From the AGA Journals

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors had no disclosures.

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors had no disclosures.

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors 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.

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.

In this issue of Gastroenterology and in an upcoming issue of Clinical Gastroenterology and Hepatology, an important behind-the-scenes change is occurring. Specifically, both journals will continue to publish important and timely reviews and commentaries, but the formulation and design of some of these articles will now be driven by a new committee. The newly formed American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) is charged with providing authoritative and balanced articles for the two journals that have the greatest impact on the clinical practice of gastroenterology and hepatology. Potential subjects for these articles will derive from several sources in coordination with the AGA Institute Clinical Guidelines Committee.

First, important topics that are proposed initially for an AGA guideline but do not meet rigid criteria for guideline grading will be sent to the CPUC for review and consideration. Second, ideas for topics will also be generated by the CPUC members and journal editors, as well as by other AGA committees and AGA members themselves. Third, summaries of important symposia such as the yearly Freston Conference will be included. Topics can be presented in the form of a comprehensive, narrative review or, for particularly timely issues in gastroenterology, hepatology, and health care in general, as a rapid commentary.

We believe that the vetting process of these articles is important. All prospective topics and selected authors will be approved by the CPUC with guidance from the AGA Institute Governing Board. At least 2 authors who are recognized authorities will be invited to write an article and will be chosen from different institutions. It is anticipated that the authors will often have differing opinions, to help ensure balance and achieve consensus. A member of the CPUC with expertise in the field will guide the writing to ensure the highest quality and greatest balance in the final product. Once an article is written, it will be submitted for evaluation by the Editors of Gastroenterology and Clinical Gastroenterology and Hepatology, who will decide whether to accept the paper or send it for further review before acceptance.

With seasoned and motivated authors and the guidance of the CPUC, we expect outstanding reviews that will be published in a timely manner and provide AGA members and readers of the journals the most up-to-date and scholarly information across the spectrum of gastroenterology, hepatology, and nutrition. We are excited about this new process as a means to enhance our already outstanding journals, which are dedicated to publishing the best research and practice information in our field. Because this is a new process, we welcome feedback and suggestions for improvement and look forward to providing content that helps your research and clinical practice.

Dr. Katzka is at Mayo Clinic, Rochester, Minn.; Dr. Friedman is at Newton-Wellesley Hospital, Newton, Mass.; Dr. Inadomi is at University of Washington School of Medicine, Seattle; Dr. Kalloo is at Johns Hopkins Hospital, Baltimore; Dr. Kim is at South Denver Gastroenterology, P.C., Littleton, Colo.; Dr. Koch is at Virginia Mason Medical Center, Seattle; Dr. Lieberman is at Oregon Health and Science University, Portland; Dr. Lichtenstein is at the Hospital of the University of Pennsylvania, Merion Station, Penn.: Dr. Lim is at Yale University School of Medicine, New Haven, Conn.; Dr. Pandolfino is at Northwestern University, Chicago; Dr. Shin is at Indiana University School of Medicine, Indianapolis; and Dr. Siedler is Committee Liaison, American Gastroenterological Association.

In this issue of Gastroenterology and in an upcoming issue of Clinical Gastroenterology and Hepatology, an important behind-the-scenes change is occurring. Specifically, both journals will continue to publish important and timely reviews and commentaries, but the formulation and design of some of these articles will now be driven by a new committee. The newly formed American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) is charged with providing authoritative and balanced articles for the two journals that have the greatest impact on the clinical practice of gastroenterology and hepatology. Potential subjects for these articles will derive from several sources in coordination with the AGA Institute Clinical Guidelines Committee.

First, important topics that are proposed initially for an AGA guideline but do not meet rigid criteria for guideline grading will be sent to the CPUC for review and consideration. Second, ideas for topics will also be generated by the CPUC members and journal editors, as well as by other AGA committees and AGA members themselves. Third, summaries of important symposia such as the yearly Freston Conference will be included. Topics can be presented in the form of a comprehensive, narrative review or, for particularly timely issues in gastroenterology, hepatology, and health care in general, as a rapid commentary.

