).

“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”

Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”

During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”

The research is hospital-funded. Dr. Laursen had no financial disclosures to report.

SAN DIEGO – Taking selective serotonin reuptake inhibitors (SSRIs) was not associated with an increased risk of endoscopy-refractory bleeding, rebleeding, or in-hospital mortality among 14,343 consecutive patients admitted with bleeding peptic ulcer in Denmark.

The study suggests that patients with bleeding peptic ulcers can “continue SSRI treatment if the treatment is well indicated,” and that these patients can otherwise receive treatment similar to that of other patients with peptic ulcer bleeding, Dr. Stig B. Laursen reported at the annual Digestive Disease Week.

Observational research has linked use of SSRI antidepressants to an approximately 1.5-fold increase in upper GI bleeding in peptic ulcer bleeding cases, said Dr. Laursen of Odense (Denmark) University Hospital. Studies, mostly in vitro ones, indicate SSRIs decrease the function of thrombocytes and fibrin formation via lowered levels of serotonin. Therefore, it has been suggested that temporarily discontinuing SSRIs may benefit patients with bleeding peptic ulcers.

However, sudden cessation of SSRIs can be associated with withdrawal symptoms, which have been reported in up to one-third of such patients.

Dr. Laursen and his associates prospectively analyzed data for 14,343 consecutive patients admitted with bleeding peptic ulcers in Denmark from 2006 to 2014. They investigated associations between SSRI use and several outcomes, adjusted for confounding factors including age, sex, comorbidity, anemia, medication use, circulatory failure at hospital admission, location of ulcer, stigmata of bleeding, and weekend admission.

After adjustment for confounding risk factors, SSRIs were not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] 95% confidence interval [CI]: 1.01 [0.78-1.30]), rebleeding (OR [95% CI]: 0.94 [0.81-1.10]), or in-hospital mortality (hazard ratio [95% CI]: 0.84 [0.68-1.05]).

“Patients taking SSRIs have the same outcomes following peptic ulcer bleeding as non-SSRI users. This suggests that there is no clinically significant impairment of hemostatic function,” Dr. Laursen said. “Therefore, it seems safe to continue SSRI treatment in patients developing peptic ulcer bleeding and thereby avoid development of withdrawal symptoms.”

Dr. Laursen noted that the study has several limitations. It’s not a randomized controlled trial, he said, and there’s no information about the types of SSRIs that the patients were taking. Also, there’s a lack of information about possible discontinuation of SSRIs during hospitalization. However, he said, “that doesn’t seem to be a major confounder.”

During the question-and-answer session following his presentation, Dr. Laursen said the increased risk of poor outcome is quite low, but “there may be a small risk that we haven’t found yet. But if it’s small, maybe it doesn’t have an impact in day-to-day practice.”

The research is hospital-funded. Dr. Laursen had no financial disclosures to report.

SAN DIEGO – The experimental drug Metavert was effective in a mouse model of aggressive pancreatic cancer, and phase I trials in humans are expected to begin in early 2017.

“Metavert significantly slows tumor growth with less toxicity in preclinical trials. The drug prevents metastasis and reduces resistance to chemotherapy. Hopefully the drug will be a good partner with other drugs,” said presenting author Mouad Edderkaoui, Ph.D., of Cedars-Sinai, Los Angeles. “We hope this drug will improve the outcome of treatment of pancreatic cancer, knowing that the drugs now available are not effective and outcome is dismal. The last drug approved for pancreatic cancer – nab-paclitaxel – extended survival by only 7 weeks.”

Dr. Edderkaoui and Dr. Stephen Pandol, director, basic and translational pancreas research, gastroenterology, at Cedars-Sinai, are cofounders of Avenzoar Pharmaceuticals, the developer of Metavert.

Metavert is a small molecular dual inhibitor that targets two procancer pathways. Preclinical results show strong prevention of pancreatic cancer growth and metastasis with no significant toxicity, according to Dr. Edderkaoui, who explained that the novel agent has two linked moieties that target the glycogen synthase kinase–3 (GSK-3) beta and histone deacetylase (HDAC).

GSK-3 beta, which is highly expressed in pancreatic cancer, stimulates proliferation and resistance to apoptosis in cancer cells. HDAC inhibits epithelial cells. In combination, the two should simultaneously affect proliferation and metastasis.

The investigators studied pancreatic cell lines and KPC mice – an animal model of aggressive pancreatic cancer that carries KRAS and p53 mutations. Metavert reduced the survival of cancer cell lines but not of normal cells.

“The [combination] drug was more potent in cell lines than the two inhibitors separately,” he said. In dose-dependent fashion, Metavert inhibited GSK-3 beta and HDAC, decreased markers of epithelial to mesenchymal transition, and decreased migration of pancreatic cancer cells.

Further, Metavert sensitized pancreatic cancer cells to chemotherapy with gemcitabine and to radiation.

In KPC mice with advanced pancreatic cancer, treatment with Metavert increased survival by about 50%. At 6 months, all control mice had died, while 42% of Metavert-treated mice were still alive.

