Pancreas and Biliary Tract

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

IgG4-related disease can be grouped into four distinct clusters based on the distribution of organs involved, according to researchers who analyzed a large, multicenter cohort of patients with this heterogeneous, autoimmune-mediated condition.

The four groups also varied by age, race, sex, time to diagnosis, and concentration of serum IgG4, according to the investigators, led by Zachary S. Wallace, MD, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, both in Boston.

“These phenotypes may be used by clinicians to improve recognition of IgG4-related disease,” Dr. Wallace and his coauthors wrote in a report on the study that appears in the Annals of the Rheumatic Diseases.

First described in a Japanese population, IgG4-related disease has been subsequently seen in all racial and ethnic groups, according to the researchers. It is associated with organ failure and can affect nearly any organ or anatomic site, most notably the lungs, kidneys, lymph nodes, salivary glands, pancreatobiliary structures, and retroperitoneum.


In the present study, Dr. Wallace and his coinvestigators used a novel cluster analysis method, called latent class analysis, to categorize 765 cases of IgG4-related disease submitted by 52 investigators from 17 countries. The investigators included 493 of those cases in a primary study population, and the remaining 272 in a smaller cohort used to replicate the results.

In the larger, primary study cohort, about 65% of cases were male, 58% were non-Asian and 40% were white, and the mean age at diagnosis was 59.5 years. The replication cohort had similar characteristics, according to the investigators.

The clustering analysis revealed four distinct subgroups, characterized by pancreato-hepatobiliary, accounting for 31% of cases; retroperitoneal fibrosis and/or aortitis in 24%; disease generally limited to head and neck structures in 24%, and head and neck disease consistent with Mikulicz syndrome plus systemic involvement in 22%.

The highest IgG4 concentrations were seen in the group of patients with Mikulicz syndrome and systemic involvement, according to Dr. Wallace and his coauthors. The serum concentration was 1,170 mg/dL in that group, compared with 445 mg/dL in the group of patients with head and neck-limited disease, 316 mg/dL in the pancreato-hepatobiliary group, and just 178 mg/dL in the retroperitoneal fibrosis/aorta group.

Female and Asian patients were overrepresented in the group characterized by head and neck involvement, investigators also found. Moreover, that group had a significantly lower mean age at diagnosis than did the other groups.

Those variations suggested differences in genetic or environmental risk factors between clusters, according to the investigators.

“Given the similar distribution of subspecialists among investigators in this study practicing in Asian and non-Asian countries, the observed differences are unlikely to be the result of detection or selection biases,” they said in their report.

The findings of this study help to inform subsequent investigations intended to evaluate those factors in more detail, they said.

Dr. Wallace and his coauthors reported no conflicts of interest related to their work, which was previously presented at the American College of Rheumatology annual meeting.

SOURCE: Wallace ZS et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214603

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

Compared with younger patients, elderly patients admitted for acute biliary pancreatitis have increased rates of severe acute pancreatitis and mortality, according to an analysis of a nationally representative database.

Mortality was almost three times as high in elderly patients after stringent matching for confounding variables, wrote researcher Kishan Patel, MD, of the Ohio State University, Columbus, and coauthors.

These findings represent a “current health care concern,” since the elderly population in the United States is expected to double within the next several decades and the prevalence of acute pancreatitis is on the rise, Dr. Patel and colleagues wrote in a report on the analysis in the Journal of Clinical Gastroenterology.

The analysis is the first, to the investigators’ knowledge, that addresses national-level outcomes associated with acute biliary pancreatitis in elderly patients.

To evaluate clinical outcomes of elderly patients with acute biliary pancreatitis, Dr. Patel and colleagues queried the Nationwide Readmissions Database, which is the largest inpatient readmission database in the United States.

The investigators looked at outcomes associated with index hospitalizations, defined as a patient’s first hospitalization in a calendar year, and found 184,763 adult patients who received a diagnosis of acute biliary pancreatitis between 2011 and 2014. Of those, 41% were elderly.

