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Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.

The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”

SOURCE: American Gastroenterological Society

The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).

Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.

Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”

The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.

Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.

The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”

SOURCE: American Gastroenterological Society

The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).

Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.

Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”

The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.

Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.

The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”

SOURCE: American Gastroenterological Society

The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).

Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.

Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”

The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.

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.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

There is good news for people who avoid colonoscopies because of the day-long preparation with a clear liquid cleansing diet. New research shows that consuming small portions of low-residue (low-fiber) solid foods on the day before colonoscopy led to improved colonoscopies, compared with a clear liquid diet.

In addition, people who consumed low-residue foods had more energy on the day before and the day of the procedure, compared with those on a clear liquid diet.

“Colonoscopies prevent death from colorectal cancer, yet millions of people avoid this screening. Many cite dietary restrictions as a deterrent. The clear liquid diet is standard of care [for colonoscopy preparation] in the U.S. We found that low-residue foods led to a better colonoscopy compared to a liquid diet. Also, patients were more comfortable, less hungry, and less fatigued on the morning of colonoscopy,” said lead author Dr. Jason Samarasena, associate professor at the University of California, Irvine. He presented this research at a teleconference at the annual Digestive Disease Week.

In this single-center, randomized trial, people assigned to the low-residue diet could eat small portions of protein, carbohydrate, and fat at three meals on the day before colonoscopy. The group assigned to the clear liquid diet could drink only broth, black coffee, tea, and other clear liquids. Both groups drank standard bowel-cleansing liquid on the night before and the morning of the procedure.

Dr. Samarasena explained that low-residue foods, such as eggs, yogurt, cheese, bread, cottage cheese, chicken nuggets, and macaroni and cheese, are easily broken down in the stomach and cleaned out by the bowel preparation.

“High-residue foods, such as fruit, nuts, or vegetables, don’t break down as much and make it more difficult to visualize the colon,” he said.

The study included 83 patients who underwent colonoscopies at two sites over a 1-year period from 2014 to 2015. An adequate bowel preparation was defined as a Boston Bowel Preparation Scale (BBPS) score greater than 6. All endoscopists were blinded and all colonoscopies were video recorded.

In an interim blinded analysis, the low-residue diet allowed a significantly higher number of adequate bowel preparations, compared with the clear liquid diet group: mean BBPS was 7.98 for the low-residue diet group and 7.54 for the clear liquid diet group (P = .05).

People assigned to the low-residue diet expressed a much higher level of satisfaction for the diet: 97% versus 46% who rated the clear liquid diet satisfactory.

In addition, people assigned to the low-residue group had significantly lower hunger scores on a scale from 1 to 10, with 10 being most hungry on the evening before the colonoscopy (3.5 for the low-residue diet versus 6.9 for the clear liquid diet, P = .001), and lower fatigue scores (3.5 versus 6, respectively, P = .01) on a 10-point scale on the morning of the procedure, compared with the clear liquid diet group.

There was no significant difference between the two groups for mean symptom scores for nausea, vomiting, bloating, abdominal cramping, and overall discomfort.

“Patients slated to undergo colonoscopy often have to miss at least a day of work. A low-residue diet may allow patients to work on the day before the procedure,” Dr. Samarasena noted.

Dr. Samarasena and his coinvestigators plan to enroll more patients for a larger sample size to compare both diets.

“This will be one of the largest studies in the U.S. to evaluate a low-residue diet. We hope this will encourage gastroenterologists in the U.S. to use a low-residue diet and that more patients will then undergo colonoscopy screening,“ he said.

There is good news for people who avoid colonoscopies because of the day-long preparation with a clear liquid cleansing diet. New research shows that consuming small portions of low-residue (low-fiber) solid foods on the day before colonoscopy led to improved colonoscopies, compared with a clear liquid diet.

In addition, people who consumed low-residue foods had more energy on the day before and the day of the procedure, compared with those on a clear liquid diet.

“Colonoscopies prevent death from colorectal cancer, yet millions of people avoid this screening. Many cite dietary restrictions as a deterrent. The clear liquid diet is standard of care [for colonoscopy preparation] in the U.S. We found that low-residue foods led to a better colonoscopy compared to a liquid diet. Also, patients were more comfortable, less hungry, and less fatigued on the morning of colonoscopy,” said lead author Dr. Jason Samarasena, associate professor at the University of California, Irvine. He presented this research at a teleconference at the annual Digestive Disease Week.

