Pancreas and Biliary Tract

Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.

Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.

To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.

The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).

This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.

This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.

Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.

Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.

To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.

The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).

This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.

This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.

Mild to moderate hypertriglyceridemia, not just severe hypertriglyceridemia, is associated with increased risk of acute pancreatitis, according to a report published in JAMA Internal Medicine.

Severe hypertriglyceridemia is a recognized risk factor for acute pancreatitis, but “there is no consensus on a clear threshold above which triglycerides” raise that risk. The American College of Gastroenterology and The Endocrine Society state that levels over 1,000 mg/dL should be considered a risk factor, while the European Society of Cardiology and the European Atherosclerosis Society set the cutoff at 885 mg/dL, said Simon B. Pedersen, MD, of the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University, Denmark, and his associates.

To examine whether lower triglyceride levels also put patients at risk for acute pancreatitis, the investigators analyzed data from two large prospective longitudinal studies of the general Danish population. They included 116,550 consecutive men and women who provided nonfasting triglyceride measurements and were followed for a median of 6.7 years. During that time, 434 of these participants developed acute pancreatitis.

The risk of developing acute pancreatitis increased with increasing triglyceride levels starting at the mildly elevated level of only 177 mg/dL. Compared with normal triglyceride levels of less than 89 mg/dL, the risk increased with a hazard ratio (HR) of 1.6 at 89-176 mg/dL, an HR of 2.3 at 177-265 mg/dL, an HR of 2.9 at 266-353 mg/dL, an HR of 3.9 at 354-442 mg/dL, and an HR of 8.7 at 443 mg/dL or above, Dr. Pedersen and his associates said (JAMA Intern. Med. 2016;176:1834-42).

This linear association persisted after the data were adjusted to account for potential confounders such as patient age, sex, body mass index, smoking status, alcohol intake, and education level, as well as the presence or absence of hypertension, diabetes, alcohol use, gallstone disease, and statin therapy.

This study was supported by the Herlev and Gentofte Hospital and Copenhagen University Hospital. Dr. Pedersen reported having no relevant financial disclosures; one of his associates reported ties to AstraZeneca, Merck, Omthera, Ionis, and Kowa.

While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.

“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).

Sebastian Kaulitzki/Fotolia

Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.

“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”

No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.

[email protected]

While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.

“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).

Sebastian Kaulitzki/Fotolia

Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.

“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”

No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.

[email protected]

While associations are known to exist between primary biliary cholangitis (PBC) and many different types of thyroid disease (TD), a new study shows that the mere presence of thyroid disease does not have any bearing on the hepatic complications or progression of PBC.

“The prevalence of TD in PBC reportedly ranges between 7.24% and 14.4%, the most often encountered thyroid dysfunction being Hashimoto’s thyroiditis,” wrote the study’s authors, led by Annarosa Floreani, MD, of the University of Padua (Italy).

Sebastian Kaulitzki/Fotolia

Of the 921 total patients enrolled, 150 (16.3%) had TD. The most common TD patients had were Hashimoto’s thyroiditis, which 94 (10.2%) individuals had; Graves’ disease, found in 15 (1.6%) patients; multinodular goiter, which 22 (2.4%) patients had; thyroid cancer, which was found in 7 (0.8%); and “other thyroid conditions,” which affected 12 (1.3%) patients. Patients from Padua had significantly more Graves’ disease and thyroid cancer than those from Barcelona: 11 (15.7%) versus 4 (5.0%) for Graves’ (P = .03), and 6 (8.6%) versus 1 (1.3%) for thyroid cancer (P = .03), respectively. However, no significant differences were found in PBC patients who had TD and those who did not, when it came to comparing the histologic stages at which they were diagnosed with PBC, hepatic decompensation events, occurrence of hepatocellular carcinoma, or liver transplantation rate. Furthermore, TD was not found to affect PBC survival rates, either positively or negatively.