Tumor shrinkage was observed in Metavert-treated mice. Micrometastasis was seen in 29% of controls and in none of the Metavert-treated mice.

Fibrosis was not significantly affected by treatment, and the level of M2 macrophages significantly declined in treated mice.

SAN DIEGO – The experimental drug Metavert was effective in a mouse model of aggressive pancreatic cancer, and phase I trials in humans are expected to begin in early 2017.

“Metavert significantly slows tumor growth with less toxicity in preclinical trials. The drug prevents metastasis and reduces resistance to chemotherapy. Hopefully the drug will be a good partner with other drugs,” said presenting author Mouad Edderkaoui, Ph.D., of Cedars-Sinai, Los Angeles. “We hope this drug will improve the outcome of treatment of pancreatic cancer, knowing that the drugs now available are not effective and outcome is dismal. The last drug approved for pancreatic cancer – nab-paclitaxel – extended survival by only 7 weeks.”

Dr. Edderkaoui and Dr. Stephen Pandol, director, basic and translational pancreas research, gastroenterology, at Cedars-Sinai, are cofounders of Avenzoar Pharmaceuticals, the developer of Metavert.

Metavert is a small molecular dual inhibitor that targets two procancer pathways. Preclinical results show strong prevention of pancreatic cancer growth and metastasis with no significant toxicity, according to Dr. Edderkaoui, who explained that the novel agent has two linked moieties that target the glycogen synthase kinase–3 (GSK-3) beta and histone deacetylase (HDAC).

GSK-3 beta, which is highly expressed in pancreatic cancer, stimulates proliferation and resistance to apoptosis in cancer cells. HDAC inhibits epithelial cells. In combination, the two should simultaneously affect proliferation and metastasis.

The investigators studied pancreatic cell lines and KPC mice – an animal model of aggressive pancreatic cancer that carries KRAS and p53 mutations. Metavert reduced the survival of cancer cell lines but not of normal cells.

“The [combination] drug was more potent in cell lines than the two inhibitors separately,” he said. In dose-dependent fashion, Metavert inhibited GSK-3 beta and HDAC, decreased markers of epithelial to mesenchymal transition, and decreased migration of pancreatic cancer cells.

Further, Metavert sensitized pancreatic cancer cells to chemotherapy with gemcitabine and to radiation.

In KPC mice with advanced pancreatic cancer, treatment with Metavert increased survival by about 50%. At 6 months, all control mice had died, while 42% of Metavert-treated mice were still alive.

Tumor shrinkage was observed in Metavert-treated mice. Micrometastasis was seen in 29% of controls and in none of the Metavert-treated mice.

Fibrosis was not significantly affected by treatment, and the level of M2 macrophages significantly declined in treated mice.

SAN DIEGO – The experimental drug Metavert was effective in a mouse model of aggressive pancreatic cancer, and phase I trials in humans are expected to begin in early 2017.

“Metavert significantly slows tumor growth with less toxicity in preclinical trials. The drug prevents metastasis and reduces resistance to chemotherapy. Hopefully the drug will be a good partner with other drugs,” said presenting author Mouad Edderkaoui, Ph.D., of Cedars-Sinai, Los Angeles. “We hope this drug will improve the outcome of treatment of pancreatic cancer, knowing that the drugs now available are not effective and outcome is dismal. The last drug approved for pancreatic cancer – nab-paclitaxel – extended survival by only 7 weeks.”

Dr. Edderkaoui and Dr. Stephen Pandol, director, basic and translational pancreas research, gastroenterology, at Cedars-Sinai, are cofounders of Avenzoar Pharmaceuticals, the developer of Metavert.

Metavert is a small molecular dual inhibitor that targets two procancer pathways. Preclinical results show strong prevention of pancreatic cancer growth and metastasis with no significant toxicity, according to Dr. Edderkaoui, who explained that the novel agent has two linked moieties that target the glycogen synthase kinase–3 (GSK-3) beta and histone deacetylase (HDAC).

GSK-3 beta, which is highly expressed in pancreatic cancer, stimulates proliferation and resistance to apoptosis in cancer cells. HDAC inhibits epithelial cells. In combination, the two should simultaneously affect proliferation and metastasis.

The investigators studied pancreatic cell lines and KPC mice – an animal model of aggressive pancreatic cancer that carries KRAS and p53 mutations. Metavert reduced the survival of cancer cell lines but not of normal cells.

“The [combination] drug was more potent in cell lines than the two inhibitors separately,” he said. In dose-dependent fashion, Metavert inhibited GSK-3 beta and HDAC, decreased markers of epithelial to mesenchymal transition, and decreased migration of pancreatic cancer cells.

Further, Metavert sensitized pancreatic cancer cells to chemotherapy with gemcitabine and to radiation.

In KPC mice with advanced pancreatic cancer, treatment with Metavert increased survival by about 50%. At 6 months, all control mice had died, while 42% of Metavert-treated mice were still alive.

Tumor shrinkage was observed in Metavert-treated mice. Micrometastasis was seen in 29% of controls and in none of the Metavert-treated mice.

Fibrosis was not significantly affected by treatment, and the level of M2 macrophages significantly declined in treated mice.

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.