The mortality rate associated with the index admission was 1.96% (n = 356) for the elderly patients, compared with just 0.32% (n = 1,473) for nonelderly patients (P less than .001), according to the report.

Mortality was increased in the elderly versus nonelderly patients, with an odds ratio of 2.8 (95% CI, 2.2-3.5), according to results of a propensity score matched analysis. Likewise, severe acute pancreatitis was increased in the elderly, with an OR of 1.2 (95% CI: 1.1-1.3) in that analysis.

By contrast, patient age did not impact 30-day readmission rates, according to results of a multivariate analysis that adjusted for confounding factors.

Mortality and severe acute pancreatitis both increased with age within the elderly cohort, further multivariate analysis showed. For example, the ORs for mortality were 1.39 for patients aged 75-84 years and 2.21 for patients aged 85 years and older, the results show.

The elderly population in the United States is expected to almost double by 2050, rising from 48 to 88 million, Dr. Patel and colleagues said. The number of those aged 85 years or older is expected to increase from 5.9 to 18 million by 2050, at which time they will make up nearly 5% of the total U.S. population.

“This specific demographic is more susceptible to common medical ailments, more troubling is acute pancreatitis is one of the most frequent causes of hospitalization in gastroenterology,” Dr. Patel and colleagues wrote.

Dr. Patel and coauthors reported no conflicts of interest related to the analysis.

SOURCE: Patel K et al. J Clin Gastroenterol. 2018 Aug 28. doi: 10.1097/MCG.0000000000001108.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

For the pancreatobiliary session, Michelle Ann Anderson, MD, of the University of Michigan, Ann Arbor, reminded us about appropriate patient selection given the risk of pancreatitis after endoscopic retrograde cholangiopancreatography pancreatitis, also known as post-ERCP pancreatitis. Strategies to prevent post-ERCP pancreatitis include using pancreatic duct stents and using wire rather than contrast for cannulation. She recommended rectal indomethacin for all patients. Because of encouraging data, she recommended 2-3 L of lactated Ringer’s solution during the procedure and recovery. 

Katie Morgan, MD, from the Medical University of South Carolina, Charleston, reviewed her group’s experience with 195 total pancreatectomies with islet autotransplants for chronic pancreatitis. Quality of life improved with major reductions in narcotic use, and 25% of patients were insulin free. 

Bret Petersen, MD, of Mayo Clinic, Rochester, Minn., discussed multidrug resistant infection in ERCP endoscopes. He reminded us of the risk of lapses in endoscope reprocessing steps and the need for monitoring. He commented on recent Food and Drug Administration’s culture guidance and new technologies in development. 

James Scheiman, MD, from the University of Virginia, Charlottesville, discussed pancreatic cysts. He reviewed the controversy between the more conservative American Gastroenterological Association guidelines and the more aggressive International Consensus guidelines. He advised considering patient preferences with a multidisciplinary approach.
For the liver session, Guadalupe García-Tsao, MD, of Yale University, New Haven, Conn., discussed the controversy regarding nonselective beta-blockers. She advised caution if refractory ascites are present because of risk for renal dysfunction, but she also highlighted the benefits including reduced first and recurrent variceal hemorrhage. 

Rohit Loomba, MD, from the University of California at San Diego addressed fibrosis assessments in fatty liver. In his algorithm, patients with low Nonalcoholic Fatty Liver Disease Fibrosis Score or Fibrosis-4 scores would have continued observation, while patients with medium or high scores would undergo transient elastography or magnetic resonance elastography. 

Patrick Northup, MD, from the University of Virginia discussed anticoagulation for portal vein thrombosis. He also discussed consideration of transjugular intrahepatic portosystemic shunt if there are high-risk varices. Duration of anticoagulation is controversial, but this strategy may prevent decompensation and affect transplant outcomes. 

Daryl Lau, MD, MSc, MPH, from Harvard Medical School, Boston, reviewed the hepatitis B virus therapy controversy for e-antigen–negative patients with prolonged viral suppression. She recommended caution in general and emphasized that stage 3-4 fibrosis patients should not discontinue therapy. 