“The results of our study confirm that TDs are often associated with PBC, especially Hashimoto’s thyroiditis, which shares an autoimmune etiology with PBC,” the authors concluded, adding that “More importantly … the clinical characteristics and natural history of PBC were much the same in the two cohorts, as demonstrated by the absence of significant differences regarding histological stage at diagnosis (the only exception being more patients in stage III in the Italian cohort); biochemical data; response to UDCA [ursodeoxycholic acid]; the association with other extrahepatic autoimmune disorders; the occurrence of clinical events; and survival.”

No funding source was reported for this study. Dr. Floreani and her coauthors did not report any financial disclosures relevant to this study.

[email protected]

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

Brain abnormalities associated with primary biliary cholangitis (PBC) can be observed via magnetic resonance imaging before significant liver damage occurs, according to V.B.P. Grover, MD, and associates at the Liver Unit and Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London.

In a study of 13 newly diagnosed precirrhotic PBC patients and 17 healthy volunteers, mean magnetization transfer ratios (MTR) were lower in the thalamus, putamen, and head of caudate in PBC patients, compared with the control group, with the greatest difference seen in the thalamus. Severity of PBC symptoms did not have any significant effect on MTR.

parisvas/Thinkstock

An increase in the apparent diffusion coefficient was seen in the thalamus of PBC patients; however, no significant difference in cerebral metabolite ratios or pallidal index was observed. No correlation between neuroimaging data, lab data, symptom severity scores, or age was observed.

“Larger scale, and in particular linear studies, will be needed to explore the relationship of this change to symptoms and its response to therapies such as UDCA [ursodeoxycholic acid] and OCA [obeticholic acid]. The presence of brain change so early in the disease process would, however, suggest that the current step-up approach to therapy in which treatment change follows failure of a therapy type may allow the progressive accumulation of brain injury whilst waiting for adequate therapeutic response,” the investigators concluded.

Find the full study in Alimentary Pharmacology & Therapeutics (doi: 10.1111/apt.13797).

[email protected]

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

MONTREAL – Once children have a first bout of acute pancreatitis, a second, separate episode of acute pancreatitis most often occurs in patients with genetically triggered pancreatitis, those who are taller or weigh more than average, and patients with pancreatic necrosis, based on multicenter, prospective data collected from 83 patients.

This is the first reported study to prospectively follow pediatric cases of acute pancreatitis, and additional studies with more patients are needed to better identify the factors predisposing patients to recurrent episodes of acute pancreatitis and to quantify the amount of risk these factors pose, Katherine F. Sweeny, MD, said at the annual meeting of the Federation of the International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

Mitchel L. Zoler/Frontline Medical News

Dr. Sweeny had no disclosures.

[email protected]

On Twitter @mitchelzoler

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

LAS VEGAS – In fluid derived from pancreatic cysts, methylated DNA markers predict the presence of high-grade dysplasia (HGD) or cancer, and could help physicians decide whether to surgically remove cysts – a procedure that often has serious complications.

If validated in larger studies, the biomarkers have the potential to supplant the Fukuoka criteria that is currently used. “The markers could cause a paradigm shift in how we approach these lesions in our clinical practice,” Shounak Majumder, MD, a fellow at the Mayo Clinic in Rochester, Minn., said in an interview.

Courtesy Dr. Lance Liotta Laboratory

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

Youth is no ally when it comes to primary biliary cholangitis, according to a review of 1,990 patients in the United Kingdom–PBC cohort, the largest primary biliary cholangitis cohort in the world.

The investigators previously found that younger patients are less likely to respond to the mainstay treatment, ursodeoxycholic acid (UDCA), and more likely to eventually need a liver transplant and die from the chronic autoimmune disease. Their new study found that they also suffer most from symptoms and have the lowest quality of life.

There was a linear relationship between age and quality of life (QoL) in this study of 1,990 primary biliary cholangitis patients; people who presented at age 20 had more than a 50% chance of reporting a poor QoL, while those presenting at age 70 had less than a 30% chance.

