From the AGA Journals

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.

Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.

“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.

©Thinkstock

Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).

During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.

Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.

The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.

Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.

“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.

©Thinkstock

Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).

During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.

Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.

The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.

Women with Crohn’s disease who were prescribed combination oral contraceptive pills for more than 3 years were 68% more likely to need gastrointestinal surgery than patients who did not use oral contraceptives, according to a national prospective cohort study reported in the June issue of Gastroenterology.

“Our data suggest the importance of carefully evaluating contraceptive options among women with established Crohn’s disease. Future studies should focus on mechanisms by which oral contraceptive use alters risk and progression,” said Dr. Hamed Khalili of Harvard Medical School in Boston and his associates at Harvard and Karolinska Institutet, Solna, Sweden.

©Thinkstock

Several studies have linked OC exposure to Crohn’s disease itself. But past studies of OCs and Crohn’s disease progression were small, retrospective, or did not adequately ascertain OC exposure, Dr. Khalili and his associates said. To help fill this gap, they identified 4,036 women with Crohn’s disease aged 16-51 years through the Swedish National Patient Register, and ascertained OC exposure by analyzing Sweden’s national prescription database (Gastroenterology. 2016 Feb 23. doi: 10.1053/j.gastro.2016.02.041).

During a median follow-up period of 58 months, 482 patients (12%) underwent surgery related to Crohn’s disease, the researchers said. Use of OCs was associated with surgery, but the link only reached statistical significance among women prescribed combination (estrogen-containing) regimens for more than 3 years (adjusted hazard ratio, 1.68; 95% confidence interval, 1.06-2.67) or for more than 900 doses (aHR, 1.60; 95% CI, 1.1-2.34). For each additional year that combination OCs were prescribed, surgery risk rose by nearly 30% (aHR, 1.29; 95% CI, 1.05-1.57). Thus, one extra surgery was needed for every 83 patients who received combination OCs for at least 1 year, said the investigators. Progestin-only prescriptions did not increase the likelihood of needing surgery, and there was no link between current or prior OC exposure and the chances of being prescribed steroids, they noted.

Only one other study has linked OC exposure with Crohn’s disease progression, and it included only 158 patients followed for just a year, Dr. Khalili and his associates said. Exactly how estrogen exposure might trigger Crohn’s disease progression is unclear, but OCs have been linked to changes in intestinal barrier function, increased humoral immunity, and modulation of testosterone levels, which in turn affects cytokine function, they added. “Regardless of the potential mechanism, the effect of OCs on Crohn’s disease progression appears to be related to consistent and long-term use of these medications. Similar patterns of associations have also been reported with other chronic illnesses, such as breast cancer and cardiovascular diseases,” said the researchers. Current OC use itself might not have predicted surgery in the study because about one in four women in Sweden stop taking OCs or switch to a nonhormonal form within 6 months of being prescribed them, they added.

The work was funded by the Crohn’s and Colitis Foundation of America, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Gastroenterological Association, and the American College of Gastroenterology. Dr. Khalili reported receiving consulting fees from Abbvie. One coinvestigator reported consulting relationships with Bayer Healthcare, Pfizer, and Pozen. The other investigators had no disclosures.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Using checklists and electronic decision support in an inpatient liver unit, quality improvement (QI) care protocols reduced 30-day readmissions of patients with cirrhosis by 40%, due mostly to a drop in readmissions for hepatic encephalopathy (HE) according to a report published in the May issue of Clinical Gastroenterology and Hepatology.

For patients initially admitted for overt HE, the 30-day readmission rate was 26.0% (27 of 104), compared with 48.9% (66 of 135) before implementation of QI. The proportion of total readmissions due to HE after QI was 9.6% (14 of 146), compared with 40.7% (79 of 194) before QI. In addition, length of stay for HE patients was significantly reduced (–1.34 days; 95% confidence interval, –2.38 to –0.32; P = .01). There were no significant changes in 90-day mortality.

Source: American Gastroenterological Association

“Our study advances the current literature on QI for patients with cirrhosis by presenting an inexpensive, easy to implement, and generalizable approach,” wrote Dr. Elliot Tapper of Beth Israel Deaconess Medical Center, Boston, and his colleagues. Previous studies have addressed readmission interventions among patients with cirrhosis, but the protocols required costly infrastructure, expertise, and institutional commitments. The current study supports the value of standard checklists and education, according to the investigators, “showing that outcomes improve further when checklist items are hard-wired into the ordering system.” (Clin Gastroenterol Hepatol. 2016 Apr 7. doi: 10.1016/j.cgh.2015.08.041).