The final talk was my review of hepatitis C virus treatment. I emphasized that pretreatment fibrosis assessments are critical given continued risk of hepatocellular carcinoma after cure. Challenges include identifying the remaining patients and supporting them through treatment. HCV therapies demonstrate what is possible when breakthroughs are translated to clinical care, and I was honored to participate in this course that highlighted many advances in our field.

Dr. Muir is a professor of medicine, director of gastroenterology & hepatology research at Duke Clinical Research Institute, and chief of the division of gastroenterology in the department of medicine at Duke University, all in Durham, N.C. He has received research grants from and served on the advisory boards for AbbVie, Gilead Sciences, Merck, and several other pharmaceutical companies. This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2018.

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

iStock/ThinkStock

“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

Long-term pancreatic surveillance of high-risk patients identified cancers while they were still resectable, and 85% of such patients remained alive 3 years after diagnosis, researchers reported.

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“Among individuals undergoing pancreatic surveillance, specific detectable lesions with worrisome features predicted neoplastic progression. The short-term outcomes of patients with screening-detected PDACs [pancreatic ductal adenocarcinomas] improved,” wrote Marcia Irene Canto, MD, MHS, of the Johns Hopkins University, Baltimore, together with her associates in the September issue of Gastroenterology.

The lifetime risk of PDAC is about 1.5%, the researchers noted. Consequently, the U.S. Preventive Services Task Force does not recommend pancreatic surveillance at a population level. However, pancreatic screening is being evaluated for individuals who are at significantly elevated risk of PDAC, including those with at least two first-degree relatives with PDAC or who have germline mutations in BRCA1, BRCA2, PALB2, PRSS1 (hereditary pancreatitis), CDKN2A, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), or STK11 (Peutz-Jeghers syndrome).

For the study, Dr. Canto and her associates analyzed data from 354 such high-risk individuals enrolled in the CAPS (Cancer of the Pancreas Screening) cohort studies, which were conducted at tertiary care academic centers during 1998-2014. All participants underwent endoscopic ultrasound at baseline, followed by surveillance with endoscopic ultrasound, magnetic resonance imaging, computed tomography, or some combination of these modalities. Patients who developed pancreatic cancer or high-grade dysplasia were offered surgery.

In all, 68 patients (19%) developed pancreatic lesions with worrisome features, such as solid masses, multiple cysts, mural nodules, thickened or enhancing walls, cysts exceeding 3 cm in size or that grew more than 4 mm annually, a greater than 5-mm dilation of the main pancreatic duct, or an abrupt change in duct caliber. The lesions developed over a median of 13.1 months (interquartile range, 0.2-52 months).

A total of 7% of patients had neoplastic progression, including 14 cases of PDAC and 10 cases of high-grade dysplasia. Median times from baseline to detection of PDAC were 4.8 years overall (IQR, 1.6-6.9 years), 1.7 years (IQR, 0.5-4.4 years) among patients aged at least 60 years at baseline, and 5.2 years among younger patients (IQR, 0.4-8 years). Patients developed PDAC at a median of 67 years old.

Among 10 PDACs detected by surveillance, 9 were resectable. Three patients subsequently died of PDAC, while one patient died of complications of gastric cancer surgery. However, 85% of patients survived for at least 3 years after surgical resection of PDAC. The remaining four cases of PDAC were detected outside surveillance or after patients stopped surveillance.

The 10 cases of high-grade dysplasia consisted of intraductal papillary mucinous neoplasm with high-grade dysplasia or high-grade pancreatic intraepithelial neoplasia. Patients whose PDAC or high-grade dysplasia was detected by surveillance survived a median of 5.3 years, while patients whose surveillance was late or stopped and who subsequently developed neoplasia survived a median of only 1.4 years after diagnosis (P less than .0001).