Overall perception of primary biliary cholangitis (PBC)-related QoL and individual severity of all symptoms, as is true with UDCA response, were strongly related to the age of onset of disease, with younger presenting patients experiencing the greatest impact. Each 10-year increase in presentation age was associated with a 14% decrease in the risk of poor QoL (OR, 0.86; 95% CI, 0.75–0.98; P less than .05), after adjustment for gender, disease severity, UDCA response, and disease duration. Presentations before the age of, perhaps, 50 years signal the need for greater vigilance (Aliment Pharmacol Ther. 2016 Nov;44[10]:1039-50).

The findings challenge “the view that PBC is a relatively benign condition of typically older people with limited clinical impact.” The biology “or natural history of PBC may differ between different patient groups, with younger-presenting patients having a more aggressive or materially different form of the disease.” Alternatively, the “enhanced symptom impact in younger patients may be [due to] age-related differences in [the expectation] of chronic disease, personal coping skills, and support networks,” said Jessica Dyson, MBBS, of Newcastle University, Newcastle upon Tyne (England), and her associates.

QoL was most affected by social isolation. “Addressing and treating this single aspect could improve global quality of life significantly... Approaches could range from simple counseling to alert patients to the potential for social isolation, to the development of support groups, to the development of newer digital approaches to social networking through social media,” Dr. Dyson and her colleagues said.

Fatigue, anxiety, and depression also were especially vexing for younger patients, and could “be related to fear of the future and ability to cope, uncertainty as to disease prognosis, and frustration at limitations to life quality,” they said.

“Specifically targeting fatigue is likely to pay dividends,” but “there are currently no therapies able to do that.” However, “a more sociological approach targeting social isolation and the depression and anxiety which may accompany it are very viable approaches.” The findings should help guide future intervention trials, the team said.

QoL was assessed by the PBC-40, a 40 item questionnaire about fatigue; itch; and emotional, social, cognitive, and general symptoms. Each item is scored from 1 to 5, with higher scores indicating greater symptom severity.

The team used the results to assign patients a global QoL score from 1-5 points; scores of 1-3 indicated neutral or good QoL, while 4-5 signaled poor QoL. Overall, two-thirds of patients reported neutral/good scores, and a third had poor scores.

Meanwhile, patients doing well had a median of 18 of 50 possible points on the PBC-40 social score, while those not doing well had a median score of 34 points.

Patients in the study, 91% of whom were women, presented at a median age of 55 years, but 493 presented before the age of 50.

This research was supported by the British Medical Research Council and the National Institute for Health Research, among others. Dr. Dyson had no disclosures, but other authors reported relationships with a range of pharmaceutical companies, including Abbvie, GSK, Intercept, Novartis, and Pfizer.

[email protected]

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

The session at the annual Digestive Disease Week entitled Pancreaticobiliary Potpourri encompassed three lectures. Suresh Chari, MD, from Mayo Clinic, Rochester, Minn., presented a lecture titled, “The cystic pancreas.” Gregory Gores, MD, AGAF, also of Mayo Clinic presented a lecture on “Managing the possibly malignant biliary stricture.” Finally, I, Todd H. Baron, MD, from the University of North Carolina at Chapel Hill delivered a lecture titled, “Preventing and managing complications of acute pancreatitis.”

Dr. Gores relayed that there are a variety of etiologies of biliary strictures. Discerning benign from malignant causes involves the use of cross-sectional imaging, PET-CT, serum tests, and endoscopy to include endoscopic retrograde cholangiopancreatography (ERCP) and EUS. IgG4, or autoimmune disease, is an important treatable cause of biliary obstruction. The diagnosis requires a high index of suspicion. Notably, an elevated serum IgG4 level can be seen in patients with cholangiocarcinoma. Fluorescence in situ hybridization (FISH) applied to biliary brush samples at the time of cytologic evaluation has been shown to markedly improve the sensitivity, compared with standard brush cytology. Cholangioscopy with targeted biopsies has been shown to have a sensitivity of 66% and specificity of 97%.