In this single-center, randomized trial, people assigned to the low-residue diet could eat small portions of protein, carbohydrate, and fat at three meals on the day before colonoscopy. The group assigned to the clear liquid diet could drink only broth, black coffee, tea, and other clear liquids. Both groups drank standard bowel-cleansing liquid on the night before and the morning of the procedure.

Dr. Samarasena explained that low-residue foods, such as eggs, yogurt, cheese, bread, cottage cheese, chicken nuggets, and macaroni and cheese, are easily broken down in the stomach and cleaned out by the bowel preparation.

“High-residue foods, such as fruit, nuts, or vegetables, don’t break down as much and make it more difficult to visualize the colon,” he said.

The study included 83 patients who underwent colonoscopies at two sites over a 1-year period from 2014 to 2015. An adequate bowel preparation was defined as a Boston Bowel Preparation Scale (BBPS) score greater than 6. All endoscopists were blinded and all colonoscopies were video recorded.

In an interim blinded analysis, the low-residue diet allowed a significantly higher number of adequate bowel preparations, compared with the clear liquid diet group: mean BBPS was 7.98 for the low-residue diet group and 7.54 for the clear liquid diet group (P = .05).

People assigned to the low-residue diet expressed a much higher level of satisfaction for the diet: 97% versus 46% who rated the clear liquid diet satisfactory.

In addition, people assigned to the low-residue group had significantly lower hunger scores on a scale from 1 to 10, with 10 being most hungry on the evening before the colonoscopy (3.5 for the low-residue diet versus 6.9 for the clear liquid diet, P = .001), and lower fatigue scores (3.5 versus 6, respectively, P = .01) on a 10-point scale on the morning of the procedure, compared with the clear liquid diet group.

There was no significant difference between the two groups for mean symptom scores for nausea, vomiting, bloating, abdominal cramping, and overall discomfort.

“Patients slated to undergo colonoscopy often have to miss at least a day of work. A low-residue diet may allow patients to work on the day before the procedure,” Dr. Samarasena noted.

Dr. Samarasena and his coinvestigators plan to enroll more patients for a larger sample size to compare both diets.

“This will be one of the largest studies in the U.S. to evaluate a low-residue diet. We hope this will encourage gastroenterologists in the U.S. to use a low-residue diet and that more patients will then undergo colonoscopy screening,“ he said.

There is good news for people who avoid colonoscopies because of the day-long preparation with a clear liquid cleansing diet. New research shows that consuming small portions of low-residue (low-fiber) solid foods on the day before colonoscopy led to improved colonoscopies, compared with a clear liquid diet.

In addition, people who consumed low-residue foods had more energy on the day before and the day of the procedure, compared with those on a clear liquid diet.

“Colonoscopies prevent death from colorectal cancer, yet millions of people avoid this screening. Many cite dietary restrictions as a deterrent. The clear liquid diet is standard of care [for colonoscopy preparation] in the U.S. We found that low-residue foods led to a better colonoscopy compared to a liquid diet. Also, patients were more comfortable, less hungry, and less fatigued on the morning of colonoscopy,” said lead author Dr. Jason Samarasena, associate professor at the University of California, Irvine. He presented this research at a teleconference at the annual Digestive Disease Week.

In this single-center, randomized trial, people assigned to the low-residue diet could eat small portions of protein, carbohydrate, and fat at three meals on the day before colonoscopy. The group assigned to the clear liquid diet could drink only broth, black coffee, tea, and other clear liquids. Both groups drank standard bowel-cleansing liquid on the night before and the morning of the procedure.

Dr. Samarasena explained that low-residue foods, such as eggs, yogurt, cheese, bread, cottage cheese, chicken nuggets, and macaroni and cheese, are easily broken down in the stomach and cleaned out by the bowel preparation.

“High-residue foods, such as fruit, nuts, or vegetables, don’t break down as much and make it more difficult to visualize the colon,” he said.

The study included 83 patients who underwent colonoscopies at two sites over a 1-year period from 2014 to 2015. An adequate bowel preparation was defined as a Boston Bowel Preparation Scale (BBPS) score greater than 6. All endoscopists were blinded and all colonoscopies were video recorded.