Funders included the Pancreatic Cancer Action Network, Lustgarten Foundation for Pancreatic Cancer Research, the John and Peter Hooven Memorial Endowment, Hugh and Rachel Victor, and ChiRhoClin. Dr. Canto had no disclosures. Three coinvestigators disclosed royalties for licensing of PALB2 as a pancreatic cancer susceptibility gene.

SOURCE: Canto MI et al. Gastroenterology. 2018 May 24. doi: 10.1053/j.gastro.2018.05.035

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Meanwhile, hospital admissions and length of stay dropped, but ED and inpatient charges increased, according to the analysis by Sushil K. Garg, MD, of the division of gastroenterology and hepatology at the Mayo Clinic, Rochester, Minn., and his coauthors.

“This study identifies important patient populations, specifically young patients with alcohol abuse, to target in order to develop programs to assist in reduction of ED utilization for acute pancreatitis,” Dr. Garg and his colleagues reported in the Journal of Clinical Gastroenterology.

The retrospective analysis was focused on nearly 2.2 million ED visits during 2006-2012 in the National Emergency Department Sample (NEDS) database. The cohort was limited to adults at least 18 years of age with a primary diagnosis of acute pancreatitis.

Overall, there was a nonsignificant 5.5% increase in visits per 10,000 U.S. population during 2006-2012, the researchers found. However, the total number of ED visits in this sample increased significantly – from 292,902 in 2006 to a peak of 326,376, an average rate of increase of 7,213 visits per year (P = .0086), according to the report.

Younger patients had a significant increase in the number of pancreatitis-related ED visits over the study period, while older patients had a significant decrease, according to investigators. Visits were up 9.2% for patients aged 18-44 years and 8.6% for those aged 45-64 but down 13.4% for patients aged 65-84 years and 20.1% for those aged 85 years or older.

The incidence of visits secondary to biliary disease was virtually flat over time, Dr. Garg and his coinvestigators found when looking at visits grouped by the most common presenting etiologies. By contrast, there were significant increases in visits for acute pancreatitis associated with alcohol abuse or chronic pancreatitis.

Specifically, acute pancreatitis associated with biliary disease averaged 20.7% of yearly pancreatitis-related ED visits and did not significantly change over time, the researchers reported.

By contrast, acute pancreatitis associated with alcohol abuse, which accounted for 24.1% of visits on average, increased by 15.9% over the study period, an increase driven by an increase among age groups younger than 65 years.

Acute pancreatitis associated with chronic pancreatitis, which made up 11.5% of visits on average, increased “substantially” in all age groups, according to study authors, with the largest increase in the group aged 45-64 years. Overall, the percentage increase over 7 years was 59.5%.

Rates of hospitalization decreased significantly over time, from 76.2% in 2006 to 72.7% in 2012 (P = .0026), and likewise, the length of stay dropped from 5.36 to 4.64 days (P = .0001), according to the analysis.

Inpatient charges, adjusted for inflation and expressed in 2012 dollars, increased from $32,130.63 to $34,652.00 (P = .0011), an average rate of increase of $489/year.

Predictors of hospitalization included age older than 84 years, alcohol use, smoking, and a Charlson comorbidity score of 1 or greater, according to the results of a multivariate regression analysis.

“Factors which may place patients at higher risk for severe or complicated acute pancreatitis requiring admission, such as obesity, alcohol use, and increasing age, are identified and should be explored in further studies and potentially targeted to improve ED and inpatient care,” Dr. Garg and his coauthors said.

Dr. Garg and his coauthors had no disclosures related to the study.

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

Researchers have identified laminin 511 as a novel antigen in autoimmune pancreatitis (AIP). A truncated form of the antigen was found in about half of human patients, but fewer than 2% of controls, and mice that were immunized with the antigen responded with induced antibodies and suffered pancreatic injury.

Laminin 511 plays a key role in cell–extracellular matrix (ECM) adhesion in pancreatic tissue. The results, published in Science Translational Medicine, could improve the biologic understanding of AIP and could potentially be a useful diagnostic marker for the disease.