The QI initiative encompassed several aspects of care. All HE patients were designated to receive rifaximin, and their lactulose dosing was adjusted to mental status using the Richmond Agitation and Sedation Scale. For patients with spontaneous bacterial peritonitis (SBP), timely administration of the correct dose of antibiotics and albumin was promoted, as were prophylactic measures for all patients, such as variceal hemorrhage prophylaxis and subcutaneous heparin for the prevention of venous thrombosis.

The three-part program entailed a run-in phase for preliminary checklist troubleshooting, a hand-held checklist phase, including the HE protocol, SBP treatment, and prophylactic measures, and a final electronic phase in which checklist items were incorporated into the hospital’s electronic provider order entry system using mandatory preset doses and linked medications.

Individual protocol items were demonstrated to affect the readmission rate. Rifaximin use for HE patients rose from 78.1% to 96.3%, and use of rifaximin was associated with lower adjusted odds of 30-day readmission (OR, 0.39; 95% CI, 0.16-0.87; P = .02). The dose/frequency of lactulose for HE patients increased, and patients who had 6 or more cups of lactulose on the day of their readmission had significantly lower adjusted length of stay (–2.36 days; 95% CI, –3.40 to –1.31; P less than .0001). Patients taking SBP prophylaxis had lower readmission rates (OR, 0.51; 95% CI, 0.31-0.83; P = .007).

The prospective study from 2011 to 2013 evaluated patients with cirrhosis who were admitted to the liver unit of Beth Israel Deaconess Medical Center, Boston. Patients were diagnosed with cirrhosis caused by hepatitis C (44.9%), alcoholic liver disease (34%), hepatitis B (5.4%), and biliary cirrhosis (1.8%). In total, 824 unique patients were admitted 1,720 times; 485 (58.9%) were admitted once, 268 (32.5%) were admitted 2-4 times, and 71 (8.6%) were admitted 5 or more times. The median length of stay for all patients was 4.0 days (interquartile range, 2.0-8.0).

Dr. Tapper and his coauthors reported having no disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Although black patients with colon cancer received significantly less treatment than white patients, particularly for late stage disease, much of the overall survival disparity between black and white patients was explained by tumor presentation at diagnosis rather than treatment differences, according to an analysis of SEER data.

Among demographically matched black and white patients, the 5-year survival difference was 8.3% (P less than .0001). Presentation match reduced the difference to 5.0% (P less than .0001), which accounted for 39.8% of the overall disparity. Additional matching by treatment reduced the difference only slightly to 4.9% (P less than .0001), which accounted for 1.2% of the overall disparity. Black patients had lower rates for most treatments, including surgery, than presentation-matched white patients (88.5% vs. 91.4%), and these differences were most pronounced at advanced stages. For example, significant differences between black and white patients in the use of chemotherapy was observed for stage III (53.1% vs. 64.2%; P less than .0001) and stage IV (56.1% vs. 63.3%; P = .001).

Courtesy Wikimedia Commons/Nephron/Creative Commons License

“Our results indicate that tumor presentation, including tumor stage, is indeed one of the most important factors contributing to the racial disparity in colon cancer survival. We observed that, after controlling for demographic factors, black patients in comparison with white patients had a significantly higher proportion of stage IV and lower proportions of stages I and II disease. Adequately matching on tumor presentation variables (e.g., stage, grade, size, and comorbidity) significantly reduced survival disparities,” wrote Dr. Yinzhi Lai of the Department of Medical Oncology at Sidney Kimmel Cancer Center, Philadelphia, and colleagues (Gastroenterology. 2016 Apr 4. doi: 10.1053/j.gastro.2016.01.030).