In an interim blinded analysis, the low-residue diet allowed a significantly higher number of adequate bowel preparations, compared with the clear liquid diet group: mean BBPS was 7.98 for the low-residue diet group and 7.54 for the clear liquid diet group (P = .05).

People assigned to the low-residue diet expressed a much higher level of satisfaction for the diet: 97% versus 46% who rated the clear liquid diet satisfactory.

In addition, people assigned to the low-residue group had significantly lower hunger scores on a scale from 1 to 10, with 10 being most hungry on the evening before the colonoscopy (3.5 for the low-residue diet versus 6.9 for the clear liquid diet, P = .001), and lower fatigue scores (3.5 versus 6, respectively, P = .01) on a 10-point scale on the morning of the procedure, compared with the clear liquid diet group.

There was no significant difference between the two groups for mean symptom scores for nausea, vomiting, bloating, abdominal cramping, and overall discomfort.

“Patients slated to undergo colonoscopy often have to miss at least a day of work. A low-residue diet may allow patients to work on the day before the procedure,” Dr. Samarasena noted.

Dr. Samarasena and his coinvestigators plan to enroll more patients for a larger sample size to compare both diets.

“This will be one of the largest studies in the U.S. to evaluate a low-residue diet. We hope this will encourage gastroenterologists in the U.S. to use a low-residue diet and that more patients will then undergo colonoscopy screening,“ he said.

SAN DIEGO – The investigational oral drug, naldemedine, was found effective in treating opioid-induced constipation (OIC) in patients with noncancer chronic pain, according to results of two identically designed phase III trials (COMPOSE I and II). Naldemedine achieved durable efficacy and consistent safety, with a low incidence of gastrointestinal side effects, and importantly did not compromise or interfere with the analgesic effect of opioids.

In both studies, the drug met the primary endpoint and significantly improved all secondary endpoints. Improved frequency of spontaneous bowel movements (SBMs) was observed for at least 9 weeks out of the 12 weeks (the primary endpoint) in 47.6% of naldemedine-treated patients, compared with 34.6% of placebo patients in COMPOSE I. In COMPOSE II, 52.5% versus 33.6%, respectively, had improved frequency of SMB for at least 9 out of 12 weeks.

“Improvement with naldemedine was seen early and was durable, with no evidence of opiate withdrawal. This is good news for patients with OIC, given the significant impact this condition can have and the difficulty they can have in finding a safe and effective treatment,” said presenting author Dr. Martin Hale, an orthopedic surgeon and pain management specialist. He presented results of both trials at the annual Digestive Disease Week.

Naldemedine is a naltrexone-based, once-daily, oral, peripherally acting mu-opioid–receptor antagonist being developed by Shionogi. The fact that it is not centrally acting suggests that its side effect profile would be acceptable. Opiates work on mu receptors, reducing GI motility and fluid secretion, resulting in OIC.

“Laxatives have limited efficacy for OIC and do not address the underlying problem,” Dr. Hale of Gold Coast Research, Plantation, Fla., said. Thus, better treatments are needed.

Study details

Both studies were 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. COMPOSE I included 547 patients, and COMPOSE II, 553 patients. To be included, patients had to be on opioid therapy for at least 3 months and on a stable dose of opioids for at least 4 weeks. They had to have noncancer pain accompanied by OIC.

Patients were randomized in a 1:1 ratio to oral naldemedine 0.2 mg with or without food versus placebo. “Being able to take the drug with food makes it more acceptable to patients,” Dr. Hale noted.

Responses were observed early in the course of the 12-week trial and remained durable. Naldemedine treatment significantly improved the frequency of SBMs per week, compared with placebo (P less than .0001 in both studies), and SBMs without straining per week from baseline to the last 2 weeks of the study (P = .0003 in COMPOSE I and P = .0011 in COMPOSE II).

Adverse events were similar across all four arms of both studies. Treatment-related adverse events were reported in about 48% of patients across both trials. Major adverse cardiovascular events (MACE) of concern occurred in 1 patient in treated with naldemedine and 1 in the placebo group. “MACE is not relevant with this drug,” Dr Hale told listeners.