We believe that the vetting process of these articles is important. All prospective topics and selected authors will be approved by the CPUC with guidance from the AGA Institute Governing Board. At least 2 authors who are recognized authorities will be invited to write an article and will be chosen from different institutions. It is anticipated that the authors will often have differing opinions, to help ensure balance and achieve consensus. A member of the CPUC with expertise in the field will guide the writing to ensure the highest quality and greatest balance in the final product. Once an article is written, it will be submitted for evaluation by the Editors of Gastroenterology and Clinical Gastroenterology and Hepatology, who will decide whether to accept the paper or send it for further review before acceptance.

With seasoned and motivated authors and the guidance of the CPUC, we expect outstanding reviews that will be published in a timely manner and provide AGA members and readers of the journals the most up-to-date and scholarly information across the spectrum of gastroenterology, hepatology, and nutrition. We are excited about this new process as a means to enhance our already outstanding journals, which are dedicated to publishing the best research and practice information in our field. Because this is a new process, we welcome feedback and suggestions for improvement and look forward to providing content that helps your research and clinical practice.

Dr. Katzka is at Mayo Clinic, Rochester, Minn.; Dr. Friedman is at Newton-Wellesley Hospital, Newton, Mass.; Dr. Inadomi is at University of Washington School of Medicine, Seattle; Dr. Kalloo is at Johns Hopkins Hospital, Baltimore; Dr. Kim is at South Denver Gastroenterology, P.C., Littleton, Colo.; Dr. Koch is at Virginia Mason Medical Center, Seattle; Dr. Lieberman is at Oregon Health and Science University, Portland; Dr. Lichtenstein is at the Hospital of the University of Pennsylvania, Merion Station, Penn.: Dr. Lim is at Yale University School of Medicine, New Haven, Conn.; Dr. Pandolfino is at Northwestern University, Chicago; Dr. Shin is at Indiana University School of Medicine, Indianapolis; and Dr. Siedler is Committee Liaison, American Gastroenterological Association.

In this issue of Gastroenterology and in an upcoming issue of Clinical Gastroenterology and Hepatology, an important behind-the-scenes change is occurring. Specifically, both journals will continue to publish important and timely reviews and commentaries, but the formulation and design of some of these articles will now be driven by a new committee. The newly formed American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) is charged with providing authoritative and balanced articles for the two journals that have the greatest impact on the clinical practice of gastroenterology and hepatology. Potential subjects for these articles will derive from several sources in coordination with the AGA Institute Clinical Guidelines Committee.

First, important topics that are proposed initially for an AGA guideline but do not meet rigid criteria for guideline grading will be sent to the CPUC for review and consideration. Second, ideas for topics will also be generated by the CPUC members and journal editors, as well as by other AGA committees and AGA members themselves. Third, summaries of important symposia such as the yearly Freston Conference will be included. Topics can be presented in the form of a comprehensive, narrative review or, for particularly timely issues in gastroenterology, hepatology, and health care in general, as a rapid commentary.

We believe that the vetting process of these articles is important. All prospective topics and selected authors will be approved by the CPUC with guidance from the AGA Institute Governing Board. At least 2 authors who are recognized authorities will be invited to write an article and will be chosen from different institutions. It is anticipated that the authors will often have differing opinions, to help ensure balance and achieve consensus. A member of the CPUC with expertise in the field will guide the writing to ensure the highest quality and greatest balance in the final product. Once an article is written, it will be submitted for evaluation by the Editors of Gastroenterology and Clinical Gastroenterology and Hepatology, who will decide whether to accept the paper or send it for further review before acceptance.

With seasoned and motivated authors and the guidance of the CPUC, we expect outstanding reviews that will be published in a timely manner and provide AGA members and readers of the journals the most up-to-date and scholarly information across the spectrum of gastroenterology, hepatology, and nutrition. We are excited about this new process as a means to enhance our already outstanding journals, which are dedicated to publishing the best research and practice information in our field. Because this is a new process, we welcome feedback and suggestions for improvement and look forward to providing content that helps your research and clinical practice.