Some autoantibodies are known to be associated with AIP, but the seropositive frequency is low among patients.

The researchers previously demonstrated that injecting IgG from AIP patients into neonatal mice led to pancreatic injury. The IgG was bound to the basement membrane of the pancreatic acini, suggesting the presence of autoantibodies that recognize an antigen in the ECM.

The researchers then screened previously known proteins from the pancreatic ECM against sera from AIP patients, performing Western blot analyses and immunosorbent column chromatography with human and mouse pancreas extracts, and AIP patient IgG. But this approach yielded no results.

The team then conducted an enzyme-linked immunosorbent assay using known pancreatic ECM proteins, which included the laminin subunits 511-FL, 521-FL, 511-E8, 521-E8, 111-EI, 211-E8, and 332-E8. The E8 designates a truncated protein produced by pancreatic elastase that contains the integrin-binding site.

That experiment revealed that 511-E8 is a consistent autoantigen, and a survey of AIP patients found that 26 of 51 (51.0%) had autoantibodies against 511-E8, compared with just 2 of 122 (1.6%) of controls (P less than .001). Further immunohistochemistry studies confirmed that patient IgG binds to laminin in pancreatic tissue.

When the researchers injected 511-E8, 511-FL, 521-FL, or ovalbumin into 8-week-old mice, and then again after 28 days and 56 days, only those who received 511-E8 showed evidence of pancreatic injury 28 days after the final immunization. The mice generated autoantibodies to 511-E8 but not ovalbumin.

The findings may have clinical significance. Patients with antibodies to laminin 511-E8 had a lower frequency of malignancies (0% vs. 32%; P =.0017) and allergic diseases (12% vs. 48%; P =.0043) than patients with no laminin 511-E8 antibodies.

The study was funded by the Japan Society for the Promotion of Science; the Japanese Ministry of Health, Labour, and Welfare; the Practical Research Project for Rare/Intractable Diseases Grant,; the Agency for Medical Research and Development; and the Takeda Science Foundation. One of the authors has filed a patent related to the study results.

SOURCE: Shiokawa M et al. Sci. Transl. Med. 2018 Aug 8. doi: 10.1126/scitranslmed.aaq0997.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

The number of U.S. emergency department visits for acute pancreatitis associated with alcohol abuse, chronic pancreatitis history, and younger age was on the rise in recent years, an analysis of a nationally representative database has suggested.

Katarzyna Bialasiewicz/Thinkstock

Help your patients better understand pancreatitis and available tests and treatments by using AGA patient education materials, https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

SOURCE: Garg SK et al. J Clin Gastroenterol. 2018 Apr 6. doi: 10.1097/MCG.0000000000001030.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.

Patients with acute pancreatitis should receive “goal-directed” fluid therapy with normal saline or Ringer’s lactate solution rather than hydroxyethyl starch (HES) fluids, states a new guideline from the AGA Institute.

In a single-center randomized trial, hydroxyethyl starch fluids conferred a 3.9-fold increase in the odds of multiorgan failure (95% confidence interval for odds ratio, 1.2-12.0) compared with normal saline in patients with acute pancreatitis, wrote guideline authors Seth D. Crockett, MD, MPH, of the University of North Carolina, Chapel Hill, and his associates. This trial and another randomized study found no mortality benefit for HES compared with fluid resuscitation. The evidence is “very low quality” but mirrors the critical care literature, according to the experts. So far, Ringer’s lactate solution and normal saline have shown similar effects on the risk of organ failure, necrosis, and mortality, but ongoing trials should better clarify this choice, they noted (Gastroenterology. doi: 10.1053/j.gastro.2018.01.032).

The guideline addresses the initial 2-week period of treating acute pancreatitis. It defines goal-directed fluid therapy as titration based on meaningful targets, such as heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and hematocrit. Studies of goal-directed fluid therapy in acute pancreatitis have been unblinded, have used inconsistent outcome measures, and have found no definite benefits over nontargeted fluid therapy, note the guideline authors. Nevertheless, they conditionally recommend goal-directed fluid therapy, partly because a randomized, blinded trial of patients with severe sepsis or septic shock (which physiologically resembles acute pancreatitis) had in-hospital mortality rates of 31% when they received goal-directed fluid therapy and 47% when they received standard fluid therapy (P = .0009).