Abdominal pain and diarrhea were the only treatment-related adverse events reported in greater than 5% of patients treated with naldemedine versus placebo. Abdominal pain was reported in 6.3% of the treated groups in COMPOSE I and 5.2% of the treated group in COMPOSE II versus 1.8% and 2.9%, respectively, in the placebo groups. Diarrhea was reported in 6.6% of the naldemedine patients in COMPOSE I and in 8.9% in COMPOSE II, compared with 2.9% and 1.8%, respectively, on placebo. Nausea was reported in 4.8% of naldemedine-treated patients in both trials, compared with 2.6% and 3.3%, respectively, in the placebo arms.

“Most treatment-emergent adverse events were mild or moderate. Back pain and flatulence were rare,” he commented.

Two scales were used to measure opiate withdrawal: Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Score (SOWS). The graph curves were superimposable for naldemedine and placebo at all time points, showing that naldemedine did not interfere with the analgesic effect of opioids.

The study was funded by Shionogi, Florham Park, N.J.

[email protected]

SAN DIEGO – The investigational oral drug, naldemedine, was found effective in treating opioid-induced constipation (OIC) in patients with noncancer chronic pain, according to results of two identically designed phase III trials (COMPOSE I and II). Naldemedine achieved durable efficacy and consistent safety, with a low incidence of gastrointestinal side effects, and importantly did not compromise or interfere with the analgesic effect of opioids.

In both studies, the drug met the primary endpoint and significantly improved all secondary endpoints. Improved frequency of spontaneous bowel movements (SBMs) was observed for at least 9 weeks out of the 12 weeks (the primary endpoint) in 47.6% of naldemedine-treated patients, compared with 34.6% of placebo patients in COMPOSE I. In COMPOSE II, 52.5% versus 33.6%, respectively, had improved frequency of SMB for at least 9 out of 12 weeks.

“Improvement with naldemedine was seen early and was durable, with no evidence of opiate withdrawal. This is good news for patients with OIC, given the significant impact this condition can have and the difficulty they can have in finding a safe and effective treatment,” said presenting author Dr. Martin Hale, an orthopedic surgeon and pain management specialist. He presented results of both trials at the annual Digestive Disease Week.

Naldemedine is a naltrexone-based, once-daily, oral, peripherally acting mu-opioid–receptor antagonist being developed by Shionogi. The fact that it is not centrally acting suggests that its side effect profile would be acceptable. Opiates work on mu receptors, reducing GI motility and fluid secretion, resulting in OIC.

“Laxatives have limited efficacy for OIC and do not address the underlying problem,” Dr. Hale of Gold Coast Research, Plantation, Fla., said. Thus, better treatments are needed.

Study details

Both studies were 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. COMPOSE I included 547 patients, and COMPOSE II, 553 patients. To be included, patients had to be on opioid therapy for at least 3 months and on a stable dose of opioids for at least 4 weeks. They had to have noncancer pain accompanied by OIC.

Patients were randomized in a 1:1 ratio to oral naldemedine 0.2 mg with or without food versus placebo. “Being able to take the drug with food makes it more acceptable to patients,” Dr. Hale noted.

Responses were observed early in the course of the 12-week trial and remained durable. Naldemedine treatment significantly improved the frequency of SBMs per week, compared with placebo (P less than .0001 in both studies), and SBMs without straining per week from baseline to the last 2 weeks of the study (P = .0003 in COMPOSE I and P = .0011 in COMPOSE II).

Adverse events were similar across all four arms of both studies. Treatment-related adverse events were reported in about 48% of patients across both trials. Major adverse cardiovascular events (MACE) of concern occurred in 1 patient in treated with naldemedine and 1 in the placebo group. “MACE is not relevant with this drug,” Dr Hale told listeners.

Abdominal pain and diarrhea were the only treatment-related adverse events reported in greater than 5% of patients treated with naldemedine versus placebo. Abdominal pain was reported in 6.3% of the treated groups in COMPOSE I and 5.2% of the treated group in COMPOSE II versus 1.8% and 2.9%, respectively, in the placebo groups. Diarrhea was reported in 6.6% of the naldemedine patients in COMPOSE I and in 8.9% in COMPOSE II, compared with 2.9% and 1.8%, respectively, on placebo. Nausea was reported in 4.8% of naldemedine-treated patients in both trials, compared with 2.6% and 3.3%, respectively, in the placebo arms.