Dr. Katzka is at Mayo Clinic, Rochester, Minn.; Dr. Friedman is at Newton-Wellesley Hospital, Newton, Mass.; Dr. Inadomi is at University of Washington School of Medicine, Seattle; Dr. Kalloo is at Johns Hopkins Hospital, Baltimore; Dr. Kim is at South Denver Gastroenterology, P.C., Littleton, Colo.; Dr. Koch is at Virginia Mason Medical Center, Seattle; Dr. Lieberman is at Oregon Health and Science University, Portland; Dr. Lichtenstein is at the Hospital of the University of Pennsylvania, Merion Station, Penn.: Dr. Lim is at Yale University School of Medicine, New Haven, Conn.; Dr. Pandolfino is at Northwestern University, Chicago; Dr. Shin is at Indiana University School of Medicine, Indianapolis; and Dr. Siedler is Committee Liaison, American Gastroenterological Association.

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.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

©roxanabalint/Thinkstock

Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

©roxanabalint/Thinkstock

Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

©roxanabalint/Thinkstock

Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.

Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.

©iStock / ThinkStockPhotos.com

Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.

Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).

Source: American Gastroenterological Association

In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.

A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.

The University of California San Diego Health Care System supported the study. The investigators had no disclosures.

Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.

©iStock / ThinkStockPhotos.com

Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.

Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).

Source: American Gastroenterological Association

In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.

A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.

The University of California San Diego Health Care System supported the study. The investigators had no disclosures.

Only 1% of adults with asymptomatic neoplastic pancreatic cysts developed invasive pancreatic adenocarcinoma after more than 5 years of follow-up, according to a multicenter retrospective study reported in the June issue of Clinical Gastroenterology and Hepatology.

©iStock / ThinkStockPhotos.com

Furthermore, there were no malignant conversions among patients lacking American Gastroenterological Association high-risk features – that is, mural nodules, dilated pancreatic ducts, or cysts measuring more than 3 cm, said Dr. Wilson Kwong at the University of California San Diego Health Sciences in La Jolla. “There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years,” he and his associates wrote.

Up to 20% of cross-sectional imaging studies reveal incidental pancreatic cysts, the researchers noted. Cysts with neoplastic features are recommended for indefinite surveillance, even though there is little or no data on their natural history and malignant potential beyond 5- 10 years, they added. Therefore, they studied 310 patients who underwent endoscopic ultrasound of pancreatic cysts at an academic medical center, a Veterans’ Affairs hospital, and two community health care systems in California between 2002 and 2010. The most common age at enrollment was 66 years, 60% of patients were women, and the median follow-up period was 87 months (range, 60 to 189 months). A total of 90% of patients were followed for 5-10 years, while 10% were followed for more than 10 years (Clin Gastroenterol Hepatol. 2016 Feb 10. doi: 10.1016/j.cgh.2015.11.013).

Source: American Gastroenterological Association

In all, three patients developed invasive pancreatic malignancies after 6, 8, and 11 years of follow-up, for an overall conversion rate of 1%. Conversion rates by subgroup were 0% for patients with no high-risk AGA features, 1% (one case) for patients with one high-risk feature, and 15% (two cases) for patients with two high-risk features. “Because the risk of malignant transformation beyond 5 years is lower than the 1.4% mortality risk of pancreatic resection at high-volume centers, the argument can be made that discontinuing surveillance after 5 years is justified,” the researchers said. Specifically, surveillance could be discontinued after 5 years for neoplastic pancreatic cysts with up to one high-risk feature, particularly if patients have significant comorbidities that increase their risk of imminent death from other causes, they added. In contrast, healthy patients in their 60s and 70s might benefit from long-term surveillance given their longer life expectancy, they said. “Among patients with two high-risk features who remain surgically fit, discussion of surgery or surveillance beyond 5 years should be considered,” they emphasized.

A total of two patients developed high-grade dysplasia – a risk factor for invasive pancreatic cancer – but even so, the aggregate rate of cancer and high-grade dysplasia was 1.6%, only slightly higher than the fatality rate associated with pancreatic resection, the researchers noted. By excluding patients with recent acute pancreatitis (because of the likelihood of pseudocysts), they might have inadvertently excluded “a small number” of patients with pancreatic intraductal papillary mucinous neoplasms, they added.

The University of California San Diego Health Care System supported the study. The investigators had no disclosures.