The guideline recommends against routine use of two interventions: prophylactic antibiotics and urgent endoscopic retrograde cholangiopancreatography (ERCP) for patients with acute pancreatitis. The authors note that no evidence supports routine prophylactic antibiotics for acute pancreatitis patients without cholangitis, and that urgent ERCP did not significantly affect the risk of mortality, multiorgan failure, single-organ failure, infected pancreatic and peripancreatic necrosis, or necrotizing pancreatitis in eight randomized controlled trials of patients with acute gallstone pancreatitis.

Source: Crockett SD et al. Gastroenterology. doi: 10.1053/j.gastro.2018.01.032.

Gadolinium-based contrast agents (GBCAs) used for MRI will now carry a warning regarding their potential retention in the bodies and brains of treated patients, according to the Food and Drug Administration.

The FDA is requiring the new class warning, along with other safety measures, based on evidence showing that trace amounts of gadolinium can be retained in the body for months to years after treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Specifically, the agency will require that patients receiving GBCAs first receive a Medication Guide and that GBCA manufacturers conduct human and animal studies to further assess GBCA safety. At this time, the only known adverse health effect of gadolinium retention is nephrogenic systemic fibrosis, which affects a small subgroup of patients with pre-existing kidney failure. No causal association has been established between gadolinium retention and reported adverse events in those with normal kidney function.

The FDA recommended that health care professionals consider the retention characteristics of GBCAs for patients who may be at higher risk for retention, including those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions, but stressed that, although repeated GBCA imaging studies should be minimized when possible, they should not be avoided or deferred when they are necessary. In the safety alert, the FDA noted that administration of the GBCAs Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol) produce the lowest gadolinium levels in the body, and the three agents leave similar gadolinium levels in the body.

The agency encourages reports of adverse events or side effects related to the use of GBCAs to its MedWatch Safety information and Adverse Event Reporting Program. Reports can be submitted online at www.fda.gov/MedWatch/report or by calling 1-800-332-1088 to request a preaddressed form that can be mailed or faxed to 1-800-FDA-0178.

sworcester@frontlinemedcom.com

Gadolinium-based contrast agents (GBCAs) used for MRI will now carry a warning regarding their potential retention in the bodies and brains of treated patients, according to the Food and Drug Administration.

The FDA is requiring the new class warning, along with other safety measures, based on evidence showing that trace amounts of gadolinium can be retained in the body for months to years after treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Specifically, the agency will require that patients receiving GBCAs first receive a Medication Guide and that GBCA manufacturers conduct human and animal studies to further assess GBCA safety. At this time, the only known adverse health effect of gadolinium retention is nephrogenic systemic fibrosis, which affects a small subgroup of patients with pre-existing kidney failure. No causal association has been established between gadolinium retention and reported adverse events in those with normal kidney function.

The FDA recommended that health care professionals consider the retention characteristics of GBCAs for patients who may be at higher risk for retention, including those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions, but stressed that, although repeated GBCA imaging studies should be minimized when possible, they should not be avoided or deferred when they are necessary. In the safety alert, the FDA noted that administration of the GBCAs Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol) produce the lowest gadolinium levels in the body, and the three agents leave similar gadolinium levels in the body.

The agency encourages reports of adverse events or side effects related to the use of GBCAs to its MedWatch Safety information and Adverse Event Reporting Program. Reports can be submitted online at www.fda.gov/MedWatch/report or by calling 1-800-332-1088 to request a preaddressed form that can be mailed or faxed to 1-800-FDA-0178.

sworcester@frontlinemedcom.com

Gadolinium-based contrast agents (GBCAs) used for MRI will now carry a warning regarding their potential retention in the bodies and brains of treated patients, according to the Food and Drug Administration.