“Most treatment-emergent adverse events were mild or moderate. Back pain and flatulence were rare,” he commented.

Two scales were used to measure opiate withdrawal: Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Score (SOWS). The graph curves were superimposable for naldemedine and placebo at all time points, showing that naldemedine did not interfere with the analgesic effect of opioids.

The study was funded by Shionogi, Florham Park, N.J.

[email protected]

SAN DIEGO – The investigational oral drug, naldemedine, was found effective in treating opioid-induced constipation (OIC) in patients with noncancer chronic pain, according to results of two identically designed phase III trials (COMPOSE I and II). Naldemedine achieved durable efficacy and consistent safety, with a low incidence of gastrointestinal side effects, and importantly did not compromise or interfere with the analgesic effect of opioids.

In both studies, the drug met the primary endpoint and significantly improved all secondary endpoints. Improved frequency of spontaneous bowel movements (SBMs) was observed for at least 9 weeks out of the 12 weeks (the primary endpoint) in 47.6% of naldemedine-treated patients, compared with 34.6% of placebo patients in COMPOSE I. In COMPOSE II, 52.5% versus 33.6%, respectively, had improved frequency of SMB for at least 9 out of 12 weeks.

“Improvement with naldemedine was seen early and was durable, with no evidence of opiate withdrawal. This is good news for patients with OIC, given the significant impact this condition can have and the difficulty they can have in finding a safe and effective treatment,” said presenting author Dr. Martin Hale, an orthopedic surgeon and pain management specialist. He presented results of both trials at the annual Digestive Disease Week.

Naldemedine is a naltrexone-based, once-daily, oral, peripherally acting mu-opioid–receptor antagonist being developed by Shionogi. The fact that it is not centrally acting suggests that its side effect profile would be acceptable. Opiates work on mu receptors, reducing GI motility and fluid secretion, resulting in OIC.

“Laxatives have limited efficacy for OIC and do not address the underlying problem,” Dr. Hale of Gold Coast Research, Plantation, Fla., said. Thus, better treatments are needed.

Study details

Both studies were 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. COMPOSE I included 547 patients, and COMPOSE II, 553 patients. To be included, patients had to be on opioid therapy for at least 3 months and on a stable dose of opioids for at least 4 weeks. They had to have noncancer pain accompanied by OIC.

Patients were randomized in a 1:1 ratio to oral naldemedine 0.2 mg with or without food versus placebo. “Being able to take the drug with food makes it more acceptable to patients,” Dr. Hale noted.

Responses were observed early in the course of the 12-week trial and remained durable. Naldemedine treatment significantly improved the frequency of SBMs per week, compared with placebo (P less than .0001 in both studies), and SBMs without straining per week from baseline to the last 2 weeks of the study (P = .0003 in COMPOSE I and P = .0011 in COMPOSE II).

Adverse events were similar across all four arms of both studies. Treatment-related adverse events were reported in about 48% of patients across both trials. Major adverse cardiovascular events (MACE) of concern occurred in 1 patient in treated with naldemedine and 1 in the placebo group. “MACE is not relevant with this drug,” Dr Hale told listeners.

Abdominal pain and diarrhea were the only treatment-related adverse events reported in greater than 5% of patients treated with naldemedine versus placebo. Abdominal pain was reported in 6.3% of the treated groups in COMPOSE I and 5.2% of the treated group in COMPOSE II versus 1.8% and 2.9%, respectively, in the placebo groups. Diarrhea was reported in 6.6% of the naldemedine patients in COMPOSE I and in 8.9% in COMPOSE II, compared with 2.9% and 1.8%, respectively, on placebo. Nausea was reported in 4.8% of naldemedine-treated patients in both trials, compared with 2.6% and 3.3%, respectively, in the placebo arms.

“Most treatment-emergent adverse events were mild or moderate. Back pain and flatulence were rare,” he commented.

Two scales were used to measure opiate withdrawal: Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Score (SOWS). The graph curves were superimposable for naldemedine and placebo at all time points, showing that naldemedine did not interfere with the analgesic effect of opioids.

The study was funded by Shionogi, Florham Park, N.J.

[email protected]