Treatment differences in advanced-stage patients, compared with early-stage patients, explained a higher proportion of the demographic-matched survival disparity. For example, in stage II patients, treatment match resulted in modest reductions in 2-, 3-, and 5-year survival rate disparities (2.7%-2.8%, 4.1%-3.6%, and 4.6%-4.0%, respectively); by contrast, in stage III patients, treatment match resulted in more substantial reductions in 2-, 3-, and 5-year survival rate disparities (4.5%-2.2%, 3.1%-2.0%, and 4.3%-2.8%, respectively). A similar effect was observed in patients with stage IV disease. The results suggest that, “to control survival disparity, more efforts may need to be tailored to minimize treatment disparities (especially chemotherapy use) in patients with advanced-stage disease,” the investigators wrote.

The retrospective data analysis used patient information from 68,141 patients (6,190 black, 61,951 white) aged 66 years and older with colon cancer identified from the National Cancer Institute SEER-Medicare database. Using a novel minimum distance matching strategy, investigators drew from the pool of white patients to match three distinct comparison cohorts to the same 6,190 black patients. Close matches between black and white patients bypassed the need for model-based analysis.

The primary matching analysis was limited by the inability to control for substantial differences in socioeconomic status, marital status, and urban/rural residence. A subcohort analysis of 2,000 matched black and white patients showed that when socioeconomic status was added to the demographic match, survival differences were reduced, indicating the important role of socioeconomic status on racial survival disparities.

Significantly better survival was observed in all patients who were diagnosed in 2004 or later, the year the Food and Drug Administration approved the important chemotherapy medicines oxaliplatin and bevacizumab. Separating the cohorts into those who were diagnosed before and after 2004 revealed that the racial survival disparity was lower in the more recent group, indicating a favorable impact of oxaliplatin and/or bevacizumab in reducing the survival disparity.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Patients with chronic gastroesophageal reflux disease (GERD) who have failed long-term proton pump inhibitor (PPI) therapy can benefit from surgical intervention with magnetic sphincter augmentation, according to a new study that has validated the long-term safety and efficacy of this procedure.

All 85 patients in the cohort had used PPIs at baseline, but this declined to 15.3% at 5 years. Moderate or severe regurgitation also decreased significantly. It was present in 57% of patients at baseline, but in 1.2% at the 5-year follow-up.

In a second related study, researchers found that compared with patients on esomeprazole therapy, GERD patients who underwent laparoscopic antireflux surgery (LARS), experienced significantly greater reductions in 24-hour esophageal acid exposure after 6 months and at 5 years. Both procedures were effective in achieving and maintaining a reduction in distal esophageal acid exposure down to a normal level, but LARS nearly abolished gastroesophageal acid reflux.

©nebari/Thinkstock.com

Both studies were published in the May issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.05.028; doi: 10.1016/j.cgh.2015.07.025).

Gastroesophageal reflux disease (GERD) is caused by excessive exposure of esophageal mucosa to gastric acid. Left unchecked, it can lead to chronic symptoms and complications, and is associated with a higher risk for Barrett’s esophagus and esophageal adenocarcinoma.

In the first study, Dr. Robert A. Ganz of Minnesota Gastroenterology PA, Plymouth, Minn., and colleagues, conducted a prospective international study that looked at the safety and efficacy of a magnetic device in adults with GERD.

The Food and Drug Administration approved this magnetic device in 2012, which augments lower esophageal sphincter function in patients with GERD, and the current paper now reports on the final results after 5 years of follow-up.

Quality of life, reflux control, use of PPIs, and side effects were evaluated, and the GERD health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device.

A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs. off PPI were compared.

During the follow-up period, there were no device erosions, migrations, or malfunctions. The median GERD-HRQL score was 27 in patients not taking PPIs and 11 in patients on PPIs at the start of the study. After 5 years with the device in place, this score decreased to 4.

All patients reported that they had the ability to belch and vomit if they needed to. The proportion of patients reporting bothersome swallowing was 5% at baseline and 6% at 5 years (P = .739), and bothersome gas-bloat was present in 52% at baseline but decreased to 8.3% at 5 years.

“Without a procedure to correct an incompetent lower esophageal sphincter, it is unlikely that continued medical therapy would have improved these reflux symptoms, and the severity and frequency of the symptoms may have worsened,” wrote the authors.

In the second study, Dr. Jan G. Hatlebakk of Haukeland University Hospital, Bergen, Norway, and his colleagues analyzed data from a prospective, randomized, open-label trial that compared the efficacy and safety of LARS with esomeprazole (20 or 40 mg/d) over a 5-year period in patients with chronic GERD.