The FDA is requiring the new class warning, along with other safety measures, based on evidence showing that trace amounts of gadolinium can be retained in the body for months to years after treatment.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Specifically, the agency will require that patients receiving GBCAs first receive a Medication Guide and that GBCA manufacturers conduct human and animal studies to further assess GBCA safety. At this time, the only known adverse health effect of gadolinium retention is nephrogenic systemic fibrosis, which affects a small subgroup of patients with pre-existing kidney failure. No causal association has been established between gadolinium retention and reported adverse events in those with normal kidney function.

The FDA recommended that health care professionals consider the retention characteristics of GBCAs for patients who may be at higher risk for retention, including those requiring multiple lifetime doses, pregnant women, children, and patients with inflammatory conditions, but stressed that, although repeated GBCA imaging studies should be minimized when possible, they should not be avoided or deferred when they are necessary. In the safety alert, the FDA noted that administration of the GBCAs Dotarem (gadoterate meglumine), Gadavist (gadobutrol), and ProHance (gadoteridol) produce the lowest gadolinium levels in the body, and the three agents leave similar gadolinium levels in the body.

The agency encourages reports of adverse events or side effects related to the use of GBCAs to its MedWatch Safety information and Adverse Event Reporting Program. Reports can be submitted online at www.fda.gov/MedWatch/report or by calling 1-800-332-1088 to request a preaddressed form that can be mailed or faxed to 1-800-FDA-0178.

sworcester@frontlinemedcom.com

In patients with malignant biliary strictures, radiofrequency ablation may improve stent patency and prolong survival, according to results of a recent meta-analysis.

Radiofrequency ablation was also safe and well tolerated. The report appears in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.10.029).

Although the data to date are limited and mostly observational, radiofrequency ablation “may be a promising adjuvant therapy in patients with malignant biliary obstruction who otherwise have dismal outcomes with current standard of therapy,” wrote Aijaz Ahmed Sofi, MD, of the department of gastroenterology, Arizona Center for Digestive Health, Gilbert, and coauthors.

Use of radiofrequency ablation is thought to improve the patency of biliary stents placed as a palliative measure in patients with unresectable malignant biliary strictures. However, several studies evaluating this and other endpoints have produced “variable results,” the authors said in the report.

In a comprehensive literature search, Dr. Sofi and colleagues identified nine studies including 505 patients. Only one of the studies was randomized and controlled, and results from it were preliminary, they noted.

Combined results showed a 50.6-day pooled weighted mean difference in stent patency (95% confidence interval, 32.83-68.48) in favor of radiofrequency ablation, according to reported data. In addition, there was a significant difference in survival favoring use of radiofrequency ablation (hazard ratio, 1.395; 95% confidence interval, 1.145-1.7; P less than .001).

While there was no difference between groups in risk of cholangitis, pancreatitis, hemobilia, and acute cholecystitis, abdominal pain after the procedure was more frequent in the radiofrequency ablation group (31% vs. 20%, P = .003).

This is the first systematic review and meta-analysis evaluating radiofrequency ablation as an adjuvant therapy in patients who receive biliary stents for malignant biliary obstruction, according to the investigators.

Despite the findings, Dr. Sofi and colleagues were careful to emphasize the limitations of the analysis, writing that it provides “very low quality evidence” in favor of radiofrequency ablation therapy for management of malignant biliary strictures.

“The results of currently ongoing controlled studies examining the role of RFA [radiofrequency ablation] in malignant biliary obstruction are keenly awaited,” they wrote.

Dr. Sofi and colleagues reported no potential conflicts of interest associated with the study.

In patients with malignant biliary strictures, radiofrequency ablation may improve stent patency and prolong survival, according to results of a recent meta-analysis.

Radiofrequency ablation was also safe and well tolerated. The report appears in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.10.029).