I emphasized the importance of preventing pancreatitis by careful selection of patients for ERCP, by limiting contrast injection during ERCP, and by the use of rectally administered nonsteroidal anti-inflammatory agents at the time of ERCP. Prevention of complications after onset of ERCP is the focus in patients with clinically severe acute pancreatitis, which is usually the result of pancreatic and/or peripancreatic necrosis. Early management consists of prompt and appropriate volume resuscitation, with recent evidence showing Lactated Ringer’s solution being superior to saline. Routine administration of antibiotics is not recommended, but early enteral feeding is recommended. Finally, interventions should be delayed as long as possible with minimally invasive techniques, including endoscopic drainage for walled-off pancreatic necrosis favored over traditional open procedures.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016. Dr. Baron is professor of medicine and director of advanced therapeutic endoscopy in the division of gastroenterology and hepatology in the school of medicine at the University of North Carolina at Chapel Hill. He has consulted and been a speaker for BSCI, Cook Endoscopy, and Olympus; and consulted for W.L. Gore.

At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.

Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.

Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.

The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.

Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).

The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.

Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.

“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”

Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.

When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.

The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.

However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).

Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.

“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.

DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.

“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”

The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.

The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.

At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.

Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.

Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.

The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.

Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).

The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.

Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.

“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”

Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.

When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.

The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.

However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).

Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.

“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.

DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.

“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”

The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.

The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.

At least two incretin-based drugs – glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors – do not appear to increase the risk of acute pancreatitis in individuals with diabetes but are associated with an increased risk of bile duct and gallbladder disease.

Two studies examining the impact on the pancreas of incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, have been published online August 1 in JAMA Internal Medicine.

Incretin-based drugs have been associated with increased risk of elevated pancreatic enzyme levels, while GLP-1 has been shown to increase the proliferation and activity of cholangiocytes, which have raised concerns of an impact on the bile duct, gallbladder, and pancreas.

The first study was an international, population-based cohort study using the health records of more than 1.5 million individuals with type 2 diabetes, who began treatment with antidiabetic drugs between January 2007 and June 2013.

Analysis of these data showed there was no difference in the risk of hospitalization for acute pancreatitis between those taking incretin-based drugs and those on two or more other oral antidiabetic medications (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1522).

The study also found no significant increase in the risk of acute pancreatitis either with DPP-4 inhibitors or GLP-1 agonists, nor was there any increase with a longer duration of use or in patients with a history of acute or chronic pancreatitis.

Most previous observational studies of incretin-based drugs and pancreatitis had reported null findings, but four studies did find a positive association. Laurent Azoulay, PhD, from the Lady Davis Institute at Montreal’s Jewish General Hospital, and his coauthors suggested this heterogeneity was likely the result of methodologic shortcomings such as the use of inappropriate comparator groups and confoundings.

“Although it remains possible that these drugs may be associated with acute pancreatitis, the upper limit of our 95% [confidence interval] suggests that this risk is likely to be small,” the authors wrote. “Thus, the findings of this study should provide some reassurance to patients treated with incretin-based drugs.”

Meanwhile, a second population-based cohort study in 71,368 patients starting an antidiabetic drug found the use of GLP-1 analogues was associated with a significant 79% increase in the risk of bile duct and gallbladder disease, compared with the use of at least two other oral antidiabetic medications.

When stratified by duration of use, individuals taking GLP-1 analogues for less than 180 days showed a twofold increase in the risk of bile duct and gallbladder disease (adjusted hazard ratio, 2.01; 95% CI, 1.23-3.29) but those taking the drugs for longer than 180 days did not show an increased risk.

The use of GLP-1 analogues was also associated with a two-fold increase in the risk of undergoing a cholecystectomy.

However, the study found no increased risk of bile duct or gallbladder disease with DPP-4 inhibitors (JAMA Intern Med. 2016 Aug 1. doi: 10.1001/jamainternmed.2016.1531).

Jean-Luc Faillie, MD, PhD, of the University of Montpellier (France) and his associates suggested that rapid weight loss associated with GLP-1 analogues may explain the association with bile duct and gallbladder disease, which would also account for the observation that the association did not occur in patients taking the drugs for a longer period of time.