Among patients in the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P less than .001 vs. baseline).

In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P less than .001, therapy vs. baseline, and LARS vs. esomeprazole).

Gastric acidity was stable in both groups, and patients who needed a dose increase to 40 mg/d experienced more severe supine reflux at baseline, but less esophageal acid exposure (P less than .02) and gastric acidity after their dose was increased. Esophageal and intragastric pH parameters, both on and off therapy, did not seem to long-term symptom breakthrough.

“We found that neither intragastric nor intraesophageal pH parameters could predict the short- and long-term therapeutic outcome, which indicates that response to therapy in patients with GERD is individual and not related directly to normalization of acid reflux parameters alone,” wrote Dr. Hatlebakk and coauthors.

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Patients who receive rectal indomethacin after undergoing endoscopic retrograde cholangiopancreatography (ERCP) are not any less likely to develop pancreatitis than individuals who don’t, according to the findings of a recent study published in Gastroenterology (2016 Jan 9. doi: 10.1053/j.gastro.2015.12.018).

“These results are in contrast to recent studies highlighting the benefit of rectal NSAIDS to prevent PEP [post-ECRP pancreatitis] in high-risk patients [and] counter the guidelines espoused by the European Society for Gastrointestinal Endoscopy, which recently recommended giving rectal indomethacin to prevent PEP in all patients undergoing ERCP,” said the study authors, led by Dr. John M. Levenick of Penn State University in Hershey, Pa.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Levenick and his coinvestigators screened 604 consecutive patients undergoing ERCP, with and without endoscopic ultrasound, at the Dartmouth-Hitchcock Medical Center between March 2013 and December 2014, eventually enrolling and randomizing 449 subjects into two cohorts: one in which subjects were given indomethacin after undergoing ERCP (n = 223), and one in which subjects were simply given a placebo (n = 226). Randomization happened after subjects’ major papilla had been reached, and cannulation attempts were started.

Individuals were excluded if they had active acute pancreatitis or had undergone ERCP to treat or diagnose acute pancreatitis, if they had any contraindications or allergies to NSAIDs, or were younger than 18 years of age, among other factors. The mean age of the indomethacin cohort was 64.9 years, with 118 (52.9%) females; in the placebo cohort, mean age was 64.3 years and 118 (52.2%) were female.

Pancreatitis occurred in 27 subjects overall, 16 (7.2%) of whom were in the indomethacin cohort and the other 11 (4.9%) were on placebo followed ERCP (P = .33). No subjects receiving indomethacin had severe or moderately severe PEP, but one subject had severe PEP and one had moderately severe PEP in the placebo cohort (P = 1.0). There was no necrotizing pancreatitis in either cohort, nor were there any significant differences in gastrointestinal bleeding (P = .75), death (P = .25), or 30-day hospital readmission (P = .1) between the two cohorts.

“Prophylactic rectal indomethacin did not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP,” Dr. Levenick and his coauthors concluded, adding that “guidelines that recommend the administration of rectal indomethacin in all patients undergoing ERCP should be reconsidered.”

This study was funded by the National Pancreas Foundation and a grant from the National Institutes of Health. Dr. Levenick and his coauthors did not report any financial disclosures.

[email protected]

Patients who receive rectal indomethacin after undergoing endoscopic retrograde cholangiopancreatography (ERCP) are not any less likely to develop pancreatitis than individuals who don’t, according to the findings of a recent study published in Gastroenterology (2016 Jan 9. doi: 10.1053/j.gastro.2015.12.018).

“These results are in contrast to recent studies highlighting the benefit of rectal NSAIDS to prevent PEP [post-ECRP pancreatitis] in high-risk patients [and] counter the guidelines espoused by the European Society for Gastrointestinal Endoscopy, which recently recommended giving rectal indomethacin to prevent PEP in all patients undergoing ERCP,” said the study authors, led by Dr. John M. Levenick of Penn State University in Hershey, Pa.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Levenick and his coinvestigators screened 604 consecutive patients undergoing ERCP, with and without endoscopic ultrasound, at the Dartmouth-Hitchcock Medical Center between March 2013 and December 2014, eventually enrolling and randomizing 449 subjects into two cohorts: one in which subjects were given indomethacin after undergoing ERCP (n = 223), and one in which subjects were simply given a placebo (n = 226). Randomization happened after subjects’ major papilla had been reached, and cannulation attempts were started.