Although the data to date are limited and mostly observational, radiofrequency ablation “may be a promising adjuvant therapy in patients with malignant biliary obstruction who otherwise have dismal outcomes with current standard of therapy,” wrote Aijaz Ahmed Sofi, MD, of the department of gastroenterology, Arizona Center for Digestive Health, Gilbert, and coauthors.

Use of radiofrequency ablation is thought to improve the patency of biliary stents placed as a palliative measure in patients with unresectable malignant biliary strictures. However, several studies evaluating this and other endpoints have produced “variable results,” the authors said in the report.

In a comprehensive literature search, Dr. Sofi and colleagues identified nine studies including 505 patients. Only one of the studies was randomized and controlled, and results from it were preliminary, they noted.

Combined results showed a 50.6-day pooled weighted mean difference in stent patency (95% confidence interval, 32.83-68.48) in favor of radiofrequency ablation, according to reported data. In addition, there was a significant difference in survival favoring use of radiofrequency ablation (hazard ratio, 1.395; 95% confidence interval, 1.145-1.7; P less than .001).

While there was no difference between groups in risk of cholangitis, pancreatitis, hemobilia, and acute cholecystitis, abdominal pain after the procedure was more frequent in the radiofrequency ablation group (31% vs. 20%, P = .003).

This is the first systematic review and meta-analysis evaluating radiofrequency ablation as an adjuvant therapy in patients who receive biliary stents for malignant biliary obstruction, according to the investigators.

Despite the findings, Dr. Sofi and colleagues were careful to emphasize the limitations of the analysis, writing that it provides “very low quality evidence” in favor of radiofrequency ablation therapy for management of malignant biliary strictures.

“The results of currently ongoing controlled studies examining the role of RFA [radiofrequency ablation] in malignant biliary obstruction are keenly awaited,” they wrote.

Dr. Sofi and colleagues reported no potential conflicts of interest associated with the study.

In patients with malignant biliary strictures, radiofrequency ablation may improve stent patency and prolong survival, according to results of a recent meta-analysis.

Radiofrequency ablation was also safe and well tolerated. The report appears in Gastrointestinal Endoscopy (2017. doi: 10.1016/j.gie.2017.10.029).

Although the data to date are limited and mostly observational, radiofrequency ablation “may be a promising adjuvant therapy in patients with malignant biliary obstruction who otherwise have dismal outcomes with current standard of therapy,” wrote Aijaz Ahmed Sofi, MD, of the department of gastroenterology, Arizona Center for Digestive Health, Gilbert, and coauthors.

Use of radiofrequency ablation is thought to improve the patency of biliary stents placed as a palliative measure in patients with unresectable malignant biliary strictures. However, several studies evaluating this and other endpoints have produced “variable results,” the authors said in the report.

In a comprehensive literature search, Dr. Sofi and colleagues identified nine studies including 505 patients. Only one of the studies was randomized and controlled, and results from it were preliminary, they noted.

Combined results showed a 50.6-day pooled weighted mean difference in stent patency (95% confidence interval, 32.83-68.48) in favor of radiofrequency ablation, according to reported data. In addition, there was a significant difference in survival favoring use of radiofrequency ablation (hazard ratio, 1.395; 95% confidence interval, 1.145-1.7; P less than .001).

While there was no difference between groups in risk of cholangitis, pancreatitis, hemobilia, and acute cholecystitis, abdominal pain after the procedure was more frequent in the radiofrequency ablation group (31% vs. 20%, P = .003).

This is the first systematic review and meta-analysis evaluating radiofrequency ablation as an adjuvant therapy in patients who receive biliary stents for malignant biliary obstruction, according to the investigators.

Despite the findings, Dr. Sofi and colleagues were careful to emphasize the limitations of the analysis, writing that it provides “very low quality evidence” in favor of radiofrequency ablation therapy for management of malignant biliary strictures.

“The results of currently ongoing controlled studies examining the role of RFA [radiofrequency ablation] in malignant biliary obstruction are keenly awaited,” they wrote.

Dr. Sofi and colleagues reported no potential conflicts of interest associated with the study.