“Weight loss leads to supersaturation of cholesterol in the bile, a known risk factor for gallstones,” the authors wrote.

DPP-4 inhibitors have different effects on the GLP-1 pharmacologic factors and a weaker incretin action, which the authors suggested may explain the lack of association with bile duct and gallbladder disease, as well as their lower incidence of gastrointestinal adverse events.

“Although further studies are needed to confirm our findings and the mechanisms involved, physicians prescribing GLP-1 analogues should be aware of this association and carefully monitor patients for biliary tract complications.”

The first study was enabled by data-sharing agreements with the Canadian Network for Observational Drug Effect Studies, which is funded by the Canadian Institutes of Health Research. Two authors declared consulting fees, grant support, or financial compensation from the pharmaceutical industry, but there were no other conflicts of interest declared.

The second study was funded by the Canadian Institutes of Health Research. No conflicts of interest were declared.

A single, 100-mg rectal dose of indomethacin cut the odds of moderate to severe pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) by 85% in a single-center retrospective study of more than 4,000 patients reported in the August issue of Gastroenterology.

The effect extended to low-risk patients and those with malignant biliary obstruction, who make up the majority of ERCP patients in community practice, said Nikhil R. Thiruvengadam, MD, and his associates at the University of Pennsylvania. “Usage of rectal indomethacin in current clinical practice is low, as most endoscopists outside of referral centers perform ERCP for indications that are considered low-risk for PEP [post-ERCP pancreatitis], and until now, there were no data to support a benefit of rectal NSAIDs in this population,” they wrote in Gastroenterology. Their “real-world analysis” clearly shows the benefits of rectal indomethacin in low-risk patients and supports its increased use after ERCP, they added.

Pancreatitis, the most common complication of ERCP, affected 2%-9% of patients in prior studies and costs about $200 million in the United States annually, the investigators noted. Pancreatic duct stents help prevent post-ERCP pancreatitis, but require experience to place and have their own complications that limit their use in low-risk patients. Past studies of rectal indomethacin after ERCP reported mixed results and mainly focused on high-risk patients, leaving questions about whether to routinely use this NSAID after ERCP, said the researchers (Gastroenterology. 2016 May 20. doi: 10.1053/j.gastro.2016.04.048). Their study included 4,017 patients who underwent ERCP at the University of Pennsylvania between 2009 and 2015. From 2012 onward, nearly all patients received 100 mg rectal indomethacin immediately after the duodenoscope was withdrawn. This indomethacin group included 2,007 patients, while 2,010 patients in the study did not receive rectal indomethacin. In all, 95 (4.73%) untreated patients developed post-ERCP pancreatitis, compared with only 40 (1.99%) patients who received indomethacin, for a 65% reduction in the odds of post-ERCP pancreatitis (odds ratio, 0.35; 95% confidence interval, 0.24-0.51; P less than .001). Rectal indomethacin also led to an 83% drop in the odds of moderate to severe post-ERCP pancreatitis (OR, 0.17; 95% CI, 0.09-0.32; P less than .001) and showed very similar protective effects for patients with malignant obstruction (OR, 0.35; 95% CI, 0.17-0.75; P less than .001] and 0.20; 95% CI, 0.07-0.63; P less than 0.001, respectively).

Rectal indomethacin was particularly beneficial for patients with malignant obstruction and pancreatic adenocarcinoma, the investigators noted. Such patients had post-ERCP rates of 2.31% when they received rectal indomethacin and 7.53% otherwise (P less than .001). They also had a nearly sevenfold lower rate of moderate to severe post-ERCP pancreatitis when they received rectal indomethacin (P = .001).

Treatment did not affect the chances of perforation and did not cause anaphylaxis, but was tied to a slightly higher rate of postprocedural gastrointestinal bleeding among sphincterotomy patients (0.65% with treatment versus 0.45% without; P = .52). However, sphincterotomy patients were much less likely to develop pancreatitis when they received rectal indomethacin than when they did not (0% and 9.58% of patients, respectively; P = .003).