Individuals were excluded if they had active acute pancreatitis or had undergone ERCP to treat or diagnose acute pancreatitis, if they had any contraindications or allergies to NSAIDs, or were younger than 18 years of age, among other factors. The mean age of the indomethacin cohort was 64.9 years, with 118 (52.9%) females; in the placebo cohort, mean age was 64.3 years and 118 (52.2%) were female.

Pancreatitis occurred in 27 subjects overall, 16 (7.2%) of whom were in the indomethacin cohort and the other 11 (4.9%) were on placebo followed ERCP (P = .33). No subjects receiving indomethacin had severe or moderately severe PEP, but one subject had severe PEP and one had moderately severe PEP in the placebo cohort (P = 1.0). There was no necrotizing pancreatitis in either cohort, nor were there any significant differences in gastrointestinal bleeding (P = .75), death (P = .25), or 30-day hospital readmission (P = .1) between the two cohorts.

“Prophylactic rectal indomethacin did not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP,” Dr. Levenick and his coauthors concluded, adding that “guidelines that recommend the administration of rectal indomethacin in all patients undergoing ERCP should be reconsidered.”

This study was funded by the National Pancreas Foundation and a grant from the National Institutes of Health. Dr. Levenick and his coauthors did not report any financial disclosures.

[email protected]

Patients who receive rectal indomethacin after undergoing endoscopic retrograde cholangiopancreatography (ERCP) are not any less likely to develop pancreatitis than individuals who don’t, according to the findings of a recent study published in Gastroenterology (2016 Jan 9. doi: 10.1053/j.gastro.2015.12.018).

“These results are in contrast to recent studies highlighting the benefit of rectal NSAIDS to prevent PEP [post-ECRP pancreatitis] in high-risk patients [and] counter the guidelines espoused by the European Society for Gastrointestinal Endoscopy, which recently recommended giving rectal indomethacin to prevent PEP in all patients undergoing ERCP,” said the study authors, led by Dr. John M. Levenick of Penn State University in Hershey, Pa.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Levenick and his coinvestigators screened 604 consecutive patients undergoing ERCP, with and without endoscopic ultrasound, at the Dartmouth-Hitchcock Medical Center between March 2013 and December 2014, eventually enrolling and randomizing 449 subjects into two cohorts: one in which subjects were given indomethacin after undergoing ERCP (n = 223), and one in which subjects were simply given a placebo (n = 226). Randomization happened after subjects’ major papilla had been reached, and cannulation attempts were started.

Individuals were excluded if they had active acute pancreatitis or had undergone ERCP to treat or diagnose acute pancreatitis, if they had any contraindications or allergies to NSAIDs, or were younger than 18 years of age, among other factors. The mean age of the indomethacin cohort was 64.9 years, with 118 (52.9%) females; in the placebo cohort, mean age was 64.3 years and 118 (52.2%) were female.

Pancreatitis occurred in 27 subjects overall, 16 (7.2%) of whom were in the indomethacin cohort and the other 11 (4.9%) were on placebo followed ERCP (P = .33). No subjects receiving indomethacin had severe or moderately severe PEP, but one subject had severe PEP and one had moderately severe PEP in the placebo cohort (P = 1.0). There was no necrotizing pancreatitis in either cohort, nor were there any significant differences in gastrointestinal bleeding (P = .75), death (P = .25), or 30-day hospital readmission (P = .1) between the two cohorts.

“Prophylactic rectal indomethacin did not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP,” Dr. Levenick and his coauthors concluded, adding that “guidelines that recommend the administration of rectal indomethacin in all patients undergoing ERCP should be reconsidered.”

This study was funded by the National Pancreas Foundation and a grant from the National Institutes of Health. Dr. Levenick and his coauthors did not report any financial disclosures.

[email protected]

As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).

“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.

Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.

The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.

The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).

Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.

“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”

Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.

This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.

[email protected]

As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).

“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.

Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.

The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.

The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).

Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.

“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”

Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.

This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.

[email protected]

As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).

“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.

Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.

The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.

The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).

Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.

“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”

Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.

This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.

[email protected]