“The majority of ERCPs were performed by experienced endoscopists at a tertiary care center, which may have limited the effects of variable procedural skills on the risk of PEP,” the researchers said. “Therefore, generalizability of our findings to other populations may be limited. However, it should be noted that the overall PEP rate in both the unexposed and indomethacin groups was fairly low and similar to large community-based estimates, suggesting that our overall patient population was of similar overall risk.” The study was not powered to assess the combined effects of rectal indomethacin and pancreatic duct stents, they noted.

The investigators reported no funding sources and had no disclosures.

A single, 100-mg rectal dose of indomethacin cut the odds of moderate to severe pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) by 85% in a single-center retrospective study of more than 4,000 patients reported in the August issue of Gastroenterology.

The effect extended to low-risk patients and those with malignant biliary obstruction, who make up the majority of ERCP patients in community practice, said Nikhil R. Thiruvengadam, MD, and his associates at the University of Pennsylvania. “Usage of rectal indomethacin in current clinical practice is low, as most endoscopists outside of referral centers perform ERCP for indications that are considered low-risk for PEP [post-ERCP pancreatitis], and until now, there were no data to support a benefit of rectal NSAIDs in this population,” they wrote in Gastroenterology. Their “real-world analysis” clearly shows the benefits of rectal indomethacin in low-risk patients and supports its increased use after ERCP, they added.

Pancreatitis, the most common complication of ERCP, affected 2%-9% of patients in prior studies and costs about $200 million in the United States annually, the investigators noted. Pancreatic duct stents help prevent post-ERCP pancreatitis, but require experience to place and have their own complications that limit their use in low-risk patients. Past studies of rectal indomethacin after ERCP reported mixed results and mainly focused on high-risk patients, leaving questions about whether to routinely use this NSAID after ERCP, said the researchers (Gastroenterology. 2016 May 20. doi: 10.1053/j.gastro.2016.04.048). Their study included 4,017 patients who underwent ERCP at the University of Pennsylvania between 2009 and 2015. From 2012 onward, nearly all patients received 100 mg rectal indomethacin immediately after the duodenoscope was withdrawn. This indomethacin group included 2,007 patients, while 2,010 patients in the study did not receive rectal indomethacin. In all, 95 (4.73%) untreated patients developed post-ERCP pancreatitis, compared with only 40 (1.99%) patients who received indomethacin, for a 65% reduction in the odds of post-ERCP pancreatitis (odds ratio, 0.35; 95% confidence interval, 0.24-0.51; P less than .001). Rectal indomethacin also led to an 83% drop in the odds of moderate to severe post-ERCP pancreatitis (OR, 0.17; 95% CI, 0.09-0.32; P less than .001) and showed very similar protective effects for patients with malignant obstruction (OR, 0.35; 95% CI, 0.17-0.75; P less than .001] and 0.20; 95% CI, 0.07-0.63; P less than 0.001, respectively).

Rectal indomethacin was particularly beneficial for patients with malignant obstruction and pancreatic adenocarcinoma, the investigators noted. Such patients had post-ERCP rates of 2.31% when they received rectal indomethacin and 7.53% otherwise (P less than .001). They also had a nearly sevenfold lower rate of moderate to severe post-ERCP pancreatitis when they received rectal indomethacin (P = .001).

Treatment did not affect the chances of perforation and did not cause anaphylaxis, but was tied to a slightly higher rate of postprocedural gastrointestinal bleeding among sphincterotomy patients (0.65% with treatment versus 0.45% without; P = .52). However, sphincterotomy patients were much less likely to develop pancreatitis when they received rectal indomethacin than when they did not (0% and 9.58% of patients, respectively; P = .003).

“The majority of ERCPs were performed by experienced endoscopists at a tertiary care center, which may have limited the effects of variable procedural skills on the risk of PEP,” the researchers said. “Therefore, generalizability of our findings to other populations may be limited. However, it should be noted that the overall PEP rate in both the unexposed and indomethacin groups was fairly low and similar to large community-based estimates, suggesting that our overall patient population was of similar overall risk.” The study was not powered to assess the combined effects of rectal indomethacin and pancreatic duct stents, they noted.

The investigators reported no funding sources and had no disclosures.

A single, 100-mg rectal dose of indomethacin cut the odds of moderate to severe pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) by 85% in a single-center retrospective study of more than 4,000 patients reported in the August issue of Gastroenterology.

The effect extended to low-risk patients and those with malignant biliary obstruction, who make up the majority of ERCP patients in community practice, said Nikhil R. Thiruvengadam, MD, and his associates at the University of Pennsylvania. “Usage of rectal indomethacin in current clinical practice is low, as most endoscopists outside of referral centers perform ERCP for indications that are considered low-risk for PEP [post-ERCP pancreatitis], and until now, there were no data to support a benefit of rectal NSAIDs in this population,” they wrote in Gastroenterology. Their “real-world analysis” clearly shows the benefits of rectal indomethacin in low-risk patients and supports its increased use after ERCP, they added.

Pancreatitis, the most common complication of ERCP, affected 2%-9% of patients in prior studies and costs about $200 million in the United States annually, the investigators noted. Pancreatic duct stents help prevent post-ERCP pancreatitis, but require experience to place and have their own complications that limit their use in low-risk patients. Past studies of rectal indomethacin after ERCP reported mixed results and mainly focused on high-risk patients, leaving questions about whether to routinely use this NSAID after ERCP, said the researchers (Gastroenterology. 2016 May 20. doi: 10.1053/j.gastro.2016.04.048). Their study included 4,017 patients who underwent ERCP at the University of Pennsylvania between 2009 and 2015. From 2012 onward, nearly all patients received 100 mg rectal indomethacin immediately after the duodenoscope was withdrawn. This indomethacin group included 2,007 patients, while 2,010 patients in the study did not receive rectal indomethacin. In all, 95 (4.73%) untreated patients developed post-ERCP pancreatitis, compared with only 40 (1.99%) patients who received indomethacin, for a 65% reduction in the odds of post-ERCP pancreatitis (odds ratio, 0.35; 95% confidence interval, 0.24-0.51; P less than .001). Rectal indomethacin also led to an 83% drop in the odds of moderate to severe post-ERCP pancreatitis (OR, 0.17; 95% CI, 0.09-0.32; P less than .001) and showed very similar protective effects for patients with malignant obstruction (OR, 0.35; 95% CI, 0.17-0.75; P less than .001] and 0.20; 95% CI, 0.07-0.63; P less than 0.001, respectively).

Rectal indomethacin was particularly beneficial for patients with malignant obstruction and pancreatic adenocarcinoma, the investigators noted. Such patients had post-ERCP rates of 2.31% when they received rectal indomethacin and 7.53% otherwise (P less than .001). They also had a nearly sevenfold lower rate of moderate to severe post-ERCP pancreatitis when they received rectal indomethacin (P = .001).

Treatment did not affect the chances of perforation and did not cause anaphylaxis, but was tied to a slightly higher rate of postprocedural gastrointestinal bleeding among sphincterotomy patients (0.65% with treatment versus 0.45% without; P = .52). However, sphincterotomy patients were much less likely to develop pancreatitis when they received rectal indomethacin than when they did not (0% and 9.58% of patients, respectively; P = .003).

“The majority of ERCPs were performed by experienced endoscopists at a tertiary care center, which may have limited the effects of variable procedural skills on the risk of PEP,” the researchers said. “Therefore, generalizability of our findings to other populations may be limited. However, it should be noted that the overall PEP rate in both the unexposed and indomethacin groups was fairly low and similar to large community-based estimates, suggesting that our overall patient population was of similar overall risk.” The study was not powered to assess the combined effects of rectal indomethacin and pancreatic duct stents, they noted.

The investigators reported no funding sources and had no disclosures.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.